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Background: Increasing attention to liver-bone crosstalk has spurred interest in targeted interventions for various forms of osteoporosis. Liver injury induced by different liver diseases can cause an imbalance in bone metabolism, indicating a novel regulatory paradigm between the liver and bone. However, the role of the liver-bone axis in both primary and secondary osteoporosis remains inadequately elucidated. Therefore, exploring the exact regulatory mechanisms of the liver-bone axis may offer innovative clinical approaches for treating diseases associated with the liver and bone. Methods: Here, we summarize the latest research on the liver-bone axis by searching the PubMed and Web of Science databases and discuss the possible mechanism of the liver-bone axis in different types of osteoporosis. The literature directly reporting the regulatory role of the liver-bone axis in different types of osteoporosis from the PubMed and Web of Science databases has been included in the discussion of this review (including but not limited to the definition of the liver-bone axis, clinical studies, and basic research). In addition, articles discussing changes in bone metabolism caused by different etiologies of liver injury have also been included in the discussion of this review (including but not limited to clinical studies and basic research). Results: Several endocrine factors (IGF-1, FGF21, hepcidin, vitamin D, osteocalcin, OPN, LCAT, Fetuin-A, PGs, BMP2/9, IL-1/6/17, and TNF-α) and key genes (SIRT2, ABCB4, ALDH2, TFR2, SPTBN1, ZNF687 and SREBP2) might be involved in the regulation of the liver-bone axis. In addition to the classic metabolic pathways involved in inflammation and oxidative stress, iron metabolism, cholesterol metabolism, lipid metabolism and immunometabolism mediated by the liver-bone axis require more research to elucidate the regulatory mechanisms involved in osteoporosis. Conclusion: During primary and secondary osteoporosis, the liver-bone axis is responsible for liver and bone homeostasis via several hepatokines and osteokines as well as biochemical signaling. Combining multiomics technology and data mining technology could further advance our understanding of the liver-bone axis, providing new clinical strategies for managing liver and bone-related diseases.The translational potential of this article is as follows: Abnormal metabolism in the liver could seriously affect the metabolic imbalance of bone. This review summarizes the indispensable role of several endocrine factors and biochemical signaling pathways involved in the liver-bone axis and emphasizes the important role of liver metabolic homeostasis in the pathogenesis of osteoporosis, which provides novel potential directions for the prevention, diagnosis, and treatment of liver and bone-related diseases.

Background: A milestone goal of the Healthy China Program (2019–2030) is to achieve 5-year cancer survival at 43.3% for all cancers combined by 2022. To assess the progress towards this target, we analyzed the updated survival for all cancers combined and 25 specific cancer types in China from 2019 to 2021. Methods: We conducted standardized data collection and quality control for cancer registries across 32 provincial-level regions in China, and included 6,410,940 newly diagnosed cancer patients from 281 cancer registries during 2008–2019, with follow-up data on vital status available until December 2021. We estimated the age-standardized 5-year relative survival overall and by site, age group, and period of diagnosis using the International Cancer Survival Standard Weights, and quantified the survival changes to assess the progress in cancer control. Results: In 2019–2021, the age-standardized 5-year relative survival for all cancers combined was 43.7% (95% confidence interval [CI], 43.6–43.7). The 5-year relative survival varied by cancer type, ranging from 8.5% (95% CI, 8.2–8.7) for pancreatic cancer to 92.9% (95% CI, 92.4–93.3) for thyroid cancer. Eight cancers had 5-year survival of over 60%, including cancers of the thyroid, breast, testis, bladder, prostate, kidney, uterus, and cervix. The 5-year relative survival was generally lower in males than in females. From 2008 to 2021, we observed significant survival improvements for cancers of the lung, prostate, bone, uterus, breast, cervix, nasopharynx, larynx, and bladder. The most significant improvement was in lung cancer. Conclusions: Progress in cancer control was evident in China. This highlights the importance of a comprehensive approach to control and prevent cancer.

Abstract Purpose To investigate the repeatability and reproducibility of a new method for centration analysis after small incision lenticule extraction (SMILE) and femtosecond laser-assisted LASIK (FS-LASIK). Methods This study comprised 29 eyes treated with SMILE and 24 with FS-LASIK. Decentrations were analyzed using tangential and pachymetry difference maps respectively. Both difference maps were generated with a Scheimpflug tomographer (Pentacam) for each eye, using preoperative and 3-month postoperative scans. Repeatability and reproducibility were evaluated by calculating the intraclass correlation coefficient (ICC), within-subject standard deviation (Sw), and coefficient of repeatability (CR). Results ICC, Sw, and CR showed good to excellent repeatability in locating the coordinates of the optical zone (OZ) center on both maps, with values ranging from 0.84 to 0.96, 0.03 to 0.13, and 0.08 to 0.36 respectively. The repeatability of the total decentration from the preoperative corneal vertex on the tangential curvature difference maps( $$d_{TC}$$ d TC ) and the pachymetry difference maps( $$d_{PC}$$ d PC ) were moderate and good, respectively. The ICC, Sw, and CR of $$d_{TC}$$ d TC were 0.63, 0.09, and 0.25, respectively. The ICC, Sw, and CR of $$d_{PC}$$ d PC were 0.77, 0.10, and 0.28, respectively. The reproducibility of the OZ center measurements was excellent for the tangential difference maps (ICC $$\ge 0.97$$ ≥ 0.97 ) and good for the pachymetry difference maps (ICC $$\ge$$ ≥ 0.86). ICC, Sw, and CR showed excellent reproducibility of $$d_{TC}$$ d TC , with values of 0.95, 0.03, and 0.08, respectively. ICC, Sw, and CR showed good reproducibility of $$d_{PC}$$ d PC , with values of 0.89, 0.06, and 0.17, respectively. Conclusion The centration analysis method used in this study showed good to excellent repeatability and reproducibility in locating the coordinates of the center of the OZ on the tangential and pachymetry difference maps.

Abstract Background Nursing interns encounter numerous professional pressures during clinical practice. Assessing adversity quotient levels and understanding the influencing factors are crucial for supporting students’ seamless transition to professional nurses. Purpose This study examined the adversity quotient subtypes of nursing interns and explored the relationships between adversity quotient and depression, coping styles, positive psychological capital, and professional adaptability. Methods This study employed a cross-sectional research design, involving a survey of 287 nursing interns in five general hospitals in Shanghai, China. Latent profile analysis was conducted to explore the subtypes of adversity quotient with the four domains as input variables. Multinomial logistic regression models and multiple correspondence analysis were used for subsequent data analysis. Results The average adversity quotient score of the nursing interns was 116.63 ± 32.22. A three-profile solution was obtained based on the latent profile analysis results. Three distinct subtypes emerged: a high-adversity quotient subtype (n = 50, 17.4%), a medium-adversity quotient subtype (n = 189, 65.9%), and a relatively low-adversity quotient subtype (n = 48, 16.7%). Multinomial logistic regression revealed that nursing interns in the high-adversity quotient subtype tended to be male, and had higher scores for positive psychological capital, negative coping style, and professional adaptability (p

Abstract Salivary proteins of insect herbivores can suppress plant defenses, but the roles of many remain elusive. One such protein is glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the saliva of the Recilia dorsalis (RdGAPDH) leafhopper, which is known to transmit rice gall dwarf virus (RGDV). Here we show that RdGAPDH was loaded into exosomes and released from salivary glands into the rice phloem through an exosomal pathway as R. dorsalis fed. In infected salivary glands of R. dorsalis, the virus upregulated the accumulation and subsequent release of exosomal RdGAPDH into the phloem. Once released, RdGAPDH consumed H2O2 in rice plants owing to its –SH groups reacting with H2O2. This reduction in H2O2 of rice plant facilitated R. dorsalis feeding and consequently promoted RGDV transmission. However, overoxidation of RdGAPDH could cause potential irreversible cytotoxicity to rice plants. In response, rice launched emergency defense by utilizing glutathione to S-glutathionylate the oxidization products of RdGAPDH. This process counteracts the potential cellular damage from RdGAPDH overoxidation, helping plant to maintain a normal phenotype. Additionally, salivary GAPDHs from other hemipterans vectors similarly suppressed H2O2 burst in plants. We propose a strategy by which plant viruses exploit insect salivary proteins to modulate plant defenses, thus enabling sustainable insect feeding and facilitating viral transmission.

Abstract Image denoising aims to remove noise from images and improve the quality of images. However, most image denoising methods heavily rely on pairwise training strategies and strict prior knowledge about image structure or noise distribution. While these methods exhibit significant results when handling known types of noise, their generalization performance diminishes when confronted with images containing unknown noise distributions. To address this issue, a two‐stage approach is introduced for enhancing the generalizability of image denoising. The proposed method does not rely on a large amount of paired data or prior knowledge of the noise type and level. Instead, it constructs a denoising pipeline with improved generalizability through an MLP‐based denoiser and generative diffusion prior. Specifically, in the first stage, an initial denoised image is predicted with a structure resembling that of the underlying clean image by introducing an MLP‐based U‐shaped denoising network aided by an implicit structural prior. In the second stage, the generalizability and quality of the denoiser are further enhanced by conditioning the result obtained from the previous stage on the pretrained denoising diffusion null‐space model. Extensive experimentation on multiple datasets demonstrates that this method exhibits better denoising performance and generalizability than other image denoising methods.

Abstract Background Plague is an acute infectious disease caused by the Yersinia pestis. Historically, it has been a major pandemic with high mortality rates, known as the “Black Death” in the 14th century, which resulted in millions of deaths in Europe. With increasing economic prosperity, more and more people are traveling to Xizang. However, this trend also hides significant safety hazards. Currently, there are few recent reports on plague, especially those with imaging manifestations available. In this study, we report the detailed clinical and radiological data of the patient with pneumonic plague in Xizang, China, in 2023. Case presentation We report a case of pneumonic plague in Xizang, which occurred in a herdsman living in an area where dead marmots were found. The patient presented with symptoms such as fever, hemoptysis, dyspnea and coma. Chest computed tomography (CT) scans showed multiple nodules distributed in the central regions of lung lobes, consolidation distributed in secondary pulmonary lobules, and had a gravity-dependent distribution pattern. These imaging findings were consistent with pulmonary hemorrhage and diffuse alveolar damage. Despite emergency treatment, the patient died within 48 h of admission. Through retrospective medical history investigation, laboratory examination and autopsy, the final diagnosis was confirmed as pneumonic plague. Conclusion Pneumonic plague is the most deadly infectious disease, and its pathological features mainly include damage to the alveoli, pulmonary hemorrhage, and pulmonary edema. Corresponding to CT, it manifests as acute and rapidly progressing pneumonia, alveolar damage, and pulmonary hemorrhage. The value of this article lies in the completeness and typicality of the imaging data, vivid hand-drawn illustrations of transmission pathways, and comprehensive literature review, all of which serve to enhance public understanding of plague and play an important warning role.

Abstract Objectives This study aimed to investigate the association of cystatin C, serum creatinine and sarcopenia index with cardiovascular and all-cause death in general population. Methods Data of participants from the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2004 were used and all participants were followed up regularly until December 31, 2019. Multivariable Cox analysis was used to investigate the association of cystatin C, serum creatinine and sarcopenia index with cardiovascular and all-cause death. Restricted cubic spline was conducted to evaluate the nonlinear association. Results A total of 9894 participants with a mean age of 45.64 years were enrolled and followed up for a mean duration of 15.62 ± 4.68 years. Approximately 50.3% were male and there were a total of 2681 all-cause deaths and 691 cardiovascular deaths recorded during the follow-up period. In final adjusted model, compared with the first quartile of cystatin C (

Abstract. Background:. Non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) have shown similar worsening epidemic patterns globally and shared various overlapping pathophysiological mechanisms. However, evidence on the relationship between NAFLD and IBD risk is lacking. We aimed to investigate the associations between long-term risk of incident IBD and NAFLD in a large prospective cohort. Methods:. Participants from the United Kingdom Biobank cohort (https://biobank.ndph.ox.ac.uk/) who were free of IBD and alcoholic liver disease at baseline were enrolled. Baseline non-alcoholic fatty liver degree was measured by the well-established fatty liver index (FLI). The outcomes of interest included incident IBD, ulcerative colitis (UC), and Crohn's disease (CD). Multivariable Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results:. Among 418,721 participants (mean FLI: 48.11 ± 30.11), 160,807 (38.40%) participants were diagnosed as NAFLD at baseline. During a median of 12.4 years' follow-up, 2346 incident IBD cases (1545 UC, 653 CD, and 148 IBD-unclassified) were identified. Due to limited events, those IBD-unclassified were combined in UC or CD when examining the associated risk of UC or CD, separately. Compared with the lowest quartile of FLI, the highest quartile showed a separately 36.00%, 25.00%, and 58.00% higher risk of incident IBD (HRQ4 vs. Q1 = 1.36, 95% CI: 1.19–1.55, Ptrend

Abstract Reactive oxygen species (ROS)-associated anticancer approaches usually suffer from two limitations, i.e., insufficient ROS level and short ROS half-life. Nevertheless, no report has synchronously addressed both concerns yet. Herein, a multichannel actions-enabled nanotherapeutic platform using hollow manganese dioxide (H-MnO2) carriers to load chlorin e6 (Ce6) sonosensitizer and CO donor (e.g., Mn2(CO)10) has been constructed to maximumly elevate ROS level and trigger cascade catalysis to produce CO. Therein, intratumoral H2O2 and ultrasound as endogenous and exogeneous triggers stimulate H-MnO2 and Ce6 to produce •OH and 1O2, respectively. The further cascade reaction between ROS and Mn2(CO)10 proceeds to release CO, converting short-lived ROS into long-lived CO. Contributed by them, such a maximumly-elevated ROS accumulation and long-lived CO release successfully suppresses the progression, recurrence and metastasis of lung cancer with a prolonged survival rate. More significantly, proteomic and genomic investigations uncover that the CO-induced activation of AKT signaling pathway, NRF-2 phosphorylation and HMOX-1 overexpression induce mitochondrial dysfunction to boost anti-tumor consequences. Thus, this cascade catalysis strategy can behave as a general means to enrich ROS and trigger CO release against refractory cancers. Graphic Abstract

Abstract Background The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. Methods We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. Results Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. Conclusion Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.

Abstract Exploring the promiscuity of native enzymes presents a promising strategy for expanding their synthetic applications, particularly for catalyzing challenging reactions in non-native contexts. In this study, we explore the promiscuous potential of old yellow enzymes (OYEs) to facilitate the Morita-Baylis-Hillman reaction (MBH reaction), leveraging substrate similarities between MBH reaction and reduction reaction. Using mass spectrometry and spectroscopic techniques, we confirm promiscuity of GkOYE in both MBH and reduction reactions. By blocking H- and H+ transfer pathways, we engineer GkOYE.8, which loses its reduction ability but enhances its MBH activity. The structural basis of MBH reaction catalyzed by GkOYE.8 is obtained through mutation studies and kinetic simulations. Furthermore, enantiocomplementary mutants GkOYE.11 and GkOYE.13 are obtained by directed evolution, exhibiting the ability to accept various aromatic aldehydes and alkenes as substrates. This study demonstrates the potential of leveraging substrate similarities to unlock enzyme functionalities, enabling the catalysis of new-to-nature reactions.

Abstract Background Genetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent–offspring trios and proband only analysis. Methods We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation. Results Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications. Conclusion CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.

Abstract This study presents the construction of an urban underground sensing system using distributed acoustic sensing (DAS) technology, which utilizes the existing optical fiber infrastructure around urban roads for communication. To address the challenges posed by the complexity and variability of DAS data in infrastructure monitoring environments such as urban roads, as well as the difficulty and poor effectiveness of raw data visualization, a novel method for visualizing DAS data is proposed. This method involves preprocessing the data through wavelet threshold denoising, combining it with the root-mean-square (RMS) energy index to generate a visualization, and applying the dynamic threshold method to remove and suppress abnormal data indicators. Finally, this paper tested the visualization performance to assess the effectiveness of the proposed method in improving urban road safety management. The study focused on three typical urban road safety risk events: vehicle driving, construction, and road subsurface cavity incidents. The results demonstrate the efficacy of the data visualization method, showing improved visualization of vehicle trajectory directions and numbers, construction segment behaviors, and approximate road subsurface cavity locations in the time domain compared to the original data.

The microbial genome remains a huge treasure trove for the discovery of diverse natural products. Saccharopolyspora erythraea NRRL23338, the industry producer of erythromycin, has a dozen of biosynthetic gene clusters whose encoding products are unidentified. Heterologous expression of one of the polyketide clusters pks7 in Streptomyces albus B4 chassis resulted in the characterization of its function responsible for synthesizing both 6-methylsalicyclic acid and 6-ethylsalicyclic acid. Meanwhile, two new 6-ethylsalicyclic acid ester derivatives were isolated as shunt metabolites. Their structures were identified by comprehensive analysis of MS and NMR experiments. Putative functions of genes within the pks7 BGC were also discussed.

Lake sediments record the environment during the lake sedimentation whose characteristics can infer environmental changes and human activities. In this study, the 210Pb chronologies and sedimentation rate of the sediment core in Honghu Lake were calculated by the Constant Rate of Supply model. The characteristics of the sedimentary environment were analysed by using physical and chemical indicators. Four stages were divided as follows: Stage A (before 1900): The relatively low sedimentation rate and nutrient content indicated an extremely stable sedimentary environment. Stage B (1900–1949): With the growth of population, the intensity of land use began to increase, with an averaged sedimentation rate of 0.252 g·cm−2·a−1. Stage C (1949–1980): The sedimentation rate and nutrient content increased markedly. The intense human activity has damaged the surrounding vegetation leading to soil erosion and accelerated sedimentation rate. With the deterioration of the lake water environment, the organic matter source was mainly the internal source represented by algae and bacteria. Stage D (1980–2011): Influenced by the difference in land use types along the coast, the sedimentation rate of HH-A (0.570 g·cm−2·a−1) is higher than that of HH-B (0.445 g·cm−2·a−1). The results are of significance to the management of rural lakes and reservoirs.

In this pilot study, diachronic semantic analysis is employed to probe the origin and semantic evolution of the classifier 架 (jià). The study has three objectives. Firstly, it intends to probe the emergence and development of the Chinese classifier 架 (jià). Secondly, it seeks to attest to the perspective of the fundamental role of human cognition and perception in the classifier language system, as indicated by Tai and Wang (1990). Finally, it suggests pragmatic classifiers teaching approaches in alignment with cognitive linguistic perceptions. The preliminary analysis of this study signifies that the classifier 架 (jià) is not an arbitrary linguistic device. Instead, its utilization throughout history reflects human categorization based on the perceptual property of the supporting framework of the referents. To enhance the efficiency of teaching Chinese classifiers and provide learners with a more natural and comprehensive acquisition mode, future studies on classifier acquisition are expected to align with the conceptual structure of the classifiers’ domains and the cognitive linguistic approach.

In the present study, a comparison of the dry reforming of a gas mixture containing methane, carbon dioxide and nitrogen without contaminants to a ruthenium-based Ru/Al2O3 catalyst was carried out in a microreactor for the first time. The influence of the contact time, temperature and composition of the feed on the conversion was exhaustively investigated. The optimal operating conditions were found to be a contact time of 80 milliseconds, a temperature of 700 °C and a CH4:CO2 ratio of 1. The assessment of diffusional limitations reveals that there is no resistance to mass transfer, which reveals the potential benefit of the determination of intrinsic reaction kinetics within a microreactor.

Abstract Background Disease can drastically impair common bean (Phaseolus vulgaris L.) production. Anthracnose, caused by the fungal pathogen Colletotrichum lindemuthianum (Sacc. and Magnus) Briosi and Cavara, is one of the diseases that are widespread and cause serious economic loss in common bean. Results Transcriptome analysis of the early response of common bean to anthracnose was performed using two resistant genotypes, Hongyundou and Honghuayundou, and one susceptible genotype, Jingdou. A total of 9,825 differentially expressed genes (DEGs) responding to pathogen infection and anthracnose resistance were identified by differential expression analysis. By using weighted gene coexpression network analysis (WGCNA), 2,051 DEGs were found to be associated with two resistance-related modules. Among them, 463 DEGs related to anthracnose resistance were considered resistance-related candidate genes. Nineteen candidate genes were coexpressed with three resistance genes, Phvul.001G243600, Phvul.001G243700 and Phvul.001G243800. To further identify resistance genes, 46 candidate genes were selected for experimental validation using salicylic acid (SA) and methyl jasmonate (MeJA). The results indicated that 38 candidate genes that responded to SA/MeJA treatment may be involved in anthracnose resistance in common bean. Conclusions This study identified 38 resistance-related candidate genes involved in the early response of common bean, and 19 resistance-related candidate genes were coexpressed with anthracnose resistance genes. This study identified putative resistance genes for further resistance genetic investigation and provides an important reference for anthracnose resistance breeding in common bean.

Abstract Background Relapsed or refractory classic Hodgkin lymphoma (RRcHL) associates with poor prognosis and heavy disease burden to patients. This study evaluated the cost-effectiveness of brentuximab vedotin (BV) in comparison to conventional chemotherapy in patients with RRcHL, from a Chinese healthcare perspective. Methods The lifetime cost and quality adjusted life years (QALYs) were estimated through a partitioned survival model with three health states (progression free, post progression, and death). Two cohorts for each BV arm and chemotherapy arm were built, representing patients with and without transplant after BV or chemotherapy, respectively. Clinical parameters were retrieved from BV trials and the literature. Resource utilization data were mainly collected from local expert surveys and cost parameters were reflecting local unit prices. Utility values were sourced from the literature. A discount rate of 5% was employed according to the Chinese guideline. A series of deterministic and probabilistic sensitivity analyses were conducted to evaluate the robustness and uncertainty associated with the model. Results Results of the base case analysis showed that the incremental cost-effectiveness ratio (ICER) for BV versus chemotherapy was $2,867 (¥19,774). The main model driver was the superior progression-free and overall survival benefits of BV. The ICERs were relatively robust in a series of sensitivity analyses, all under a conventional decision threshold (1 time of Chinese per capita GDP). With this conventional threshold, the probability of BV being cost-effective was 100%. Conclusions Brentuximab vedotin can be considered a cost-effective treatment versus conventional chemotherapy in treating relapsed or refractory classic Hodgkin lymphoma in China.

Objective: This study aims to estimate the overall in vitro activity of bedaquiline (BDQ) against clinical isolates of Mycobacterium abscessus complex (MABS) and M. avium complex (MAC), considering BDQ as a repurposed drug for non-tuberculous mycobacteria (NTM) infections. Methods: We conducted a systematic review of publications in PubMed/ MEDLINE, Web of Science, and Embase up to 15 April 2023. Studies were included if they followed the Clinical and Laboratory Standards Institute (CLSI) criteria for drug susceptibility testing (DST). Using a random effects model, we assessed the overall in vitro BDQ resistance rate in clinical isolates of MABS and MAC. Sources of heterogeneity were analysed using Cochran's Q and the I2 statistic. All analyses were performed using CMA V3.0. Results: A total of 24 publications (19 reports for MABS and 11 for MAC) were included. Using 1 µg/mL and 2 µg/mL as the breakpoint for BDQ resistance, the pooled rates of in vitro BDQ resistance in clinical isolates of MABS were found to be 1.8% (95% confidence interval [CI], 0.7–4.6%) and 1.7% (95% CI, 0.6–4.4%), respectively. In the case of MAC, the pooled rates were 1.7% (95% CI, 0.4–6.9%) and 1.6% (95% CI, 0.4–6.8%) for 1 µg/mL and 2 µg/mL, respectively. Conclusion: This study reports the prevalence of BDQ resistance in clinical isolates of MABS and MAC. The findings suggest that BDQ holds potential as a repurposed drug for treating MABS and MAC infections.

This paper considers two classical age-based replacement models within a discrete-time framework: a standard age replacement model and an opportunistic age replacement model. Specifically, our analysis incorporates the concept of replacement priority in situations where failure replacement and preventive replacement occur at a given age or opportunity. We explore two priority cases within each replacement model. First, we formulate optimal preventive replacement policies aimed at minimizing the associated expected cost rate in the age replacement model and the opportunistic age replacement model by the familiar renewal reward argument. Next, we extend the findings presented earlier to scenarios involving discounting. We develop formulations for the expected total discounted costs over an infinite time horizon and obtain optimal preventive replacement policies minimizing these total expected costs. Additionally, we explore unified models incorporating probabilistic priority. To provide practical insights, we present numerical illustrations using real failure data from pole air switches, comparing the performance of these optimal preventive policies.

Abstract Herpes simplex virus type 1 (HSV-1) infection of the eyes results in herpes simplex keratitis (HSK), which has led to vision loss and even blindness in patients. However, the rate of drug resistance in HSV is on the rise; therefore, new antiviral agents with sufficient safety profiles must be developed. At present, we assessed the anti-HSV-1 activity of 502 natural compounds and their ability to reduce the HSV-1-induced cytopathic effect. We chose harmol for further studies because it exhibited the highest antiviral activity. We found that harmol inhibited both HSV-1 F and HSV-1/153 (a clinical drug-resistant strain) replication, with an EC50 of 9.34 µM and 5.84 µM, respectively. Moreover, harmol reduced HSV-1 replication in corneal tissues and viral progeny production in tears, and also alleviated early corneal surface lesions related to HSK. For example, harmol treatment preserved corneal thickness and nerve density in HSK mice. Interestingly, harmol also showed a promising antiviral effect on HSV-1/153 induced HSK in mouse model. Furthermore, harmol combined with acyclovir (ACV) treatment showed a greater antiviral effect than either one alone in vitro. Therefore, harmol may be a promising therapeutic agent for managing HSK.

Abstract Objective Acute ischemic stroke (AIS) is a significant health burden in China, affecting a sizable portion of the population. Conventional pharmacological treatments frequently fall short of desirable outcomes. Therefore, exploring alternative therapies is crucial. Remote ischemic postconditioning (RIPostC) is a noninvasive and cost-effective adjunctive therapy. This study aimed to investigate the efficacy and safety of RIPostC as an adjunctive therapy for AIS to inform clinical practice. Methods A comprehensive search was conducted across the PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, Weipu (VIP), and China Biology Medicine disc (CBM) databases up to October 2023. All included studies underwent bias risk assessment using the Cochrane risk-of-bias assessment tool. The primary outcome measure was the National Institute of Health Stroke Scale (NIHSS), with secondary outcomes including the Barthel index (BI), D-dimer, C-reactive protein (CRP), fibrinogen (FIB), brain-derived neurotrophic factor (BDNF), modified Rankin scale (mRS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. The data were analyzed using fixed-effects and random-effects models in Review Manager, with mean differences (MDs) and 95% confidence intervals (CIs) calculated for each outcome. The grading of recommendations, assessment, development, and evaluations (GRADE) approach was used to evaluate the level of evidence for each outcome measure. Results This meta-analysis included 38 studies, encompassing 4334 patients. Compared with the control group, the RIPostC group had significantly lower NIHSS scores, serum CRP, D-dimer, IL-6, TNF-α, and FIB levels, and increased BDNF levels. Moreover, it improved the patient’s BI and mRS scores. According to the GRADE approach, the quality of evidence for mRS was deemed “moderate,” while the NIHSS, BI, and CRP were rated as “low” quality. IL-6, TNF-α, FIB, D-dimer, and BDNF received “very low” quality ratings. Conclusion The findings suggest that RIPostC activates endogenous protective mechanisms, providing benefits to patients with AIS.

Abstract The aim of this study was to determine the role of lncRNA PART1 and downstream FUT6 in tumorigenesis and progression of head and neck cancer (HNC). Bioinformatics analysis and qRT-PCR revealed that lncRNA PART1 was expressed at low levels in HNC patients. The proliferation, apoptosis, migration and flow cytometry results showed that low expression of lncRNA PART1 inhibited apoptosis and promoted HNC cell migration and proliferation. In addition, animal experiments have also shown that low expression of lncRNA PART1 can promote tumor growth. LncRNA PART1 overexpression promoted apoptosis and inhibited HNC cell migration and proliferation. Through bioinformatics analysis, FUT6 was found to be expressed at low levels in HNC and to be correlated with patient survival. Immunohistochemical and qRT-PCR results revealed that FUT6 was underexpressed in tumour tissues and HNC cells. Cell and animal experiments showed that overexpression of FUT6 could inhibit tumour proliferation and migration. Bioinformatics analysis revealed that lncRNA PART1 was positively correlated with FUT6. By qRT-PCR and western blot, we observed that after knockdown of lncRNA PART1, both the mRNA and protein expression levels of FUT6 were reduced. The above results indicated that lncRNA PART1 and FUT6 play an important role in HNC, and that lncRNA PART1 affected the development of tumor by downstream FUT6.

Abstract Background Marfan syndrome (MFS) is an autosomal dominant connective tissue disease with wide clinical heterogeneity, and mainly caused by pathogenic variants in fibrillin-1 (FBN1). Methods A Chinese 4-generation MFS pedigree with 16 family members was recruited and exome sequencing (ES) was performed in the proband. Transcript analysis (patient RNA and minigene assays) and in silico structural analysis were used to determine the pathogenicity of the variant. In addition, germline mosaicism in family member (Ι:1) was assessed using quantitative fluorescent polymerase chain reaction (QF-PCR) and short tandem repeat PCR (STR) analyses. Results Two cis-compound benign intronic variants of FBN1 (c.3464–4 A > G and c.3464-5G > A) were identified in the proband by ES. As a compound variant, c.3464-5_3464-4delGAinsAG was found to be pathogenic and co-segregated with MFS. RNA studies indicated that aberrant transcripts were found only in patients and mutant-type clones. The variant c.3464-5_3464-4delGAinsAG caused erroneous integration of a 3 bp sequence into intron 28 and resulted in the insertion of one amino acid in the protein sequence (p.Ile1154_Asp1155insAla). Structural analyses suggested that p.Ile1154_Asp1155insAla affected the protein’s secondary structure by interfering with one disulfide bond between Cys1140 and Cys1153 and causing the extension of an anti-parallel β sheet in the calcium-binding epidermal growth factor-like (cbEGF)13 domain. In addition, the asymptomatic family member Ι:1 was deduced to be a gonadal mosaic as assessed by inconsistent results of sequencing and STR analysis. Conclusions To our knowledge, FBN1 c.3464-5_3464-4delGAinsAG is the first identified pathogenic intronic indel variant affecting non-canonical splice sites in this gene. Our study reinforces the importance of assessing the pathogenic role of intronic variants at the mRNA level, with structural analysis, and the occurrence of mosaicism.

Abstract Background Extreme weather events like heatwaves and fine particulate matter (PM2.5) have a synergistic effect on mortality, but research on the synergistic effect of cold waves and PM2.5 on outpatient visits for respiratory disease, especially at high altitudes in climate change-sensitive areas, is lacking. Methods we collected time-series data on meteorological, air pollution, and outpatient visits for respiratory disease in Xining. We examined the associations between cold waves, PM2.5, and outpatient visits for respiratory disease using a time-stratified case-crossover approach and distributional lag nonlinear modeling. Our analysis also calculated the relative excess odds due to interaction (REOI), proportion attributable to interaction (AP), and synergy index (S). We additionally analyzed cold waves over time to verify climate change. Results Under different definitions of cold waves, the odds ratio for the correlation between cold waves and outpatient visits for respiratory disease ranged from 0.95 (95% CI: 0.86, 1.05) to 1.58 (1.47, 1.70). Exposure to PM2.5 was significantly associated with an increase in outpatient visits for respiratory disease. We found that cold waves can synergize with PM2.5 to increase outpatient visits for respiratory disease (REOI > 0, AP > 0, S > 1), decreasing with stricter definitions of cold waves and longer durations. Cold waves’ independent effect decreased over time, but their interaction effect persisted. From 8.1 to 21.8% of outpatient visits were due to cold waves and high-level PM2.5. People aged 0–14 and ≥ 65 were more susceptible to cold waves and PM2.5, with a significant interaction for those aged 15–64 and ≥ 65. Conclusion Our study fills the gap on how extreme weather and PM2.5 synergistically affect respiratory disease outpatient visits in high-altitude regions. The synergy of cold waves and PM2.5 increases outpatient visits for respiratory disease, especially in the elderly. Cold wave warnings and PM2.5 reduction have major public health benefits.

Abstract Nuclear receptors are ligand-activated transcription factors that can often be useful drug targets. Unfortunately, ligand promiscuity leads to two-thirds of receptors remaining clinically untargeted. PXR is a nuclear receptor that can be activated by diverse compounds to elevate metabolism, negatively impacting drug efficacy and safety. This presents a barrier to drug development because compounds designed to target other proteins must avoid PXR activation while retaining potency for the desired target. This problem could be avoided by using PXR antagonists, but these compounds are rare, and their molecular mechanisms remain unknown. Here, we report structurally related PXR-selective agonists and antagonists and their corresponding co-crystal structures to describe mechanisms of antagonism and selectivity. Structural and computational approaches show that antagonists induce PXR conformational changes incompatible with transcriptional coactivator recruitment. These results guide the design of compounds with predictable agonist/antagonist activities and bolster efforts to generate antagonists to prevent PXR activation interfering with other drugs.

Conventional Al–Ti–B and Al–Ti–C refiners fail to refine Al–Si casting alloys with high Si content due to the well-known “Si-poisoning” effect. Developing a novel grain refiner with superior grain refinement efficiency for Al–Si casting alloys is the research focus in recent years. In this work, a superior anti Si-poisoning α-Al grain refiner Al–2La–1B alloy with fine LaB6 particles was successfully fabricated via the aluminum melt reaction method. The microstructural evolution, grain refinement performance and refinement mechanisms of the Al–2La–1B alloy were comprehensively investigated based on the experiment results and first-principles calculations. The currently designed Al–2La–1B refiner presents supreme grain refinement efficiency on Al–Si casting alloys. The average grain size of Al–7Si alloy inoculated with 0.5% Al–2La–1B alloy can be refined to 67 ± 5 μm. The superior grain refinement performance can be attributed to the presence of fine LaB6 particles in the refiner. These particles are highly stable in Al–Si alloy melt and can directly act as the potent nucleation sites for α-Al due to the small lattice misfit and low interfacial energy. Moreover, the nucleation potency of the LaB6 particles will not be influenced by the solute Si element. Our work provides an effective strategy for designing a superior α-Al grain refiner for Al–Si casting alloys.

Huainan mining area is a typical high-gas area, with broken soft coal seam, low permeability, high gas content, and difficulty in extraction. In order to probe into the technical feasibility and gas control effect of the horizontal well for segmental hydraulic fracture in roof of coal seam in mining area, a three-dimensional in-situ stress test of coal seam was carried out using the stress relief method based on the analysis of the characteristics of the 13-1 coal reservoir, which was the main coal seam in the mining area. The results shown that, the three-dimensional stress field was mainly σh,max > σv > σh,min, which had sufficient conditions for the implementation of horizontal well with segmental hydraulic fracture in roof of coal seam. MFrac Suite software was used to simulate the fracture parameters of horizontal section at 1, 3 and 5 m from the coal seam. The maximum half-length of the fracture was 107.33 m and the minimum was 89.47 m, which was ideal for fracturing, indicating that the horizontal well with segmental hydraulic fracture had better geological adaptability and feasibility in Huainan mining area. Taking the CBM01 well, a horizontal well with L-type roof segmental fracturing in the 13-1 coal seam of Panyi coal mine, as the research object, the effect of gas control and management was comprehensively analyzed by means of borehole detection and numerical simulation. The results shown that, CBM01 well significantly reduced the gas pressure and gas content of coal seam after 415 d of extraction. The gas pressure at 50 and 65 m from the horizontal well decreased from 6.4 MPa to 2.6 and 2.7 MPa, respectively, by more than 55%. The gas content decreased from 13.5 m3/t to a maximum of 9.11 m3/t, a minimum of 6.92 m3/t, an average of 7.92 m3/t in an area of about 15-20 m on each side of the horizontal section, and decreased to less than 8 m3/t within about 10 m. Finally, a numerical simulation method was used to predict the gas production effect of CBM 01 well extracting for 10 a and the effect with gas control. The cumulative gas production of gas well was about 272.08×104 m3 in 10 a, and the gas content in the range of about 150 m on one side of the horizontal section was reduced to less than 8 m3/t, and the pressure was reduced to less than 3 MPa. Comprehensive research results shown that the horizontal well technology of segmental hydraulic fracturing in roof of coal seam had greater advantage and application effect in gas control and management in Huainan mining area.

Abstract Objective Amidst climate change, extensive research has centered on the health impacts of heatwaves, yet the consequences of cold spells, particularly in cooler, higher-altitude regions, remain under-explored. Methods Analyzing climatic data and non-accidental mortality in Xining, China’s second-highest provincial capital, from 2016 to 2020, this study defines cold spells as daily mean temperatures below the 10th, 7.5th, or 5th percentiles for 2–4 consecutive days. A time-stratified case-crossover approach and distributional lag nonlinear modeling were used to assess the link between cold spells and mortality, calculating attributable fractions (AFs) and numbers (ANs) of deaths. The study also examined the impact of cold spells over different periods and analyzed the value of a statistical life (VSL) loss in 2018, a year with frequent cold spells. Stratified analyses by sex, age, and education level were conducted. Results A significant association was found between cold spells and non-accidental mortality, with a relative risk of 1.548 (95% CI: 1.300, 1.845). The AF was 33.48%, with an AN of 9,196 deaths during the study’s cold period. A declining trend in mortality risk was observed from 2019–2020. The 2018 VSL was approximately 2.875 billion CNY, about 1.75% of Xining’s GDP. Higher risks were noted among males, individuals aged ≥ 65, and those with lower education levels. Conclusion The findings underscore the vulnerability and economic losses of high-altitude cities to cold spells. Implementing interventions such as improved heating, educational programs, and community support is vital for mitigating these adverse health effects.

Abstract Background Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role of the GSDMD/Drp1 signaling pathway in cognitive impairments in a mouse model of SAE. Methods C57BL/6 male mice were subjected to cecal ligation and puncture (CLP) to establish an animal model of SAE. In the interventional study, mice were treated with the GSDMD inhibitor necrosulfonamide (NSA) or the Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1). Surviving mice underwent behavioral tests, and hippocampal tissues were harvested for histological analysis and biochemical assays at corresponding time points. Haematoxylin-eosin staining and TUNEL assays were used to evaluate neuronal damage. Golgi staining was used to detect synaptic dendritic spine density. Additionally, transmission electron microscopy was performed to assess mitochondrial and synaptic morphology in the hippocampus. Local field potential recordings were conducted to detect network oscillations in the hippocampus. Results CLP induced the activation of GSDMD, an upregulation of Drp1, leading to associated mitochondrial impairment, neuroinflammation, as well as neuronal and synaptic damage. Consequently, these effects resulted in a reduction in neural oscillations in the hippocampus and significant learning and memory deficits in the mice. Notably, treatment with NSA or Mdivi-1 effectively prevented these GSDMD-mediated abnormalities. Conclusions Our data indicate that the GSDMD/Drp1 signaling pathway is involved in cognitive deficits in a mouse model of SAE. Inhibiting GSDMD or Drp1 emerges as a potential therapeutic strategy to alleviate the observed synaptic damages and network oscillations abnormalities in the hippocampus of SAE mice.

Abstract Bladder cancer (BLCA) is a common malignant tumor in urinary system all over the world. However, due to its high recurrence rate and complex causes, clinicians often have limited options for surgical and drug treatments. Recent researchs on the molecular mechanism of BLCA have reveals its biological progress and potential for early diagnosis. Serine hydroxymethyltransferase 1/2 (SHMT1/2) is a crucial enzyme in the one-carbon metabolism of tumor cells, and the expression levels of these isozymes have been found to be associated with the biological progression of various malignant tumors. However, the impact of SHMT1/2 on the biological progression of bladder cancer and its molecular regulation mechanism remain unclear. In this research utilizes BLCA clinical sample data, the TCGA database, and in vitro cell experiments to predict the expression levels of SHMT1/2 in BLCA. The findings indicate that SHMT1 remained unchanged, while SHMT2 expression is increased in BLCA, which was related to poor prognosis. Additionally, SHMT2 affects the growth, migration, and apoptosis of bladder cancer cells in vitro. It also influences the expression levels of E-cadherin and N-cadherin, ultimately impacting the malignant biological progression of bladder tumors. These results establish a correlation between SHMT2 and the malignant biological progression of BLCA, providing a theoretical basis for the early diagnosis and treatment of bladder cancer.

Abstract Objective This study aimed to assess the functions of cell division cycle protein 45 (CDC45) in Non-small cell lung cancer (NSCLC) cancer and its effects on stemness and metastasis. Methods Firstly, differentially expressed genes related to lung cancer metastasis and stemness were screened by differential analysis and lasso regression. Then, in vitro, experiments such as colony formation assay, scratch assay, and transwell assay were conducted to evaluate the impact of CDC45 knockdown on the proliferation and migration abilities of lung cancer cells. Western blotting was used to measure the expression levels of related proteins and investigate the regulation of CDC45 on the cell cycle. Finally, in vivo model with subcutaneous injection of lung cancer cells was performed to verify the effect of CDC45 on tumor growth. Results This study identified CDC45 as a key gene potentially influencing tumor stemness and lymph node metastasis. Knockdown of CDC45 not only suppressed the proliferation and migration abilities of lung cancer cells but also caused cell cycle arrest at the G2/M phase. Further analysis revealed a negative correlation between CDC45 and cell cycle-related proteins, stemness-related markers, and tumor mutations. Mouse experiments confirmed that CDC45 knockdown inhibited tumor growth. Conclusion As a novel regulator of stemness, CDC45 plays a role in regulating lung cancer cell proliferation, migration, and cell cycle. Therefore, CDC45 may serve as a potential target for lung cancer treatment and provide a reference for further mechanistic research and therapeutic development.

The osteochondral defects (OCDs) resulting from the treatment of giant cell tumors of bone (GCTB) often present two challenges for clinicians: tumor residue leading to local recurrence and non-healing of OCDs. Therefore, this study focuses on developing a double-layer PGPC-PGPH scaffold using shell-core structure nanofibers to achieve “spatiotemporal control” for treating OCDs caused by GCTB. It addresses two key challenges: eliminating tumor residue after local excision and stimulating osteochondral regeneration in non-healing OCD cases. With a shell layer of protoporphyrin IX (PpIX)/gelatin (GT) and inner cores containing chondroitin sulfate (CS)/poly(lactic-co-glycolic acid) (PLGA) or hydroxyapatite (HA)/PLGA, coaxial electrospinning technology was used to create shell-core structured PpIX/GT-CS/PLGA and PpIX/GT-HA/PLGA nanofibers. These nanofibers were shattered into nano-scaled short fibers, and then combined with polyethylene oxide and hyaluronan to formulate distinct 3D printing inks. The upper layer consists of PpIX/GT-CS/PLGA ink, and the lower layer is made from PpIX/GT-HA/PLGA ink, allowing for the creation of a double-layer PGPC-PGPH scaffold using 3D printing technique. After GCTB lesion removal, the PGPC-PGPH scaffold is surgically implanted into the OCDs. The sonosensitizer PpIX in the shell layer undergoes sonodynamic therapy to selectively damage GCTB tissue, effectively eradicating residual tumors. Subsequently, the thermal effect of sonodynamic therapy accelerates the shell degradation and release of CS and HA within the core layer, promoting stem cell differentiation into cartilage and bone tissues at the OCD site in the correct anatomical position. This innovative scaffold provides temporal control for anti-tumor treatment followed by tissue repair and spatial control for precise osteochondral regeneration.

IntroductionAs a widely used traditional Chinese medicine with hot property, aconite can significantly promote energy metabolism. However, it is unclear whether the gut microbiota and bile acids contribute to the energy metabolism-promoting properties of aconite. The aim of this experiment was to verify whether the energy metabolism-promoting effect of aconite aqueous extract (AA) is related to gut microbiota and bile acid (BA) metabolism.MethodsThe effect of AA on energy metabolism in rats was detected based on body weight, body temperature, and adipose tissue by HE staining and immunohistochemistry. In addition, 16S rRNA high-throughput sequencing and targeted metabolomics were used to detect changes in gut microbiota and BA concentrations, respectively. Antibiotic treatment and fecal microbiota transplantation (FMT) were also performed to demonstrate the importance of gut microbiota.ResultsRats given AA experienced an increase in body temperature, a decrease in body weight, and an increase in BAT (brown adipose tissue) activity and browning of WAT (white adipose tissue). Sequencing analysis and targeted metabolomics indicated that AA modulated gut microbiota and BA metabolism. The energy metabolism promotion of AA was found to be mediated by gut microbiota, as demonstrated through antibiotic treatment and FMT. Moreover, the energy metabolism-promoting effect of aconite is associated with the bile acid receptor TGR5 (Takeda G-protein-coupled receptor 5)-UCP1 (uncoupling protein 1) signaling pathway.ConclusionThe energy metabolism-promoting effect of aconite is associated with gut microbiota and bile acid receptor TGR5-UCP1 signaling.

Climate change and air pollution are major challenges facing the world today. Cold waves and air pollution significantly impact ischemic heart disease (IHD), but the extent of these effects at different altitudes remains unclear, especially their interactions. We collected daily meteorological, pollutant, and IHD hospitalization data from Xining and Xinxiang from 2016 to 2021. Using a time-stratified case-crossover approach, we fitted conditional Poisson regression models to assess the association between cold waves, PM2.5, and IHD hospitalizations and quantified their interactions. Additionally, we calculated the attributable fraction (AF) and attributable number (AN) of hospitalizations due to exposure to cold waves and medium to high-level PM2.5. We also performed stratified analyses by altitude, gender, and age. Both cold waves and PM2.5 were positively associated with IHD hospitalization rates in Xining and Xinxiang, but the differences between the two regions were not significant. The relative risk of cold waves was 1.15 (1.07, 1.24) in Xining and 1.16 (1.11, 1.21) in Xinxiang. In Xining, there was an interaction between cold waves and different levels of PM2.5. We estimated the attributable fraction due to the joint exposure of cold waves and PM2.5 to be 0.14–0.49 in Xining and 0.26–0.36 in Xinxiang. Older adults and males faced higher risks. This study highlights the importance of reducing PM2.5 exposure and optimizing extreme weather warning systems and suggests further exploration of the impacts of individual behaviors and regional characteristics on IHD.

In solar energy utilization, photocatalytic hydrogen production has been widely researched. To address issues such as low efficiency of photocatalysts, Cu-doped Zn0.5Cd0.5S composite photocatalysts were prepared using a hydrothermal method for photocatalytic hydrogen production. The Cu/Zn0.5Cd0.5S photocatalyst was characterized using XRD, XPS, SEM, TEM, UV–vis-DRS, fluorescence spectrophotometer, and electrochemical workstation. The results indicate that Cu doping alters the crystal and band structures of Zn0.5Cd0.5S. Hydrogen production experiments were conducted under xenon lamp irradiation, and at 45 °C, the highest hydrogen production rate was 2.72 and 1.63 times that of single Zn0.5Cd0.5S and Cu-doped Zn0.5Cd0.5S at room temperature (25 °C), respectively. Cu doping imparted a photothermal effect to the photocatalytic hydrogen production experiment, enhancing its efficiency.Cu doping captured electrons by replacing some Zn, constructing an internal electric field, forming defect energy levels, which hindered electron-hole recombination. Additionally, Cu ions acted as a plasma, inducing a plasma effect during hydrogen production, accelerating the rate of solar energy conversion to thermal energy, thus improving hydrogen production efficiency. This research not only provides a photocatalyst for photocatalytic hydrogen production but also utilizes it for photothermal synergistic catalysis.

Summary: Background: The government-led community-based Chinese National Integrated Demonstration Areas for the Prevention and Control of Noncommunicable Diseases programme was launched in 2011, but no rigorous impact evaluation has been conducted to date. We aimed to evaluate the causal effects of this programme on behavioural risk factors. Methods: We used data from the latest five waves of the China Chronic Disease and Risk Factor Surveillance. The primary outcome is a behavioural risk score combining current smoking, passive smoking, drinking in last month, regular exercise, body mass index, and waist circumference. We applied the synthetic difference-in-differences method and constructed synthetic controls from the non-demonstration areas with the outcome. The average treatment effects on the treated were estimated for overall effect and by short- (1–2), medium- (3–4), and long-term (6–7 years) effects. Findings: We identified 26 demonstration areas (N = 72,193) and 100 non-demonstration areas (N = 275,397). Participants in the demonstration areas had higher education and income levels and different pre-implementation trends than non-demonstration areas. Using synthetic controls instead of non-demonstration areas reduced these pre-implementation differences. Compared to the synthetic controls, declines were observed in current smoking (−1.78% [−4.51%, 0.96%]), passive smoking (−8.09% [−14.27%, −1.90%]), and drinking in last month (−4.04% [−8.75%, 0.67%]) but not in the other factors. Behavioural risk score declined by 1.05 short-term (95% CI: −1.84, −0.26), 1.15 medium-term (95% CI: −2.08, −0.22), 2.82 long-term (95% CI: −4.79, −0.85), and 1.54 overall (95% CI: −2.51, −0.56). Interpretation: The programme improved behavioural risk scores, primarily through reductions in the prevalence of smoking and drinking, and the effect was long-lasting. Our findings provided empirical evidence for utilizing an integrated prevention and control strategy to fight against NCD in China and other countries facing similar challenges. Funding: The China National Key Research and Development Program (2018YFC1315304 and 2017YFC1310902); National Natural Science Foundation of China (81872721).

T-2 toxin, a mycotoxin found in foods and feeds, poses a threat to female reproductive health in both humans and animals. LncRNA CUFF.253988.1 (CUFF.253988.1), highly expressed in pigs, has an undisclosed regulatory role. This study aimed to establish a model of T-2 toxin-induced ovarian injury in sows, both in vivo and in vitro, and to explore the regulatory role and potential mechanisms of CUFF.253988.1. The results showed that feeding T-2 toxin-contaminated feed (1 mg/kg) induced ovarian follicle atresia and mitochondrial structural damage, accompanied by a significant upregulation of CUFF.253988.1 expression in the ovaries. Additionally, T-2 toxin inhibited the SIRT3/PGC1-α pathway associated with mitochondrial function. Moreover, T-2 toxin induced cell apoptosis by upregulating the expression of Cyt c, Bax, cleaved-caspase-9, and cleaved-caspase-3 proteins. In T-2 toxin-induced injury to the ovarian granulosa AVG-16 cells at concentrations of 10, 40 and 160 nM, not only were the previously mentioned effects observed, but also a decrease in mitochondrial membrane potential, ATP content, and an elevation in ROS levels. However, downregulating CUFF.253988.1 reversed T-2 toxin's inhibition of the SIRT3/PGC1-α pathway, alleviating mitochondrial dysfunction and reducing cell apoptosis. Notably, this may be attributed to the inhibition of T-2 toxin-induced enrichment of CUFF.253988.1 in mitochondria. In conclusion, CUFF.253988.1 plays a pivotal role in T-2 toxin-induced ovarian damage, operating through the inhibition of the SIRT3/PGC1-α pathway and promotion of cell apoptosis.

Background: Early diagnosis of primary Sjögren’s syndrome (pSS) remains difficult due to its insidious onset. Objectives: To identify whether meibomian gland dropout (MGD) is a sensitive and noninvasive predictor of pSS by studying its association with histopathology in labial salivary gland biopsy in patients with clinically suspected pSS. Design: Prospective, randomized, multicenter, comparative effectiveness study. Methods: The study was conducted from July 2022 to July 2023. In all, 56 eligible participants with clinically suspected pSS were recruited from three combined ophthalmology medicine/rheumatology SS clinics. All participants with suspected pSS were evaluated and diagnosed by ophthalmology and rheumatology consultants and underwent infrared imaging of the meibomian glands using Keratograph 5M and histopathological evaluation of labial salivary gland biopsies. The length, width, and tortuosity of the meibomian glands were measured; the dropout rate in the nasal, temporal, and total eyelids was analyzed; and the dropout score was calculated using meibography grading scales. Results: Among the 56 participants, 34 were identified with pSS, and 22 were diagnosed with non-SS dry eye (NSSDE) and served as the control group. We recorded significant differences in the temporal and total MGD rates of the upper eyelids between the pSS and NSSDE groups (all p

BackgroundCurrently, evidence regarding the causal relationship between primary immunodeficiency-related genes and varicella-zoster virus reactivation syndrome is limited and inconsistent. Therefore, this study employs Mendelian randomization (MR) methodology to investigate the causal relationship between the two.MethodsThis study selected 110 single-nucleotide polymorphisms (SNPs) of primary immunodeficiency-related genes as instrumental variables (IVs). Genetic associations of primary immunodeficiency-related genes were derived from recent genome-wide association studies (GWAS) data on human plasma protein levels and circulating immune cells. Data on genes associated with varicella-zoster virus reactivation syndrome were obtained from the GWAS Catalog and FINNGEN database, primarily analyzed using inverse variance weighting (IVW) and sensitivity analysis.ResultsThrough MR analysis, we identified 9 primary immunodeficiency-related genes causally associated with herpes zoster and its subsequent neuralgia; determined causal associations of 20 primary immunodeficiency-related genes with three vascular lesions (stroke, cerebral aneurysm, giant cell arteritis); revealed causal associations of 10 primary immunodeficiency-related genes with two ocular diseases (retinopathy, keratitis); additionally, three primary immunodeficiency-related genes each were associated with encephalitis, cranial nerve palsy, and gastrointestinal infections.ConclusionsThis study discovers a certain association between primary immunodeficiency-related genes and varicella-zoster virus reactivation syndrome, yet further investigations are warranted to explore the specific mechanisms underlying these connections.

Background Gastric intestinal metaplasia(GIM) is an independent risk factor for GC, however, its pathogenesis is still unclear. Ferroptosis is a new type of programmed cell death, which may be involved in the process of GIM. The purpose of this study was to analyze the expression of ferroptosis-related genes (FRGs) in GIM tissues and to explore the relationship between ferroptosis and GIM. Method The results of GIM tissue full transcriptome sequencing were downloaded from Gene Expression Omnibus(GEO) database. R software (V4.2.0) and R packages were used for screening and enrichment analysis of differentially expressed genes(DEGs). The key genes were screened by least absolute shrinkage and selection operator(LASSO) and support vector machine-recursive feature elimination(SVM-RFE) algorithm. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of key genes in GIM. Clinical samples were used to further validate hub genes. Results A total of 12 differentially expressed ferroptosis-related genes (DEFRGs) were identified. Using two machine learning algorithms, GOT1, ALDH3A2, ACSF2 and SESN2 were identified as key genes. The area under ROC curve (AUC) of GOT1, ALDH3A2, ACSF2 and SESN2 in the training set were 0.906, 0.955, 0.899 and 0.962 respectively, and the AUC in the verification set were 0.776, 0.676, 0.773 and 0.880, respectively. Clinical samples verified the differential expression of GOT1, ACSF2, and SESN2 in GIM. Conclusion We found that there was a significant correlation between ferroptosis and GIM. GOT1, ACSF2 and SESN2 can be used as diagnostic markers to effectively identify GIM.

Alzheimer's disease is a neurodegenerative disease induced by multiple interconnected mechanisms. Peptide drug candidates with multi-modal efficacy generated from fusion strategy are suitable for addressing multi-facet pathology. However, clinical translation of peptide drugs is greatly hampered by their low permeability into brain. Herein, a hybrid peptide HNSS is generated by merging two therapeutic peptides (SS31 and S-14 G Humanin (HNG)), using a different approach from the classical shuttle-therapeutic peptide conjugate design. HNSS demonstrated increased bio-permeability, with a 2-fold improvement in brain distribution over HNG, thanks to its structure mimicking the design of signal peptide-derived cell-penetrating peptides. HNSS efficiently alleviated mitochondrial dysfunction through the combined effects of mitochondrial targeting, ROS scavenging and p-STAT3 activation. Meanwhile, HNSS with increased Aβ affinity greatly inhibited Aβ oligomerization/fibrillation, and interrupted Aβ interaction with neuron/microglia by reducing neuronal mitochondrial Aβ deposition and promoting microglial phagocytosis of Aβ. In 3× Tg-AD transgenic mice, HNSS treatment efficiently inhibited brain neuron loss and improved the cognitive performance. This work validates the rational fusion design-based strategy for bio-permeability improvement and efficacy amplification, providing a paradigm for developing therapeutic peptide candidates against neurodegenerative disease.

Basin water pollution caused by livestock, poultry and fish breeding is still a serious problem for remote villages, however, reliable regional breeding management programming have the potentials to improve pollution status. This paper focuses on the optimal model design and water quality analysis of the livestock, poultry and fish breeding system for Wenchang City, China. Methods of multi-objective programming (MOP), interval parameter programming (IPP), fuzzy-stochastic parameter programming (FSPP), and chance constrained programming (CCP) were incorporated into the developed model to tackle multi uncertainties described by interval values, probability distributions, fuzzy membership function. Based on the estimation of local breeding potential and current situation of surface water section, a multi-objective mixed fuzzy-stochastic nonlinear programming optimization model is presented with one-dimensional water quality model. In order to evaluate the environmental carrying capacity of livestock, poultry and fishery manure, predict its development trend and investigate the implementation effect of different emission reduction policies, this paper designs quantization system of the urban water environmental carrying capacity for the model. The results indicated that the water environment pollutant absorption capacity and carrying capacity of Wenchang city have approached the limit especially the towns in the northeast of City which limited the overall development space of the City. The modeling results are valuable for supporting the adjustment of the existing livestock, poultry and fish breeding schemes within a complicated system benefit and surface water quality situation under uncertainty.

ObjectivesTo construct deep learning-assisted diagnosis models based on automatic segmentation of ultrasound images to facilitate radiologists in differentiating benign and malignant parotid tumors.MethodsA total of 582 patients histopathologically diagnosed with PGTs were retrospectively recruited from 4 centers, and their data were collected for analysis. The radiomics features of six deep learning models (ResNet18, Inception_v3 etc) were analyzed based on the ultrasound images that were obtained under the best automatic segmentation model (Deeplabv3, UNet++, and UNet). The performance of three physicians was compared when the optimal model was used and not. The Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI) were utilized to evaluate the clinical benefit of the optimal model.ResultsThe Deeplabv3 model performed optimally in terms of automatic segmentation. The ResNet18 deep learning model had the best prediction performance, with an area under the receiver-operating characteristic curve of 0.808 (0.694−0.923), 0.809 (0.712−0.906), and 0.812 (0.680−0.944) in the internal test set and external test sets 1 and 2, respectively. Meanwhile, the optimal model-assisted clinical and overall benefits were markedly enhanced for two out of three radiologists (in internal validation set, NRI: 0.259 and 0.213 [p = 0.002 and 0.017], IDI: 0.284 and 0.201 [p = 0.005 and 0.043], respectively; in external test set 1, NRI: 0.183 and 0.161 [p = 0.019 and 0.008], IDI: 0.205 and 0.184 [p = 0.031 and 0.045], respectively; in external test set 2, NRI: 0.297 and 0.297 [p = 0.038 and 0.047], IDI: 0.332 and 0.294 [p = 0.031 and 0.041], respectively).ConclusionsThe deep learning model constructed for automatic segmentation of ultrasound images can improve the diagnostic performance of radiologists for PGTs.

BackgroundThe rehabilitation of children with disabilities has received considerable attention from the United Nations. However, the state of rehabilitation services for children with disabilities worldwide remains far from optimistic, even in economically affluent middle- and high-income countries. ObjectiveThis scoping review aimed to identify the rehabilitation needs of children with disabilities and their barriers to rehabilitation services in middle- and high-income countries. MethodsA systematic search was conducted using MEDLINE and Web of Science for papers published from January 2013 to December 2023. Studies were included if they were peer-reviewed, full-text articles related to children with disabilities, reporting on their access to rehabilitation services, and conducted in countries classified by the World Bank 2023 as middle- and high-income economies. Exclusion criteria included duplicates, unavailable full texts, and studies without distinct outcomes. A total of 27 studies were selected following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, focusing on children, their families, or service providers. ResultsThe suitability, availability, and affordability of rehabilitation services were identified as the major needs and barriers for children with disabilities in middle- and high-income countries. This included communication barriers, a need for more personnel and facilities, and the stagnation and inadequacy of economic subsidies. ConclusionsMiddle- and high-income countries have relatively well-established rehabilitation infrastructure and support systems. They are nevertheless insufficient for meeting the needs of children with disabilities. More attention should be paid to these issues to improve the well-being of children with disabilities. The data provided by this review can help raise awareness of rehabilitation needs and barriers at the policy level.

Background: The incidence of colorectal neuroendocrine tumors (NETs) is increasing, causing a social burden. At present, there is no specific prognostic model for colorectal NETs. Thus, an accurate model is needed to predict the prognosis of patients with colorectal NETs. Aim: We aimed to create a new nomogram to predict the prognosis of patients with colorectal NETs. Furthermore, we compared nomogram we established and the 8th edition of the AJCC TNM staging system in terms of prediction ability and accuracy. Methods: A total of 3353 patients with colorectal NETs were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier analyses were used to assess overall survival (OS) and cancer-specific survival (CSS). Additionally, LASSO regression was used to select variables for constructing the nomogram. Furthermore, the C-index and time-dependent receiver operating characteristic (tdROC) curve were used to evaluate the nomogram. Decision curve analysis (DCA) was performed to compare the clinical utility of the nomogram with that of the TNM system. An external validation cohort (N = 61) was established to evaluate the nomogram's prediction accuracy. Results: A total of 9 factors (age, sex, marital status, tumor size, T stage, M stage, N stage, grade, and surgery) were selected based on the results of LASSO analysis. The C-indexes of the nomogram in the training and validation sets were 0.807 and 0.775, respectively, which indicated that the nomogram had better prediction accuracy than TNM staging (C-index = 0.700 in the training set and 0.652 in the validation set). The C-index of the nomogram in the external validation cohort was 0.954, indicating that the nomogram had satisfactory prediction accuracy. The results of DCA revealed that the survival nomogram possessed greater utility in clinical practice. Conclusion: We determined the OS and CSS of patients with colorectal NETs and developed a robust and clinically useful survival nomogram.

Achieving carbon neutrality through increasing carbon sinks is a crucial strategy for reaching long-term climate objectives. During rapid urbanization, the degradation of vegetation structure and quantity in fragmented patches leads to the reduction of the carbon sink capacity. Establishing the well-design ecological spatial network is crucial for improving the carbon sink capacity. This study focuses on enhancing the carbon sink capacity in the Wuhan Metropolitan Area (WMA) through a four-step approach–identification, construction, assessment, and optimization–to improve the ecological spatial structure of carbon sink patches and increase carbon sink capacity. The results show that we initially built 27 carbon sink patches and 52 networks, prioritizing 15 core networks. Due to the low connectivity between the Western and other regions, we added 18 steppingstones and 12 networks to enhance overall connectivity and stability of spatial network. Verification shows that our scheme benefits the connectivity and stability of whole ecological network of WMA, and increases the total carbon sink by 11.17 Mt CO2. This research enriches methods for increasing carbon sinks in urban areas and provides theoretical support for achieving carbon neutrality.