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Introduction: The proportion of animal based foods in daily diet of consumers is constantly increasing, with chicken being highly favored due to its high protein and low fat characteristics. The consumption of chicken around the world is steadily increasing. Intramuscular fat (IMF) is a key indicator affecting meat quality. Object: High IMF content can contribute to improve the quality of chicken meat. The regulatory mechanism of IMF deposition in chicken is poorly understood, so its complete elucidation is essential to improve chicken meat quality. Method: Here, we performed whole genome resequencing on 516 yellow feather chickens and single-cell RNA sequencing on 3 63-day-old female JXY chickens. In addition, transcriptome sequencing techniques were also performed on breast muscle tissue of JXY chickens at different developmental stages. And 13C isotope tracing technique was applied. Results: In this study, a large-scale genetic analysis of an IMF-selected population and a control population identified fatty acid synthase (FASN) as a key gene for improving IMF content. Also, contrary to conventional view, de novo lipogenesis (DNL) was deemed to be an important contributor to IMF deposition. As expected, further analyses by isotope tracing and other techniques, confirmed that DNL mainly occurs in myocytes, contributing about 40% of the total fatty acids through the regulation of FASN, using the available FAs as substrates. Additionally, we also identified a relevant causal mutation in the FASN gene with effects on FA composition. Conclusion: These findings contribute to the understanding of fat metabolism in muscle tissue of poultry, and provide the feasible strategy for the production of high-quality chicken meat.

Although several synthetic hydrogels with defined stiffness have been developed to facilitate the proliferation and maintenance of human pluripotent stem cells (hPSCs), the influence of biochemical cues in lineage-specific differentiation and functional cluster formation has been rarely reported. Here, we present the application of Supragel, a supramolecular hydrogel formed by synthesized biotinylated peptides, for islet-like cluster differentiation. We observed that Supragel, with a peptide concentration of 5 mg/mL promoted spontaneous hPSCs formation into uniform clusters, which is mainly attributable to a supporting stiffness of ∼1.5 kPa as provided by the Supragel matrix. Supragel was also found to interact with the hPSCs and facilitate endodermal and subsequent insulin-secreting cell differentiation, partially through its components: the sequences of RGD and YIGSR that interacts with cell membrane molecules of integrin receptor. Compared to Matrigel and suspension culturing conditions, more efficient differentiation of the hPSCs was also observed at the stages 3 and 4, as well as the final stage toward generation of insulin-secreting cells. This could be explained by 1) suitable average size of the hPSCs clusters cultured on Supragel; 2) appropriate level of cell adhesive sites provided by Supragel during differentiation. It is worth noting that the Supragel culture system was more tolerance in terms of the initial seeding densities and less demanding, since a standard static cell culture condition was sufficient for the entire differentiation process. Our observations demonstrate a positive role of Supragel for hPSCs differentiation into islet-like cells, with additional potential in facilitating germ layer differentiation.

Abstract Background Human Papillomavirus (HPV) DNA screening was a crucial element in the fight against cervical cancer and had been adopted in many countries, including China. However, the onset of the COVID-19 pandemic in March 2020 disrupted this program significantly. Methods The aim of this study is to investigate the prevalence and distribution of HPV genotypes among the population undergoing cervical cancer screening during the pandemic period. From January 2017 to December 2022, Peking Union Medical College Hospital gathered 45,496 cervical swabs from individuals undergoing cervical cancer screening. These samples were analyzed to detect fifteen high-risk HPV (HR-HPV) DNA types and a combination of two low-risk HPV (LR-HPV) types. Results The study revealed an overall infection rate of 11.24% (5,114/45,496), with 11.06% (5,032/45,496) of individuals infected with HR-HPV. The number of HPV screening patients and the infection rates of HPV, HR-HPV, LR-HPV, multiple genotype HPV (M-HPV), and single genotype HPV (S-HPV) during the pandemic were lower than those observed before the pandemic. Moreover, the age group with the highest percentage of infected individuals was under 45–49 years, with HPV52, HPV58, HPV16, and HPV51 being the most prevalent genotypes. Notably, HPV66 emerged as the fifth most commonly detected genotype during the pandemic. Additionally, among the eleven age groups examined, women under 25 exhibited the highest detection rate, with HPV52 and HPV16 infection rates exceeding those observed in the pre-pandemic period. Conclusions The findings of this study offer significant insights for shaping HPV prevention strategies and enhancing cervical cancer screening initiatives in China following the epidemic.

Abstract Background Two-line hybrid wheat technology system is one way to harness wheat heterosis both domestically and internationally. Seed vigor is a crucial parameter for assessing seed quality, as enhanced seed vigor can lead to yield increments of over 20% to a certain extent. MicroRNAs (miRNAs) were known to participate in the development and vigor of seed in plants, but its impact on seed vigor in two-line hybrid wheat remains poorly elucidated. Results The hybrid (BS1453/11GF5135) wheat exhibited superiority in seed vigor and anti-aging capacity, compared to its male parent (11GF5135, MP) and female parent (BS1453, FP). We identified four miRNAs associated with seed vigor, all of which are novel miRNAs. The majority of targets of miRNAs were related to ubiquitin ligases, kinases, sucrose synthases and hydrolases, involving in starch and sucrose metabolism, hydrolysis, catalysis, plant hormone signal transduction, and other pathways, which played crucial roles in seed development. Additionally, we also found miR531 was differentially expressed in both male parent and hybrid, and its target gene was a component of the E1 subunit of α-ketoate dehydrogenase complex, which interacted with dihydrolipoamide acetyltransferase (E2) and dihydrolipoyl dehydrogenase (E3). Finally, We established a presumptive interaction model to speculate the relationship of miR531 and seed vigor. Conclusions This study analyzed the seed vigor of two-line hybrid wheat, and screened seed vigor-related miRNAs. Meanwhile speculated the genetic relationship of hybrid and parents, in terms of miRNAs. Consequently, the present study provides new insights into the miRNA-mediated gene and protein interaction network that regulates seed vigor. These findings hold significance for enhancing the yield and quality of two-line hybrid wheat, facilitating its future applications.

Abstract Drug-resistant epilepsy with frequent seizures are considered to undergo surgery to become seizure-free, but seizure-free rates have not dramatically improved, partly due to imprecise intervention locations. To address this clinical need, we construct effective connectivity to reveal epilepsy brain dynamics. Based on the propagation path captured by the high order effective connectivity, calculate the control centrality evaluation scheme of the excised area. We used three datasets: simulation dataset, clinical dataset, and public dataset. The epileptogenic propagation network was quantified by calculating high-order effective connection to obtain accurate propagation path, based on this, combined with the outdegree index for virtual resection. By removing electrodes and recalculating control centrality, we quantify each electrode or region’s control centrality to evaluate the virtual resection scheme. Three datasets obtained consistent results. We track the accurate propagation path and find the obvious inflection points occurring during the excision process. The minimum intervention targets were obtained by comparing different schemes without recurrence. The clinical data with multiple seizures found that after resection, the brain reaches a stable state and is less likely to continue spreading. By quantitative analysis of control centrality to evaluate the possible excision scheme, finally we obtain the best intervention area for epilepsy, which assist in developing surgical plans.

Abstract Objective The purpose of this study was to translate the Vicarious Posttraumatic Growth Inventory (VPTGI) into Chinese and to assess its reliability and validity in Nurses, Additionally, it explored the correlations between vicarious posttraumatic growth (VPTG), Secondary Traumatic Stress (STS) and demographic variables. Methods The Brislin translation model was used to translate the VPTGI into Chinese. Validity analysis involved exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and assessments of convergent validity, discriminant validity, and content validity. Reliability analysis included split-half reliability, internal consistency reliability, and test-retest reliability. Item analysis employed the Critical Ratio Decision Value (CR) method, item-total correlation method, and reliability change method. Single-factor analysis was conducted to examine the relationship between demographic variables and VPTG, while correlation analysis explored the association between STS and VPTG. Results The Chinese version VPTGI demonstrated robust content validity (I-CVI: 0.83-1, S-CVI: 0.97), supported by EFA (KMO: 0.933) and significant Bartlett’s test (p

Abstract Thyroid hormones (THs) may affect chronic thyrotoxic myopathy (CTM). The relationship between TH sensitivity and CTM is inconsistent. We aimed to investigate the associations between TH sensitivity and the risk of CTM and to screen potential CTMs with strength and function tests. A total of 162 Chinese patients (36.58% men) with Graves’ disease were enrolled and divided into CTM and non-CTM groups. TH and sensitivity indices were measured. Muscle power and function were assessed by grip, upper-limb fatigue (ULFT), lower-limb fatigue (LLFT), and squat-up (SUT) tests, and walking pace. Association between sensitivity to TH indices and the risk of developing CTM was assessed via multivariate logistic regression. The diagnostic effectiveness of muscle power and function for predicting CTM was evaluated via receiver operating characteristic (ROC) curves. Thyroid feedback quantile-based index FT3 (TFQIFT3) and the parametric TFQIFT3 (PTFQIFT3), TFQIFT4, and PTFQIFT4 were positively associated with CTM risk by using inverse probability of treatment weighting multivariate logistic regression. For each 1-SD increase in TFQIFT3 and PTFQIFT3, TFQIFT4 and PTFQIFT4, the odds ratios for CTM were 1.67 (95% CI = 1.17–2.48) ,1.64 (95% CI = 1.51–2.93), 1.60 (95%CI = 1.12–2.32), 1.58 (95%CI = 1.11–2.30), respectively. LLFT and SUT best predicted male/female CTM, respectively (AUC = 0.89/0.85). In Graves’ disease patients, TH sensitivity is associated with CTM development, which can be predicted by SUT and LLFT results.

Abstract Objectives Repeatability is crucial for ensuring the generalizability and clinical utility of radiomics-based prognostic models. This study aims to investigate the repeatability of radiomic feature (RF) and its impact on the cross-institutional generalizability of the prognostic model for predicting local recurrence-free survival (LRFS) and overall survival (OS) in esophageal squamous cell cancer (ESCC) receiving definitive (chemo) radiotherapy (dCRT). Methods Nine hundred and twelve patients from two hospitals were included as training and external validation sets, respectively. Image perturbations were applied to contrast-enhanced computed tomography to generate perturbed images. Six thousand five hundred ten RFs from different feature types, bin widths, and filters were extracted from the original and perturbed images separately to evaluate RF repeatability by intraclass correlation coefficient (ICC). The high-repeatable and low-repeatable RF groups grouped by the median ICC were further analyzed separately by feature selection and multivariate Cox proportional hazards regression model for predicting LRFS and OS. Results First-order statistical features were more repeatable than texture features (median ICC: 0.70 vs 0.42–0.62). RFs from LoG had better repeatability than that of wavelet (median ICC: 0.70–0.84 vs 0.14–0.64). Features with smaller bin widths had higher repeatability (median ICC of 8–128: 0.65–0.47). For both LRFS and OS, the performance of the models based on high- and low-repeatable RFs remained stable in the training set with similar C-index (LRFS: 0.65 vs 0.67, p = 0.958; OS: 0.64 vs 0.65, p = 0.651), while the performance of the model based on the low-repeatable group was significantly lower than that based on the high-repeatable group in the external validation set (LRFS: 0.61 vs 0.67, p = 0.013; OS: 0.56 vs 0.63, p = 0.013). Conclusions Applying high-repeatable RFs in modeling could safeguard the cross-institutional generalizability of the prognostic model in ESCC. Critical relevance statement The exploration of repeatable RFs in different diseases and different types of imaging is conducive to promoting the proper use of radiomics in clinical research. Key Points The repeatability of RFs impacts the generalizability of the radiomic model. The high-repeatable RFs safeguard the cross-institutional generalizability of the model. Smaller bin width helps improve the repeatability of RFs. Graphical Abstract

Abstract Background Neonatal respiratory distress syndrome (NRDS) is a primary cause of morbidity and mortality in premature infants. Platelets have a unique role in lung repair and remodeling. This study aimed to determine the relationship between platelet count and NRDS severity. Methods The study included 234 newborns diagnosed with NRDS from January 2019 to August 2023. This study employed two methods of grouping: the first based on platelet count, dividing participants into thrombocytopenia (platelet count

Abstract Background Pseudouridine (Ψ), a C5-glycoside isomer of uridine, stands as one of the most prevalent RNA modifications in all RNA types. Distinguishing from the C-N bond linking uridine to ribose, the link between Ψ and ribose is a C-C bond, endowing Ψ modified RNA distinct properties and functions in various biological processes. The conversion of uridine to Ψ is governed by pseudouridine synthases (PUSs). RNA pseudouridylation is implicated in cancer biology and therapeutics. Objectives In this review, we will summarize the methods for detecting Ψ, the process of Ψ generation, the impact of Ψ modification on RNA metabolism and gene expression, the roles of dysregulated Ψ and pseudouridine synthases in cancers, and the underlying mechanism. Methods We conducted a comprehensive search of PubMed from its inception through February 2024. The search terms included “pseudouridine”; “pseudouridine synthase”; “PUS”; “dyskerin”; “cancer”; “tumor”; “carcinoma”; “malignancy”; “tumorigenesis”; “biomarker”; “prognosis” and “therapy”. We included studies published in peer-reviewed journals that focused on Ψ detection, specific mechanisms involving Ψ and PUSs, and prognosis in cancer patients with high Ψ expression. We excluded studies lacking sufficient methodological details or appropriate controls. Results Ψ has been recognized as a significant biomarker in cancer diagnosis and prognosis. Abnormal Ψ modifications mediated by various PUSs result in dysregulated RNA metabolism and impaired RNA function, promoting the development of various cancers. Overexpression of PUSs is common in cancer cells and predicts poor prognosis. PUSs inhibition arrests cell proliferation and enhances apoptosis in cancer cells, suggesting PUS-targeting cancer therapy may be a potential strategy in cancer treatment. Discussion High Ψ levels in serum, urine, and saliva may suggest cancer, but do not specify the type, requiring additional lab markers and imaging for accurate diagnosis. Standardized detection methods are also crucial for reliable results. PUSs are linked to cancer, but more researches are needed to understand their mechanisms in different cancers. Anticancer treatments targeting PUSs are still under developed.

Abstract Background Colonoscopic enteral tube placement using current methods has some shortcomings, such as the complexity of the procedure and tube dislodgement. The magnetic navigation technique (MNT) has been proven effective for nasoenteral feeding tube placement, and is associated with reduced cost and time to initiation of nutrition. This study attempted to develop a novel method for enteral tube placement using MNT. Methods The MNT device consisted of an external magnet and a 12 Fr tube with a magnet at the end. Ten swine were used, and bowel cleansing was routinely performed before colonoscopy. Intravenous anesthesia with propofol and ketamine was administered. A colonoscopic enteral tube was placed using the MNT. The position of the end of the enteral tube was determined by radiography, and angiography was performed to check for colonic perforations. Colonoscopy was used to detect intestinal mucosal damage after tube removal. Results MNT-assisted colonoscopic enteral tube placement was successfully completed in all pigs. The median operating time was 30 (26–47) min. No colon perforation was detected on colonography after enteral tube placement, and no colonic mucosal bleeding or injury was detected after the removal of the enteral tube. Conclusions MNT-assisted colonoscopic enteral tube placement is feasible and safe in swine and may represent a valuable method for microbial therapy, colonic drainage, and host-microbiota interaction research in the future.

Background: Probiotic supplementation has a positive effect on endurance exercise performance and body composition in athletes, but the underlying mechanisms remain unclear. Gut microbiota can provide measurable markers of immune function in athletes, and microbial composition analysis may be sensitive enough to detect stress and metabolic disorders caused by exercise. Methods: Nineteen healthy active amateur marathon runners (15 male and 4 female) with a mean age of 29.11 years volunteered to participate in this double-blind controlled study. Based on the performance of the Cooper 12-min running test (CRT), the participants were allocated into two groups to receive either a probiotic formulation comprising lactobacillus acidophilus and bifidobacterium longum (n = 10) or placebo containing maltodextrin (n = 9) for five weeks. Consistency of diet and exercise was ensured throughout the experimental period. Before and after the intervention, all participants were assessed for CRT, emotional stability and gastrointestinal symptoms, gut microbiota composition, body composition and magnetic resonance imaging (MRI) indicators of skeletal muscle microcirculation. Results: Compared to before the intervention, the probiotics group showed an increase in CRT score (2.88 ± 0.57 vs 3.01 ± 0.60 km, P＜0.05), significant improvement in GSRS and GIQLI (9.20 ± 4.64 vs 7.40 ± 3.24, 118.90 ± 12.30 vs 127.50 ± 9.85, P＜0.05), while these indicators remained unchanged in the control group, with a significant time-group interaction effect on gastrointestinal symptoms. Additionally, some MRI metabolic cycling indicators of the thigh skeletal muscle also changed in the probiotics group (P＜0.05). Regarding microbiota abundance, the probiotics group exhibited a significant increase in the abundance of beneficial bacteria and a significant decrease in the abundance of harmful bacteria post-intervention (P＜0.05). Conclusion: As a sports nutritional supplement, probiotics have the potential to improve athletic performance by optimizing the balance of gut microbiota, alleviating gastrointestinal symptoms.

Abstract Background The initial randomized, double‐blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first‐line therapy in epidermal growth factor receptor (EGFR)‐mutated advanced non‐small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study. Methods Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double‐blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow‐up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological‐BICR). The primary endpoint for this subgroup analysis was CNS progression‐free survival (PFS). Results Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological‐BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17‐0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11‐0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non‐CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed. Conclusions These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR‐mutated advanced NSCLC with baseline CNS metastases. Trial registration ClinicalTrials.gov number, NCT03849768

Abstract Background The post-processing technology of CTA offers significant advantages in evaluating left atrial enlargement (LAE) in patients with persistent atrial fibrillation (PAF). This study aims to identify parameters for rapidly and accurately diagnosing LAE in patients with PAF using CT cross-sections. Methods Left atrial pulmonary venous (PV) CT was performed to 300 PAF patients with dual-source CT, and left atrial volume (LAV), left atrial anteroposterior diameter (LAD1), left atrial transverse diameter (LAD2), and left atrial area (LAA) were measured in the ventricular end systolic (ES) and middle diastolic (MD). LA index (LAI) = LA parameter/body surface area (BSA). Left atrial volume index (LAVIES) > 77.7 ml/m2 was used as the reference standard for the LAE diagnosis. Results 227 patients were enrolled in the group, 101 (44.5%) of whom had LAE. LAVES and LAVMD (r = 0.983), LAVIES and LAVIMD (r = 0.984), LAAES and LAVIES (r = 0.817), LAAMD and LAVIES (r = 0.814) had strong positive correlations. The area under curve (AUC) showed that all measured parameters were suitable for diagnosing LAE, and the diagnostic efficacy was compared as follows: LAA/LAAI> LAD> the relative value index of LAD, LAD2> LAD1. LAA and LAAI demonstrated comparable diagnostic efficacy, with LAA being more readily available than LAAI. Conclusions The axial LAA measured by CTA can be served as a parameter for the rapid and accurate diagnosis of LAE in patients with PAF.

Abstract Background The pathogenesis of intermittent exotropia (IXT) remains unclear. The study aims to investigate alterations of resting-state networks (RSNs) in IXT adult patients using resting-state functional magnetic resonance imaging (rs-fMRI) data to explore the potential neural mechanisms. Methods Twenty-six IXT adult patients and 22 age-, sex-, handedness-, and education-matched healthy controls (HCs) underwent fMRI scanning and ophthalmological examinations. Brain areas with significant functional connectivity (FC) differences between the IXT and HC groups were selected as regions of interest (ROI) and mean z-scores were calculated to control for individual differences. Results Compared with HCs, IXT patients exhibited altered FC in various brain regions within RSNs involved in binocular fusion, stereopsis, ocular movement, emotional processes and social cognition, including the default mode network (DMN), the dorsal attention network (DAN), the visual network (VN), the sensorimotor network (SMN), the executive control network (ECN), the frontoparietal network (FPN) and the auditory network (AN). The degree of exodeviation was positively correlated with FC value of left middle occipital gyrus (MOG) within the VN. Correspondingly, we found a negative correlation between the degree of exodeviation and the FC value of left angular gyrus (AG) within FPN (P

Abstract As one of the two main histologic subtypes of gastric cancer (GC), diffuse-type gastric cancer (DGC) containing poorly cohesive gastric carcinoma (PCC) components has a worse prognosis and does not respond well to typical therapies. Despite the large number of studies revealing the complex pathogenic network of DGC, the molecular heterogeneity of DGC is still not fully understood. We obtained single-cell RNA-seq data and bulk data from the tumor immune single cell hub, the public gene expression omnibus, and the cancer genome atlas databases. A series of bioinformatics analyses were performed using R software. Immunofluorescence staining, hematoxylin and eosin staining, western blot, and functional experiments were used for experimental validation. Caudin-3, -4 and -7 were lowly expressed in DGC and their expression levels were further reduced in PCC. The PCC components were mainly located in the deeper layers of the DGC and had a high level of hypoxic Wnt/β-catenin signaling and stemness. We further identified Insulin Like Growth Factor Binding Protein 7 (IGFBP7) as a marker for PCC components in the deep layer. IGFBP7 is stimulated by hypoxia and promotes cancer cell invasiveness and reduced claudin expression. In addition, programmed death-1 ligand (PD-L1) was specifically expressed in the deep layer, reflecting deep layer-specific immunosuppression. The PCC components are predominantly situated in the deeper layers of DGC. Initial molecular characterization of these PCC components revealed distinct features, including low expression of claudin-3, -4, and -7, high expression of IGFBP7, and the presence of PD-L1. These molecular traits may partially account for the pronounced tumor heterogeneity observed in GC.

Abstract Objectives This study aimed to quantify the global cardiovascular disease (CVD) burden attributable to diet low in fiber among adults aged 60 years and older using data from the Global Burden of Disease (GBD) Study 2019. Methods We extracted data on CVD mortality, disability-adjusted life-years (DALYs), and risk-factor exposures from the GBD 2019 study for people aged 60 and older. Age-period-cohort models were used to estimate the overall annual percentage change in mortality and DALY rate (net drift, % per year), mortality and DALY rate for each age group from 1990 to 2019 (local drift, % per year), longitudinal age-specific rate corrected for period bias (age effect), and mortality and Daly rate for each age group from 1990 to 2019 (local drift, % per year). And period/cohort relative risk (period/cohort effect). Results From 1990 to 2019, global age-standardized cardiovascular disease (CVD) mortality rates attributable to low dietary fiber intake decreased by 2.37% per year, while disability-adjusted life years (DALYs) fell by 2.48% annually. Decreases were observed across all sociodemographic index regions, with fastest declines in high and high-middle SDI areas. CVD mortality and DALY rates attributable to low fiber increased exponentially with age, peaking at 85–89 years, and were higher in men than women. Regarding period effects, mortality and DALY rates declined since 2000, reaching nadirs in 2015–2019. For birth cohort patterns, risks attributable to low fiber intake peaked among early 1900s births and subsequently fell, with more pronounced reductions over time in women. Conclusions Low dietary fiber intake is a leading contributor to the global cardiovascular disease burden, accounting for substantial mortality and disability specifically among older adults over recent decades.

Abstract Acute pancreatitis (AP) is an inflammatory disease of the pancreas. Despite of a steadily increasing in morbidity and mortality, there is still no effective therapy. Gut microbial dysbiosis and its derived-metabolites disorder have been shown to play an important role in the development of AP, however, little is known regarding the crosstalk between gut microbiota and metabolites. In this study, we assessed the alterations in gut microbiota and metabolites by constructing three AP mouse models by means of metagenomic and metabolomic sequencing, and further clarified their relationship by correlation analysis. The results revealed that each model exhibited unique flora and metabolite profiles. KEGG analysis showed that the differential flora and metabolite-enriched pathway functions were correlated with lipid metabolism and amino acid metabolism. Moreover, two core differential bacterial species on Burkholderiales bacterium YL45 and Bifidobacterium pseudolongum along with eleven differential metabolites appeared to exert certain effects during the course of AP. In conclusion, further exploration of the crosstalk between microbiota and derived metabolites may provide novel insights and strategies into the diagnosis and treatment of AP.

Abstract Abscisic acid (ABA) is the primary preventing factor of seed germination, which is crucial to plant survival and propagation. ABA-induced seed germination inhibition is mainly mediated by the dimeric PYR/PYL/RCAR (PYLs) family members. However, little is known about the relevance between dimeric stability of PYLs and seed germination. Here, we reveal that stabilization of PYL dimer can relieve ABA-induced inhibition of seed germination using chemical genetic approaches. Di-nitrobensulfamide (DBSA), a computationally designed chemical probe, yields around ten-fold improvement in receptor affinity relative to ABA. DBSA reverses ABA-induced inhibition of seed germination mainly through dimeric receptors and recovers the expression of ABA-responsive genes. DBSA maintains PYR1 in dimeric state during protein oligomeric state experiment. X-ray crystallography shows that DBSA targets a pocket in PYL dimer interface and may stabilize PYL dimer by forming hydrogen networks. Our results illustrate the potential of PYL dimer stabilization in preventing ABA-induced seed germination inhibition.

Abstract Ferroptosis is a promising strategy for cancer therapy, with numerous inhibitors of its braking axes under investigation as potential drugs. However, few studies have explored the potential of activating the driving axes to induce ferroptosis. Herein, phosphatidylcholine peroxide decorating liposomes (LIPPCPO) are synthesized to induce ferroptosis by targeting divalent metal transporter 1 (DMT1). LIPPCPO is found to boost lysosomal Fe2+ efflux by inducing cysteinylation of lysosomal DMT1, resulting in glutathione peroxidase 4 (GPX4) suppression, glutathione depletion and ferroptosis in breast cancer cells and xenografts. Importantly, LIPPCPO induced ferroptotic cell death is independent of acquired resistance to radiation, chemotherapy, or targeted agents in 11 cancer cell lines. Furthermore, a strong synergistic ferroptosis effect is observed between LIPPCPO and an FDA-approved drug, artesunate, as well as X rays. The formula of LIPPCPO encapsulating artesunate significantly inhibits tumor growth and metastasis and improves the survival rate of breast cancer-bearing female mice. These findings provide a distinct strategy for inducing ferroptosis and highlight the potential of LIPPCPO as a vector to synergize the therapeutic effects of conventional ferroptosis inducers.

Abstract Background To evaluate the clinical performance of two deep learning methods, one utilizing real clinical pairs and the other utilizing simulated datasets, in enhancing image quality for two-dimensional (2D) fast whole-body scintigraphy (WBS). Methods A total of 83 patients with suspected bone metastasis were retrospectively enrolled. All patients underwent single-photon emission computed tomography (SPECT) WBS at speeds of 20 cm/min (1x), 40 cm/min (2x), and 60 cm/min (3x). Two deep learning models were developed to generate high-quality images from real and simulated fast scans, designated 2x-real and 3x-real (images from real fast data) and 2x-simu and 3x-simu (images from simulated fast data), respectively. A 5-point Likert scale was used to evaluate the image quality of each acquisition. Accuracy, sensitivity, specificity, and the area under the curve (AUC) were used to evaluate diagnostic efficacy. Learned perceptual image patch similarity (LPIPS) and the Fréchet inception distance (FID) were used to assess image quality. Additionally, the count-level consistency of WBS was compared between the two models. Results Subjective assessments revealed that the 1x images had the highest general image quality (Likert score: 4.40 ± 0.45). The 2x-real, 2x-simu and 3x-real, 3x-simu images demonstrated significantly better quality than the 2x and 3x images (Likert scores: 3.46 ± 0.47, 3.79 ± 0.55 vs. 2.92 ± 0.41, P 0.05), whereas the diagnostic efficacy for the 3x-real and 3x-simu was better than that for the 3x images (accuracy: 65.1%, 66.35% vs. 59.0%; sensitivity: 63.64%, 63.64% vs. 64.71%; specificity: 66.67%, 69.23% vs. 55.1%. All P

The study examined the functional properties of lactic yeast-fermented Tartary buckwheat sprout with passion and pineapple juice (Tatary buckwheat sprout juice). Pineapple and passion fruit were included during fermentation to improve the sensory and nutritional quality of the juice. We initially created a juice with Tartary buckwheat sprouts, and then fermented it with Lactobacillus plantarum and yeast (Saccharomyces cerevisiae) to produce a novel fermented sprout juice. Our results indicated that the best organoleptic quality was achieved when the inoculum of Lactobacillus plantarum was 2%, the inoculum of yeast was 1%, and the fermentation time was 30 hours. The results showed that fermentation resulted in a 1.55-fold increase in the total amino acid content, with fresh sweet amino acids increasing by 1.75-fold and sour-bitter amino acids increasing by 1.33-fold. Additionally, the levels of acetic acid, lactic acid, citric acid, and tartaric acid in the buckwheat sprout juice increased by 12.31%, 11.45%, 4.22%, and 3.88%, respectively. GC-MS analysis revealed a significant increase of volatile flavoring substances, such as alcohols and esters, by more than 24.7% in the fermentation products. From the results, yeast-Lactobacillus fermentation process may effectively improve the nutritional values of Tartary buckwheat sprout juice.

This paper investigated the influence of ultraviolet (UV) illumination on the corrosion behavior of 7A04 aluminum alloy in 3.5% NaCl solutions with various pH values (pH=5.0, 7.0, and 10.0) using weight loss measurement, electrochemical methods, and surface analysis techniques. The research results indicated that the corrosion products of 7A04 alloy in salt solutions with different pH values all exhibited n-type semiconductor properties and could trigger the photovoltaic effect under UV illumination. Simultaneously, UV illumination reduced the compactness of the corrosion products, inhibited the enrichment of copper compounds (Cu2O), and promoted the generation of hydroxyl radicals in the solution. Therefore, UV illumination significantly accelerated the corrosion process of 7A04 alloy, with the overall acceleration effect ranking as follows: alkaline > neutral > acidic. In addition, the corrosion mechanism of 7A04 alloy in the test solutions with and without UV illumination was also discussed in this paper.

Abstract Metal hydrides are crucial intermediates in numerous catalytic reactions. Intensive efforts have been dedicated to constructing molecular metal hydrides, where toxic precursors and delicate mediators are usually involved. Herein, we demonstrate a facile pressure-induced methodology to generate a cost-effective heterogeneous electrocatalytic metal hydride surface for sustainable hydrogen transfer. Taking carbon dioxide (CO2) electroreduction as a model system and zinc (Zn), a well-known carbon monoxide (CO)-selective catalyst, as a model catalyst, we showcase a homogeneous-type hydrogen atom transfer process induced by heterogeneous hydride surfaces, enabling direct hydrogenation pathways traditionally considered “prohibited”. Specifically, the maximal Faradaic efficiency for formate is enhanced by ~fivefold to 83% under ambient conditions. Experimental and theoretical analyses reveal that unlike the distal hydrogenation route for CO2 to CO over pristine Zn, the Zn hydride surface enables direct hydrogenation at the carbon site of CO2 to form formate. This work provides a promising material platform for sustainable synthesis.

Abstract Chemotherapy is one of the conventional treatments for cancer in clinical practice. However, poor delivery efficiency, systemic toxicity, and the lack of pharmacokinetic monitoring during treatment are the critical limitations of current chemotherapy. Herein, we reported a brand-new antitumor drug delivery strategy that harnesses an optical fiber endoscopically therapeutic probe. The fiber probe carries photosensitizers in the fiber core and antitumor agents on the fiber surface mediated by a temperature-responsive hydrogel film, giving rise to an activable photothermal-chemotherapy that orchestrates the localized hyperthermia and thermal-stimuli drug release to the tumor lesion. Furthermore, the dynamical drug release and in-situ temperature can be real-time supervised through the built-in fiber sensors, including the reflective Mach–Zehnder interferometer and fiber Bragg grating, to visualize the therapy process and thus improve the safety of treatment. Compared with conventional methods, the fiber-optic drug delivery can adequately take advantage of the chemotherapeutics through collaboratively recruiting the photoheating-mediated enhanced permeability and the hydrogel particle-assisted high drug retention, shedding new light on a “central-to-peripheral” drug pervasion and retention mechanism to destroy tumors completely. The fiber-optic chemotherapy strategy incorporates precise drug delivery, accurate controllability of drug release, high drug permeability and retention in tumor, low off-target rate, and real-time drug release and temperature feedback, performing a straightforward and precise photothermal-chemotherapy pathway. More than that, the proposed strategy holds tremendous promise to provide a revolutionized on-demand drug delivery platform for the highly efficient evaluation and screening of antitumor pharmaceuticals.

For the development of new energy automobile industry and the trend of automobile lightweight have put forward a huge demand for high-strength lightweight materials, so developing high strength aluminum alloys is particularly momentous. As the most widely used aluminum alloy, 6000 series aluminum alloys (Al–Mg–Si alloys) have the advantages such as better mechanical properties, outstanding welding properties, excellent formability and fine processing capability, and therefore have obtained great attention as the structural materials. In addition, the Al–Mg–Si alloys with low density and corrosion resistance not only reduce the total weight of the car, but also extend the service life when subjected to chemical corrosion, which effectively achieve energy saving and emission reduction. This paper summarizes the research progress of 6000 series aluminum alloys, in particular, and reviews the methods of microalloying and particle strengthening, and their effects on the microstructure and properties of the alloy, thus providing a reference for the subsequent development of high-performance aluminum alloys in automobile and aerospace industries.

Rapid growth in industrial sectors such as automotive and shipbuilding has highlighted the significance of strip casting technology to produce lightweight alloys, particularly aluminum alloys widely used in both industrial production and daily life. Twin-roll casting (TRC), as an economically and environmentally friendly method for slab/strip production and processing, has attracted significant interest from researchers. However, the development of TRC aluminum alloys faces many challenges due to limited understanding of microstructural characteristics and control mechanisms. To further enhance comprehension of TRC aluminum alloys, this article reviews the influencing parameters, control methods, and existing issues related to TRC sub-rapid solidification (SRS) microstructure. It firstly summarizes TRC equipment types and their solidification characteristics, followed by a detailed analysis on key parameters affecting the evolution of TRC microstructure including rolling speed, roll separation force (RSF), and heat transfer coefficient (HTC). Finally, solutions to TRC defects are summarized and evaluated alongside their underlying mechanisms. This article provides a comprehensive review of the characteristics and control mechanisms of TRC microstructure while offering valuable insights for the future production of high-quality TRC aluminum strips.

With the continuing development of the aquaculture industry, the stress associated with many environmental factors has severely restricted the growth of fish, reduced fish resistance to disease, and had a large negative impact on fishery production. Therefore, it is of great importance for the sustainable development of aquaculture to cultivate new fish varieties with strong stress resistance. Traditional hybridization and gynogenesis, selective breeding, modern breeding techniques such as molecular marker-assisted breeding and whole genome selection breeding can be used to develop efficient and accurate fish breeding strategies, and to cultivate new fish varieties with high stress resistance. This paper reviews the status of research on fish breeding for disease resistance, cold resistance, high temperature tolerance, hypoxia tolerance, salt tolerance, saline-alkali tolerance as well as non-specific stress resistance traits, analyzes trends in research on fish breeding for stress tolerance, and explores future development directions. Furthermore, this paper proposes new ideas for fish seed industry innovation to promote its continuous and sustainable development.

ABSTRACTThe role of ferroptosis-associated gene SLC7A11 in esophageal cancer progression is largely unknown, therefore, the effects of blocking SLC7A11 on esophageal squamous cell carcinoma (ESCC) cells are evaluated. Results showed that SLC7A11 was overexpressed in ESCC tissues both in mRNA and protein levels. Blocking SLC7A11 using Erastin suppressed the proliferation and colony formation of ESCC cells, decreased cellular ATP levels, and improved ROS production. Sixty-three SLC7A11-binding proteins were identified using the IP-MS method, and these proteins were enriched in four signaling pathways, including spliceosome, ribosome, huntington disease, and diabetic cardiomyopathy. The deubiquitinase inhibitors PR-619, GRL0617, and P 22077 could reduce at least 40% protein expression level of SLC7A11 in ESCC cells, and PR-619 and GRL0617 exhibited suppressive effects on the cell viability and colony formation ability of KYSE30 cells, respectively. Erastin downregulated GPX4 and DHODH and also reduced the levels of β-catenin, p-STAT3, and IL-6 in ESCC cells. In conclusion, SLC7A11 was overexpressed in ESCC, and blocking SLC7A11 using Erastin mitigated malignant phenotypes of ESCC cells and downregulated key ferroptosis-associated molecules GPX4 and DHODH. The therapeutic potential of targeting SLC7A11 should be further evaluated in the future.

Multimodal sentiment analysis has become a hot research direction in affective computing by extending unimodal analysis to multimodal environments with information fusion. Word-level representation fusion is a key technique for modeling cross-modal interactions by capturing interplay between different modal elements. And word-level representation fusion faces two main challenges: local interactions between modal elements and global interactions along the temporal dimension. Existing methods often adopt attention mechanisms to model correlations between overall features across modalities when modeling local interactions, while ignoring interactions between adjacent elements and local features, and are computationally expensive. To address these issues, a multi-channel temporal convolution fusion (MCTCF) model is proposed, which uses 2D convolutions to obtain local interactions between modal elements. Specifically, local connections can capture associations between neighboring elements, multi-channel convolutions learn to fuse local features across modalities, and weight sharing greatly reduces computations. On the locally fused sequences, temporal LSTM networks further model global correlations along the temporal dimension. Extensive experiments on MOSI and MOSEI datasets demonstrate the efficacy and efficiency of MCTCF. Using just one convolution kernel (three channels, 28 weight parameters), it achieves state-of-the-art or competitive results on many metrics. Ablation studies confirm that both local convolution fusion and global temporal modeling are crucial for the superior performance. In summary, this paper enhances word-level representation fusion through feature interactions, and reduces computational complexity.

Since the late Cenozoic, the reactivated Tianshan orogenic belt has accommodated crustal shortening exceeding 200 km, primarily due to the far-field effects of the India-Eurasia plate collision. However, the details of the strain partitioning in the Tianshan Mountain range remain elusive. We interpret a new compilation of GPS velocities covering the whole Tianshan range with a classic elastic block model. Compared to previous studies with a block modeling approach, the Tianshan orogenic belt is further subdivided into several blocks based on geological fault traces and a clustering analysis approach. In addition to obvious crustal shortening on the bounding thrust faults of the Tianshan, our inverted fault slip rates also reveal that faults within the Tianshan orogenic belt, such as the Nalati Fault and the southern margin of the Issyk-Kul Lake Fault, which plays a crucial role in accommodating the tectonic crustal shortening. In the 72°E−78°E region, the internal shortening rate within the mountain is approximately 5–7 mm/yr. Besides crustal shortening, strike-slip motion occurs on faults in the interior of the mountain range as well as in the foreland fold-and-thrust belts, especially in the southern margin of the Tianshan. These findings suggest that the crustal deformation in the Tianshan Mountain range is more complex than previously thought, and the oblique convergence between the Tarim Basin and the Tianshan probably results in both strike-slip and thrust motion.

The structures and properties of the composite films formed by soy protein isolate (SPI) and xanthan gum (XG) with different other matrices were investigated. The composite films were prepared with SPI and XG by adding sodium alginate (SA), carboxymethyl cellulose (CMC), gelatin (GEL), pectin (PEC) and agar (Agar), respectively. The thickness, mechanical properties, oxygen permeability and opacity of the composite films were measured, and their structures were characterized. The results showed that the thicknesses of composite films with 1.5 g of different other matrices were significantly higher (P

Polysaccharides are one of the most important natural bioactive ingredients in pumpkin. Pumpkin polysaccharides have variable structure and complex monosaccharide composition, and possess a variety of biological activities such as hypoglycemia and antioxidant. In recent years, with the increasing incidence of diabetes, the hypoglycemic effect of pumpkin polysaccharides has attracted more and more attentions of scholars. The research focuses on the structure, monosaccharide composition and different mechanism of action of pumpkin polysaccharides. Therefore, this paper systematically summarizes the structural characteristics, mechanisms of hypoglycemic action and influence factors of hypoglycemic activity of pumpkin polysaccharides, and looks forward to its research direction and application prospects, and proposes the suggestions, with a view to providing reference for the subsequent research of pumpkin polysaccharides on diabetes.

In this paper, the content of active ingredients and antioxidant capacity of different parts of Hoxylon and Red Willow Cistanche deserticola, from Hotan Cele County, Xinjiang, were evaluated. The results showed that the active substances, including total phenols, total flavonoids, total sugars, and verbascoside of Red Willow Cistanche deserticola, were the highest in the lower part of the plant, and decreased in the middle and upper parts. In terms of total phenols and total flavonoids, the contents of the lower part of Red Willow Cistanche deserticola (38.35 mg GAE/g DW, 35.61 mg RE/g DW) were 2.47 and 10.95 times compared to the lower part of Hoxylon Cistanche deserticola, respectively. The upper part of Hoxylon Cistanche deserticola showed the highest content of echinacoside with 92.93 mg/g DW. And the total triterpene content of the lower part-especially that of Hoxylon Cistanche deserticola was significantly higher than the upper and middle part (P

Citrus bacterial canker (CBC) is resulted from Xanthomonas citri subsp. citri (Xcc) infection and poses a significant threat to citrus production. Glutathione S-transferases (GSTs) are critical in maintaining redox homeostasis in plants, especially in relation to abiotic and biotic stress responses. However, the function of GSTs in resisting CBC remains unclear. Here, citrus glutathione S-transferases were investigated applying a genome-wide approach. In total, 69 CsGSTs belonging to seven classes were identified, and the phylogeny, chromosomal distribution, gene structures and conserved motifs were analyzed. Several CsGSTs responded to Xcc infection, as observed in the upregulation of CsGSTF1 and CsGSTU18 in the CBC-sensitive ‘Wanjincheng’ variety but not in the resistant ‘Kumquat’ variety. CsGSTF1 and CsGSTU18 were localized at the cytoplasm. Transient overexpression of CsGSTF1 and CsGSTU18 mediated reactive oxygen species (ROS) scavenging, whereas the virus-induced gene silencing (VIGS) of CsGSTF1 and CsGSTU18 caused strong CBC resistance and ROS burst. The present study investigated the characterization of citrus GST gene family, and discovered that CsGSTF1 and CsGSTU18 negatively contributed to CBC through modulating ROS homeostasis. These findings emphasize the significance of GSTs in infection resistance in plants.

Nuclear factor kappa-B(NF-κB), an intricate nuclear transcription factor, is ubiquitously present within the myriad tissues and cells of the human corpus, engaging in a multiplicity of biological processes such as the development of the immune system, immune responses, inflammatory reactions, angiogenesis, and tumorigenesis. Its cardinal role in the pathogenesis of ocular diseases is increasingly illuminated by its prevalence. Owing to the unique architecture of the ocular globe, burgeoning studies have identified the excessive activation or dysregulation of the NF-κB signaling pathway as intimately associated with the progression of a multitude of ocular conditions, including, but not limited to, cataracts, dry eye syndrome, and glaucoma. The modulation of NF-κB activation, by targeting it, offers a potent mechanism for regulating ocular inflammation and mitigating disease progression, holding promise as a potential therapeutic strategy for ophthalmic disorders. An in-depth examination of the NF-κB signaling pathway's role in ocular diseases not only enriches our comprehension of the underlying mechanisms of these ailments, but also lays a crucial foundation for the innovation of new treatment modalities. Therefore, this article endeavors to provide a compendious review of the regulatory effects exerted by the NF-κB signaling pathway in ophthalmic conditions throughout recent years.

AIM: To study the causal relationship between obesity-related anthropometric traits and myopia and the mediating role of educational attainment (EA). METHODS: Univariable Mendelian randomization (UVMR) was performed to evaluate the causal association between body mass index (BMI), height, waist-hip ratio (WHR, adjusted for BMI), and mean spherical equivalent (MSE). BMI was divided into fat and fat-free mass and included in multivariable Mendelian randomization (MVMR) to explore the roles of different BMI components in the causal relationship between BMI and MSE. A mediation analysis based on two-step Mendelian randomization (MR) was carried out. Specifically, UVMR was conducted to estimate the causal effect of BMI on EA. The direct effect of EA on MSE was estimated from MVMR. The mediation effect of EA in the BMI-EA-MSE model was calculated by the product of coefficients method. Expression quantitative trait loci (eQTL)-MR, reverse MR, and Linkage Disequilibrium Score Regression (LDSC) were performed to assess the robustness. RESULTS: Genetically predicted higher BMI had a positive total effect on MSE (βIVW=0.26 D, 95%CI=0.14 to 0.37 D, P

AIM: To investigate the causal effect of inflammatory bowel disease (IBD) on ocular inflammation using Mendelian randomization (MR) analysis. METHODS: Genetic instruments associated with inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn's disease (CD) were derived from the largest genome-wide association studies (GWAS) published to date. The FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis, keratitis, iridocyclitis, chorioretinitis, episcleritis, and optic neuritis. All participants were of European ancestry. Three methods which included inverse variance weighting (IVW), weighted median (WM), and MR-Egger regression were performed to estimate the causal association in this study. IVW took the inverse variance of each study as the weight to calculate the weighted average of effect sizes, to summarize the effect sizes of multiple independent studies, which could provide the most precise estimated results. IVW was used as the primary outcome, while WM and MR-Egger were used to improve the estimation of IVW. RESULTS: A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis, keratitis, iridocyclitis, and optic neuritis, but not on chorioretinitis or episcleritis. After Bonferroni correction, the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis (IVW: OR, 1.17; 95%CI, 1.10-1.24, P=2.54×10-7). CD was significantly associated with conjunctivitis (IVW: OR, 1.05; 95%CI, 1.03-1.08, P=3.20×10-5), keratitis (IVW: OR, 1.06; 95%CI, 1.02-1.09; P=1.13×10-3), and iridocyclitis (IVW: OR, 1.09; 95%CI, 1.04-1.14; P=1.43×10-4). CONCLUSION: IBD causally poses a risk of inflammation of conjunctiva, cornea, Iris-ciliary body complex, and optic neuritis. CD is more closely associated with the eye inflammation than UC. These impliy that the relationship of IBD and different parts of the eye structure are different, and provide novel evidence linking based on the association of the gut-eye axis.

AIM: To compare the differences of choroidal neovascularization (CNV) measurements between swept-source and spectral-domain optical coherence tomography angiography (SS-OCTA and SD-OCTA) in neovascular age-related macular degeneration (nAMD) and the imaging reliability of the two devices. METHODS: Prospective comparative study. SS-OCTA and SD-OCTA were used to scan the same eye with the modes of 3×3 and 6×6 mm2 centered on the neovascularization. Only qualified images were chosen and the border of CNV was manually delineated by two graders independently. The area of CNV (ACNV), vascular perfusion density (PD), and vessel length density (VLD) within the delineation were calculated using Image J. The differences of CNV measurements between the two OCTA devices were compared using Bland-Altman analysis. The agreement between the two graders on the measurements of each device was compared using the intraclass correlation coefficient (ICC). RESULTS: A total of 18 patients (22 eyes) with nAMD were included. The measurements of ACNV, PD, and VLD were 7.247±4.586 and 4.901±3.741 mm2, 43.202±9.636 and 34.904±10.489, 6.339±1.228 and 5.908±1.741 mm-1 for SS-OCTA and SD-OCTA, respectively. The differences between the two devices were 2.346±3.030 mm2 (Z= -3.782, P

Myopia is a huge health problem due to its high frequency, vision losses and public health cost. According to the World Health Organization, at least 2.2 billion people have vision impairment. Although myopia can be controlled at its early and middle stages, unfortunately, no cure can be achieved so far. Among the methods to control myopia, atropine, a muscarinic receptor antagonist, is the oldest but still the most effective for retardation of myopia progression. Despite such a fact, standard protocols have not been established for clinicians to use atropine for treatment of myopia. In this article, a concise and up to date summary of myopia epidemiology and pathogenesis and summarized therapeutic effects and side effects, possible mechanisms and application methods of atropine were provided in hope for clinical doctors to effectively control this problematic disease. At present, the protocol is recommend: use higher dose (1%) of atropine intermittently to effectively slowdown myopia progression in schoolchildren for 2y, and to significantly reduce side effects of atropine by decrease of atropine frequency for 1y and inhibit myopic rebound by withdrawal of topical atropine gradually for 1y. Application of a lower dose (0.05%) atropine regime should also be considered due to its effectiveness and application at regular basis.

Introduction: Neurological dysfunction induced by fluoride contamination is still one of major concern worldwide. Recently, neuroprotective roles of silent information regulator 1 (SIRT1) focusing on mitochondrial function have been highlighted. However, what roles SIRT1 exerts and the underlying regulative mechanisms, remain largely uncharacterized in such neurotoxic process of fluoride. Objectives: We aimed at evaluating the regulatory roles of SIRT1 in human neuroblastoma SH-SY5Y cells and Sprague-Dawley rats with fluoride treatment, and to further identify potential miRNA directly targeting SIRT1. Methods: Pharmacological suppression of SIRT1 by nicotinamide (NIC) and promotion of SIRT1 by adenovirus (Ad-SIRT1) or resveratrol (RSV) were employed to assess the effects of SIRT1 in mitochondrial dysfunction induced by fluoride. Also, miRNAs profiling and bioinformatic prediction were used to screen the miRNAs which can regulate SIRT1 directly. Further, chemical mimic or inhibitor of chosen miRNA was applied to validate the modulation of chosen miRNA. Results: NIC exacerbated defects in mitochondrial network dynamics and cytochrome c (Cyto C) release-driven apoptosis, contributing to fluoride-induced neuronal death. In contrast, the ameliorative effects were observed when overexpressing SIRT1 by Ad-SIRT1 in vitro or RSV in vivo. More importantly, miR-708-3p targeting SIRT1 directly was identified. And interestingly, moreover, treatment with chemically modified miR-708-3p mimic aggravated, while miR-708-3p inhibitor suppressed fluoride-caused neuronal death. Further confirmedly, overexpressing SIRT1 effectively neutralized miR-708-3p mimic-worsened fluoride neuronal death via correcting mitochondrial network dynamics. On contrary, inhibiting SIRT1 counteracted the promotive effects of miR-708-3p inhibitor against neurotoxic response by fluoride through aggravating abnormal mitochondrial network dynamics. Conclusion: These data underscore the functional importance of SIRT1 to mitochondrial network dynamics in neurotoxic process of fluoride and further screen a novel unreported neuronal function of miR-708-3p as an upstream regulator of targeting SIRT1, which has important theoretical implications for a potential therapeutic and preventative target for treatment of neurotoxic progression by fluoride.

Introduction: Numerous studies demonstrated that NLRP3 has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Mesenchymal stem cells (MSCs) regulated the NLRP3 inflammasome, which has emerged as a novel therapeutic approach for treating IBD. Objectives: The exact role of NLRP3 in regulating MSCs’ function is unclear. Our study aimed to explore how NLRP3 affects the therapeutic effects of MSCs in colitis. Methods: We extracted MSCs from the bone marrow of C57BL/6 mice and Nlrp3 KO mice, and identified them using differentiation assays and flow cytometry. In vitro, Both WT MSCs and Nlrp3 KO MSCs were stimulated with inflammatory factor Lipopolysaccharide (LPS), and only WT MSCs were stimulated with varying concentrations of the NLRP3 inhibitor MCC950, then, quantified IL-10 levels in the supernatant. RNA-seq was performed to examine gene expression patterns and Seahorse was used to assess oxidative phosphorylation (OXPHOS) and glycolysis levels. Western blot was used to evaluate protein expression. In vivo, we treated DSS-induced colitis with either WT or Nlrp3 KO MSCs, monitoring weight, measuring colon length, and further evaluation. We also treated DSS-induced colitis with pretreated MSCs (BAY876, oe-Glut1, or oe-NLRP3), following the same experimental procedures as described above. Results: Our results demonstrate that Nlrp3 deletion did not affect MSC phenotypes, but rather promoted osteogenic differentiation. However, the absence of Nlrp3 reduced IL-10 production in MSCs in the presence of LPS, leading to impaired protection on DSS-induced colitis. Conversely, overexpression of NLRP3 promotes the production of IL-10, enhancing therapeutic effects. Further investigation revealed that Nlrp3 deficiency downregulated Glut1 expression and glycolysis activation in MSCs, resulting in decreased IL-10 production. Notably, overexpressing Glut1 in Nlrp3 KO MSCs restored their therapeutic effect that was previously dampened due to Nlrp3 deletion. Conclusion: Our findings demonstrate that NLRP3 heightens the therapeutic effects of MSC treatment on DSS-induced colitis.

A straw interlayer added to soil can effectively reduce soil salinity effects on plant growth, however, the effects of soil moisture, salt and microbial community composition on plant growth under a straw interlayer are unclear. A rhizobox study was conducted to investigate the role of straw interlayer thickness on soil moisture, salt migration, microbial community composition, as well as root growth in sunflower. The study included four treatments: Control (no straw interlayer); S3 (straw interlayer of 3.0 cm); S5 (straw interlayer of 5.0 cm); S7 (straw interlayer of 7.0 cm). Straw interlayer treatments increased soil moisture by 8.2–11.0% after irrigation and decreased soil salt content after the bud stage in 0–40 cm soil. Total root length, total root surface area, average root diameter, total root volume and the number of root tips of sunflower plants were higher under straw interlayer treatments than in the control, and were the highest under the S5 treatment. This stimulated root growth was ascribed to the higher abundance of Chloroflexi and Verrucomicrobia bacteria in soil with a straw interlayer, which was increased by 55.7 and 54.7%, respectively, in the S5 treatment. Addition of a straw interlayer of 5 cm thickness is a practical and environmentally feasible approach for improving sunflower root growth in saline-alkali soil.

Phthalate esters (PAEs) are an emerging pollutant due to widespread distribution in environmental mediums that have attracted widespread attention over recent years. However, there is little information about tea plantation soil PAEs. A total of 270 soil samples collected from 45 tea plantations in the major high-quality tea-producing regions of Jiangsu, Zhejiang, and Anhui provinces in China were analyzed for seven PAEs. The detection frequency of PAEs in tea plantation soil was 100%. DBP, DEHP, and DiBP were the main congeners in tea plantation soil. The PAEs concentrations in the upper soil were significantly higher than those in the lower soil. The concentration of tea plantation soil PAEs in Jiangsu Province was significantly lower than those in Zhejiang and Anhui provinces. Intercropping with chestnuts can effectively reduce the contamination level of PAEs in tea plantation soil. Correlation analysis, redundancy analysis, partial correlation analysis, and structural equation modeling methods further confirmed the strong direct influence of factors such as chestnut–tea intercropping, temperature, and agricultural chemicals on the variation of PAEs in tea plantation soil. The health and ecological risk assessments indicated that non-carcinogenic risk was within a safe range and that there was a high carcinogenic risk via the dietary pathway, with DBP posing the highest ecological risk.

Stress relaxation with synchronous aging (SRSA) could not only reduce springback but as well improve the performance of titanium alloy components. To reveal the relaxation mechanisms during SRSA, solution treatments of Ti-6.5Al–2Zr–1Mo–1V alloy under different temperatures were carried out to obtain diverse initial microstructures. The evolutions of microstructure including phase transformation, dislocation movement and stress-induced twinning were meticulously characterized. The progress of activation energy was analyzed quantitatively by the Kohlrausch-Williams-Watts equation. Results show that SRSA under all different conditions exhibits a rapid stress decline initially followed by a quasi-static stage, due to a shift in the driving force from stress-driven to thermally activated driven. The activation energy changes from a quasi-static state to a rapid rise with relaxation time. After two-phase solution treatment, the primary α (αp) dominant mechanism is the dislocation movement, including dislocation tangles and then recovery. The relaxation mechanism of the supersaturated metastable β phase is phase transformation (precipitation and growth of secondary α (αs)) and stress-induced twinning, and the αs realizes stress release through the globularization in the later stage. The full martensite microstructure was obtained by solution treatment in a single-phase region, and the main relaxation mechanism involves stacking faults, stress-induced twinning and then globularization. The enhancement in strength following SRSA is primarily attributed to the formation of αs, dislocation strengthening, and stress-induced twinning.

In this paper, the directional modification behavior of rare earth Ce on sulfide inclusions in steel is studied by thermodynamic calculation and experiment methods, and the mechanism of directional modification of rare earth Ce on sulfide inclusions in U71Mn heavy rail steel is proved. The results show that U71Mn heavy rail steel contained more large-sized inclusions and their distribution is more concentrated without the addition of rare earth Ce element. After the addition of rare earth Ce element, the average size of sulfur-containing inclusions in the steel decrease from 5.22 μm to 1.85 μm, and the number density of sulfur-containing inclusions in the steel increase from 83.65 mm−2 to 217.68 mm−2, indicating that the number of sulfur-containing inclusions in the steel increases after the addition of Ce element, and more small-sized sulfur-containing inclusions will form in the steel. The addition of rare earth Ce element can effectively reduce the existence of large-sized inclusions in the steel and modify large-sized inclusions into small-sized inclusions.

This study systematically investigated the electrochemical corrosion and static immersion corrosion behavior of the novel Ti6422 (Ti–6Al–4V–2Mo–2Fe) alloy with equiaxed (EM) and lamellar structure (LM) in HCl solution. The differences in corrosion performance between EM and LM samples were analyzed based on the characteristics of the passive film and substrate microstructure. Results indicated that the LM sample contained higher contents of TiO₂, Al₂O₃, and MoO₃ with higher stability compared with the EM sample, and the thickness of passive film was approximately twice that of the EM sample. Additionally, the donor density of LM sample was lower than EM sample. These findings indicate that the passive film on LM samples is thicker, with fewer defects and higher density. Electrochemical corrosion results revealed that the corrosion current of LM samples was lower and the polarization resistance was higher than these of EM samples, both suggesting superior corrosion resistance of LM samples. Immersion corrosion further confirmed that the LM sample had a lower corrosion rate. The enhanced corrosion resistance in LM samples was primarily due to higher content of corrosion-resistant β phase. Conversely, the numerous micro-galvanic cells between αs precipitates and adjacent β phase in EM samples weakened the corrosion resistance. Overall, these results demonstrated that regulating microstructure through heat treatment is an effective strategy for improving corrosion resistance of titanium alloys.

The microstructure and properties of Cu66.6(FeCo)33.4 and Cu60(FeCo)40 alloys were investigated. Microstructural observations show that CuFeCo alloys have formed dual-phase heterostructures comprising face-centered cubic (FCC) and body-centered cubic (BCC) phases. The average grain size of the CuFeCo alloys after cold rolling and aging is less than 10 μm. Cu66.6(FeCo)33.4 has better elongation and electrical conductivity, while Cu60(FeCo)40 has better tensile strength, hardness, saturation magnetization, and electromagnetic interference shielding effectiveness. An increased FeCo content in a finer second phase with a larger volume fraction, leading to more phase boundaries. This enhances the strength of the CuFeCo alloys while simultaneously reducing their elongation. The obtained results can be used for further development of alloys with FCC/BCC dual-phase heterostructures.

In the field of cancer therapy, inhibiting autophagy has emerged as a promising strategy. However, pharmacological disruption of autophagy can lead to the upregulation of programmed death-ligand 1 (PD-L1), enabling tumor immune evasion. To address this issue, we developed innovative ROS-responsive cationic poly(ethylene imine) (PEI) nanogels using selenol chemistry-mediated multicomponent reaction (MCR) technology. This procedure involved simple mixing of low-molecular-weight PEI (LMW PEI), γ-selenobutylacetone (γ-SBL), and poly(ethylene glycol) methacrylate (PEGMA). Through high-throughput screening, we constructed a library of AxSeyOz nanogels and identified the optimized A1.8Se3O0.5/siPD-L1 nanogels, which exhibited a size of approximately 200 nm, excellent colloidal stability, and the most effective PD-L1 silencing efficacy. These nanogels demonstrated enhanced uptake by tumor cells, excellent oxidative degradation ability, and inhibited autophagy by alkalinizing lysosomes. The A1.8Se3O0.5/siPD-L1 nanogels significantly downregulated PD-L1 expression and increased the expression of major histocompatibility complex class I (MHC-I), resulting in robust proliferation of specific CD8+ T cells and a decrease in MC38 tumor growth. As a result, the A1.8Se3O0.5/siPD-L1 nanogels inhibited tumor growth through self-inhibition of autophagy, upregulation of MHC-I, and downregulation of PD-L1. Designed with dynamic diselenide bonds, the A1.8Se3O0.5/siPD-L1 nanogels showed synergistic antitumor efficacy through self-inhibition of autophagy and prevention of immune escape.