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The Pacific white shrimp or white leg shrimp, Penaeus vannamei, is native to the tropical coastal regions of Central and South America. It is one of the three major shrimp species with high production worldwide. It was brought from Hawaii, USA, in 1988 and introduced into China. It has been widely promoted and cultivated due to its adaptability to the environment, fast growth rate, and suitability for high-density industrial farming. As of 2022, China's total production of P. vannamei reached 2.09 million tons, accounting for > 90% of the country's total shrimp farming production. It has become one of the pillar industries in China's aquaculture sector.With the continuous expansion of aquaculture, diseases are becoming increasingly severe. Among them, acute hepatopancreatic necrosis disease (AHPND) hinders the development of the global shrimp farming industry and causes catastrophic economic losses. After infection, most shrimp show hepatopancreatic enlargement, which appears pale white or light yellow. In the later stages of infection, some diseased shrimp may exhibit atrophy of the hepatopancreas, appearing reddish-brown and blackened, with a hardened texture. Within 20–30 d after infection, death can occur, with a mortality rate of up to 90%. As of 2021, the economic losses caused by this disease to the major P. vannamei farming areas (China, Malaysia, Thailand, Vietnam, and Mexico) have exceeded 43 billion US dollars. Cultivating novel P. vannamei germplasm with AHPND resistance is an effective way to solve AHPND.Recently, domestic researchers have established independent shrimp breeding systems and cultivated 12 novel P. vannamei strains, such as "Hai Xing Nong No.2", "Ren Hai No.1", and "Zheng Jin Yang No.1". These varieties mainly target traits such as growth, resistance to white spot syndrome virus, farming survival rate, and temperature, salinity, and ammonia nitrogen tolerance. However, no reports of novel varieties specifically targeting AHPND resistance are available. Growth traits are essential economic traits in the genetic breeding of aquatic animals. Among the 12 novel P. vannamei varieties in China, 11 have excellent traits related to growth. Evaluating the genetic relationship between growth and AHPND resistance in the core breeding population of P. vannamei is important for fully utilizing existing high-quality germplasm and breeding novel varieties with composite traits and AHPND resistance.Genetic parameters reflect the genetic variation of target traits in a breeding population and are important references for breeding decisions. Due to the complex genetic background of existing P. vannamei germplasm resources in China, genetic parameters are influenced considerably by the tested population, infection methods, and other factors. Before breeding, stable infection tests must be conducted on the base population and obtain accurate parameters.This study used two independently bred P. vannamei strains as research objects to test their growth and AHPND resistance. Among them, 40 families were selected for high resistance (20 individuals per family, total 800 experimental individuals), and 30 families were selected for fast growth (32 individuals per family, total 960 experimental individuals). The test was conducted at P70–P90 by feeding with VpAHPND quantitative oral infection. Feeding with toxic bait was stopped after 50% of the experimental individuals died. The genetic heritability and correlation of the weight, individual survival time after VpAHPND infection, and half-lethal survival rate of the two strains were evaluated using individual animal and male and female threshold models. The results showed that the weight heritability estimate of the highly resistant strain was 0.599±0.120, indicating a high level of genetic heritability. The heritability estimates of survival time and half-lethal survival rate were 0.240±0.072 and 0.173±0.051, respectively, indicating a moderate to low level of genetic heritability, and all significantly different from 0 (P < 0.01). The weight heritability estimate of the fast-growth strain was 0.266±0.082, indicating a low level of genetic heritability. The heritability estimates of survival time and half-lethal survival rate were 0.374± 0.096 and 0.257±0.048, respectively, indicating a moderate level of genetic heritability, and all significantly different from 0 (P < 0.01). The genetic correlation between weight and AHPND resistance traits (survival time and half-lethal survival rate) in both strains showed a low positive correlation (0.061–0.235), and no significant difference was observed from 0 (P > 0.05). The genetic correlation between survival time and half-lethal survival rate in both strains was highly positively correlated, with estimates of 0.997±0.129 and 0.967±0.044, respectively. The results indicate that growth and AHPND resistance can be included as selection indicators in the comprehensive selection index for breeding and seed production in the actual breeding process. Under limited conditions, the infection program can be simplified, and the half-lethal survival rate can be used as the AHPND resistance indicator for the breeding population. This study provides a primary reference for utilizing existing germplasm resources to develop high-quality P. vannamei strains for growth and AHPND resistance breeding.

177Lu- prostate specific membrane antigen (PSMA) radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China. Based on domestic clinical practice and experimental data and referred to international experience and viewpoints, the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

The Pacific white shrimp Penaeus vannamei is one of the most productive shrimp species in China and the world. Domestic demand for P. vannamei has increased annually because of its fast growth, easy breeding, strong resistance to stress and disease, and high meat yield. The primary challenge in the development of the shrimp industry is seed rearing. The demand for broodstocks of P. vannamei in China is as high as 1, 000, 000 pairs per year, and the total weight of shrimp seedlings exceeds 1.3 trillion. China needs to import 300, 000 pairs of P. vannamei every year. The cost of each pair of P. vannamei is approximately 200 US＄, thus equating to hundreds of millions of US＄ in total. During the production of P. vannamei, the spawning frequency varies greatly among female shrimp. Cultivating high-fecundity P. vannamei through genetic improvement is an effective way to reduce the cost of seedling farms and improve economic benefits.To further study the molecular mechanisms of fecundity differences in female P. vannamei, the ovarian histology and expression of four candidate genes in populations with high- and low-fecundity were analyzed in this study. Before the experiment, the 7-month-old parent shrimp of P. vannamei were fed a commercial parent shrimp fortified diet, a maturation promoting diet, and squid for nutritional enhancement. After one month of promoting maturity, the unilateral eyestalk of female shrimp was cut using forceps, and next-generation family construction began after 15–20 days of recovery. The spawning frequency of 439 female shrimp in the 30-day production cycle was calculated and used to indicate fecundity. Those with a spawning frequency of 0 were included in the low-fecundity group, while those with a spawning frequency of > 3 were included in the high-fecundity group. The ovarian development of P. vannamei was divided into four stages (proliferation, small growth, large growth, and maturation) according to the color, size, and shape of the ovaries. In the high-fecundity group, the ovaries exhibited development up to stageⅣ, indicating their attainment of maturity. In the low-fecundity group, ovarian development was limited to stageⅢ, with progression to stageⅣ proving difficult. Ovarian tissues from the same part of female shrimp of stageⅠ–Ⅳ in the high-fecundity group and stageⅠ–Ⅲ in the low-fecundity group were taken and immediately immersed in tissue fixative for paraffin sectioning. The research team previously identified candidate genes related to fecundity in genomic regions undergoing selective sweep in isolated populations. These included thioredoxin 2 (TRX2), partitioning-defective 3 (PARD3), phospholipase Cβ4 (PLCβ4), and arginine-glutamate acid dipeptide repeats (RERE), which play important roles in oocyte maturation, cell proliferation, and early development in other species. qRT-PCR was used to analyze and compare their expression in the ovary and eyestalk tissues of high- and low-fecundity females at different stages of ovarian development.The results of paraffin section showed that the ovarian development of the low-fecundity group was slower than that of the high-fecundity group. In the high-fecundity group, stageⅠ ovaries primarily consisted of oogonia and oocytes during the early phase of yolk formation, with the emergence of small spherical yolk granules. StageⅠ ovaries in the low-fecundity group primarily consisted of oogonia, with no observable yolk granule formation. StageⅡ ovaries in the high-fecundity group were mainly composed of oocytes with vitelline formation, accompanied by a notable augmentation in both the size and number of yolk granules. StageⅡ ovaries in the low-fecundity group primarily comprised oocytes in the early phase of vitelline formation with yolk granules beginning to form. StageⅢ ovaries in the high-fecundity group consisted mainly of oocytes during the late phase of yolk formation. Many spherical yolk granules were formed in the cytoplasm, and cortical rods began to appear, although the lengths of the cortical rods were short. StageⅢ ovaries in the low-fecundity group were composed of oocytes during yolk formation. The cytoplasm was full of spherical yolk granules in the absence of cortical rods. In the high-fecundity group, stage Ⅳ ovaries were filled with mature oocytes, large yolk granules filled the entire cytoplasm, and thick cortical rods were formed in the oocytes. qRT-PCR showed that the four genes maintained high expression levels in the mature ovaries of the high-fecundity group. Their expression levels in the ovaries of the high-fecundity group were higher than those in the ovaries of the low-fecundity group in the small and large growth stages. TRX2, PLCβ4, and RERE expression levels were significantly different between the groups (P < 0.05). In eyestalk tissues at different stages, TRX2, PARD3, PLCβ4, and RERE expression levels in the low-fecundity group were higher than those in the high-fecundity group. The results suggest that these four genes may play important roles in the ovarian development of P. vannamei. The expression levels of all four genes in the high-fecundity group were lower than those in the low-fecundity group in eyestalk tissues. However, in ovarian tissues, except for the PARD3 gene in stageⅠ, which was expressed at lower levels in the high-fecundity group than in the low-fecundity group, the expression levels of all four genes in the other stages were higher in the high-fecundity group than those in the low-fecundity group, which is opposite to the expression trend in eyestalk tissues. Therefore, we speculate that these genes also promote cell proliferation, development, and target gene expression in the eyestalks of the low-fecundity group. Their high expression in the eyestalks of the low-fecundity group may enhance the secretion of ovarian inhibitory factors, thereby inhibiting ovarian development. Further research is needed to reveal their functional mechanisms. The above results provide an important reference for the in-depth study of the molecular mechanisms of differences in the fecundity of female P. vannamei.

Penaeus vannamei, also known as white foot shrimp, is globally one of the three high-yield shrimp farming varieties. The wild species is found along the Pacific coast of South America. Since 1988, China has introduced P. vannamei. Due to its strong environmental adaptability, high feed conversion rate, fast growth rate, and high tolerance to ammonia nitrogen and nitrite, it has been widely promoted in aquaculture. By 2021, the aquaculture output of P. vannamei in China reached 1.977 million tons, accounting for approximately 37% of the world's total production, and has extremely high economic value.Growth traits are among the most important economic factors in the production of P. vannamei. With the intensive development of shrimp farming and degradation of germplasm, the white spot syndrome virus (WSSV) is a serious disease faced by the global shrimp industry. The infection can cause symptoms such as reduced food intake, enlarged liver and pancreas, pale red body color, and white spots on the head and chest armor in shrimp, resulting in widespread death.At present, China has cultivated 12 new varieties of P. vannamei, which to some extent alleviates its dependence on imports for high-quality P. vannamei. However, the excellent traits of domestic shrimp species are singular, and cultivating new varieties of P. vannamei with fast growth and strong disease resistance is an urgent demand in the market. Genetic parameter evaluation is the fundamental work of selection breeding. Heritability reflects the genetic variation in traits in the breeding population, which is of great significance in the development of a selection index, prediction of selection response, comparison of selection methods, selection breeding planning, and other breeding processes. There are different degrees of genetic correlation among various quantitative traits of shrimp, and genetic correlation coefficients are important for selecting target traits. The estimation of genetic correlation can be used to develop a comprehensive selection index and breeding program of multiple traits, which can improve the selection efficiency and breed better varieties with multiple traits. The higher the genetic correlation between traits, the better the effect of indirect selection. The estimation of genetic parameters is greatly affected by the test population, breeding management, analysis methods, and other factors. To ensure the accuracy of multi-trait composite breeding for growth and WSSV resistance, accurate evaluation of growth and WSSV resistance needs to be carried out for specific breeding populations. There are two commonly used target traits for measuring WSSV resistance in P. vannamei: individual survival time after infection and half-lethal survival rate (SS50) of families. In practice, measuring the half-lethal survival rate of families is more convenient. However, the correlation between these two traits has not yet been reported.To promote the growth and WSSV resistance of P. vannamei, 59 families (1, 770 individuals) were tested for WSSV infection. We recorded the survival time and individual body length of shrimp after infection and analyzed the mean, standard deviation, maximum and minimum values, and coefficient of variation of half-lethal survival rate and test traits for each line. The heritability and genetic correlation coefficients of growth, survival time, and half-lethal survival rate were calculated. Variance components and genetic parameters for growth and survival traits were estimated using a two-trait animal model and a sire-dam threshold model. The genetic parameters of body length were corrected by including age as a covariate. The genetic parameters of WSSV survival time were corrected by including body length as a covariate. The estimated heritability of body length was medium (0.17±0.05), and the estimated heritabilities of survival time and half-lethal survival rate were medium (0.18±0.05 and 0.14±0.05). Further, the estimated heritabilities of the three traits were significantly different from zero (P < 0.01). The genetic correlation between body length and survival time and that of body length and half-lethal survival rate were low (0.15±0.20 and 0.25±0.22). There were no significant differences between the genetic correlations and zero (P > 0.05). The genetic correlation between survival time and half-lethal survival rate was high (0.96±0.03). There was no significant difference between the genetic correlation and one (P > 0.05). The results showed that a comprehensive selection index of growth and WSSV resistance of P. vannamei can be established to carry out multi-trait composite breeding. In this breeding population, the growth and WSSV resistance of P. vannamei can be combined with multiple traits according to the breeding requirements, and the comprehensive selection index can be formulated by assigning values. In addition, to optimize the breeding of each generation, the half-lethal survival rate of WSSV can be used as an indicator of WSSV resistance. This study provides basic data and theoretical support for breeding varieties of P. vannamei with excellent growth and WSSV resistance.

Pacific white shrimp Penaeus vannamei, as one of the most productive and economically valuable shrimp species in the world, have many favorable characteristics, such as a short growth cycle, strong adaptability and disease resistance, and a low nutritional demand. They are omnivorous animals whose diet mainly consists of animal-derived food. Conventional feed used in their culture contains fishmeal as the main protein source. Feed costs account for 40%~60% of their production costs. Therefore, breeding P. vannamei strains without demand for fishmeal would be an effective way to address the issues of fishmeal shortage and high feed costs. Improving utilization efficiency for diets without fishmeal is key to breeding such P. vannamei strains. In this study, genetic parameters for feed efficiency traits (feed efficiency ratio, feed intake, and weight gain) and genotype by environment interaction were evaluated using two diets, one without fishmeal (38% protein) and one with 25% fishmeal (42% protein).Thirty families of P. vannamei were selected for a 40-day feeding experiment. A total of 900 shrimp (30 animals per family) were selected. Fifteen animals per family were fed a zero-fishmeal diet, and the other 15 animals were fed a high fishmeal diet. The feed intake and body weight of all animals were measured for calculating the feed efficiency ratio and weight gain. The variance components for these traits were estimated using a univariate model and an average information restricted maximum likelihood algorithm, and genetic (phenotypic) correlations between traits were estimated using bivariate analysis.The results showed that shrimp fed a high fishmeal diet exhibited a significantly higher mean weight gain (62.00%) and feed efficiency ratio (124.00%) than those fed a zero-fishmeal diet, which had a mean weight gain of 23.50% and feed efficiency ratio of 49.40%. There was a small difference in the mean feed intake between shrimp fed a high fishmeal diet (7.09 g) and those fed a zero-fishmeal diet (7.28 g).The heritability estimates for feed intake of shrimp fed zero- and high fishmeal diets were 0.699 ±0.155 and 0.556±0.139, respectively. For weight gain, the heritability estimates of shrimp fed zero- and high fishmeal diets were 0.458±0.140 and 0.667±0.146, respectively, which were high. However, the differences between diets and between traits were not statistically significant (P > 0.05). The heritability estimates for feed efficiency ratio of shrimp fed zero- and high fishmeal diets were 0.186 ±0.098 and 0.341±0.110, respectively, which were low to medium. The differences in feed efficiency ratio between diets was not statistically significant (P > 0.05). All the above heritability estimates were overestimated, to some extent, because common environmental effects were not estimated. Therefore, there was not much genetic variation in feed efficiency ratio in shrimp fed a zero-fishmeal diet, suggesting limited potential in selection breeding of this trait.Regardless of diet, genetic correlations among feed intake, weight gain, and feed efficiency ratio were moderate to high (0.580±0.188 to 0.945±0.040). Genetic correlations between diets were 0.580± 0.171 and 0.676±0.155 for feed intake and weight gain, respectively, indicating that these two traits had moderate genotype by diet interactions. The genetic correlation between diets was only 0.299±0.304 for feed efficiency ratio, which indicates a serious genotype by diet interaction. According to the above results, use of a zero-fishmeal diet is not good for the culture and breeding of P. vannamei. In the future, fishmeal content in the diet may be appropriately increased, and genetic parameters and potential feed efficiency traits should be evaluated in low fishmeal diets.

Background: As a physiological function of body, immunity can maintain health by identifying itself and excluding others. With economic development and increasingly fierce social competition, the number of sub-healthy population is gradually increasing, and the most basic problem exposed is human hypoimmunity. Hypoimmunity can be manifested as often feeling tired, catching colds, mental depression, etc. In order to enhance immunity, eating healthy foods with the effect of enhancing immunity may become an effective choice. KRG has pharmacological effects of enhancing immunity. Because the screening and evaluation method of immune population are not unified, there are relatively few KRG immunity tests for sub-health population. It is of great significance to study the effect of KRG on people with hypoimmunity to improve sub-health status. Methods: This was a 180-day, randomized, double-blind, placebo-controlled clinical trial. According to the trial scheme design, 119 qualified subjects were included and randomly divided into the test group taking KRG and the placebo control group. Subjects need to check safety indicators (blood pressure and heart rate, blood routine, liver and kidney function, urine routine and stool routine) and efficacy indicators (main and secondary) inspection at baseline, efficacy indicators inspection during the mid-term of the test (90th days of administration), safety and efficacy indicators inspection after the test (180th days of administration). Results: After the test, the safety indicators of placebo control group and KRG test group were basically within the normal range, and there is no significant difference in fireness score between the two groups. Through follow-up interviews, it was found that the subjects in the test group and the control group had no adverse reactions and allergic reactions such as nausea, flatulence, diarrhea, and abdominal pain during the test period. Self-comparison of the test group, the results of the main efficacy indicators: (1) immune related health scores were significantly improved in the mid-term and after the test (P

Abstract Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive thyroid cancer with poor prognosis. Killing cancer cells by inducing DNA damage or blockage of DNA repair is a promising strategy for chemotherapy. It is reported that aldehyde-reactive alkoxyamines can capture the AP sites, one of the most common DNA lesions, and inhibit apurinic/apyrimidinic endonuclease 1(APE1)-mediated base excision repair (BER), leading to cell death. Whether this strategy can be employed for ATC treatment is rarely investigated. The aim of this study is to exploit GSH-responsive AP site capture reagent (AP probe-net), which responses to the elevated glutathione (GSH) levels in the tumor micro-environment (TME), releasing reactive alkoxyamine to trap AP sites and block the APE1-mediated BER for targeted anti-tumor activity against ATC. In vitro experiments, including MTT andγ-H2AX assays, demonstrate their selective cytotoxicity towards ATC cells over normal thyroid cells. Flow cytometry analysis suggests that AP probe-net arrests the cell cycle in the G2/M phase and induces apoptosis. Western blotting (WB) results show that the expression of apoptotic protein increased with the increased concentration of AP probe-net. Further in vivo experiments reveal that the AP probe-net has a good therapeutic effect on subcutaneous tumors of the ATC cells. In conclusion, taking advantage of the elevated GSH in TME, our study affords a new strategy for targeted chemotherapy of ATC with high selectivity and reduced adverse effects.

Based on the objective evaluation of the regional ecological quality (Urban Cluster in Mid-inner Zhejiang) by Remote Sensing based Ecological Index (RSEI), it was proposed to study the spatial-temporal response of the regional ecological quality to the urban built-up areas, impervious surface, land use and “production-living-ecological” space under urban settlement change to quantitatively describe the mechanism of human activities’ influence on the regional ecology. The results showed that: (1) From 1985 to 2020, the RSEI of the Urban Cluster in Mid-inner Zhejiang was above 0.50 as a whole, showing a trend of first decreasing and then increasing with a slight decrease in some parts. (2) From the perspective of the urban built-up areas, it was dominated by ecological level 2–3, gradually changing from ecological level 3 to ecological level 2. (3) From the perspective of the impervious surface, it was dominated by ecological level 2–3, accounting for more than 75.00% of the total study area. (4) From the perspective of land use, the cropland, forestland, water and construction land were mainly ecological level 2–4, 3–4, 3–4 and 2–3. (5) From the perspective of “production-living-ecological” space, production space, ecological space and living space were dominated by ecological level 3, 3–4 and 2–3. The results can deepen the understanding of the impact of urban settlement development on the regional ecological quality, avoid the unbalanced situation of blindly pursuing socio-economic development while ignoring the ecological environment, which scientifically helps the sustainable construction and high-quality development of the Urban Cluster in Mid-inner Zhejiang.

Abstract Background Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR) and is often accompanied by mild cognitive impairment (MCI). The detrimental effects of T2DM and IR on the hippocampus have been extensively demonstrated. Few studies have examined the effects of IR on structure and function of hippocampal subfields in T2DM‐MCI patients. Method A total of 104 T2DM patients were recruited in this prospective study and divided into four groups (T2DM‐MCI‐higherIR, n = 17; T2DM‐MCI‐lowerIR, n = 32; T2DM‐nonMCI‐higherIR, n = 19; T2DM‐nonMCI‐lowerIR, n = 36). Structure and function MRI data were captured. Clinical variables and neuropsychological scores were determined for all participants. Hippocampal subfield volume and functional connectivity were compared among four groups. Partial correlation analysis was performed between imaging indicators, clinical variables, and neuropsychological scores in all patients. Results T2DM‐MCI‐higher IR group had the smallest volumes of bilateral hippocampal tail, right subiculum‐body, right GC‐ML‐DG‐body, and right CA4‐body. IR in right hippocampal tail, right subiculum‐body, and right GC‐ML‐DG‐body exerted main effect. Furthermore, elevated functional connectivity was found between right subiculum‐body and bilateral dorsolateral prefrontal cortex and right anterior cingulate–medial prefrontal cortex. Hippocampal subfield volume positively correlates with total cholesterol and triglycerides and negatively correlates with fasting insulin. Conclusion The present study found that T2DM‐MCI patients have structural and functional alterations in hippocampal subfields, and IR is a negative factor influencing the alteration of hippocampal subfields volume. These findings support the importance of IR in T2DM‐MCI patients and might be potential neuroimaging biomarkers of cerebral impairment in T2DM‐MCI patients.

ObjectiveNasopharyngeal carcinoma (NPC) patients frequently present with distant metastasis (DM), which is typically associated with poor prognosis. This study aims to develop and apply machine learning models to predict DM, overall survival (OS), and cancer-specific survival (CSS) in NPC patients to provide optimal tools for improved predictive accuracy and performance.MethodsWe retrieved over 8,000 NPC patient samples with associated clinical information from the Surveillance, Epidemiology, and End Results (SEER) database. Utilizing two methods for handling missing values—imputation or deletion—we created various cohorts: DM-all, DM-slim, OS-all, OS-slim, CSS-all, and CSS-slim. Five machine learning models were deployed for the binary classification task of DM, and their performance was evaluated using the area under the curve (AUC). For the survival prediction tasks of OS and CSS, we constructed 45 combinations using nine survival machine learning algorithms. The Concordance Index (C-index), 5-year AUC, and Brier score assessed model accuracy. Patients were stratified into two risk groups for survival analysis, and the survival curves were presented.ResultsThis study examines the relationships between clinical factors and survival in NPC patients. The analysis, visualized through forest plots, indicates that demographic and clinical variables like gender, marital status, tumor grade, and stage significantly affect metastatic risks and survival. Specifically, factors such as advanced stages increase metastasis and survival risks, while enhanced treatments improve survival rates. In the cohort for DM prediction, results revealed that the random forest model was the most effective, with an AUC of 0.687. In contrast, when predicting overall survival (OS), the random survival forest (RSF) model consistently showed superior performance with the highest mean C-index of 0.802, a 5-year AUC of 0.857, and a Brier score of 0.167. Similarly, for cancer-specific survival (CSS) prediction, the RSF model demonstrated a mean C-index of 0.822, a 5-year AUC of 0.884, and a Brier score of 0.165. An online Shiny server was developed to allow the models to be used freely and efficiently via http://npcml.shinyapps.io/NPCpre.ConclusionThis study successfully established an online tool by machine learning models for NPC metastasis and survival prediction, providing valuable references for clinicians.

Objective Focal cervical kyphotic deformity (FCK) without neurologic compression is not uncommon in patients with cervical spondylotic myelopathy (CSM) who underwent anterior cervical decompression and fusion (ACDF) surgery. It remains unclear whether FCK at non‐responsible levels needs to be treated simultaneously. This study aims to investigate whether FCK at non‐responsible levels is the prognostic factor for CSM and elucidate the surgical indication for FCK. Methods Patients with CSM who underwent ACDF between January 2016 and April 2021 were included. Patients were divided into two groups according to the presence of FCK and two classifications according to global cervical sagittal alignment. Clinical outcomes were compared using Japanese Orthopaedic Association (JOA) scores and recovery rate (RR) of neurologic function. Univariate and multivariate analysis based on RR assessed the relationship between various possible prognostic factors and clinical outcomes. The receiver operating characteristic curve (ROC) was used to determine the optimal cutoff value of the focal Cobb angle to predict poor clinical outcomes. Results A total of 94 patients were included, 41 with FCK and 53 without. Overall, the RR of neurologic function was significantly lower in the FCK than in the non‐FCK group. Further analysis showed that the RR difference between the two groups was only observed in hypo‐lordosis classification (kyphotic and sigmoid alignment), but not in the lordosis classification. Multivariate analysis showed that the preoperative focal Cobb angle in the FCK level (OR = 0.42; 95% CI = 0.18–0.97) was independently associated with clinical outcomes in the hypo‐lordosis classification. The optimal cutoff point of the preoperative focal kyphotic Cobb angle was calculated at 4.05°. Conclusion For CSM with hypo‐lordosis, FCK was a risk factor for poor postoperative outcomes. Surgeons may consider treating the FCK simultaneously if the focal kyphotic Cobb angle of FCK is greater than 4.05° and is accompanied by cervical global kyphotic or sigmoid deformity.

Abstract Background The treatment of lung adenocarcinoma is difficult due to the limited therapeutic options. Cancer-associated fibroblasts play an important role in the development of cancers. This study aimed to identify a promising molecular target associated with cancer-associated fibroblasts for the treatment of lung adenocarcinoma. Methods The Cancer Genome Atlas lung adenocarcinoma dataset was used to screen hub genes associated with cancer-associated fibroblasts via the EPIC algorithm and Weighted Gene Co-expression Network Analysis. Multiple databases were used together with our data to verify the differential expression and survival of COL11A1. Functional enrichment analysis and the single-cell TISCH database were used to elucidate the mechanisms underlying COL11A1 expression. The correlation between COL11A1 and immune checkpoint genes in human cancers was also evaluated. Results Using the EPIC algorithm and Weighted Gene Co-expression Network Analysis, 13 hub genes associated with cancer-associated fibroblasts in lung adenocarcinoma were screened. Using the GEPIA database, Kaplan-Meier Plotter database, GSE72094, GSE75037, GSE32863, and our immunohistochemistry experiment data, we confirmed that COL11A1 overexpresses in lung adenocarcinoma and that high expression of COL11A1 is associated with a poor prognosis. COL11A1 has a genetic alteration frequency of 22% in patients with lung adenocarcinoma. COL11A1 is involved in the extracellular matrix activities of lung adenocarcinoma. Using the TISCH database, we found that COL11A1 is mainly expressed by cancer-associated fibroblasts in the tumor microenvironment rather than by lung adenocarcinoma cells. Finally, we found that COL11A1 is positively correlated with HAVCR2(TIM3), CD274 (PD-L1), CTLA4, and LAG3 in lung adenocarcinoma. Conclusion COL11A1 may be expressed and secreted by cancer-associated fibroblasts, and a high expression of COL11A1 may result in T cell exhaustion in the tumor microenvironment of lung adenocarcinoma. COL11A1 may serve as an attractive biomarker to provide new insights into cancer therapeutics.

Abstract Without intervention, a considerable proportion of patients with metabolism‐associated fatty liver disease (MAFLD) will progress from simple steatosis to metabolism‐associated steatohepatitis (MASH), liver fibrosis, and even hepatocellular carcinoma. However, the molecular mechanisms that control progressive MAFLD have yet to be fully determined. Here, we unraveled that the expression of the N6-methyladenosine (m6A) methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD, whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation, liver injury, and fibrosis. Conversely, hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet (HFD). Notably, in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner, which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1 + Ccr2 + monocyte-derived macrophages (Mo-macs). In detail, Cx3cr1 + Ccr2 + Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells (HSCs) to promote liver fibrosis. Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1 + Ccr2 + Mo-macs. Restoration of METTL14 or GLS2, or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis. Taken together, these findings indicate potential therapies for the treatment of MAFLD progression.

Anaplastic thyroid carcinoma is one of the highly fatal cancers and poses a serious threat to human health. Ferroptosis has been widely studied and proved to have an important role in tumor suppression, providing new avenues for cancer therapy; glutathione peroxidase 4(GPX4) and selenoprotein thioredoxin reductase(TXNRD1) are important regulatory targets in ferroptosis.Warburg effect is one of the important energy sources for cancer hypermetabolism, and pyruvate kinase isoenzyme 2 (PKM2) is a key metabolism enzyme that is important in this effect. Shikonin(SKN) is a Chinese herb that has been extensively studied for its anti-tumor ability. The aim of this study was to investigate the mechanism of anti-tumor effect of SKN in ATC cells and to elucidate the role played by ferroptosis and glycolysis in this inhibitory mechanism. The effects of SKN in ATC cell lines CAL-62 and 8505C cells were detected by flow cytometry, Western blotting,real-time quantitative PCR and a fluorescent probe for reactive oxygen species (ROS) to detect changes in intracellular ROS positivity; glucose and lactate assay kits to detect the levels of the raw material of glucose metabolism, glucose (GLU), and the product of glucose metabolism, lactate (LD); and the establishment of the BALB/C nude mice subcutaneous tumor model to analyse the inhibitory effect of SKN on ATC in vivo. The present study demonstrated that SKN inhibits the expression of NF-κB,GPX4,TXNRD1,PKM2,GLUT1.SKN inhibits ATC cell growth by down-regulating the occurrence of intracellular ferroptosis and inhibiting glycolysis in ATC cells.

BackgroundCompared to testicular germ cell tumors, the incidence of extragonadal germ cell tumors (EGCTs) is relatively low. While the lungs are a common site for metastasis of malignant germ cell tumors, primary pulmonary germ cell tumors are extremely rare.ObjectiveTo enhance the understanding of the diagnosis and treatment of germ cell tumors, particularly extragonadal germ cell tumors (EGCTs).MethodsA Case Report of Recurrent Testicular Germ Cell Tumor in a Patient with Primary Pulmonary Germ Cell Tumor and a Review of the Literature.Clinical dataThe patient was initially diagnosed with primary pulmonary germ cell tumor and received standard treatment. Five years later, the patient developed a recurrent testicular germ cell tumor. The pathological results from the two surgeries were different, indicating embryonal carcinoma in the first instance and seminoma in the second.ConclusionFor cases with a high suspicion of extragonadal germ cell tumors (EGCTs), early pathological biopsy is essential to confirm the histological subtype and to guide the selection of the most appropriate and sensitive treatment regimen.

Background: The effect of combined radiation and chemotherapy (combination therapy) versus monotherapy on anaplastic thyroid carcinoma (ATC) has not yet been clear. Methods: We identified 516 ATC patients during 2010–2015 from the Surveillance, Epidemiology and End Results (SEER) database and evaluated their survival outcome using the Kaplan-Meier method, Cox regression analysis and propensity score matching (PSM) technique. Results: The median overall survival (OS) among the entire cohort was 3 months (95 % confidence interval [CI], 2.58–3.42 months), and the 6- and 12-month OS rates were 29 % (95 % CI, 25.01%–32.88 %) and 13 % (95 % CI, 10.60%–16.58 %), respectively. Multivariable analysis demonstrated that ATC patients not receiving radiotherapy or chemotherapy were unquestionably associated with worse OS (hazard ratio [HR] 3.000, 95 % CI, 2.390–3.764) and cancer-specific survival (CSS) (HR = 3.107, 95 % CI, 2.388–4.043), compared with those receiving combination therapy. However, combination therapy did not predict better prognosis compared with monotherapy (all P > 0.05). After PSM, the median OS and CSS were also not significantly improved in patients undergoing chemoradiotherapy versus chemotherapy alone (OS, P = 0.382; CSS, P = 0.420) or radiotherapy alone (OS, P = 0.065; CSS, P = 0.251). Conclusion: Combination therapy, compared to monotherapy, does not have the expected improvement in survival beyond the benefits achievable with each single-modality treatment, necessitating further prospective research to tailor its treatment management.

Abstract Background Breastfeeding (BF) confers metabolic benefits to infants, including reducing risks of metabolic syndrome such as obesity and diabetes later in life. However, the underlying mechanism is not yet fully understood. Hence, we aim to investigate the impacts of BF on the metabolic organs of infants. Methods Previous literatures directly studying the influences of BF on offspring’s metabolic organs in both animal models and humans were comprehensively reviewed. A microarray dataset of intestinal gene expression comparing infants fed on breastmilk versus formula milk was analyzed. Results Reanalysis of microarray data showed that BF is associated with enhanced intestinal gluconeogenesis in infants. This resembles observations in other mammalian species showing that BF was also linked to increased gluconeogenesis. Conclusions BF is associated with enhanced intestinal gluconeogenesis in infants, which may underpin its metabolic advantages through finetuning metabolic homeostasis. This observation seems to be conserved across species, hinting its biological significance.

Litopenaeus vannamei, also known as the Pacific white shrimp or white foot shrimp, is a member of the Crustacea, Decapoda, Palaemonidae, and Litopenaeus families. This species is mainly distributed on the Mexican and Pacific coasts of South America. Owing to its excellent immune characteristics, L. vannamei is currently one of the most important economic shrimp species in China.In the aquaculture process and under natural environmental conditions, low dissolved oxygen (DO) condition or even hypoxia frequently occurs. Under high-density culture operations, acute hypoxia is one of the major factors affecting the survival rate of shrimp and the quality of aquaculture water, causing not only a large number of shrimp deaths in the short term but also water decay and fermentation, increased turbidity, and other phenomena. The genetic improvement of L. vannamei, as well as the screening and breeding of exceptionally tolerant species under low DO conditions, are crucial to the sustainable development of the shrimp industry. Global selective breeding efforts based on quantitative genetics to improve genetic progress in L. vannamei have been extensive, and the main targeted traits were growth, survival, disease resistance, and stress tolerance. Few studies have been conducted on the evaluation of genetic parameters and screening of strains for hypoxic tolerance traits in L. vannamei; in particular, the genetic parameters and cytological characteristics of key tissues of L. vannamei under short-term highly lethal DO levels (0.3–0.5 mg/L) have not been reported.In this study, we used two strains of L. vannamei, GK (a strain with high disease resistance) and K (a strain with fast growth characteristics), each with a total of 6 560 shrimp from 41 families, to count survival traits at highly lethal DO levels, analyze differences in hypoxia tolerance traits between strains and within families of the same strain, and evaluate genetic parameters. Individual gill, muscle, and hepatopancreas tissues from families with significantly different tolerance levels were histologically investigated and compared at the cellular level. The results showed that there was a significant difference (P < 0.05) in semi-lethal survival (SS50) between families within both the GK and K strains when overall semi-lethality was reached under hypoxic environmental conditions of 0.3 mg/L, with SS50 values of 49.30% for GK and 42.52% for K. The coefficients of variation for survival times of families within each strain were 60% and 45% for GK and K, respectively. Using the threshold trait animal model, the genetic parameters were estimated to be between 0.345±0.031 and 0.378±0.029 using the survival status of the individual at semi-lethal levels as the observed value (1 for survival and 0 for death), and the heritability was between 0.219±0.031 and 0.237±0.029 following transformation on a continuously varying scale of observed values, indicating a moderate level of heritability. Moreover, the gill, muscle, and hepatopancreas tissues of the hypoxia-tolerant and hypoxia-sensitive families in the GK strain exhibited varying degrees of damage and different degrees of variations in the physiological characteristics of resistance among different families. This may be related to the resistance tolerance strength of different GK families. In contrast to the gill, muscle, and hepatopancreas tissues of the control shrimp, the equivalent tissues of shrimp from tolerant and sensitive families showed different degrees of changes following stress. The gill lumen of the filaments of the experimental group from sensitive families increased, the number of blood cells increased, the structure of the epithelial layer was gradually destroyed or even disintegrated, the vacuolation of the hepatopancreas was severe, the lumen of the ducts became irregularly deformed, and the muscle tissue muscle bundle interval widened with a certain degree of deformation. These results suggested that there was abundant genetic variation in the tolerance traits of L. vannamei at highly lethal DO levels and that this species was amendable to selective breeding practices. This study provides a reference and basis for the selection and breeding of hypoxia-tolerant traits in L. vannamei.

Background: The pathogenesis of diabetes and its microvascular complications are intimately associated with renin angiotensin system dysregulation. Evidence suggests the angiotensin converting enzyme 2 (ACE2)/angiotensin 1-7 (Ang 1–7)/Mas receptor (MasR) axis regulates metabolic imbalances, inflammatory responses, reduces oxidative stress, and sustains microvascular integrity, thereby strengthening defences against diabetic conditions. This study aims to conduct a comprehensive analysis of the ACE2/Ang 1–7/MasR axis in diabetes and its microvascular complications over the past two decades, focusing on key contributors, research hotspots, and thematic trends. Methods: This cross-sectional bibliometric analysis of 349 English-language publications was performed using HistCite, VOSviewer, CiteSpace, and Bibliometrix R for visualization and metric analysis. Primary analytical metrics included publication count and keyword trend dynamics. Results: The United States, contributing 105 articles, emerged as the most productive country, with the University of Florida leading institutions with 18 publications. Benter IF was the most prolific author with 14 publications, and Clinical Science was the leading journal with 13 articles. A total of 151 of the 527 author's keywords with two or more occurrences clustered into four major clusters: diabetic microvascular pathogenesis, metabolic systems, type 2 diabetes, and coronavirus infections. Keywords such as “SARS”, “ACE2”, “coronavirus”, “receptor” and “infection” displayed the strongest citation bursts. The thematic evolution in this field expanded from focusing on the renin angiotensin system (2002–2009) to incorporating ACE2 and diabetes metabolism (2010–2016). The latter period (2017–2023) witnessed a significant surge in diabetes research, reflecting the impact of COVID-19 and associated conditions such as diabetic retinopathy and cardiomyopathy. Conclusions: This scientometric study offers a detailed analysis of the ACE2/Ang 1–7/MasR axis in diabetes and its microvascular complications, providing valuable insights for future research directions.

PurposeTo investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves’ disease (GD) and to further assess predictive value of changes in early stage retrospectively.MethodsWe studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered.ResultsThe levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05).ConclusionBTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.

Abstract Background The effects of obesity and diabetes on the clinical outcomes of differentiated thyroid cancer (DTC) remain unclear. Objectives To explore the association between obesity and diabetes with pathological features and therapeutic response of DTC. Methods Patients were categorized based on body mass index (BMI) and glycemic status. Compare the correlation between BMI and glycemic status with pathological features and therapeutic response of DTC. To analyze the independent risk factors for the aggressiveness of DTC. Results The proportion of patients with bilateral tumors was higher in the overweight, obese and diabetes group (P = 0.001, 0.045). The overweight group demonstrated a higher TNM stage (P = 0.004), while the T and TNM stages were higher in the diabetes group (P = 0.032, 0.000). The probability of distant metastasis increases by 37.4% for each unit of BMI increase (odds ratio (OR) = 1.374, CI 95% 1.061–1.778, P

This study investigates the impact of propylene glycol (PRG) on ketotic cows, focusing on alleviating oxidative stress and enhancing immunity through modulating amino acid and lipid metabolism. Ketosis, a prevalent metabolic disease in dairy cows, negatively affects productivity and health. PRG, known for its gluconeogenic properties, was administered to cows with ketosis daily for three days and compared to an untreated group. Serum samples were taken to measure the biochemical parameters, and metabolomic and lipidomic analyses were performed with ultra-high-performance liquid chromatography–mass spectrometry. The results showed significant reductions in serum non-esterified fatty acids, beta-hydroxybutyrate, and C-reactive protein levels, alongside increased glucose, anti-inflammatory factor interleukin-10, superoxide dismutase, and glutathione peroxidase activities. Metabolomic and lipidomic analyses revealed significant alterations, including increased levels of glucogenic amino acids like glutamate and proline, and decreased levels of ceramide species. A pathway analysis indicated that PRG affects multiple metabolic pathways, including alanine, aspartate, glutamate metabolism, and sphingolipid metabolism. These findings suggest that PRG not only mitigates oxidative stress, but also enhances immune function by restoring metabolic homeostasis. This study provides valuable insights into the biochemical mechanisms underlying PRG’s therapeutic effects, offering potential strategies for the effective management and treatment of ketosis in dairy cows.

Ocean Thermal Energy Conversion (OTEC) is a process that can produce electricity by utilizing the temperature difference between deep cold water and surface warm water. The cold-water pipe (CWP) is a key component of OTEC systems, which transports deep cold water to the floating platform. The CWP is subjected to various environmental and operational loads, such as waves, currents, internal flow, and platform motion, which can affect its dynamic response and stability. In this paper, we establish a computational model of the mechanical performance of the CWP based on the Euler–Bernoulli beam theory and the Morrison equation, considering the effects of internal flow, sea current, and wave excitation. We use the differential quadrature method (DQM) to obtain a semi-analytical solution of the lateral displacement and bending moment of the CWP. We verify the correctness and validity of our model by comparing it with the finite element simulation results using OrcaFlex software. We also analyze the effects of operating conditions—such as wave intensity, clump weight at the bottom, and internal flow velocity—on the dynamic response of the CWP using numerical simulation and the orthogonal experimental method. The results show that changing the wave strength and internal flow velocity has little effect on the lateral displacement of the CWP but increasing the current velocity can significantly increase the lateral displacement of the CWP, which can lead to instability. The effects of waves, clump weight, internal flow, and sea current on the maximum bending moment of the CWP are similar; all of them increase sharply at first and then decrease gradually until they level off. The differences in the effects are mainly reflected in the different locations of the pipe sections. This paper suggests some design guidance for CWP in terms of dynamic responses depending on the operating conditions. This paper contributes to the journal’s scope by providing a novel and efficient method for analyzing the mechanical performance of CWP for OTEC systems, which is an important ocean energy resource.

Objective: This study aimed to investigate the underlying reasons for unexplained elevated thyroglobulin (Tg) in postoperative papillary thyroid cancer (PTC) patients according to follow-up results post RAT and to explore the long-term clinical outcomes and prognostic factors associated with these patients. Methods: From April 2016 to June 2019, a retrospective study was conducted on postoperative PTC patients who underwent RAT at our institution. Patients with preablative stimulated thyroglobulin (psTg) > 10 ng/mL but no structurally evident disease were enrolled. The causal categorization for elevated Tg was analyzed 6 months post RAT and the long-term therapeutic responses were assessed at the end of follow-up. To identify risk factors influencing recurrence-free survival (RFS), both univariate and multivariate Cox regression analysis were employed. Kaplan-Meier method was utilized for plotting survival curves. Results: A cohort of 165 subjects was enrolled for the analyses. Based on the results of a six-month follow-up, the postoperative unexplained elevated Tg among 165 patients could be ultimately attributed to thyroid remnant in 13.94% (23/165), biochemical disease in 60.00% (99/165), and structural disease in 26.06% (43/165). With a median follow-up of 58 months, 51 (30.91%), 34 (20.60%), 21 (12.73%), and 59 (35.76%) of the 165 patients achieved ER, IDR, BIR and SIR, respectively. Univariate analysis showed that N stage, TNM stage and suppressed Tg 6 months post RAT may be prognostic factors affecting RFS. Multivariate analysis showed that N1b stage [HR:2.749, P = 0.003] and II/III stage [HR:2.910, P = 0.001] were independent risk factors for RFS. Conclusion: The proportion of 165 postoperative PTC patients with unexplained elevated Tg developing structural disease within nearly 5 years was over 30%. Patients with N1b stage and higher TNM stage were more likely to develop structural disease.

Background: The synergistic effects of antiangiogenic inhibitor bevacizumab and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) therapy were encouraging in patients with EGFR-mutant advanced NSCLC, though some controversy remains. The specific subgroup of patients who might benefit most from the EGFR-TKI and bevacizumab combination therapy is yet to be determined.Methods: Randomized clinical trials (RCTs) that had compared the clinical efficacy of EGFR-TKI and bevacizumab combination therapy with EGFR-TKI monotherapy in treating EGFR-mutant advanced NSCLC patients published before 23 December 2022 were searched in the Cochrane, PubMed and Embase. We performed a meta-analysis for the overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events with a grade equal or more than 3 (grade≥3 TRAEs). Subgroup analyses of PFS and OS stratified by clinical characteristics and treatment were conducted.Results: We included 10 RCTs involving 1520 patients. Compared with EGFR-TKI monotherapy, addition of bevacizumab to EGFR-TKI resulted in a significantly higher PFS (hazard ratio (HR) = 0.74, 95% confidence interval (95% CI): 0.62–0.87)) and ORR (risk ratio (RR) = 1.07, 95% CI: 1.01–1.13). However, no significant difference in OS (HR = 0.96, 95% CI: 0.83–1.12) was noticed. Patients with EGFR-mutant advanced NSCLC receiving combination therapy showed PFS improvement regardless of gender (male or female), Eastern Cooperative Oncology Group performance status (0 or 1), baseline central nervous system (CNS) metastasis (presence or absence) and EGFR mutation type (19del or 21L858R). Subgroup analyses showed that, with the treatment of bevacizumab and EGFR-TKI, patients who ever smoked achieved significantly better OS and PFS benefits (HR = 0.68, 95% CI: 0.48–0.95; HR = 0.59, 95% CI: 0.46–0.74, respectively), and those aged

Abstract Background This study aimed to develop and validate an AI (artificial intelligence)-aid method in myocardial perfusion imaging (MPI) to differentiate ischemia in coronary artery disease. Methods We retrospectively selected 599 patients who had received gated-MPI protocol. Images were acquired using hybrid SPECT-CT systems. A training set was used to train and develop the neural network and a validation set was used to test the predictive ability of the neural network. We used a learning technique named “YOLO” to carry out the training process. We compared the predictive accuracy of AI with that of physician interpreters (beginner, inexperienced, and experienced interpreters). Results Training performance showed that the accuracy ranged from 66.20% to 94.64%, the recall rate ranged from 76.96% to 98.76%, and the average precision ranged from 80.17% to 98.15%. In the ROC analysis of the validation set, the sensitivity range was 88.9 ~ 93.8%, the specificity range was 93.0 ~ 97.6%, and the AUC range was 94.1 ~ 96.1%. In the comparison between AI and different interpreters, AI outperformed the other interpreters (most P-value

Abstract Drilling cuttings method is a commonly used method to detect the risk of rockburst, which has been widely recognized and applied in coal mines. However, in the current theoretical research on the relationship between drilling cuttings method and coal stress, it is generally considered that the mechanical parameters of coal at different positions of roadway are unchanged, and the influence of surrounding rock plastic zone and elastic zone is not considered. Therefore, according to the secondary distribution characteristics of roadway side stress, the theoretical calculation formula of drilling cuttings in the plastic zone and elastic zone of the roadway side is established in this paper. The example shows that the distribution of cuttings on the roadway side is obviously consistent with the abutment pressure. The cuttings in the plastic zone and the elastic zone are in linear and power function with the coal stress, respectively, and the cuttings in the plastic zone are greater than those in the elastic zone. With the increase of the hole diameter, the slope of the relationship curve between the drill‐cutting weight and stress gradually increases, and the response of the drill‐cutting weight with a large hole diameter to the change of coal stress is more obvious. The numerical simulation results show that the error of the theoretical calculation formula of the drilling cuttings method is less than 9%, which can meet the engineering application needs of estimating the drill‐cutting weight in coal and the stress of coal. Using the theoretical formula, the stress field in the leading area of the working face is measured, and the leading influence range and the accurate position of the high stress concentration area are determined, which provides more comprehensive stress information for the early warning of impact danger and pressure relief.

The current study aimed to provide a precise assessment of the genetic parameters associated with growth and white spot syndrome virus (WSSV) resistance traits in Pacific white shrimp (Litopenaeus vannamei). This was achieved through a controlled WSSV challenge assay and the analysis of phenotypic values of five traits: body weight (BW), overall length (OL), body length (BL), tail length (TL), and survival hour post-infection (HPI). The analysis included test data from a total of 1017 individuals belonging to 20 families, of which 293 individuals underwent whole-genome resequencing, resulting in 18,137,179 high-quality SNP loci being obtained. Three methods, including pedigree-based best linear unbiased prediction (pBLUP), genomic best linear unbiased prediction (GBLUP), and single-step genomic BLUP (ssGBLUP) were utilized. Compared to the pBLUP model, the heritability of growth-related traits obtained from GBLUP and ssGBLUP was lower, whereas the heritability of WSSV resistance was higher. Both the GBLUP and ssGBLUP models significantly enhanced prediction accuracy. Specifically, the GBLUP model improved the prediction accuracy of BW, OL, BL, TL, and HPI by 4.77%, 21.93%, 19.73%, 19.34%, and 63.44%, respectively. Similarly, the ssGBLUP model improved prediction accuracy by 10.07%, 25.44%, 25.72%, 19.34%, and 122.58%, respectively. The WSSV resistance trait demonstrated the most substantial enhancement using both genomic prediction models, followed by body size traits (e.g., OL, BL, and TL), with BW showing the least improvement. Furthermore, the choice of models minimally impacted the assessment of genetic and phenotypic correlations. Genetic correlations among growth traits ranged from 0.767 to 0.999 across models, indicating high levels of positive correlations. Genetic correlations between growth and WSSV resistance traits ranged from (−0.198) to (−0.019), indicating low levels of negative correlations. This study assured significant advantages of the GBLUP and ssGBLUP models over the pBLUP model in the genetic parameter estimation of growth and WSSV resistance in L. vannamei, providing a foundation for further breeding programs.

Dairy cows face metabolic challenges around the time of calving, leading to a negative energy balance and various postpartum health issues. Adipose tissue is crucial for cows during this period, as it regulates energy metabolism and supports immune function. Naringin, one of the main flavonoids in citrus fruit and their byproducts, is a potent antioxidant and anti-inflammatory phytoconstituent. The study aimed to evaluate the effects of supplemental naringin on performance, systemic inflammation, oxidative status, and adipose tissue metabolic status. A total of 36 multiparous Holstein cows (from ~21 d prepartum through 35 d postpartum) were provided a basal control (CON) diet or a CON diet containing naringin (NAR) at 30 g/d per cow. Supplemental NAR increased the yield of raw milk and milk protein, without affecting dry matter intake. Cows fed NAR showed significantly lower levels (p < 0.05) of serum non-esterified fatty acid (NEFA), C-reactive protein, IL-1β, IL-6, malonaldehyde, lipopolysaccharide (LPS), aspartate aminotransferase, and alanine aminotransferase, but increased (p < 0.05) glutathione peroxidase activity relative to those fed CON. Supplemental NAR increased (p < 0.05) adipose tissue adiponectin abundance, decreased inflammatory responses, and reduced oxidative stress. Lipidomic analysis showed that cows fed NAR had lower concentrations of ceramide species (p < 0.05) in the serum and adipose tissue than did the CON-fed cows. Adipose tissue proteomics showed that proteins related to lipolysis, ceramide biosynthesis, inflammation, and heat stress were downregulated (p < 0.05), while those related to glycerophospholipid biosynthesis and the extracellular matrix were upregulated (p < 0.05). Feeding NAR to cows may reduce the accumulation of ceramide by lowering serum levels of NEFA and LPS and increasing adiponectin expression, thereby decreasing inflammation and oxidative stress in adipose tissue, ultimately improving their systemic metabolic status. Including NAR in periparturient cows’ diets improves lactational performance, reduces excessive lipolysis in adipose tissue, and decreases systemic and adipose tissue inflammation and oxidative stress. Integrating lipidomic and proteomic data revealed that reduced ceramide and increased glycerophospholipids may alleviate metabolic dysregulations in adipose tissue, which in turn benefits systemic metabolic status.

Ketosis, especially its subclinical form, is frequently observed in high-yielding dairy cows and is linked to various diseases during the transition period. Although adipose tissue plays a significant role in the development of metabolic disorders, its exact impact on the emergence of subclinical ketosis (SCK) is still poorly understood. The objectives of this study were to characterize and compare the profiling of transcriptome and lipidome of blood and adipose tissue between SCK and healthy cows and investigate the potential correlation between metabolic disorders and lipid metabolism. We obtained blood and adipose tissue samples from healthy cows (CON, n = 8, β-hydroxybutyric acid concentration < 1.2 mmol/L) and subclinical ketotic cows (SCK, n = 8, β-hydroxybutyric acid concentration = 1.2–3.0 mmol/L) for analyzing biochemical parameters, transcriptome, and lipidome. We found that serum levels of nonesterified fatty acids, malonaldehyde, serum amyloid A protein, IL-1β, and IL-6 were higher in SCK cows than in CON cows. Levels of adiponectin and total antioxidant capacity were higher in serum and adipose tissue from SCK cows than in CON cows. The top enriched pathways in whole blood and adipose tissue were associated with immune and inflammatory responses and sphingolipid metabolism, respectively. The accumulation of ceramide and sphingomyelin in adipose tissue was paralleled by an increase in genes related to ceramide biosynthesis, lipolysis, and inflammation and a decrease in genes related to ceramide catabolism, lipogenesis, adiponectin production, and antioxidant enzyme systems. Increased ceramide concentrations in blood and adipose tissue correlated with reduced insulin sensitivity. The current results indicate that the lipid profile of blood and adipose tissue is altered with SCK and that certain ceramide species correlate with metabolic health. Our research suggests that disruptions in ceramide metabolism could be crucial in the progression of SCK, exacerbating conditions such as insulin resistance, increased lipolysis, inflammation, and oxidative stress, providing a potential biomarker of SCK and a novel target for nutritional manipulation and pharmacological therapy.

Abstract Background Sex disparities constitute a significant issue in hepatocellular carcinoma (HCC). However, the mechanism of gender dimorphism in HCC is still not completely understood. Methods 5‐Hydroxymethylcytosine (5hmC)‐Seal technology was utilised to detect the global 5hmC levels from four female and four male HCC samples. Methylation of XIST was detected by Sequenom MassARRAY methylation profiling between HCC tissues (T) and adjacent normal liver tissues (L). The role of Tet methylcytosine dioxygenase 2 (TET2) was investigated using diethylnitrosamine (DEN)‐administered Tet2−/− female mice, which regulated XIST in hepatocarcinogenesis. All statistical analyses were carried out by GraphPad Prism 9.0 and SPSS version 19.0 software. Results The results demonstrated that the numbers of 5hmC reads in the first exon of XIST from female HCC tissues (T) were remarkably lower than that in female adjacent normal liver tissues (L). Correspondingly, DNA methylation level of XIST first exon region was significantly increased in female T than in L. By contrast, no significant change was observed in male HCC patients. Compared to L, the expression of XIST in T was also significantly downregulated. Female patients with higher XIST in HCC had a higher overall survival (OS) and more extended recurrence‐free survival (RFS). Moreover, TET2 can interact with YY1 binding to the promoter region of XIST and maintain the hypomethylation state of XIST. In addition, DEN‐administered Tet2−/− mice developed more tumours than controls in female mice. Conclusions Our study provided that YY1 and TET2 could interact to form protein complexes binding to the promoter region of XIST, regulating the methylation level of XIST and then affecting the expression of XIST. This research will provide a new clue for studying sex disparities in hepatocarcinogenesis. Highlights XIST was significantly downregulated in HCC tissues and had gender disparity. Methylation levels in the XIST first exon were higher in female HCC tissues, but no significant change in male HCC patients. The TET2–YY1 complex regulate XIST expression in female hepatocytes. Other ways regulate XIST expression in male hepatocytes.

Purpose: To examine the use of multimodal data and multi-omics strategies for optic nerve disease screening. Methods: This was a single-center retrospective study. A deep learning model was created from fundus photography and infrared reflectance (IR) images of patients with diabetic optic neuropathy, glaucomatous optic neuropathy, and optic neuritis. Patients who were seen at the Ophthalmology Department of First Affiliated Hospital of Nanchang University in Jiangxi Province from November 2019 to April 2023 were included in this study. The data were analyzed in single and multimodal modes following the traditional omics, Resnet101, and fusion models. The accuracy and area-under-the-curve (AUC) of each model were compared. Results: A total of 312 images fundus and infrared fundus photographs were collected from 156 patients. When multi-modal data was used, the accuracy of the traditional omics mode, Resnet101, and fusion models with the training set were 0.97, 0.98, and 0.99, respectively. The accuracy of the same models with the test sets were 0.72, 0.87, and 0.88, respectively. We compared single- and multi-mode states by applying the data to the different groups in the learning model. In the traditional omics model, the macro-average AUCs of the features extracted from fundus photography, IR images, and multimodal data were 0.94, 0.90, and 0.96, respectively. When the same data were processed in the Resnet101 model, the scores were 0.97 equally. However, when multimodal data was utilized, the macro-average AUCs in the traditional omics, Resnet101, and fusion modesl were 0.96, 0.97, and 0.99, respectively. Conclusion: The deep learning model based on multimodal data and multi-omics strategies can improve the accuracy of screening and diagnosing diabetic optic neuropathy, glaucomatous optic neuropathy, and optic neuritis.

ABSTRACTDietary fiber plays a crucial role in maintaining gut and overall health. The objective of this study was to investigate whether different types of dietary fiber elicited specific changes in gut microbiota composition and the production of short-chain fatty acids. To test this, a longitudinal crossover study design was employed, in which healthy adult women consumed three distinct dietary fiber supplements: Inulin (fructo-oligosaccharide), Vitafiber (isomalto-oligosaccharide), and Fibremax (mixture of different fiber) during a one-week intervention period, followed by a 2-week washout period. A total of 15 g of soluble fiber was consumed daily for each supplement. Samples were collected before and after each intervention to analyze the composition of the gut microbiota by 16S rRNA sequencing and fecal levels of short-chain fatty acids measured using nuclear magnetic resonance. Phenotypic changes in peripheral blood mononuclear cells were studied in subsets of participants with higher SCFA levels post-intervention using spectral flow cytometry. The results revealed substantial stability and resilience of the overall gut bacterial community toward fiber-induced changes. However, each supplement had specific effects on gut bacterial alpha and beta diversity, SCFA production, and immune changes. Inulin consistently exerted the most pronounced effect across individuals and certain taxa were identified as potential indicators of SCFA production in response to inulin supplementation. This distinguishing feature was not observed for the other fiber supplements. Further large-scale studies are required to confirm these findings. Overall, our study implies that personalized dietary fiber intervention could be tailored to promote the growth of beneficial bacteria to maximize SCFA production and associated health benefits.

IntroductionAs a N6-methyladenosine reader protein, Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is a critical player in tumor progression and metastasis. However, its specific function in head and neck squamous carcinoma (HNSCC) has yet to be determined. The present study aimed to determine the role of IGF2BP2 in HNSCC.MethodsThe expression of IGF2BP2 in HNSCC was analyzed using The Cancer Genome Atlas (TCGA) dataset and detected in HNSCC tissues and cells, respectively. Gain- and loss- of function methods were employed to study the effects of IGF2BP2 on HNSCC cell proliferation and tumorigenesis in vitro and in vivo. MicroRNAs (miRNAs) regulating IGF2BP2 were predicted using online tools and confirmed experimentally.ResultsWe showed augmented IGF2BP2 expression in HNSCC, which correlated with poor clinical outcomes. Functional studies showed that IGF2BP2 promoted HNSCC cell proliferation by facilitating cell cycle progression while inhibiting apoptosis. We further demonstrated that IGF2BP2 could enhance HNSCC cell tumorigenesis in vivo. Mechanistically, our data revealed that miR-98-5p could directly target IGF2BP2. The interplay between IGF2BP2 and miR-98-5p is essential to drive the progression of HNSCC via the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (Akt) pathway signaling pathway.DiscussionThe current study revealed the oncogenic role of IGF2BP2 and provided insights into its potential mechanism in HNSCC tumorigenesis. Additionally, IGF2BP2 might represent a promising therapeutic target and serve as prognostic biomarker in patients with HNSCC.

Background: Whether the mechanism of thyroid papillary carcinoma (PTC) is the same in patients with a Hashimoto's thyroiditis (HT) background as compared with patients with a normal background remains a highly debated and controversial issue. In this study, we aimed to analyze the differences and similarities of the metabolic mechanism of PTC in normal and HT background, and to explore the relationship between HT and PTC. Methods: The ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF/MS) technology was used to analyze 61 PTC patient tissues (31 HT background and 30 normal tissue (NC) background). Potential biomarkers were screened from principal component analysis (PCA) to orthogonal partial least square (OPLS) discriminant analysis. HMDB was searched to identify potential differential metabolites and final metabolic pathway analysis was performed by MetaboAnalyst 5.0. We analyzed the differential metabolites diagnostic accuracy through receiver operating characteristic (ROC) curves analysis. Results: Seven different metabolites were screened from HT group and NC group, including arginine, glutamic acid, cysteine, citric acid, malic acid, uracil and taurine. Logistic regression model combined with ROC analysis of these 7 biomarkers had good discriminability for PTC (area under operating characteristic curve of HT group and NC group were 0.867 and 0.973, respectively). The HT group had specific metabolic pathways, including aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism. Conclusions: The metabolic profiles of the NC and HT groups had important similarities and differences in PTC. The correlation of PTC with HT may be related to aminoacyl-tRNA biosynthesis, serine and threonine metabolism.

Highlights 1. Cycloplegic drugs have effects on the ocular biological parameters of children at different ages. 2. The effects of different types of cycloplegic drugs were almost the same in children within the same age groups. 3. There were significant differences in the effects of different types of cycloplegic drugs on ocular biological parameters in children of different age groups.

The current study aimed to elucidate the effects of Sevoflurane on neuronal autophagy and ischemic brain injury by regulating miR-7a/ATG7 axis. The rat model of middle cerebral artery occlusion (MCAO) was established by thread embolization. The expression pattern of microRNA-7a (miR-7a) and autophagy-related gene 7 (ATG7) was subsequently determined in Sevoflurane-treated MCAO rats with their relation and effects on neuronal autophagy and ischemic brain injury further analyzed. Bioinformatics analysis confirmed that miR-7a could target to inhibit ATG7 in ischemic brain injury samples. Sevoflurane could alleviate ischemic brain injury in rats by reducing the level of neuronal autophagy-related factors. The expression of miR-7a was up-regulated and ATG7 was down-regulated in the brain tissues of MCAO rats after Sevoflurane treatment. ATG7 was found to induce neuronal autophagy during autophagy in the brain tissues of MCAO rats. In summary, Sevoflurane exerts protective effects on ischemic brain injury via inhibiting autophagy of neurons and microglia through the miR-7a-mediated downregulation of ATG7.

Applying blockchain to supply chain financing is an effective way to solve the problems of financing difficulties, high financing costs, and slow financing for small and medium-sized enterprises (SMZEs). Using evolutionary game theory, this study constructs a tripartite game model and analyzes the influence of blockchain technology on the evolutionary stability strategies for financial institutions (FIs), core enterprises (CEs), and SMZEs, in which the default losses of CEs and SMZEs are assumed to be dynamic. The results of this study are as follows: (1) When CEs and SMZESs’ default losses are lower than some critical value, they tend to break their promises. (2) When accounts receivable are greater than some critical value, CEs cannot repay on time because they can make a relatively large profits from delayed repayment, whereas SMZEs can be constrained to be trustworthy. Finally, the results using numerical simulation show that both relatively large default losses and enough large, trustworthy income sources can make CEs and SMZEs tend to keep their promises; in turn, CEs would be non-paying and the SMZEs tend to be trustworthy for relatively large accounts receivable. The results provide theoretical support for realizing healthy and sustainable development for supply chain finance.

Parkinson’s disease (PD) is a well-known neurodegenerative disorder characterized by the degeneration of dopaminergic neurons, and oxidative stress and neuroinflammation are also associated with the pathogenesis of PD. Mitochonic acid 5 (MA-5), an analogue of indole-3-acetic acid, exerts key protective roles in inhibiting apoptosis, oxidative stress and neuroinflammation in multiple diseases. However, whether MA-5 can be beneficial for PD remains unclear. Hence, the aim of this study was to investigate the neuroprotective role of MA-5 in PD. In the current study, MPTP-challenged mice were treated as the in vivo model, and the effect of MA-5 on the motor function, neuronal survival, oxidative stress, neuroinflammation and the underlying mechanisms involved with AMPK and autophagy were determined. We revealed that MA-5 obviously up-regulated the phosphorylation of AMPK and promoted the autophagy (indicated by the increased LC3II/LC3I, parkin, pink and decreased p62) in substantia nigra (SN), ameliorated the motor deficits, up-regulated the expression of TH, suppressed the inflammation (indicated by the decreased protein levels of interleukin (IL)-1b, IL-6, tumour necrosis factor a) in SN in MPTP-induced mice. However, these patterns were reversed after the treatment of Compound C, an inhibitor of AMPK; also, after the application of CSA, an inhibitor of autophagy, MA-5 cannot play against the neurotoxicity of MPTP in mice. These combined results suggest that MA-5 can protect against MPTP-induced neurotoxicity to ameliorate the impaired motor function, which may be modulated via activation of AMPK-induced autophagy.

The Pacific whiteleg shrimp (Penaeus vannamei) is a highly significant species in shrimp aquaculture. In the production of shrimp larvae, noticeable variations in the reproductive capacity among female individuals have been observed. Some females experience slow gonadal development, resulting in the inability to spawn, while others undergo multiple maturations and contribute to the majority of larval supply. Despite numerous studies that have been conducted on the regulatory mechanisms of ovarian development in shrimp, the factors contributing to the differences in reproductive capacity among females remain unclear. To elucidate the underlying mechanisms, this study examined the differences in the ovarian characteristics between high and low reproductive bulks at different maturity stages, focusing on the cellular and molecular levels. Transmission electron microscopy analysis revealed that the abundance of the endoplasmic reticulum, ribosomes, mitochondria, and mitochondrial cristae in oocytes of high reproductive bulk was significantly higher than that of the low reproductive bulk in the early stages of ovarian maturation (stages I and II). As the ovaries progressed to late-stage maturation (stages III and IV), differences in the internal structures of oocytes between females with different reproductive capacities gradually diminished. Transcriptome analysis identified differentially expressed genes (DEGs) related to the mitochondria between two groups, suggesting that energy production processes might play a crucial role in the observed variations in ovary development. The expression levels of the ETS homology factor (EHF) and PRDI-BF1 and RIZ homology domain containing 9 (PRDM9), which were significantly different between the two groups, were compared using qRT-PCR in individuals at different stages of ovarian maturation. The results showed a significantly higher expression of the EHF gene in the ovaries of high reproductive bulk at the II and IV maturity stages compared to the low reproductive bulk, while almost no expression was detected in the eyestalk tissue of the high reproductive bulk. The PRDM9 gene was exclusively expressed in ovarian tissue, with significantly higher expression in the ovaries of the high reproductive bulk at the four maturity stages compared to the low reproductive bulk. Fluorescence in situ hybridization further compared the expression patterns of EHF and PRDM9 in the ovaries of individuals with different fertility levels, with both genes showing stronger positive signals in the high reproductive bulk at the four ovarian stages. These findings not only contribute to our understanding of the regulatory mechanisms involved in shrimp ovarian development, but also provide valuable insights for the cultivation of new varieties aimed at improving shrimp fecundity.

Background: The multidose Sabin-strain inactivated poliovirus vaccine (sIPV) has the potential to significantly aid in the eradication of poliomyelitis, particularly in low- and middle-income countries. As part of a phase III clinical trial in which infants were given three doses of primary immunization at 2, 3, and 4 months of age, this study aimed to evaluate immune persistence following primary immunization, as well as the safety and immunogenicity of a booster of the 5-dose sIPV in infants aged 18 months. Methods: Infants aged 18 months were given one booster dose of 5-dose sIPV in stage one, which was open-label. Unblinding was performed for stage two after completing primary immunization, which was randomized, blinded, and controlled; infants aged 18 months in the test group I–III, IPV group, and single-dose sIPV group were given one booster dose of 5-dose sIPV, conventional IPV, and single-dose sIPV, respectively, in stage two. Results: This study included 1438 infants in the immune persistence and safety set and 1387 infants in the booster per-protocol set. Fourteen months after primary immunization, the seropositivity rates (≥1:8) for types 1–3 were 100%, 99.88%, and 99.53% in the 5-dose sIPV groups; 100%, 98.97%, and 97.23% in the IPV group; and 99.66%, 100%, and 99.66% in the single-dose sIPV group. A total of 30 days after booster immunization, the seropositivity rates (≥1:8) of 3 serotypes in all the groups reached 100%. The geometric mean titers of neutralizing antibodies for types 1–3 in the 5-dose sIPV group were 9962.89, 10273, and 7870.21, with geometric mean increases of 15.76, 33.15, and 24.5, compared to the pre-booster level. The overall incidence of adverse reactions was 8.97%, with fever being the most common, observed at rates of 7.1%, 5.52%, and 7.96% in the 5-dose sIPV, IPV, and single-dose groups, respectively (p = 0.4845). Conclusions: The 5-dose sIPV has shown promising immune persistence and robust immune response following a booster immunization, coupled with an acceptable safety profile.

Abstract Background Traumatic impacts to the articular joint surface are known to lead to cartilage degeneration, as in post-traumatic osteoarthritis (PTOA). Limited progress in the development of disease-modifying OA drugs (DMOADs) may be due to insufficient mechanistic understanding of human disease onset/progression and insufficient in vitro models for disease and therapeutic modeling. In this study, biomimetic hydrogels laden with adult human mesenchymal stromal cells (MSC) are used to examine the effects of traumatic impacts as a model of PTOA. We hypothesize that MSC-based, engineered cartilage models will respond to traumatic impacts in a manner congruent with early PTOA pathogenesis observed in animal models. Methods Engineered cartilage constructs were fabricated by encapsulating adult human bone marrow-derived mesenchymal stem cells in a photocross-linkable, biomimetic hydrogel of 15% methacrylated gelatin and promoting chondrogenic differentiation for 28 days in a defined medium and TGF-β3. Constructs were subjected to traumatic impacts with different strains or 10 ng/ml IL-1β, as a common comparative method of modeling OA. Cell viability and metabolism, elastic modulus, gene expression, matrix protein production and activation of catabolic enzymes were assessed. Results Cell viability staining showed that traumatic impacts of 30% strain caused an appropriate level of cell death in engineered cartilage constructs. Gene expression and histo/immunohistochemical analyses revealed an acute decrease in anabolic activities, such as COL2 and ACAN expression, and a rapid increase in catabolic enzyme expression, e.g., MMP13, and inflammatory modulators, e.g., COX2. Safranin O staining and GAG assays together revealed a transient decrease in matrix production 24 h after trauma that recovered within 7 days. The decrease in elastic modulus of engineered cartilage constructs was coincident with GAG loss and mediated by the encapsulated cells. The acute and transient changes observed after traumatic impacts contrasted with progressive changes observed using continual IL-1β treatment. Conclusions Traumatic impacts delivered to engineered cartilage constructs induced PTOA-like changes in the encapsulated cells. While IL-1b may be appropriate in modeling OA pathogenesis, the results of this study indicate it may not be appropriate in understanding the etiology of PTOA. The development of a more physiological in vitro PTOA model may contribute to the more rapid development of DMOADs.

Secretory IgA plays vital roles interfacing between the host immune system and the resident microbiota at the mucosal surface. Here the authors explore the effect of dietary protein on the production of secretory IgA, driven by the production of extracellular vesicles by the intestinal microbiota.

To explore the performance differences among offspring obtained by the intra- and inter-strain crosses, strain A with outstanding WSSV resistance and strain B with outstanding growth of Litopenaeus vannamei were used to construct four experimental groups in a complete diallel cross. 27 growth-related phenotypic traits and WSSV resistance represented by the surviving hours post-infection were obtained via the growth and the virus challenge test. Mixed linear model along with physical pedigree were utilized to calculate the least squares means, correlations, heritability and heterosis. The results showed that crossbreeding can realize character complementation of advantage strain. The performance of WSSV resistance was ranked AA> BA> AB> BB, and the reciprocal crosses performed significantly better than intra-strain group BB. Most growth-related traits in two reciprocal cross groups were also significantly better than those in AA group. Comparisons between the two reciprocal crosses showed that BA cross was better than AB in terms of WSSV resistance and growth. Heterosis of WSSV resistance in BA cross was 5.74∼10.18% greater than that in AB, meanwhile the absolute weight gain rate of BA cross was 4.83% higher than that of AB. The heritability estimates of body length and body weight were 0.0278 and 0.339, both of which reached medium level. The genetic and phenotypic correlations among growth-related traits were from 0.36 to 0.99 and 0.32 to 0.99, respectively. In term of WSSV resistance, the heritability estimate was 0.135 ± 0.082. The genetic and phenotypic correlations between WSSV resistance and growth-related traits were from − 0.034 to − 0.573 and − 0.001 to − 0.202, respectively. The results showed that hybrid offspring obtained by crossing female parents with outstanding WSSV resistance and male parents with outstanding growth culminated in a superior heterosis in both traits. This study provides basic reference data for L. vannamei breeding of new strains that are disease resistant and fast-growing.

Abstract The incidence of post-operative cognitive dysfunction (POCD) remains a relatively prevalent complication in the elderly after surgery, especially in those receiving sevoflurane (Sevo) anesthesia. microRNA (miR)−140-3p has been demonstrated to orchestrate neuroinflammation and neuron apoptosis. However, the role of miR-140-3p in POCD remains largely unknown. In this context, this research was designed to explore whether miR-140-3p mediated Sevo inhalation-induced POCD in rats. A POCD rat model was established by Sevo inhalation, and a Sevo cell model was constructed in primary hippocampal neurons isolated from rats, followed by detection of miR-140-30 and HTR2A expression. Then, gain- and loss-of-function assays were implemented in rats and neurons. In rats, the cognitive function was evaluated by Water maze test and step-through test, and neuron apoptosis by TUNEL staining. In neurons, cell viability, apoptosis, and pyroptosis-related factors were tested by MTT, flow cytometry, and Western blot analysis respectively. Interaction between HTR2A and DNMT1 was assessed by MSP, and ChIP assay, and interaction between miR-140-3p and DNMT1 by dual-luciferase reporter assay, RIP and RNA pull-down. HTR2A and miR-140-3p were downregulated in POCD rats and Sevo-treated hippocampal neurons. Mechanistically, miR-140-3p negatively targeted DNMT1 to decrease HTR2A promoter methylation, thus upregulation HTR2A to activate ERK/Nrf2 pathway. miR-140-3p or HTR2A overexpression or activation of ERK/Nrf2 pathway elevated neuron viability and diminished their apoptosis and pyroptosis while alleviating Sevo-induced POCD in rats. Collectively, miR-140-3p might repress neuron pyroptosis to alleviate Sevo inhalation-induced POCD in rats via DNMT1/HTR2A/ERK/Nrf2 axis.

Abstract Exosomes are nanoscale monolayer membrane vesicles that are actively endogenously secreted by mammalian cells. Currently, multifunctional exosomes with tumor-targeted imaging and therapeutic potential have aroused widespread interest in cancer research. Herein, we developed a multifunctional HEK-293T exosome-based targeted delivery platform by engineering HEK-293T cells to express a well-characterized exosomal membrane protein (Lamp2b) fused to the αv integrin-specific iRGD peptide and tyrosine fragments. This platform was loaded with doxorubicin (Dox) and labeled with radioiodine-131 (131I) using the chloramine-T method. iRGD exosomes showed highly efficient targeting and Dox delivery to integrin αvβ3-positive anaplastic thyroid carcinoma (ATC) cells as demonstrated by confocal imaging and flow cytometry in vitro and an excellent tumor-targeting capacity confirmed by single-photon emission computed tomography-computed tomography after labeling with 131I in vivo. In addition, intravenous injection of this vehicle delivered Dox and 131I specifically to tumor tissues, leading to significant tumor growth inhibition in an 8505C xenograft mouse model, while showing biosafety and no side effects. These as-developed multifunctional exosomes (denoted as Dox@iRGD-Exos-131I) provide novel insight into the current treatment of ATC and hold great potential for improving therapeutic efficacy against a wide range of integrin αvβ3-overexpressing tumors. Graphical Abstract

The transportation of seawater on a grand scale via an ultra-large cold-water pipe situated within the context of ocean thermal energy conversion (OTEC) floating installations inherently presents challenges associated with instability and potential malfunction in the face of demanding operational circumstances. This study endeavors to augment the stability and security of cold-water pipe (CWP) operations by scrutinizing their vibrational attributes across diverse boundary configurations. Initially, we invoke Euler–Bernoulli beam theory to forge the analytical framework and proffer a semi-analytical resolution by utilizing the generalized integral transform technique (GITT). Subsequently, we authenticate the convergence and precision of our proposed approach through comparative analysis with extant theories. Our findings underscore the conspicuous influence of boundary conditions on the convergence of transverse displacement. The influence of internal flow on the transverse displacement and the natural frequency manifests substantial variability under different boundary conditions. Significantly, an escalation in the internal flow velocity triggers a concomitant reduction in the natural frequency, ultimately culminating in instability once the critical velocity threshold is reached. Additionally, the reliance of the transverse displacement and the natural frequency on the clump weight at the bottom is markedly pronounced. Our discoveries propose that pipe stability can be ameliorated by adjusting the clump weight at the bottom. Furthermore, the novel insights obtained through our proposed approach can significantly aid in the early-stage design and analysis of CWP.

NAFLD is a series of liver disorders, and it has become the most prevalent hepatic disease to date. However, there are no approved and effective pharmaceuticals for NAFLD owing to a poor understanding of its pathological mechanisms. While emerging studies have demonstrated that m6A modification is highly associated with NAFLD. In this review, we summarize the general profile of NAFLD and m6A modification, and the role of m6A regulators including erasers, writers, and readers in NAFLD. Finally, we also highlight the clinical significance of m6A in NAFLD.

The successful operation of a large-diameter cold water pipeline installation is crucial for harnessing the potential of ocean thermal energy conversion. However, there is a shortage of research focused on mechanical performance analysis during installation. This study establishes a pipeline response analysis model based on a nonlinear beam theory to elucidate the underlying mechanical behaviour. Employing the method of singular perturbation, the general solution for the exterior region of the pipeline, the solution at the boundary layer, and the valid solution across the entire domain are derived. A comparison with numerical solutions is conducted to validate the accuracy and effectiveness of the theoretical model. Based on the theoretical analysis, the influence of installation depth and pipeline curvature on the pipeline’s shape, tension, curvature, and stress is discussed. The results indicate that increasing the installation depth leads to intensified pipeline bending and significant deformation, reaching a maximum bending moment of 3.92 MN∙m at a distance of 50~100 m from the bottom of the pipeline. The results also show that, as the pipeline’s arc length increases from 0 to 100 m, the bending curvature, Von Mises stress, and bending stress exhibit a trend of initial growth followed by a decline, peaking at 7.45 MPa, and 6.83 Mpa, respectively, while the actual tension and axial tension decrease initially and then increase, reaching −0.17 MN and −0.17 MPa, respectively, at the maximum arc length. The findings of this study provide valuable insights for practical cold-water pipe installation and laying.