Search

Abstract Lipid metabolism reprogramming has emerged as a hallmark of malignant tumors. Lipids represent a complex group of biomolecules that not only compose the essential components of biological membranes and act as an energy source, but also function as messengers to integrate various signaling pathways. In tumor cells, de novo lipogenesis plays a crucial role in acquiring lipids to meet the demands of rapid growth. Increasing evidence has suggested that dysregulated lipid metabolism serves as a driver of cancer progression. Posttranslational modifications (PTMs), which occurs in most eukaryotic proteins throughout their lifetimes, affect the activity, abundance, function, localization, and interactions of target proteins. PTMs of crucial molecules are potential intervention sites and are emerging as promising strategies for the cancer treatment. However, there is limited information available regarding the PTMs that occur in cancer lipid metabolism and the potential treatment strategies associated with these PTMs. Herein, we summarize current knowledge of the roles and regulatory mechanisms of PTMs in lipid metabolism. Understanding the roles of PTMs in lipid metabolism in cancer could provide valuable insights into tumorigenesis and progression. Moreover, targeting PTMs in cancer lipid metabolism might represent a promising novel therapeutic strategy.

Abstract Background Hyperglycemia upon admission is associated with poor prognosis of many cardiovascular diseases. However, the relationship of stress hyperglycemia ratio (SHR), admission blood glucose (ABG), and hemoglobin A1c (HbA1c) with pulmonary hypertension has not been reported. This study aimed to explore the association of hyperglycemia indices with disease severity and long-term adverse outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH). Methods This multi-center cohort study included 625 consecutive patients diagnosed with or treated for IPAH between January 2015 and June 2023. SHR was calculated using the followings: ABG (mmol/L)/(1.59 × HbA1c [%] − 2.59). The primary endpoint was defined as clinical worsening events. Multivariable Cox regression and restricted cubic spline analyses were employed to evaluate the association of SHR, ABG, and HbA1c with endpoint events. The mediating effect of pulmonary hemodynamics was evaluated to investigate the potential mechanism between hyperglycemia and clinical outcomes. Results During a mean follow-up period of 3.8 years, 219 (35.0%) patients experienced all-cause death or clinical worsening events. Hyperglycemia indices correlated with well-validated variables that reflected the severity of IPAH, such as the World Health Organization functional class, 6-min walk distance, and N-terminal pro-brain natriuretic peptide levels. Multivariable Cox regression analyses indicated that SHR (hazard ratio [HR] 1.328, 95% confidence intervals [CI]: 1.185, 1.489 per 0.1-unit increment, P

A new species Serangium xinpingensis Huang & Wang, sp. nov. is described from Yunnan Province, China, as a newly discovered predator on Bemisia tabaci Gennadius (Hemiptera, Sternorrhyncha, Aleyrodidae). The new species is a valuable addition to the 14 species of this genus in China known before. A diagnosis, detailed description, including the structure of its immature stages, illustrations, and the distribution of the new species are provided.

Abstract Background Patients with chronic obstructive pulmonary disease (COPD) often require hospital readmission because of exacerbation of their condition. These frequent exacerbations reduce quality of life, work performance, and emotional health. However, few studies have investigated the risk factors for readmission and readmission rates in Asian patients with COPD. We conducted a systematic review to identify and understand the major risk factors for readmission in patients with COPD in Asia and the readmission rate. Method We searched PubMed, MEDLINE, Embase, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and China Biomedical Literature Database from database inception to September 2023 to identify studies on the readmission rate and risk factors for COPD in Asian patients. Chinese search terms included “COPD,” “chronic obstructive pulmonary disease,” “risk factors,” “recurrence,” “readmission,” and “acute exacerbation.” English search terms included “chronic obstructive pulmonary disease,” “COPD,” “lung emphysema,” “hospital admission,” “patient readmission,” and “readmission.” We extracted first author, publication year, research area, sample size, sex, risk factors, and readmission rates. The included studies’ quality was evaluated using the Agency of Healthcare Research and Quality. Meta-synthesis was conducted on readmission rates and risk factors for readmission. Subgroups were formed by age, research area, sample size, and research type, and meta-regression analysis was conducted on the 30-day, 90-day, and 365-day readmission rates of patients to determine the source of heterogeneity. Finally, the results’ robustness was evaluated using sensitivity analysis. Begg and Egger tests were used to evaluate publication bias. Results Meta-analysis of 44 studies, with 169,255 participants, indicated that risk factors for COPD readmission in Asia included: history of multiple hospital admissions, ≥ 3 comorbidities, male sex, ratio of eosinophils percentage ≥ 2%, body mass index < 18.5, smoking history, pulmonary heart disease comorbidity, COPD assessment test score > 20, nutritional disorder, Neutrophil-to-Lymphocyte ratio > 7, and FEV1 < 50. The 30-, 90-, and 365-day readmission rates of patients were 19%, 31%, and 42%, respectively. Conclusions Patients with COPD in Asia generally have high readmission rates and different risk factors. To reduce healthcare, economic, and social burdens, interventions should address major risk factors, early prevention, and screening.

Abstract Background Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear. Methods We combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays. Results We identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells. Conclusions We identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.

Abstract Background Lung cancer still ranks first in the mortality rate of cancer. Uric acid is a product of purine metabolism in humans. Its presence in the serum is controversial; some say that its high levels have a protective effect against tumors, others say the opposite, that is, high levels increase the risk of cancer. Therefore, the aim of this study was to investigate the potential causal association between serum uric acid levels and lung cancer. Methods Mendelian randomization was used to achieve our aim. Sensitivity analyses was performed to validate the reliability of the results, followed by reverse Mendelian analyses to determine a potential reverse causal association. Results A significant causal association was found between serum uric acid levels and lung cancer in East Asian and European populations. Further sublayer analysis revealed a significant causal association between uric acid and small cell lung cancer, while no potential association was observed between uric acid and non-small cell lung cancer, squamous lung cancer, and lung adenocarcinoma. The sensitivity analyses confirmed the reliability of the results. Reverse Mendelian analysis showed no reverse causal association between uric acid and lung cancer. Conclusions The results of this study suggested that serum uric acid levels were negatively associated with lung cancer, with uric acid being a potential protective factor for lung cancer. In addition, uric acid level monitoring was simple and inexpensive. Therefore, it might be used as a biomarker for lung cancer, promoting its wide use clinical practice.

Abstract Introduction Postherpetic neuralgia (PHN), a complication of herpes zoster, significantly impacts the quality of life of affected patients. Research indicates that early intervention for pain can reduce the occurrence or severity of PHN. This study aims to develop a predictive model and scoring table to identify patients at risk of developing PHN following acute herpetic neuralgia, facilitating informed clinical decision-making. Methods We conducted a retrospective review of 524 hospitalized patients with herpes zoster at The First Affiliated Hospital of Zhejiang Chinese Medical University from December 2020 to December 2023 and classified them according to whether they had PHN, collecting a comprehensive set of 30 patient characteristics and disease-related indicators, 5 comorbidity indicators, 2 disease score values, and 10 serological indicators. Relevant features associated with PHN were identified using the least absolute shrinkage and selection operator (LASSO). Then, the patients were divided into a training set and a test set in a 4:1 ratio, with comparability tested using univariate analysis. Six models were established in the training set using machine learning methods: support vector machines, logistic regression, random forest, k-nearest neighbor, gradient boosting, and neural network. The performance of these models was evaluated in the test set, and a nomogram based on logistic regression was used to create a PHN prediction score table. Results Eight non-zero characteristic variables selected from the LASSO regression results were included in the model, including age [area under the curve (AUC) = 0.812, p

Abstract Background Schizophrenia (SZ), a psychiatric disorder for which there is no precise diagnosis, has had a serious impact on the quality of human life and social activities for many years. Therefore, an advanced approach for accurate treatment is required. New method In this study, we provide a classification approach for SZ patients based on a spatial–temporal residual graph convolutional neural network (STRGCN). The model primarily collects spatial frequency features and temporal frequency features by spatial graph convolution and single-channel temporal convolution, respectively, and blends them both for the classification learning, in contrast to traditional approaches that only evaluate temporal frequency information in EEG and disregard spatial frequency features across brain regions. Results We conducted extensive experiments on the publicly available dataset Zenodo and our own collected dataset. The classification accuracy of the two datasets on our proposed method reached 96.32% and 85.44%, respectively. In the experiment, the dataset using delta has the best classification performance in the sub-bands. Comparison with existing methods Other methods mainly rely on deep learning models dominated by convolutional neural networks and long and short time memory networks, lacking exploration of the functional connections between channels. In contrast, the present method can treat the EEG signal as a graph and integrate and analyze the temporal frequency and spatial frequency features in the EEG signal. Conclusion We provide an approach to not only performs better than other classic machine learning and deep learning algorithms on the dataset we used in diagnosing schizophrenia, but also understand the effects of schizophrenia on brain network features.

BackgroundPostherpetic itch (PHI) is an easily overlooked complication of herpes zoster that greatly affects patients' quality of life. Studies have shown that early intervention can reduce the occurrence of itch. The aim of this study was to develop and validate a predictive model through a machine learning approach to identify patients at risk of developing PHI among patients with herpes zoster, making PHI prevention a viable clinical option.MethodWe conducted a retrospective review of 488 hospitalized patients with herpes zoster at The First Affiliated Hospital of Zhejiang Chinese Medical University and classified according to whether they had PHI. Fifty indicators of these participants were collected as potential input features for the model. Features associated with PHI were identified for inclusion in the model using the least absolute shrinkage selection operator (LASSO). Divide all the data into five pieces, and then use each piece as a verification set and the others as a training set for training and verification, this process is repeated 100 times. Five models, logistic regression, random forest (RF), k-nearest neighbor, gradient boosting decision tree and neural network, were built in the training set using machine learning methods, and the performance of these models was evaluated in the test set.ResultsSeven non-zero characteristic variables from the Lasso regression results were selected for inclusion in the model, including age, moderate pain, time to recovery from rash, diabetes, severe pain, rash on the head and face, and basophil ratio. The RF model performs better than other models. On the test set, the AUC of the RF model is 0.84 [(95% confidence interval (CI): 0.80–0.88], an accuracy of 0.78 (95% CI: 0.69–0.86), a precision of 0.61 (95% CI: 0.45–0.77), a recall of 0.73 (95% CI: 0.58–0.89), and a specificity of 0.79 (95% CI: 0.70–0.89).ConclusionsIn this study, five machine learning methods were used to build postherpetic itch risk prediction models by analyzing historical case data, and the optimal model was selected through comparative analysis, with the random forest model being the top performing model.

Purpose: To evaluate the efficacy of retinal massage combined with autologous blood covering in the treatment of persistent macular holes following vitrectomy in eyes with high myopia. Settings and Design: Retrospective, consecutive case series in a tertiary eye center. Methods: A total of 12 highly myopic eyes with persistent macular holes after vitrectomy and internal limiting membrane peeling received combined retinal massage, air/fluid exchange, autologous blood covering, and gas/silicone oil tamponade. Best-corrected visual acuity, axial length, and optical coherence tomographic images before and after the treatment were compared. Results: The mean hole diameter before this intervention was 931.58 ± 244.58 μm (range, 508–1270), and the axial length was 30.39 ± 2.13 mm (range, 27.08–34.64). During the 6-month follow-up period, hole closure was achieved in eight eyes (66.67%). The mean best-corrected visual acuity improved significantly from 1.40 ± 0.50 logarithm of the minimum angle of resolution (logMAR) at baseline to 1.10 ± 0.30 logMAR (P < 0.05). No complications were observed. Conclusions: Combined retinal massage and autologous blood covering, which is easy to manipulate, can promote the closure of persistent macular holes after vitrectomy and improve vision in high myopia with an axial length less than 29 mm.

ObjectiveThe purpose of this meta-analysis is to investigate the efficacy and safety of a subcutaneous injection of botulinum toxin in the treatment of postherpetic neuralgia (PHN) compared to analgesics.MethodsWe searched PubMed, Cochrane Library, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang for randomized controlled trials (RCTs) from inception to 10 September 2023. The primary clinical outcomes included visual analog scale (VAS) pain scores and clinical effective rates. The secondary clinical outcome included the adverse event rate during follow-up.ResultsA total of 14 studies with 1,358 participants were included in the meta-analysis. Among the included patients, 670 participants received botulinum toxin A injections and 688 participants received other medication treatments. The botulinum toxin-A (BTX-A) group exhibited lower pain scores [week 2: Mean difference (MD): −1.91, 95% confidence interval (CI): −2.63 to −1.20, and p

Abstract The management of surgical instruments is related to the safety and efficiency of surgical operations, and a surgical instruments information management system (SIIMS) has been developed. The aim of the current study is to explore the application value of the SIIMS in sports medicine specialty. A set of self-developed SIIMS for sports medicine surgeries was applied to the study. The application value of the SIIMS was verified by comparing the safety and efficiency of instrument manipulation before and after its application, with instrument accidents, instrument repair rate, instrument scrap rate and instrument use efficiency as indicators. Through the application of the SIIMS, the incidence of surgical instrument accidents decreased from 3.7 times to 1.8 times (P = 0.02), the number of instrument repair decreased from 7.7 times to 2.9 times (P = 0.00), and the number of scrapped instruments decreased from 5.1 to 2.3 (P = 0.03), when referred to per thousand operations. Before and after the application of the SIIMS, the average instrument use efficiency was 74.0% ± 3.3% and 88.2% ± 4.4%, respectively, with statistically significant difference (P = 0.00). The application of the SIIMS in sports medicine specialty is helpful to the fine management of surgical instruments, improve surgical safety and instrument use efficiency.

Background and purpose: Despite the superior dose conformity of proton therapy, the dose distribution is sensitive to daily anatomical changes, which can affect treatment accuracy. This study evaluated the dose recalculation accuracy of two synthetic computed tomography (sCT) generation algorithms in a commercial treatment planning system. Materials and methods: The evaluation was conducted for head-and-neck, thorax-and-abdomen, and pelvis sites treated with proton therapy. Thirty patients with two cone-beam computed tomography (CBCT) scans each were selected. The sCT images were generated from CBCT scans using two algorithms, Corrected CBCT (corrCBCT) and Virtual CT (vCT). Dose recalculations were performed based on these images for comparison with “ground truth” deformed CTs. Results: The choice of algorithm influenced dose recalculation accuracy, particularly in high dose regions. For head-and-neck cases, the corrCBCT method showed closer agreement with the “ground truth”, while for thorax-and-abdomen and pelvis cases, the vCT algorithm yielded better results (mean percentage dose discrepancy of 0.6 %, 1.3 % and 0.5 % for the three sites, respectively, in the high dose region). Head-and-neck and pelvis cases exhibited excellent agreement in high dose regions (2 %/2 mm gamma passing rate >98 %), while thorax-and-abdomen cases exhibited the largest differences, suggesting caution in sCT algorithm usage for this site. Significant systematic differences were observed in the clinical target volume and organ-at-risk doses in head-and-neck and pelvis cases, highlighting the importance of using the correct algorithm. Conclusions: This study provided treatment site-specific recommendations for sCT algorithm selection in proton therapy. The findings offered insights for proton beam centers implementing adaptive radiotherapy workflows.

BackgroundSarcopenia is a disease characterized by decreased skeletal muscle mass and function in elderly individuals. Decreased hemoglobin levels is a marker of anemia. According to reports, there may be an association between anemia and sarcopenia, but research is inconsistent. Therefore, this meta-analysis aims to explore the association between sarcopenia and low hemoglobin levels.MethodsWe searched PubMed, Embase, the Cochrane Library, Web of Science, Ovid, China National Knowledge Infrastructure (CNKI), and Wan Fang databases until September 2022. The present study included cross-sectional and case-control studies regarding low hemoglobin levels and sarcopenia. The studies were selected using inclusion and exclusion criteria. Studies were meta-analyzed by Review Manager 5.4 and Stata 16.0. We performed the heterogeneity test using the I2 test. Subgroup analysis was carried out to explore the cause of heterogeneity. Egger test was used to evaluate publication bias.ResultsOut of 1,550 initial studies, 16 studies were meta-analyzed. Sarcopenia participants had significantly lower levels of hemoglobin than controls (MD = −0.53, 95% CI: −0.68 to −0.37, p

AimPeople with diabetes mellitus have a higher risk of dental caries than the general population. Diet is one of the most important factors affecting the risk of dental caries. This study aimed to evaluate the effect of dietary fiber to carbohydrate ratio (FCR) on the risk of dental caries in diabetic patients.MethodsData of this cross-sectional study were extracted from the 2015–2020 cycle of the National Health and Nutrition Examination Survey (NHANES) database. FCR levels were divided into two categories based on the median (0.13). The outcomes were untreated dental caries and dental caries experience. The associations of FCR with untreated dental caries and dental caries experience were assessed using multivariable logistic regression analysis and reported as odds ratio (OR) and 95% confidence interval (CI). Stratified analyses were performed according to age (

Background: Previous research has established carbon monoxide (CO) as a significant air pollutant contributing to coronavirus disease 2019 (COVID-19) transmission. The spatiotemporal heterogeneity in the relationship between short-duration CO exposure and COVID-19 incidence remain underexplored. Investigating such heterogeneity plays a crucial role in designing region-specific cost-effective public health policies, exploring the reasons for heterogeneity, and understanding the temporal trends in the association between CO and an emerging infectious disease such as COVID-19. Methods: The 49 states of the continental United States (U.S.) were examined in this study. Initially, we developed time-series generalized additive models (GAMs) for each state to assess the preliminary correlation between daily COVID-19 cases and short-term CO exposure from April 1, 2020, to December 31, 2021. Subsequently, the correlations were compiled utilizing Leroux-prior-based conditional autoregression (LCAR) to achieve a smoothed spatial distribution. Finally, we integrated a time-varying component into the GAM and LCAR to analyze temporal correlations and illuminate the factors contributing to spatiotemporal heterogeneity. Results: Our analysis revealed that, across the 49 states, a 10-ppb increase in CO concentration was associated with a 1.33 % (95%CI: 0.86%–1.81 %) increase in COVID-19 cases on average. Furthermore, spatial variability was noted, with weaker correlations observed in the central and southeastern regions, stronger associations in the northeastern regions, and negligible associations in the western regions. Temporally, the correlation was not significant from April 2020 to June 2021, but began to increase steadily thereafter until the end of 2021. Additionally, vaccination and temperature were determined to be potential causes contributing to the heterogeneity, indicating stronger positive associations in areas with higher vaccination rates and temperatures. Conclusion: The findings of this study underscore the importance of monitoring CO pollution in the central and northeastern US, especially in the aftermath of the pandemic.

In this study, a UPLC-MS/MS method was developed for the rapid detection of 71 neuropsychotropic drugs in human serum for drug concentration monitoring and toxicity screening. The analytes were separated from the biological matrix by protein precipitation using a methanol-acetonitrile solvent mixture. The chromatographic separation was performed on a Kromasil ClassicShell C18 column (2.1*50 mm, 2.5 μ m) with gradient elution using acetonitrile-0.2 % acetic acid and 10 mM ammonium acetate as the mobile phases (flow rate 0.4 mL/min, column temperature 40 °C, injection volume 5 μL). An electrospray ion source in both positive and negative ion modes with multiple ion monitoring was used. The total run time was 6 min. All compounds were quantified using the isotope internal standard method. Totally, 71 drugs were detected within their linear ranges with correlation coefficients greater than 0.990. The intra- and inter-batch precision relative standard deviations (RSDs) for the low, medium, and high concentration points were less than 15 %, with an accuracy of 90%–110 %. All compounds except Moclobemide N-oxindole are stabilised within 7 days. The relative matrix effect results for each analyte were within ±20 % of the requirements. The method is validated according to Clinical and Laboratory Standards Institute guidelines, easy to use, and has a low cost.

Abstract Objective To evaluate the efficacy of urokinase (UK) treatment for tuberculous pleural effusion (TPE). Methods We searched Chinese biomedical literature database, WanFang data, CNKI, PubMed, EMbase, Web of Science and The Cochrane Library for the randomized controlled trials (RCTs) of urokinase treatment for tuberculous pleurisy from January 2000 to February 2023. Pleural tuberculosis, urokinase and randomized controlled trial were used as keywords. The eligible studies were meta-analyzed by using Revman 5.4.1: risk of bias was assessed, mean difference (MD) and 95% CI were used for continuous variables, pooled studies were conducted using random-effects or fixed-effects models, forest plots were drawn to analyze efficacy, and funnel plots were drawn to discuss publication bias. Results Twenty-nine RCTs were included. The meta-analyzed results showed that, on the basis of routine anti-tuberculosis, comparison between the treatment group treated with urokinase and the control group treated with antituberculosis alone, the time of pleural effusion absorption [MD-5.82, 95%CI (− 7.77, − 3.87); P

Abstract Modular and regio-/stereoselective syntheses of all-carbon tetrasubstituted olefins from simple alkene materials remain a challenging project. Here, we demonstrate that a remote-carbonyl-directed palladium-catalyzed Heck/isomerization/C(sp2)–H arylation sequence enables unactivated 1,1-disubstituted alkenes to undergo stereoselective terminal diarylation with aryl iodides, thus offering a concise approach to construct stereodefined tetrasubstituted olefins in generally good yields under mild conditions; diverse carbonyl groups are allowed to act as directing groups, and various aryl groups can be introduced at the desired position simply by changing aryl iodides. The stereocontrol of the protocol stems from the compatibility between the E/Z isomerization and the alkenyl C(sp2)–H arylation, where the vicinal group-directed C(sp2)–H arylation of the Z-type intermediate product thermodynamically drives the reversible E to Z isomerization. Besides, the carbonyl group not only promotes the Pd-catalyzed sequential transformations of unactivated alkenes by weak coordination, but also avoids byproducts caused by other possible β-H elimination.

AIM: To quantify changes in radial peripapillary capillary vessel density (ppVD) and the peripapillary retinal nerve fiber layer (pRNFL) in children with type 1 diabetes without clinical diabetic retinopathy by optical coherence tomography angiography (OCTA), providing a basis for early retinopathy in children with type 1 diabetes. METHODS: This was a retrospective study. A total of 30 patients (3–14y) with type 1 diabetes without clinical diabetic retinopathy (NDR group) were included. A total of 30 age-matched healthy subjects were included as the normal control group (CON group). The HbA1c level in the last 3mo was measured once in the NDR group. The pRNFL thickness and ppVD were automatically measured, and the mean pRNFL and ppVD were calculated in the nasal, inferior, temporal, and superior quadrants. The changes in ppVD and pRNFL in the two groups were analyzed. RESULTS: Compared with CON group, the nasal and superior ppVDs decreased in the NDR group (all P0.05). Person and Spearman correlation analysis of ppVD and pRNFL thickness in each quadrant of the NDR group showed a positive correlation between nasal and superior (all P0.05). There was no significant correlation between the HbA1c level and ppVD and pRNFL in any quadrant (all P>0.05). There was no significant correlation between the course of diabetes mellitus and ppVD and pRNFL in any quadrant (all P>0.05). CONCLUSION: ppVD and pRNFL decrease in eyes of children with type 1 diabetes before clinically detectable retinopathy and OCTA is helpful for early monitoring．

The existing strawberry ripeness detection algorithm has the problems of a low precision and a high missing rate in real complex scenes. Therefore, we propose a novel model based on a hybrid attention mechanism. Firstly, a partial convolution-based compact inverted block is developed, which significantly enhances the feature extraction capability of the model. Secondly, an efficient partial hybrid attention mechanism is established, which realizes the remote dependence and accurate localization of strawberry fruit. Meanwhile, a multi-scale progressive feature pyramid network is constructed, and the fine-grained features of strawberry targets of different sizes are accurately extracted. Finally, a Focaler-shape-IoU loss function is proposed to effectively solve the problem of the difficulty imbalance between strawberry samples and the influence of the shape and size of the bounding box on the regression. The experimental results show that the model’s precision and mAP0.5 reach 92.1% and 92.7%, respectively, which are 2.0% and 1.7% higher than the baseline model. Additionally, our model is better in detection performance than most models with fewer parameters and lower FLOPs. In summary, the model can accurately identify the maturity of strawberry fruit under complex farmland environments and provide certain technical guidance for automated strawberry-picking robots.

Zinc is a trace element, which plays an important role in many biological processes. The deficiency of zinc will lead to many diseases. Thus, it is of great significance to develop fast and efficient quantitative detection technology for zinc ions. In this study, a novel fluorescence probe FP2 was designed for Zn2+ quantification based on pyrano[3,2-c] carbazole. The structure of FP2 was characterized by 1HNMR, 13CNMR, HRMS, and X-ray diffraction. In the HEPES buffer solution, FP2 is responsive to Zn2+ and greatly enhanced. The pH value and reaction time were investigated, and the optimum reaction conditions were determined as follows: the pH was 7~9 and the reaction time was longer than 24 min. Under the optimized conditions, the concentration of FP2 and Zn2+ showed a good linear relationship in the range of 0~10 μM, and the LOD was 0.0065 μmol/L. In addition, through the 1H NMR titration experiment, density functional theory calculation, and the job plot of FP2 with Zn2+ in the HEPES buffer solution, the binding mode of FP2 and Zn2+ was explained. Finally, the method of flame atomic absorption spectrometry (FAAS) and FP2 were used to detect the content of Zn2+ in the water extract of tea. The results showed that the FP2 method is more accurate than the FAAS method, which shows that the method described in this work could be used to detect the content of Zn2+ in practical samples and verify the practicability of this method.

Alzheimer’s disease (AD) is a multifactorial brain disorder and infectious diseases are considered as one of the predisposing factors for AD. Toxoplasma gondii, an obligate intracellular parasitic protozoan, is suspected of being associated with AD. Serum samples were collected from 109 AD patients and 114 age-matched healthy controls. ELISA was performed using recombinant T. gondii cyst wall protein 1 (CST1) to detect T. gondii antibodies. A parallel experiment was performed with Toxoplasma gondii tachyzoites lysate protein. To analyze whether factors associated with the onset of AD included chronic T. gondii infection, a multivariate logistic regression model was applied, further validating the correlation between chronic T. gondii infection and AD. AD patients exhibited significantly higher levels of Toxoplasma-specific antibodies in their serum compared to the control group, with statistically significant differences (p < 0.05). Multivariate logistic regression analysis revealed that Toxoplasma infection is a risk factor for AD (p < 0.01), and the CST1 antigen can significantly improve the model’s performance in predicting the occurrence of AD. The results indicate that chronic infection with Toxoplasma gondii could be one of the risk factors for the development of AD, potentially predisposing individuals with underlying health conditions to the disease. This further validates the correlation between Toxoplasma gondii and AD.

Research on air pollution, one of the most common environmental factors, has primarily focused on its effects on physical, mental, and cognitive health. However, air pollution-induced achromatic color of an environment, which is a prominent feature of air pollution, has received little attention. This study explored the visual effects of air pollution on the variety-seeking purchase behavior of consumers through two scenario-based experiments and primed manipulation (Study 1 and Study 2) and one natural experiment using data from a local fruit chain store (Study 3). Study 1 tested the main effect of air pollution on the variety-seeking behavior and found that primed air pollution increased variety-seeking when consumers purchased beverages. Study 2 broadened the category and tested the mechanism, and the results indicated that primed air pollution increased the variety of purchased chocolates and demonstrated the mediating effect of the need for arousal. Study 3 tested the boundary condition and extended the external validity with actual purchases. The results revealed that severe air pollution increased the purchased SKUs by 22.9% and visibility reduced the moderation effect. This research extended the literature on the visual effect of air pollution by providing evidence of the effects of air pollution on variety-seeking behavior through the need for arousal. And, product managers could leverage the results by offering a greater variety of goods on days with air pollution to increase sales.

Quiescence (G0) maintenance and exit are crucial for tissue homeostasis and regeneration in mammals. Here, we show that methyl-CpG binding protein 2 (Mecp2) expression is cell cycle-dependent and negatively regulates quiescence exit in cultured cells and in an injury-induced liver regeneration mouse model. Specifically, acute reduction of Mecp2 is required for efficient quiescence exit as deletion of Mecp2 accelerates, while overexpression of Mecp2 delays quiescence exit, and forced expression of Mecp2 after Mecp2 conditional knockout rescues cell cycle reentry. The E3 ligase Nedd4 mediates the ubiquitination and degradation of Mecp2, and thus facilitates quiescence exit. A genome-wide study uncovered the dual role of Mecp2 in preventing quiescence exit by transcriptionally activating metabolic genes while repressing proliferation-associated genes. Particularly disruption of two nuclear receptors, Rara or Nr1h3, accelerates quiescence exit, mimicking the Mecp2 depletion phenotype. Our studies unravel a previously unrecognized role for Mecp2 as an essential regulator of quiescence exit and tissue regeneration.

Background: GLI3 gene mutations can result in various forms of polysyndactyly, such as Greig cephalopolysyndactyly syndrome (GCPS, MIM: #175700), Pallister–Hall syndrome (PHS, MIM: #146510), and isolated polydactyly (IPD, MIM: #174200, #174700). Reports on IPD-associated GLI3 mutations are rare. In this study, a novel GLI3 mutation was identified in a Chinese family with IPD. Results: We report a family with six members affected by IPD. The family members demonstrated several special phenotypes, including sex differences, abnormal finger joint development, and different polydactyly types. We identified a novel frameshift variant in the GLI3 gene (NM_000168.6: c.1820_1821del, NP_000159.3: p.Tyr607Cysfs*9) by whole-exome sequencing. Further analysis suggested that this mutation was the cause of polydactyly in this family. Conclusions: The discovery of this novel frameshift variant in our study further solidifies the relationship between IPD and GLI3 and expands the previously established spectrum of GLI3 mutations and associated phenotypes.

This study addresses the low water productivity (WP) of traditional flood irrigation (FI) and the mismatch between the wet zone of surface drip irrigation (SDI) and the root activity layer of fragrant pear. A fixed field experiment was conducted in Xinjiang, northwest China in 2021 − 2023. The experiment was designed as a two-factor, completely randomized trial with three lateral depths of Subsurface drip irrigation (SSDI) gradients set at 20 cm (D1), 30 cm (D2) and 40 cm (D3) and three irrigation gradients: W1 (3750 m³ ha−1); W2 (5250 m³ ha−1); and W3 (6750 m³ ha−1), using SDI (6750 m³ ha−1) and FI (9750 m³ ha−1) as the controls. The effects of these factors on soil moisture, crop water consumption (ETc), fruit quality, yield, WP and net profit were analyzed. The results revealed that the average soil moisture content increased with the lateral depth and irrigation amount. Principal component analysis determined D2W3 to be the treatments with the best overall quality in 2021–2023. On average, compared with SDI and FI, SSDI increased yield by 13.14% and 17.03%, and WP by 44.65% and 137.23%, respectively. A comprehensive Moisture-Yield-Quality-Efficiency evaluation model was established using the Projection Pursuit Classification model based on the Real Coded Accelerating Genetic Algorithm (RAGA-PPC). The comprehensive evaluation was optimized at the lateral depth of 30 cm and an irrigation amount of 6750 m³ ha−1. This study is a crucial reference for further research on perennial fruit trees to improve fruit quality and WP.

Objectives There are limited data on the relationship between sleep duration and possible sarcopenia. Hence, this study aimed to investigate the associations of sleep duration with possible sarcopenia and its defining components based on the China Health and Retirement Longitudinal Study (CHARLS).Design A retrospective cohort study.Setting This study was conducted on participants aged over 45 years applying the 2011 baseline and 2015 follow-up survey from CHARLS covering 450 villages, 150 counties and 28 provinces.Participants Data from 5036 individuals (2568 men and 2468 women) free of possible sarcopenia at baseline were analysed.Primary and secondary outcome measures The dose-response relationship between sleep duration and possible sarcopenia.Results During 4 years of follow-up, 964 (19.14%) participants developed possible sarcopenia. Compared with participants who slept 6–8 hours per night, those with shorter sleep duration (8 hours per night) was not significantly associated with incident possible sarcopenia. The plots of restricted cubic splines exhibited an atypical inverse J-shaped association between sleep duration and possible sarcopenia. Subgroup analysis showed a stronger association between sleep duration and possible sarcopenia in participants aged 45–59 years and composed of male populations.Conclusions Short sleep duration was a potential risk factor for possible sarcopenia and low handgrip strength. The improvement of sleep duration should be considered a target in early preventive and administrative strategies against the development of handgrip strength decline and further reduced the occurrence of sarcopenia.

IntroductionSignal peptide peptidase (SPP) is an intramembrane protease involved in a variety of biological processes, it participates in the processing of signal peptides after the release of the nascent protein to regulate the endoplasmic reticulum associated degradation (ERAD) pathway, binds misfolded membrane proteins, and aids in their clearance process. Additionally, it regulates normal immune surveillance and assists in the processing of viral proteins. Although SPP is essential for many viral infections, its role in silkworms remains unclear. Studying its role in the silkworm, Bombyx mori , may be helpful in breeding virus-resistant silkworms.MethodsFirst, we performed RT-qPCR to analyze the expression pattern of BmSPP. Subsequently, we inhibited BmSPP using the SPP inhibitor 1,3-di-(N-carboxybenzoyl-L-leucyl-L-leucylaminopropanone ((Z-LL)2-ketone) and downregulated the expression of BmSPP using CRISPR/Cas9 gene editing. Furthermore, we assessed the impact of these interventions on the proliferation of Bombyx mori nucleopolyhedrovirus (BmNPV).ResultsWe observed a decreased in the expression of BmSPP during viral proliferation. It was found that higher concentration of the inhibitor resulted in greater inhibition of BmNPV proliferation. The down-regulation of BmSPP in both in vivo and in vitro was found to affect the proliferation of BmNPV. In comparison to wild type silkworm, BmSPPKO silkworms exhibited a 12.4% reduction in mortality rate.DiscussionCollectively, this work demonstrates that BmSPP plays a negative regulatory role in silkworm resistance to BmNPV infection and is involved in virus proliferation and replication processes. This finding suggests that BmSPP servers as a target gene for BmNPV virus resistance in silkworms and can be utilized in resistance breeding programs.

Abstract Intercropping can obtain yield advantages, but the mechanism of yield advantages of maize-legume intercropping is still unclear. Then, we explored the effects of cropping systems and N input on yield advantages in a two-year experiment. Cropping systems included monoculture maize (Zea mays L.) (MM), monoculture soybean (Glycine max L. Merr.) (MS), monoculture peanut (Arachis hypogaea L.) (MP), maize-soybean substitutive relay intercropping (IMS), and maize-peanut substitutive strip intercropping (IMP). N input included without N (N0) and N addition (N1). Results showed that maize’s leaf area index was 31.0% and 34.6% higher in IMS and IMP than in MM. The specific leaf weight and chlorophyll a (chl a) of maize were notably higher by 8.0% and 18.8% in IMS, 3.1%, and 18.6% in IMP compared with MM. Finally, N addition resulted in a higher thousand kernels weight of maize in IMS and IMP than that in MM. More dry matter accumulated and partitioned to the grain, maize's averaged partial land equivalent ratio and the net effect were 0.76 and 2.75 t ha−1 in IMS, 0.78 and 2.83 t ha−1 in IMP. The leaf area index and specific leaf weight of intercropped soybean were 16.8% and 26% higher than MS. Although soybean suffers from shade during coexistence, recovered growth strengthens leaf functional traits and increases dry matter accumulation. The averaged partial land equivalent ratio and the net effect of intercropped soybean were 0.76 and 0.47 t ha−1. The leaf area index and specific leaf weight of peanuts in IMP were 69.1% and 14.4% lower than in the MP. The chlorophyll a and chlorophyll b of peanut in MP were 17.0% and 24.4% higher than in IMP. A less dry matter was partitioned to the grain for intercropped peanut. The averaged pLER and NE of intercropped peanuts were 0.26 and -0.55 t ha−1. In conclusion, the strengthened leaf functional traits promote dry matter accumulation, maize-soybean relay intercropping obtained a win–win yield advantage, and maize-peanut strip intercropping achieved a trade-off yield advantage.

Objective To investigate the clinical utility of identifying circulating tumor cells (CTC) and circulating tumorigenic endothelial cells (CTEC) in skin malignancies. Methods Subtraction enrichment-immunostaining and fluorescence in situ hybridization (SE-iFISH) were used to detect the number of CTC and CTEC in the peripheral blood of 5 patients with skin tumor (tumor group) and 14 healthy individuals (healthy controls), and the detection rate was calculated. The subtype characteristics of CTC/CTEC and the correlation between the number of CTC/CTEC and the clinical characteristics of the patients were analyzed. Results The positive rates of CTC and CTEC in the tumor group were 100%. The average CTC were (6.93±8.18) /mL and CTEC were (1.60±1.03) /mL in the peripheral blood of the tumor group. The positive rates of CTC and CTEC in the healthy controls were both 64%. The average CTC were (0.19±0.21) /mL, and CTEC were (0.30±0.33) /mL in the peripheral blood of the healthy controls. Patients with larger diameter of tumor, lymph node metastasis, and clinical stages of III and IV had higher levels of CTC and CTEC; Large CTC accounted for 88.46% (184/208) of the total tumor cells, while large CTEC accounted for 81.25% (39/48) of the total tumor cells, which mainly were ≥ pentaploid CTC and CTEC. Conclusions Using SE-iFISH, the detection rates of CTC/CTEC are high in patients with skin tumors. The amounts of CTC and CTEC are correlated with the clinical features of patients. A higher proportion of CTC and CTEC is large multiploid cells in peripheral blood of subjects with skin tumors.

Abstract Formamidine lead triiodide (FAPbI3) perovskites have attracted increasing interest for photovoltaics attributed to the optimal bandgap, high thermal stability, and the record power conversion efficiency (PCE). However, the materials still face several key challenges, such as phase transition, lattice defects, and ion migration. Therefore, external ions (e.g., cesium ions (Cs+)) are usually introduced to promote the crystallization and enhance the phase stability. Nevertheless, the doping of Cs+ into the A‐site easily leads to lattice compressive strain and the formation of pinholes. Herein, trioctylphosphine oxide (TOPO) is introduced into the precursor to provide tensile strain outside the perovskite lattice through intermolecular forces. The special strain compensation strategy further improves the crystallization of perovskite and inhibits the ion migration. Moreover, the TOPO molecule significantly passivates grain boundaries and undercoordinated Pb2+ defects via the forming of P═O─Pb bond. As a result, the target solar cell devices with the synergistic effect of Cs+ and TOPO additives have achieved a significantly improved PCE of 22.71% and a high open‐circuit voltage of 1.16 V (voltage deficit of 0.36 V), with superior stability under light exposure, heat, or humidity conditions.

Background: There are limited published data on mortality trends in pulmonary hypertension (PH) worldwide. The objective of this study was to assess the PH-related mortality and time trends in the general population over the past 20 years. Material and methods: We used country-level PH mortality data from the World Health Organization (WHO) mortality database (2000–19), using the International Classification of Diseases, tenth revision (ICD-10) codes (I27.0, I27.2, I27.8, or I27.9). The average annual percentage changes (AAPCs) were calculated to describe mortality trends. Results: Fifty-four countries were included in this study. Between 2017 and 2019, the average age-standardized death rates (per 100,000) were 0.80 and 0.87 for males and females, respectively. Joinpoint analyses revealed a decreasing PH mortality trend for the overall population from 2000 to 2019 (AAPC -3.2 [95% confidence interval (CI) −4.1 to −2.4]), which was consistent between males and females (males: AAPC -5.3 [95% CI –6.2 to −4.4], females: AAPC -1.7 [95% CI –2.4 to −0.9]). When the estimates were stratified by etiology, we found that the mortality rates from idiopathic pulmonary arterial hypertension (I27.0) and pulmonary heart disease (unspecified, I27.9) had decreased significantly, while the mortality rates in other secondary PH (I27.2) and other specified pulmonary heart diseases (I27.8) had significantly increased. In addition, there were substantial differences in mortality rates and time trends across countries. Conclusion: Although an overall decrease in PH mortality trends over the past two decades, there were substantial differences across countries. For countries with high or rising mortality rates, more efforts are needed to reduce the mortality.

The United Nations Convention on the Law of the Sea (UNCLOS) include the term of “effective control” in its sponsorship provisions but do not clarify its meaning. To arrive at a consensus on its connotation, the International Seabed Authority (ISA) began discussions on the concept of “effective control” that have been ongoing since 2014 but have still not yielded any definite conclusion. The interpretation and application of this concept tend to be construed as a regulatory standard in current discussion documents and practices of the ISA, where this allow contractors from developed countries to easily use the method of “sponsoring states of convenience” to apply for and obtain contracts to reserved areas. This is inimical to the goals of effective marine environmental protection and the implementation of preferential treatment for developing countries. The international community should pay attention to this issue and correct the unreasonable tendencies of the ISA in this regard.

Background and purpose: High-density dental fillings pose a non-negligible impact on head and neck cancer treatment. For proton therapy, stopping power ratio (SPR) prediction will be significantly impaired by the associated image artifacts. Dose perturbation is also inevitable, compromising the treatment plan quality. While plenty of work has been done on metal or amalgam fillings, none has touched on composite resin (CR) and glass ionomer cement (GIC) which have seen an increasing usage. Hence, this work aims to provide a detailed characterisation of SPR and dose perturbation in proton therapy caused by CR and GIC. Materials and methods: Four types of fillings were used: CR, Fuji Bulk (FB), Fuji II (FII) and Fuji IX (FIX). The latter three belong to GIC category. Measured SPR were compared with SPR predicted using single-energy computed tomography (SECT) and dual-energy computed tomography (DECT). Dose perturbation of proton beams with lower- and higher-energy levels was also quantified using Gafchromic films. Results: The measured SPR for CR, FB, FII and FIX were 1.68, 1.77, 1.77 and 1.76, respectively. Overall, DECT could predict SPR better than SECT. The lowest percentage error achieved by DECT was 19.7 %, demonstrating the challenge in estimating SPR, even for fillings with relatively lower densities. For both proton beam energies and all four fillings of about 4.5 mm thickness, the maximum dose perturbation was 3 %. Conclusion: This study showed that dose perturbation by CR and GIC was comparatively small. We have measured and recommended the SPR values for overriding the fillings in TPS.

IntroductionAutism spectrum disorder (ASD) is a multifaceted developmental condition that commonly appears during early childhood. The etiology of ASD remains multifactorial and not yet fully understood. The identification of biomarkers may provide insights into the underlying mechanisms and pathophysiology of the disorder. The present study aimed to explore the causes of ASD by investigating the key biomedical markers, trace elements, and microbiota factors between children with autism spectrum disorder (ASD) and control subjects.MethodsMedline, PubMed, ProQuest, EMBASE, Cochrane Library, PsycINFO, Web of Science, and EMBSCO databases have been searched for publications from 2012 to 2023 with no language restrictions using the population, intervention, control, and outcome (PICO) approach. Keywords including “autism spectrum disorder,” “oxytocin,” “GABA,” “Serotonin,” “CRP,” “IL-6,” “Fe,” “Zn,” “Cu,” and “gut microbiota” were used for the search. The Joanna Briggs Institute (JBI) critical appraisal checklist was used to assess the article quality, and a random model was used to assess the mean difference and standardized difference between ASD and the control group in all biomedical markers, trace elements, and microbiota factors.ResultsFrom 76,217 records, 43 studies met the inclusion and exclusion criteria and were included in this meta-analysis. The pooled analyses showed that children with ASD had significantly lower levels of oxytocin (mean differences, MD = −45.691, 95% confidence interval, CI: −61.667, −29.717), iron (MD = −3.203, 95% CI: −4.891, −1.514), and zinc (MD = −6.707, 95% CI: −12.691, −0.722), lower relative abundance of Bifidobacterium (MD = −1.321, 95% CI: −2.403, −0.238) and Parabacteroides (MD = −0.081, 95% CI: −0.148, −0.013), higher levels of c-reactive protein, CRP (MD = 0.401, 95% CI: 0.036, 0.772), and GABA (MD = 0.115, 95% CI: 0.045, 0.186), and higher relative abundance of Bacteroides (MD = 1.386, 95% CI: 0.717, 2.055) and Clostridium (MD = 0.281, 95% CI: 0.035, 0.526) when compared with controls. The results of the overall analyses were stable after performing the sensitivity analyses. Additionally, no substantial publication bias was observed among the studies.InterpretationChildren with ASD have significantly higher levels of CRP and GABA, lower levels of oxytocin, iron, and zinc, lower relative abundance of Bifidobacterium and Parabacteroides, and higher relative abundance of Faecalibacterium, Bacteroides, and Clostridium when compared with controls. These results suggest that these indicators may be a potential biomarker panel for the diagnosis or determining therapeutic targets of ASD. Furthermore, large, sample-based, and randomized controlled trials are needed to confirm these results.

Summary: Intercellular adhesion molecule 1 (ICAM-1) plays prominent roles in mediating cell-cell adhesion which also facilitates B cell activation and differentiation with the help from CD4+ T cells. Here, we have reported a unique phenomenon that increased ICAM-1 on purified human CD4+ T cells upon anti-CD3/CD28 stimulation enhanced CD4+ T-B cell adhesion whereas induced less B cell differentiation and IgG production. This was largely due to increased PD-1 expression on CD19hi B cells after coculturing with hyperactivated CD4+ T cells. Consequently, ICAM-1 blockade during CD4+ T cell-B cell coculture promoted IgG production with the activation of ERK1/2 and Blimp-1/IRF4 upregulation. Consistently, CD4+ T cells from moderate-to-severe SLE patients with high ICAM-1 expression mediated less IgG production after T-B coculture. Therefore, ICAM-1-mediated human CD4+ T-B cell adhesion provides dual roles on B cell differentiation and IgG production partially depending on expression levels of PD-1 on B cells, supporting cell adhesion and subsequent PD-1 induction as an alternative intrinsic checkpoint for B cell differentiation.

Abstract Background Based on its objective characteristics, laboratory markers have always been the research direction of clinical diagnosis and assessment of mental disorders including Alzheimer's disease. Methods MTT Colorimetric Assay, ELISA, and quantitative PCR were used to investigate the responsiveness of peripheral blood mononuclear cells (PBMCs) to mitogen Lipopolysaccharides (LPS) and Phytohemagglutinin (PHA), PBMCs genomic methylation and hydroxymethylation levels, nuclear DNA and mitochondrial DNA damage, respiratory chain enzyme activities, and circulating cell-free mitochondrial DNA levels were detected in 90 patients with Alzheimer's disease. Results In the Alzheimer's disease group, LPS stimulated PBMCs viability, TNF-α secretion, PHA stimulated IL-10 secretion, genomic DNA methylation levels, circulating cell-free mitochondrial DNA copies, citrate synthase activity were reduced compared to the control; while the LPS stimulated PBMCs IL-1α secretion, PHA stimulated IL-1α and IFN-γ secretion, plasma IL-6 and TNF-α, mitochondrial DNA damages were increased compared to the control. Conclusions The reactivity of peripheral blood mononuclear cells to mitogens, mitochondrial DNA integrity characteristics, and cell-free mitochondrial DNA copies may be used as candidate laboratory biomarkers to help clinical management of Alzheimer's disease.

Endoplasmic reticulum, the largest cellular organelle where protein synthesis, folding, transportation, and the maintenance of Ca2+ homeostasis occurred, is sensitive to the imbalance of its inner environment. Particularly, overproduction of reactive oxygen species in endoplasmic reticulum region can initiate endoplasmic reticulum stress and is tightly related to many metabolic diseases. In this respect, to retain normal function of endoplasmic reticulum, it is highly important to synthesize antioxidants with endoplasmic reticulum-targeting capability for precisely clearing excessively generated reactive oxygen species in endoplasmic reticulum. Herein, we demonstrate the preparation of endoplasmic reticulum-targeting Se-doped carbon nanodots and assays with HeLa cells as well as in vivo tests with mice have shown that the prepared carbon nanodots can significantly eliminate both •OH and O2•−. Experimental results declared that the fabricated carbon nanodots with powerful scavenging capabilities toward •OH and O2•-, low cytotoxicity and endoplasmic reticulum targetability can be utilized to protect cells against raised levels of reactive oxygen species in endoplasmic reticulum. What’s more, the fabricated carbon nanodots effectively alleviated phorbol 12-myristate 13-acetate induced ear inflammation in live mice.

A class of generalized proportional-integral-derivative (PID) control with feedforward compensation (FFC) is obtained for a class of cascade integral systems by equivalence analysis of the cascade control and such the analysis is obtained by using the information of the model and outermost loop feedback. Firstly, a new type of error related to the traditional error such as proportional (P) or proportional integral (PI) is given. Secondly, by analyzing cascade control for a class of ideal cascade integral systems, the generalized PID control with FFC is presented based on the proposed new type of error. Then, the generalized PID control with FFC is extended to a class of non-ideal cascade integral systems to reduce the number of feedback loop and sensors. Finally, the simulation results of the speed/position servo system of direct current motor are given to verify the theoretical analysis results.

Abstract DEAD box helicase 17 (DDX17) has been reported to be involved in the initiation and development of several cancers. However, the functional role and mechanisms of DDX17 in colorectal cancer (CRC) malignant progression and metastasis remain unclear. Here, we reported that DDX17 expression was increased in CRC tissues compared with noncancerous mucosa tissues and further upregulated in CRC liver metastasis compared with patient-paired primary tumors. High levels of DDX17 were significantly correlated with aggressive phenotypes and worse clinical outcomes in CRC patients. Ectopic expression of DDX17 promoted cell migration and invasion in vitro and in vivo, while the opposite results were obtained in DDX17-deficient CRC cells. We identified miR-149-3p as a potential downstream miRNA of DDX17 through RNA sequencing analysis, and miR-149-3p displayed a suppressive effect on the metastatic potential of CRC cells. We demonstrated that CYBRD1 (a ferric reductase that contributes to dietary iron absorption) was a direct target of miR-149-3p and that miR-149-3p was required for DDX17-mediated regulation of CYBRD1 expression. Moreover, DDX17 contributed to the metastasis and epithelial to mesenchymal transition (EMT) of CRC cells via downregulation of miR-149-3p, which resulted in increased CYBRD1 expression. In conclusion, our findings not only highlight the significance of DDX17 in the aggressive development and prognosis of CRC patients, but also reveal a novel mechanism underlying DDX17-mediated CRC cell metastasis and EMT progression through manipulation of the miR-149-3p/CYBRD1 pathway.

Abstract Background Human cytomegalovirus (HCMV), a member of the β-herpesvirus family, causes the establishment of a latent infection that persists throughout the life of the host and can be reactivated when immunity is weakened. To date, there is no vaccine to prevent HCMV infection, and clinically approved drugs target the stage of viral replication and have obvious adverse reactions. Thus, development of novel therapeutics is urgently needed. Methods In the current study, we identified a naturally occurring pterostilbene that inhibits HCMV Towne strain replication in human diploid fibroblast WI-38 cells through Western blotting, qPCR, indirect immunofluorescence assay, tissue culture infective dose assays. The time-of-addition experiment was carried out to identify the stage at which pterostilbene acted. Finally, the changes of cellular senescence biomarkers and reactive oxygen species production brought by pterostilbene supplementation were used to partly elucidate the mechanism of anti-HCMV activity. Results Our findings revealed that pterostilbene prevented lytic cytopathic changes, inhibited the expression of viral proteins, suppressed the replication of HCMV DNA, and significantly reduced the viral titre in WI-38 cells. Furthermore, our data showed that pterostilbene predominantly acted after virus cell entry and membrane fusion. The half-maximal inhibitory concentration was determined to be 1.315 μM and the selectivity index of pterostilbene was calculated as 26.73. Moreover, cell senescence induced by HCMV infection was suppressed by pterostilbene supplementation, as shown by a decline in senescence-associated β-galactosidase activity, decreased production of reactive oxygen species and reduced expression of p16, p21 and p53, which are considered biomarkers of cellular senescence. Conclusion Together, our findings identify pterostilbene as a novel anti-HCMV agent that may prove useful in the treatment of HCMV replication.

The concept of dense granular-flow target (DGT) for the China Initiative Accelerator Driven Subcritical system (CiADS) is an attractive choice for high heat removal ability, low chemical toxicity, and radiotoxicity. A wobbling hollow beam is proposed to enhance the homogeneity of temperature rise of flowing particles in beam-target coupling zone. In this paper, the design procedure of target and beam parameters was discussed firstly. Then we simulated the heat deposition and transfer of the scanning beam in DGT to study the effect of beam parameters. The results show the flux density of proton beam plays a crucial role in the distribution of temperature rise while the contributions from scanning frequency heat transfer are also obvious. Moreover, heat transfer in transversal directions is insignificant, resulting in a low heat flux towards the sidewalls of DGT. This work not only contributes to the design of DGT, but also beneficial for understanding the beam-target coupling in porous materials.

Abstract Ca2+ signaling is altered substantially in many cancers. The ryanodine receptors (RYRs) are among the key ion channels in Ca2+ signaling. This study aimed to establish the mutational profile of RYR in cancers and investigate the correlation between RYR alterations and cancer phenotypes. The somatic mutation and clinical data of 11,000 cancer patients across 33 cancer types was downloaded from The Cancer Genome Atlas (TCGA) database. Subsequent data processing was performed with corresponding packages of the R software. Mutational profile was analyzed and its correlation with tumor mutational burden (TMB), patient prognosis, age and smoking status was analyzed and compared. All three RYR isoforms exhibited random mutational distribution without hotspot mutations when all cancers were analyzed together. The number of mutations in RYR2 (2388 mutations) far overweight that of RYR1 (1439 mutations) and RYR3 (1573 mutations). Linear correlation was observed between cumulative TMB and cumulative number of mutations for all RYR isoforms. Patients with RYR mutations exhibited significantly higher TMB than those without RYR mutations for most cancer types. Strong correlation was also revealed in the average number of mutations per person between pairs of RYR isoforms. No stratification of patient overall survival (OS) by mutational status was found for all three RYR isoforms when all cancers were analyzed together, however, significant stratification of OS by RYR mutations was revealed in several individual cancers, most strikingly in LUAD (P = 0.0067, RYR1), BLCA (P = 0.00071, RYR2), LUSC (P = 0.036, RYR2) and KIRC (P = 0.0042, RYR3). Furthermore, RYR mutations were correlated with higher age, higher smoking history grading and higher number of pack years. Characteristic mutation profile of RYRs in cancers has been revealed for the first time. RYR mutations were correlated with TMB, age, smoking status and capable of stratifying the prognosis of patients in several cancer types.

Cul3 encodes Cullin-3, a core component of the ubiquitin E3 ligase that is involved in protein ubiquitination. Recent studies have identified Cul3 as a high-confidence risk gene in neurodevelopmental disorders (NDDs), especially autism spectrum disorder (ASD). Different strategies have been used to generate animal models with Cul3 deficiency in the central nervous system, including whole-brain knockout (KO), cell-type specific conditional KO (cKO), and brain region-specific knockdown. In this review, we revisited the basic properties of CUL3 and its function under physiological and pathological conditions. Recent clinical studies including case reports and large cohort sequencing studies related to CUl3 in NDDs have been summarized. Moreover, we characterized the behavioral, electrophysiological, and molecular changes in newly developed Cul3 deficiency models. This would guide further studies related to Cul3 in CNS and provide potential therapeutic targets for Cul3-deficiency-induced NDDs, including ASD.

Background: Prostate cancer (PCa) is among the most generally diagnosed cancers in males. A long non-coding RNA (lncRNA) called AC245100.4 has been discovered and linked to PCa carcinogenesis. However, its specific and potential mechanism is uncertain in PCa. In this research, we investigated the role of AC245100.4 in cell proliferation and the underlying mechanism in PCa cells. Methods: qRT-PCR assays were utilized to detect AC245100.4 expression and confirm its downstream target. The pathways related to AC245100.4 were identified by RAP-MS. PCa cell proliferation was experimented by Cell Counting Kit-8 and Colony formation assays. Western blot was performed to detect PAR2, AKT, p-AKT, Cyclin D1 and PCNA expression. Results: AC245100.4/PAR2 overexpression promotes PCa cell proliferation and the opposite results are obtained after AC245100.4/PAR2 knockdown. Mechanistically, we found that PAR2 is confirmed as the AC245100.4 downstream target and AC245100.4 promotes PCa cell proliferation by regulating PAR2. AC245100.4 promotes PCa cell proliferation via PI3K/AKT pathway. Rescue assays validated that PAR2 knockdown reversed the impact of AC245100.4 overexpression on increasing p-AKT protein levels. Conclusion: This research revealed that AC245100.4 enhances cell proliferation in PCa cells through modulating the PAR2/PI3K/AKT axis, which may offer novel tumor markers and potential therapeutic targets for PCa.

Traditional single-fiber spectroscopy provides a single galaxy spectrum, forming the basis for crucial parameter estimation. However, its accuracy can be compromised by various sources of contamination, such as the prominent H α emission line originating from both star-forming (SF) regions and non-star-forming (NonSF) regions, including active galactic nuclei. The potential to dissect a spectrum into its SF and NonSF constituents holds the promise of significantly enhancing precision in parameter estimates. In contrast, integral field unit (IFU) surveys present a solution to minimize contamination. These surveys examine spatially localized regions within galaxies, reducing the impact of mixed sources. Although an IFU survey’s resulting spectrum covers a smaller region of a galaxy than single-fiber spectroscopy, it can still encompass a blend of heterogeneous sources. Our study introduces an innovative model informed by insights from the Mapping Nearby Galaxies at Apache Point Observatory IFU survey. This model enables the decomposition of galaxy spectra, including those from the Sloan Digital Sky Survey, into SF and NonSF components. Applying our model to these survey data sets produces two distinct spectra, one for SF and another for NonSF components, while conserving flux across wavelength bins. When these decomposed spectra are visualized on a Baldwin, Phillips, and Terlevich (BPT) diagram, interesting patterns emerge. There is a significant shift in the placement of the NonSF decomposed spectra, as well as the emergence of two distinct clusters in the Low-ionization Nuclear Emission-line Region and the Seyfert region. This shift highlights the key role of SF “contamination” in influencing the positioning of NonSF spectra within the BPT diagram.

Abstract Metastasis is a major cause of colorectal cancer (CRC) mortality, but its molecular mechanisms are still not fully understood. Here, we show that upregulated DDX39B correlates with liver metastases and aggressive phenotypes in CRC. DDX39B is an independent prognostic factor associated with poor clinical outcome in CRC patients. We demonstrate that Sp1 potently activates DDX39B transcription by directly binding to the GC box of the DDX39B promoter in CRC cells. DDX39B overexpression augments the proliferation, migration, and invasion of CRC cells, while the opposite results are obtained in DDX39B-deficient CRC cells. Mechanistically, DDX39B interacts directly with and stabilizes PKM2 by competitively suppressing STUB1-mediated PKM2 ubiquitination and degradation. Importantly, DDX39B recruits importin α5 to accelerate the nuclear translocation of PKM2 independent of ERK1/2-mediated phosphorylation of PKM2, leading to the transactivation of oncogenes and glycolysis-related genes. Consequently, DDX39B enhances glucose uptake and lactate production to activate Warburg effect in CRC. We identify that Arg319 of DDX39B is required for PKM2 binding as well as PKM2 nuclear accumulation and for DDX39B to promote CRC growth and metastasis. In addition, blocking PKM2 nuclear translocation or treatment with glycolytic inhibitor 2-deoxy-D-glucose efficiently abolishes DDX39B-triggered malignant development in CRC. Taken together, our findings uncover a key role for DDX39B in modulating glycolytic reprogramming and aggressive progression, and implicate DDX39B as a potential therapeutic target in CRC.

The dense granular flow spallation target is a new target concept proposed for an Accelerator-Driven Sub-critical (ADS) system. In this paper, the beam-target configurations of a tungsten granular flow target for the ADS with a thermal power of 1 GW is explored. The beam profile options using different scanning methods are discussed. The critical geometry parameters are adjusted to investigate the performance of the granular target from the aspects of neutron efficiency, stability and temperature distribution in target medium. To figure out how the target under accident conditions would behave, different clogging conditions are induced in the simulation. The dynamic processes are analyzed and some important parameters such as abnormal temperature rise and beam cutoff time window are obtained. The response of the sub-critical reactor to a clogging accident is also investigated. It is indicated that the monitoring of the granular flow by the neutron detectors in the sub-critical core will be effective.