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Analyzing rock mass seepage using the discrete fracture network (DFN) flow model poses challenges when dealing with complex fracture networks. This paper presents a novel DFN flow model that incorporates the actual connections of large-scale fractures. Notably, this model efficiently manages over 20,000 fractures without necessitating adjustments to the DFN geometry. All geometric analyses, such as identifying connected fractures, dividing the two-dimensional domain into closed loops, triangulating arbitrary loops, and refining triangular elements, are fully automated. The analysis processes are comprehensively introduced, and core algorithms, along with their pseudo-codes, are outlined and explained to assist readers in their programming endeavors. The accuracy of geometric analyses is validated through topological graphs representing the connection relationships between fractures. In practical application, the proposed model is employed to assess the water-sealing effectiveness of an underground storage cavern project. The analysis results indicate that the existing design scheme can effectively prevent the stored oil from leaking in the presence of both dense and sparse fractures. Furthermore, following extensive modification and optimization, the scale and precision of model computation suggest that the proposed model and developed codes can meet the requirements of engineering applications.

Abstract Background It is uncertain whether the weekend warrior pattern is associated with all-cause mortality among adults living with type 2 diabetes. This study explored how the ‘weekend warrior’ physical activity (PA) pattern was associated with all-cause mortality among adults living with type 2 diabetes. Methods This prospective cohort study investigated US adults living with type 2 diabetes in the National Health and Nutrition Examination Survey (NHANES). Mortality data was linked to the National Death Index. Based on self-reported leisure-time and occupational moderate-to-vigorous PA (MVPA), participants were categorized into 3 groups: physically inactive (

Abstract Effective monitoring and early warning of overhead power lines are critical for ensuring power supply stability and personnel safety. However, existing methods that rely solely on single vision or light detection and ranging (LiDAR) have limitations such as numerous invalid alarms, hardware equipment constraints, and lack of real‐time monitoring capabilities. This article proposes an intelligent monitoring method for safety distance of the powerline corridor based on heterogeneous sensor information. Firstly, an optimised single‐stage detector is designed to detect safety hazard objects. In the detector, the backbone network and the sample matching strategy are improved; in addition, the learning strategy is adjusted. Next, the pose transformation relationship is obtained through the visual matching of prior LiDAR information and images. The back projection transformation of 2D–3D is achieved according to the relationship. Finally, a monocular camera‐based end‐to‐end distance measurement scheme is proposed by combining 2D object information with coordinate transformation relationships. The scheme is applied to the distance measurements from hazard objects to powerlines. The experimental results show that the optimisation method improves the detection accuracy and reduces the computational complexity of the model. Also, case experiments with continuous frame data verify the effectiveness of the safety distance monitoring scheme.

Abstract Background Cyp19a1a is a key enzyme in the pathway that converts androgens into estrogen and is regulated by TGF-β signaling. Smad4 and FoxH1 are downstream effectors of TGF-β signaling and may play important roles in ovarian development in M. albus. Methods We investigated the expression pattern of the Smad4 and FoxH1 using qRT‒PCR and immunofluorescence, then tested the changes of smad4 and foxh1 by qRT‒PCR after ovary incubation with FSH in vitro, and analysed the regulation of cyp19a1a transcription by Smad4 and FoxH1 by dual-luciferase reporter assays. Results We found that Smad4 encoded a putative protein of 449 amino acids and harbored the three conserved domains typical of this protein family. Smad4 and foxh1 exhibited similar expression patterns during ovarian development and after FSH incubation, with Pearson’s coefficients of 0.873 and 0.63–0.81, respectively. Furthermore, Smad4, FoxH1 and Cyp19a1a colocalized in the granulosa cells and theca cells of ovaries during the mid-to-late vitellogenic stage. Smad4 repressed cyp19a1a activity via SBE1 (− 1372/−1364) and SBE2 (− 415/−407) in the cyp19a1a promoter, whereas mutating SBE1 or SBE2 restored cyp19a1a promoter activity. Co-overexpression of Smad4 and FoxH1 significantly reduced cyp19a1a promoter activity. Conclusions This study provides new insights into the potential functions of transcription factors Smad4 and FoxH1 in ovarian development and the transcriptional regulation mechanism of cyp19a1a in M. albus, which will reveal Smad4/FoxH1-mediated TGF-β signaling in reproduction and the regulation of the cyp19a1a. Plain English summary Aromatase, encoded by cyp19a1a, is involved in ovarian development and plays an important role in the quality of eggs, as well the sex ratio, of the teleost fish, M. albus. The research on the transcriptional regulation of cyp19a1a has contributed to the understanding of its role in ovarian development. In previous study, it was shown that FoxH1 inhibits cyp19a1a transcription. In the present study, Smad4 was confirmed as a cyp19a1a transcriptional repressor and Smad4 may also coordinate with FoxH1 to repress cyp19a1a transcription. At present, we provide a new perspective for the transcriptional regulation of cyp19a1a by transcription factors Smad4 and FoxH1 in teleost fish ovary. In the future, the regulatory networks of Smad4 and FoxH1 will be further studied and the gene editing technology will be applied to screen specific regulatory factors of cyp191a1a gene, so as to alter the female cycle and modulate the sex ratio of the eggs production.

Nickel foam is widely used as a collector for electrocatalysts because of its excellent electrical conductivity; however, it is prone to react with elements such as oxygen, sulfur, and phosphorus during the growth of electrode materials, which makes it brittle and fragile, thus limiting its large-scale application. In this study, bifunctional electrocatalysts with flexible multilevel Ni-based nanoclusters Ni@(Ni,Fe)Se2/Ni@CC were synthesized on carbon cloth (CC) by hydrothermal and electrodeposition methods; these flexible electrocatalysts are convenient for subsequent industrial applications. At a current density of 10 mA cm−2, the overpotentials of the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) reached 98 and 224 mV, respectively, exceeding the catalytic effects of most metal-based collectors. The overall water-splitting potential of the catalyst was only 1.56 V at 10 mA cm−2, and the performance was maintained after a 24 h stability test. Ni@(Ni,Fe)Se2/Ni@CC significantly improved the activity in alkaline environments by modulating the center of the d-band, thereby increasing the adsorption capacity of the catalyst for H ions. In this study, we improved the intrinsic activity and charge transfer of transition metal electrocatalysts by modifying the carbon cloth and constructing multilevel Ni-based nanoclusters, which provided some insights into the rational design of flexible bifunctional electrocatalysts.

The rational selection of non-geological hazard samples is of great significance to improve the accuracy of geological hazard susceptibility prediction. This study uses Liulin County as a case study, where appropriate impact factors were selected, and the random forest (RF) model was employed for susceptibility assessment based on GIS technology. A total of twenty sets of models were created by varying the ratio of geological hazard to non-geological hazard points (1∶1, 1∶1.5, 1∶3, 1∶5 and 1∶10) and the distance from non-geological hazard points to known hazard points (100,500,800,1000 m). The results demonstrate that: (1) Through error index, confusion matrix, and ROC curve tests, the sample proportion and distance from the known hazard point significantly influenced the geological hazard susceptibility evaluation. As the sample proportion decreased and the distance from known hazard points increased, the overall MAE and RMSE of the models decreased, while the overall ACC increased. All models achieved AUC value greater than 0.8, indicating excellent predictive performance. When the sample proportion was less than 1∶3, the increasing distance from the known hazard points on model error and accuracy became less pronounced, stabilizing the results. The most suitable model for the study area was found to have a sample ratio of 1∶10 and a distance of 1000 m from known hazard points. (2) High and very high susceptibility areas were primarily located in the central and northern regions, adjacent to roads and rivers, making them key areas for hazard prevention and reduction in Liulin County. (3) Differences in sample selection led to varying susceptibility results mainly due to changes in the RF model's data feature collection and judgment during the modeling process, as well as the representativeness of the samples. These research findings hold significant implications for the implementation of hazard prevention and reduction measures.

Abstract Background Ureteral cancer is a rare cancer. This study aimed to provide an up-to-date and comprehensive analysis on the global trends of ureteral cancer incidence and its association with lifestyle and metabolic risk factors. Methods The incidence of ureteral cancer was estimated from the Cancer Incidence in Five Continents Plus and Global Cancer Observatory databases. We analyzed the (1) global incidence of ureteral cancer by region, country, sex, and age group by age-standardized rates (ASR); (2) associated risk factors on a population level by univariable linear regression with logarithm transformation; and (3) incidence trend of ureteral cancer by sex and age group in different countries by Average Annual Percentage Change (AAPC). Results The global age-standardized rate of ureteral cancer incidence in 2022 was 22.3 per 10,000,000 people. Regions with higher human development index (HDI), such as Europe, Northern America, and East Asia, were found to have a higher incidence of ureteral cancer. Higher HDI and gross domestic product (GDP) and a higher prevalence of smoking, alcohol drinking, physical inactivity, unhealthy dietary, obesity, hypertension, diabetes, and lipid disorder were associated with higher incidence of ureteral cancer. An overall increasing trend of ureteral cancer incidence was observed for the past decade, especially among the female population. Conclusions Although ureteral cancer was relatively rare, the number of cases reported was rising over the world. The rising trends among females were more evident compared with the other subgroups, especially in European countries. Further studies could be conducted to examine the reasons behind these epidemiological changes and confirm the relationship with the risk factors identified.

Abstract Background Gastric cancer (GC) is a malignant digestive tract tumor with a high recurrence rate and poor prognosis. Fucosylation is important in tumor glycosylation, in which the key enzyme is fucosyltransferase (FUT). FUT11 is a member of the fucosyltransferase family and has been closely associated with the development of multiple cancers. However, the specific relationship between FUT11 and GC prognosis and its molecular mechanism has not been fully studied. This study explored FUT11 expression, clinical correlation, and its role in GC occurrence and development to deepen understanding of its function. Methods FUT11 expression in 33 cancers was preliminarily analyzed using the Tumor Immunoassay Resource (TIMER2.0) database. FUT11 expression in GC was evaluated using The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD) and Gene Expression Profiling Interactive Analysis (GEPIA2) data and verified using the Gene Expression Omnibus (GEO) GSE65801 dataset. Furthermore, we studied the survival prognosis of FUT11 in GC and analyzed its effect on the survival rate of patients with GC using the KM-plotter. We also performed COX regression analysis on TCGA GC clinical data and analyzed FUT11 expression in the pathway using the STRING and LinkedOmics databases. Moreover, the relationship between FUT11 and GC immune infiltration level was examined, and the Kaplan–Meier survival analysis diagram was constructed. The FUT11 genetic variation information was retrieved using cBioPortal, and its drug sensitivity was analyzed using CellMiner. Finally, differential FUT11 expression in GC tissues was verified using immunohistochemistry. Results The data mining and analysis demonstrated that FUT11 expression was abnormally elevated in GC tissues and correlated with poor patient prognosis. The FUT11 expression level was an independent prognostic factor for GC. The difference in FUT11 expression level resulted in different degrees of immune cell infiltration in the patients with GC, which might regulate the tumor microenvironment. FUT11 affected GC development by participating in cancer pathways such as PI3K–AKT, neuroactive ligand–receptor, and MAPK. Immunohistochemical staining revealed that FUT11 was highly expressed in GC. Conclusions This study revealed that FUT11 expression is significantly increased in GC tissues. This increase is associated with poor prognosis and might affect immune regulation. FUT11 might have immunological and targeted therapeutic value, providing a new approach to GC treatment.

Objective: Depression is a mental disorder characterized by persistent feelings of sadness, decreased interest or pleasure in activities and reduced energy. As a highly prevalent disorder, it seriously endangers the psychosocial functioning of patients. Many scholars have conducted clinical studies on the treatment of depression using different herbal remedies, but there are no studies that integrate these remedies to explore the general medication rule. This study aims to explore the medication pattern of Traditional Chinese Medicine (TCM) treatment for depression through data mining methods, so as to provide scientific theoretical basis and reference for clinical treatment and new prescription development. Methods: Based on the PRISMA principle, 121 articles involving 10810 patients with depression of TCM treatment were collected. We then performed frequency, association rule, and hierarchical clustering analysis of Chinese herbs using Microsoft Excel 2016, SPSS Modeler 18.0 and IBM SPSS Statistics 23. Results: Among the 270 herbs collected, the three most frequently occurring herbs are Gancao, Chaihu, and Shaoyao. The categories of high-frequency herbs are mainly deficiency-tonifying, Qi-regulating and blood-activating and stasis-eliminating herbs. Through the Apriori algorithm, we mined 21 herbal groups of association rules, and among which the combination of Chaihu-Shaoyao-Gancao has the highest level of support. Furthermore, five novel clustering combinations were identified, predominantly derived from Xiaoyao-San, Chaihu-Shugan-San, Sini powder, Kaixin-San and Chaihu-Jia-Longgu-Muli Decoction. Conclusion: The current study not only concluded the frequent combinations but also developed five new drug cluster combinations for depression, which can provide evidence-based references for the future clinical treatment and is helpful to understand the potential pharmaceutical mechanism from the properties, tastes, meridian tropisms and categories. The clinical effectiveness of these combinations needs to be verified by future study.

To develop an environmentally sustainable and efficient extraction method for flavonoids from Moringa oleifera Lam. (M. oleifera) leaves, natural deep eutectic solvents (NADES) with ultrasound-assisted extraction was utilized in this study. After optimization of extraction parameters of NADES, including ultrasonic power, ultrasonic time, and liquid–solid ratio, the extraction yield of ultrasound-assisted NADES (UAN) composed of betaine and urea (Bet-Urea) reached 54.69 ± 0.19 mg RE/g DW, which made a 1.7-fold increase compared to traditional ultrasound-assisted traditional solvent (UATS). UPLC-Q Exactive/MS analysis revealed that M. oleifera leaves flavonoids (MOLF) was mainly composed of Quercetin 3-β-D-glucoside, Rutin, Kaempferol-3-O-glucoside, Vitexin and Quercetin. Furthermore, the COSMO-RS model was employed to verify the optimal compatibility of solubility and activity coefficient between Bet-Urea and the five primary flavonoids in MOLF. In vitro antioxidant assays verified that MOLF extracted by UAN exhibited superior antioxidant activity compared to MOLF extracted by UATS. Overall, the devised process not only augmented the extraction yield of MOLF but also effectively preserved the bioactive compounds, thus promoting the utilization of green extraction solvents in the food industry.

ABSTRACT Introduction Breast cancer poses significant health risks to women and strains healthcare systems extensively. In low‐ and middle‐income countries (LMICs), limited resources and inadequate healthcare infrastructures further exacerbate the challenges of breast cancer prevention, treatment, and awareness. Methods We examined the prevalence, risk factors, and trends of breast cancer in LMICs. Data on disability‐adjusted life years (DALYs) and breast cancer risk factors were extracted from the Global Burden of Disease (GBD) databases for 203 countries or territories from 1990 to 2019. LMIC DALY rates were examined using joinpoint regression analysis. Results Among the income groups, the lower middle‐income category had the highest DALYs value, with 1787 years per 100,000 people. LMICs collectively accounted for 74% of the global burden of DALYs lost due to breast cancer in 2019. However, it remained relatively consistent in lower middle income countries (LMCs). In LMCs, the risk associated with metabolic syndromes was higher compared to that with behavioral factors alone. For the past three decades, breast cancer incidences increased significantly in LMCs (average annual percent change [AAPC]: 1.212, confidence intervals [CI]: 1.51–1.87, p

Background: Schizophrenia (SCZ) is a severe mental disorder, but its pathogenesis is still unknown, and its clinical treatment effect is very limited. Transient receptor potential vanilloid 1 (TRPV1) channel and the Endocannabinoid System (ECS)have been confirmed to be involved in the pathogenesis of SCZ, although their actions have not been fully clarified yet. The objective is to examine TRPV1 and ECS expression in the blood of schizophrenia patients and investigate their correlation with disease severity. Methods: This is a cross-sectional investigation. Peripheral blood samples were gathered from normal controls (NC, n=37), as well as individuals with schizophrenia, including first episode (n=30) and recurrent (n=30) cases. We employed western blot and ELISA techniques to quantify TRPV1, cannabinoid receptors 1(CB1), anandamide (AEA), and 2-arachidonoylglycerol (2-AG), and assess the severity of the patient's symptoms by means of the PANSS scale. Results: Compared to NC, TRPV1 levels showed a noticeable decrease in both first episode schizophrenia (f-SCZ group) and recurrent schizophrenia (r-SCZ group) subjects. Additionally, CB1 levels appeared increased in f-SCZ group. Furthermore, 2-AG levels were found to be elevated in both f-SCZ group and r-SCZ group compared to NC, whereas AEA levels were decreased in f-SCZ group but increased in r-SCZ group. Moreover, among schizophrenia patients, TRPV1 demonstrated a negative correlation with negative symptoms. Within r-SCZ subjects, CB1 displayed a negative correlation with relapse number, while 2-AG showed a correlation in the opposite direction. Conclusions: This study provides initial clinical evidence of changed TRPV1 expression in schizophrenia, potentially linked to negative symptoms. These results suggest a possible dysfunction of TRPV1 and the endocannabinoid system (ECS), which might offer new avenues for medical interventions.

Introduction: Classification criteria for systemic lupus erythematosus (SLE) include American College of Rheumatology (ACR) 1997, Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 and European Alliance of Associations for Rheumatology (EULAR)/ACR 2019 criteria. Their performance in an Asian childhood-onset SLE (cSLE) population remains unclear as the clinical manifestations differ. We aim to evaluate the diagnostic performance in a cSLE cohort in Singapore. Method: Cases were physician-diagnosed cSLE, while controls were children with mixed and undifferentiated connective tissue disease that posed an initial diagnostic challenge. Data were retrospectively reviewed to establish the 3 criteria fulfilled at diagnosis and over time. Results: The study population included 120 cSLE cases and 36 controls. At diagnosis, 102 (85%) patients fulfilled all criteria. SLICC-2012 had the highest sensitivity (97.5%, 95% confidence interval [CI] 92.3–99.5), while ACR-1997 had the highest specificity (91.7%, 95% CI 77.5–98.3). All criteria had diagnostic accuracies at more than 85%. Over time, 113 (94%) fulfilled all criteria. SLICC-2012 remained the criteria with the highest sensitivity (99.2%, 95% CI 95.4–99.9), while ACR-1997 had the highest specificity (75.0%, 95% CI 57.8–87.9). Only SLICC-2012 and ACR-1997 had more than 85% diagnostic accuracy over time. Using a cutoff score of ≥13 for EULAR/ACR-2019 criteria resulted in improved diagnostic performance. Conclusion: SLICC-2012 criteria had the highest sensitivity early in the disease course in this first study evaluating the SLE classification criteria performance in a Southeast Asian cSLE cohort, while the ACR-1997 criteria had the highest specificity. Using a cutoff score of ≥13 for EULAR/ACR-2019 improved the diagnostic performance.

Background: The cartilage stem/progenitor cells (CSPC) play a critical role in maintaining cartilage homeostasis. However, the effects of phenotypic fluctuations of CSPC on cartilage degeneration and the role of CSPC in the pathogenesis of OA is largely unknown. Methods: The cartilage samples of 3 non-OA and 10 OA patients were collected. Human CSPC (hCSPC) derived from these patients were isolated, identified, and evaluated for cellular functions. Additionally, chondrocytes derived from OA patients were isolated. The effect of Yes-associated protein (YAP) expression on hCSPC was investigated in vitro. The OA rat model was established by Hulth's method. Lentivirus-mediated YAP (Lv-YAP) or lentivirus-mediated YAP RNAi (Lv-YAP-RNAi) was injected intra-articularly to modulate YAP expression in rat joints. In addition, allogeneic rat CSPC (rCSPC) overexpressing or silencing YAP were transplanted by intra-articularly injection. We also evaluated the functions of rCSPC and the OA-related cartilage phenotype in the rat model. Finally, the transcriptome of OA rCSPC overexpressing YAP was examined to explore the potential downstream targets of YAP in rCSPC. Results: hCSPC derived from OA patients exhibited differential chondrogenesis capacity. Among them, a subset of hCSPC showed pronounced dysfunction, including impaired chondrogenic differentiation, inhibition of proliferation and migration, and downregulation of lubricin. Additionally, YAP was lowly expressed in quiescent non-OA hCSPC, upregulated in activated OA hCSPC, but significantly downregulated in dysfunctional OA hCSPC. Notably, the overexpression of YAP in OA hCSPC improved the proliferation, lubricin production, cell migration, and senescence, while silencing YAP had the opposite effect. In vivo, upregulation of YAP in the joint delayed OA progression and improved the cartilage regeneration capacity of rCSPC. Using transcriptomic analysis, we found that YAP may regulate rCSPC function by upregulating Baculoviral IAP repeat-containing 2 (BIRC2). Importantly, the knockdown of BIRC2 partly blocked the regulation of YAP on the CSPC function. Conclusion: Dysfunction of CSPC compromises the intrinsic repair capacity of cartilage and impairs cartilage homeostasis in OA. Notably, the transcriptional co-activator YAP plays a critical role in maintaining CSPC function through potential target gene BIRC2. The Translational Potential of this Article: In this study, we observed targeting the YAP-BIRC2 axis improved the CSPC function and restored the cartilage homeostasis in OA. This study provides a potential stem cell-modifying OA therapy.

Abstract Proton pump inhibitors (PPIs) are commonly used for gastric acid-related disorders, but their safety profile and risk stratification for high-burden diseases need further investigation. Analyzing over 2 million participants from five prospective cohorts from the US, the UK, and China, we found that PPI use correlated with increased risk of 15 leading global diseases, such as ischemic heart disease, diabetes, respiratory infections, and chronic kidney disease. These associations showed dose-response relationships and consistency across different PPI types. PPI-related absolute risks increased with baseline risks, with approximately 82% of cases occurring in those at the upper 40% of the baseline predicted risk, and only 11.5% of cases occurring in individuals at the lower 50% of the baseline risk. While statistical association does not necessarily imply causation, its potential safety concerns suggest that personalized use of PPIs through risk stratification might guide appropriate decision-making for patients, clinicians, and the public.

In recent years, the coverage path planning (CPP) of unmanned aerial vehicles (UAVs) has attracted attention in reconnaissance, patrol, and search and rescue efforts, aiming to plan the paths for UAVs to cover a specified area as efficiently as possible. This paper proposes a UAV path fast coverage model to prioritize important targets with domain composition based on the starting point and location of the targets, combined with the domain decomposition strategy of important targets. Considering the constraints of the number of UAVs, the number of operators, and the flight time, the parallel search strategy can plan the coverage scheme with the shortest search time for the search range, and further obtain the coordinate points and path coordinates of the UAV turning. Finally, through multiple simulation experiments in four maps of various islands, the proposed method is verified to have an improved performance compare to the two track path coverage algorithms methods in terms of the coverage efficiency and the time complexity, thus providing a more scientific basis for the path coverage research of multi-target searches.

Abstract Background To assess the long-term association between organised colorectal cancer (CRC) screening strategies and CRC-relate mortality. Methods We systematically reviewed studies on organised CRC screening through PubMed, Ovid Medline, Embase and Cochrane from the inception. We retrieved characteristics of organised CRC screening from included literature and matched mortality (over 50 years) of those areas from the International Agency for Research on Cancer in May 2023. The variations of mortality were reported via the age-standardised mortality ratio. A random-effects model was used to synthesis results. Results We summarised 58 organised CRC screening programmes and recorded > 2.7 million CRC-related deaths from 22 countries where rollout screening programmes were performed. The CRC screening strategy with faecal tests (guaiac faecal occult blood test (gFOBT) or faecal immunochemical tests (FIT)) or colonoscopy as the primary screening offer was associated with a 41.8% reduction in mortality, which was higher than those offered gFOBT (4.4%), FIT (16.7%), gFOBT or FIT (16.2%), and faecal tests (gFOBT or FIT) or flexible sigmoidoscopy (16.7%) as primary screening test. The longer duration of screening was associated with a higher reduction in the pooled age-standardised mortality ratio. In particular, the pooled age-standardised mortality ratio became non-significant when the screening of FIT was implemented for less than 5 years. Conclusions A CRC screening programme running for > 5 years was associated with a reduction of CRC-related mortality. Countries with a heavy burden of CRC should implement sustainable, organised screening providing a choice between faecal tests and colonoscopy as a preferred primary test.

Abstract Chemical structure segmentation constitutes a pivotal task in cheminformatics, involving the extraction and abstraction of structural information of chemical compounds from text-based sources, including patents and scientific articles. This study introduces a deep learning approach to chemical structure segmentation, employing a Vision Transformer (ViT) to discern the structural patterns of chemical compounds from their graphical representations. The Chemistry-Segment Anything Model (ChemSAM) achieves state-of-the-art results on publicly available benchmark datasets and real-world tasks, underscoring its effectiveness in accurately segmenting chemical structures from text-based sources. Moreover, this deep learning-based approach obviates the need for handcrafted features and demonstrates robustness against variations in image quality and style. During the detection phase, a ViT-based encoder-decoder model is used to identify and locate chemical structure depictions on the input page. This model generates masks to ascertain whether each pixel belongs to a chemical structure, thereby offering a pixel-level classification and indicating the presence or absence of chemical structures at each position. Subsequently, the generated masks are clustered based on their connectivity, and each mask cluster is updated to encapsulate a single structure in the post-processing workflow. This two-step process facilitates the effective automatic extraction of chemical structure depictions from documents. By utilizing the deep learning approach described herein, it is demonstrated that effective performance on low-resolution and densely arranged molecular structural layouts in journal articles and patents is achievable.

Major depressive disorder (MDD) is common, and successful treatment remains challenging. Resveratrol, a naturally occurring polyphenol, has been shown to alleviate depression-like behaviors, but the underlying mechanisms remain unclear. We previously developed a new model of depression by inducing hippocampal ferroptosis in rats, suggesting that ferroptosis may be involved in the development of MDD. Here, we further explored the antidepressant-like effect of resveratrol and its association with ferroptosis. Male rats were exposed to chronic unpredictable mild stress (CUMS), with or without resveratrol, followed by comprehensive behavioral testing. In PC12 cells in vitro, LY294002 (an AKT inhibitor) and ML385 (an NRF2 inhibitor) were used to elucidate the involvement of AKT/NRF2 signaling in resveratrol-mediated ferroptosis. mRNA and protein levels of AKT/NRF2 pathway and ferroptosis-related targets were measured. Ferroptosis was quantified by measuring malondialdehyde (MDA), glutathione (GSH), and Fe2+ content and superoxide dismutase (SOD) activity. Resveratrol ameliorated depression-like behaviors in rats, simultaneously restoring AKT/NRF2 pathway and ferroptosis-related targets in the hippocampus downregulated by CUMS. Elevated markers of oxidative stress in plasma were attenuated by resveratrol. Furthermore, erastin induced ferroptosis and inhibited AKT/NRF2 signaling in PC12 cells, which was counteracted by resveratrol. Additionally, the impact of resveratrol on erastin-induced ferroptosis was reversed by LY294002 and ML385. This study demonstrates that resveratrol ameliorates depression-like behaviors by inhibiting ferroptosis via the AKT/NRF2 pathway.

Bacterial-infected wounds could cause delayed wound healing due to increased inflammation, especially wounds infected by drug-resistant bacteria remain a major clinical problem. However, traditional treatment strategies were gradually losing efficacy, such as the abuse of antibiotics leading to enhanced bacterial resistance. Therefore, there was an urgent need to develop an antibiotic-free multifunctional dressing for bacterially infected wound healing. This study demonstrated the preparation of a multifunctional injectable hydrogel and evaluated its efficacy in treating acute and infected wounds. The hydrogel was prepared by a one-step mixing method, and cross-linked by natural deep eutectic solvent (DES), polyvinyl alcohol (PVA), chitosan (CS), tannic acid (TA), and Cu2+ through non-covalent interactions (hydrogen bonds and metal coordination bonds). PVA/CS/DES/CuTA500 hydrogel has multiple functional properties, including injectability, tissue adhesion, biocompatibility, hemostasis, broad-spectrum antibacterial, anti-inflammatory, and angiogenesis. Most importantly, in the MRSA-infected skin wound model, PVA/CS/DES/CuTA500 hydrogel could ultimately accelerate infected wound healing by killing bacteria, activating M2 polarization, inhibiting inflammation, and promoting angiogenesis. In summary, the PVA/CS/DES/CuTA500 hydrogel showed great potential as a wound dressing for bacterial infected wounds treatment in the clinic.

Small mothers against decapentaplegic2/3 (Smad2/3) are two signalling intermediates in the transforming growth factor beta (TGF-β) signalling pathway, which plays a critical role in gonad development. However, a systemic analysis of Smad2/3 in Monopterus albus (M. albus) has not been performed. The smad2 sequence in M. albus was characterized in our previous publication. In this study, we characterized the nucleotide sequence of smad3 and reported that smad3 is widely expressed in different tissues of M. albus. Importantly, the expression of smad3 significantly increased at the early vitellogenic stage in the ovary and decreased with oocyte maturation. Next, we aimed to identify the upstream factors that regulate Smad2/3 transcription. The 5′ flanking sequences of smad2/3 were cloned, and their core promoter regions were determined to be between −447 bp and −100 bp and between −1520 bp and −927 bp, respectively. The Jun and Foxo1 binding sites were conserved in the smad2 promoter region, and the Sp1, Bcl-6, and Nobox binding sites were conserved in the smad3 promoter region. Through dual-luciferase reporter gene experiments, we showed that Jun and Foxo1 binding sites may be involved in the regulation of smad2 transcription, whereas the Nobox binding site may be involved in the activation of the smad3 promoter.

AbstractBackground Reducing avoidable hospital admissions is a global healthcare priority, with optimal primary care recognised as pivotal for achieving this objective. However, in developing systems like China, where primary care is evolving without compulsory gatekeeping, the relationship between patient-perceived primary care quality and hospital utilisation remains underexplored.Objectives This study aimed to explore the association between patient-perceived primary care quality and self-reported hospital utilisation in China.Methods Data were collected from 16 primary care settings. Patient-perceived quality of primary care was measured using the Assessment Survey of Primary Care scale across six domains (first-contact care, continuity, comprehensiveness, accessibility, coordination, and patient-centredness). Hospital utilisation included patient self-reported outpatient visits, hospital admissions, and emergency department (ED) visits in the last six months. Logistic regression analyses were examined associations between self-reported hospital utilisation and perceived primary care quality adjusted for potential confounders.Results Of 1,185 patients recruited, 398 (33.6%) reported hospital utilisation. Logistic regression analyses showed that higher total scores for patient-perceived quality of primary care were associated with decreased odds of hospital utilisation (adjusted odds ratio(AOR): 0.417, 95% confidence interval (CI): 0.308–0.565), outpatient visits (AOR: 0.394, 95% CI: 0.275–0.566) and hospital admissions (AOR: 0.496, 95% CI: 0.276–0.891). However, continuity of care was positively associated with ED visits (AOR: 2.252, 95% CI: 1.051–4.825).Conclusion Enhanced patient-perceived quality of primary care in China is associated with a reduction in self-reported overall hospital utilisation, including outpatient visits and hospital admissions. However, better continuity of care may be associated with increased ED visits. Further research is warranted for precise insights and validation of these findings.

BackgroundDietary behaviors significantly influence health outcomes across populations. Unhealthy diets are linked to serious diseases and substantial economic burdens, contributing to approximately 11 million deaths and significant disability-adjusted life years annually. Digital dietary interventions offer accessible solutions to improve dietary behaviors. However, attrition, defined as participant dropout before intervention completion, is a major challenge, with rates as high as 75%-99%. High attrition compromises intervention validity and reliability and exacerbates health disparities, highlighting the need to understand and address its causes. ObjectiveThis study systematically reviews the literature on attrition in digital dietary interventions to identify the underlying causes, propose potential solutions, and integrate these findings with behavior theory concepts to develop a comprehensive theoretical framework. This framework aims to elucidate the behavioral mechanisms behind attrition and guide the design and implementation of more effective digital dietary interventions, ultimately reducing attrition rates and mitigating health inequalities. MethodsWe conducted a systematic review, meta-analysis, and thematic synthesis. A comprehensive search across 7 electronic databases (PubMed, MEDLINE, Embase, CENTRAL, Web of Science, CINAHL Plus, and Academic Search Complete) was performed for studies published between 2013 and 2023. Eligibility criteria included original research exploring attrition in digital dietary interventions. Data extraction focused on study characteristics, sample demographics, attrition rates, reasons for attrition, and potential solutions. We followed ENTREQ (Enhancing the Transparency in Reporting the Synthesis of Qualitative Research) and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used RStudio (Posit) for meta-analysis and NVivo for thematic synthesis. ResultsOut of the 442 identified studies, 21 met the inclusion criteria. The meta-analysis showed mean attrition rates of 35% for control groups, 38% for intervention groups, and 40% for observational studies, with high heterogeneity (I²=94%-99%) indicating diverse influencing factors. Thematic synthesis identified 15 interconnected themes that align with behavior theory concepts. Based on these themes, the force-resource model was developed to explore the underlying causes of attrition and guide the design and implementation of future interventions from a behavior theory perspective. ConclusionsHigh attrition rates are a significant issue in digital dietary interventions. The developed framework conceptualizes attrition through the interaction between the driving force system and the supporting resource system, providing a nuanced understanding of participant attrition, summarized as insufficient motivation and inadequate or poorly matched resources. It underscores the critical necessity for digital dietary interventions to balance motivational components with available resources dynamically. Key recommendations include user-friendly design, behavior-factor activation, literacy training, force-resource matching, social support, personalized adaptation, and dynamic follow-up. Expanding these strategies to a population level can enhance digital health equity. Further empirical validation of the framework is necessary, alongside the development of behavior theory–guided guidelines for digital dietary interventions. Trial RegistrationPROSPERO CRD42024512902; https://tinyurl.com/3rjt2df9

Objective To investigate the cerebroprotective effects of leptin in vitro and in vivo via the Janus kinase-2 (JAK2)/transcription factor signal transducer and activators of transcription-3 (STAT3) pathway and leptin receptors (LEPR). Methods The study used the cellular oxygen-glucose deprivation (OGD) model in PC12 cells and the middle cerebral artery occlusion (MCAO) rat model of cerebral ischaemia–reperfusion injury (CIRI) to assess changes in gene expression and protein levels following leptin pretreatment. The methylated DNA immunoprecipitation (MeDIP) assay measured DNA methylation levels. Results The optimal leptin concentration for exerting neuroprotective effects against ischaemia–reperfusion injury in PC12 cells was 200 ng/ml in vitro , but excessive leptin diminished this effect. Leptin pretreatment in the MCAO rat model demonstrated a similar effect to previously reported leptin administration post-CIRI. In addition to regulating the expression of inflammation-related cytokines, Western blot analysis showed that leptin pretreatment upregulated BCL-2 and downregulated caspase 3 levels. The MeDIP analysis demonstrated that DNA methylation regulated LEPR gene expression in the MCAO rat model when leptin pretreatment was used. Conclusion Exogenous leptin might bind to extra-activated LEPR by reducing the methylation level of the LEPR gene promoter region, which leads to an increase in phosphorylated JAK2/STAT3 and apoptotic signalling pathways.

Abstract Background and Aim Obesity has been a global public health issue due to the increasing mortality rate and prevalence among children. However, there are scarce studies on obesity prevalence in Hong Kong children. The study aims to identify the risk factors of obesity among primary and secondary school students by assessing the relationship between sociodemographic factors, health‐related behaviors, and social relationships. Methods Self‐administrated surveys were collected from 30 primary schools and 25 secondary schools participating in the “Quality Education Fund Thematic Network on Health Schools” project. Descriptive analysis was conducted to examine the proportions of different characteristics and to compare the disparity between primary and secondary school students with obesity. Results A total of 4884 responses were collected. A larger proportion of primary school students with obesity were male (adjusted odds ratio [aOR]: 2.55, 95% confidence interval [CI]: 1.77–3.67, p

BackgroundThe incidence of early-onset colorectal cancer (EOCRC) is increasing globally. This study aims to describe the temporal trends of incidence and explore related risk exposures in early-life at the country level based on the GBD 2019.MethodsData on the incidence and attributable risk factors of EOCRC were obtained from the GBD 2019. Temporal trends of age-standardized incidence were evaluated by average annual percentage change (AAPC). Early-life exposures were indicated as summary exposure values (SEV) of selected factors, SDI and GDP per capita in previous decades and at ages 0–4, 5–9, 10–14 and 15–19 years. Weighted linear or non-linear regressions were applied to evaluate the ecological aggregate associations of the exposures with incidences of EOCRC.ResultsThe global age-standardized incidence of EOCRC increased from 3.05 (3.03, 3.07) to 3.85 (3.83, 3.86) per 100,000 during 1990 and 2019. The incidence was higher in countries with high socioeconomic levels, and increased drastically in countries in East Asia and Caribbean, particularly Jamaica, Saudi Arabia and Vietnam. The GDP per capita, SDI, and SEVs of iron deficiency, alcohol use, high body-mass index, and child growth failure in earlier years were more closely related with the incidences of EOCRC in 2019. Exposures at ages 0–4, 5–9, 10–14 and 15–19 years were also associated with the incidences, particularly for the exposures at ages 15–19 years.ConclusionThe global incidence of EOCRC increased during past three decades. The large variations at regional and national level may be related with the distribution of risk exposures in early life.

Abstract Background Schizothorax o’connori is an endemic fish distributed in the upper and lower reaches of the Yarlung Zangbo River in China. It has experienced a fourth round of whole gene replication events and is a good model for exploring the genetic differentiation and environmental adaptability of fish in the Qinghai-Tibet Plateau. The uplift of the Qinghai-Tibet Plateau has led to changes in the river system, thereby affecting gene exchange and population differentiation between fish populations. With the release of fish whole genome data, whole genome resequencing has been widely used in genetic evolutionary analysis and screening of selected genes in fish, which can better elucidate the genetic basis and molecular environmental adaptation mechanisms of fish. Therefore, our purpose of this study was to understand the population structure and adaptive characteristics of S. o’connori using the whole-genome resequencing method. Results The results showed that 23,602,746 SNPs were identified from seven populations, mostly distributed on chromosomes 2 and 23. There was no significant genetic differentiation between the populations, and the genetic diversity was relatively low. However, the Zangga population could be separated from the Bomi, Linzhi, and Milin populations in the cluster analysis. Based on historical dynamics analysis of the population, the size of the ancestral population of S. o’connori was affected by the late accelerated uplift of the Qinghai Tibet Plateau and the Fourth Glacial Age. The selected sites were mostly enriched in pathways related to DNA repair and energy metabolism. Conclusion Overall, the whole-genome resequencing analysis provides valuable insights into the population structure and adaptive characteristics of S. o’connori. There was no obvious genetic differentiation at the genome level between the S. o’connori populations upstream and downstream of the Yarlung Zangbo River. The current distribution pattern and genetic diversity are influenced by the late accelerated uplift of the Qinghai Tibet Plateau and the Fourth Ice Age. The selected sites of S. o’connori are enriched in the energy metabolism and DNA repair pathways to adapt to the low temperature and strong ultraviolet radiation environment at high altitude.

Abstract Background Cervical cancer is a major global health concern, disproportionately affecting women in developing countries. Cervical cancer has two primary subtypes, squamous cell carcinoma (SCC) and adenocarcinoma (AC), each with distinct characteristics and screening effectiveness. In this study, we aimed to estimate the global incidence of cervical cancer according to histological subtype to inform prevention strategies. Methods Using data from population-based cancer registries, we computed the rates of SCC, AC, and other specified histology among all cervical cancer cases by country and by 5-year age group. Proportions were subsequently applied to the estimated number of cervical cancer cases from the Global Cancer Observatory 2020. Age-standardized incidence rates were calculated. Results SCC accounted for 82.72% of global cervical cancer cases, with AC contributing 12.18%. The highest SCC incidence was in Sub-Saharan Africa (29.79 per 100,000 population). The AC incidence was highest in South-Eastern Asia (3.67 per 100,000 population). Age-specific trends showed SCC peaking at approximately age 55 years and AC plateauing after age 45 years. Conclusions This study provided a comprehensive estimate of cervical cancer incidence by histological subtype. SCC remained the dominant subtype globally, whereas the incidence of AC varied across regions. These findings highlighted the need for tailored prevention strategies, especially testing for human papillomavirus to detect AC in high burden areas.

[Introduction] The distribution characteristics of mountain fires by using the historical disaster data of mountain fires related to transmission lines in Hubei province has been analyzed. [Method] Based on the mountain fire disaster data of transmission lines in Hubei Province from 2016 to 2021, the methods of mathematical statistics, climate statistics and GIS spatial superposition were used to analyze the spatiotemporal distribution of transmission line mountain fires in Hubei Province as well as the characteristics of the relationship between mountain fires and meteorological, underlying surface, and social humanities factors. [Result] In terms of time, 2019 is the year in which mountain fires occurred most frequently on transmission lines in Hubei in recent years. Autumn and winter are peak seasons for mountain fires, with February and September being the months with a higher risk of occurrence. In terms of space, the eastern part of Hubei Province is the region with frequent mountain fires, while the Yichang and Jingmen regions are the second highest risk areas. The relationship between the mountain fire and the meteorology shows that the precipitation in the month before the occurrence of most mountain fires is 30% to 100% less than the normal level, the temperature is 0.5 ℃ to 3 ℃ higher than the normal level, the humidity is 3.8% to 23% lower than the normal level, and the wind speed is 0.1 to 1.9 m/s higher than the normal level. The relationship between mountain fire and underlying surface shows that mountain fire mainly occurs in cultivated land, accounting for 50.32% of the total. The mountain fires are mainly concentrated in the areas with an altitude below 150 meters and a slope below 6°, and 76.90% of the mountain fires occur on the sunny slope. The relationship between mountain fire and social humanities shows that mountain fire mainly occurs in the towns around the urban circle with a population density of 100~600 people/square kilometer, as well as the buffer zone about 1.6 kilometers away from the road. [Conclusion] Mastering the distribution characteristics of mountain fires related to Hubei transmission lines can help select indicators and determine thresholds for mountain fire risk warning models.

Hydrogen energy plays an important role in clean energy system and is considered the core energy source for future technological development owing to its lightweight nature, high calorific value, and clean combustion products. The electrocatalytic conversion of water into hydrogen is considered a highly promising method. An electrocatalyst is indispensable in the electrocatalytic process, and finding an efficient electrocatalyst is essential. However, the current commercial electrocatalysts (such as Pt/C and Ru) are expensive; therefore, there is a need to find an inexpensive and efficient electrocatalyst with high stability, corrosion resistance, and high electrocatalytic efficiency. In this study, we developed a cost-effective bifunctional electrocatalyst by incorporating molybdenum into nickel sulfide (Ni3S2) and subsequently tailoring its structure to achieve a one-dimensional (1D) needle-like configuration. The hydrogen production efficiency of nickel sulfide was improved by changing the ratio of Mo doping. By analyzing the electrochemical performance of different Mo-doped catalysts, we found that the Ni3S2-Mo-0.1 electrocatalyst exhibited the best electrocatalytic effect in 1 M KOH; at a current density of 10 mA cm−2, it exhibited overpotentials of 120 and 279 mV for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), respectively; at a higher current density of 100 mA cm−2, the HER and OER overpotentials were 396 and 495 mV, respectively. Furthermore, this electrocatalyst can be used in a two-electrode water-splitting system. Finally, we thoroughly investigated the mechanism of the overall water splitting of this electrocatalyst, providing valuable insights for future hydrogen production via overall-water-splitting.

Abstract The sensory neocortex has been suggested to be a substrate for long-term memory storage, yet which exact single cells could be specific candidates underlying such long-term memory storage remained neither known nor visible for over a century. Here, using a combination of day-by-day two-photon Ca2+ imaging and targeted single-cell loose-patch recording in an auditory associative learning paradigm with composite sounds in male mice, we reveal sparsely distributed neurons in layer 2/3 of auditory cortex emerged step-wise from quiescence into bursting mode, which then invariably expressed holistic information of the learned composite sounds, referred to as holistic bursting (HB) cells. Notably, it was not shuffled populations but the same sparse HB cells that embodied the behavioral relevance of the learned composite sounds, pinpointing HB cells as physiologically-defined single-cell candidates of an engram underlying long-term memory storage in auditory cortex.

Adversarial attacks on Graph Neural Networks (GNNs) have emerged as a significant threat to the security of graph learning. Compared with Graph Modification Attacks (GMAs), Graph Injection Attacks (GIAs) are considered more realistic attacks, in which attackers perturb GNN models by injecting a small number of fake nodes. However, most existing black-box GIA methods either require comprehensive knowledge of the dataset and the ground-truth labels or a large number of queries to execute the attack, which is often unfeasible in many scenarios. In this paper, we propose an unsupervised method for leveraging the rich knowledge contained in the graph data themselves to enhance the success rate of graph injection attacks on the initial query. Specifically, we introduce GraphContrastive Learning-based Graph Injection Attack (GCIA), which consists of a node encoder, a reward predictor, and a fake node generator. The Graph Contrastive Learning (GCL)-based node encoder transforms nodes for low-dimensional continuous embedding, the reward predictor acts as a simplified surrogate for the target model, and the fake node generator produces fake nodes and edges based on several carefully designed loss functions, utilizing the node encoder and reward predictor. Extensive results demonstrate that the proposed GCIA method achieves a first query success rate of 91.2% on the Reddit dataset and improves the success rate to over 99.7% after 10 queries.

Abstract Background and Aim Colorectal cancer (CRC) is the third most common cancer in the world. This study devises and validates a clinical scoring system for risk prediction of advanced colorectal neoplasia (ACN) to guide colonoscopy evaluation among diabetic patients. Methods We identified 55 964 diabetic patients who received colonoscopies from a large database in a Chinese population (2008–2018). We recruited a derivation cohort based on random sampling. The risk factors of CRC evaluated by univariate analysis were examined for ACN, defined as advanced adenoma, CRC, or any combination thereof using binary logistic regression analysis. We used the adjusted odds ratios (aORs) for independent risk factors to devise a risk score, ranging from 0 to 6: 0–4 “average risk” (AR) and 5–6 “high risk” (HR). The other subjects acted as an independent validation cohort. Results The prevalence of ACN in both the derivation and validation cohorts was 2.0%. Using the scoring system constructed, 78.5% and 21.5% of patients in the validation cohort were classified as AR and HR, respectively. The prevalence of ACN in the AR and HR groups was 1.5% and 4.1%, respectively. Individuals in the HR group had a 2.78‐fold increased prevalence of ACN than the AR group. The concordance (c‐) statistics was 0.70, implying a good discriminatory capability of the risk score to stratify high‐risk individuals who should consider colonoscopy. Conclusion The clinical risk scoring system based on age, gender, smoking, presence of hypertension, and use of aspirin is useful for ACN risk prediction among diabetic patients.

Seawater contains a variety of mineral ions, such as Na+, Mg2+, Ca2+, and K+. Although previous studies have shown that brackish water can promote ovarian development of the Chinese mitten crab (Eriocheir sinensis), it remains unclear whether these ions directly affect the ovarian development and vitellogenesis of E. sinensis. Therefore, this study was designed, using in vitro tissue incubation mediums with different concentrations of Na+ (280, 320, 360, and 400 mmol/L), Mg2+ (5, 10, and 15 mmol/L), Ca2+ (5, 10, 15, and 20 mmol/L), and K+ (5.5, 9, and 13 mmol/L), to investigate their effects on Vg/Vn contents and the expression of ovarian development-related genes in the hepatopancreas and ovaries of E. sinensis. The results showed that: (1) Different Na+ concentrations had no significant impact on vitellogenesis and the expression of ovarian development-related genes in both tissues, except for an enhancement of the esEcR2-mRNA levels in the hepatopancreas. (2) The Mg2+ (15 mmol/L) significantly increased the Vg/Vn content in hepatopancreas and ovary. However, the 10 mmol/L Mg2+ group decreased esVgR-mRNA levels and esEcR2-mRNA levels in the ovary compared to the control group. (3) Ca2+ (10 ∼ 15 mmol/L) significantly promoted Vg/Vn content and esVg-mRNA levels in both tissues, which also upregulated the expression of ovarian development-related genes (esERR, esEcR2, and esRXR). (4) Increasing K+ content significantly decreased the Vg/Vn content in hepatopancreas and ovaries. Furthermore, the K+ significantly reduced esRXR-mRNA levels in the ovaries but significantly increased esERR-mRNA levels in both tissues. In summary, under in vitro conditions, Na+ concentration had no significant effect on the vitellogenesis, while Ca2+ (10 ∼ 15 mmol/L) and Mg2+ (15 mmol/L) significantly promoted the vitellogenesis in the hepatopancreas and ovaries of E. sinensis. Additionally, Ca2+ significantly enhanced the expression of genes related to ovarian development, while K+ had a negative impact on the vitellogenesis.

In addressing the performance degradation issue of district cooling systems, although various evaluation methods exist, they either neglect design objectives or focus on independent equipment, overlooking the synergies between devices. Therefore, the study establishes a comprehensive performance assessment framework, encompassing efficiency, environmental impact, economic factors, and technological aspects. The Analytic Hierarchy Process (AHP) and Entropy Weight Method are employed to determine the comprehensive weights for each indicator. In a specific case study, the operational status of an existing district cooling system is assessed, considering collaborative interactions among equipment. A fault tree analysis is applied to scrutinize 13 potential events contributing to system inefficiency and their logical relationships with relevant parameter variations. Based on these findings, specific optimization measures, such as check valve replacement and adjustments to pump and fan frequencies, are recommended. The performance of the optimized system is then re-evaluated, demonstrating substantial improvements with comprehensive performance scores increasing from 18.3 to 27.8 and 29.5, respectively.

ABSTRACT: The avian influenza virus is infected through the mucosal route, thus mucosal barrier defense is very important. While the inactivated H9N2 vaccine cannot achieve sufficient mucosal immunity, adjuvants are needed to induce mucosal and systemic immunity to prevent poultry from H9N2 influenza virus infection. Our previous study found that polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles (AMP-ZnONPs) had immune-enhancing effects in vitro. This study aimed to evaluate the mucosal immune responses of oral whole-inactivated H9N2 virus (WIV)+AMP-ZnONPs and its impact on the animal challenge protection, and the corresponding changes of pulmonary metabolomics after the second immunization. The results showed that compared to the WIV, the combined treatment of WIV and AMP-ZnONPs significantly enhanced the HI titer, IgG and specific sIgA levels, the number of goblet cells and intestinal epithelial lymphocytes (iIELs) as well as the expression of J-chain, polymeric immunoglobulin receptor (pIgR), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β). In viral attack experiments, WIV combing with AMP-ZnONPs effectively reduced lung damage and viral titers in throat swabs. Interestingly, significant changes of both the IgA intestinal immune network and PPAR pathway could also be found in the WIV+AMP-ZnONPs group compared to the non-infected group. Taken together, these findings suggest that AMP-ZnONPs can serve as a potential mucosal vaccine adjuvant, thereby avoiding adverse stress and corresponding costs caused by vaccine injection.

Abstract Background and Aims Unhealthy diets were found to be the main contributor to the overweight problem among adolescents. In this study, we aim to identify the factors causing unhealthy eating habits in adolescents. Methods School‐aged children and adolescents participated in this cross‐sectional observational study with additional school and parental consent. A self‐administered survey was conducted by 30 primary schools and 25 secondary schools. Participants were asked about the frequency of consuming unhealthy food and the types of unhealthy food consumed. A descriptive analysis was performed to demonstrate the proportions of characteristics. The prevalence of the outcome among participants of various factors was also analyzed using separate binary regression models. Results A total of 4884 responses were collected. Among primary school students (grade 4, mean age: 10.06), people who (1) were actively gaining weight (aOR: 1.651, 95% CI 1.006–2.708, p = 0.047), (2) went to bed after 11 p.m. (aOR: 1.652, 95% CI 1.065–2.563, p = 0.025), (3) had more than 2 h of gaming (aOR: 2.833, 95% CI 1.913–4.195, p

Abstract Background Non‐Hodgkin lymphoma (NHL) accounts for 90% of all malignant lymphomas. This study aimed to evaluate the global incidence, mortality, associated risk factors, and temporal trends of NHL by sex, age, and country. Methods Data from 185 countries globally were used for analysis. NHL incidence and mortality were collected via the GLOBOCAN (2020), CI5 series I‐X, WHO mortality database, the Nordic Cancer Registries, and the SEER Program. The WHO Global Health Observatory provided country‐level, age‐standardized prevalence of lifestyle and metabolic risk factors. Trends were examined and reported based on average annual percentage change (AAPC) calculated using Joinpoint regression analysis. Incidence and AAPC are based on data for the last 10 years across countries. Results Globally, age‐standardized incidence and mortality rates for NHL were recorded at 5.8 and 2.6 per 100,000 individuals, respectively. At country‐level, NHL incidence was significantly associated with various factors, including HDI (Human Development Index), GDP per capita, prevalence of tobacco and alcohol consumption, sedentary lifestyle, obesity, hypertension, diabetes and hypercholesterolaemia. Rising trend in NHL incidence was observed, with the highest increase recorded in Estonia (AAPCmale = 4.15, AAPCfemale = 5.14), Belarus (AAPCfemale = 5.13), and Lithuania (AAPCfemale = 4.68). While overall NHL mortality has been decreasing, certain populations experienced increased mortality over the decade. In Thailand, AAPC for mortality was 31.28% for males and 30.26% for females. Estonia saw an AAPC of 6.46% for males, while Slovakia experienced an AAPC of 4.24% for females. Colombia's AAPC was 1.29% for males and 1.51% for females. Conclusions This study indicates a rising trend of NHL incidence over the past decade‐ particularly in developed countries, older males, and younger populations. Further research should investigate deeper insights into specific etiology and prognosis of NHL across subtypes, and potential contributors towards these epidemiologic trends.

IntroductionColorectal cancer (CRC) presents a substantial challenge characterized by unacceptably high mortality and morbidity, primarily attributed to delayed diagnosis and reliance on palliative care. The immune response of the host plays a pivotal role in carcinogenesis, with IL-38 emerging as a potential protective factor in CRC. However, the precise involvement of IL-38 among various leucocytes, its interactions with PD-1/PD-L1, and its impact on metastasis require further elucidation.ResultsOur investigation revealed a significant correlation between IL-38 expression and metastasis, particularly concerning survival and interactions among diverse leucocytes within draining lymph nodes. In the mesentery lymph nodes, we observed an inverse correlation between IL-38 expression and stages of lymph node invasions (TNM), invasion depth, distance, and differentiation. This aligns with an overall survival advantage associated with higher IL-38 expression in CRC patients’ nodes compared to lower levels, as well as elevated IL-38 expression on CD4+ or CD8+ cells. Notably, a distinct subset of patients characterized by IL-38high/PD-1low expression exhibited superior survival outcomes compared to other combinations.DiscussionOur findings demonstrate that IL-38 expression in colorectal regional nodes from CRC patients is inversely correlated with PD-1/PD-L1 but positively correlated with infiltrating CD4+ or CD8+ lymphocytes. The combined assessment of IL-38 and PD-1 expression in colorectal regional nodes emerges as a promising biomarker for predicting the prognosis of CRC.

IntroductionWound healing poses a clinical challenge in diabetes mellitus (DM) due to compromised host immunity. CD64, an IgG-binding Fcgr1 receptor, acts as a pro-inflammatory mediator. While its presence has been identified in various inflammatory diseases, its specific role in wound healing, especially in DM, remains unclear.ObjectivesWe aimed to investigate the involvement of CD64 in diabetic wound healing using a DM animal model with CD64 KO mice.MethodsFirst, we compared CD64 expression in chronic skin ulcers from human DM and non-DM skin. Then, we monitored wound healing in a DM mouse model over 10 days, with or without CD64 KO, using macroscopic and microscopic observations, as well as immunohistochemistry.ResultsCD64 expression was significantly upregulated (1.25-fold) in chronic ulcerative skin from DM patients compared to non-DM individuals. Clinical observations were consistent with animal model findings, showing a significant delay in wound healing, particularly by day 7, in CD64 KO mice compared to WT mice. Additionally, infiltrating CD163+ M2 macrophages in the wounds of DM mice decreased significantly compared to non-DM mice over time. Delayed wound healing in DM CD64 KO mice correlated with the presence of inflammatory mediators.ConclusionCD64 seems to play a crucial role in wound healing, especially in DM conditions, where it is associated with CD163+ M2 macrophage infiltration. These data suggest that CD64 relies on host immunity during the wound healing process. Such data may provide useful information for both basic scientists and clinicians to deal with diabetic chronic wound healing.

Abstract Background Worldwide, gastric cancer is a leading cause of cancer incidence and mortality. This study aims to devise and validate a scoring system based on readily available clinical data to predict the risk of gastric cancer in a large Chinese population. Methods We included a total of 6,209,697 subjects aged between 18 and 70 years who have received upper digestive endoscopy in Hong Kong from 1997 to 2018. A binary logistic regression model was constructed to examine the predictors of gastric cancer in a derivation cohort (n = 4,347,224), followed by model evaluation in a validation cohort (n = 1,862,473). The algorithm's discriminatory ability was evaluated as the area under the curve (AUC) of the mathematically constructed receiver operating characteristic (ROC) curve. Results Age, male gender, history of Helicobacter pylori infection, use of proton pump inhibitors, non‐use of aspirin, non‐steroidal anti‐inflammatory drugs (NSAIDs), and statins were significantly associated with gastric cancer. A scoring of ≤8 was designated as “average risk (AR)”. Scores at 9 or above were assigned as “high risk (HR)”. The prevalence of gastric cancer was 1.81% and 0.096%, respectively, for the HR and LR groups. The AUC for the risk score in the validation cohort was 0.834, implying an excellent fit of the model. Conclusions This study has validated a simple, accurate, and easy‐to‐use scoring algorithm which has a high discriminatory capability to predict gastric cancer. The score could be adopted to risk stratify subjects suspected as having gastric cancer, thus allowing prioritized upper digestive tract investigation.

Abstract Background Decomposition of plant biomass is vital for carbon cycling in terrestrial ecosystems. In waterlogged soils including paddy fields and natural wetlands, plant biomass degradation generates the largest natural source of global methane emission. However, the intricate process of plant biomass degradation by diverse soil microorganisms remains poorly characterized. Here we report a chemical and metagenomic investigation into the mechanism of straw decomposition in a paddy soil. Results The chemical analysis of 16-day soil microcosm incubation revealed that straw decomposition could be divided into two stages based on the dynamics of methane, short chain fatty acids, dissolved organic carbon and monosaccharides. Metagenomic analysis revealed that the relative abundance of glucoside hydrolase (GH) encoding genes for cellulose decomposition increased rapidly during the initial stage (3–7 days), while genes involved in hemicellulose decomposition increased in the later stage (7–16 days). The increase of cellulose GH genes in initial stage was derived mainly from Firmicutes while Bacteroidota contributed mostly to the later stage increase of hemicellulose GH genes. Flagella assembly genes were prevalent in Firmicutes but scarce in Bacteroidota. Wood–Ljungdahl pathway (WLP) was present in Firmicutes but not detected in Bacteroidota. Overall, Bacteroidota contained the largest proportion of total GHs and the highest number of carbohydrate active enzymes gene clusters in our paddy soil metagenomes. The strong capacity of the Bacteroidota phylum to degrade straw polymers was specifically attributed to Bacteroidales and Chitinophagales orders, the latter has not been previously recognized. Conclusions This study revealed a collaborating sequential contribution of microbial taxa and functional genes in the decomposition of straw residues in a paddy soil. Firmicutes with the property of mobility, WLP and cellulose decomposition could be mostly involved in the initial breakdown of straw polymers, while Bacteroidota became abundant and possibly responsible for the decomposition of hemicellulosic polymers during the later stage.

Abstract Background Fecal immunochemical test (FIT) is a commonly used initial test for colorectal cancer (CRC) screening. Parallel use of FIT with risk assessment (RA) could improve the detection of non‐bleeding lesions, but at the expense of compromising sensitivity. In this study, we evaluated the accuracy of FIT and/or RA in the Shanghai CRC screening program, and systematically reviewed the relevant evaluations worldwide. Methods RA and 2‐specimen FIT were used in parallel in the Shanghai screening program, followed by a colonoscopy among those with positive results. Sensitivity, specificity, detection rate of CRC, positive predictive value (PPV), and other measures with their 95% confident intervals were calculated for each type of tests and several assumed combined tests. We further searched PubMed, Embase, Web of Science, and Cochrane Library for relevant studies published in English up to January 5, 2022. Results By the end of 2019, a total of 1,901,360 participants of the screening program completed 3,045,108 tests, with 1,901,360 first‐time tests and 1,143,748 subsequent tests. Parallel use of RA and 2‐specimen FIT achieved a sensitivity of 0.78 (0.77–0.80), a specificity of 0.78 (0.78–0.78), PPV of 0.89% (0.86–0.92), and a detection rate of 1.99 (1.93–2.05) for CRC per 1000 among participants enrolled in the first screening round, and performed similarly among those who participated for several times. A meta‐analysis of 103 published observational studies demonstrated a higher sensitivity [0.76 (0.36, 0.94)] but a much lower specificity [0.59 (0.28, 0.85)] of parallel use of RA and FIT for detecting CRC in average‐risk populations than in our subjects. One‐specimen FIT, the most commonly used initial test, had a pooled specificity comparable to the Shanghai screening program (0.92 vs. 0.91), but a much higher pooled sensitivity (0.76 vs. 0.57). Conclusion Our results indicate the limitation of FIT only as an initial screening test for CRC in Chinese populations, and highlight the higher sensitivity of parallel use of RA and FIT. Attempts should be made to optimize RA to improve effectiveness of screening in the populations.

Abstract Background Lip, oral and pharyngeal cancers make up a small percentage of total cancer cases worldwide and have reported lower rates of cancer‐related deaths globally in 2020, but their 5‐year survival rate in either early or advanced stages is different. The study evaluated the global incidence, mortality, risk factors, and temporal trends by age, gender, and geographical locations of lip, oral cavity, and pharyngeal cancer. Methods Incidence and mortality rates were extracted from Cancer Incidence in Five Continents (CI5) volumes I‐XI, the Nordic Cancer Registries (NORDCAN), the Surveillance, Epidemiology, and End Results (SEER) Program, and the WHO IARC mortality database. Joinpoint regression was used to calculate the Average Annual Percentage Change to examine trends. Results The highest incidence rates were found in Melanesia and South‐Central Asia and mortality rates were 8.2 and 7.5. Risk factors associated with incidence and mortality included HDI, tobacco use, alcohol consumption, poor diet, and chronic health conditions such as hypertension. Increasing trends of incidence and mortality were observed in females from Malta; males aged 50 and above from the United Kingdom, and females aged 50 and above from Slovakia reporting the largest increase. Conclusions Although global incidence and mortality trends reported an overall decrease, significant increases were found for older age groups and female subjects. Incidence increase may be due to the growing prevalence of lifestyle, metabolic risk factors, and HPV infections, especially in developed countries.

Abstract Backgrounds Grazing prohibition and reduced grazing intensity, as two important “vegetation close‐to‐nature recovery” methods, have been suggested as economical and effective technologies for enhancing forage production. However, numerous studies have found that the yield of forage could be increased by removing or reducing grazing in a short time in some steady stage of alpine Kobresia meadows, but not in others. To reveal the mechanism behind this phenomenon, we proposed a series of experiments. Methods We monitored the plant and soil characteristics in the key steady stages of Kobresia meadows under reduced and prohibited grazing conditions in the same geographic and climatic environments in the northeastern Qinghai‐Tibet Plateau for 6 years. We estimated the relationships between the plant community and soil nutrients and obtained the following results. Results All measured variables were positively correlated with each other. The plant community structure had higher path coefficients to aboveground biomass, soil organic matter, total nitrogen, and nitrate nitrogen than to other factors. The plant community structure played an important role in response to grazing intensity. Different plant functional groups (PFGs) had different responses to grazing intensity, which led to plant community re‐establishment or re‐organization under different grazing intensities. Poaceae and Kobresia were more sensitive to grazing intensity than other PFGs, and the ratio of Kobresia biomass (including Kobresia humilis and Kobresia pygmaea) to the total biomass of Poaceae and Kobresia could be used as an indicator of regime shifts within plant communities. With Kobresia pygmaea as the dominant species, the prohibition of grazing was not an efficient approach to increase the yield in the steady stages because this treatment needed more time to recover aboveground biomass. If Poaceae is the dominant PFG, grazing should only be prohibited for 3 years in the steady stages because the aboveground biomass will decrease if grazing is prohibited for more than 3 years. Conclusions Therefore, the different steady stages of alpine meadows require different recovery methods to increase recovery efficiency and speed.

Sorting high-quality sperm with intact DNA, normal morphology, and active motility is crucial for clinically assisted reproductive technology, which influences the success of treatment and the health of offspring. Currently, microfluidic technology has been developed as a powerful platform for sperm sorting owing to its ability to manipulate fluid at the microscale and handle small samples. Specifically, microfluidic technology provides the necessary stimuli including fluid stimulus, chemical induction, and shape sift, which supports researchers in developing various sperm-sorting devices. According to the sorting principle, these devices can be divided into three categories: active sorting devices based on sperm rheological properties, passive sorting devices based on sperm physical properties, and external stimuli-induced sorting devices. Hence, we review a broad range of researches about sperm sorting with microfluidics and briefly present the properties of sperm and female reproductive tract to assist the design of microfluidic sperm sorting devices.

Abstract Background Health literacy is essential in the promotion of healthy lifestyle habits and chronic disease prevention. Objective To assess the health literacy level among Hong Kong adolescents; to evaluate the association between access of an online health information platform (GoSmart Channel) and health literacy level; and to examine the association between health literacy level and various unhealthy behaviours. Design This study recruited students from 10 local secondary schools in Hong Kong to assess the health literacy level among adolescents. Settings and Participants Participants were required to complete a self‐administered questionnaire on health behaviours and health literacy using the Health Literacy Measure for Adolescents (HELMA). Main Outcome Measure Data were analysed using descriptive statistics and multivariate regression modelling. Results A total of 777 responses were collected. Overall, most (74.4%) of the adolescents in Hong Kong have limited health literacy (HELMA score

This paper deals with the semigroup generation of anti-triangular operator matrices M with unbounded entries in Hilbert space. Based on the space decomposition, some necessary and sufficient conditions are given for M to generate contraction semigroups. In addition, the anti-triangular differential system, converted from the damping wave equation, is used to explain our work, and it is proved that the corresponding anti-triangular operator matrix satisfies the conditions and generates a contraction semigroup.

In this research, five groups of steel fiber reinforced cementitious composite (SFRCC) with different fiber volume content (0%, 0.5%, 1.0% 1.5%, and 2.0%) were designed to perform four-point flexural tests on beam specimens to study the effects of polar temperature (20, 0, −25, −50, −75, and −100°C) and fiber volume content on the flexural properties. The flexural toughness index and load holding capacity index were calculated based on the load–displacement curve, and the enhancement and toughening mechanisms of SFRCC by low temperature and steel fibers were analyzed in conjunction with experimental observations. The results of the proposed flexural toughness evaluation method show that the flexural toughness of SFRCC can significantly improve than that of ambient temperature when the temperature is lower than 0°C. With the decrease in temperature, the flexural property of SFRCC increases first and then decreases, and the temperature point of this transition is around −50–−75°C. The flexural property enhancement effect of 1.0% fiber volume content SFRCC is more significant in low temperatures according to the flexural toughness index and load holding capacity index. The conclusion can provide a reference for the application of SFRCC in cryogenic engineering, as well as a simple and quantifier evaluation method for flexural toughness is proposed.