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Abstract Background A blood-based diagnostic test is a promising strategy for colorectal cancer (CRC). The MethyDT test (IColohunter), which detects methylation levels of NTMT1 and MAP3K14 -AS1, exhibited potential in discriminating CRC, but its clinical performance needs to be validated in large-scale populations. Methods A multicenter, double-blinded, cross-sectional study that enrolled 1194 participants was performed. Plasma samples were collected to detect methylation levels of NTMT1 and MAP3K14 -AS1 using quantitative methylation-specific PCR with the MethyDT test, and the accuracy was further evaluated by Sanger sequencing. Results The sensitivities of the MethyDT test for detecting CRC, early stages of CRC (I and II), advanced adenoma (AA), and high-grade intraepithelial neoplasia (HGIN) were 91.2% (95% confidence interval [CI], 88.4–94.0), 87.4% (95% CI, 82.5–92.2), 43.5% (95% CI, 35.7–51.4), and 72.7% (95% CI, 57.5–87.9), respectively. The specificities for participants with non-AA, interfering diseases (ID), and no evidence of disease (NED) were 85.0% (95% CI, 78.8–91.3), 93.7% (95% CI, 91.4–95.9) and 97.3% (95% CI, 90.5–99.7), respectively, and its overall specificity for all-controls was 92.4% (95% CI, 90.3–94.4). The consistency of the MethyDT test with pathology for CRC was high with a kappa value of 0.830 (95% CI, 0.795–0.865). Additionally, the MethyDT test was comparable to Sanger sequencing for detecting methylation with kappa values > 0.97. Conclusions The MethyDT test demonstrates excellent sensitivity and specificity for CRC and high consistency with Sanger sequencing for methylation, suggesting it may serve as a potential noninvasive diagnostic tool for the detection of CRC. Trial registration This clinical trial has been registered in ClinicalTrials.gov (NCT05508503).

Abstract In robotic-assisted surgery (RAS), traditional surgical instruments without sensing capability cannot perceive accurate operational forces during the task, and such drawbacks can be largely intensified when sophisticated tasks involving flexible and slender arms with small end-effectors, such as in gastrointestinal endoscopic surgery (GES). In this study, we propose a microelectromechanical system (MEMS) piezoresistive 3-axial tactile sensor for GES forceps, which can intuitively provide surgeons with online force feedback during robotic surgery. The MEMS fabrication process facilitates sensor chips with miniaturized dimensions. The fully encapsulated tactile sensors can be effortlessly integrated into miniature GES forceps, which feature a slender diameter of just 3.5 mm and undergo meticulous calibration procedures via the least squares method. Through experiments, the sensor’s ability to accurately measure directional forces up to 1.2 N in the Z axis was validated, demonstrating an average relative error of only 1.18% compared with the full-scale output. The results indicate that this tactile sensor can provide effective 3-axial force sensing during surgical operations, such as grasping and pulling, and in ex vivo testing with a porcine stomach. The compact size, high precision, and integrability of the sensor establish solid foundations for clinical application in the operating theater.

BackgroundHelicobacter pylori (H. pylori) eradication has been reported to affect gut microbiota distribution. This study aimed to evaluate the effect of probiotic supplementation on the gastrointestinal microbiota during eradication and the efficacy of bismuth-containing quadruple therapy.MethodsOne hundred treatment-naïve H. pylori-positive patients were randomly assigned 1:1 to receive 14-day bismuth-containing quadruple therapy (esomeprazole, bismuth, amoxicillin, and clarithromycin) combined with the probiotic (Bifidobacterium animalism subsp. lactis BLa80) or placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was completed before and after treatment. Stool samples were collected for 16S rRNA gene sequencing at weeks 0, 2, and 10.ResultsNo significant difference in the eradication rate was observed between the two groups. The incidence of adverse events, especially nausea (p = 0.029), was lower in the probiotic group. After treatment, the GSRS score decreased significantly in the probiotic group (p = 0.039). The gut microbiota underwent considerable changes immediately following eradication treatment, predominantly characterized by an increase in Proteobacteria at the expense of commensal Firmicutes and Bacteroidota, but gradually returned to baseline after eight weeks. By week 10, beneficial genera such as Lachnoclostridium, Parasutterella, Hungatella, and Akkermansia were notably enriched in the probiotic group. Additionally, the correlation networks in the probiotic group were closer to their initial levels at week 10 compared to the placebo group.ConclusionDisturbances in the gut microbiota following H. pylori treatment appeared to be temporary, and probiotic supplementation could mitigate antibiotic-induced alterations in the gut microbiota. This study also provided evidence supporting the effectiveness of probiotics in alleviating gastrointestinal symptoms.

Abstract The correlation between liver disease and the progression of ulcerative colitis (UC) has remained elusive. In this study, it demonstrates that liver injury is intricately linked to the heightened severity of UC in patients, and causes more profound intestinal damage during DSS‐induced colitis in mice. Metabolomics analysis of plasma from liver cirrhosis patients shows liver injury compromising nicotinamide supply for NAD+ biosynthesis in the intestine. Subsequent investigation identifies intestinal group 2 innate lymphoid cells (ILC2s) are responsible for liver injury‐exacerbated colitis. Reconstitution of ILC2s or the restoration of NAD+ metabolism proves effective in relieving liver injury‐aggravated experimental colitis. Mechanistically, the NAD+ salvage pathway regulates gut ILC2s in a cell‐intrinsic manner by supporting the generation of succinate, which fuels the electron transport chain to sustaining ILC2s function. This research deepens the understanding of cellular and molecular mechanisms in liver disease‐UC interplay, identifying a metabolic target for innovative treatments in liver injury‐complicated colitis.

Male ageing is always accompanied by decreased fertility. The forkhead O (FOXO) transcription factor FOXO4 is reported to be highly expressed in senescent cells. Upon activation, it binds p53 in the nucleus, preventing senescent cell apoptosis and maintaining senescent cells in situ. Leydig cells play key roles in assisting spermatogenesis. Leydig cell senescence leads to deterioration of the microenvironment of the testes and impairs spermatogenesis. In this study, we observed that FOXO4-DRI, a specific FOXO4- p53 binding blocker, induced apoptosis in senescent Leydig cells, reduced the secretion of certain Senescence-Associated Secretory Phenotype and improved the proliferation of cocultured GC-1 SPG cells. In naturally aged mice, FOXO4-DRI-treated aged mice exhibited increased sperm quality and improved spermatogenesis.

IntroductionInvestigating and assessing native fish diversity and conducting regional assessments of threats are vital for the conservation of aquatic biodiversity. For this specific study, the Daqing River basin in China was chosen as the research area. Field surveys were carried out between 2018 and 2019, supplemented by a review of pertinent literature and other records.MethodsTo evaluate fish diversity, the following parameters are selected for analysis: Relative abundance (Pi), Frequency of occurrence (Fi), Margalef richness index (D) , Shannon Wiener diversity index (H′) , and Pielou evenness index (J′).Relative abundance levels are categorized as follows: dominant species make up more than 10%, common species account for 1%–10%, and occasional species constitute less than 1%. Canoco 5.0 software was utilized to conduct Redundancy Analysis (RDA) on the fish species composition and environmental factors at 34 sampling sites.ResultsThe findings revealed that 85 fish species have been recorded in the basin, consisting of 78 freshwater species categorized into 8 orders, 17 families, and 59 genera, among which Cypriniformes comprised 64% of the total catch. The low proportion of threatened and endemic species was an important feature of the fish diversity of the Daqing River. Despite the theoretical presence of 85 species, field surveys managed to collect only 42 species, of which 33 were confirmed as naturally occurring within the basin. The average values of Margalef richness index, 22 Shannon Wiener diversity index and Pielou evenness index were 1.72, 2.04 and 0.80 respectively, signifying a low fish diversity with relatively uniform distribution across the sampled regions.DiscussionThis study found that the community structure and diversity of fish were closely related to environmental factors, particularly water quality. Among these factors, ammonia nitrogen emerged as a significant determinant of fish diversity. High concentrations of ammonia nitrogen inhibit fish growth, endanger health, and can even lead to death. Additionally, dams and other water infrastructure also impact fish community structure and diversity. This baseline study can provide a basis for the protection and ecological restoration of fish resources in the Daqing River.

Abstract Background and Aims The resect‐and‐discard strategy for colorectal polyps based on accurate optical diagnosis remains challenges. Our aim was to investigate the feasibility of hyperspectral imaging (HSI) for identifying colorectal polyp properties and diagnosis of colorectal cancer in fresh tissues during colonoscopy. Methods 144,900 two dimensional images generated from 161 hyperspectral images of colorectal polyp tissues were prospectively obtained from patients undergoing colonoscopy. A residual neural network model was trained with transfer learning to automatically differentiate colorectal polyps, validated by histopathologic diagnosis. The diagnostic performances of the HSI‐AI model and endoscopists were calculated respectively, and the auxiliary efficiency of the model was evaluated after a 2‐week interval. Results Quantitative HSI revealed histological differences in colorectal polyps. The HSI‐AI model showed considerable efficacy in differentiating nonneoplastic polyps, non‐advanced adenomas, and advanced neoplasia in vitro, with sensitivities of 96.0%, 94.0%, and 99.0% and specificities of 99.0%, 99.0%, and 96.5%, respectively. With the assistance of the model, the median negative predictive value of neoplastic polyps increased from 50.0% to 88.2% (p = 0.013) in novices. Conclusion This study demonstrated the feasibility of using HSI as a diagnostic tool to differentiate neoplastic colorectal polyps in vitro and the potential of AI‐assisted diagnosis synchronized with colonoscopy. The tool may improve the diagnostic performance of novices and facilitate the application of resect‐and‐discard strategy to decrease the cost.

Summary: Background: Oesophagogastroduodenoscopy (OGD) quality and identification of the early upper gastrointestinal (UGI) neoplasm play an important role in detecting the UGI neoplasm. However, the optimal method for quality control in daily OGD procedures is currently lacking. We aimed to evaluate the efficacy of a real-time intelligent quality-control system (IQCS), which combines OGD quality control with lesion detection of early UGI neoplasms. Methods: We performed a multicentre, single-blinded, randomised controlled trial at 6 hospitals in China. Patients aged 40–80 years old who underwent painless OGD were screened for enrolment in this study. Patients with a history of advanced UGI cancer, stenosis, or obstruction in UGI tract were excluded. Eligible subjects were randomly assigned (1:1) to either the routine or IQCS group to undergo standard OGD examination and OGD examination aided by IQCS, respectively. Patients were masked to the randomisation status. The primary outcome was the detection of early UGI neoplasms. All analyses were done on a per-protocol basis. This trial is registered with ClinicalTrials.gov, NCT04720924. Findings: Between January 16, 2021 and December 23, 2022, 1840 patients were randomised (IQCS group: 919, routine group: 921). The full analysis set consisted of 914 in the IQCS group and 915 in the routine group. The early UGI neoplasms detection rate in the IQCS group (6.1%, 56/914) was significantly higher than in the routine group (2.3%, 21/915; P = 0.0001). The IQCS group had fewer blind spots (2.3 vs. 6.2, P

Abstract As testicular mesenchymal stromal cells, stem Leydig cells (SLCs) show great promise in the treatment of male hypogonadism. The therapeutic functions of mesenchymal stromal cells are largely determined by their reciprocal regulation by immune responses. However, the immunoregulatory properties of SLCs remain unclear. Here, we observe that SLCs transplantation restore male fertility and testosterone production in an ischemia‒reperfusion injury mouse model. SLCs prevent inflammatory cascades through mitochondrial transfer to macrophages. Reactive oxygen species (ROS) released from activated macrophages inducing mitochondrial transfer from SLCs to macrophages in a transient receptor potential cation channel subfamily member 7 (TRPM7)-mediated manner. Notably, knockdown of TRPM7 in transplanted SLCs compromised therapeutic outcomes in both testicular ischemia‒reperfusion and testicular aging mouse models. These findings reveal a new mechanism of SLCs transplantation that may contribute to preserve testis function in male patients with hypogonadism related to immune disorders.

Background Submucosal fibrosis is associated with adverse events of endoscopic submucosal dissection (ESD). The present study mainly aimed to establish a predictive model for submucosal fibrosis in patients with early gastric cancer (EGC) undergoing ESD.Methods Eligible patients with EGC, identified at Qilu Hospital of Shandong University from April 2013 to December 2023, were retrospectively included and randomly split into a training set and a validation set in a 7:3 ratio. Logistic regression analyses were used to pinpoint the risk factors for submucosal fibrosis. A nomogram was developed and confirmed using receiver operating characteristic (ROC) curves, calibration plots, Hosmer-Lemeshow (H-L) tests, and decision curve analysis (DCA) curves. Besides, a predictive model for severe submucosal fibrosis was further conducted and tested.Results A total of 516 cases in the training group and 220 cases in the validation group were recruited. The nomogram for submucosal fibrosis contained the following items: tumour location (long axis), tumour location (short axis), ulceration, and biopsy pathology. ROC curves showed high efficiency with an area under the ROC of 0.819 in the training group, and 0.812 in the validation group. Calibration curves and H-L tests indicated good consistency. DCA proved the nomogram to be clinically beneficial. Furthermore, the four items were also applicable for a nomogram predicting severe fibrosis, and the model performed well.Conclusion The predictive models, initially constructed in this study, were validated as convenient and feasible for endoscopists to predict submucosal fibrosis and severe fibrosis in patients with EGC undergoing ESD.

PurposeThis meta-analysis was conducted to collect all available data and estimate the relationship between refractive error and the risk of diabetic retinopathy (DR) in patients with diabetes, and to assess whether vision-threatening DR (VTDR) is associated with refractive error.MethodsWe systematically searched several literature databases including PubMed, Embase, Cochrane Library, Web of Science, CNKI, CBM, Wan Fang Data, and VIP databases. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using fixed or random effects models. Four models were developed to assess the relationship between refractive error and the risk and DR, VTDR: hyperopia and DR, VTDR; myopia and DR, VTDR; spherical equivalent (SE per D increase) and DR, VTDR; and axial length (AL per mm increase) and DR, VTDR. The included literature was meta-analyzed using Stata 12.0 software, and sensitivity analysis was performed. Publication bias in the literature was evaluated using a funnel plot, Begg's test, and Egger's test.ResultsA systematic search identified 3,198 articles, of which 21 (4 cohorts, 17 cross-sectional studies) were included in the meta-analysis. Meta-analysis showed that hyperopia was associated with an increased risk of VTDR (OR: 1.23; 95% CI: 1.08–1.39; P = 0.001), but not with DR (OR: 1.05; 95% CI: 0.94–1.17; P = 0.374). Myopia was associated with a reduced risk of DR (OR: 0.74; 95% CI: 0.61–0.90; P = 0.003), but not with VTDR (OR: 1.08; 95% CI: 0.85–1.38; P = 0.519). Every 1 diopter increase in spherical equivalent, there was a 1.08 increase in the odds ratio of DR (OR: 1.08; 95% CI: 1.05–1.10; P

One-dimensionalcarbon nanotube field-effect transistors (CNFETs) have offered a solution for obtaining high transistor performance in a compatible low-temperature BEOL process, enabling monolithic 3D integration benefits for more functional circuits. Currently, CNT transistors need to further improve their performance with a more stable process and explore the most suitable circuit application scene. In this study, we successfully enhanced the performance of CNFETs through special Y2O3 film passivation and vacuum annealing processes. The on-state current of the optimized device was improved by $36.6\times $ compared to the device without these processes. Besides, the subthreshold swing (SS) was notably reduced from 259 mV/dec to 215 mV/dec and the threshold voltage was decreased from 2.02 V to 1.79 V due to the reduction of the interface state. Meanwhile, the devices’ optoelectronic characteristics were significantly improved and exhibited a $72\times $ increase in $\Delta $ Ids under identical illumination. With an improved annealing process, the $\Delta $ Ids were further increased to $231\times $ compared to the original device because of the reduction of defects within the device. Finally, the tentative Morse code communication applications all by the optimized CNFETs were obtained. These technologies and functional implementations provided a promising approach for future 3D functional communication systems with CNT technology.

Acetylene (C2H2) is often employed to assess soil total denitrification (N2O + N2) due to its ease of implementation. However, this technique underestimates soil denitrification in soils with low nutrient contents, particularly those supporting grain yields. To our knowledge, there are limited studies that have specifically investigated the impact of C2H2 on nutrient-rich vegetable soils, especially concerning the emissions of N2 and N2O and the nitrogenous gas product ratio (i.e., N2O/(N2O + N2)). In this study, we conducted both anoxic and oxic incubations at various C2H2 concentrations (0%, 0.01%, and 10%, v/v) and utilized a robotized sampling and analysis system to quantify soil N2, N2O, and CO2 emissions. Our findings revealed that the cumulative N2O production in soil treated with 10%C2H2 was significantly lower than that in soil treated with 0.01%C2H2 and soil without C2H2. Contrarily, high concentrations of C2H2 (10%, v/v) led to increased N2 production. Similar trends were observed under oxic conditions, where 10%C2H2 concentration did not enhance N2O production but markedly increased N2 and CO2 emissions. Moreover, the N2O/(N2O + N2) product ratio was notably higher in soils treated with 0%C2H2 compared to the 10%C2H2 treatment under anoxic conditions. These findings indicate that high concentrations of acetylene could facilitate the reduction of N2O to N2 and lead to underestimated soil total denitrification in vegetable soil, regardless of anoxic or oxic conditions. This discovery underscores the drawbacks when employing high concentrations of acetylene to evaluate actual total denitrification in intensive greenhouse vegetable soils, highlighting the necessity for further investigation into alternative methodologies.

The slope erosion in the distribution area of completely weathered granite is often relatively severe, causing serious ecological damage and property loss. Ecological restoration is the most effective means of soil erosion control. Taking completely weathered granite backfill soil as the research object, two types of slope protection plants, Vetiver grass and Pennisetum hydridum, were selected. We analyzed these two herbaceous plants’ soil reinforcement and slope protection effects through artificial planting experiments, indoor simulated rainfall experiments, and direct shear tests. The test results showed that the runoff and sediment production rates of the two herbaceous plant slopes were significantly lower than those of the bare slope, with the order of bare slope > Vetiver grass slope > Pennisetum hydridum slope. Compared with the bare slope, the cumulative sediment production of the Vetiver grass slope at 60 min decreased by 56.73–60.09%, and the Pennisetum hydridum slope decreased by 75.97–78.45%. The indoor direct shear test results showed that soil cohesion decreases with increasing water content. As the root content of Vetiver grass roots increases, soil cohesion first increases and then decreases, reaching a maximum value when the root content is 1.44%. As the root content of Pennisetum hydridum increases, soil cohesion increases. The internal friction angle increases slightly with increasing water content, while the root content does not significantly affect the internal friction angle. Therefore, the shear strength of soil decreases when the water content increases. The shear strength of the Vetiver grass root-soil composite reaches a peak at a root content of 1.44%, while the shear strength of the giant king grass root-soil composite increases as the root content increases. At the same root content, the shear strength of the Vetiver grass root-soil composite is slightly higher than that of giant king grass. The reinforcement effect of roots on shallow soil is better than on deep soil. Both herbaceous plants have an excellent soil-fixing and slope-protecting impact on the fully weathered granite backfill slope. Pennisetum hydridum’s soil and water conservation effect is significantly better than that of the Vetiver grass. In contrast, Vetiver grass roots slightly outperform Pennisetum hydridum in enhancing the shear strength of the soil. The research results can provide a theoretical basis for the vegetation slope protection treatment of fully weathered granite backfill slopes.

Essential trace minerals play vital roles in maintaining human and animal health. However, an overdose of the existing inorganic trace minerals is prone to induce detrimental effects that outweigh positive benefits. In this study, an extracellular polymeric substances (EPS)-producing bacterium, identified as Bacillus licheniformis CCTCC M2020298, was isolated from marine using glutinous rice processing wastewater as enrichment medium. The EPS yield of Bacillus licheniformis CCTCC M2020298 could reach 8.62 g/L by using glutinous rice-processing wastewater containing medium. Furthermore, the potential of the EPS as a carrier for synthesizing EPS-iron (Fe) and EPS-copper (Cu) complex was explored. The results showed that the optimum condition for the synthesis EPS-Fe were the reaction temperature 70°C, pH 8.5–9.0 and mass ratio of EPS to trisodium citrate 2:1. The iron content of EPS-Fe reached 77.4 mg/g. Under the same condition, the copper content of EPS-Cu reached 90.7 mg/g. The elemental composition, functional groups and valence state of the mineral elements of EPS-Fe and EPS-Cu were well characterized. The EPS-Fe and EPS-Cu exhibited antioxidant activity in scavenging ·OH, DPPH and ·O2− free radicals, thereby leading to reduced oxidative stress and apoptosis levels in human colonic epithelial cells in vitro. They also inhibited the proliferation of mouse hepatocellular carcinoma H22 and the growth of intestinal pathogens in vitro. This study provided an effective avenue for EPS production from glutinous rice processing wastewater and proved the potential of EPS-Fe and EPS-Cu complexes as a new-type comprehensive essential trace mineral supplement.

Abstract Kaempferol has demonstrated notable positive effects on the osteogenic differentiation of mesenchymal stem cells (MSC) and osteoblasts. A substantial body of research has emphasized the role of dislodged titanium particles in aseptic loosening following joint replacement surgery. This study predominantly investigates the suppressive influence of Kaempferol on osteolysis induced by titanium (Ti) alloy particles. In vitro investigations disclosed that Kaempferol effectively enhanced mineralization and alkaline phosphatase (ALP) activity in bone-marrow mesenchymal stem cells exposed to Ti particles. In addition, we conducted a comprehensive analysis of osteogenic differentiation microarray data_sets (GSE37676, GSE79814, and GSE114474) to identify differentially expressed genes. Significantly, Kaempferol upregulated the expression of critical osteogenic markers, including Runt-related transcription factor 2 (Runx2), osteocalcin (OCN), osterix/Sp-7, and β-catenin. In vivo experiments, including H&E staining and Immunohistochemistry, provided compelling evidence that Kaempferol exerted a robust inhibitory effect on periprosthetic osteolysis in mice, with particularly pronounced results at higher doses. Moreover, it elevated the expression levels of osteogenic factors and Wnt/β-catenin signaling components. These findings collectively indicate that Kaempferol mitigates the hindrance to osteogenesis posed by titanium particles by activating the Runx2 and Wnt/β-catenin signaling pathways. This research lays a solid foundation for the prospective utilization of Kaempferol in the management of aseptic loosening following arthroplasty, offering promising therapeutic potential.

Abstract Background Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is a new prokinetic agent for FD. This updated meta-analysis aimed to explore the efficacy and safety of prokinetics for FD. Methods An updated study search in Pubmed, EMBASE, Cochrane Library and Web of Science was conducted in literatures published from July 2015 to March 2023. Randomized controlled trials investigating the use of prokinetics in adult FD patients were included. The primary outcome was the total efficacy rate and the secondary outcome was adverse events. A Bayesian network meta-analysis was performed using R software. Results A total of 28 studies were included. Network meta-analysis showed that metoclopramide had a higher total efficacy rate than mosapride (OR: 3.53, 95%CI: 1.70–7.47), domperidone (OR: 2.29, 95%CI: 1.16–4.63), itopride(OR: 2.77, 95%CI: 1.41–5.59), acotiamide(OR: 2.63, OR: 1.33–5.36), and placebo(OR: 5.68, 95%CI: 2.98–11.10), however similar to cinitapride (OR: 1.62, 95%CI: 0.75–3.53). Cinitapride had a higher total efficacy rate than mosapride (OR: 2.18, 95%CI: 1.16–4.14) and placebo (OR: 3.52, 95%CI: 2.01–6.24). Cinitapride had lower risk of total adverse events than domperidone. There was no difference in the risk of drug-related adverse events between the prokinetics. Conclusions Metoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events. Further studies using uniform definitions or validated tools to measure the total efficacy rate are needed.

Colorectal cancer (CRC) represents a significant challenge in oncology, with increasing incidence and mortality rates worldwide, particularly among younger adults. Despite advancements in treatment modalities, the urgent need for more effective therapies persists. Immunotherapy has emerged as a beacon of hope, offering the potential for improved outcomes and quality of life. This review delves into the critical interplay between ferroptosis, an iron-dependent form of regulated cell death, and immunotherapy within the CRC context. Ferroptosis’s influence extends beyond tumor cell fate, reshaping the tumor microenvironment (TME) to enhance immunotherapy’s efficacy. Investigations into Ferroptosis-related Genes (OFRGs) reveal their pivotal role in modulating immune cell infiltration and TME composition, closely correlating with tumor responsiveness to immunotherapy. The integration of ferroptosis inducers with immunotherapeutic strategies, particularly through novel approaches like ferrotherapy and targeted co-delivery systems, showcases promising avenues for augmenting treatment efficacy. Furthermore, the expression patterns of OFRGs offer novel prognostic tools, potentially guiding personalized and precision therapy in CRC. This review underscores the emerging paradigm of leveraging ferroptosis to bolster immunotherapy’s impact, highlighting the need for further research to translate these insights into clinical advancements. Through a deeper understanding of the ferroptosis-immunotherapy nexus, new therapeutic strategies can be developed, promising enhanced efficacy and broader applicability in CRC treatment, ultimately improving patient outcomes and quality of life in the face of this formidable disease.

Regulating the microstructure of powder metallurgy (P/M) nickel-based superalloys to achieve superior mechanical properties through heat treatment is a prevalent method in turbine disk design. However, in the case of dual-performance turbine disks, the complexity and non-uniformity of the heat treatment process present substantial challenges. The prediction of yield strength is typically derived from the analysis of microstructures under various heat treatment regimes. This method is time-consuming, expensive, and the accuracy often depends on the precision of microstructural characterization. This study successfully employed a coupled method of Artificial Neural Network (ANN) and finite element analysis (FEA) to reveal the relationship between the heat treatment process and yield strength. The coupled method accurately predicted the location specified and temperature-dependent yield strength based on the heat treatment parameters such as holding temperatures and cooling rates. The root mean square error (RMSE) and mean absolute percentage deviation (MAPD) for the training set are 50.37 and 3.77, respectively, while, for the testing set, they are 50.13 and 3.71, respectively. Furthermore, an integrated model of FEA and ANN is established using a Abaqus user subroutine. The integrated model can predict the yield strength based on temperature calculation results and automatically update material properties of the FEA model during the loading process simulation. This allows for an accurate calculation of the stress–strain state of the turbine disk during actual working conditions, aiding in locating areas of stress concentration, plastic deformation, and other critical regions, and provides a novel reliable reference for the rapid design of the turbine disk.

2-methylfuran is a significant organic chemical raw material which can be produced by hydrolysis, dehydration, and selective hydrogenation of biomass hemicellulose. 2-methylfuran can be converted into value-added chemicals and liquid fuels. This article reviews the latest progress in the synthesis of liquid fuel precursors through hydroxyalkylation/alkylation reactions of 2-methylfuran and biomass-derived carbonyl compounds in recent years. 2-methylfuran reacts with olefins through Diels–Alder reactions to produce chemicals, and 2-methylfuran reacts with anhydrides (or carboxylic acids) to produce acylated products. In the future application of 2-methylfuran, developing high value-added chemicals and high-density liquid fuels are two good research directions.

Abstract Antimicrobial peptides (AMPs) are important mediators of intestinal immune surveillance. However, the regional heterogeneity of AMPs and its regulatory mechanisms remain obscure. Here, we clarified the regional heterogeneity of intestinal AMPs at the single-cell level, and revealed a cross-lineages AMP regulation mechanism that bile acid dependent transcription factors (BATFs), NR1H4, NR1H3 and VDR, regulate AMPs through a ligand-independent manner. Bile acids regulate AMPs by perturbing cell differentiation rather than activating BATFs signaling. Chromatin accessibility determines the potential of BATFs to regulate AMPs at the pre-transcriptional level, thus shaping the regional heterogeneity of AMPs. The BATFs-AMPs axis also participates in the establishment of intestinal antimicrobial barriers of fetuses and the defects of antibacterial ability during Crohn’s disease. Overall, BATFs and chromatin accessibility play essential roles in shaping the regional heterogeneity of AMPs at pre- and postnatal stages, as well as in maintenance of antimicrobial immunity during homeostasis and disease.

Colon cancer is increasing worldwide and is commonly regarded as hormone independent, yet recent reports have implicated sex hormones in its development. Nevertheless, the role of hormones from the hypothalamus–hypophysis axis in colitis-associated colorectal cancer (CAC) remains uncertain. In this study, we observed a significant reduction in the expression of the oxytocin receptor (OXTR) in colon samples from both patient with colitis and patient with CAC. To investigate further, we generated mice with an intestinal-epithelium-cell-specific knockout of OXTR. These mice exhibited markedly increased susceptibility to dextran-sulfate-sodium-induced colitis and dextran sulfate sodium/azoxymethane-induced CAC compared to wild-type mice. Our findings indicate that OXTR depletion impaired the inner mucus of the colon epithelium. Mechanistically, oxytocin was found to regulate Mucin 2 maturation through β1-3-N-acetylglucosaminyltransferase 7 (B3GNT7)-mediated fucosylation. Interestingly, we observed a positive correlation between B3GNT7 expression and OXTR expression in human colitis and CAC colon samples. Moreover, the simultaneous activations of OXTR and fucosylation by l-fucose significantly alleviated tumor burden. Hence, our study unveils oxytocin’s promising potential as an affordable and effective therapeutic intervention for individuals affected by colitis and CAC.

Isoetes orientalis is an endangered hexaploidy species of Isoetaceae in China and the complete chloroplast genome of this species has not been reported. In the present study, a complete chloroplast genome of Isoetes orientalis (Isoetaceae) was assembled and annotated. This chloroplast genome has a circular structure of 145,504 bp in length, comprising a pair of inverted repeat (IR) regions of 13,207 bp each, a large single-copy (LSC) region of 91,864 bp, and a small single-copy (SSC) region of 27,226 bp. The chloroplast genome contains 136 genes, including 84 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis showed that I. orientalis was closely related to I. sinensis. These results provide additional resources for future studies on Isoetes from China and across the globe.

Nearly all modern life depends on artificial light; however, it does cause health problems. With certain restrictions of artificial light emitting technology, the influence of the light spectrum is inevitable. The most remarkable problem is its overload in the short wavelength component. Short wavelength artificial light has a wide range of influences from ocular development to mental problems. The visual neuronal pathway, as the primary light-sensing structure, may contain the fundamental mechanism of all light-induced abnormalities. However, how the artificial light spectrum shapes the visual neuronal pathway during development in mammals is poorly understood. We placed C57BL/6 mice in three different spectrum environments (full-spectrum white light: 400–750 nm; violet light: 400 ± 20 nm; green light: 510 ± 20 nm) beginning at eye opening, with a fixed light time of 7:00–19:00. During development, we assessed the ocular axial dimension, visual function and retinal neurons. After two weeks under short wavelength conditions, the ocular axial length (AL), anterior chamber depth (ACD) and length of lens thickness, real vitreous chamber depth and retinal thickness (LLVR) were shorter, visual acuity (VA) decreased, and retinal electrical activity was impaired. The density of S-cones in the dorsal and ventral retinas both decreased after one week under short wavelength conditions. In the ventral retina, it increased after three weeks. Retinal ganglion cell (RGC) density and axon thickness were not influenced; however, the axonal terminals in the lateral geniculate nucleus (LGN) were less clustered and sparse. Amacrine cells (ACs) were significantly more activated. Green light has few effects. The KEGG and GO enrichment analyses showed that many genes related to neural circuitry, synaptic formation and neurotransmitter function were differentially expressed in the short wavelength light group. In conclusion, exposure to short wavelength artificial light in the early stage of vision-dependent development in mice delayed the development of the visual pathway. The axon terminus structure and neurotransmitter function may be the major suffering.

Abstract The neutrophil-to-lymphocyte ratio is used to reflect body's inflammatory status with prognostic value in different cancers. We aimed to investigate the influence of preoperative NLR in the prognosis of CRLM patients receiving surgery using meta-analysis. Data in Cochrane Library, PubMed, Embase, and Web of Science databases created before October 2022 were recruited. Meta-analysis was carried out with RevMan 5.3 and Stata16 software, and the primary outcome indicators included overall survival (OS), and secondary outcome indicators included disease-free survival (DFS) and relapse-free survival (RFS). The pooled risk ratio (HR) and 95% confidence interval (CI) for each outcome indicator were determined using random-effects models or fixed-effects models. The pooled odds ratio (OR) and corresponding 95% confidence intervals (CI) for NLR and clinicopathological characteristics were determined with a fixed-effects model. 18 papers published between 2008 and 2022 (3184 patients in total) were included. The pooled analysis found that high preoperative NLR was correlated with poor OS (multivariate HR = 1.83, 95% CI = 1.61–2.08, p

Abstract Major depressive disorder (MDD) is a severe brain disease associated with a significant risk of suicide. Identification of suicidality is sometimes life-saving for MDD patients. We aimed to explore the use of dynamic functional network connectivity (dFNC) for suicidality detection in MDD patients. A total of 173 MDD patients, including 48 without suicide risk (NS), 74 with suicide ideation (SI), and 51 having attempted suicide (SA), participated in the present study. Thirty-eight healthy controls were also recruited for comparison. A sliding window approach was used to derive the dFNC, and the K-means clustering method was used to cluster the windowed dFNC. A linear support vector machine was used for classification, and leave-one-out cross-validation was performed for validation. Other machine learning methods were also used for comparison. MDD patients had widespread hypoconnectivity in both the strongly connected states (states 2 and 5) and the weakly connected state (state 4), while the dysfunctional connectivity within the weakly connected state (state 4) was mainly driven by suicidal attempts. Furthermore, dFNC matrices, especially the weakly connected state, could be used to distinguish MDD from healthy controls (area under curve [AUC] = 82), and even to identify suicidality in MDD patients (AUC = 78 for NS vs. SI, AUC = 88 for NS vs. SA, and AUC = 74 for SA vs. SI), with vision-related and default-related inter-network connectivity serving as important features. Thus, the dFNC abnormalities observed in this study might further improve our understanding of the neural substrates of suicidality in MDD patients.

Abstract Purpose Stereotactic radiosurgery (SRS) has become a standard approach for the treatment of patients with few metastatic brain lesions. However, the optimal treatment approach for the use radiotherapy in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases (BMs) remain unclear. This study aimed to compare the survival outcomes and intracranial local control in NSCLC patients with 1–4 BMs who are treated with SRS using linear accelerators (LINAC-SRS), whole-brain radiotherapy (WBRT), or WBRT plus radiotherapy boost (WBRT + RTB). Materials and methods We retrospectively analyzed 156 NSCLC patients with 1–4 BMs who received LINAC-SRS, WBRT, and WBRT + RTB. The median overall survival (OS), intracranial progression-free survival (iPFS), and distant brain failure-free survival (DBF-FS) and related prognostic factors were analyzed. Results The median follow-up period was 31.6 months. The median OS times in the LINAC-SRS, WBRT, and WBRT + RTB groups were not reached, 33.3 months and 27.9 months, respectively. The difference in survival rate was non-significant (P = 0.909). The 2-year iPFS and DBF-FS rates in the LINAC-SRS, WBRT and WBRT + RTB groups were 51.6% and 37.5%; 42.0% and 50.4%; and 51.1% and 56.1%, respectively. There was no significant difference in 2-year iPFS or DBF-FS among the three groups (P = 0.572 for iPFS, P = 0.628 for DBF-FS). Multivariate analysis showed that the independent adverse prognostic factors for OS, iPFS, and DBF-FS were neurological symptoms, recursive partitioning analysis (RPA) class, and targeted therapy. Conclusion LINAC-SRS did not result in significantly superior survival times or intracranial local control compared to WBRT or WBRT + RTB in the treatment of NSCLC patients with 1–4 BMs.

FAM76B has been reported to be a nuclear speckle-localized protein with unknown function. In this study, FAM76B was first demonstrated to inhibit the NF-κB-mediated inflammatory pathway by affecting the translocation of hnRNPA2B1 in vitro. We further showed that FAM76B suppressed inflammation in vivo using a traumatic brain injury (TBI) mouse model. Lastly, FAM76B was shown to interact with hnRNPA2B1 in human tissues taken from patients with acute, organizing, and chronic TBI, and with different neurodegenerative diseases. The results suggested that FAM76B mediated neuroinflammation via influencing the translocation of hnRNPA2B1 in vivo during TBI repair and neurodegenerative diseases. In summary, we for the first time demonstrated the role of FAM76B in regulating inflammation and further showed that FAM76B could regulate the NF-κB-mediated inflammatory pathway by affecting hnRNPA2B1 translocation, which provides new information for studying the mechanism of inflammation regulation.

Protein post-translational modification (PTM) is a regulatory mechanism for protein activity modulation, localization, expression, and interactions with other cellular molecules. It involves the addition or removal of specific chemical groups on the amino acid residues of proteins. Its common forms include phosphorylation, ubiquitylation, methylation, and acetylation. Emerging research has highlighted lactylation, succinylation, and glycosylation. PTMs are involved in vital biological processes. The occurrence and development of diseases depends on protein abundance and is regulated by various PTMs. In addition, advancements in tumor immunotherapy have revealed that protein PTM is also involved in the proliferation, activation, and metabolic reprogramming of immune cells in tumor microenvironment. These PTMs play an important role in tumor immunotherapy. In this review, we comprehensively summarize the role of several types of PTMs in tumor immunotherapy. This review could provide new insights and future research directions for tumor immunotherapy.

Climate change is expected to result in more extreme rainfall regimes that are characterized by intensified rainfall events and prolonged dry intervals. However, to date, the response of the dryland ecosystems to changes in the rainfall regime has remained unresolved. To better understand the effects of individual dry intervals and extreme rainfall regimes on the aboveground/belowground net primary productivity (ANPP/BNPP) and species diversity of semi-arid sandy grassland, this study aimed to assess the influence of the timing and frequency of prolonged dry intervals on the function of a degraded sandy grassland under a constant total growing-season rainfall. A field rainfall manipulation experiment was carried out in northeast China. The results showed that the 30 day dry interval caused a significant decrease in ANPP and plant cover, except for April. The 30 day dry interval substantially increased the allocation of total net primary productivity (NPP) to BNPP in July, while decreasing the species richness in May and June. The extreme rainfall regimes with lower frequency and longer dry intervals significantly decreased the ANPP, BNPP, plant cover, species richness and species diversity index, while increasing the allocation of the NPP to BNPP and plant density. The mean duration of the dry interval exhibited significant negative correlations with the ANPP, plant cover, species richness, and Simpson index. Variability in dry interval’s mean length also had a negative correlation with ANPP, plant cover, and species richness. Our results suggest that annuals in the semiarid sandy land were highly responsive to changes in rainfall regime. Even if rainfall amount remained constant, increases in duration of the dry intervals and the frequency of extreme intervals were more likely to reduce net primary productivity and species diversity in semiarid sandy annual grasslands, and even contribute to desertification. The findings also provide new evidence for the vital roles of dry interval frequency, duration, and timing, as determinants of semiarid ecosystem function and structure.

The one strain many compounds (OSMAC) strategy is an effective method for activating silent gene clusters by cultivating microorganisms under various conditions. The whole genome sequence of the marine-derived strain Streptomyces globisporus SCSIO LCY30 revealed that it contains 30 biosynthetic gene clusters (BGCs). By using the OSMAC strategy, three types of secondary metabolites were activated and identified, including three angucyclines, mayamycin A (1), mayamycin B (2), and rabolemycin (3); two streptophenazines (streptophenazin O (4) and M (5)); and a macrolide dimeric dinactin (6), respectively. The biosynthetic pathways of the secondary metabolites in these three families were proposed based on the gene function prediction and structural information. The bioactivity assays showed that angucycline compounds 1–3 exhibited potent antitumor activities against 11 human cancer cell lines and antibacterial activities against a series of Gram-positive bacteria. Mayamycin (1) selectively exhibited potent cytotoxicity activity against triple-negative breast cancer (TNBC) cell lines such as MDA-MB-231, MDA-MB-468, and Bt-549, with IC50 values of 0.60–2.22 μM.

Abstract Background Partial trisomy 13q is a less common chromosomal abnormality with a great clinical variability, among them, isolated partial trisomy 13q is extremely rare. Here, we report two new unrelated cases of partial trisomy 13q in Chinese families aiming to emphasize the genotype–phenotype correlation in partial trisomy 13q. Methods Enrolled in this study were two unrelated cases of partial 13q trisomy from two families in Quanzhou region South China. Karyotpe and single-nucleotide polymorphism (SNP) array analysis were employed to identify chromosome abnormalities and copy number variants in the families. Results A 72.9-Mb duplication in 13q14.11q34 region was identified using SNP array analysis in Patient 1 with an intellectual disability, developmental delay, seizures, gastric perforation, and other congenital malformations from a family with paternal inv(13)(p12q14.1). SNP array detection in Patient 2 revealed a 92.4-Mb duplication in 13q12.11q34 region combined with an 8.4-Mb deletion in Xq27.3q28 region with intellectual disability, developmental delay, cleft palate, and duplication of the cervix and the vagina. No chromosomal abnormality was elicited from the parents of Patient 2. Conclusions In this study, we presented two new unrelated cases of partial trisomy 13q with variable features in Chinese population, which may enrich the spectrum of the phenotypes partial trisomy 13q and further confirm the genotype–phenotype correlation.

Background and aimsCompared with self-prepared LRD, a prepackaged low-residue diet (LRD) can improve patient compliance, but whether it can further improve the quality of bowel preparation is uncertain. The study aimed to compare the application of the prepackaged formula LRD with self-prepared LRD in bowel preparation for colonoscopy.MethodsA multicenter randomized controlled trial was conducted in 15 centers. The eligible subjects were randomly assigned to one of two groups: the formula LRD group and the self-prepared LRD group. On the day before the colonoscopy, subjects in the self-prepared LRD group were instructed to consume a restricted LRD prepared by themselves, while subjects in the formula LRD group were given six bags of prepackaged formula LRD and instructed to consume them according to their individual need. The primary outcome was an adequate bowel preparation rate. Secondary outcomes mainly included Boston Bowel Preparation Scale (BBPS) scores, dietary restriction compliance rate, tolerance, satisfaction, adenoma detection rate (ADR), and adverse reactions. The trial was registered at ClinicalTrials.gov under the identifier NCT03943758.ResultsA total of 550 subjects were recruited. Compared with the self-prepared LRD group, the formula LRD group showed a higher adequate bowel preparation rate (94.5 vs. 80.4%; P < 0.01), BBPS scores (7.87 ± 1.13 vs. 6.75 ± 1.47; P < 0.01), dietary compliance rate (92.4 vs. 78.9%; P < 0.01), tolerance (P < 0.01 in degree of hunger, intensity of physical strength, and negative influence on daily activities), satisfaction (8.56 ± 1.61 vs. 7.20 ± 2.02; P < 0.01), and ADR (25.6 vs. 16.0%; P < 0.01). There was no significant difference in adverse reactions.ConclusionCompared with self-prepared LRD, the formula LRD showed similar safety and higher bowel preparation quality, compliance, and tolerance in bowel preparation. More formula LRDs could be designed according to different dietary habits and ethnic populations, and further researches are warranted to confirm their effect.Clinical trial registrationhttps://register.clinicaltrials.gov, identifier: NCT03943758.

Abstract Phosphatidylinositol 3 kinase (PI3K)/AKT (also called protein kinase B, PKB) signalling regulates various cellular processes, such as apoptosis, cell proliferation, the cell cycle, protein synthesis, glucose metabolism, and telomere activity. Corneal epithelial cells (CECs) are the outermost cells of the cornea; they maintain good optical performance and act as a physical and immune barrier. Various growth factors, including epidermal growth factor receptor (EGFR) ligands, insulin-like growth factor 1 (IGF1), neurokinin 1 (NK-1), and insulin activate the PI3K/AKT signalling pathway by binding their receptors and promote antiapoptotic, anti-inflammatory, proliferative, and migratory functions and wound healing in the corneal epithelium (CE). Reactive oxygen species (ROS) regulate apoptosis and inflammation in CECs in a concentration-dependent manner. Extreme environments induce excess ROS accumulation, inhibit PI3K/AKT, and cause apoptosis and inflammation in CECs. However, at low or moderate levels, ROS activate PI3K/AKT signalling, inhibiting apoptosis and stimulating proliferation of healthy CECs. Diabetes-associated hyperglycaemia directly inhibit PI3K/AKT signalling by increasing ROS and endoplasmic reticulum (ER) stress levels or suppressing the expression of growth factors receptors and cause diabetic keratopathy (DK) in CECs. Similarly, hyperosmolarity and ROS accumulation suppress PI3K/AKT signalling in dry eye disease (DED). However, significant overactivation of the PI3K/AKT signalling pathway, which mediates inflammation in CECs, is observed in both infectious and noninfectious keratitis. Overall, upon activation by growth factors and NK-1, PI3K/AKT signalling promotes the proliferation, migration, and anti-apoptosis of CECs, and these processes can be regulated by ROS in a concentration-dependent manner. Moreover, PI3K/AKT signalling pathway is inhibited in CECs from individuals with DK and DED, but is overactivated by keratitis.

To improve the efficiency of coal seam water injection, the influence of nanofluids on coal surface wettability was studied based on the nano drag reduction and injection enhancement technology in the field of tertiary oil recovery. The composition optimization and performance evaluation of nanofluids with nano-silica and sodium lauryl sulfate as the main components were carried out, and the effects of the nanofluid with the optimal ratio on coal wettability were studied through spontaneous upward imbibition experiments. The results show that the composite nanofluid has a lower surface tension, and the lowest value of the interfacial tension is 15.79 mN/m. Therefore, the composite nanofluid can enhance the wettability of coal. However, its effects on coal samples with different metamorphic degrees is different, that is, low rank coal is the largest, middle rank coal is the second, and high rank coal is the least. In addition, a functional relationship between time and imbibition height is found for pulverized coal with different particle sizes. When the particle size of pulverized coal is 60–80 mesh, the wettability of nanofluid to coal is best. The findings in this paper provide a new perspective for improving the water injection efficiency for coal seams with low permeability.

Abstract Purpose Lung cancer is the leading cause of cancer-related mortality. STEAP1 and STEAP2 are overexpressed in various cancers. The purpose of this study was to evaluate the expression and prognostic value of STEAP1 and STEAP2 in patients with lung cancer. Methods The mRNA expression and protein expression of STEAP1 and STEAP2 and their prognostic characteristics were examined using Oncomine, GEPIA, and Kaplan-Meier (KM) plotters. The correlation analysis of STEAP1 and STEAP2 gene and protein levels was conducted using GeneMANIA and STRING. KEGG pathway analysis was used to explore the related signal pathways of STEAP 1 and STEAP2. Immunohistochemical methods were used to compare the expression of STEAP2 in normal lung and non-small cell lung cancer (NSCLC) tissues. Real-time quantitative polymerase chain reaction, western blotting, and immunocytochemistry were used to evaluate the expression of STEAP1 and STEAP2 in three lung cancer cell lines and normal lung epithelial cell lines. Results Analysis of the Oncomine database and GEPIA showed that STEAP1 was upregulated and STEAP2 was downregulated in lung cancer tissue, and both expressions were related to the clinical stage of lung cancer. Immunohistochemical analysis showed that STEAP1 protein expression was significantly upregulated in lung cancer compared to that in adjacent tissues. The expression of STEAP1 was positively correlated with the migration and invasion abilities of lung cancer cells. Compared with paracancer tissues, the expression of STEAP2 protein in lung cancer was significantly downregulated and was correlated with the histological grade of squamous cell carcinoma, pathological classification of adenocarcinoma, tumor, lymph node, and metastasis clinical stage, and lymph node metastasis. The expression of STEAP2 was negatively correlated with the migration and invasion abilities of lung cancer cells. The KM curve showed that the downregulation of STEAP1 expression and upregulation of STEAP2 expression were related to a good lung cancer prognosis. Conclusion STEAP1 and STEAP2 are expected to be potential diagnostic and prognostic markers for lung cancer, which may provide more accurate prognostic indicators for lung cancer.

Aldehyde dehydrogenase (ALDH), a common oxidoreductase in organisms, is an aldehyde scavenger involved in various metabolic processes. However, its function in different pathogenic fungi remains unknown. Fusarium graminearum causes Fusarium head blight in cereals, which reduces grain yield and quality and is an important global food security problem. To elucidate the pathogenic mechanism of F. graminearum, seven genes encoding ALDH were knocked out and then studied for their function. Single deletions of seven ALDH genes caused a decrease in spore production and weakened the pathogenicity. Furthermore, these deletions altered susceptibility to various abiotic stresses. FGSG_04194 is associated with a number of functions, including mycelial growth and development, stress sensitivity, pathogenicity, toxin production, and energy metabolism. FGSG_00139 and FGSG_11482 are involved in sporulation, pathogenicity, and SDH activity, while the other five genes are multifunctional. Notably, we found that FGSG_04194 has an inhibitory impact on ALDH activity, whereas FGSG_00979 has a positive impact. RNA sequencing and subcellular location analysis revealed that FGSG_04194 is responsible for biological process regulation, including glucose and lipid metabolism. Our results suggest that ALDH contributes to growth, stress responses, pathogenicity, deoxynivalenol synthesis, and mitochondrial energy metabolism in F. graminearum. Finally, ALDH presents a potential target and theoretical basis for fungicide development.

The plasticity of welded 441 ferritic stainless steel joints was controlled by varying the laser beam spot diameter during laser welding. A stainless steel plate thickness of 1.2 mm was used. The microstructures of the welded joints were analyzed for various spot diameters. The elongation of breaks and the reduced area of tensile specimens were analyzed to study the effects of spot diameter on plasticity of the welded joints. The results showed that the weld melt width and weld column crystal size increased with the spot diameter, but isometric crystals in the center of the weld were gradually reduced. Increasing spot diameter resulted in decreased tensile strength, elongation after breaks, and area reduction. So the parameter must be controlled during the laser welding.

Zinc (Zn)-enriched pears, which are derived from genetically related cultivars or crops fortified using agronomic methods, have the potential to partly satisfy the human demand for Zn nutrition and diversify consumer choices. However, a standard for the Zn fortification level in pears is lacking, and the disparity in literature-reported fruit Zn concentrations can vary by substantial amounts. Before investigating the Zn concentrations in fruits of the main pear cultivars in China, common sample preparation methods were compared. Among the pre-treatment methods tested, the freeze-dry technique had a greater degree of discrete variation, whereas oven drying (fresh weight) was the optimal method for determining fruit Zn concentrations. Based on the optimal method, no significant distribution patterns of fruit Zn concentration were found among the regions and strains examined. The averaged pulp Zn concentration in all 26 cultivars was 0.72 mg kg−1, with the Hongxiangsu, Jinfeng, and 420 cultivars having the highest concentrations. Combined with the findings from our previous field experiments on Zn-fortified pears, a Zn concentration of ≥0.90 mg kg−1 is the suggested standard for pear enrichment. These results help us to better understand pear Zn nutrition levels and facilitate the marketisation of the fortified fruit.

Land Use/Land Cover (LULC) is a main factor that affects the hydrological process of catchments. A better understanding of its influence is of great significance to future land use planning and water resources management. Since 2011, the local government has implemented a land remediation plan, and the LULC in the Yanghe Reservoir Basin has undergone major changes. This paper uses The Soil and Water Assessment Tool (SWAT) model to study blue water (BW) and green water (GW) resources in three typical years (a wet year, dry year, and normal year) under two LULC scenarios in the basin in 2010 and 2017. The results show that from 2010 to 2017, the area of cultivated land and residential construction land increased by 227.28% and 269.23%, respectively; the area of unused land, woodland, and grassland decreased by 98.84%, 35.90% and 39.52%, respectively. Compared with the results of the 2010 LULC scenario, the average BW of the three typical years under the 2017 LULC scenario decreased by 11.66%, 52.32%, and 21.95%, respectively, and the average GW flow increased by 6.72%, 2.90%, and 6.83%, respectively, and the average GW reserves decreased by 14.80%, 11.39%, and 7.67%, respectively. Therefore, this study believes that changes of LULC have led to a significant decrease in runoff and an increase in evapotranspiration in the basin. HIGHLIGHTS A SWAT model was used to study the blue water and green water resources in three typical years under two LULC scenarios in 2010 and 2017 for the Yanghe Reservoir basin.; The increase in the area of arable land in the Yanghe Reservoir basin has led to an increase in the green water coefficient.;

ABSTRACT Men with nonobstructive azoospermia (NOA) face the dual problems of low sperm count and low sperm quality. Most men with NOA without a clear cause are classified as having idiopathic NOA (iNOA). Previous studies found that microbes exist in semen, and the semen microbes of NOA men are different from those of normal men. However, the relevant mechanism is not clear. In this study, we answered the three questions of “who is there,” “what is it doing,” and “who is doing it” by combining 16s rRNA, nontargeted metabolome detection and metabolite traceability analysis. We found that the composition and interaction of seminal plasma microbes in the iNOA group changed. Metabolite traceability analysis and metabolic pathway analysis revealed that microbial abnormalities in the NOA group were closely related to the decrease of microbial degradation of toluene and the increase of metabolism of fructose or mannose. In addition, the metabolic relationship between microbes and the host in male semen in iNOA revealed that such microbes can produce harmful metabolites that affect sperm quality, the microbes compete with sperm for essential nutrients, and their presence reduces sperm production of essential nutrients. IMPORTANCE Idiopathic nonobstructive azoospermia is one of the great challenges in assisted reproductive therapy. Although microdissection testicular sperm extraction technology is currently available, many men with iNOA still face the problem of poor sperm retrieval and poor sperm quality. The role of seminal plasma microbes in male disease has been continuously investigated since semen was demonstrated to harbor commensal microbes. To our knowledge, this is the first detailed description of the microbe-host relationship in iNOA semen. This study is an important complement to research on the treatment and etiology of iNOA and the rationale for our ongoing research.

In this paper, according to the one-dimensional heat transfer mechanism between fabric and human body, it is found that different thermal properties affect different heat transfer stages of fabric. Therefore, we used the maximum heat flux q max as the index to characterize the transient contact cool feeling of fabrics, and measured the thermal properties, various specifications and surface morphology of 40 kinds of summer fabrics. Firstly, we discussed the influence of the above properties on the transient cool feeling. Secondly, according to multivariate stepwise regression, the significant representative variables are selected, and the prediction model of transient coolness and fabric properties is established. Furthermore, the model was verified to explore the subjective and objective consistency. The results show that, in the transient heat transfer stage, the influencing factors that are significantly related to the cool feeling of fabric include fabric thickness, grammage, volumetric heat capacity, thermal conductivity, warp and weft density, and roughness. The main component representative variables of the cooling sensation regression equation are volumetric heat capacity and thickness, and other variables can be explained by these two variables. Changing them is the key to enhance the cooling sensation. The predicted value of coolness is in good agreement with the subjective evaluation of cooling sensation, which has a certain guiding effect on the actual human cool feeling. The purpose of this study is to find out the main factors that affect the cool feeling, and then apply the established cool feeling model to the development of fabrics in summer, so as to meet the thermal comfort requirements of human body’s fabrics.

IntroductionInflammatory bowel diseases (IBDs) are associated with both immune abnormalities and dysbiosis, characterized by a loss of Faecalibacterium prausnitzii (F. prausnitzii). However, the reason for F. prausnitzii deficiency remains unclear.Methods16S rDNA seque­ncing and IgA enzyme-linked immunosorbent assay (ELISA) were applied to identify bacterial community and IgA changes in ulcerative colitis (UC) patients. Forced immunization with F. prausnitzii in rabbits was conducted. To screen for potential IgA-reactive proteins in F. prausnitzii lysates, we performed western blotting and mass spectrometry analyses. Pyruvate: ferredoxin oxidoreductase (PFOR) was cloned and purified, then the immunoreactivity of PFOR was verified in peripheral blood mononuclear cells (PBMCs) through PCR, ELISpot assay and single-cell sequencing (scRNA-seq). Finally, the UC fecal dysbiosis was re-analyzed in the context of the phylogenetic tree of PFOR.ResultsF. prausnitzii was underrepresented in UC patients with elevated F. prausnitzii-reactive IgA in the fecal supernatant. Forced immunization with F. prausnitzii in rabbits led to high interferon-γ (IFN-γ) transcription in the colon, along with beta diversity disturbance and intestinal inflammation. PFOR was identified as an IgA-binding antigen of F. prausnitzii and the immunoreactivity was validated in PBMCs, which showed elevated expression of inflammatory cytokines. The scRNA-seq revealed enhanced signals in both T regulatory cells (Tregs) and monocytes after PFOR incubation. Furthermore, phylogenetic analysis revealed that PFOR was a common but conserved protein among the gut bacteria.DiscussionOur results collectively suggest that PFOR is a bioactive protein in the immune system and may contribute to host-microbial crosstalk. Conserved but bioactive microbial proteins, such as PFOR, warrant more attention in future host-microbial interaction studies.

PurposeWe performed this study to determine the relationship between serum vitamin D levels and refractive status in adolescents aged 12–19 years.MethodsCross-sectional study using the National Health and Nutrition Examination Survey (NHANES) database from 2001 to 2006. We used weighted multivariate linear regression models to assess the association between serum vitamin levels and adolescent refractive status and then built a smooth curve fitting to investigate their internal non-linear relationships. Finally, subgroup analysis was performed according to gender, and the threshold effect of serum vitamin D levels on spherical equivalent degree was analyzed using a two-piecewise linear regression model.ResultA total of 5,901 adolescents aged 12 to 19 years were included in this study. After adjusting for all confounding factors, the multiple linear regression model showed no significant correlation between adolescent spherical equivalent degree and serum vitamin D [0.0019 (−0.0018, 0.0046)]. However, smooth curve fitting analysis showed an inverted U-shaped curve relationship between spherical equivalent degree and serum vitamin D levels in adolescents (turning point: 58.1 nmol/L). In analyses by gender subgroup, this inverted U-shaped relationship was found to be more pronounced in female adolescents (turning point: 61.6 nmol/L).ConclusionOur results suggest that the correlation between refractive status and serum vitamin D in adolescents differs by gender. When serum vitamin D concentrations were

Medullary thyroid carcinoma (MTC) is one of the common malignant endocrine tumors, which seriously affects human health. Although surgical resection offers a potentially curative therapeutic option to some MTC patients, most patients do not benefit from it due to the difficulty to access the tumors and tumor metastasis. The survival rate of MTC patients has improved with the recent advances in the research, which has improved our understanding of the molecular mechanism underlying MTC and enabled the development and approval of novel targeted drugs. In this article, we reviewed the molecular mechanisms related to MTC progression and the principle for the design of molecular targeted drugs, and proposed some future directions for prospective studies exploring targeted drugs for MTC.

Abstract Background Accumulating evidence supports the pivotal role of intestinal flora in irritable bowel syndrome (IBS). Serotonin synthesis by enterochromaffin (EC) cells is influenced by the gut microbiota and has been reported to have an interaction with IBS. The comparison between the microbiota of the caecal and colonic mucosa in IBS has rarely been studied. The aim of this study was to investigate the relationship between the gut microbiota, EC cells in caecum and descending colon, and diarrhoea-predominant IBS (IBS-D) symptoms. Results A total of 22 IBS-D patients and 22 healthy controls (HCs) were enrolled in our study. Hamilton anxiety (HAM-A) and Hamilton depression (HAM-D) grades increased significantly in IBS-D patients. In addition, the frequency of defecation in IBS-D patients was higher than that in HCs. Among the preponderant bacterial genera, the relative abundance of the Ruminococcus_torques_ group increased in IBS-D patients in caecum samples while Raoultella and Fusobacterium were less abundant. In the descending colon, the abundance of the Ruminococcus_torques_group and Dorea increased in IBS-D patients and Fusobacterium decreased. No difference was observed between the descending colon and caecum in regards to the mucosal-associated microbiota. The number of EC cells in the caecum of IBS-D patients was higher than in HCs and the expression of TPH1 was higher in IBS-D patients both in the caecum and in the descending colon both at the mRNA and protein level. Correlation analysis showed that the Ruminococcus_torques_group was positively associated with HAM-A, HAM-D, EC cell number, IBS-SSS, degree of abdominal pain, frequency of abdominal pain and frequency of defecation. The abundance of Dorea was positively associated with EC cell number, IBS-SSS, HAM-A, HAM-D and frequency of abdominal pain. Conclusions EC cell numbers increased in IBS-D patients and the expression of TPH1 was higher than in HCs. The Ruminococcus torques group and Dorea furthermore seem like promising targets for future research into the treatment of IBS-D patients.

Abstract Considering that the working temperature is much higher in high‐voltage direct‐current (HVDC) convert transformers than in conventional AC transformers, the combination of thermally upgraded paper and natural ester might be a better choice to withstand high temperature in long‐term operation. This study compares the chemical structure, DC breakdown voltage, space charge and trap distribution of thermally upgraded paper aged in natural esters and mineral oil. The relationship between DC breakdown and accumulated charges was analyzed. Results show that the thermally upgraded paper aged in natural ester (NEI‐TUP) has a higher volume resistivity and DC breakdown voltage than that aged in mineral oil (MOI‐TUP). The NEI‐TUP group has a larger deep trap density than the MOI‐TUP group due to the chemical structure of natural ester. The larger deep trap density could contribute to the lower charge accumulation quantity and higher DC breakdown voltage. The thermally upgraded paper immersed in natural ester presents better insulation capability under thermal and DC electrical stress than that immersed in conventional mineral oil. This research indicated that the combination of thermally upgraded paper and natural ester might be a potential alternative for the mineral oil immersed paper in the future.

Abstract Aβ42 is one of the most extensively studied blood and Cerebrospinal fluid (CSF) biomarkers for the diagnosis of symptomatic and prodromal Alzheimer’s disease (AD). Because of the heterogeneity and transient nature of Aβ42 oligomers (Aβ42Os), the development of technologies for dynamically detecting changes in the blood or CSF levels of Aβ42 monomers (Aβ42Ms) and Aβ42Os is essential for the accurate diagnosis of AD. The currently commonly used Aβ42 ELISA test kits usually mis-detected the elevated Aβ42Os, leading to incomplete analysis and underestimation of soluble Aβ42, resulting in a comprised performance in AD diagnosis. Herein, we developed a dual-target lateral flow immunoassay (dLFI) using anti-Aβ42 monoclonal antibodies 1F12 and 2C6 for the rapid and point-of-care detection of Aβ42Ms and Aβ42Os in blood samples within 30 min for AD diagnosis. By naked eye observation, the visual detection limit of Aβ42Ms or/and Aβ42Os in dLFI was 154 pg/mL. The test results for dLFI were similar to those observed in the enzyme-linked immunosorbent assay (ELISA). Therefore, this paper-based dLFI provides a practical and rapid method for the on-site detection of two biomarkers in blood or CSF samples without the need for additional expertise or equipment. Graphical Abstract

With the implementation of low impact development (LID) in urban areas, it is necessary to quantify the actual effectiveness of LID facilities. In this study, a coupled hydrology-hydrodynamic numerical model was utilized to investigate the runoff control effectiveness of permeable pavements in the city centre of Shijiazhuang, China. Two groups of designed rainfall events with the same duration but different rainfall amounts and peak rainfall intensity locations were presented, and the effectiveness of permeable pavement was demonstrated by the reduction in the total runoff volume, water depth, and inundated area. The results indicate that the rainfall amount is the main factor affecting the runoff control of permeable pavements, and their effectiveness decreases with increasing rainfall amounts and peak intensity coefficients. Moreover, permeable pavements are more effective in reducing the residential waterlogging area, and the proportion of the inundated area above a depth of 0.2 m is considerably diminished. This study reveals the response of the runoff control of permeable pavements to different rainfall patterns, which is essential for supporting the design and practical operation of permeable pavements. HIGHLIGHTS Simulation scenarios with different rainfall patterns were presented to investigate the runoff control effectiveness of permeable pavement.; A series of indicators, including runoff volume, water depth, and inundated area, were presented to illustrate the runoff control effectiveness.; The effect of the relationship between rainfall intensity and infiltration rate on runoff generation was analysed.;

Abstract Aims There is little knowledge about partial trisomy 4q and the genotype–phenotype correlation. In this study, we presented the detail of two Chinese families with partial distal 4q duplication in an attempt to clarify the correlation between the genotype and the phenotype. Methods Two pedigrees with distal 4q duplication were enrolled in this study. Karyotype analysis and single-nucleotide polymorphism (SNP) array detection were performed for prenatal diagnosis. Fluorescence in situ hybridization analysis. (FISH) was conducted to verify the copy number variants. Results Two families with partial trisomy 4q were identified. The fetus in pedigree 1 exhibited multiple ultrasound anomalies including intrauterine growth restriction and an atrioventricular septal defect who had a duplication of 4q28.3-qter associate with 6p25.2-p25.3 deletion, which resulted from balanced translocation carried by his father t(4;6)(q28.3;p25.2). The fetus in pedigree 2 had a distal 4q28.3-qter duplication combined with monosomy of Xp21.3-p22.3, and the karyotype was described as 46,X,der(X)t(X;4)(p21.3;q28.3)mat, which originally inherited from the pregnant woman who exhibited a mild clinical phenotype limited to short stature. Conclusions In our study, we for the first time identified the partial trisomy 4q associate with 6p or Xp deletion. In addition, our finding further strengthens that mild clinical phenotype in 4q duplication case may be due to the spreading of X inactivation to the autosomal in derivation of chromosome X.