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In order to solve the problem of poor performance of welded joints of steel and aluminum dissimilar materials, this study proposes the use of ceramic particle-reinforced aluminum alloy as an alternative to traditional aluminum alloy for welding, effectively overcoming this problem. In this paper, the laser welding of stainless steel/6061 aluminum alloy (SA) and stainless steel/TiC–TiB2 duplex nanoparticle-reinforced 6061 aluminum alloy (SRA) was realized. The effect of ceramic nanoparticles on the microstructure and mechanical properties of SRA joint was systematically studied, and the strengthening mechanism of nanoparticles was revealed. Under the same process parameters, the melting zone of SRA joint is larger and the intermetallic compound (IMCs) layer is narrower. Moreover, the grain size of the brittle Fe–Al compound phase in the IMCs layer is significantly reduced, which effectively inhibits the initiation of cracks at the steel/aluminum interface. The study shows that ceramic particles have a pinning effect on the dislocations, limiting the grain growth, reducing the thickness of the intermetallic compound layer, and decreasing the content of the brittle FeAl3 phase. Moreover, ceramic nanoparticles promote the formation of Mg2Si strengthened phase at the grain boundary, further hinder the dislocation movement and improve the strength of the joint. Under the welding power of 3400 W and welding speed of 31 mm/s, SRA joint achieves the maximum tensile shear of 1718 N, which is 15% higher than the strength of SA joint.

Objective: To assess if there is a relationship between residential radon exposure and two lung cancer histological types, small-cell carcinoma (diagnosed in people with a smoking history) and adenocarcinoma (the most commonly diagnosed histologic type in people who have never smoked) among males and females in Canada. Methods: With survey data of long-term radon measurements in residential homes, long-term averaged tobacco consumption rates in the units of cigarettes per day per person and long-term averaged age-standardized lung cancer incidence rates at provincial level, simple linear fitting (ANOVA linear regression) was applied in this study to determine the effect on lung cancer induction by smoking and exposure to indoor radon, and to assess if there is a relationship between residential radon exposure and lung cancer histological types. Results: Lung cancer incidence rates correlate very well with the tobacco consumption rates (P ​

Fasting is typically used before feeding metabolizable energy assessment in broilers. Previous studies have shown that fasting cause atrophy of the intestinal villus. Whether fasting affects intestinal permeability during refeeding by altering barrier function and nutrient absorption is of concern. Here, 23-d-old broilers were randomly assigned to 5 treatments, fasted for 0, 12, 24, 36, and 48 h, respectively, and then refed for 2 d, to study the impact of different duration of fasting on the intestinal regeneration and barrier function during refeeding. Results showed that the intestinal morphology in fasted birds was recovered in 2 d of refeeding at most. As fasting durations increased, enterocytes per intestinal villus were linearly and quadratically increased (both P

High-purity tantalum is used as the sputtering target material for integrated circuits, requiring fine grains and random texture. Understanding different orientation deformation mechanisms, especially the metastable orientation (here {112} crystallographic orientations), is beneficial for controlling the structure of tantalum target materials. This paper employs EBSD and crystallographic calculations to regulate the grain deformation behavior by introducing a reverse strain at 135° clock rolling. The deformation behavior and dislocation density distribution of the metastable oriented grains under different strain paths are quantitatively analyzed. Results show that unidirectional rolling (UR) generates stress concentration, causing an uneven distribution of geometrically necessary dislocation density. The splitting behavior of {112} and {111} grains is promoted, and they have similar deformation behavior in UR process, while the deformation of {100} oriented grains is significantly suppressed. Furthermore, changing the strain path promotes the splitting of {100} grains, and makes the {112} change from the soft orientation to the hard orientation. This change makes it easier to start multi-slipping, resulting in a more uniform deformation. Additionally, crystallographic calculations show that Schmid factor is ineffective in explaining the strain localization problem in BCC metals. However, Schmid factor difference ratio makes it possible to analyze the distribution of dislocation density in local regions through the quantitative calculation of multi-slipping.

Purpose: The current study aims to implement steady-state visual evoked potentials (SSVEPs) in quantifying the binocular imbalance of amblyopia and to assess the predictive value of SSVEP-derived indices for amblyopic stereoacuity. Methods: We measure frequency-tagged SSVEP responses elicited by each eye (F1 = 6 Hz through the fellow eye; F2 = 7.5 Hz through the amblyopic eye) within a binocular rivalry paradigm among a cohort of anisometropic amblyopic observers (n = 29, mean age: 12 years). Binocular suppression was quantified by assessing the disparity in SSVEP amplitudes between the eyes, while the strength of interocular interaction was evaluated through the intermodulation response at F1+F2 = 13.5 Hz. Subsequent analyses explored the associations between these neural indices and relevant behavioral metrics in amblyopia. Results: Results reveal a significant difference in SSVEP amplitudes elicited from the fellow eye and the amblyopic eye, with the former exhibiting notably higher responses. Moreover, the fellow eye demonstrated prolonged dominance duration compared to its amblyopic counterpart. Furthermore, a negative correlation between binocular suppression and interocular interaction was observed, with stereoacuity showing a significant correlation with binocular suppression. Utilizing stepwise mulptiple linear regression analysis, we established that a predictive model combining binocular suppression and visual acuity of the amblyopic eye provided the best prediction of stereoacuity. Conclusions: These results highlight the potential of binocular suppression, as assessed by SSVEPs within a binocular rivalry paradigm, as a promising neural predictor of stereopsis in amblyopia.

The aim of this study is to investigate novel strategies for reducing adverse reactions caused by erdafitinib through a drug combination based on its pharmacokinetic characteristics. The spectrum and characterizations of drugs that can inhibit the metabolism of erdafitinib are examined both in vitro and in vivo. The efficacy of combination regimens are then evaluated using subcutaneous xenograft tumor models. The results demonstrated that sertraline and duloxetine, out of more than 100 screened drugs, inhibited the metabolism of erdafitinib through mixed and non-competitive inhibition, respectively. This inhibition primarily occurred via the CYP2C9 and CYP2D6 pathways. The primary alleles of CYP2C9 and CYP2D6 not only determine the metabolic characteristics of erdafitinib but also influence the strength of drug-drug interactions. Co-administration of sertraline or duloxetine with erdafitinib in rats and mice resulted in nearly a three-fold increase in the blood exposure of erdafitinib and its major metabolite M6. When sertraline or duloxetine was combined with 1/3 of the erdafitinib dosage, the anti-proliferative and pro-apoptotic effects on SNU-16 xenografts were comparable to those of the original full dose of erdafitinib. However, the combination regimen significantly mitigated hyperphosphatemia, retinal damage, intestinal villus damage, and gut microbiome dysbiosis. This study utilized pharmacokinetic methods to propose a new formulation of erdafitinib combined with sertraline or duloxetine. The findings suggest that this combination has potential for clinical co-administration based on a database analysis, thereby providing a novel strategy for anti-tumor treatment with fibroblast growth factor receptor (FGFR) inhibitors.

Rice–turtle co-culture is an ecological method involving a low exogenous input of chemicals and excessive feeding might increase the cost and reduce the mutual beneficial effect. To determine the optimal feeding level for co-cultured P. sinensis and for its adaptation, the turtles (878.0±10.3 g) were fed at feeding levels of 0.7 %, 1.4 % and 2.1 % for 90 days. The observation of feeding behavior showed that a low feeding level prompted the turtles to move into field paddies and prolonged their stay. The specific growth rate increased with increasing feeding level, but did not further increase when it exceeded 1.4 %, and the feed conversion ratio increased with increasing feeding level from 0.7 % to 2.1 %. The activities of digestive enzymes were higher in the group with a low feeding level. The plasma triglyceride and total cholesterol levels increased with increasing feeding level, while the creatinine level was significantly lower at a high feeding level of 2.1 %. The trend analysis of gene expression showed that the expression of most of differentially expressed genes (DEGs) in the brain decreased with increasing feeding levels from 0.7 % to 1.4 % and did not further decrease at a feeding level of 2.1 %, while in the gut, most of the genes were significantly downregulated or upregulated at a feeding level of 1.4 %. In the brain, the pathways associated with the DEGs were involved in the relaxin signaling pathway, melanogenesis and the age–rage signaling pathway in diabetic complications. In the gut, the DEGs were most associated with pancreatic secretion, protein digestion and absorption. The related genes expression was consistent with feeding behavior, growth and physiological metabolism. These findings suggest that co-cultured turtles can adapt to different feeding levels, that the optimal feeding level for co-cultured turtles is 1.4 %, and that additional feeding reduced the economic and ecological benefits of co-culture.

Summary: We investigated the effects of 35 inflammatory cytokines on respiratory outcomes, including COVID-19, asthma (atopic and non-atopic), chronic obstructive pulmonary disease (COPD), and pulmonary function indices, using Mendelian randomization and colocalization analyses. The emerging associations were further explored using observational analyses in the UK Biobank. We found an inverse association between genetically predicted macrophage colony stimulating factor (MCSF), soluble intercellular adhesion molecule-1 (sICAM), and soluble vascular cell adhesion molecule-1 with risk of COVID-19 outcomes. sICAM was positively associated with atopic asthma risk, whereas tumor necrosis factor-alfa showed an inverse association. A positive association was shown between interleukin-18 and COPD risk (replicated in observational analysis), whereas an inverse association was shown for interleukin-1 receptor antagonist (IL-1ra). IL-1ra and monocyte chemotactic protein-3 were positively associated with lung function indices, whereas inverse associations were shown for MCSF and interleukin-18 (replicated in observational analysis). Our results point to these cytokines as potential pharmacological targets for respiratory traits.

The escalating prevalence of non-alcoholic fatty liver disease (NAFLD), driven by inadequate dietary habits and metabolic imbalances, underscores the urgent need for effective dietary interventions. This study investigated the potential of 80 % peanut diacylglycerol (DAG) as a functional lipid component in preventing NAFLD and associated intestinal microenvironment based on a high-cholesterol diet (HCD)-induced zebrafish model. We first found that the zebrafish fatty liver model shared multiple similar pathways like lipid-induced atherosclerosis, insulin resistance with NAFLD patient in terms of lipid metabolism. Employing larvae and grown zebrafish, we aimed to elucidate the preventive and alleviating effect of a DAG diet on NAFLD respectively. Results showed that DAG post-intervention significantly decreased hepatic lipid accumulation and diminished intestinal inflammatory in fatty liver zebrafish model. Notably, transcriptomic sequencing illuminated upregulation in genes related to lipid metabolism (e.g., fasn, mogat2, cd36), suggesting that peanut DAG accelerated lipid transportation and fostered a metabolic environment less conducive to NAFLD symptoms. Besides, reduced liver lipid droplets and hepatic inflammatory suggested DAG feeding could also prevent the formation of NAFLD. The study provided compelling evidence supporting the incorporation of DAG into the diet as a strategy for the prevention and management of fatty liver disease, proposing a novel approach to functional food development aimed at combating metabolic diseases.

Background: To prospectively assess the individual and joint effects of birth weight and the life’s essential 8 (LE8)-defined cardiovascular health (CVH) on myocardial infarction (MI) risk in later life. Methods: In 144,803 baseline MI-free participants who were recruited in the UK Biobank cohort between 2006 and 2010, Cox proportional hazard models were used to estimate the associations of birth weight, LE8 score, and their interactions with incident MI. LE8 was defined on the basis of diet, physical activity, nicotine exposure, sleep health, body mass index, blood pressure, blood glucose, and blood lipids. Results: Low birth weight was associated with higher risk of MI [hazard ratio (HR) 1.17, 95% confidence interval 1.02–1.35, P = 0.025], while no significant correlation between high birth weight and MI was observed after adjustment. Low CVH was associated with higher MI risk [HR 6.43 (3.71–11.15), P

Analog circuit is an crucial component of electronic equipment, and the ability to diagnose its fault state quickly and accurately is essential for ensuring the safety and reliability of these electronic equipment. This paper addresses the problems of low diagnostic accuracy and the difficulties associated with model parameter selection in traditional fault diagnosis methods, particularly when dealing with nonlinear and non-stationary fault signals. A fault diagnosis method for analog circuits is proposed, which utilizes Ensemble Empirical Mode Decomposition (EEMD) for features extraction, the Maximum Information Coefficient algorithm (MIC) for features selection, and Particle Swarm Optimization (PSO) for optimizing Support Vector Machine (SVM) classification. Firstly, EEMD is used to adaptively decompose the fault signals in the circuit to extract multi-scale fault features. Secondly, the extracted features are quantitatively evaluated using the Pearson correlation coefficient and energy value analysis, leading to the construction of a fault feature vector is constructed. On this basis, the MIC feature selection algorithm is applied to further optimize the feature vector. Finally, an efficient fault classification model is developed by optimizing the hyperparameters of the SVM model using PSO. The simulation results show that the proposed method effectively overcome the problems of model complexity and low classification accuracy caused by improper selection of wavelet basis function. The accuracy of fault diagnosis and the efficiency of model training are significantly superior to those of traditional methods.

β-elemene has been observed to exert inhibitory effects on a multitude of tumors, primarily through multiple pathways such as the inhibition of cancer cell proliferation and the induction of apoptosis. The present study is designed to elucidate the role and underlying mechanisms of β-elemene in the therapeutic intervention of non-small cell lung cancer (NSCLC). Both in vitro and in vivo experimental models corroborate the inhibitory potency of β-elemene on NSCLCs. Our findings indicate that β-elemene facilitates the maturation of miR-127-3p by inhibiting CBX8. Functioning as an upstream regulator of MAPK4, miR-127-3p deactivates the Akt/mTOR/p70S6K pathway by targeting MAPK4, thereby inducing autophagy in NSCLCs. Additionally, β-elemene augments the packaging of miR-127-3p into exosomes via SYNCRIP. Exosomal miR-127-3p further stimulates M1 polarization of macrophages by suppressing ZC3H4. Taken together, the detailed understanding of the mechanisms through which β-elemene induces autophagy in NSCLCs and facilitates M1 polarization of macrophages provides compelling scientific evidence supporting its potential utility in NSCLC treatment.

Background: The research trends regarding standardised patients(SPs) in the education of health professions students have not been systematically studied. Methods: All published literature on SPs from January 1994 to January 2024 in Web of Science was screened by two reviewers. Bibliometric analysis and knowledge mapping visualisation analysis were performed using Cite Space software. The country, institution, journal, keyword co-occurrence, and keyword emergence were visualised. Result: A total of 3259 records were analysed. The amount of relevant literature in the past 30 years showed an upward trend involving 109 disciplinary categories, with the United States dominating. The five central research teams were from the United States and Canada. Nursing education is increasingly using SPs, especially in advanced nursing practice. As for the hotspot and trend analysis, the results indicate that there is still continuous attention to the impact of applying standardised patients on improving the communication ability, competence and performance of medical students. Additionally, there is a growing interest in exploring the application of visual simulation or artificial intelligence in standardised patient-related research. Conclusions: Research on SPs' has received continued attention. To cater to the diverse requirements of education and clinical context, there is a need for further exploration of SPs utilisation. AI-relevant SPs might be a new alternative for various scenarios in the future.

A growing body of evidence suggests that university green space (UGS) can substantially enhance students' perceived restoration. This study employed virtual reality technology to assess the characteristics of audio-visual elements in three types of UGS, then utilized Peason correlation analysis and structural equation modeling (SEM) to explored environmental audio-visual perception, perceived restoration, and their associations with emotional state. Findings indicate that: (1) Within the same UGS type, the dominance of different audio-visual elements was relatively consistent across various locations. However, there were differences among different UGS types: artificial sounds were dominant in Commuter Green Spaces, while natural sounds were more prominent in Natural Green Spaces, and the perception trends for visual elements were similar to those of the sound sources. (2) Soundscape pleasantness was significantly positively correlated with three dimensions of perceived restoration and positive emotion, negatively correlated with negative emotion, and had similar findings to soundscape pleasantness in visual perception and soundscape eventfulness. (3) The SEM results showed that soundscape pleasantness and eventfulness could directly influence visual perception and positive emotion. In addition, our study also found a cascading mediating effect with visual perception and perceived restoration as core elements. These findings deepen our understanding of how audio-visual perceptions influence emotional restoration and well-being, potentially enhancing both student experiences and the quality of UGS. Furthermore, the findings underscore the complexities involved in perception assessment, influenced by variations in social backgrounds, cultural factors, and individual characteristics. This emphasizes the need for future research to consider these variables comprehensively, aiming to provide a deeper understanding of the specific physical attributes of restorative environments.

ABSTRACT: Exposure to copper (Cu) has been associated with metabolic disorders in animals and humans, but the underlying mechanism remains unclear. One-day-old broiler chickens, numbering a total of 192, were nourished with dietary intakes that contained varying concentrations of Cu, specifically 11, 110, 220, and 330 mg/kg of Cu, for a period extending over a duration of 7 wk. As a result of the study, Cu exposure resulted in vacuolization, fragmentation of mitochondria cristae, and the increase of autophagosomes in hepatocytes. Metabolomics analysis illustrated that Cu caused a total of 59 different metabolites in liver, predominantly associated with the glycerophospholipid metabolic pathway, leading to metabolic disruption. Moreover, high-Cu diet markedly reduced the levels of AMPKα1, p-AMPKα1, mTOR, and p-mTOR and enhanced the expression levels of the autophagy-related factors (Atg5, Dynein, Beclin1, and LC3-II). Overall, Cu exposure caused chicken liver injury and resulted in disturbed metabolic processes and mediated autophagy primarily through the AMPK-mTOR axis.

Isobavachalcone (IBC) as a bioactive chalcone isolated from the seeds of Psoralea corylifolia Linn has shown promising anticancer activities. However, its main anticancer mechanism in colorectal cancer cells has not been well-explored. Recently, the interaction of therapeutic compounds with survivin, an antiapoptotic marker, has been indicated to be a potential approach for advancing anticancer compounds. Therefore, in this study, IBC was evaluated for its anticancer activities against metastatic colorectal adenocarcinoma, LoVo, followed by exploring its interaction with survivin. It was observed that incubation of the human LoVo colorectal cancer cells with the IBC at 24 h resulted in a significant reduction in cell viability with an IC50 of about 35 µM as well as a significant membrane damage. Also, it was deduced that IBC could result in the formation of excessive ROS, lipid peroxidation, reduction of SOD/CAT activity, as well as downregulation of Nrf2 and HO-1 mRNA levels. Further studies showed that IBC could induce MMP reduction, cytochrome c (Cyt c) release, overexpression of Bax/Bcl-2 mRNA ratio as well as caspase-9 and −3. Moreover, it was deduced that IBC mitigated the expression of survivin at mRNA and protein levels. Then, binding parameters indicated that IBC strongly binds to one molecule of survivin at physiological temperature. Also, it was revealed that IBC substantially induced the conformational changes of survivin. Ultimately, through hydrogen bonding and hydrophobic forces, IBC has a substantial binding affinity with survivin (–9.80 kcal/mol) at a region that is critical to the dimerization process, according to molecular docking studies. Overall, this study showed that IBC may be used in future research to assess its clinical and in vivo behaviors in the modulation of colorectal cancer mediated by deactivation and downregulation of antiapoptotic survivin.

Breast cancer remains a leading cause of mortality in women worldwide. Triple-negative breast cancer (TNBC) is a particularly aggressive subtype characterized by rapid progression, poor prognosis, and lack of clear therapeutic targets. In the clinic, delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges. Within the scope of our study, high heterogeneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples. Notably, TNBC exhibited significant specificity regarding cell proliferation, differentiation, and disease progression. Significant associations between tumor grade, prognosis, and TNBC oncogenes were established via pseudotime trajectory analysis. Consequently, we further performed comprehensive characterization of the TNBC microenvironment. A crucial epithelial subcluster, E8, was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC. Additionally, epithelial-mesenchymal transition (EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions, contributing to tumor growth. Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC. The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs, such as pelitinib. We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model. Overall, our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.

The adhesion of bacteria to the surface leads to formation of biofilms causing numerous infection problems in implanting medical devices or interventional therapy. Traditional treatment for such problems is generally to administrate patients with antibiotics or antifungal agent. Alternatively, devices are taken out of the body to mechanically destroy the biofilm and re-used by surgery. In this study, a straightforward method was developed to remove biofilms using a MXene-based photothermal hydrogel. The hydrogel consists of dynamic crosslinking network formed by Schiff-base reaction between aldehyde-containing xyloglucan (OXG) and amine-containing MXene (NH2-MXene), which showed efficient killing of both gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli) bacteria upon near-infrared (NIR) laser irradiation. The NH2-MXene/OXG nanocomposite hydrogel showed a high photothermal antibacterial efficiency and stable photothermal conversion, demonstrated by efficient removal of biofilms ex vivo.

Rationale & Objective: Matrix metalloproteinase 2 (MMP-2) plays an important role in the development of fibrosis, the final common pathway of chronic kidney disease (CKD). This study aimed to assess the relationship between repeated measures of MMP-2 and CKD progression in a large, diverse prospective cohort. Study Design: In a prospective cohort of Chronic Renal Insufficiency Cohort (CRIC) participants (N = 3,827), MMP-2 was measured at baseline. In a case-cohort design, MMP-2 was additionally measured at year 2 in a randomly selected subcohort and cases of estimated glomerular filtration rate (eGFR) halving or kidney replacement therapy (KRT) (N = 1,439). Setting & Participants: CRIC is a multicenter prospective cohort of adults with CKD. Exposure: MMP-2 measured in plasma at baseline and at year 2. Outcomes: A composite kidney endpoint (KRT/eGFR halving) Analytical Approach: Weighted Cox proportional hazards models for case-cohort participants. Results: Participants were followed for a median of 4.6 years from year 2 and 6.9 years from the baseline. Persistently elevated MMP-2 (≥300 ng/mL at both baseline and year 2) increased the hazard of the composite kidney endpoint (HR, 1.61; 95% CI, 1.07-2.42; P = 0.09) after adjusting for covariates. The relationship of persistently elevated MMP-2 was modified by levels of inflammation, with a 2.6 times higher rate of the composite kidney endpoint in those with high-sensitivity C-reactive protein

β2 adrenergic receptor (β2AR) is a G-protein-coupled receptor involved in cardiac protection. In chronic heart failure (CHF), persistent sympathetic nervous system activation occurs, resulting in prolonged β2AR activation and subsequent receptor desensitization and downregulation. Notoginsenoside R1 (NGR1) has the functions of enhancing myocardial energy metabolism and mitigating myocardial fibrosis. The mechanisms of NGR1 against ischemic heart failure are unclear. A left anterior descending (LAD) artery ligation procedure was performed on C57BL/6 J mice for four weeks. From the 4th week onwards, they were treated with various doses (3, 10, 30 mg/kg/day) of NGR1. Subsequently, the impacts of NGR1 on ischemic heart failure were evaluated by assessing cardiac function, morphological changes in cardiac tissue, and the expression of atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). H9c2 cells were protected by NGR1 when exposed to OGD/R conditions. H9c2 cells were likewise protected from OGD/R damage by NGR1. Furthermore, NGR1 increased β2AR levels and decreased β2AR ubiquitination. Mechanistic studies revealed that NGR1 enhanced MDM2 protein stability and increased the expression of MDM2 and β-arrestin2 while inhibiting their interaction. Additionally, under conditions produced by OGD/R, the protective benefits of NGR1 on H9c2 cells were attenuated upon administration of the MDM2 inhibitor SP141. According to these findings, NGR1 impedes the interplay between β-arrestin2 and MDM2, thereby preventing the ubiquitination and degradation of β2AR to improve CHF.

Study region: Poyang Lake Plain at the south bank of the middle Yangtze River Study focus: The dynamics of the groundwater budget, prominently driven by the surface water-groundwater interaction, present significant challenges for water resources and the eco-environment in extensive river-lake-floodplain systems. This research utilizes a groundwater flow model through the application of the MODFLOW-NWT numerical simulator, aiming to explore the patterns of exchange between surface water and groundwater due to intensive seasonal lake inundation, and its consequential impact on the annual and seasonal groundwater storage within the vast Poyang Lake floodplain, China. New hydrological insights for the region: Simulation results indicate that the change in groundwater storage during the dry year (i.e., –24.96×107 m3/yr in 2022) has decreased by 186.35×107 m3 compared to the wet year (i.e., 161.38×107 m3/yr in 2020). The contribution of surface water infiltration is approximately 45 % of the regional groundwater budget during wet seasons, and groundwater discharge into surface waterbodies accounts for over 60 % of the groundwater budget during dry seasons. The lake infiltration during wet years is approximately 3 times that in dry years, and the flow of infiltrated lake water into plain aquifers is approximately 5 times that in dry years. The present study contributes significant knowledge regarding the impact of intensifying seasonal inundation on variations in regional groundwater budget in large lake-aquifer system.

The annex A of the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) 2020/2021 Report presented a comprehensive global estimate of frequencies and doses from medical exposure to ionizing radiation, their distribution and trends for the period 2009–2018. The annex considered four general categories of medical practice using ionizing radiation: (a) diagnostic radiology, including dental radiology and computed tomography, (b) interventional radiology (image-guided interventional procedures), (c) nuclear medicine, and (d) radiation therapy. In the period 2009–2018, about 4.2 billion medical radiological examinations were performed annually, resulting in an annual effective dose of 0.57 ​mSv per caput. The use of computed tomography has continued to grow and the contribution from interventional radiology has increased rapidly in recent years. The annual number of radionuclide therapy treatments has increased by 60% since the UNSCEAR 2008 Report, while the number of courses of radiation therapy has increased by 22%. Medical exposure remains by far the largest human-made source of radiation exposure to the public. The Committee's evaluation relies on the collection of up-to-date and representative exposure data from all Member States of the United Nations. Future exposure survey should be more relevant and useful and adapted to changing data sources and changing uses of radiation across the world.

The annex D of the United Nations Scientific Committee on the Effects of Atomic Radiation （UNSCEAR） 2020/2021 Report presented a comprehensive global estimate of occupational exposure to ionizing radiation. The worldwide annual number of workers exposed to natural and human-made sources of ionizing radiation was estimated to be approximately 24 million in the period 2010–2014. About 52% of those were employed in the sectors that involve exposure to natural sources of radiation. The worldwide average annual effective dose for all workers during the period 2010–2014 was estimated to be around 1.2 ​mSv – about two thirds of the value estimated for the period 1995–1999. The annual effective dose was estimated to be around 2.0 ​mSv for workers exposed to natural sources and 0.5 ​mSv for workers exposed to human-made sources. The overriding limitation of current evaluation was the low rate of participation by United Nations Member States in providing occupational exposure monitoring data, especially data from non-nuclear sectors and occupational sectors involving naturally occurring radioactive materials. As the assessment of the worldwide occupational exposure is a complex task, the Committee relies on the collection of up-to-date data on occupational exposure from United Nations Member States in a broad range of occupational sectors, and continues collaboration with international organizations.

Introduction: The epithelial immunomodulation and regeneration are intrinsic critical events against inflammatory bowel disease (IBD). MiR-7 is well documented as a promising regulator in the development of various diseases including inflammatory diseases. Objectives: This study aimed to assess the effect of miR-7 in intestinal epithelial cells (IECs) in IBD. Methods: MiR-7def mice were given dextran sulfate sodium (DSS) to induce enteritis model. The infiltration of inflammatory cells was measured by FCM and immunofluorescence assay. 5′deletion assay and EMSA assays were performed to study the regulatory mechanism of miR-7 expression in IECs. The inflammatory signals and the targets of miR-7 were analyzed by RNA-seq and FISH assay. IECs were isolated from miR-7def, miR-7oe and WT mice to identify the immunomodulation and regeneration capacity. IEC-specific miR-7 silencing expression vector was designed and administered by the tail vein into murine DSS-induced enteritis model to evaluate the pathological lesions of IBD. Results: We found miR-7 deficiency improved the pathological lesions of DSS-induced murine enteritis model, accompanied by elevated proliferation and enhanced transduction of NF-κB/AKT/ERK signals in colonic IECs, as well as decreased local infiltration of inflammatory cells. MiR-7 was dominantly upregulated in colonic IECs in colitis. Moreover, the transcription of pre-miR-7a-1, orchestrated by transcription factor C/EBPα, was a main resource of mature miR-7 in IECs. As for the mechanism, EGFR, a miR-7 target gene, was downregulated in colonic IECs in colitis model and Crohn's disease patients. Furthermore, miR-7 also controlled the proliferation and inflammatory-cytokine secretion of IECs in response to inflammatory-signals through EGFR/NF-κB/AKT/ERK pathway. Finally, IEC-specific miR-7 silencing promoted the proliferation and transduction of NF-κB pathway in IECs and alleviated the pathological damage of colitis. Conclusion: Our results present the unknown role of miR-7/EGFR axis in IEC immunomodulation and regeneration in IBD and might provide clues for the application of miRNA-based therapeutic strategies in colonic diseases.

ABSTRACT: Objectives: This study reports the whole-genome sequences of two strains of extended-spectrum beta-lactamase (ESBL)-producing and multidrug-resistant (MDR) K. pneumoniae ST268 and explores their acquired antibiotic resistance genes (ARGs) and the mobile genetic elements (MGEs). Methods: Two strains of K. pneumoniae ST268 were isolated from different samples of one patient. Assessment of antimicrobial susceptibility was performed, and then whole-genome sequencing was conducted. Acquired ARGs, insertion sequences, and transposons harboured by the two strains of K. pneumoniae ST268 were identified, and then the genetic contexts associated with the ARGs were analysed systematically. Results: Two strains of K. pneumoniae ST268 were found to carry the 118.6-kb hybrid IncFIIK:IncQ1:repBR1701 plasmid. All the acquired ARGs carried by the IncF plasmid were found to be situated on the 25.3-kb MDR region bracketed by ISKpn19 and IS26, which was widely present in the plasmids in 14 STs of strains in K. pneumoniae but also in IncF plasmids from Shigella flexneri and Klebsiella quasipneumoniae. Notably, the IncF plasmids harbouring the 25.3-kb MDR region were geographically distributed mainly in China, and the pKP161637-1/pKP160802-1 in our study was the first report on the IncF plasmid carrying the 25.3-kb MDR region bracketed in K. pneumoniae ST268. Conclusions: Two strains of ESBL-producing K. pneumoniae ST268 with a MDR IncF plasmid were identified in a hospital in China. The ARGs were identified on the 25.3-kb MDR region, bracketed by ISKpn19 and IS26, of the IncF plasmids, which were present not only in the K. pneumoniae but also in the S. flexneri and K. quasipneumoniae.

Conventional polymer damping materials are extensively utilized to mitigate vibration and noise in various fields, yet suffer from the drawback of a narrow effective damping temperature range. Herein, we innovatively synthesized an asymmetrically structured chain extender (AIS) with double disulfide bonds that provided polyurethane elastomer (PUE) with ultra-high energy dissipation over a wide temperature range, which was unattainable by conventional chain extenders. This was achieved by enhancing the bond exchange rate of dynamic disulfide bonds in the PUE. Specifically, the asymmetric structure of AIS was strategically designed to disrupt the regularity of the hard segments of the PUE, enabling the disulfide bonds to break and reorganize efficiently, thus depleting mechanical energy. The results demonstrated that the effective damping temperature range (Tan δ > 0.3) of the PUE cured by AIS can reach 130 °C (−15 °C–115 °C), which is 210 % higher than that of the matrix, and a stable damping plateau was observed in the region from room temperature to high temperature. Moreover, the introduction of AIS significantly enhanced the mechanical properties of the PUE. This study encourages further investigation and application of disulfide bonds in the field of damping.

The Partner Agencies of the International Space Station (ISS) maintain separate career exposure limits and shared Flight Rules that control the ionising radiation exposures that crewmembers can experience due to ambient environments throughout their space missions. In low Earth orbit as well as further out in space, energetic ions referred to as galactic cosmic radiation (GCR) easily penetrate spacecraft and spacecraft contents and consequently are always present at low dose rates. Protons and electrons that are trapped in the Earth’s geomagnetic field are encountered intermittently, and a rare energetic solar particle event (SPE) may expose crew to (mostly) energetic protons. Space radiation protection goals are to optimize radiation exposures to maintain deleterious late effects at known and acceptable levels and to prevent any early effects that might compromise crew health and mission success. The conventional radiation protection metric effective dose provides a basic framework for limiting exposures associated with human spaceflight and can be communicated to all stakeholders. Additional metrics and uncertainty analyses are required to understand more completely and to convey nuanced information about potential impacts to an individual astronaut or to a space mission. Missions to remote destinations well beyond low Earth orbit (BLEO) are upcoming and bestow additional challenges that shape design and radiation protection needs. NASA has recently adopted a more permissive career exposure limit based upon effective dose and new restrictions on mission exposures imposed by nuclear technologies. This manuscript reviews the exposure limits that apply to the ISS crewmembers. This work was performed in collaboration with the advisory and guidance efforts of International Commission on Radiological Protection (ICRP) Task Group 115 and will be summarized in an upcoming ICRP Report.

The International Partner Agencies of the International Space Station (ISS) present a comparison of the ionizing radiation absorbed dose and risk quantities used to characterize example missions in lunar space. This effort builds on previous collaborative work that characterizes radiation environments in space to support radiation protection for human spaceflight on ISS in low-Earth orbit (LEO) and exploration missions beyond (BLEO). A “shielded” ubiquitous galactic cosmic radiation (GCR) environment combined with––and separate from––the transient challenge of a solar particle event (SPE) was modelled for a simulated 30-day mission period. Simple geometries of relatively thin and uniform shields were chosen to represent the space vehicle and other available shielding, and male or female phantoms were used to represent the body’s self-shielding. Absorbed dose in organs and tissues and the effective dose were calculated for males and females. Risk parameters for cancer and other outcomes are presented for selected organs. The results of this intracomparison between ISS Partner Agencies itself provide insights to the level of agreement with which space agencies can perform organ dosimetry and calculate effective dose. This work was performed in collaboration with the advisory and guidance efforts of the International Commission on Radiological Protection (ICRP) Task Group 115 and will be presented in an ICRP Report

Introduction and Objectives: Primary biliary cholangitis (PBC) may progress to clinically significant portal hypertension (CSPH) before the development of cirrhosis. This study aimed to investigate CSPH incidence as well as the clinicopathological characteristics and predictive value of these features for the prognosis of patients with PBC, especially at early histologic stage. Patients and Methods: Patients diagnosed with PBC between January 2013 and April 2022 were retrospectively enrolled. The prognostic value of baseline clinicopathological characteristics for long-term outcomes in PBC patients with CSPH was assessed using Kaplan–Meier survival analysis and COX regression analysis. Results: Among 280 patients with PBC, 104 underwent liver biopsy and 68 were at early histologic stage. CSPH was present in 47.2 % of participants with 20.6 % at early histologic stage. CSPH was a risk factor for predicting the liver transplant-free survival in PBC patients (hazard ratio [HR], 6.78; 95 % CI, 2.94–15.63), especially those at early stage. Perisinusoidal fibrosis and nodular regenerative hyperplasia (NRH) were common histopathological features in PBC patients with CSPH at the early stages. Fibrous septa formation in the hepatic lobules (HR, 4.85; 95 % CI, 1.51–15.52) and cholestasis (HR, 7.70; 95 % CI, 2.56–23.18) were independent predictors of adverse outcomes. Conclusions: CSPH indicates an increased risk of adverse outcomes in PBC patients, especially those in early histologic stage. Perisinusoidal fibrosis and NRH are valuable histological features of CSPH in patients with early-stage PBC. Identification of clinicopathological features and assessment of portal hypertension (especially at early stage), contribute to the development of personalized strategies.

Cinnamomum cassia Presl is a major food spice as well as traditional herbal medicine with anti-inflammatory, analgesic, and stomachic properties, which must be dried to preserve its quality, but mostly by using traditional, ineffective drying method. In order to find a scientific drying method by evaluating different drying methods that could influence the quality of C. cassia, ten indices were employed to evaluate different drying methods in C. cassia using the Analytic Hierarchy Process (AHP) method though calculating the total scores and ranking the priority. Four quality markers (Q-Markers) (coumarin, cinnamyl alcohol, cinnamaldehyde and o-methoxycinnamaldehyde) were isolated from the samples and analyzed by high performance liquid chromatography (HPLC) method under different drying methods. The results showed that various drying methods had multiple effects on the physicochemical qualities, essential oil content, and Q-Marker contents. Compared with other drying methods, oven-drying of 45 °C (45OD) maintained optimal levels of color and aroma, it also significantly shortened the drying time by 225 h than traditionally shade-drying (SHD) method with the drying rate (48.35 %), and obtained the highest essential oil content (3.05 %) and Q-Marker contents (30.23 mg g−1). Furthermore, the ash content (4.22 %) were satisfied with the stipulation of Chinese pharmacopoeia in 45OD samples. Applying AHP allowed us to identify 45OD as the optimal drying method with the highest total score (9.00), followed by the traditional shade-drying (SHD) method (7.88). The present study is the first report to apply the AHP method for quality evaluation of drying processing in C. cassia. It can provide the theoretical basis for evaluating an excellent method for C. cassia drying processing, as well as the rational use of different drying methods to furtherly develop the high quality C. cassia industry.

Summary: Macrophages play crucial roles in organ-specific functions and homeostasis. In the adrenal gland, macrophages closely associate with sinusoidal capillaries in the aldosterone-producing zona glomerulosa. We demonstrate that macrophages preserve capillary specialization and modulate aldosterone secretion. Using macrophage-specific deletion of VEGF-A, single-cell transcriptomics, and functional phenotyping, we found that the loss of VEGF-A depletes PLVAP+ fenestrated endothelial cells in the zona glomerulosa, leading to increased basement membrane collagen IV deposition and subendothelial fibrosis. This results in increased aldosterone secretion, called “haptosecretagogue” signaling. Human aldosterone-producing adenomas also show capillary rarefaction and basement membrane thickening. Mice with myeloid cell-specific VEGF-A deletion exhibit elevated serum aldosterone, hypokalemia, and hypertension, mimicking primary aldosteronism. These findings underscore macrophage-to-endothelial cell signaling as essential for endothelial cell specialization, adrenal gland function, and blood pressure regulation, with broader implications for other endocrine organs.

Over recent decades, China has risen to a preeminent global position in both solar photovoltaic (PV) adoption and production, a feat underpinned by a suite of pivotal policy measures. With a burgeoning demand for PV systems on the horizon, there is an urgent need to reassess past policies and chart new directions. This study employs bibliometrics and content analysis to systematically scrutinize China's PV policies across distinct phases, delineating the underlying rationale and overarching evolutionary trajectory. It offers a comprehensive overview of these policies, encapsulating their metamorphosis through four discernible stages. The findings of this study shed light on a discernible policy trajectory within China's dynamic PV sector. Initially, policies were meticulously tailored to nurture domestic technological capabilities and ensure a comprehensive PV supply chain. Subsequently, the focus shifted towards the widespread application of PV technology. More recently, policies have evolved to prioritize regulatory refinement, subsidy reduction, and optimizing solar power consumption. These empirical insights underscore the pivotal role of supportive policies in propelling China's PV industry growth, with far-reaching implications for emerging sectors.

This is a case report of a 6-year-old girl with relapsed B cell acute lymphoblastic leukemia in which adoptive cell therapy was applied successfully to treat refractory human parvovirus (HPV) B19 infection. Allogenic chimeric antigen receptor (CAR) T-cell therapy (bispecific CD19/CD22) was bridged to hematopoietic stem cell transplantation (HSCT) using a haploidentical paternal donor. However, HPV B19 DNAemia progressed and transfusion-related graft versus host disease occurred. After finding a third-party related donor with a better HLA match, haploidentical HPV B19-seropositive CD45RA+ depleted cells (16.5 × 106/kg) were administered and paternal TCRαβ+ depleted stem cell were retransplanted. The HPV B19 DNAemia became negative within 1 week and the reticulocyte, neutrophil, hemoglobin, and platelet counts gradually normalized. The patient remained stable during the 1-year outpatient follow-up period. Thus, our case report highlights that persistent B19 infection can lead to pancytopenia, aplastic crisis, and graft rejection and TCRαβ+ depleted haplo-HSCT is an effective means of hematopoiesis recovery. CD45RO memory T-cell therapy is the key to treating and preventing the development of refractory severe HPV B19 infection.

Background: Oral lichen planus (OLP) is a common chronic oral mucosal disease with 1.4 % malignant transformation rate, and its etiology especially immune pathogenesis remains unclear. This study was aimed at investigating the immune cells related molecular underlying the pathophysiology of OLP through bioinformatics analysis. Methods: The dataset GSE52130 obtained from the Gene Expression Omnibus (GEO) database was conducted a comprehensive analysis in this study. The CIBERSORTx was used for investigating immune cells infiltration. The gene set enrichment analysis (GSEA) and gene ontology (GO) enrichment were performed for exploring the biological functions and gene annotation. The protein-protein interactions (PPI) were constructed by STRING database and visualized by Cytoscape software. The cytohubba plugin was utilized for screening hub genes. The receiver operating characteristic (ROC) was performed for evaluating diagnostic value of hub genes. The miRNAs, lncRNAs and drugs were respectively predicted by NetworkAnalyst, miRTarbase, ENCORI, and DGIdb database. Results: This study identified 595 differentially expressed genes (DEGs). The GSEA indicated keratinization, innate immune system and biological oxidation were involved in OLP. GO analysis showed extracellular matrix and keratinocyte were mainly enriched. And we found the activated memory CD4+ T cells were lowly infiltrated in OLP. We identified 101 activated memory CD4+ T-cells-related DEGs. Three hub genes (APP, IL1B, TF) were selected. APP and IL1B were significantly up-regulated, whereas TF was down-regulated in OLP. The three hub genes show high diagnostic value in OLP. Additionally, they were involved in MAPK signal, NF-kappaB signal and iron metabolism in OLP. What's more, NEAT1/XIST - miR - 15a - 5p/miR - 155–5p - APP/IL1B signal axis was focused in competing endogenous RNA (ceRNA) network. In addition, 35 drugs were predicted for OLP. Conclusion: Three activated memory CD4+ T-cells-related DEGs were identified by integrative analysis. It may provide novel insight into the pathogenesis of OLP and suggest potential therapeutic targets for OLP.

Diabetic neuropathy (DN) represents a common and debilitating complication of diabetes, affecting a significant proportion of patients. Despite available treatments focusing on symptom management, there remains an unmet need for therapies that address the underlying pathophysiology. In pursuit of novel interventions, this study evaluated the therapeutic effects of caffeic acid—a natural phenolic compound prevalent in various foods—on diabetic neuropathy using a mouse model, particularly examining its interaction with the Insulin-like Growth Factor 1 (IGF-1) signaling pathway. Caffeic acid was administered orally at two dosages (5 mg/kg and 10 mg/kg), and a comprehensive set of outcomes including fasting blood glucose levels, body weight, sensory behavior, spinal cord oxidative stress markers, inflammatory cytokines, and components of the IGF-1 signaling cascade were assessed. Additionally, to determine the specific contribution of IGF-1 signaling to the observed benefits, IGF1R inhibitor Picropodophyllin (PPP) was co-administered with caffeic acid. Our results demonstrated that caffeic acid, at both dosages, effectively reduced hyperglycemia and alleviated sensory behavioral deficits in diabetic mice. This was accompanied by a marked decrease in oxidative stress markers and an increase in antioxidant enzyme activities within the spinal cord. Significantly lowered microglial activation and inflammatory cytokine expression highlighted the potent antioxidative and anti-inflammatory effects of caffeic acid. Moreover, increases in both serum and spinal levels of IGF-1, along with elevated phosphorylated IGF1R, implicated the IGF-1 signaling pathway as a mediator of caffeic acid's neuroprotective actions. The partial reversal of caffeic acid's benefits by PPP substantiated the pivotal engagement of IGF-1 signaling in mediating its effects. Our findings delineate the capability of caffeic acid to mitigate DN symptoms, particularly through reducing spinal oxidative stress and inflammation, and pinpoint the integral role of IGF-1 signaling in these protective mechanisms. The insights gleaned from this study not only position caffeic acid as a promising dietary adjunct for managing diabetic neuropathy but also highlight the therapeutic potential of targeting spinal IGF-1 signaling as part of a strategic treatment approach.

Introduction: Chronic insomnia in adults affects the health and quality of life of patients. Chinese patent medicines (CPMs) combined with benzodiazepines/non-benzodiazepines (BZDs/N-BZDs) are used frequently in routine clinical practice. However, evidence on the efficacy and safety of these combined interventions is lacking. A multiple treatment meta-analysis (MTMA) was conducted to evaluate the comparative efficacy and safety of 16 CPMs combined with BZDs/N-BZDs for the treatment of chronic insomnia in adults. Methodology: We systematically reviewed 171 randomized controlled trials (RCTs) involving 16,874 participants (8506 in intervention groups and 8368 in control groups) from the inception of several databases to 2023. This review encompassed electronic databases, regulatory-agency websites, and international registers of published trials involving adult patients with chronic insomnia who received CPM + BZDs/N-BZDs therapies. A random-effects MTMA was undertaken using Stata/MP17, RevMan (5.3), and R. Outcome measures were the Pittsburgh Sleep Quality Index (PSQI), overall efficacy rate, as well as the incidence of dry mouth, dizziness, and somnolence. Results: Our MTMA showed that BZD/N-BZD therapy as a co-intervention for Tianmengjiaonang (TMJN) was likely to be the optimal option for improving the PSQI (surface under the cumulative sorting curve (SUCRA) = 95.00 %), whereas shensongyangxinjiaonang (SSYXJN) had the highest probability of improving overall effectiveness (SUCRA = 88.20 %). Jiaotaiwan (JTW), Bailemian (BLMJN), and Wulinjiaonang (WLJN) had the highest probability of reducing the incidence of somnolence (SUCRA = 90.00 %), dry mouth (SUCRA = 72.90 %), and dizziness (SUCRA = 84.40 %). Conclusions: All CPMs in combination with BZDs/N-BZDs were more efficacious and safer than using BZDs/N-BZDs alone in adults with chronic insomnia. SSYXJN + BZDs/N-BZDs and TMJN + BZDs/N-BZDs are likely to be optimal CPMs because they improve overall efficacy and sleep quality and reduce the risk of adverse effects. However, the effects of these interventions may vary from person to person. Hence, patients, carers, and clinicians should carefully consider the efficacy, safety, and risk–benefit profile of all active interventions for patients with insomnia based on real-world data.

Optimizing the pattern of territorial space utilization is one of the key tasks to achieve the sustainable development goals. With the accelerating rate of global urbanization, the understanding of territorial space utilization efficiency, role and potential is a prerequisite for alleviating contradictions in urban and rural space distribution. The city cluster is the main form of organization for urban development in future, so the study attempted to explore the urban and rural space utilization efficiency (URSUE) in Chengdu-Chongqing urban agglomeration (CCEC) from coupling coordination degree (CCD) perspective. Considering the gradual increase in the trend of remote interactions between URSUE, we further introduced the Local and Tele-coupling coordination (LTCCD) model that takes into account interactive development relationship between different systems. The results of the study show that: In CCEC, the more economically developed cities indicated that urban spatial utilization efficiency lags behind rural spatial utilization efficiency; The LTCCD in the geographic center region will indicate a higher level but the LTCCD in the economic core cities is higher compared with their CCD level, especially in Chengdu City. This suggests that the LTCCD model is better able to take into account regional development correlations and spatial spillovers effect. This study attempts to explore several key issues of urban-rural spatial allocation in the process of urbanization development and to provide guidance for the territorial space utilization planning in urban agglomerations.

To accurately, efficiently, and environmentally prepare carrageenan oligosaccharides, we have developed a method that uses H2O2 and TiO2 as catalysts for the photodegradation of κ-carrageenan (KC). The photodegradation of KC was monitored using various amounts of TiO2 and H2O2 and different concentrations of KC via HPLC and it could decrease the average molecular weight of KC into 1.6 kDa within 2 h. Further research under optimal conditions. As a control, the effects of UV, UV/H2O2, UV/TiO2, and H2O2/TiO2 treatments were studied. In contrast, UV/H2O2/TiO2 treatments showed a coordinated effect. The effect of degradation on the structure of KC was investigated by FT-IR, XRD, and there was no obvious remotion of sulfate groups. Furthermore, oral administration of KCO prolonged the healthy lifespan of nematodes induced by ultraviolet stress and significantly regulated oxidative stress. This study suggests that the precise preparation and application of KCO may be beneficial.

Habitat fragmentation has become a serious threat to amphibian populations worldwide. Concrete anti-seepage, widely applied in waterway construction, has posed a threat by causing amphibians to easily fall into concrete irrigation channels and struggle to escape. However, our understanding of the impact of irrigation channels on frog movement and survival remains limited. In this study, we evaluated the effects of concrete-lined irrigation channels on the escape ability of a common Chinese frog (Pelophylax nigromaculatus). We also analyzed the correlation between the morphology and locomotion ability of the frogs, tested the impact of irrigation channel slope gradient and substrate material on their escape ability, and proposed an optimized design for frog ramps to assist trapped frogs in escaping. The results showed that the frogs have easily fallen into these channels and encountered difficulties in escaping during field activities. As body size was positively related to the frogs’ ability to climb the slope of irrigation channels, the design parameters of the frog ramps should focus on the movement ability of the frogs. The maximum climbing gradients for most frogs on concrete, reverse slope (the protruding structure is placed in the opposite direction of the channel slope), grass and crushed stone are 40°, 50°, 60° and 65°, respectively. Based on experimental tests of the ability of the frogs to climb on various slopes and substrates, we suggest that the slope gradient of concrete irrigation channels should be less than 40°. The findings offer references for scholars and engineers to improve ecological engineering designs of irrigation channels throughout the world.

Short peptides have become the focus of recent research due to their variable bioactivities, good digestibility and wide existences in food-derived protein hydrolysates. However, due to the high complexity of the samples, identifying short peptides still remains a challenge. In this work, a tool, named PeposX-Exhaust, was developed for short peptide identification. Through validation with known peptides, PeposX-Exhaust identified all the submitted spectra and the accuracy rate reached 75.36%, and the adjusted accuracy rate further reached 98.55% when with top 5 candidates considered. Compared with other tools, the accuracy rate by PeposX-Exhaust was at least 70% higher than two database-search tools and 15% higher than the other two de novo-sequencing tools, respectively. For further application, the numbers of short peptides identified from soybean, walnut, collagen and bonito protein hydrolysates reached 1145, 628, 746 and 681, respectively. This fully demonstrated the superiority of the tool in short peptide identification.

Background: Sotorasib has been approved for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). Due to the limitations of clinical trials, potential adverse events (AEs) and long-term safety issues cannot be detected. The presented study aimed to evaluate sotorasib-associated AEs using the FDA Adverse Event Reporting System (FAERS) database. Methods: Post-marketing AE reports of sotorasib in the database were collected for analysis. Disproportionality analyses, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC) and empirical bayes geometric mean (EBGM) algorithms, were performed to mine the signals of sotorasib-associated AEs. The median duration, quartiles and the Weibull shape parameter (WSP) test were used to assess the onset time data. Results: The database contained 1538 cases of sotorasib as primary suspect (PS), with 27 signals detected, scattering in 5 SOCs. The SOC of hepatobiliary disorders (182, ROR 4.48, PRR 4.07, IC 2.02, EBGM 4.07) met the four methodological thresholds. The median onset time of sotorasib-associated AEs was 42 days (interquartile range [IQR] 14–86.75 days). Different SOCs had different types of risk over time. Conclusion: After obtaining marketing authorization, the study identified all potentially relevant adverse event (AE) signals expected to have a reporting frequency higher than anticipated and characterized them during sotorasib treatment.

Background: Polycystic ovary syndrome (PCOS) is main cause of anovulatory infertility in women with gestational age. There are currently four distinct phenotypes associated with individualized endocrinology and metabolism. Growth differentiation factor 9 (GDF9) is a candidate as potential biomarker for the assessment of oocyte competence. The effect on oocyte capacity has not been evaluated and analyzed in PCOS phenotypes. Objective: We aimed to screen the expression levels of GDF9 in mature follicles of women with controlled ovarian hyperstimulation (COS) with different PCOS phenotypes. To determine the correlation between the expression level of GDF9 and oocyte development ability. Methods: In Part 1, we conducted a retrospective study comparing the clinical outcomes and endocrine characteristics of patients with PCOS according to different subgroups (depending on the presence or absence of the main features of polycystic ovarian morphology (PCOM), hyperandrogenism (HA), and oligo-anovulation (OA)) and non-PCOS control group. We stratified PCOS as phenotype A (n = 29), phenotype B (n = 18) and phenotype D (n = 24). In Part 2, the expression of GDF9 in follicular fluid (FF) and cumulus cells (CCs) were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. Results: In Part 1, the baseline clinical, hormonal, and ultrasonographic characteristics of the study population were matched with the presence or absence of the cardinal features of each PCOS phenotypes showed a clear difference. Phenotypes A and D had statistically significant associations with blastocyst formation and clinical pregnancy compared with phenotypes B (p

Continuous fiber-reinforced silicon carbide composites have received significant attention due to their high-temperature mechanical stability. However, their widespread implementation has been hindered by intricate fracture mechanisms and limited toughness. This study presents a real-time approach for identifying damage type in 2.5D SiCf/SiC composites and highlights the significant impact of minor eccentric loading angle on the fracture behavior and mechanical properties using acoustic emission (AE). Even a slight degree of eccentric loading angle can significantly alter the fracture behaviors, leading to a significant increase in fracture toughness. The fracture damage evolution law of 2.5D SiCf/SiC under varying eccentric loading angles was investigated with the help of the AE damage identification, fracture morphology and finite element analysis. These findings provide valuable insights for multi-axis stress analysis of 2.5D high-performance composites.

Objective: In this study, we aimed to utilize computed tomography (CT)-derived radiomics and various machine learning approaches to differentiate between invasive mucinous adenocarcinoma (IMA) and invasive non-mucinous adenocarcinoma (INMA) preoperatively in solitary pulmonary nodules (SPN) ≤3 cm. Methods: A total of 538 patients with SPNs measuring ≤3 cm were enrolled, categorized into either the IMA group (n = 50) or INMA group (n = 488) based on postoperative pathology. Radiomic features were extracted from non-contrast-enhanced CT scans and identified using the least absolute shrinkage and selection operator (LASSO) algorithm. In constructing radiomics-based models, logistic regression, support vector machines, classification and regression trees, and k-nearest neighbors were employed. Additionally, a clinical model was developed, focusing on CT radiological features. Subsequently, this clinical model was integrated with the most effective radiomic model to create a combined model. Performance assessments of these models were conducted, utilizing metrics such as the area under the receiver operating characteristic curve (AUC), DeLong's test, net reclassification index (NRI), and integrated discrimination improvement (IDI). Results: The support vector machine approach showed superior predictive efficiency, with AUCs of 0.829 and 0.846 in the training and test cohorts, respectively. The clinical model had AUCs of 0.760 and 0.777 in the corresponding cohorts. The combined model had AUCs of 0.847 and 0.857 in the corresponding cohorts. Furthermore, compared to the radiomic model, the combined model significantly improved performance in both the training (DeLong test P = 0.045, NRI 0.206, IDI 0.024) and test cohorts (P = 0.029, NRI 0.125, IDI 0.032), as well as compared to the clinical model in both the training (P = 0.01, NRI 0.310, IDI 0.09) and test cohorts (P = 0.047, NRI 0.382, IDI 0.085). Conclusion: the combined model exhibited excellent performance in distinguishing between IMA and INMA in SPNs ≤3 cm.

The frequent occurrence of major public health emergencies (MPHEs) significantly challenges national security, economic stability, social operation and the safety of people's lives and property worldwide. Consequently, enhancing the emergency management of MPHEs is critically urgent. This paper constructs a game model involving local government, social organisations, and the public for MPHE management, exploring strategy combinations and influencing factors across various scenarios. Several results were obtained. (1) Local government, social organisations, and the public each have positive and negative strategy choices based on cost–benefit analysis, leading to eight different strategy combinations. Furthermore, all three take positive strategies as the optimal way to achieve the game equilibrium. (2) The transformation of strategy combinations is primarily influenced by the cost-benefit gap and the strategic decisions of local government. (3) Altering a subject's initial strategy value doesn't change its final choice but impacts the time to achieve a stable strategy equilibrium. The severity of local government punishments on social organisations influences their strategic choices and the time to optimal strategy, whereas rewards to the public or social organisations only affect the time to achieve this strategy. The findings of this study can not only help improve the collaborative governance system of MPHEs but also provide scientific guidance on how governments can manage MPHEs.

Semantic segmentation of urban-scale point clouds can effectively assist people in understanding and perceiving 3D urban scenes. Although a considerable number of deep learning models for the semantic segmentation of point clouds have been proposed, some methods are plagued by information loss caused by sampling and insufficient perception of the spatial relationship between points. To address this issue, this paper proposes an end-to-end space-aware DeepLab deep learning network, named SADNet. In the SADNet, a space-aware attentive residual module (SARM) is incorporated to extract rich point cloud features with the assistance of perceiving spatial relationships between points. Then, in combination with a point cloud atrous spatial pyramid pooling module (PCaspp), SADNet extracts multiscale point cloud features while effectively avoiding information loss from pooling and downsampling. Finally, a dilated local feature extraction (DLFE) module is designed to enhance the detection ability for small objects by dilating the feature map. Furthermore, to validate the superiority of the SADNet, extensive experiments are conducted on two publicly available benchmarks, Sensaturban and Hessigheim 3D. The results demonstrate the state-of-the-art performance on both datasets, which achieves the mean IoU of 66.8% on Sensaturban and overall accuracy of 91.77%, mean F1-score of 82.81% on Hessigheim 3D. Overall, SADNet is a promising approach for urban-scale point cloud semantic segmentation and has the potential to enhance understanding and perception of real-world urban scenes.

Background: Colorectal cancer (CRC) is a prevalent malignancy of the digestive tract. A new prognostic scoring model for colon adenocarcinoma (COAD) is developed in this study based on the genes involved in tumor cell-mediated killing of T cells (GSTTKs), accurately stratifying COAD patients, thus improving the current status of personalized treatment. Method: The GEO and TCGA databases served as the sources of the data for the COAD cohort. This study identified GSTTKs-related genes in COAD through single-factor Cox analysis. These genes were used to categorize COAD patients into several subtypes via unsupervised clustering analysis. The biological pathways and tumor microenvironments of different subgroups were compared. We performed intersection analysis between different subtypes to obtain intersection genes. Single-factor Cox regression analysis and Lasso-Cox analysis were conducted to establish clinical prognostic models. Two methods are used to assess the accuracy of model predictions: ROC and Kaplan-Meier analysis. Next, the prediction model was further validated in the validation cohort. Differential immune cell infiltration between various risk categories was identified via single sample gene set enrichment analysis (ssGSEA). The COAD model's gene expression was validated via single-cell data analysis and experiments. Result: We established two distinct GSTTKs-related subtypes. Biological processes and immune cell tumor invasion differed significantly between various subtypes. Clinical prognostic models were created using five GSTTKs-related genes. The model's risk score independently served as a prognostic factor. COAD patients were classified as low- or high-risk depending on their risk scores. Patients in the low-risk category recorded a greater chance of surviving. The outcomes from the validation cohort match those from the training set. Risk scores and several tumor-infiltrating immune cells were strongly correlated, according to ssGSEA. Single-cell data illustrated that the model's genes were linked to several immune cells. The experimental results demonstrated a significant increase in the expression of HOXC6 in colon cancer tissue. Conclusion: Our research findings established a new gene signature for COAD. This gene signature helps to accurately stratify the risk of COAD patients and improve the current status of individualized care.

Background: Immunotherapy favors patients with tumors; however, only 3–26.3% of patients with cervical cancer benefit from single-agent immune checkpoint inhibitors. Combined immunotherapy and chemotherapy has been explored against tumor; however, the combination remains controversial. This study aimed to investigate the tumor immune microenvironment (TIME) and the effects of platinum-based neoadjuvant chemotherapy (NACT) in cervical cancer to identify the clinical value of combining chemotherapy with immunotherapy. Methods: Multiplex immunohistochemistry (IHC) with 11 markers (cluster of differentiation [CD]3, CD8, CD4, CD11c, CD68, forkhead box P3 [Foxp3], programmed cell death 1 [PD-1], programmed cell death 1 ligand 1 [PD-L1], indoleamine 2,3-dioxygenase [IDO], cyclin-dependent kinase inhibitor 2A [p16], and cytokeratin [CK]) was performed to evaluate TIME from 108 matched pre- and post-NACT cervical cancer samples. The mechanism of antitumor immunity triggered by NACT was explored using RNA sequencing (RNA-seq) from four paired samples and subsequently verified in 41 samples using IHC. Results: The infiltration rate of the CD8+ T cells in treatment-naive cervical cancer was 0.73%, and those of Foxp3+ regulatory T cells (Tregs) and IDO+ cells were 0.87% and 17.15%, respectively. Moreover, immunoreactive T cells, dendritic cells, and macrophages were more in the stromal than the intratumor region. NACT increased dendritic, CD3+ T, CD8+ T, and CD4+ T cells and decreased Tregs. The aforementioned alterations occurred predominantly in the stromal region and were primarily in responders. Non-responders primarily showed decreased Tregs and no increase in CD8+ T or dendritic cell infiltration. Furthermore, dendritic cells interacted more closely with CD3+ T cells after NACT, an effect primarily observed in responders. RNA-seq data revealed activation of the antigen receptor-mediated signaling pathway and upregulation of major histocompatibility complex (MHC) I and MHC II after chemotherapy, validated using IHC. Conclusions: NACT can reduce Tregs, and when tumor cells are effectively killed, antigen presentation is enhanced, subsequently activating antitumor immunity finitely. Our study provides the molecular characteristics and theoretical basis for the simultaneous or sequential combination of platinum-based NACT and immunotherapy for cervical cancer.

Background & Aims: As the most abundant memory T cells and major source of tumor necrosis factor α in the intestinal mucosa of Crohn’s disease (CD) patients, CD4+ tissue-resident memory T (TRM) cells play a critical role in CD pathogenesis. We investigated the role of metabolic reprogramming in the regulation of proinflammatory and apoptosis-resistant phenotype for CD4+ TRM cells. Methods: CD4+ TRM cells were collected from intestinal resection tissues from control and CD patients. Transcriptomic and metabolomic analysis were performed to identify metabolic characteristics of CD4+ TRM cells. Enzyme-linked immunosorbent assay and quantitative polymerase chain reaction experiments were used to assess cytokines level in CD4+ TRM cells; activation-induced cell apoptosis rate was evaluated by flow cytometry. Transwell assay and wound healing assay were performed to detect the effect of CD4+ TRM cells on the migration of normal intestinal epithelial cells. Results: Transcriptomic data combined with unbiased metabolomic analysis revealed an increased fatty acid oxidation (FAO) phenotype existed in CD4+ TRM cells from CD patients. The lipidomic data and stable isotope tracer experiments demonstrated that CD4+ TRM cells up-regulated their lipid lipolysis and fatty acid uptake to fuel FAO in CD patients. Mechanistically, the activated nuclear factor kappa B signaling increased transcription of genes involved in lipid lipolysis, fatty acid uptake, and oxidation in CD4+ TRM cells from CD patients. Targeting FAO of CD4+ TRM cells reversed their apoptosis-resistant and proinflammatory phenotype in CD patients. Conclusions: CD4+ TRM cells process an accelerated FAO mediated by activated nuclear factor kappa B signaling in CD patients; targeting FAO could reverse their apoptosis-resistant and proinflammatory phenotype. These findings shed a new light on the pathogenic mechanism investigation and novel therapy development in CD patients.