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Abstract Pancreatic neuroendocrine neoplasms (Pan-NEN) represent a group of highly heterogeneous cancers, characterized by complex and diverse biological behavior. The objective of this study was to systematically investigate the immunological features of the tumor microenvironment (TME) in Pan-NEN, aiming to identify prognostic biomarkers and explore the therapeutic potential of immunotherapy for Pan-NEN. Tumor and adjacent normal tissues were collected from 56 patients with Pan-NEN. Immunohistochemical analysis was conducted on tumor tissues using a panel of monoclonal antibodies targeting key immune markers. The expression levels of these markers were quantitatively assessed and correlated with clinicopathological features and overall survival. Low expression of CD3, CD8, CD4, CD68, CD163, Foxp3, CD56, CD69, GZMB, HLA-1, HLA-II, PD-1, and PD-L1 were observed in the majority of Pan-NEN patient samples. PD-1 expression was positively correlated with CD4 and Foxp3 expression, while PD-L1 expression was positively correlated with CD68, CD163, and Foxp3 expression; HLA-II expression was positively correlated with GZMB expression. Infiltration of lymphocytes (CD3 + or CD8+) and macrophages (CD68 + or CD163+) and expression of PD-1/PD-L1 were more pronounced in poorly differentiated neuroendocrine carcinoma (Pan-NEC) compared to well-differentiated neuroendocrine tumors (Pan-NET), while CD68 and PD-L1 correlated with advanced disease stage. Conversely, HLA-I antigen expression was commonly downregulated in Pan-NEC. Univariate Cox proportional hazard analysis demonstrated that tumor grade, stage; CD4+, CD68+, and CD163 + cell count; and expression of PD-1 and PD-L1 were significantly associated with poor survival outcomes, while the positive expression of HLA-I was correlated with a more favorable survival prognosis. Furthermore, multivariate Cox proportional hazard analyses revealed that tumor grade, stage, and PD-1 expression are independent prognostic factors. The immunological landscape of Pan-NEN offers potential prognostic value and therapeutic targets. The findings suggest that immunotherapy, particularly targeting the PD-1/PD-L1 pathway, may serve as a promising strategy for the treatment of Pan-NEN, especially for Pan-NEC patients.

Abstract Community detection is a critical component of network analysis and a hot topic in social computing. Detecting community structure in dynamic networks has important theoretical and practical implications for understanding the intrinsic function of networks and predicting network behavior. However, the majority of existing dynamic community detection methods adopt shallow models, which have limited ability to excavate complex non-linear structures and tend to generate undesirable community structures. In order to obtain an accurate and robust community structure in dynamic networks, we are inspired by network representation learning and utilize the deep learning to detect evolving communities in dynamic networks. In this paper, we propose a novel dynamic community detection method by fusing Deep Learning and Evolutionary Clustering (DLEC). This work attempts to combine deep learning and evolutionary clustering into a unified framework. First, we propose a matrix construction strategy to fully reveal the inherent community structures via the underlying community memberships. Then, we develop a novel multi-layer deep autoencoder framework that consists of multiple non-linear functions to extract the latent deep representation of the dynamic network. Based on the evolutionary clustering framework, a graph regularization term is introduced to ensure the smoothness of the community evolution. Finally, we employ the K-means clustering algorithm on the low-dimensional network space to obtain the community structure. Extensive experimental results on synthetic and real-world networks show that the proposed DLEC algorithm can effectively detect high-quality communities in dynamic networks.

Abstract To evaluate the association of uric acid (UA) with adverse outcomes and its potential mediator in patients with left ventricular diastolic dysfunction (LVDD) and pulmonary hypertension (PH). We retrospectively analyzed 234 patients with LVDD and PH. The baseline characteristics of patients with low UA (≤ 330 µmol/L) group were compared with high UA (> 330 µmol/L) group. Adverse outcomes included all-cause mortality, cardiac death and heart failure (HF) hospitalization. Their association with UA and the mediator were evaluated using Cox regression and mediation analysis. The mediation proportion was further quantified by the R mediation package. During a mean follow-up of 50 ± 18 months, there were 27 all-cause deaths, 18 cardiovascular deaths and 41 incidents of HF hospitalization. Multivariable Cox regression analysis showed UA was an independent risk factor of adverse outcomes in LVDD and PH patients, even after adjusting for age, sex, body mass index, medical histories, systolic blood pressure, fasting blood glucose, total cholesterol, triglyceride, eGFR, BNP and medications. The hazard ratios (HRs) for UA (per 10 µmol/L increase) were as below: for all-cause mortality, HR 1.143, 95% CI 1.069–1.221, P

Abstract Chronic kidney disease (CKD) affects more than 10% population worldwide and becomes a huge burden to the world. Recent studies have revealed multifold interactions between CKD and gut microbiome and their pathophysiological implications. The gut microbiome disturbed by CKD results in the imbalanced composition and quantity of gut microbiota and subsequent changes in its metabolites and functions. Studies have shown that both the dysbiotic gut microbiota and its metabolites have negative impacts on the immune system and aggravate diseases in different ways. Herein, we give an overview of the currently known mechanisms of CKD progression and the alterations of the immune system. Particularly, we summarize the effects of uremic toxins on the immune system and review the roles of gut microbiota in promoting the development of different kidney diseases. Finally, we discuss the current sequencing technologies and novel therapies targeting the gut microbiome.

BackgroundRecently, several randomized controlled trials (RCTs) of fluvoxamine have been successfully conducted for the treatment of patients with coronavirus disease 2019 (COVID-19). This systematic review and meta-analysis was to evaluate the efficacy and safety of fluvoxamine in patients with COVID-19.MethodsMEDLINE, EMBASE, Cochrane Library and clinicaltrials.gov were searched for RCTs which were performed to evaluate fluvoxamine and placebo up to January 31, 2024. Review Manager 5.3 was used to perform meta-analysis. The risk ratio (RR) and mean difference (MD) was analyzed and calculated with a random effect model.ResultsWe pooled 4,711 participants from six RCTs (2,382 in the fluvoxamine group and 2,329 in the placebo group). Compared to the placebo group, the fluvoxamine group had a significantly lower rate of clinical deterioration (RR, 0.73; P = 0.004; 95% CI, 0.59 to 0.90; I2 = 0%) and hospitalization (RR, 0.76; P = 0.04; 95% CI, 0.59 to 0.99; I2 = 0%). In the meantime, compared with the placebo group, fluvoxamine group did not show any higher risk of AEs (P = 0.13 and 0.91, respectively) in safety outcomes analysis. The subgroup analysis showed that fluvoxamine treatment performed more than 200 mg daily appears to be more effective than those performed less than 200 mg daily in reducing clinical deterioration and hospitalization risks, while not exhibiting higher AE and SAE risks than placebo group.ConclusionFluvoxamine for patients with COVID-19, especially those who take 200 mg or more daily, is superior to the placebo group in reducing clinical deterioration and hospitalization, and did not show any higher risk of AEs and SAEs in safety concerns, which might be a promising intervention for COVID-19.

Abstract Coagulation/flocculation is one of the most widely used and cost-effective pretreatment methods for improving the dewaterability of sludge. In this study, a cationic modified starch-based flocculant (St-CTA) in conjunction with a popular clay, attapulgite (ATP), was used for the conditioning of waste-activated sludge. The dewatering properties, including the filter cake moisture content, filtration specific resistance, capillary suction time, filtration rate and compressibility coefficient, were measured and compared by varying the doses of St-CTA and ATP. By combination of the apparent dewatering performance and the changes in the contents and distributions of the extracellular polymeric substance (EPS) fractions and components, sludge flocs, and microstructures of sludge cakes, the dewatering mechanisms were discussed in detail. St-CTA in conjunction with ATP can exhibit an enhanced dewaterability of sludge and the water content in final sludge cake can be stably reduced below 80% owing to the synergistic effects of St-CTA and ATP. In addition to the efficient charge neutralization of St-CTA, ATP not only acts as a skeleton builder in the sludge dewatering process which makes the sludge flocs more compact and improves the filterability and permeability, but also tightly interacts with the proteins in EPS of the sludge which reduces the protein content and further enhances the dewatering effect. This study provides an economical, green, and effective way to further improve the dewaterability of sludge.

Background: Proteinśprotein interaction (PPI) between lens epithelium-derived growth factor (LEDGF/p75) and human immunodeficiency virus (HIV) integrase (IN) becomes an attractive target for anti-HIV drug development.Methods: The blockade of this interaction by small molecules could potentially inhibit HIV-1 replication. In this study, a panel of 99 structurally related flavonoids were was tested, concerning their ability to inhibit IN-LEDGF/p75 interaction, using a homogeneous time time-resolved fluorescence (HTRF) assay. Results: From the obtained results, it was possible to observe that the flavonoid with hydroxyl group in C3-, C4-, C5- and C7-position on the A-ring, C4′- and C5′-position of the B-ring, a carbonyl group of the C-ring, was more active against IN-LEDGF/p75 interaction, through competitive inhibition. Moreover, the binding modes of representative compounds, including myricetin, luteolin, dihydrorobinetin, naringenin, epicatechin, genistein and helichrysetin, were analyzedanalysed by molecular docking. Biolayer interferometry assay confirmed that these representative compounds disrupted the PPI by binding to IN with KD values ranging from 1.0 to 3.6 µM.Conclusion: This study presents the first to quantitative comparation of the effect of flavonoids with different structural subclasses on IN-LEDGF/p75 interaction. Our findings provide new insights into the development of inhibitors targeting IN-LEDGF/p75 interaction using flavonoids. Key MessagesHIV-1 integrase (IN)-LEDGF/p75 interaction is an attractive target for antiviral drug development.For the first time, the structure-activity relationship of flavonoids belonging to seven flavonoidic subclasses on IN-LEDGF/p75 interaction was determined.This study comprehends an HTRF-based screening system, biolayer interferometry and an in silico molecular docking analysis.

Obesity-associated complications are causing increasing morbidity and mortality worldwide. Expansion of adipose tissue in obesity leads to a state of low-grade chronic inflammation and dysregulated metabolism, resulting in insulin resistance and metabolic syndrome. Adipose tissue macrophages (ATMs) accumulate in obesity and are a source of proinflammatory cytokines that further aggravate adipocyte dysfunction. Macrophages are rich sources of cyclooxygenase (COX), the rate limiting enzyme for prostaglandin E2 (PGE2) production. When mice were fed a high-fat diet (HFD), ATMs increased expression of COX-2. Selective myeloid cell COX-2 deletion resulted in increased monocyte recruitment and proliferation of ATMs, leading to increased proinflammatory ATMs with decreased phagocytic ability. There were increased weight gain and adiposity, decreased peripheral insulin sensitivity and glucose utilization, increased adipose tissue inflammation and fibrosis, and abnormal adipose tissue angiogenesis. HFD pair-feeding led to similar increases in body weight, but mice with selective myeloid cell COX-2 still exhibited decreased peripheral insulin sensitivity and glucose utilization. Selective myeloid deletion of the macrophage PGE2 receptor subtype, EP4, produced a similar phenotype, and a selective EP4 agonist ameliorated the metabolic abnormalities seen with ATM COX-2 deletion. Therefore, these studies demonstrated that an ATM COX-2/PGE2/EP4 axis plays an important role in inhibiting adipose tissue dysfunction.

Laccase, as a copper-containing polyphenol oxidase, primarily functions in the process of lignin, anthocyanin biosynthesis, and various abiotic/biotic stresses. In this study, forty-eight laccase members were identified in the eggplant genome. Only forty-two laccase genes from eggplant (SmLACs) were anchored unevenly in 12 chromosomes, the other six SmLACs were mapped on unanchored scaffolds. Phylogenetic analysis indicated that only twenty-five SmLACs were divided into six different groups on the basis of groups reported in Arabidopsis. Gene structure analysis revealed that the number of exons ranged from one to 13. Motif analysis revealed that SmLACs included six conserved motifs. In aspects of gene duplication analysis, twenty-one SmLACs were collinear with LAC genes from Arabidopsis, tomato or rice. Cis-regulatory elements analysis indicated many SmLACs may be involved in eggplant morphogenesis, flavonoid biosynthesis, diverse stresses and growth/development processes. Expression analysis further confirmed that a few SmLACs may function in vegetative and reproductive organs at different developmental stages and also in response to one or multiple stresses. This study would help to further understand and enrich the physiological function of the SmLAC gene family in eggplant, and may provide high-quality genetic resources for eggplant genetics and breeding.

Quantitative studies of the multiple factors influencing the mountain-mass effect, which causes higher temperatures in mountainous than non-mountainous regions, remain insufficient. This study estimated the air temperature in the Yellow River Basin, which spans three different elevation ranges, using multi-source data to address the uneven distribution of regional meteorological stations. The differences in mountain-mass effect for different geomorphic regions at the same altitude were then compared. The Manner–Kendall nonparametric test was used to analyse time series changes in temperature. Moreover, we employed the geographically weighted regression (GWR) model, with MODIS land-surface and air-temperature data, station-based meteorological data, vertical temperature gradients corresponding to the 2000–2015 period, and elevation data, to estimate the correlation between monthly mean surface temperature and air temperature in the Yellow River Basin. The following major results were obtained. (1) The GWR method and ground station-based observations enhanced the accuracy of air-temperature estimates with an error of only ± 0.74°C. (2) The estimated annual variations in the spatial distributions of 12-month average temperatures showed that the upper Tibetan Plateau is characterised by low annual air temperatures with a narrow spatial distribution, whereas north-eastern areas upstream of the Inner Mongolia Plateau are characterised by higher air temperatures. Changes in the average monthly air temperature were also high in the middle and lower reaches, with a narrow spatial distribution. (3) Considering the seasonal variation in the temperature lapse rate, the mountain-mass effect in the Yellow River Basin was very high. In the middle of each season, the variation of air temperature at a given altitude over the Tibetan Plateau was higher than that over the Loess Plateau and Jinji Mountain. The results of this study reveal the unique temperature characteristics of the Yellow River Basin according to its geomorphology. Furthermore, this research contributes to quantifying mountain-mass effects.

Background Rupture of the deltoid ligament (DL) in acute ankle fracture is very common. However, there is still insufficient evidence on whether to repair the DL in acute ankle fracture. Therefore, a systematic review and meta-analysis of comparative studies was performed to report the outcome of DL repair in acute ankle fracture. Methods The PubMed, Cochrane Library, EMBASE and Web of Science databases were searched from the inception dates to October 31, 2020, for comparative studies. The methodological quality was evaluated based on the risk-of-bias tool of the Cochrane Collaboration for Randomized Controlled Trials (RCTs) or the Risk-of-Bias Assessment Tool for Non-randomized Studies (RoBANS). The post-operative medial clear space (MCS), final MCS, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, visual analogue scale (VAS) score and incidence of complications were analysed. Results A total of 8 comparative studies involving 388 participants who suffered Weber type B or C ankle fractures were included in this meta-analysis. The results showed that the post-operative MCS, final MCS, AOFAS score and rate of complications were statistically superior in the DL repair group. For the VAS score, there was no significant difference between the DL repair group and the DL non-repair group. Conclusions In this meta-analysis of comparative studies, DL repair offered great advantages in terms of the post-operative MCS, final MCS, AOFAS score and rate of complications compared with non-repair. The repair of the DL in patients with acute ankle fractures might be beneficial to ankle joint stability and assist in improving the quality of ankle reduction. More high-quality and prospective studies with long follow-up durations are needed to further demonstrate the superiority of DL repair over non-repair.

The larvae of Holotrichia parallela, a destructive belowground herbivore, may cause yield losses of up to 20% in maize in a typical year. To understand the protein-level mechanisms governing the response of maize to this herbivore, tandem mass tag (TMT) quantitative proteomics was used for the comparative analysis of protein abundance in the maize roots after H. parallela larval attack. A total of 351 upregulated proteins and 303 downregulated proteins were identified. Pathway enrichment analysis revealed that the differentially abundant proteins (DAPs) were most strongly associated with carbohydrate and energy metabolism pathways, such as glycolysis, pentose phosphate pathway and fructose and mannose metabolism. Most glycolysis-related proteins were significantly induced. In addition, H. parallela larval attack decreased the glucose concentrations in the roots. This study demonstrates that maize can manipulate carbohydrate metabolism by modifying glycolysis and pentose phosphate pathway response to root-feeding herbivorous attackers. The results of this study may help to establish a foundation for further functional studies of key protein-mediated responses to H. parallela larvae in maize.

In most cases, sorafenib-resistant HCC cells exhibit significant mesenchymal phenotype and stemness features. In this context, tumor cells might undergo cell fate transition in response to sorafenib or other targeted drugs in the presence or absence of genetic mutations. Therefore, understanding the major characteristics of drug-resistant cells state helps to discover new treatments that overcome drug resistance. To note, little is known about the metabolic or microenvironmental aspects of the certain tumor cell states beyond the genome. This review mainly focuses on the underlying mechanisms of acquired sorafenib resistance based on CSCs and EMT models, which explain tumor heterogeneity and have been considered the major cause of secondary sorafenib resistance. In particular, it discusses how the tumor microenvironment and tumor metabolism regulate cell stemness, mesenchymal state, and sorafenib resistance through epigenetic regulations, and provides reliable targets that might have synergetic effect with sorafenib. Keywords: Tumor metabolism, Tumor microenvironment, Hypoxia, Cancer stem cells, Epithelial-mesenchymal transition, Sorafenib resistance

This study used the literature method to systematically review correlation studies on the sports performance of school-aged children aged 7–12 years. Twenty related studies were summarized and sorted out. The results showed that most of the studies used the motion sensor method to measure the intensity of physical activity, and few used the observation and survey methods. Most studies measured sports performance on the basis of changes in various physical fitness indicators to reflect differences in sports performance. Moderate- and high-intensity comprehensive sports were beneficial in improving the sports performance of school-aged children. At present, differences in the positive effects of various physical activities on children’s sports performance need to be further compared. The research results can provide theoretical scientific guidance for the selection of children’s physical activities and sports methods and the development of comprehensive courses such as school sports activities, as well as help children’s sports performance improvement and effective development of physical and mental health.

Abstract Based on a panel of 30 provinces and a timeframe from January 2009 to December 2013, we estimate the association between monthly human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) incidence and the relevant Internet search query volumes in Baidu, the most widely used search engine among the Chinese. The pooled mean group (PMG) model show that the Baidu search index (BSI) positively predicts the increase in HIV/AIDS incidence, with a 1% increase in BSI associated with a 2.1% increase in HIV/AIDS incidence on average. This study proposes a promising method to estimate and forecast the incidence of HIV/AIDS, a type of infectious disease that is culturally sensitive and highly unevenly distributed in China; the method can be taken as a complement to a traditional HIV/AIDS surveillance system.

Background: Laparoscopic total gastrectomy (LTG) is increasingly performed in patients with gastric cancer. However, the usage of intracorporeal esophagojejunostomy (IEJ) following LTG is limited, as the safety and efficacy remain unclear. The present meta-analysis aimed to evaluate the feasibility and safety of IEJ following LTG. Methods: Studies published from January 1994 to January 2017 comparing the outcomes of IEJ and extracorporeal esophagojejunostomy (EEJ) following LTG were reviewed and collected from the PubMed, EBSCO, Cochrane Library, Embase, and China National Knowledge Internet (CNKI). Operative results, postoperative recovery, and postoperative complications were compared and analyzed. The weighted mean difference (WMD) and odds ratio (OR) with a 95% confidence interval (CI) were calculated using the Review Manager 5.3. Results: Seven nonrandomized studies with 785 patients were included. Compared with EEJ, IEJ has less blood loss (WMD: −13.52 ml; 95% CI: −24.82–−2.22; P = 0.02), earlier time to first oral intake (WMD: −0.49 day; 95% CI: −0.83–−0.14; P < 0.01), and shorter length of hospitalization (WMD: −0.62 day; 95% CI: −1.08–−0.16; P < 0.01). There was no significant difference between IEJ and EEJ regarding the operation time, anastomotic time, number of retrieved lymph nodes, time to first flatus, anastomosis leakage rate, anastomosis stenosis rate, and proximal resections (all P > 0.05). Conclusions: Compared with EEJ, IEJ has better cosmesis, milder surgical trauma, and a faster postoperative recovery. IEJ can be performed as safely as EEJ. IEJ should be encouraged to surgeons with sufficient expertise.

Carbapenem resistance has posed potential harmful risks to human and animals. The objectives of this study were to understand the prevalence of blaNDM-5 in pigs and investigate the molecular characteristics of NDM-5-producing Escherichia coli isolates in Guangdong province in China. Carbapenem-resistant E. coli isolates were isolated from pigs and obtained using MacConkey plates containing 0.5 mg/L meropenem. Conjugation assay and antimicrobial susceptibility testing were conducted for the isolates and their transconjugants. Whole-genome sequence (WGS) was used to analyze the plasmid genetic feature. A total of five blaNDM-5-carrying E. coli isolates were obtained in the present investigations. They belonged to five ST types. The blaNDM-5 genes were found to be in IncX3 and IncHI2 plasmid. The IncX3 plasmid was 46,161 bp in size and identical to other reports. IncHI2 plasmid was 246,593 bp in size and similar to other IncHI2-ST3 plasmids. It consisted of a typical IncHI2 plasmid backbone region and a multiresistance region (MRR). The blaNDM-5 was closely associated with the IS3000-ISAba125-blaNDM-5-bleMBL-trpF-tat-IS26 unit. We first reported the blaNDM-5-carrying IncHI2 in E. coli isolates recovered from pigs and revealed the molecular characterization. Continued surveillance for the dissemination of blaNDM-5 among food-producing animals is required.

Abstract Histone deacetylase 9 (HDAC9) regulates hepatic gluconeogenesis by deacetylating Forkhead box O 1 (FoxO1). HDAC9 upregulation is involved in hepatitis C virus (HCV)-associated exaggerated gluconeogenesis. Herein, we found in addition to FoxO1, HDAC9 also regulates other gluconeogenic transcription factors, including peroxisomeproliferator-activated receptor-γ coactivator-1α (PGC-1α), cyclic AMP-responsive element-binding protein (CREB), and glucocorticoid receptor (GR). Unlike FoxO1, which is regulated by post-translational modification responses to HDAC9, HDAC9 regulates PGC-1α, CREB and GR by altering gene expression. Similar to PGC-1α, CREB and GR were found to be novel regulatory targets of FoxO1 by examination of the FoxO1 binding site in their promoter. PGC-1α, CREB and GR were upregulated in response to HDAC9 via FoxO1 deacetylation. These findings indicate that HDAC9-FoxO1 signalling contributes to gluconeogenesis by modulating the expression of gluconeogenic transcription factors. In particular, metabolic profiling demonstrated a clear shift towards gluconeogenesis metabolism, and HDAC9-FoxO1 signalling can be strongly induced to upregulate gluconeogenic transcription factors following HCV infection. The positive correlation between HDAC9 and gluconeogenic transcription factor expression levels in the livers of both HCV-infected patients and normal individuals further emphasizes the clinical relevance of these results. Thus, HDAC9-FoxO1 signalling axis is involved in regulating gluconeogenic transcription factors, gluconeogenesis, and HCV-induced type 2 diabetes.

Background: Laparoscopic resection (LAP) for small bowel gastrointestinal stromal tumors (GISTs) is not as common as for stomach. This study aimed to evaluate the safety and efficacy of LAP for small bowel GISTs with systematic review and meta-analysis. Methods: The Web of Science, Cochrane Library, Embase, and PubMed databases before December 2016 were comprehensively searched to retrieve comparative trials of LAP and conventional open resection (OPEN) for GISTs of small bowel with a relevance of review object. These researches reported intraoperative and postoperative clinical course (operation time, blood loss, time to first flatus and oral intake, hospital stay, morbidity, and mortality), oncologic outcomes, and long-term survival status. Results: Six studies involving 391 patients were identified. Compared to OPEN, LAP had associated with a shorter operation time (weighted mean difference [WMD] = −27.97 min, 95% confidence interval [CI]: −49.40–−6.54, P < 0.01); less intraoperative blood loss (WMD = −0.72 ml; 95% CI: −1.30–−0.13, P = 0.02); earlier time to flatus (WMD = −0.83 day; 95% CI: −1.44–−0.22, P < 0.01); earlier time to restart oral intake (WMD = −1.95 days; 95% CI: −3.31–−0.60, P < 0.01); shorter hospital stay (WMD = −3.00 days; 95% CI: −4.87–−1.13, P < 0.01); and a decrease in overall complications (risk ratio = 0.56, 95% CI: 0.33–0.97, P = 0.04). In addition, the tumor recurrence and long-term survival rate showed that there was no significant difference between the two groups of patients. Conclusions: LAP for small bowel GISTs is a safe and feasible procedure with shorter operation time, less blood loss, less overall complications, and quicker recovery. Besides, tumor recurrence and the long-term survival rate are similar to open approach. Because of the limitations of this study, methodologically high-quality studies are needed for certain appraisal.

The C2H2 zinc finger protein (C2H2-ZFP) transcription factor family regulates the expression of a wide variety of genes in response to various developmental processes or abiotic stresses; however, these proteins have not yet been comprehensively analyzed in tomato (Solanum lycopersicum). In this study, a total of 104 C2H2-ZFs were identified in an uneven distribution across the entire tomato genome, and include seven segmental duplication events. Based on their phylogenetic relationships, these genes were clustered into nine distinct categories analogous to those in Arabidopsis thaliana. High similarities were found between the exon–intron structures and conserved motifs of the genes within each group. Correspondingly, the expression patterns of the C2H2-ZF genes indicated that they function in different tissues and at different developmental stages. Additionally, quantitative real-time PCR (qRT-PCR) results demonstrated that the expression levels of 34 selected C2H2-ZFs are changed dramatically among the roots, stems, and leaves at different time points of a heat stress treatment, suggesting that the C2H2-ZFPs are extensively involved in the heat stress response but have potentially varying roles. These results form the basis for the further molecular and functional analysis of the C2H2-ZFPs, especially for those members that significantly varied under heat treatment, which may be targeted to improve the heat tolerance of tomato and other Solanaceae species.

This study aimed to explore the properties of the Chinese version of the Anxiety Sensitivity Index- 3 (ASI-3) in a sample of military personnel. Using non-probabilistic sampling, the Chinese version of the ASI-3 was administered to 3,077 valid participants aged 16 to 36 years old (M = 22.35, SD = 3.57) from nine military units. The Depression Anxiety Stress Scales-21 (DASS-21) and The State-Trait Anxiety Inventory (STAI) were used to assess the construct validity. A one-way analysis of variance was conducted to compare the differences in the services and positions of the participants. It was found that ①The indices of confirmatory factor analysis met the standard values, which supported the hypothesis of the three-factor model of the original ASI-3; ②ASI-3 was significantly associated with DASS-21 in positive ways, which indicated the high convergent validity; on the other hand, the correlation between ASI-3 and TAI was relatively low, which indicated there was an empirical discrimination between anxiety sensitivity and trait anxiety. ③The Cronbach's α coefficients were 0.926 for the total scale and 0.828-0.841 for the three subscales; ④At a cut-off score of 16, the sensitivity and specificity levels were 71.1% and 76.7%, respectively, where the sum of sensitivity and specificity becomes the maximum, accompanied with improvement of PPV and NPV; ⑤There were significant findings in the ASI and subscales among the five services and four positions. This study provides new evidence that the Chinese version of the Anxiety Sensitivity Index-3 has good validity and reliability and could be applied as an effective tool to assess anxiety sensitivity in military personnel. Our recommendations to researchers and practitioners are that the three factor model should be replicated across some different special forces and the items and constructs could be modified on Chinese culture.

Background: Gender is one of the risk factors accounting for the high prevalence of adolescent myopia. Considerable research results have shown that myopia incidence of female is higher than that of male. This study aimed to analyze the correlation between ocular parameters and serum estrogen level and to investigate the vision changes along with estrogen change in menstrual cycle of adolescent females. Methods: A total of 120 young females aged between 15 and 16 years, diagnosed with myopia were recruited. Spherical lens, cylindrical lens, axis, interpupillary distance (IPD), and vision in each tested eye of the same subject were measured by automatic optometry and comprehensive optometry, with repetition of all measurements in the menstrual cycle of the 2 nd or 3 rd days, 14 th days, and 28 th days, respectively. Serum estradiol (E 2 ) levels were assayed by chemiluminescence immunoassay at the same three times points of the menstrual cycle mentioned above. Results: In young females with myopia, the spherical lens showed a statistically significant difference among all different time in menstrual cycle (all P < 0.0001). The cylindrical lens, axis, and IPD were changed significantly during the menstrual cycle (P < 0.05). The vision of the three different time points in menstrual cycle had a significant difference (χ2 = 6.35, P = 0.042). The vision during the 14 th and 28 th day was higher compared to that on the 2 nd or 3 rd days (P = 0.021). Serum E 2 levels were significantly different at different time points in menstrual cycle (P < 0.05). E 2 levels reached its maximum value on the 14 th day and the minimum value on the 2 nd or 3 rd day. Conclusions: In adolescent females, the spherical lens and other related ocular parameters vary sensitively with different levels of E 2 in menstrual cycle. Vision in late menstrual stage is significantly higher than that in premenstrual stage.

Here, we studied the underlying mechanism of aldosterone (Aldo)-induced vascular endothelial cell damages by focusing on ceramide. We confirmed that Aldo (at nmol/L) inhibited human umbilical vein endothelial cells (HUVEC) survival, and induced considerable cell apoptosis. We propose that ceramide (mainly C18) production might be responsible for Aldo-mediated damages in HUVECs. Sphingosine-1-phosphate (S1P), an anti-ceramide lipid, attenuated Aldo-induced ceramide production and following HUVEC damages. On the other hand, the glucosylceramide synthase (GCS) inhibitor PDMP or the ceramide (C6) potentiated Aldo-induced HUVEC apoptosis. Eplerenone, a mineralocorticoid receptor (MR) antagonist, almost completely blocked Aldo-induced C18 ceramide production and HUVEC damages. Molecularly, ceramide synthase 1 (CerS-1) is required for C18 ceramide production by Aldo. Knockdown of CerS-1 by targeted-shRNA inhibited Aldo-induced C18 ceramide production, and protected HUVECs from Aldo. Reversely, CerS-1 overexpression facilitated Aldo-induced C18 ceramide production, and potentiated HUVEC damages. Together, these results suggest that C18 ceramide production mediates Aldo-mediated HUVEC damages. MR and CerS-1 could be the two signaling molecule regulating C18 ceramide production by Aldo.

The carmine spider mite (Tetranychus cinnabarinus) is one of the most serious pests on crops and its control mainly depends on chemical acaricides. The excessive and improper acaricides use has resulted in mite resistance to many acaricides, including fenpropathrin. Previous studies have indicated fenpropathrin resistance is a complex development process involving many genes, but information on resistance mechanism of post-transcription regulation is rare. Using Illumina sequencing, several categories of sRNAs were identified from susceptible (TS) and fenpropathrin-resistant strains (TR) of T. cinnabarinus, including 75 known microRNAs (miRNAs) and 64 novel miRNAs, whose target genes containing 78592 miRNA-target pairs were predicted by 6 algorithms. Also, 12 significantly differently expressed miRNAs were identified between the TS and TR libraries and RT-qPCR validation also performed a well consistency with sequencing. The targets of significantly differentially expressed miRNAs included 7 glutathione S-transferase, 7 cytochrome P450 and 16 carboxyl/choline esterase genes, their function in fenpropathrin resistance were further analyzed. The present study provides the firstly large-scale characterization of miRNAs in T. cinnabarinus and the comparison between TS and TR strains gives a clue on how miRNA involves in fenpropathrin resistance.

The type 2 transmembrane serine protease matriptase is under tight control primarily by the actions of the integral membrane Kunitz-type serine protease inhibitor HAI-1. Growing evidence indicates that HAI-2 might also be involved in matriptase inhibition in some contexts. Here we showed that matriptase inhibition by HAI-2 depends on the subcellular localizations of HAI-2, and is observed in breast cancer cells but not in mammary epithelial cells. HAI-2 is co-expressed with matriptase in 21 out of 26 human epithelial and carcinoma cells examined. HAI-2 is also a potent matriptase inhibitor in solution, but in spite of this, HAI-2 inhibition of matriptase is not observed in all contexts where HAI-2 is expressed, unlike what is seen for HAI-1. Induction of matriptase zymogen activation in mammary epithelial cells results in the formation of matriptase-HAI-1 complexes, but matriptase-HAI-2 complexes are not observed. In breast cancer cells, however, in addition to the appearance of matriptase-HAI-1 complex, three different matriptase-HAI-2 complexes, are formed following the induction of matriptase activation. Immunofluorescent staining reveals that activated matriptase is focused at the cell-cell junctions upon the induction of matriptase zymogen activation in both mammary epithelial cells and breast cancer cells. HAI-2, in contrast, remains localized in vesicle/granule-like structures during matriptase zymogen activation in human mammary epithelial cells. In breast cancer cells, however, a proportion of the HAI-2 reaches the cell surface where it can gain access to and inhibit active matriptase. Collectively, these data suggest that matriptase inhibition by HAI-2 requires the translocation of HAI-2 to the cell surface, a process which is observed in some breast cancer cells but not in mammary epithelial cells.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infections contributes to a substantial proportion of liver disease worldwide. The aim of this study was to assess the clinical and virological features of HBV-HCV co-infection.Demographic data were collected for 3238 high-risk people from an HCV-endemic region in China. Laboratory tests included HCV antibody and HBV serological markers, liver function tests, and routine blood analysis. Anti-HCV positive samples were analyzed for HCV RNA levels and subgenotypes. HBsAg-positive samples were tested for HBV DNA.A total of 1468 patients had chronic HCV and/or HBV infections. Among them, 1200 individuals were classified as HCV mono-infected, 161 were classified as HBV mono-infected, and 107 were classified as co-infected. The HBV-HCV co-infected patients not only had a lower HBV DNA positive rate compared to HBV mono-infected patients (84.1% versus 94.4%, respectively; P < 0.001). The median HCV RNA levels in HBV-HCV co-infected patients were significantly lower than those in the HCV mono-infected patients (1.18[Interquartile range (IQR) 0-5.57] versus 5.87[IQR, 3.54-6.71] Log10 IU/mL, respectively; P < 0.001). Furthermore, co-infected patients were less likely to have detectable HCV RNA levels than HCV mono-infected patients (23.4% versus 56.5%, respectively; P < 0.001). Those HBV-HCV co-infected patients had significantly lower median HBV DNA levels than those mono-infected with HBV (1.97[IQR, 1.3-3.43] versus 3.06[IQR, 2-4.28] Log10 IU/mL, respectively; P < 0.001). The HBV-HCV co-infection group had higher ALT, AST, ALP, GGT, APRI and FIB-4 levels, but lower ALB and total platelet compared to the HBV mono-infection group, and similar to that of the HCV mono-infected group.These results suggest that co-infection with HCV and HBV inhibits the replication of both viruses. The serologic results of HBV-HCV co-infection in patients suggests more liver injury compared to HBV mono-infected patients, but is similar to HCV mono-infection.

OBJECTIVE: This study explores a new, non-invasive imaging method for the specific diagnosis of insulinoma by providing an initial investigation of the use of 125I-labelled molecules of the glucagon-like peptide-1 (GLP-1) analogue liraglutide for in vivo and in vitro small-animal SPECT/CT (single-photon emission computed tomography/computed tomography) imaging of insulinomas. METHODS: Liraglutide was labelled with 125I by the Iodogen method. The labelled 125I-liraglutide compound and insulinoma cells from the INS-1 cell line were then used for in vitro saturation and competitive binding experiments. In addition, in a nude mouse model, the use of 125I-liraglutide for the in vivo small-animal SPECT/CT imaging of insulinomas and the resulting distribution of radioactivity across various organs were examined. RESULTS: The labelling of liraglutide with 125I was successful, yielding a labelling rate of approximately 95% and a radiochemical purity of greater than 95%. For the binding between 125I-liraglutide and the GLP-1 receptor on the surface of INS-1 cells, the equilibrium dissociation constant (Kd) was 128.8 ± 30.4 nmol/L(N = 3), and the half-inhibition concentration (IC50) was 542.4 ± 187.5 nmol/L(N = 3). Small-animal SPECT/CT imaging with 125I-liraglutide indicated that the tumour imaging was clearest at 90 min after the 125I-liraglutide treatment. An examination of the in vivo distribution of radioactivity revealed that at 90 min after the 125I-liraglutide treatment, the target/non-target (T/NT) ratio for tumour and muscle tissue was 4.83 ± 1.30(N = 3). Our study suggested that 125I-liraglutide was predominantly metabolised and cleared by the liver and kidneys. CONCLUSION: The radionuclide 125I-liraglutide can be utilised for the specific imaging of insulinomas, representing a new non-invasive approach for the in vivo diagnosis of insulinomas.

PURPOSE: Radionuclide reporter gene imaging holds promise for non-invasive monitoring of transplanted stem cells. Thus, the feasibility of utilizing recombinant baculoviruses carrying the sodium iodide symporter (NIS) reporter gene in monitoring stem cell therapy by radionuclide imaging was explored in this study. METHODS: Recombinant baculoviruses carrying NIS and green fluorescent protein (GFP) reporter genes (Bac-NIS and Bac-GFP) were constructed and used to infect human induced pluripotent stem cells (hiPSCs), human embryonic stem cells (hESCs) and human umbilical cord blood mesenchymal stem cells (hUCB-MSCs). Infection efficiency, total fluorescence intensity and duration of transgene expression were determined by flow cytometry. Cytotoxicity/proliferative effects of baculovirus on hUCB-MSCs were assessed using CCK-8 assays. ¹²⁵I uptake and perchlorate inhibition assays were performed on Bac-NIS-infected hUCB-MSCs. Radionuclide imaging of mice transplanted with Bac-NIS-infected hUCB-MSCs was performed by NanoSPECT/CT imaging. RESULTS: Infection efficiencies of recombinant baculovirus in hESCs, hiPSCs and hUCB-MSCs increased with increasing MOIs (27.3%, 35.8% and 95.6%, respectively, at MOI = 800). Almost no cytotoxicity and only slight effects on hUCB-MSCs proliferation were observed. Obvious GFP expression (40.6%) remained at 8 days post-infection. The radioiodide was functionally accumulated by NIS gene products and specifically inhibited by perchlorate (ClO₄⁻). Radioiodide uptake, peaking at 30 min and gradually decreasing over time, significantly correlated with hUCB-MSCs cell number (R² = 0.994). Finally, radionuclide imaging showed Bac-NIS-infected hUCB-MSCs effectively accumulated radioiodide in vivo, which gradually weakened over time. CONCLUSION: Baculovirus as transgenic vector of radionuclide reporter gene imaging technology is a promising strategy for monitoring stem cell transplantation therapy.

The invasive species Spartina alterniora Loisel was introduced to the eastern coast of China in the 1970s and 1980s for the purposes of land reclamation and the prevention of soil erosion. The resulting interspecific competition had an important influence on the distribution of native vegetation, which makes studying the patterns and mechanisms of the interactions between Spartina alterniora Loisel and the native species Phragmites australis (Cav.) Trin ex Steud in this region very important. There have been some researches on the interspecific interactions between P. australis and S. alterniora in the Dongtan wetland of Chongming, east China, most of which has focused on the comparison of their physiological characteristics. In this paper, we conducted a neighbor removal experiment along a tidal gradient to evaluate the relative competitive abilities of the two species by calculating their relative neighbor effect (RNE) index. We also looked at the influence of environmental stress and disturbance on the competitive abilities of the two species by comparing interaction strength (I) among different tidal zones both for P. australis and S. alterniora. Finally, we measured physiological characteristics of the two species to assess the physiological mechanisms behind their different competitive abilities. Both negative and positive interactions were found between P. australis and S. alterniora along the environmental gradient. When the direction of the competitive intensity index for P. australis and S. alterniora was consistent, the competitive or facilitative effect of S. alterniora on P. australis was stronger than that of P. australis on S. alterniora. The interspecific interactions of P. australis and S. alterniora varied with environmental conditions, as well as with the method used, to measure interspecific interactions.

BACKGROUND:The interleukin-28B gene (IL28B) locus has been associated with host resistance to hepatitis C virus (HCV) infection and response to PEG-IFN/RBV treatment in western populations. This study was to determine whether this gene variant is also associated with spontaneous clearance of HCV infection, treatment response and IL-28B protein production in Chinese patients. METHODS:We genotyped IL28B genetic variations (rs12980275, rs8103142, rs8099917 and rs12979860) by pyrosequencing DNA samples from cohorts consisting of 529 subjects with persistent HCV infection, 196 subjects who cleared the infection, 171 healthy individuals and 235 chronic HCV patients underwent IFN/RBV treatment. The expression of IL-28B were measured by ELISA and RT-PCR. RESULTS:We found that the four IL28B variants were in complete linkage disequilibrium (r2 = 0.97-0.98). The rs12979860 CC genotype was strongly associated with spontaneously HCV clearance and successful IFN/RBV treatment compared to the CT/TT. IL-28B levels in persistent HCV patients were significantly lower than subjects who spontaneously resolved HCV and healthy controls and were also associated with high levels of ALT (alanine aminotransferase) and AST (aspartate aminotransferase). IL-28B levels were also significantly lower in individuals carrying T alleles than CC homozygous. CONCLUSIONS:Thus, the rs12979860-CC variant upstream of IL28B gene is associated with spontaneous clearance of HCV, susceptible to IFN/RBV treatment and increased IL-28B levels in this Chinese population.

Abstract Background We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. Methods This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. Results Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI − 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). Conclusions The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.

Abstract In the process of human aging, significant age-related changes occur in brain tissue. To assist individuals in assessing the degree of brain aging, screening for disease risks, and further diagnosing age-related diseases, it is crucial to develop an accurate method for predicting brain age. This paper proposes a multi-scale feature fusion method called Tri-UNet based on the U-Net network structure, as well as a brain region information fusion method based on multi-channel input networks. These methods address the issue of insufficient image feature learning in brain neuroimaging data. They can effectively utilize features at different scales of MRI and fully leverage feature information from different regions of the brain. In the end, experiments were conducted on the Cam-CAN dataset, resulting in a minimum Mean Absolute Error (MAE) of 7.46. The results demonstrate that this method provides a new approach to feature learning at different scales in brain age prediction tasks, contributing to the advancement of the field and holding significance for practical applications in the context of elderly education.