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Yongjiao Zhang,1,2 Xiaolei Xuan,2 Diwen Ye,1,2 Dong Liu,2 Yufan Song,2 Fei Gao,2 Sumei Lu2 1School of Medical Laboratory, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Sumei Lu; Fei Gao, Email lsmqianyi@126.com; 448617003@qq.comAbstract: Absent in melanoma 2 (AIM2) is a protein encoded by the AIM2 gene located on human chromosomes, AIM2 can recognize and bind to double stranded DNA (dsDNA), leading to the assembly of the AIM2 inflammasome. The AIM2 inflammasome plays important proinflammation role in many diseases, and can induce pyroptotic cell death. It has also been closely linked to the development and progression of metabolic diseases and can be activated in obesity, diabetes, nonalcoholic fatty liver disease, and atherosclerosis. In this article, we mainly review the role of AIM2 in glucose metabolism, especially in obesity-related disorders of glucose and lipid metabolism, and provide insights to better understand the role of AIM2 in the pathogenesis, and clinical treatment of metabolic disease.Keywords: AIM2, obesity, metabolic diseases, diabetes, glucose metabolism disorders

Xiuyun Xuan,1 Yuqi Wang,2 Yanhong Sun,3 Changzheng Huang1 1Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 2Department of Radiology, Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, 221002, People’s Republic of China; 3Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People’s Republic of ChinaCorrespondence: Yanhong Sun; Changzheng Huang Tel/Fax +86 0571-87783777; Tel/Fax +86 027-85726359Email sunyh1128@zju.edu.cn; hcz0501@126.comBackground: Melanoma is one of the most malignant and aggressive skin tumors, and its incidence is increasing worldwide. However, few studies have investigated the process of tumorigenesis from normal skin to melanoma.Methods: Several bioinformatics analyses, including GEO databases, Oncomine database, TCGA database, STRING, MCODE and cytoHubba plug-ins, GEPIA, TIMER and TRRUST and DGIdb, were performed to disclose the hub genes and immunology implicated in primary melanoma tumorigenesis. Finally, immunohistochemistry (IHC) and quantitative real-time PCR (qPCR) were used to validate the results of bioinformatics analysis in vitro.Results: A total of 295 overlapping DEGs (ODEGs) (157 upregulated and 138 downregulated) and 9 hub genes were identified between primary melanoma and normal skin tissues. Functional analysis of these 9 hub genes indicated that the genes were primarily enriched in cell chemotaxis, the chemokine-mediated signaling pathway, the extracellular region, the extracellular space, chemokine activity and CXCR3 chemokine receptor binding. KEGG pathway enrichment showed that these genes were primarily involved in the chemokine signaling pathway, cytokine–cytokine receptor interaction, the toll-like receptor signaling pathway, the cytosolic DNA-sensing pathway and the TNF signaling pathway. Upregulated CCL5, CCL4, CXCL9 and CXCL10 demonstrated good overall survival (OS), and most of them have a higher expression in stage 0 and 1 of melanoma. Moreover, immune infiltration analysis showed that the above hub genes showed a strong positive correlation between their expression and infiltration of the six immune cell subsets. Transcription factor regulation network suggested that RELA and NFKB1 are the transcription factors of CCL4, CCL5, CXCL10 and CXCL2, while IRF7, IRF3 and IRF1 are the transcription factors of CCL5 and CXCL10. Drug–gene interaction analysis identified 46 drug–gene interactions. In vitro data demonstrated that the level of CCL4, CCL5, CXCL9 and CXCL10 is higher in melanoma than that in normal skin tissues, either at tissue or cell lines level.Conclusion: In summary, we identified 4 key chemokine members related to tumorigenesis and progression in primary melanoma, and these results may help to elucidate melanoma tumorigenesis and facilitate its treatment.Keywords: bioinformatic analysis, primary melanoma, normal skin, prognosis, tumorigenesis

Meixian Chen,1,* Lisheng Zhou,1,* Zhaoxia Liao,1 Xijiu Ye,1 Xujun Xuan,2 Beibei Gu,1 Fuding Lu1 1Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Andrology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fuding LuDepartment of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of ChinaTel +86-13560371081Email lfd19870901@126.comBackground: Osteosarcoma is one of the most common primary bone cancers with predominant occurrence in children and adolescents. This study aimed to determine the effects of sevoflurane treatment on the osteosarcoma progression and to explore the underlying molecular mechanisms.Materials and methods: The mRNA and protein expression levels were determined by qPCR and Western blot, respectively. Osteosarcoma cell proliferation, apoptosis and invasion were determined by MTT, caspase-3 activity, colony formation and Transwell invasion assays, respectively. The interaction between miR-203 and WNT2B 3ʹ untranslated region was confirmed by luciferase reporter assay.Results: Sevoflurane treatment for 6 hrs concentration-dependently suppressed cell viability, increased caspase-3 activity and up-regulated miR-203 expression in both U2OS and MG63 cells. MiR-203 overexpression suppressed cell viability, increased caspase-3 activity and suppressed cell growth and invasion of osteosarcoma cells. In addition, miR-203 knockdown attenuated the tumor-suppressive effects of sevoflurane treatment on osteosarcoma cells. Mechanistic studies showed that miR-203 repressed the expression of WNT2B in U2OS cells, and inhibition of miR-203 attenuated the suppressive effects of sevoflurane on WNT2B expression. More importantly, WNT2B overexpression attenuated the effects of sevoflurane treatment on cell viability, caspase-3 activity, cell growth and invasion of U2OS cells. MiR-203 overexpression suppressed Wnt/β-catenin signalling. Similarly, sevoflurane suppressed the activity of Wnt/β-catenin signalling, which was partially reversed by miR-203 knockdown and WTN2B overexpression.Conclusion: Our data showed the tumor-suppressive effects of sevoflurane on osteosarcoma cells, and mechanistic studies revealed that sevoflurane inhibited osteosarcoma cell proliferation and invasion partly via targeting the miR-203/WNT2B/Wnt/β-catenin axis.Keywords: osteosarcoma, proliferation, invasion, sevoflurane, miR-203, WNT2B, Wnt/β-catenin

Abstract Background Overweight and obesity pose a huge burden on individuals and society. While the relationship between lifestyle factors and overweight and obesity is well-established, the relative contribution of specific lifestyle factors remains unclear. To address this gap in the literature, this study utilizes interpretable machine learning methods to identify the relative importance of specific lifestyle factors as predictors of overweight and obesity in adults. Methods Data were obtained from 46,057 adults in the China Health and Nutrition Survey (2004–2011) and the National Health and Nutrition Examination Survey (2007–2014). Basic demographic information, self-reported lifestyle factors, including physical activity, macronutrient intake, tobacco and alcohol consumption, and body weight status were collected. Three machine learning models, namely decision tree, random forest, and gradient-boosting decision tree, were employed to predict body weight status from lifestyle factors. The SHapley Additive exPlanation (SHAP) method was used to interpret the prediction results of the best-performing model by determining the contributions of specific lifestyle factors to the development of overweight and obesity in adults. Results The performance of the gradient-boosting decision tree model outperformed the decision tree and random forest models. Analysis based on the SHAP method indicates that sedentary behavior, alcohol consumption, and protein intake were important lifestyle factors predicting the development of overweight and obesity in adults. The amount of alcohol consumption and time spent sedentary were the strongest predictors of overweight and obesity, respectively. Specifically, sedentary behavior exceeding 28–35 h/week, alcohol consumption of more than 7 cups/week, and protein intake exceeding 80 g/day increased the risk of being predicted as overweight and obese. Conclusion Pooled evidence from two nationally representative studies suggests that recognizing demographic differences and emphasizing the relative importance of sedentary behavior, alcohol consumption, and protein intake are beneficial for managing body weight status in adults. The specific risk thresholds for lifestyle factors observed in this study can help inform and guide future research and public health actions.

Abstract There is a significant interrelationship between cardiovascular disease and obstructive sleep apnea (OSA), as they share common risk factors and comorbidities. This study aimed to investigate the knowledge, attitude, and practice (KAP) of inpatients with cardiovascular disease towards OSA. This cross-sectional study was conducted between January, 2022 and January, 2023 at Zhongda Hospital Affiliated to Southeast University among inpatients with cardiovascular disease using a self-administered questionnaire. A self-designed questionnaire was used to assess KAP, and the STOP-Bang questionnaire was applied to evaluate participants’ OSA risk. Spearman correlation and path analyses were conducted to explore relationships among KAP scores and high OSA risk. Subgroup analyses were conducted within the high-risk population identified by the STOP-Bang questionnaire. In a study analyzing 591 questionnaires, 66.33% were males. Mean scores were 6.81 ± 4.903 for knowledge, 26.84 ± 4.273 for attitude, and 14.46 ± 2.445 for practice. Path analysis revealed high risk of OSA positively impacting knowledge (β = 2.351, P

Abstract Background Balance and mobility deficits are major concerns in stroke rehabilitation. Virtual reality (VR) training and Swiss-ball training are commonly used approaches to improve balance and mobility. However, no study has compared the efficacy of VR training, Swiss-ball training, and their combination in improving balance and mobility function or investigated cortical activation and connectivity in individuals with stroke. Methods A prospective, single-blinded, parallel-armed, multi-center randomized controlled trial with factorial design will be conducted. Seventy-six participants aged 30–80 years with stroke will be recruited. Participants will be allocated to one of the four groups: (A) the VR training + Swiss-ball training + conventional physical therapy group; (B) the Swiss-ball training + conventional physical therapy group; (C) the VR training + conventional physical therapy group; or (D) the conventional physical therapy group. All participants will receive 50 min of training per day, 5 times per week, for a total of 4 weeks. The primary outcomes will be balance and mobility measures. Secondary outcomes will include the 10-min walk test, dynamic gait index, and cortical activation. Outcomes will be measured on three occasions: at baseline, after the training, and at the 4-week follow-up. Discussion This trial will provide evidence to determine whether there are differences in clinical outcomes and cortical activation following two different types of exercise programs and their combination, and to elucidate the recovery mechanisms of balance and mobility function in individuals with stroke. Trial registration Chinese Clinical Trial Registry reference: www.chictr.org.cn (No. ChiCTR2400082135). Registered on May 24, 2024.

Abstract Background Although associations have been reported linking pretreatment thrombocytosis to cancer survival outcomes, the validity and strength of existing observational evidence have been contested. This study aimed to conduct an umbrella review to comprehensively appraise the strength, validity and credibility of these reported associations. Methods We searched Medline, Embase and Cochrane Database of Systematic Reviews from inception to 8 April 2023 to retrieve meta-analyses of observational studies. Meta-analyses were re-performed using a random-effect model and the strength of evidence was graded as convincing, highly suggestive, suggestive and weak according to seven pre-defined quantitative criteria reflecting statistical significance, amount of data, heterogeneity, and evidence of bias. The quality of review was appraised using the AMSTAR2 checklist. The umbrella review was reported adhering to the PRISMA guideline and was registered on PROSPERO (CRD42023455391). Results A total of 21 unique meta-analyses investigating ten cancer subtypes were included. All meta-analyses reported inferior survival outcome in cancer patients with pretreatment thrombocytosis, and 18 of them (85.7%) yielded statistically significant results (P 300 or 400 × 109 /L) to define thrombocytosis. Although evidence appraisal did not identify convincing evidence (Class I), the associations of thrombocytosis with inferior overall survival of lung, gastric, colorectal cancer and malignant mesothelioma were classified as highly suggestive evidence (Class II). According to AMSTAR2 ratings, no meta-analysis was identified with high or moderate quality. Conclusions Our findings consolidated the association between pretreatment thrombocytosis and poor survival outcomes in various cancers. Nonetheless, the absence of convincing associations indicates a need for further large-scale, high-quality evidence to confirm whether platelets can serve as a prognostic predictor or a therapeutic target.

Abstract Intrauterine adhesion (IUA), a prevalent etiology of female infertility, is attributed to endometrial damage. However, conventional therapeutic interventions for IUA are plagued by high recurrence rates. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUCMSC-EVs) demonstrate the promising therapeutic effects on IUA, but the current efficacy of extracellular vesicles (EVs) is hindered by lower retention and bioavailability. In this study, a thermosensitive hydrogel was utilized as a prolonged release carrier to improve the retention and bioavailability of hUCMSC-EVs in IUA treatment. The hydrogel-EVs complex effectively prolonged EVs retention in human endometrial stromal cells and an IUA mouse model. The complex exhibited superior protection against cellular injury, significantly alleviated endometrial damage, inhibited fibrosis, suppressed inflammation, and improved fertility compared to EVs alone. The results indicated that thermosensitive hydrogel enhanced the therapeutic capacity of EVs for IUA by prolonging their retention in the uterine environment. The hydrogel-EVs complex provides a novel strategy for the sustained release of hUCMSC-EVs in the treatment of IUA. Graphical Abstract

Introduction: Cell transplantation is an emerging and effective therapeutic approach for enhancing uterine adhesions caused by endometrial damage. Currently, human umbilical cord blood mononuclear cells (HUCBMCs) have been extensively for tissue and organ regeneration. However, their application in endometrial repair remains unexplored. Our investigation focuses on the utilization of HUCBMCs for treating endometrial injury. Methods: The HUCBMCs were isolated from health umbilical cord blood, and co-cultured with the injured endometrial stromal cells and injured endometrial organoids. The cell proliferation and apoptosis were measured by cck8 assays and flow cytometry. Western blotting was used to detect the expression of PTEN, AKT and p-AKT. Immunofluorescence assay revealed expression levels of epithelial-mesenchymal transition (EMT) -related markers such as E-cadherin, N-cadherin, and TGF-β1. The endometrial thickness, fibrosis level, and glandular number were examined after the intravenous injection of HUCBMCs in mouse endometrial models. Immunohistochemistry was employed to assess changes in growth factors vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) as well as fibrosis markers α-SMA and COL1A1. Additionally, expressions of EMT-related proteins E-cadherin and N-cadherin were evaluated. Results: HUCBMCs significantly improved the proliferation and reduced the apoptosis of damaged endometrial stromal cells (ESCs), accompanied by up-regulation of phospho-AKT expression. HUCBMCs increased endometrial thickness and glandular count while decreasing fibrosis and EMT-related markers in mouse endometrial models. Furthermore, EMT-related markers of ESCs and endometrial organoids were significantly decreased. Conclusions: Our findings suggest that HUCBMCs plays a pivotal role in mitigating endometrial injury through the attenuation of fibrosis. HUCBMCs may exert a reverse effect on the EMT process during the endometrium reconstruction.

Abstract Background This study aimed to compare the effects of two 12-week training intervention experimental ball games combined with standard behavioral rehabilitation against a control group solely utilizing standard behavioral rehabilitation on social communication impairments (SCI) in preschool children with Autism Spectrum Disorder (ASD). Methods A multi-arm controlled study design was implemented, involving 41 children diagnosed with ASD (mean age: 4.99 ± 0.76 years). 41 participants were randomized assigned to two experimental groups and a control group, The experimental group carried out ball combination training program group (BCTP) and mini-basketball training program group (MBTP) on the basis of routine behavioral rehabilitation, which underwent 12-week training interventions 5 times a week. The control group (n = 14) received only standard behavioral rehabilitation. Evaluations were conducted before and after interventions using the Social Responsiveness Scale, Second Edition (SRS-2). Results The results suggest that both 12-week interventions, BCTP, and MBTP, led to significant improvements in social communication impairment among children with ASD (p

Abstract For fractured gas reservoirs with strong water drive, gas phase trapping affects the gas recovery significantly. The recovery may be less than 50% for some reservoirs while it is only 12% for Beaver River gas field. The gas phase trapping mechanism has been revealed by the results of depletion experimental test. The residual pressure of the trapped gas is as high as 11.75 MPa with a 12.8 cm imbibition layer resulting in gas recovery deceased 49.5% compared with that without imbibition layer. A mathematical model is built to calculate the imbibition thickness based on capillary pressure and relative permeability of the matrix. The gas phase trapping are analyzed by two representative wells in Weiyuan gas field, the intermittent production reinforces the imbibition thickness and result in gas trapped in the matrix block with high residual pressure for the low performace gas wells, the extremely low gas recovery can be explained more rationally. That lays a foundation of improving the gas recovery for fractured reservoirs.

Background/purpose: Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease. Despite a variety of scientific articles have been available till date, merely a few scientometric analyses have been systematically carried out in this field. The objective of this study was to recognize the hotspots and research trends related to RAS via bibliometric approach. Materials and methods: The Elsevier's Scopus database was searched to retrieve qualified literature through an advanced search strategy on 9 Feb 2023. The basic information was collected as following: article type, publication year, journals, impact factor, the count of citations, citation density, keywords, authors, contributing institutions and country. Results: A list of 986 publications were identified from 1933 to 2022, and the number of citations for each paper varied from 0 to 283. A steady increasing trend in the number of documents could be observed each decade with the summit in 2010s. Controlled study (n = 334) and major clinical study (n = 192) were the most common types of study design. Scully C (n = 26) was identified as the most productive author. United States (n = 166) and Turkey (n = 101) top the list of dedicating countries. Conclusion: This report would offer profound insight into the current status of RAS research and serve as a reference source for anyone planning to enhance the quality of future work.

This study aimed to investigate the effects of different proportions of dietary fermented sweet potato residue (FSPR) supplementation as a substitute for corn on the nutrient digestibility, meat quality, and intestinal microbes of yellow-feathered broilers. Experiment 1 (force-feeding) evaluated the nutrient composition and digestibility of mixtures with different proportions of sweet potato residue (70%, 80%, 90%, and 100%) before and after fermentation. In Experiment 2 (metabolic growth), a total of 420 one-day-old yellow-feathered broilers were randomly allocated to 4 groups and fed corn-soybean meal-based diets with 0, 5%, 8%, and 10% FSPR as a substitute for corn. The force-feeding and metabolic growth experiments were performed for 9 and 70 d, respectively. The treatment of 70% sweet potato residue (after fermentation) had the highest levels of crude protein, ether extract, and crude fiber and improved the digestibility of crude protein and amino acids (P

Post-translational modification (PTM) plays a crucial role in adaptation of mammals to environmental changes, enabling them to survive in stressful situations. One such PTM is SUMO modification, which is evolutionarily conserved. It involves the covalent and reversible attachment of a small ubiquitin-like modifier (SUMO) to lysine (Lys) residues in the target protein. SUMOylation regulates various functions, including cell proliferation, differentiation, apoptosis, senescence, and maintenance of specific cellular activities. It achieves this by influencing protein-protein interactions, subcellular localization, protein stability, and DNA binding activity. Mounting evidence suggests that SUMOylation is implicated in the pathogenesis of metabolic disorders such as obesity, insulin resistance, and fatty liver. This review aims to provide an overview of the role of SUMOylation in regulating tissue adaptation to metabolic stress. Recent advancements in spectroscopic techniques have shed light on potential targets of SUMOylation and the underlying regulatory mechanisms have been elucidated, laying the theoretical foundation for the development of targeted SUMOylation interventions for metabolic syndrome while minimizing side effects.

Hexafluoroisobutylene (HFIB) is an important compound widely used in semiconductor lithography materials, refrigerants, fluorine coatings, and pharmaceutical intermediates in the fluorination industry. Owing to its toxicity, the occupational exposure in the workplace, especially for pregnant woman is the concern and there is still lack of the data of HFIB toxicity on pregnancy and fetal development. Here, for the first time, we investigated the effects of HFIB on pregnant rats and fetal development. The pregnant rats were exposed to different doses of HFIB (0 ppm, 27.2 ppm, 53.5 ppm, 105.6 ppm) via whole-body inhalation for the period of organogenesis, which from implantation (gestation day 5) to the day prior to scheduled caesarean section (gestation day 19). The results showed that the pregnant rats exposed to 105.6 ppm HFIB displayed systemic toxicity, including a decrease in body weight and food consumption, as well as tracheal inflammation, pulmonary interstitial inflammation and renal tubular swelling. Moreover, reduced fetal and placental weights, delayed ossification, and a reduced number of ossification centers were observed in fetuses delivered by pregnant rats exposed to 105.6 ppm. These effects were attributed to severe maternal weight loss. In addition, it would be useful to note that no whole-body, visceral or skeletal congenital malformations were observed. However, HFIB exposure at 53.5 ppm showed no significant adverse effects on pregnant rats and fetuses. These findings demonstrate that 105.6 ppm HFIB is a toxic concentration, while 53.5 ppm HFIB is the no-observed-adverse-effect concentration (NOAEC) for both pregnancy and fetal development. This study for the first time to provide evidence for the health risk of HFIB exposure on pregnancy and fetal development.

BackgroundPsychiatric disorders, such as major depressive disorder (MDD), anxiety disorder (AD), bipolar disorder (BD), and schizophrenia (SCZ), are disturbances in brain activity that lead to disorders of cognition, behavior, and emotion regulation. Among Sjogren syndrome (SS) patients, psychiatric disorders are more prevalent than in the general population. Identifying associated risk factors can provide new evidence for clinical diagnosis and treatment.MethodsWe selected genetic instruments based on published genome-wide association studies (GWASs) to determine predisposition. Then, we conducted a 2-sample bidirectional Mendelian randomization (MR) analysis to explore the potential causal associations between SS and four major psychiatric disorders. The primary analysis was performed using MR with the inverse-variance weighted method. Confirmation was achieved through Steiger filtering and testing to determine the causal direction. Sensitivity analyses were conducted using MR-Egger, MR-PRESSO, and “leave-one-out” method methods.ResultsOur study showed that SS was linked to BD and SCZ, indicating that individuals with SS may have a reduced risk of developing BD (IVW: OR = 0.940, P=0.014) and SCZ (IVW: OR = 0.854, P=1.47*10-4), while there was no causal relationship between SS and MDD or AD. MR−Egger regression shows no evidence of pleiotropy (BD: intercept = 0.007, p = 0.774; SCZ: intercept = 0.051, p = 0.209). The same as the MR-PRESSO analysis (BD: global test p = 1.000; SCZ: global test p = 0.160). However, the results from the leave-one-out analysis demonstrated instability. Specifically, after excluding SNP rs3117581, the effects on BD and SCZ were found to be non-significant, suggesting the potential influence of unrecognized confounding factors. The results of the reverse MR show that four major psychiatric disorders had no causal effects on SS.ConclusionsOur research findings demonstrate a causal relationship between SS and SCZ, as well as between SS and BD. There are no causal effects between the four major psychiatric disorders and SS. These findings suggest that SS may have the potential to reduce the risk of both psychiatric disorders. This study provides new insight for their prevention and treatment.

Acute retinal ischemia and ischemia-reperfusion injury are the primary causes of retinal neural cell death and vision loss in retinal artery occlusion (RAO). The absence of an accurate mouse model for simulating the retinal ischemic process has hindered progress in developing neuroprotective agents for RAO. We developed a unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) mouse model using silicone wire embolization combined with carotid artery ligation. The survival of retinal ganglion cells and visual function were evaluated to determine the duration of ischemia. Immunofluorescence staining, optical coherence tomography, and haematoxylin and eosin staining were utilized to assess changes in major neural cell classes and retinal structure degeneration at two reperfusion durations. Transcriptomics was employed to investigate alterations in the pathological process of UPOAO following ischemia and reperfusion, highlighting transcriptomic differences between UPOAO and other retinal ischemia-reperfusion models. The UPOAO model successfully replicated the acute interruption of retinal blood supply observed in RAO. 60 min of Ischemia led to significant loss of major retinal neural cells and visual function impairment. Notable thinning of the inner retinal layer, especially the ganglion cell layer, was evident post-UPOAO. Temporal transcriptome analysis revealed various pathophysiological processes related to immune cell migration, oxidative stress, and immune inflammation during the non-reperfusion and reperfusion periods. A pronounced increase in microglia within the retina and peripheral leukocytes accessing the retina was observed during reperfusion periods. Comparison of differentially expressed genes (DEGs) between the UPOAO and high intraocular pressure models revealed specific enrichments in lipid and steroid metabolism-related genes in the UPOAO model. The UPOAO model emerges as a novel tool for screening pathogenic genes and promoting further therapeutic research in RAO.

Fresh produce is traditionally labeled with plastic price lookup (PLU) stickers that are attached to the produce surface using edible glue. However, both the stickers and glue are environmental contaminants, and the stickers can still easily detach from the produce surface during handling and disrupt traceability. An alternative method of labeling, the CO2 laser-labeling technology (LLT), has been gaining attention in recent years. However, engraving Quick Response (QR) code using LLT is unique, and the performance of this technology varies from produce item to produce item, and information on its effects on postharvest quality, microbial safety, and economic feasibility has not been reported. The objectives of this study were to investigate the effect of laser-labeling technology on (1) postharvest quality, (2) microbial safety, and (3) economic analysis of this technology. Three horticultural crops, ‘Red Delicious’ apple (Malus pumila), green bell pepper (Capsicum annuum), and cucumber (Cucumis sativus) were procured from a local grocery store. Each produce was engraved with a Quick Response (QR) code or 6-digit alphanumerical (text) code using the commercially available Trotec Speedy 300 CO2 laser engraver, followed by the application of edible wax. Fresh weight loss for laser-printed produce was higher compared to controls, but no difference in visual quality ratings was observed. The laser-labeled produce was assessed for microbial contamination by artificially inoculating rifampicin-resistant Escherichia coli (E. coli) log10 6 CFU/mL to the labeled fruit. The results showed that the population of rifampicin-resistant E. coli was statistically higher in all three products labeled with text code compared to the nontreated controls. The QR-coded treatments were similar to the controls. The wax application did not affect the microbial attachment on the laser-labeled produce. The CO2 laser labeling technology has the potential for industrial application.

Gut microbiota acts as a critical regulator in the development of nonalcoholic fatty liver disease (NAFLD), making probiotics a promise therapeutic strategy. Studies are needed to identify beneficial Bacteroides strains against NAFLD. Bacteroides ovatus (B. ovatus) may also exhibit therapy effect on NAFLD. The aim of this work was to evaluate the effect of B. ovatus on NAFLD and examine the mechanism. C57BL/6 J male mice were randomly divided into three groups: a control group (NCD) that received control standard diet, a model group (M) with high-fat and high-cholesterol (HFHC) diet, and M_Bo group that was fed HFFC supplemented with B. ovatus. Treatment with B. ovatus could reduce body weight, prevent hepatic steatohepatitis and liver injury. Mechanistically, B. ovatus induced changes of gut microbial diversity and composition, characterized by a decreased Firmicutes/Bacteroidetes (F/B) ratio in M_Bo group mice, a lower abundance of Proteobacteria, Verrucomicrobiota at phylum level and Ruminococcus_torques_group, Ruminococcus_gauvreauii_group, Erysipelatoclostridium at genus level, simultaneously a remarkablely higher fecal abundance of Lachnospiraceae_NK4A136_group, norank_f__Oscillospiraceae, Colidextribacter. Compared with M group, mice treated with B. ovatus showed an markedly altered fecal short chain fatty acids (SCFAs), a decline in serum levels of lipopolysaccharide (LPS), CD163, IL-1β, TNF-α, reduced macrophages in livers. Additionally, B. ovatus treatment caused downregulation of genes involved in denovo lipogenesis (such as Srebfl, Acaca, Scd1, Fasn), which was accompanied by the upregulation of genes related with fatty acid oxidation (such as Ppara). In conclusion, this study provides evidence that B. ovatus could ameliorate NAFLD by modulating the gut–liver axis.

Abstract To evaluate the predictive and prognostic value of fibroblast growth factor 21 (FGF21) levels in retinal artery occlusion (RAO) patients. In this case–control study, serum FGF21 levels were detected by using the ELISA method. Multivariable logistic regression analyses were performed to evaluate the significance of FGF21 in assessing the risk of developing RAO and its impact on vision and concurrent ischemic stroke. Compared with control group, serum FGF21 levels were significantly higher (median [IQR] = 230.90[167.40,332.20] pg/ml) in RAO patients. Multivariate logistic regression analysis showed that elevated serum FGF21 levels were associated with a higher risk of RAO occurrence (P = 0.025, OR [95%CI] = 9.672 [2.573, 36.359]) after adjustment for multiple confounding factors. Higher serum FGF21 levels were negatively associated with visual acuity improvement (P = 0.029, OR [95%CI] = 0.466[0.235, 0.925]) and positively correlated with concurrent ischemic stroke (P = 0.04, OR [95% CI] = 1.944[1.029, 3.672]) in RAO patients. Elevated serum FGF21 levels could promote the development of RAO and indicate worse visual prognosis and increase the risk of concurrent ischemic stroke, which might help clinicians early diagnose and treat RAO patients.

Abstract Clinical research has suggested that chronic HBV infection exerts a certain effect on the occurrence of cardiovascular disease by regulating cholesterol metabolism in liver cells. High serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio plays a certain role in the above regulation, and it serves as a risk factor for cardiovascular disease. However, whether the ApoB/ApoA1 ratio is correlated with chronic HBV infection and its disease progression remains unclear. In accordance with the inclusion and exclusion criteria, all 378 participants administrated at Renmin Hospital of Wuhan University from March 2021 to March 2022, fell into Healthy Control (HC) group (50 participants), Hepatocellular carcinoma (HCC) group (107 patients), liver cirrhosis (LC) group (64 patients), chronic hepatitis B (CHB) group (62 patients), chronic hepatitis C (CHC) group (46 patients) and Hepatitis E Virus (HEV) group (49 patients). Serum ApoA1 and ApoB concentrations were measured at admission, and the ApoB/ApoA1 ratio was determined. The levels of laboratory parameters in the respective group were compared and ApoB/ApoA1 ratios in HCC patients and LC patients with different severity were further analyzed. ROC curves were plotted to analyze the early diagnostic ability of ApoB/ApoA1 ratio for HBV-associated HCC. Logistic regression and restricted cubic spline analysis were used to explore the correlation between ApoB/ApoA1 ratio and LC and HCC risk. A comparison was drawn in terms of ApoB/ApoA1 ratio between the groups, and the result was expressed in descending sequence: HEV group > CHB group > LC group > HCC group > CHC group > HC group, early-stage HCC

Compelling evidence indicates that dyslipidemia is positively associated with oral lichen planus (OLP). The types and magnitude of lipid metabolism disturbance in peripheral blood of OLP patients have been investigated in different studies. Yet, consensus on how these different lipid components varied in levels for the development of OLP lesions has not been reached so far. Herein, a total of 8 eligible studies were recognized, which enrolled 533 cases of OLP and 499 healthy controls. The analysis showed that the average total triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) levels were considerably higher, and high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in OLP patients compared to healthy controls. Collectively, the lipid profile panel maybe serve as the potential predictive indicator for screening OLP.

This study aimed to determine the regulatory mechanism of dietary zinc lactate (ZL) supplementation on intestinal oxidative stress damage in a paraquat (PQ)-induced piglet model. Twenty-eight piglets (mean body weight 9.51 ± 0.23 kg) weaned at 28 d of age were randomly divided into control, ZL, PQ, and ZL + PQ groups (n = 7 in each group). The ZL-supplemented diet had little effect on growth performance under normal physiological conditions. However, under PQ challenge, ZL supplementation significantly improved average daily gain (P

In the information age, there's a growing need to improve eldercare services for the mobile elderly population. Current Chinese eldercare often separates medical and nursing care, leading to low resource use. This study aims to integrate community healthcare with data analysis and intelligent coordination to meet the floating elderly's needs. Using a Stacking model, it identifies key indicators and develops a mobile terminal based community healthcare model. Results show that primary indicators are crucial, scoring between 4.48−5.00, with secondary and tertiary indicators also significant. The KMO value is 0.93, confirming the model's validity. Compared to traditional methods, this new approach enhances accuracy by 7%, offering a valuable framework for community-based eldercare integration in China. HIGHLIGHTS This research mainly focuses on the integration model of the elderly floating population and community health care.; The experimental results showed that the model proposed the importance of community health care indicators for the elderly floating population, with a distribution of 4.48–5.00 and a full score of 52.17–100%.;

Abstract Central retinal artery occlusion (CRAO) is an acute retinal ischaemic disease, but early diagnosis is challenging due to a lack of biomarkers. Blood samples were collected from CRAO patients and cataract patients. Gene expression profiles were distinct between arterial/venous CRAO blood (A–V group) and venous CRAO/control blood (V–C group) samples. Differentially expressed genes (DEGs) were subjected to GO and KEGG enrichment analyses. Hub genes were identified by Cytoscape and used to predict gene interactions via GeneMANIA. Immune cell infiltration was analysed by CIBERSORT. More than 1400 DEGs were identified in the A–V group and 112 DEGs in the V–C group compared to controls. The DEGs in both groups were enriched in the ribosome pathway, and those in the V–C group were also enriched in antigen processing/MHC pathways. Network analysis identified ribosomal proteins (RPS2 and RPS5) as the core genes of the A–V group and MHC genes (HLA-F) as the core genes of the V–C group. Coexpression networks showed ribosomal involvement in both groups, with additional immune responses in the V–C group. Immune cell analysis indicated increased numbers of neutrophils and T cells. Ribosomal and MHC-related genes were identified as potential CRAO biomarkers, providing research directions for prevention, diagnosis, treatment and prognosis.

Abstract Inertial Measurement Unit-based methods have great potential in capturing motion in large-scale and complex environments with many people. Sparse Inertial Measurement Unit-based methods have more research value due to their simplicity and flexibility. However, improving the computational efficiency and reducing latency in such methods are challenging. In this paper, we propose Fast Inertial Poser, which is a full body motion estimation deep neural network based on 6 inertial measurement units considering body parameters. We design a network architecture based on recurrent neural networks according to the kinematics tree. This method introduces human body shape information by the causality of observations and eliminates the dependence on future frames. During the estimation of joint positions, the upper body and lower body are estimated using separate network modules independently. Then the joint rotation is obtained through a well-designed single-frame kinematics inverse solver. Experiments show that the method can greatly improve the inference speed and reduce the latency while ensuring the reconstruction accuracy compared with previous methods. Fast Inertial Poser runs at 65 fps with 15 ms latency on an embedded computer, demonstrating the efficiency of the model.

Abstract Background Preoperative prediction of International Federation of Gynecology and Obstetrics (FIGO) stage in patients with epithelial ovarian cancer (EOC) is crucial for determining appropriate treatment strategy. This study aimed to explore the value of contrast-enhanced CT (CECT) radiomics in predicting preoperative FIGO staging of EOC, and to validate the stability of the model through an independent external dataset. Methods A total of 201 EOC patients from three centers, divided into a training cohort (n = 106), internal (n = 46) and external (n = 49) validation cohorts. The least absolute shrinkage and selection operator (LASSO) regression algorithm was used for screening radiomics features. Five machine learning algorithms, namely logistic regression, support vector machine, random forest, light gradient boosting machine (LightGBM), and decision tree, were utilized in developing the radiomics model. The optimal performing algorithm was selected to establish the radiomics model, clinical model, and the combined model. The diagnostic performances of the models were evaluated through receiver operating characteristic analysis, and the comparison of the area under curves (AUCs) were conducted using the Delong test or F-test. Results Seven optimal radiomics features were retained by the LASSO algorithm. The five radiomics models demonstrate that the LightGBM model exhibits notable prediction efficiency and robustness, as evidenced by AUCs of 0.83 in the training cohort, 0.80 in the internal validation cohort, and 0.68 in the external validation cohort. The multivariate logistic regression analysis indicated that carcinoma antigen 125 and tumor location were identified as independent predictors for the FIGO staging of EOC. The combined model exhibited best diagnostic efficiency, with AUCs of 0.95 in the training cohort, 0.83 in the internal validation cohort, and 0.79 in the external validation cohort. The F-test indicated that the combined model exhibited a significantly superior AUC value compared to the radiomics model in the training cohort (P

ABSTRACT Objective In this study, we employed a Mendelian randomization (MR) approach to investigate the independent causal associations of six body composition traits with gestational diabetes mellitus (GDM). Methods Genome‐wide significant levels (P

Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder with the predominant clinical manifestation of spasticity in the lower extremities. Patients with HSP experience spastic paralysis in both lower limbs, leading to progressive walking difficulties, increased reflexes, spasms, and extensor plantar responses. We successfully generated induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells (PBMCs) obtained from a patient diagnosed with HSP. The iPSCs exhibited a normal karyotype, expressed pluripotency markers, and differentiated into the three germ layers in vitro.

Glioblastoma multiforme (GBM) is a formidable cancer to treat due to the lack of effective drugs that can also efficiently cross the blood–brain barrier (BBB). Herein, a novel strategy involving the synthesis of p28 peptide‐conjugated, lexiscan (LEX)‐loaded, bardoxolone methyl (BM) self‐assembled nanoparticles, designated as p28‐LBM NPs, is introduced. These NPs are designed to overcome the dual challenges of effectively killing GBM cells and efficiently penetrating the brain. The p28 peptide is chosen for targeted delivery to brain tumors, and LEX is employed to enhance drug penetration across the BBB. The successful penetration of brain tumors by the p28‐LBM NPs after intravenous administration is demonstrated, with BM delivered as part of the NPs significantly inhibiting GBM tumor growth and extending the survival of mice with tumors. In conclusion, the p28‐LBM NPs present a promising approach for GBM treatment, with potential for effective and safe clinical applications in the future.

Carbon fiber (CF) is one of the conductive fillers with the best electrical conductivity, but it is expensive and difficult to disperse in cement matrix, which limits the application and development of CF conductive cement-based composites. Therefore, this paper took the conductive cement slurry with CF content of 1.0 % as the control group, and proposed to use low-cost graphite (G) and nano-carbon black (NCB) instead of some CFs to prepare conductive cement-based composites. The synergistic enhancement effect between different conductive fillers was explored to reduce the cost of materials while maintaining electrical conductivity. The results showed that the resistivity decreased first, then increased, then decreased and then increased with the increase of the proportion of particle conductive filler instead of CF. The resistivity of conductive cement slurry was 125.65 Ω·cm when G replaced 20 % CF, the resistivity of conductive cement slurry was 140.66 Ω·cm when NCB replaced 30 % CF, and the resistivity of conductive cement slurry was 122.05 Ω·cm when G and NCB replaced 30 % CF, which were close to the resistivity of the control group (122.35 Ω·cm). The purpose of reducing the cost of materials without affecting the conductivity of conductive cement slurry was achieved.

Stratified rock masses comprise various rocks with different thicknesses, lithologies, and compositions. They exhibit unique cracking morphology and failure modes when subjected to external loads. Understanding and mastering the fracture morphology and failure laws of stratified rock masses under three-dimensional mechanical conditions is crucial for researching disasters in underground engineering geology. This paper presents a three-dimensional double-layer rock mass model established using the numerical calculation method based on mesoscopic statistical damage mechanics. The model simulates the cracking mode of the rock surface under biaxial tensile conditions. The simulation results are quantified using PCAS software. Crack indexes, such as the number of cracked blocks, average cracked block area, and surface crack rate, are used to evaluate the degree of influence of different factors on the cracking of the rock surface layer. The results indicate that the degree of surface crack development varies linearly with the degree of homogeneity (m). Additionally, the layer thickness ratio (η) is positively correlated with the average fragmentation area, and the two are logarithmic. Regardless of the model scale, the average circumference of each block is approximately equal to the model side length. The model exhibits the highest degree of crack development when the loads in the x and y directions are equal. Moreover, the degree of crack development in the model is also influenced by the loading per step, and the two are proportional.

Honeycomb‐layered oxides are a class of cathode materials for sodium‐ion batteries with great potential due to their high voltage and high capacity. However, the structural instability and voltage fading during cycling limit their practical application. Herein, it is revealed that Te substitution into Na3Ni2SbO6 induces a new dual‐honeycomb structure, which can elevate the average discharge voltage of the cathode materials from 3.2 to 3.8 V with improved cycle stability and alleviated voltage decay. Synchrotron operando X‐ray diffraction demonstrates that Te substitution can suppress the O3−P3−O1‐phase transition during charge and discharge processes effectively, benefited from the strong TeO covalent bonds. The resulted Na2.2Ni2Sb0.2Te0.8O6 cathode exhibits a high capacity retention of 70.9% after 1000 cycles at 1C, with an elevated operating voltage of ≈3.8 V. Theoretical calculations reveal that the introduced TeO bonds break the symmetric distribution of charge in Ni/Sb honeycomb structure and elevate the operation voltage by increased valence band width. Proper Te substitution can promote the rate and cycle capability of the cathode by suppressing phase transition and decreasing the bandgap.

BackgroundAngiotensin II receptor blockers (ARBs) are utilized for the management of hypertension and diabetes. Previous meta-analyses suggested that azilsartan medoxomil (AZL-M) improved blood pressure (BP) reduction, but there were no safety findings or suggestions for patients with hypertension or diabetes.MethodsWe performed an efficacy and safety meta-analysis of randomized controlled trials (RCTs) evaluating AZL-M therapy for reducing BP in patients with hypertension. Patients with hypertension complicated by diabetes were analyzed. The relevant literature was searched in English and Chinese databases for RCTs involving AZL-M in hypertension. Efficacy variables included the change from baseline in the 24-h mean systolic/diastolic BP measured by ambulatory BP monitoring, the change from baseline in clinic systolic/diastolic BP, and responder rates. Safety variables included total adverse events (AEs), serious AEs, AEs leading to discontinuation, and AEs related to the study drug. The raw data from the included studies were utilized to calculate the odds ratio (OR) for dichotomous data and the mean difference (MD) for continuous data, accompanied by 95% confidence intervals (CIs). Statistical analysis was performed using R software.ResultsA total of 11 RCTs met the inclusion criteria, representing 7,608 patients, 5 of whom had diabetes. Pooled analysis suggested a reduction in BP among patients randomized to 40 mg of AZL-M vs. control therapy [24-h ambulatory blood pressure monitoring (ABPM) mean systolic blood pressure (SBP) (MD: −2.85 mmHg), clinic SBP (MD: −3.48 mmHg), and clinic diastolic blood pressure (DBP) (MD: −1.96 mmHg)] and for 80 mg of AZL-M vs. control therapy [24-h ABPM mean SBP (MD: −3.59 mmHg), 24-h ABPM mean DBP (MD: −2.62 mmHg), clinic SBP (MD: −4.42 mmHg), clinic DBP (MD: −3.09 mmHg), and responder rate (OR: 1.46)]. There was no difference in the reduction of risks, except for dizziness (OR: 1.56) in the 80-mg AZL-M group or urinary tract infection (OR: 1.82) in the 40-mg AZL-M group. Analysis of patients with diabetes revealed that AZL-M can provide superior management, while safety and tolerability were similar to those of control therapy.ConclusionsAZL-M appears to reduce BP to a greater extent than dose-control therapy and does not increase the risk of adverse events in patients with hypertension and diabetes compared with placebo.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=464284, identifier PROSPERO CRD42023464284.

IntroductionOxidative stress plays a pivotal role in modulating the balance of intestinal flora and the gut-liver axis, while also serving as a key determinant of the growth potential of weaned piglets. However, few studies have subdivided and compared acute and chronic oxidative stress.MethodsIn this study, an intestinal model of acute oxidative stress in weaned piglets using paraquat (PQ) and a chronic oxidative stress model using D-galactosa in weaned piglets were conducted. And we further systematically compare their effects.ResultsBoth acute and chronic oxidative stress models impaired intestinal barrier function and liver function. Chronic stress caused by D-galactose can result in severe redox dysregulation, while acute stress caused by paraquat can lead to inflammation and liver damage. Additionally, the components involved in the CAR pathway were expressed differently. Chronic or acute oxidative stress can reduce the diversity and composition of intestinal flora. In the PQ group, the richness of Mogibacterium and Denitratisoma improved, but in the D-gal group, the richness of Catenisphaera and Syntrophococcus increased.DiscussionNot only does this research deepen our understanding of the effects of acute and chronic oxidative stress on intestinal functions, but it also characterizes characteristic changes in the gut flora, potentially identifying novel therapeutic targets and opening new avenues for future research.

ContextDespite the recognition of attention deficit hyperactivity disorder (ADHD) as a multifaceted neurodevelopmental disorder, its core causes are still ambiguous. The objective of this study was to explore if the traits of circulating immune cells contribute causally to susceptibility to ADHD.MethodsBy employing a unified GWAS summary data covering 731 immune traits from the GWAS Catalog (accession numbers from GCST0001391 to GCST0002121), our analysis focused on the flow cytometry of lymphocyte clusters, encompassing 3,757 Sardinians, to identify genetically expected immune cells. Furthermore, we obtained summarized GWAS statistics from the Psychiatric Genomics Consortium to evaluate the genetic forecasting of ADHD. The studies employed ADHD2019 (20,183 cases and 35,191 controls from the 2019 GWAS ADHD dataset) and ADHD2022 (38,691 cases and 275,986 controls from the 2022 GWAS ADHD dataset). Through the examination of genome-wide association signals, we identified shared genetic variances between circulating immune cells and ADHD, employing the comprehensive ADHD2022 dataset. We primarily utilized inverse variance weighted (IVW) and weighted median methods in our Mendelian randomization research and sensitivity assessments to evaluate diversity and pleiotropy.ResultsAfter adjusting for false discovery rate (FDR), three distinct immunophenotypes were identified as associated with the risk of ADHD: CD33 in Im MDSC (OR=1.03, CI: 1.01~1.04, P=3.04×10−5, PFDR=0.015), CD8br NKT %T cell (OR=1.08, 95%CI: 1.04~1.12, P=9.33×10−5, PFDR=0.023), and CD8br NKT %lymphocyte (OR=1.08, 95%CI: 1.03~1.12, P=3.59×10−4, PFDR=0.066). Furthermore, ADHD showed no statistical effects on immunophenotypes. It’s worth noting that 20 phenotypes exist where ADHD’s appearance could diminish 85% of immune cells, including FSC-A in myeloid DC (β= -0.278, 95% CI: 0.616~0.931, P=0.008), CD3 in CD45RA- CD4+ (β= -0.233, 95% CI: 0.654~0.960, P=0.017), CD62L- monocyte AC (β=0.227, 95% CI: 0.038~1.518, P=0.019), CD33 in CD33br HLA DR+ CD14dim (β= -0.331, 95% CI: 0.543~0.950, P=0.020), and CD25 in CD39+ resting Treg (β=0.226, 95% CI: 1.522, P=0.022), and FSC-A in monocytes (β= -0.255, 95% CI: 0.621~0.967, P=0.234), among others.ConclusionStudies indicate that the immune system’s response influences the emergence of ADHD. The findings greatly improve our understanding of the interplay between immune responses and ADHD risk, aiding in the development of treatment strategies from an immunological perspective.

Background: There is no standard consensus on the optimal number of cycles of neoadjuvant immunotherapy prior to surgery for patients with locoregionally advanced non-small cell lung cancer (NSCLC). We carried out a systematic review to evaluate the efficacy and safety of neoadjuvant immunotherapy with different treatment cycles in order to provide valuable information for clinical decision-making. Methods: PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were systematically searched before May 2023. The included studies were categorized based on different treatment cycles of neoadjuvant immunotherapy to assess their respective efficacy and safety in patients with resectable NSCLC. Results: Incorporating data from 29 studies with 1331 patients, we found major pathological response rates of 43 % (95%CI, 34–52 %) with two cycles and 33 % (95%CI, 22–45 %) with three cycles of neoadjuvant immunotherapy. Radiological response rates were 39 % (95%CI, 28–50 %) and 56 % (95%CI, 44–68 %) for two and three cycles, respectively, with higher incidence rates of severe adverse events (SAEs) in the three-cycle group (32 %; 95%CI, 21–50 %). Despite similar rates of R0 resection between two and three cycles, the latter showed a slightly higher surgical delay rate (1 % vs. 7 %). Neoadjuvant treatment modes significantly affected outcomes, with the combination of immunotherapy and chemotherapy demonstrating superiority in improving pathological and radiological response rates, while the incidence of SAEs in patients receiving combination therapy remained within an acceptable range (23 %; 95%CI, 15–35 %). However, regardless of the treatment mode administered, an increase in the number of treatment cycles did not result in substantial improvement in pathological response rates. Conclusion: There are clear advantages of combining immunotherapy and chemotherapy in neoadjuvant settings. Increasing the number of cycles of neoadjuvant immunotherapy from two to three primarily may not substantially improve the overall efficacy, while increasing the risk of adverse events. Further analysis of the outcomes of four cycles of neoadjuvant immunotherapy is necessary.

The plant cell wall, a vital component in providing structural integrity and facilitating growth, comprises cellulose microfibrils among its major constituents. This study employed Atomic Force Microscopy (AFM) to investigate the intricate relationship between genetic mutation, cellulose microfibril organization, nanomechanical properties of cellulose microfibrils and plant growth. Focusing on the Arabidopsis thaliana wild type (WT) and ixr1–2 mutant population (known for resistance to herbicide ISOXABEN), we utilized AFM to scrutinize cellulose microfibrils on the newly synthesized cell wall in 5-day-old dark-grown hypocotyls. Our macroscopic analysis revealed significant differences in plant growth, prompting a detailed examination at the nanoscale using AFM to discover if the macroscopic disparity between these two populations gets translated in structural details, orientation, and mechanical properties of cellulose microfibrils at the nanoscale too. AFM analysis highlighted distinct organizational disparities in cellulose microfibrils between the WT and mutant population. Our results revealed that the WT manifests a more aligned and oriented microfibril structure in contrast to the mutant population that shows significantly less aligned cellulose microfibrils in the plant growth direction. Also, the WT and mutant population demonstrate nuanced differences in height, width, roughness, deformation, and stiffness. The observed nanoscale alterations in microfibril structure and nano-mechanical properties contribute to an improved understanding of the intricate dynamics governing plant cell wall structure and its pivotal role in growth and development.

Introduction: Identification of high-risk people for Alzheimer's disease (AD) is critical for prognosis and early management. Longitudinal epidemiologic studies have observed heterogeneity in the brain and cognitive aging. Brain resilience was described as above-expected cognitive function. The “resilience” framework has been shown to correlate with individual characteristics such as genetic factors and age. Besides, accumulative evidence has confirmed the association of mitochondria with the pathogenesis of AD. However, it is challenging to assess resilience through genetic metrics, in particular incorporating mitochondria-associated loci. Objectives: In this paper, we first demonstrated that polygenic risk scores (PRS) could characterize individuals' resilience levels. Then, we indicated that mitochondria-associated loci could improve the performance of PRSs, providing more reliable measurements for the prevention and diagnosis of AD. Methods: The discovery (N = 1,550) and independent validation samples (N = 2,090) were used to construct nine types of PRSs containing mitochondria-related loci (PRSMT) from both biological and statistical aspects and combined them with known AD risk loci derived from genome-wide association studies (GWAS). Individuals' levels of brain resilience were comprehensively measured by linear regression models using eight pathological characteristics. Results: It was found that PRSs could characterize brain resilience levels (e.g., Pearson correlation test Pmin = 7.96×10-9). Moreover, the performance of PRS models could be efficiently improved by incorporating a small number of mitochondria-related loci (e.g., Pearson correlation test P improved from 1.41×10-3 to 6.09×10-6). PRSs' ability to characterize brain resilience was validated. More importantly, by incorporating some mitochondria-related loci, the performance of PRSs in measuring brain resilience could be significantly improved. Conclusion: Our findings imply that mitochondria may play an important role in brain resilience, and targeting mitochondria may open a new door to AD prevention and therapy.

Rehabilitation devices, such as traditional rigid exoskeletons or exosuits, have been widely used to rehabilitate upper limb function post-stroke. In this paper, we have developed an exosuit with four degrees of freedom to enable users to involve more joints in the rehabilitation process. Additionally, a hybrid electroencephalogram-based (EEG-based) control approach has been developed to promote active user engagement and provide more control commands.The hybrid EEG-based control approach includes steady-state visual evoked potential (SSVEP) paradigm and motor imagery (MI) paradigm. Firstly, the rehabilitation movement was selected by SSVEP paradigm, and the multivariate variational mode decomposition (MVMD) and canonical correlation analysis (CCA) method was used for SSVEP EEG recognition; then, the motion intention was obtained by MI paradigm, and the convolutional neural network (CNN) and long short-term memory network (LSTM) were used to build a CNN-LSTM model for MI EEG recognition; finally, the recognition results were translated into control commands of Bowden cables to achieve multi-degree-of-freedom rehabilitation.Experimental results show that the average classification accuracy of the CNN-LSTM model reaches to 90.07% ± 2.23%, and the overall accuracy of the hybrid EEG-based control approach reaches to 85.26% ± 1.95%. The twelve subjects involved in the usability assessment demonstrated an average system usability scale (SUS) score of 81.25 ± 5.82. Additionally, four participants who underwent a 35-day rehabilitation training demonstrated an average 10.33% increase in range of motion (ROM) across 4 joints, along with a 11.35% increase in the average electromyography (EMG) amplitude of the primary muscle involved.The exosuit demonstrates good accuracy in control, exhibits favorable usability, and shows certain efficacy in multi-joint rehabilitation. Our study has taken into account the neuroplastic principles, aiming to achieve active user engagement while introducing additional degrees of freedom, offering novel ideas and methods for potential brain-computer interface (BCI)-based rehabilitation strategies and hardware development.Clinical impact: Our study presents an exosuit with four degrees of freedom for stroke rehabilitation, enabling multi-joint movement and improved motor recovery. The hybrid EEG-based control approach enhances active user engagement, offering a promising strategy for more effective and user-driven rehabilitation, potentially improving clinical outcomes.Clinical and Translational Impact Statement: By developing an exosuit and a hybrid EEG-based control approach, this study enhances stroke rehabilitation through better user engagement and multi-joint capabilities. These innovations consider neuroplasticity principles, integrating rehabilitation theory with rehabilitation device.

Abstract Handheld robots offer accessible solutions with a short learning curve to enhance operator capabilities. However, their controllable degree-of-freedoms are limited due to scarce space for actuators. Inspired by muscle movements stimulated by nerves, we report a handheld time-share driven robot. It comprises several motion modules, all powered by a single motor. Shape memory alloy (SMA) wires, acting as “nerves”, connect to motion modules, enabling the selection of the activated module. The robot contains a 202-gram motor base and a 0.8 cm diameter manipulator comprised of sequentially linked bending modules (BM). The manipulator can be tailored in length and integrated with various instruments in situ, facilitating non-invasive access and high-dexterous operation at remote surgical sites. The applicability was demonstrated in clinical scenarios, where a surgeon held the robot to conduct transluminal experiments on a human stomach model and an ex vivo porcine stomach. The time-share driven mechanism offers a pragmatic approach to build a multi-degree-of-freedom robot for broader applications.

Abstract Background Elevated levels of executive function and physical fitness play a pivotal role in shaping future quality of life. However, few studies have examined the collaborative influences of physical and mental health on academic achievement. This study aims to investigate the key factors that collaboratively influence primary school students' academic achievement from executive function, physical fitness, and demographic factors. Additionally, ensemble learning methods are employed to predict academic achievement, and their predictive performance is compared with individual learners. Methods A cluster sampling method was utilized to select 353 primary school students from Huai'an, China, who underwent assessments for executive function, physical fitness, and academic achievement. The recursive feature elimination cross-validation method was employed to identify key factors that collaboratively influence academic achievement. Ensemble learning models, utilizing eXtreme Gradient Boosting and Random Forest algorithms, were constructed based on Bagging and Boosting methods. Individual learners were developed using Support Vector Machine, Decision Tree, Logistic Regression, and Linear Discriminant Analysis algorithms, followed by the establishment of a Stacking ensemble learning model. Results Our findings revealed that sex, body mass index, muscle strength, cardiorespiratory function, inhibition, working memory, and shifting were key factors influencing the academic achievement of primary school students. Moreover, ensemble learning models demonstrated superior predictive performance compared to individual learners in predicting academic achievement among primary school students. Conclusions Our results suggest that recognizing sex differences and emphasizing the simultaneous development of cognition and physical well-being can positively impact the academic development of primary school students. Ensemble learning methods warrant further attention, as they enable the establishment of an accurate academic early warning system for primary school students.

Abstract Objective Evidence on the association between the creatinine to body weight (Cre/BW) ratio and the risk of pre-diabetes to diabetes development remains limited. Our study aimed to examine the association between the Cre/BW ratio and incident diabetes in pre-diabetic patients. Methods This retrospective cohort study included 24,506 pre-diabetic participants who underwent health checks from 2010 to 2016 in China. We used the Cox proportional-hazards regression model to explore the relationship between baseline Cre/BW ratio and diabetes risk in pre-diabetes patients. Using a Cox proportional hazards regression with cubic spline function and smooth curve fitting (cubical spline smoothing), we were able to determine the non-linear relationship between them. We also carried out a number of subgroup and sensitivity analyses. Results The age range of the participants included in this study was 20–99 years, with a majority of 16,232 individuals (66.24%) being men. The mean baseline Cre/BW ratio was 1.06 (SD 0.22) umol/L/kg. 2512 (10.25%) participants received a diabetes final diagnosis over a median follow-up period of 2.89 years. After adjusting for covariates, the Cre/BW ratio had a negative association with incident diabetes in participants with pre-diabetes, per umol/L/kg increase in Cre/BM ratio was accompanied by a 55.5% decrease in diabetes risk (HR = 0.445, 95%CI 0.361 to 0.548). The Cre/BW ratio and risk of diabetes had a non-linear connection, with 1.072 umol/L/kg serving as the ratio's inflection point. The HR were 0.294 (95%CI:0.208–0.414) and 0.712 (95%CI:0.492–1.029), respectively, on the left and right sides of the inflection point. The sensitivity analysis demonstrated the robustness of these results. Subgroup analyses indicated that the Cre/BW ratio was strongly associated with the risk of diabetes among participants who were younger than 50 years, as well as among those with diastolic blood pressure (DBP)

In order to analyze the effects of tea saponin (TS) on soy hydrolyzed peptide (SHP) structure and functional properties in SHP-TS complex, comparative analysis SHP and TS were 1:0, 1:0.5, 1:1, 1:2 (w/w) respectively. The Fourier transformed infrared spectrum, fluorescence spectrum and UV-visible absorption spectrum were used to characterize the spatial structural changes of the protein in the SHP-TS complex and to clarify the relationship between SHP conformational changes and functional properties in the complex. The results showed that the addition of TS could change the secondary structure of SHP, and the hydrogen bond was involved in the formation of the SHP-TS complex. SHP strongly interacted with TS and the spatial conformation changes. In addition, the more TS content increased, the more emulsifying and antioxidant properties of the complex were enhanced, the mean of particle size first decreased and then increased, and the absolute value of the ζ-potential first increased and then decreased. When the SHP:TS ratio was 1:1 (w/w), an excellent comprehensive SHP-TS complex was obtained. Compared with the single SHP system, the emulsion stability coefficient of the complex was the highest at this time. The mean particle size of the emulsion was the smallest and the absolute value of the ζ-potential was the highest. This study would provide a theoretical basis for the development of new emulsifiers in the food industry.

Lithium–sulfur (Li-S) batteries offer a high theoretical energy density but suffer from poor cycling stability and polysulfide shuttling, which limits their practical application. To address these challenges, we developed a PANI-modified MoS2-NG composite, where MoS2 nanoflowers were uniformly grown on graphene oxide (GO) through PANI modification, resulting in an increased interlayer spacing of MoS2. This expanded spacing exposed more active sites, enhancing polysulfide adsorption and catalytic conversion. The composite was used to prepare MoS2-NG/PP separators for Li-S batteries, which achieved a high specific capacity of 714 mAh g−1 at a 3 C rate and maintained a low capacity decay rate of 0.085% per cycle after 500 cycles at 0.5 C. The larger MoS2 interlayer spacing was key to improving redox reaction kinetics and suppressing the shuttle effect, making the MoS2-NG composite a promising material for enhancing the performance and stability of Li-S batteries.

In vertebrates, maternally supplied yolk is typically used in one of two ways: either intracellularly by endodermal cells or extracellularly via the yolk sac. This study delves into the distinctive gut development in sturgeons, which are among the most ancient extant fish groups, contrasting it with that of other vertebrates. Our observations indicate that while sturgeon endodermal cells form the archenteron (i.e., the primitive gut) dorsally, the floor of the archenteron is uniquely composed of extraembryonic yolk cells (YCs). As development progresses, during neurulation, the archenteric cavity inflates, expands laterally, and roofs a semicircle of YCs. By the pharyngula stage, the cavity fully encompasses the YC mass, which begins to be digested at the hatching stage. This suggests a notable deviation in sturgeon gut development from that in other vertebrates, as their digestive tract initiates its function by processing endogenous nutrition even before external feeding begins. Our findings highlight the evolutionary diversity of gut development strategies among vertebrates and provide new insights into the developmental biology of sturgeons.

ObjectiveTo describe the return to work of patients with severe acute pancreatitis within 6 months after discharge, and to explore the influence of demographic, clinical, and psychosocial factors on their return to work.Research designProspective 6 months follow-up study.SettingA third class hospital in Guizhou Province. Adult of severe acute pancreatitis(18-60years), with a job before admission, in the intensive care unit ≥ 24 h, were included.Main outcome measuresTo study return to work and influencing factors one, three and six months severe acute pancreatitis patients discharge. several measurements were used, including General Health Questionnaire (Demographic, disease-related, job-related and health behavior data), Readiness for Return-To-Work Scale and the Hospital Anxiety and Depression Scale.ResultsForty-three severe acute pancreatitis patients were included in our study, with mean age 41.53 years. Twenty-nine (67.44%) patients returned to work within 6 months, and fourteen patients did not return to work. The status of Readiness for Return-To-Work Scale: fourteen severe acute pancreatitis patients who did not return to work were mainly in the precontemplation dimension and prepared for action-self-evaluative dimension both 5 cases (35.71%), and the 29 patients who had returned to work were in the Proactive maintenance stage. The study showed that the independent risk factors for returning to work in SAP patients were chronic disease (OR, 0.095; 95% CI [0.011-0.822]; p=0.008), sepsis (OR, 0.071; 95% CI [0.015-0.339]; p=0.009), low education level (OR, 2.905; 95% CI [0.969-8.710]; p

Community parks in old urban areas have problems such as outdated facilities and low quality, which inhibit the development of healthy aging. However, limited research has examined the correlation between such park characteristics and park satisfaction among elderly individuals. Additionally, the mechanisms underlying this association remain unclear. In this investigation, a moderated mediation framework grounded in self-determination theory was formulated to probe the interplay between these variables, with a specific focus on the mediating influence of social self-efficacy among the elderly and the moderating effect of use intention. A questionnaire survey (N = 319) was conducted in Shamian Park, Guangzhou, employing structural equation modeling for data analysis. Findings indicate that, even after controlling for demographic factors, park characteristics not only exert a direct influence on satisfaction but also exhibit an indirect impact through the mediation of social self-efficacy, with both pathways being moderated by use intention. This study has implications for how to improve the design of community parks in old urban areas in developing countries to better meet the basic needs of the elderly and promote healthy aging.

This corrects the article published in European Journal of Histochemistry 2023;67:3535. doi: 10.4081/ejh.2023.3535