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Abstract Glioblastoma (GBM) presents significant challenges due to its invasive nature and genetic heterogeneity. In this study, we investigated the impact of Small VCP/P97-Interacting Protein (SVIP) on GBM progression. Our results revealed elevated expression of Insulin-like Growth Factor Binding Protein 2 (IGFBP-2) and STIP1 homology and U-box containing protein 1 (STUB1), coupled with reduced SVIP levels in GBM samples. Notably, high IGFBP-2 expression correlated with poor prognosis. Mechanistically, SVIP competitively inhibited STUB1, selectively binding to VCP/p97, thereby reducing PTEN degradation. This SVIP-mediated regulation exerted influence on the PTEN/PI3K/AKT/mTOR pathway, leading to the suppression of GBM progression. Co-localization experiments demonstrated that SVIP hindered PTEN ubiquitination and degradation by outcompeting STUB1 for VCP/p97 binding. Moreover, SVIP overexpression resulted in reduced activation of AKT/mTOR signaling and facilitated autophagy. In vivo experiments using a GBM xenograft model substantiated the tumor-suppressive effects of SVIP, evident by suppressed tumor growth, decreased IGFBP-2 expression, and improved survival rates. Collectively, our findings underscore the functional significance of SVIP in GBM progression. By inhibiting STUB1 and stabilizing PTEN, SVIP modulates the expression of IGFBP-2 and attenuates the activation of the PI3K/AKT/mTOR pathway, thereby emerging as a promising therapeutic target for GBM treatment.

Abstract Background In assessing the clinical utility and safety of 3.0 T intraoperative magnetic resonance imaging (iMRI) combined with multimodality functional MRI (fMRI) guidance in the resection of functional area gliomas, we conducted a study. Method Among 120 patients with newly diagnosed functional area gliomas who underwent surgical treatment, 60 were included in each group: the integrated group with iMRI and fMRI and the conventional navigation group. Between-group comparisons were made for the extent of resection (EOR), preoperative and postoperative activities of daily living based on the Karnofsky performance status, surgery duration, and postoperative intracranial infection rate. Results Compared to the conventional navigation group, the integrated navigation group with iMRI and fMRI exhibited significant improvements in tumor resection (complete resection rate: 85.0% vs. 60.0%, P = 0.006) and postoperative life self-care ability scores (Karnofsky score) (median ± interquartile range: 90 ± 25 vs. 80 ± 30, P = 0.013). Additionally, although the integrated navigation group with iMRI and fMRI required significantly longer surgeries than the conventional navigation group (mean ± standard deviation: 411.42 ± 126.4 min vs. 295.97 ± 96.48 min, P

Abstract Brain metastases (BMs) and high-grade gliomas (HGGs) are the most common and aggressive types of malignant brain tumors in adults, with often poor prognosis and short survival. As their clinical symptoms and image appearances on conventional magnetic resonance imaging (MRI) can be astonishingly similar, their accurate differentiation based solely on clinical and radiological information can be very challenging, particularly for “cancer of unknown primary”, where no systemic malignancy is known or found. Non-invasive multiparametric MRI and radiomics offer the potential to identify these distinct biological properties, aiding in the characterization and differentiation of HGGs and BMs. However, there is a scarcity of publicly available multi-origin brain tumor imaging data for tumor characterization. In this paper, we introduce a multi-center, multi-origin brain tumor MRI (MOTUM) imaging dataset obtained from 67 patients: 29 with high-grade gliomas, 20 with lung metastases, 10 with breast metastases, 2 with gastric metastasis, 4 with ovarian metastasis, and 2 with melanoma metastasis. This dataset includes anonymized DICOM files alongside processed FLAIR, T1-weighted, contrast-enhanced T1-weighted, T2-weighted sequences images, segmentation masks of two tumor regions, and clinical data. Our data-sharing initiative is to support the benchmarking of automated tumor segmentation, multi-modal machine learning, and disease differentiation of multi-origin brain tumors in a multi-center setting.

Abstract Glioma is the most common malignant tumor of the central nervous system, with EZH2 playing a crucial regulatory role. This study further explores the abnormal expression of EZH2 and its mechanisms in regulating glioma progression. Additionally, it was found that IHMT-337 can potentially be a therapeutic agent for glioma. The prognosis, expression, and localization of EZH2 were determined using bioinformatics, IHC staining, Western blot (WB) analysis, and immunofluorescence (IF) localization. The effects of EZH2 on cell function were assessed using CCK-8 assays, Transwell assays, and wound healing assays. Public databases and RT-qPCR were utilized to identify downstream targets. The mechanisms regulating these downstream targets were elucidated using MS-PCR and WB analysis. The efficacy of IHMT-337 was demonstrated through IC50 measurements, WB analysis, and RT-qPCR. The effects of IHMT-337 on glioma cells in vitro were evaluated using Transwell assays, EdU incorporation assays, and flow cytometry. The potential of IHMT-337 as a treatment for glioma was assessed using a blood–brain barrier (BBB) model and an orthotopic glioma model. Our research confirms significantly elevated EZH2 expression in gliomas, correlating with patient prognosis. EZH2 facilitates glioma proliferation, migration, and invasion alongside promoting SLC12A5 DNA methylation. By regulating SLC12A5 expression, EZH2 activates the WNK1-OSR1-NKCC1 pathway, enhancing its interaction with ERM to promote glioma migration. IHMT-337 targets EZH2 in vitro to inhibit WNK1 activation, thereby suppressing glioma cell migration. Additionally, it inhibits cell proliferation and arrests the cell cycle. IHMT-337 has the potential to cross the BBB and has successfully inhibited glioma progression in vivo. This study expands our understanding of the EZH2-SLC12A5 axis in gliomas, laying a new foundation for the clinical translation of IHMT-337 and offering new insights for precision glioma therapy.

Abstract Background Early detection of patients at risk of falling is crucial. This study was designed to develop and internally validate a novel risk score to classify patients at risk of falls. Methods A total of 334 older people from a fall clinic in a medical center were selected. Least absolute shrinkage and selection operator (LASSO) regression was used to minimize the potential concatenation of variables measured from the same patient and the overfitting of variables. A logistic regression model for 1-year fall prediction was developed for the entire dataset using newly identified relevant variables. Model performance was evaluated using the bootstrap method, which included measures of overall predictive performance, discrimination, and calibration. To streamline the assessment process, a scoring system for predicting 1-year fall risk was created. Results We developed a new model for predicting 1-year falls, which included the FRQ-Q1, FRQ-Q3, and single-leg standing time (left foot). After internal validation, the model showed good discrimination (C statistic, 0.803 [95% CI 0.749–0.857]) and overall accuracy (Brier score, 0.146). Compared to another model that used the total FRQ score instead, the new model showed better continuous net reclassification improvement (NRI) [0.468 (0.314–0.622), P

Abstract As the largest transporter family impacting on tumor genesis and development, the prognostic value of solute carrier (SLC) members has not been elucidated in colorectal cancer (CRC). We aimed to identify a prognostic signature from the SLC members and comprehensively analyze their roles in CRC. Firstly, we downloaded transcriptome data and clinical information of CRC samples from GEO (GSE39582) and TCGA as training and testing dataset, respectively. We extracted the expression matrix of SLC genes and established a prognostic model by univariate and multivariate Cox regression. Afterwards, the low-risk and high-risk group were identified. Then, the differences of prognosis traits, transcriptome features, clinical characteristics, immune infiltration and drug sensitivity between the two groups were explored. Furthermore, molecular subtyping was also implemented by non-negative matrix factorization (NMF). Finally, we studied the expression of the screened SLC genes in CRC tumor tissues and normal tissues as well as investigated the role of SLC12A2 by loss of function and gain of function. As a result, we developed a prognostic risk model based on the screened 6-SLC genes (SLC39A8, SLC2A3, SLC39A13, SLC35B1, SLC4A3, SLC12A2). Both in the training and testing sets, CRC patients in the high-risk group had the poorer prognosis and were in the more advanced pathological stage. What’s more, the high-risk group were enriched with CRC progression signatures and immune infiltration. Two groups showed different drug sensitivity. On the other hand, two distinct subclasses (C1 and C2) were identified based on the 6 SLC genes. CRC patients in the high-risk group and C1 subtype had a worse prognosis. Furthermore, we found and validated that SLC12A2 was steadily upregulated in CRC. A loss-of-function study showed that knockdown of SLC12A2 expression restrained proliferation and stemness of CRC cells while a gain-of-function study showed the contrary results. Hence, we provided a 6-SLC gene signature for prognosis prediction of CRC patients. At the same time, we identified that SLC12A2 could promote tumor progression in CRC, which may serve as a potential therapeutic target.

Abstract Background Chickens are one of the most widely farmed animals worldwide and play a crucial role in meat and egg production. Gut microbiota is essential for chickens’ health, disease, growth, and egg production. However, native chickens such as Jianghan chickens have better meat and egg production quality than centralized chickens, their intestinal microbial diversity is richer, and the potential gut microbial resources may bring health benefits to the host. Results The bacterial species composition in the gut microbiota of Jianghan chickens is similar to that of other chicken breeds, with Phocaeicola and Bacteroides being the most abundant bacterial genera. The LEfSe analysis revealed significant differences in species composition and functional profiles between samples from Jingzhou and the other three groups. Functional annotation indicated that the gut microbiota of Jianghan chickens were dominated by metabolic genes, with the highest number of genes related to carbohydrate metabolism. Several antibiotic resistance genes (ARGs) were found, and the composition of ARGs was similar to that of factory-farmed chickens, suggesting that antibiotics were widely present in the gut microbiota of Jianghan chickens. The resistance genes of Jianghan chickens are mainly carried by microorganisms of the Bacteroidota and Bacillota phylum. In addition, more than 829 isolates were selected from the microbiota of Jianghan chickens. Following three rounds of acid and bile tolerance experiments performed on all the isolated strains, it was determined that six strains of Pediococcus acidilactici exhibited consistent tolerance. Further experiments confirmed that three of these strains (A4, B9, and C2) held substantial probiotic potential, with P. acidilactici B9 displaying the highest probiotic potential. Conclusions This study elucidates the composition of the intestinal microbiota and functional gene repertoire in Jianghan chickens. Despite the absence of antibiotic supplementation, the intestinal microbial community of Jianghan chickens still demonstrates a profile of antibiotic resistance genes similar to that of intensively reared chickens, suggesting resistance genes are prevalent in free-ranging poultry. Moreover, Jianghan and intensively reared chickens host major resistance genes differently, an aspect seldom explored between free-range and pastured chickens. Furthermore, among the 829 isolates, three strains of P. acidilatici exhibited strong probiotic potential. These findings provide insights into the unique gut microbiota of Jianghan chickens and highlight potential probiotic strains offering benefits to the host. Video Abstract

Summary: The extracellular superoxide dismutases (ecSODs) secreted by Microplitis bicoloratus reduce the reactive oxygen species (ROS) stimulated by the Microplitis bicoloratus bracovirus. Here, we demonstrate that the bacterial transferase hexapeptide (hexapep) motif and bacterial-immunoglobulin-like (BIg-like) domain of ecSODs bind to the cell membrane and transiently open hemichannels, facilitating ROS reductions. RNAi-mediated ecSOD silencing in vivo elevated ROS in host hemocytes, impairing parasitoid larva development. In vitro, the ecSOD-monopolymer needed to be membrane bound to open hemichannels. Furthermore, the hexapep motif in the beta-sandwich of ecSOD49 and ecSOD58, and BIg-like domain in the signal peptides of ecSOD67 were required for cell membrane binding. Hexapep motif and BIg-like domain deletions induced ecSODs loss of adhesion and ROS reduction failure. The hexapep motif and BIg-like domain mediated ecSOD binding via upregulating innexins and stabilizing the opened hemichannels. Our findings reveal a mechanism through which ecSOD reduces ROS, which may aid in developing anti-redox therapy.

Yeasts are pivotal brewing microbes that are associated with the flavor and quality of Chinese baijiu, yet research on dominant yeasts in strong-flavor baijiu brewing remains limited. In this study, Saccharomyces cerevisiae, Pichia kudriavzevii, and Kazachstania bulderi were identified as predominated yeasts in strong-flavor baijiu. Each strain showed distinct characteristics in ethanol resistance, thermal tolerance, and lactic acid tolerance, severally. S. cerevisiae FJ1-2 excelled in ethanol and ethyl ester production, P. kudriavzevii FJ1-1 in ethyl acetate, and K. bulderi FJ1-3 in lactic acid generation. Subsequently, the reinforced Fuqu of each yeast were severally prepared for application in baijiu brewing to verify their functions. Results revealed that the relative abundance of fortified yeast in each group rose. Pichia, Kazachstania, and Saccharomyces emerged as the core microbe for each group, respectively, by co-occurrence network analysis, influencing the microbiota to regulate flavor substances. In short, P. kudriavzevii FJ1-1 enhanced ethyl acetate. K. bulderi FJ1-3 improved ethyl caproate production and decreased levels of ethyl acetate and higher alcohols by modulating yeast community between Pichia and Saccharomyces. This is a systematic endeavor to study the functions of yeasts of strong-flavor baijiu, providing a solid basis for improving baijiu quality.

Biochemical analyzers are vital instruments that utilize the principle of photoelectric colorimetry to quantify a specific chemical composition in body fluids. This analysis provides critical data for the diagnosis, treatment, prognosis, and overall health status of various diseases in clinical practice. However, the performance of a biochemical analyzer can vary significantly between different brands or over time within the same brand. Therefore, it is imperative to regularly assess the performance of the analyzer to ensure consistent results for longitudinal studies and to maintain day-to-day data consistency. Additionally, when multiple analyzers are utilized, it is necessary to evaluate the performance of each instrument to ensure accurate results across multiple platforms. In this study, we developed and verified an experimental evaluation scheme for the analytical performance of the instrument, chemometrics for biochemical analyzers, utilizing national reference materials and patient sera as the experimental subjects. We evaluated the performance of the optical system, temperature control system, sample-adding system, and detection system to confirm the feasibility of this scheme. We also compared the analytical performance of different brands of biochemical analyzers for routine biochemical tests, such as liver function, kidney function, ion, blood lipids, blood glucose, and myocardial enzyme spectrum. Using the AU 5400 as a control and the ADVIA 2400 as the comparison system, the relative variation in inter-instrument comparison data was found to be acceptable at the clinical medicine decision level. In conclusion, the performance of a biochemical analyzer can vary significantly between different brands or over time within the same brand. Regular evaluations are necessary to ensure accurate and consistent results across different analyzers. This study provides a feasible scheme for evaluating the analytical performance of biochemical analyzers that can be used to ensure the accuracy and consistency of the results of different brands of automatic chemical analyzers in the laboratory.

Abstract Background T cell-redirecting bispecific antibodies establish a connection between endogenous T cells and tumor cells, activating T cells function to eliminate tumor cells without ex vivo genetic alteration or manipulation. Here, we developed a novel dual-specific antibody (DuAb) and an enhanced DuAb (EDuAb) with different stimulation signal to activate T cells, and evaluated their impact on the treatment of acute lymphoblastic leukemia (ALL). Methods The expression plasmids of the DuAb and EDuAb containing CD80 molecule were constructed by cloning heavy chain and light chain variable fragments from anti-human CD19 (HI19a) and CD3 (HIT3a) monoclonal antibody hybridomas, respectively. The activation and the anti-tumor efficacy of human T cells mediated by DuAb and EDuAb were evaluated in vitro. B-cell ALL xenograft NSG mouse model was established to investigate the therapeutic effect in vivo. Results EDuAb promoted the optimal expansion of primary human T cells with low expression of inhibitory markers in vitro than DuAb did. Both DuAb and EDuAb showed a similar capability in inducing healthy donor T cells to specifically eliminate B-ALL cell lines and primary blasts from patients. The similar ability was also observed in the patient-derived T cells. In vivo study showed that both DuAb and EDuAb significantly alleviated tumor burden and extended survival of B-ALL xenograft NSG mice. The median survival of PBS, DuAb and EDuAb treatment groups were 27, 38 and 45 days, respectively. The phenotype of T cells and cytokine release in peripheral blood (PB) of B-ALL xenograft NSG mice on day 24 were analyzed as well. The results showed that the proportion of CD8+ T cells and cytokine levels, including IL-2, IFN-γ and TNF-α, were higher in the EDuAb group than that of DuAb. Moreover, both DuAb and EDuAb significantly decreased the residual leukemia cells in PB of B-ALL xenograft NSG mice. Conclusions Both DuAb and EDuAb showed great potential as novel treatments for B-ALL in clinical applications. However, compared to DuAb, EDuAb showed a significant advantage in promoting the proliferation and survival of T cells. Furthermore, EDuAb showed a better promising effect on eliminating tumor cells and extending survival in vivo, which provides new insights for the development of new multi-specific antibodies.

Abstract Aim To evaluate the effectiveness of massage on treating feeding intolerance (FI). Design A randomized, controlled, prospective clinical trial. Methods A total of 104 preterm infants whose gestational age between 28 and 34 weeks and birth weight between 1000 and 2000 g with diagnosis of FI were recruited. Participants were stratified by birth weight (1000–1499 g or 1500–2000 g) and randomized to either the intervention group, who will receive 7 days of massage, or the control group. The primary outcome is the time to reach full enteral nutrition. Secondary outcomes include duration of FI, change of body index, length of hospitalization, change of gastric residual volume, abdomen circumference and defecation measurement before and after 7 days of intervention. Results Results of this study, which includes index on FI and physical development, have the potential to provide evidence that massage will alleviate symptoms of FI, and contribute to the long‐term positive outcome of preterm infants.

Introduction Frailty has been currently considered as a multidimensional concept, including physical, cognitive and social frailty. Frailty has also been associated with a range of adverse events, which might increase the risks of disability, falls, fractures, delirium and death. Increasing evidence has shown that multicomponent exercise training can improve physical and cognitive function, delay or reverse frailty. However, there is still a lack of exercise intervention programmes for the frail older adults in China. This trial aims to investigate the effects of the muscle-building and antifrailty exercise combined with Baduanjin on the physical function of frail older adults, as well as the effectiveness and safety of the intervention.Methods and analysis This study is a prospective randomised controlled trial. A total of 192 patients, aged 70 years or older, who are diagnosed as prefrailty or frailty based on the Fried criteria will be included. Prior written and informed consent will be obtained from every subject. These subjects will be randomly assigned to the exercise intervention group (n=96) and the control group (n=96). The exercise intervention group will undergo different exercise programmes for different levels of physical function. They will perform the muscle-building and antifrailty exercise three times per week for 30–60 min for 24 weeks. The control group will implement health education on frailty and maintain the old lifestyle without any intervention.The primary outcomes include the change in frailty and functional capacity, assessed according to the Fried Scale and the Short Physical Performance Battery. Secondary outcomes include the changes in body composition, Activities of daily living, Mini-Mental State Examination, The Geriatric Depression Scale-15 and the haematological indicators.Ethics statement The study has been approved by the Medical Ethics Committee of the PLA General Hospital (approval no.: S2022-600-02).Trial registration number ChiCTR2300070535.

Parasitoid wasps control pests via a precise attack leading to the death of the pest. However, parasitoid larvae exhibit self-protection strategies against bracovirus-induced reactive oxygen species impairment. This has a detrimental effect on pest control. Here, we report a strategy for simulating Microplitis bicoloratus bracovirus using Mix-T dsRNA targeting 14 genes associated with transcription, translation, cell–cell communication, and humoral signaling pathways in the host, and from wasp extracellular superoxide dismutases. We implemented either one-time feeding to the younger instar larvae or spraying once on the corn leaves, to effectively control the invading pest Spodoptera frugiperda. This highlights the conserved principle of “biological pest control,” as elucidated by the triple interaction of parasitoid-bracovirus-host in a cooperation strategy of bracovirus against its pest host.

Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), which is still the leading cause of mortality from a single infectious disease worldwide. The development of novel anti-TB drugs and vaccines is severely hampered by the complicated and time-consuming genetic manipulation techniques for M. tuberculosis. Here, we harnessed an endogenous type III-A CRISPR/Cas10 system of M. tuberculosis for efficient gene editing and RNA interference (RNAi). This simple and easy method only needs to transform a single mini-CRISPR array plasmid, thus avoiding the introduction of exogenous protein and minimizing proteotoxicity. We demonstrated that M. tuberculosis genes can be efficiently and specifically knocked in/out by this system as confirmed by DNA high-throughput sequencing. This system was further applied to single- and multiple-gene RNAi. Moreover, we successfully performed genome-wide RNAi screening to identify M. tuberculosis genes regulating in vitro and intracellular growth. This system can be extensively used for exploring the functional genomics of M. tuberculosis and facilitate the development of novel anti-TB drugs and vaccines.

Abstract Background Cottonseed meal (CSM) is the main by-product of the cottonseed oil extraction process with high protein content, which is an important protein source for feed industry. However, CSM contains free gossypol (FG), a toxic substance that is detrimental to animal health and greatly limits its application. Microbial fermentation is currently considered to be one of the most effective methods to reduce FG and other anti-nutritional factors in CSM. Previously, yeast and bacteria species are used for degradation of FG in CSM, but showing less detoxification efficiency. Bacillus coagulans combines the properties of both lactic acid bacteria and Bacillus, producing both lactic acid and spores, and is considered a potential probiotic. In this study, we aimed to evaluate and optimize the effect of the solid-state fermentation process using a Bacillus coagulans to gossypol removal contained cottonseed meal. Results 36 B. coagulans strains were isolated and found to have the ability to remove free gossypol. Through the evaluation of strains and optimization of fermentation conditions including fermentation temperature, ratio of material to water, inoculation amount, fermentation time and pH, we have established a solid-state fermentation process using a Bacillus coagulans strain S17 on CSM substrate with 1:1 of the material-to-water ratio, 15% (v/w) seed inoculation, 2% expanded corn flour, 1% bran, and 0.3%-0.8% metal irons at 40 °C for 52 h. After fermentation, the FG content in CSM was reduced from 923.80 to 167.90 mg/kg with 81.83% detoxification efficiency. Meanwhile, the crude protein content in CSM increased from 47.98 to 52.82%, and importantly, the spore concentration of strain S17 reached 1.68 × 1010 CFU/g dry material. Conclusion The study showed that B. coagulans have the potential strong ability to degrade free gossypol through cottonseed meal fermentation. This study presents a feasible process for improving the resource utilization rate and nutritional value of CSM via solid-state fermentation through B. coagulans S17.

Abstract Background At present, there are several diagnostic criteria of sarcopenia were used in China, and the diagnostic criteria were not unified. This study aims to investigate the consistency between the latest sarcopenia diagnostic criteria Asian Working Group for Sarcopenia(AWGS 2019) and other common diagnostic criteria. The changes of muscle mass, muscle strength and physical function with age and their effects on the diagnosis of sarcopenia were also analyzed. Methods A total of 1009 men aged ≥60 years were enrolled from multiple communities. Skeletal muscle mass index, grip strength and 6 m gait speed were measured. The consistency of AWGS 2019 with other diagnostic criteria was analyzed and the trends of these three indicators were observed. The differences of muscle mass, muscle strength and function among different diagnostic criteria and age groups were evaluated. In addition, the change trends of these three indicators with age were observed. Results According to AWGS 2019 diagnostic criteria, the incidence of sarcopenia in male aged 60–69 years, 70–79 years and over 80 years was 1.5%, 9.6% and 33.1%, respectively. AWGS 2019 was highly consistent with other diagnostic criteria (Kappa = 0.66–0.80, P

Abstract Background Body mass index (BMI) and A Body Shape Index (ABSI) are current independent risk factors for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to explore the value of combining these two most common obesity indexes in identifying NAFLD. Methods The subjects in this study were 14,251 individuals from the NAfld in the Gifu Area, Longitudinal Analysis (NAGALA) cohort who underwent routine health examination. We integrated BMI with WC and with ABSI to construct 6 combined obesity indicators—obesity phenotypes, the combined anthropometric risk index (ARI) for BMI and ABSI, optimal proportional combination OBMI+WC and OBMI+ABSI, and multiplicative combination BMI*WC and BMI*ABSI. Several multivariable logistic regression models were established to evaluate the relationship between BMI, WC, ABSI, and the above six combined indicators and NAFLD; receiver operating characteristic (ROC) curves were drawn to compare the ability of each obesity indicator to identify NAFLD. Results A total of 2,507 (17.59%) subjects were diagnosed with NAFLD. BMI, WC, ABSI, and all other combined obesity indicators were significantly and positively associated with NAFLD in the current study, with BMI*WC having the strongest correlation with NAFLD in female subjects (OR per SD increase: 3.13) and BMI*ABSI having the strongest correlation in male subjects (OR per SD increase: 2.97). ROC analysis showed that ARI and OBMI+ABSI had the best diagnostic performance in both sexes, followed by BMI*WC (area under the curve: female 0.8912; male 0.8270). After further age stratification, it was found that ARI and multiplicative indicators (BMI*WC, BMI*ABSI) and optimal proportional combination indicators (OBMI+WC, OBMI+ABSI) significantly improved the NAFLD risk identification ability of the basic anthropometric parameters in middle-aged females and young and middle-aged males. Conclusion In the general population, BMI combined with ABSI best identified obesity-related NAFLD risk and was significantly better than BMI or WC, or ABSI. We find that ARI and the multiplicative combined indicators BMI*WC and BMI*ABSI further improved risk prediction and may be proposed for possible use in clinical practice.

The rapid rise of glacioeustatic change is the most extreme paleoenvironment alteration in the aftermath of Snowball Earth. Although geologists conducted a lot of multi-subdiscipline research on this issue previously, there still exists the potential room for further discussions of the process in detail. For decades, the practice proved that the Fischer plot is a simple and robust tool to illustrate the fluctuations of accommodation patterns v.s. cycle sets or strata depth which could be interpreted as relative sea-level changes. This research simulates the Fischer plot to unravel the sea-level change in the aftermath of Marinoan glaciation by measuring the lower Ediacaran Doushantuo Formation in Shennongjia, South China. The result shows that 131 fifth-order cycles and nine third-order cycles help us propose a completed second-order cycle variation of ice melting-forced sea-level change, i.e., (1) early high-frequency and slow to rapid stepwise rising, and (2) followed by a stable decrease in the latter. In addition, the vertical sedimentary facies of the lower Doushantuo Formation display, in ascending order, (1) intertidal carbonate rock, (2) subtidal clastics with turbidite, and (3) intertidal lagoon fine clastics, indicating the process of the relative waxing and waning of sea-level. Such interpretation of the Fischer plot and the sedimentary facies’ vertical evolution is beneficial for studying the high-frequency sea-level change and paleogeographic reconstruction of post-Marinoan deglaciation.

Astragalus is a homologous medicine and food that benefits human beings and poultry rearing. Fermented astragalus (FA) is a valuable product obtained by fermentation, but its scale-up production requires optimization and expansion of solid-state fermentation (SSF). In this study, Lactobacillus pentosus Stm was screened as the most suitable LAB strain for fermenting astragalus due to its excellent capacity. After optimization and expansion of SSF, LAB count and lactic acid content reached 206 × 108 cfu/g and 15.0%, respectively. Meanwhile, the content of bioactive compounds in FA was significantly enhanced. Feeding experiments with laying hens indicated that supplementing FA in the diet significantly improved the performance and egg quality, as evidenced by reduced feed-to-egg ratio and egg cholesterol. This was due to the promotion of intestinal health by shifting intestinal microbiota. Therefore, this is a systematical endeavor of producing scaled-up FA with promising potential as a feed additive in the poultry breeding industry.

ObjectiveTriglyceride glucose body mass index (TyG-BMI) has been shown to be strongly associated with a variety of chronic diseases. However, little is known about the associations between TyG-BMI and normal-high blood pressure (BP) values and hypertension (HTN).MethodThe current study was cross-sectional in design and included 15,464 non-diabetic participants recruited between 1994 and 2016 in the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) study. Associations between TyG-BMI and normal-high BP values and HTN were assessed using multivariate logistic regression. The ability of the TyG index, BMI, and their combined index TyG-BMI to identify normal-high BP values and HTN was compared by receiver operating characteristic (ROC) curves.ResultsAmong the 15,464 eligible non-diabetic participants, 28.56% (4,416/15,464) and 6.23% (964/15,464) had normal-high BP values and HTN, respectively. Multivariate logistic regression analysis showed positive correlations between BMI, TyG index, TyG-BMI and normal-high BP values/HTN; after standardized regression coefficients, TyG-BMI had the strongest association with normal-high BP values and HTN compared to BMI and TyG index. In the fully adjusted model, the odds ratio (OR) value corresponding to the relationship between TyG-BMI and HTN/normal-high BP values was 2.35; when TyG-BMI was used as a categorical variable, compared with the lowest quartile of TyG-BMI the regression coefficient for the association of the highest quartile of TyG-BMI with normal-high BP values increased by 426%, while the regression coefficient for the association with HTN increased by 527%. In further spline regression analysis, we also found that there was a linearly positive correlation between TyG-BMI and systolic BP/diastolic BP (SBP/DBP), which supported the linear trend between TyG-BMI and HTN/normal-high BP values (P-trend

Different aerosol types exhibit distinct radiative effects in different regions, attributed to their unique optical characteristics and regional distributions. This study focuses on North China, which is impacted by both natural and anthropogenic aerosols with high concentrations and a variety of aerosol types. While many studies on aerosol direct radiative effects have been conducted in this region, the majority have focused on a specific type of aerosol or overall aerosol, leaving limited research on the direct radiative effects and contributions of different aerosol types. In this study, we use CALIPSO satellite data from 2011 to 2020 to investigate concentrations and distributions of different aerosol types. The results reveal that dust, polluted dust, polluted continental/smoke, and elevated smoke are the dominant aerosol types in North China. Based on the radiative closure experiment, we systematically calculate the radiative effects of different aerosol types and their corresponding contributions to the energy budget by combining satellite data with the Fu–Liou radiative transfer model. The annual average net aerosol direct radiative effect (ADRE) of North China is −6.1 and −13.43 W m−2 at the TOA and surface, respectively, causing a net warming effect of 7.33 W m−2 in the atmosphere. For each main aerosol type, dust contributes 93% to the shortwave ADRE in the western dust source region, while polluted dust mainly contributes 31% and 45% of the total ADRE, in Northwest China and North China Plain, respectively. Anthropogenic pollutant aerosols account for 58% of the total ADRE in Northeast China. This study holds great significance in elucidating the dominant aerosol types and their concentrations in North China, comprehending the impacts of different aerosol types on the local energy balance.

Abstract Background The diversity of obesity-related metabolic characteristics generates different obesity phenotypes and corresponding metabolic diseases. This study aims to explore the correlation of different abdominal obesity phenotypes with non-alcoholic fatty liver disease (NAFLD). Methods The current study included 14,251 subjects, 7411 males and 6840 females. Abdominal obesity was defined as waist circumference ≥ 85 cm in males and ≥ 80 cm in females; according to the diagnostic criteria for metabolic syndrome recommended by the National Cholesterol Education Program Adult Treatment Panel III, having more than one metabolic abnormality (except waist circumference criteria) was defined as metabolically unhealthy. All subjects were divided into 4 abdominal obesity phenotypes based on the presence ( +) or absence (− ) of metabolically healthy/unhealthy (MH) and abdominal obesity (AO) at baseline: metabolically healthy + non-abdominal obesity (MH−AO−); metabolically healthy + abdominal obesity (MH−AO+); metabolically unhealthy + non-abdominal obesity (MH+AO−); metabolically unhealthy + abdominal obesity (MH+AO+). The relationship between each phenotype and NAFLD was analyzed using multivariate logistic regression. Results A total of 2507 (17.59%) subjects in this study were diagnosed with NAFLD. The prevalence rates of NAFLD in female subjects with MH−AO−, MH−AO+, MH+AO−, and MH+AO+ phenotypes were 1.73%, 24.42%, 7.60%, and 59.35%, respectively. Among male subjects with MH−AO−, MH−AO+, MH+AO−, and MH+AO+ phenotypes, the prevalence rates were 9.93%, 50.54%, 25.49%, and 73.22%, respectively. After fully adjusting for confounding factors, with the MH−AO− phenotype as the reference phenotype, male MH−AO+ and MH+AO+ phenotypes increased the risk of NAFLD by 42% and 47%, respectively (MH−AO+: OR 1.42, 95%CI 1.13,1.78; MH+AO+: OR 1.47, 95%CI 1.08,2.01); the corresponding risks of MH−AO+ and MH+AO+ in females increased by 113% and 134%, respectively (MH−AO+: OR 2.13, 95%CI 1.47,3.09; MH+AO+: OR 2.34, 95%CI 1.32,4.17); by contrast, there was no significant increase in the risk of NAFLD in the MH+AO− phenotype in both sexes. Conclusions This first report on the relationship of abdominal obesity phenotypes with NAFLD showed that both MH−AO+ and MH+AO+ phenotypes were associated with a higher risk of NAFLD, especially in the female population. These data provided a new reference for the screening and prevention of NAFLD.

Abstract Background Developing biocompatible nerve conduits that accelerate peripheral nerve regeneration, lengthening and functional recovery remains a challenge. The combined application of nerve microtissues and platelet-rich plasma (PRP) provides abundant Schwann cells (SCs) and various natural growth factors and can compensate for the deficiency of SCs in the nerve bridge, as well as the limitations of applying a single type of growth factor. Multimodal ultrasound evaluation can provide additional information on the stiffness and microvascular flow perfusion of the tissue. This study was designed to investigate the effectiveness of a novel tissue-engineered nerve graft composed of an autogenous vein, nerve microtissues and PRP in reconstructing a 12-mm tibial nerve defect and to explore the value of multimodal ultrasound techniques in evaluating the prognosis of nerve repair. Methods In vitro, nerve microtissue activity was first investigated, and the effects on SC proliferation, migration, factor secretion, and axonal regeneration of dorsal root ganglia (DRG) were evaluated by coculture with nerve microtissues and PRP. In vivo, seventy-five rabbits were equally and randomly divided into Hollow, PRP, Micro-T (Microtissues), Micro-T + PRP and Autograft groups. By analysing the neurological function, electrophysiological recovery, and the comparative results of multimodal ultrasound and histological evaluation, we investigated the effect of these new nerve grafts in repairing tibial nerve defects. Results Our results showed that the combined application of nerve microtissues and PRP could significantly promote the proliferation, secretion and migration of SCs and the regeneration of axons in the early stage. The Micro-T + PRP group and Autograft groups exhibited the best nerve repair 12 weeks postoperatively. In addition, the changes in target tissue stiffness and microvascular perfusion on multimodal ultrasound (shear wave elastography; contrast-enhanced ultrasonography; Angio PlaneWave UltrasenSitive, AngioPLUS) were significantly correlated with the histological results, such as collagen area percentage and VEGF expression, respectively. Conclusion Our novel tissue-engineered nerve graft shows excellent efficacy in repairing 12-mm defects of the tibial nerve in rabbits. Moreover, multimodal ultrasound may provide a clinical reference for prognosis by quantitatively evaluating the stiffness and microvescular flow of nerve grafts and targeted muscles.

Abstract Background Low-density lipoprotein:high-density lipoprotein cholesterol ratio (LDL:HDL ratio) has a good performance in identifying diabetes mellitus (DM) and insulin resistance. However, it is not yet clear whether the LDL:HDL ratio is associated with a high-risk state of prediabetes. Methods This cohort study retrospectively analyzed the data of 100,309 Chinese adults with normoglycemia at baseline. The outcome event of interest was new-onset prediabetes. Using multivariate Cox regression and smoothing splines to assess the association of LDL:HDL ratio with prediabetes. Results During an average observation period of 37.4 months, 12,352 (12.31%) subjects were newly diagnosed with prediabetes. After adequate adjustment for important risk factors, the LDL:HDL ratio was positively correlated with the prediabetes risk, and the sensitivity analysis further suggested the robustness of the results. Additionally, in stratified analysis, we discovered significant interactions between LDL:HDL ratio and family history of DM, sex, body mass index and age (all P-interaction

Probiotics are the treasure of the microbiology fields. They have been widely used in the food industry, clinical treatment, and other fields. The equivocal health-promoting effects and the unknown action mechanism were the largest obstacles for further probiotic’s developed applications. In recent years, various genome editing techniques have been developed and applied to explore the mechanisms and functional modifications of probiotics. As important genome editing tools, CRISPR-Cas systems that have opened new improvements in genome editing dedicated to probiotics. The high efficiency, flexibility, and specificity are the advantages of using CRISPR-Cas systems. Here, we summarize the classification and distribution of CRISPR-Cas systems in probiotics, as well as the editing tools developed on the basis of them. Then, we discuss the genome editing of probiotics based on CRISPR-Cas systems and the applications of the engineered probiotics through CRISPR-Cas systems. Finally, we proposed a design route for CRISPR systems that related to the genetically engineered probiotics.

ObjectiveHigh body mass index (BMI) is an important risk factor for non-alcoholic fatty liver disease (NAFLD). However, the association of body composition such as fat mass (FM) and lean body mass (LBM) with NAFLD has not been adequately studied. The purpose of this study was to clarify the contribution of body composition FM and LBM to NAFLD.MethodsWe analyzed data from 7,411 men and 6,840 women in the NAGALA cohort study. LBM and FM were estimated for all subjects using validated anthropometric prediction equations previously developed from the National Health and Nutrition Examination Survey (NHANES). Using multiple logistic regression and restricted cubic spline (RCS) to analyze the association and the dose-response curve of predicted LBM and FM with NAFLD in both sexes.ResultsThe prevalence of NAFLD in man and woman subjects was 27.37 and 6.99%, respectively. Predicted FM was positively and linearly associated with NAFLD in both sexes, with each 1 kg increase in predicted FM associated with a 27 and 40% increased risk of NAFLD in men and women, respectively. In contrast, predicted LBM was negatively associated with NAFLD in both sexes, with each 1 kg increase in predicted LBM reducing the risk of NAFLD by 4 and 19% in men and women, respectively. In addition, according to the RCS curve, the risk of NAFLD did not change in men when the predicted LBM was between 47 and 52 kg, and there seemed to be a saturation effect; further, the threshold value of the saturation effect was calculated to be about 52.08 kg by two-piecewise logistic regression, and the protective effect on NAFLD would be significantly enhanced when the man predicted LBM was greater than 52.08 kg.ConclusionThe current findings suggested that body composition LBM and FM had opposite associations with NAFLD in both sexes, with higher LBM associated with a lower risk of NAFLD and higher FM increasing the risk of NAFLD, especially in women.

ObjectiveObesity is the prominent modifiable risk factor known to influence the occurrence and progression of diabetes other than age, and the objective of this study was to evaluate and compare the predictive value of three simple baseline anthropometric indicators of obesity, body mass index (BMI), waist circumference (WC), and waist-height ratio (WHtR), for the occurrence of diabetes at different time points in the future.MethodsThe study subjects were 12,823 individuals with normoglycemic at baseline who underwent health screening and had measurements of BMI, WC, and WHtR. The outcome of interest was new-onset diabetes during follow-up. Time-dependent receiver operator characteristics (ROC) curves of baseline BMI, WC, and WHtR for predicting the risk of diabetes in the next 2 to 12 years were constructed and their area under the ROC curves (AUCs) and corresponding optimal threshold values were calculated for each time point, which were used to compare the accuracy and stability of the above three indicators for predicting the occurrence of diabetes in different future periods.ResultsDuring a median follow-up period of 7.02 years, with a maximum follow-up of 13 years, 320 new-onset diabetes were recorded. After adjusting for confounders and comparing standardized hazard ratios (HRs), WC was shown to be the best simple anthropometric indicator of obesity reflecting diabetes risk in all models, followed by WHtR. Time-dependent ROC analysis showed that WC had the highest AUC in predicting the occurrence of diabetes in the short term (2-5 years), and WHtR had the highest AUC in predicting the occurrence of diabetes in the medium to long term (6-12 years), while in any time point, both WC and WHtR had higher AUC than BMI in predicting future diabetes. In addition, we found relatively larger fluctuations in the thresholds of BMI and WC for predicting diabetes over time, while the thresholds of WHtR consistently remained between 0.47-0.50; comparatively speaking, WHtR may have greater application value in predicting future diabetes.ConclusionsOur analysis sustained that central obesity is a more important predictor of diabetes, and in clinical practice, we proposed measuring WHtR as a useful tool for predicting future diabetes.