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Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality, it ranks as the second most common cause of cancer deaths in China. Most HCC patients are first diagnosed at an advanced stage. In recent years, targeted therapy combined with immunotherapy has become the preferred regimen for systemic treatment of intermediate-advanced HCC, while targeted therapy combined with immunotherapy plus local treatment could further improve the efficacy in many clinical studies. To better guide the clinical treatment for effective and safe combination therapy, our interdisciplinary panel on the treatment of intermediate-advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists, radiologists, interventional radiologists and traditional Chinese medicine physicians have formulated this consensus based on current clinical studies and clinical medication experience for reference. The consensus contained 15 recommendations, including the applicable population and management, local treatment selection, conversion strategy, treatment strategy after tumor progression and management of common adverse reactions.

Two new species of Agaricales, Deconica flavum and Entocybe roseoalbus, are described from Mount Tianmu, Zhejiang Province, Eastern China. Two new species are distinct and monophyletic based on morphology and phylogenetic analyses. Deconica flavum differs from other Deconica species in that the pileus is brow shallow in the center and stipe with yellowish white fibrils, scatted on litter under coniferous and broad-leaved mixed forest at 1162 m. Entocybe roseoalbus is distinguished from other species of Entocybe by nearly blue pileus and pinkish-white stipe, scatted on humus in similar forest conditions at 1025 m. The differences are discussed between the two new taxa and their similar species morphologically, and related species phylogenetically.

Abstract To evaluate the dosimetric benefits and clinical feasibility of deep inspiratory breath-hold (DIBH) combined with volumetric modulated arc therapy (VMAT) in left-sided postmastectomy radiotherapy (PMRT). Eligible patients with left-sided breast cancer undergoing DIBH-based PMRT were prospectively included. Chest wall, supra/infraclavicular fossa, and/or internal mammary node irradiation (IMNI) were planned with a prescription dose of 43.5 Gy in 15 fractions. VMAT plans were designed on free breathing (FB)—and DIBH-CT to compare dosimetric parameters in heart, left anterior descending artery (LAD) and lung. Cone-beam computed tomography (CBCT) was performed before and after treatment to evaluate inter- and intra-fractional setup errors. Heart position and dose variations during treatment were estimated by fusing CBCT with DIBH-CT scans.Twenty patients were included with 10 receiving IMNI. In total, 193 pre-treatment and 39 pairs pre- and post-treatment CBCT scans were analyzed. The Dmean, Dmax, and V5−40 of the heart, LAD, and left lung were significantly lower in DIBH than FB (p

Abstract Background Digital health literacy (DHL) is pivotal for individuals to access trustworthy health information and make informed decisions, closely intertwined with health behaviors and psychological resilience—these factors collectively shape an individual’s approach to health management. Despite extensive research on digital health literacy in broader populations, the specific dynamics of digital health literacy in relation to health behaviors and psychological resilience among undergraduate nursing students in China remain understudied, highlighting a gap that this research endeavors to address. This study aims to assess the levels of digital health literacy among undergraduate nursing students in China, and to explore its association with health lifestyles and psychological resilience, which are considered influential factors. Methods Employing a descriptive cross-sectional research design, eligible Chinese nursing undergraduates were surveyed from June to October 2023. This study recruited a total of 418 undergraduate nursing students. After excluding 11 students on leave, 407 students participated in questionnaire completion and submission. The College Students’ Digital Health Literacy Scale, Healthy Lifestyle Assessment Scale and The Psychological Resilience Scale were used in this study. Results The mean scores for digital health literacy, health lifestyles, and psychological resilience were 74.78 ± 8.44, 127.14 ± 11.22, and 79.21 ± 11.02, respectively. Pearson correlation analysis results indicated that the correlations between digital health literacy and both health lifestyles (r = 0.707, P

Based on the daily precipitation data of 2, 424 stations and conventional weather chart data in mainland China in 2021, a statistical analysis of the main heavy rain weather processes from April to October of that year was conducted. The main influencing systems and precipitation situations were outlined, and a comparative analysis of the number of heavy rain days and major heavy rain events from 2008 to 2021 from April to October was performed. The results show that from April to October 2021, China experienced a total of 199 heavy rain days and 32 major heavy rain events. The number of heavy rain days was 10 days more than the average for the previous 13 years (2008-2020), while the number of major heavy rain events remained the same as the average for the previous 13 years. Among them, there were 7 occurrences in July, 6 in May and August each, 5 in June, 4 in September, and 3 in October, with 1 occurrence in April. Among the 32 major heavy rain events, 5 were caused by the landing or influence of tropical cyclones. The northern heavy rain from July 18th to 22nd, including the "7.20" extreme heavy rain in Zhengzhou, was the most widely affected and economically damaging major heavy rain event, with Zhengzhou in Henan Province recording the country's largest daily precipitation of 552.5 mm on July 20th of that year. The maximum accumulated rainfall for a single event in the year reached 820 mm, also occurring in Zhengzhou, Henan Province (July 18th to 22nd) and was caused by the joint influence of a trough, shear line, and warm and humid airflow.

Abstract Recent years have witnessed an increasing number of manipulated online reviews in e-commerce platforms. Previous research has provided substantial evidence that vendor manipulation of online reviews has a significant negative impact on the stakeholders involved in the e-commerce business. Many platforms take various governance measures to filter manipulated reviews. Nevertheless, the effectiveness of these measures still remains unknown to a large extent. To bridge this research gap, this paper investigates the effect of differentiated platform governance, including defined as interventions to counterattack manipulation intensity, manipulation duration, and perceived quality manipulated, on the probability of future review manipulation. We develop a game theoretical model that incorporates the strategic interactions between the platform and vendors, which yield several testable hypotheses. We then conduct an empirical analysis of platform governance and review manipulation by using the review manipulation data collected from Amazon.com. Results of the analytical model and empirical analysis show that platform governance that targets manipulation intensity and manipulation duration can both effectively mitigate review manipulation probability. On the contrary, platform governance to counterattack manipulating perceived product quality exhibits an inverted U-shape relationship with review manipulation probability. This study provides novel insights into how to better mitigate online review manipulation for e-commerce platforms.

Abstract Background This study aimed to screen southern and southwestern Chinese individuals using expanded carrier screening (ECS), which explores the carrier status of recessively inherited diseases in southern and southwestern China, evaluates the clinical effectiveness of ECS application, and helps recognize high-risk fetuses that may have genetic disorders early in pregnancy, to provide better reproductive guidance. Methods ECS for 220 diseases based on next-generation sequencing was performed on 3024 southern and southwestern Chinese individuals (1512 couples). Carrier status was analyzed; genes and loci with high frequencies of variants and on high-risk couples (ARCs) were focused to evaluate the clinical utility of our ECS technology and provide them precise fertility guidance. Results In total, Pathogenic/likely pathogenic(P/LP) variants were found in 1885 individuals, so the carrier frequency was 62.3%, and 23.2% of the individuals were carriers of multiple diseases. furthermore, 2837 variants were detected, and the average number of P/LP variants carried per subject was 0.938. Additionally, 128 ARCs carried P/LP variants of the same gene, and the theoretical incidence rate in their offspring was as high as 2.12%. Conclusion This study validated the application of our ECS technique for carrier screening in southern China, identifying carrier status and providing accurate carrier frequencies for hundreds of genetic diseases.

Abstract Background Exposure to air pollution contributes to cardiovascular disease-related deaths and morbidity, including stroke. However, few studies have examined the global stroke burden linked to air pollution. This study aimed to evaluate the global stroke morbidity and mortality associated with air pollution from 1990 to 2021. Method With the Global Burden of Disease Study (GBD) 2021, the numbers, and age-standardized rates (ASRs) of deaths and disability-adjusted life years (DALYs) for air pollution-related stroke were reported globally. Further subgroup analyses were conducted by age, sex, region and country, and stroke subtypes. A linear regression model explored global temporal trends and a cluster analysis examined temporal trends across GBD regions. To predict trends until 2040, the age-period-cohort (APC) model and the Bayesian age-period-cohort (BAPC) model were applied. Results In 2021, there were 1,989,686 (95% uncertainty interval [95% UI], 1,530,479-2,493,238) deaths and 44,962,167 (95% UI, 35,020,339 − 55,467,024) DALYs due to air pollution-related stroke. The ASRs increased with age, peaking generally over 85 years. Males, the Central African region, and Guinea-Bissau showed higher stroke burdens Intracerebral hemorrhage was the most lethal subtype, with an ASR of 11.69 (95% UI 8.94–14.69) for deaths and 276.93 (95% UI 212.21-344.36) for DALYs. From 1990 to 2021, the crude number of deaths and DALYs increased by 13.4% and 6.3%, respectively, for the global stroke burden but showed a declining trend when age-standardized. Most GBD regions in Asia and Africa experienced an increasing stroke burden linked to air pollution, while Europe and America showed a decreasing trend. Predictions indicated a gradual reduction in ASRs, with higher rates in males from 2020 to 2040. Conclusions The global stroke burden associated with air pollution remained significant despite a decreasing trend until 2021. Although future predictions suggested a reduction, the crude counts for stroke burden remained substantial, with significant regional disparities. This warranted the implementation of public health policies and ongoing efforts.

Abstract Background This study aimed to analyze the associations of cardiometabolic index (CMI) with diabetic statuses and insulin resistance (IR) using data from the National Health and Nutrition Examination Survey (NHANES) and examined the potential mediating role of inflammation in these correlations. Methods This study enrolled 9477 participants across four NHANES cycles from 2011 to 2018. The primary outcomes of the study included the risk of having prediabetes, diabetes and the level of the homeostasis model assessment of IR (HOMA-IR). Other outcomes including the levels of fasting blood glucose (FBG), hemoglobin A1c (HbA1c), oral glucose tolerance test (OGTT) results, fasting insulin, the risk of oral hypoglycemic medicine use, insulin use, and retinopathy were also collected and analyzed. Logistic regression model, subgroup analysis, restricted cubic spine (RCS), and Pearson correlation coefficients were conducted to assess the associations of CMI with diabetic statuses and IR. The mediating role of inflammation was evaluated to investigate the potential mechanism of the associations between CMI and diabetic statuses. Results Among included participants, the CMI levels in normal participants, prediabetes and diabetes in this study were 0.48, 0.73 and 1.07. After multivariable adjustment, CMI was positively associated with the risk of prediabetes (OR = 1.49, 95% CI = 1.24–1.79), diabetes (OR = 2.14, 95% CI = 1.82–2.50) and the level of HOMA-IR (β = 2.57, 95% CI = 2.14–3.01). Besides, an increased CMI was correlated with higher levels of FBG, HBA1c, OGTT results and fasting insulin as well as the greater risk of oral hypoglycemic medicine use and insulin use. The RCS showed an inverted L-shaped association of CMI with prediabetes and diabetes (P for non-linearity

The mechanical properties and insulation damage of stator end windings in permanent magnet synchronous generator (PMSG) are investigated by theoretical analysis, finite element analysis (FEA) and experiment verification. First, a theoretical model of the winding electromagnetic force (EF) and vibration response before and after eccentricity faults are established. Then, the stress/strain distribution of the end windings under different working conditions is analyzed. Finally, the insulation damage behavior of end windings with initial cracks is studied and characterized using the stress intensity factor (SIF). The results indicate that the winding EF and vibration responses vary under different faults. The stress/strain at the joint of the winding is the largest, and the insulation layer has the maximum stress/strain under the same section. Additionally, the SIF amplitude of the crack at the winding joint is the largest. And the SIF amplitude of the crack will increase with the increase of fault degree/crack depth/crack length. The contribution of this paper lies in the comprehensive analysis of the winding EF distribution, vibration response, stress and strain, and insulation damage before and after eccentricity. This analysis can provide valuable reference for the health monitoring of PMSG eccentricity faults and the prevention of winding insulation damage.

Static air-gap eccentricity (SAGE) is a common fault in generators. Current researches primarily focus on the parallel SAGE types, while the inclined static air-gap eccentricity (ISAGE) has been rarely investigated. This paper proposes an improved air-gap eccentricity model and presents a study on the electromagnetic-mechanical properties in synchronous generators under typical ISAGE running conditions. Such electromagnetic-mechanical properties include not only the magnetic flux density (MFD) variations, but also the mechanical responses of the electromagnetic torque (EMT) and rotor unbalanced magnetic pulls (UMP). The typical ISAGE factors include: 1) a varied rotor inclined angle θ, and 2) different values of axial inclined distance z (indicates the offset combination case of the two rotor ends). This work is based on the MFD analysis calculation. Theoretical analysis, finite element analysis, and experimental study are carried out, respectively, by taking a 5 kVA two-pole prototype generator as the study object. It is shown that the electromagnetic-mechanical properties of the generator will change when the inclined eccentricity occurs. The EMT, and the rotor UMP as well as the vibrations will increase as the rotor inclined θ and z increase. Specifically, the 2nd harmonic has the most significant variation.

Abstract Objective This clinical study aimed to evaluate the practical value of integrating an AI diagnostic model into clinical practice for caries detection using intraoral images. Methods In this prospective study, 4,361 teeth from 191 consecutive patients visiting an endodontics clinic were examined using an intraoral camera. The AI model, combining MobileNet-v3 and U-net architectures, was used for caries detection. The diagnostic performance of the AI model was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy, with the clinical diagnosis by endodontic specialists as the reference standard. Results The overall accuracy of the AI-assisted caries detection was 93.40%. The sensitivity and specificity were 81.31% (95% CI 78.22%-84.06%) and 95.65% (95% CI 94.94%-96.26%), respectively. The NPV and PPV were 96.49% (95% CI 95.84%-97.04%) and 77.68% (95% CI 74.49%-80.58%), respectively. The diagnostic accuracy varied depending on tooth position and caries type, with the highest accuracy in anterior teeth (96.04%) and the lowest sensitivity for interproximal caries in anterior teeth and buccal caries in premolars (approximately 10%). Conclusion The AI-assisted caries detection tool demonstrated potential for clinical application, with high overall accuracy and specificity. However, the sensitivity varied considerably depending on tooth position and caries type, suggesting the need for further improvement. Integration of multimodal data and development of more advanced AI models may enhance the performance of AI-assisted caries detection in clinical practice.

Abstract Controlling and reducing plaque formation plays a pivotal role in preventing and treating periodontal disease, often utilizing antibacterial drugs to enhance therapeutic outcomes. Mesoporous silica nanoparticles (MSN), an FDA-approved inorganic nanomaterial, possess robust physical and chemical properties, such as adjustable pore size and pore capacity, easy surface modification, and high biosafety. Numerous studies have exploited MSN to regulate drug release and facilitate targeted delivery. This study aimed to synthesize an MSN-tetracycline (MSN-TC) complex and investigate its inhibitory potential on Porphyromonas gingivalis (P. gingivalis)-induced bone resorption. The antibacterial efficacy of MSN-TC was evaluated through bacterial culture experiments. A P. gingivalis-induced bone resorption model was constructed by subcutaneously injecting P. gingivalis around the cranial bone of rats. Micro-computed tomography was employed to assess the inhibitory impact of MSN and MSN-TC on bone resorption. Furthermore, the influence of MSN and MSN-TC on osteoclast differentiation was examined in vitro. The MSN exhibited optimal pore size and particle dimensions for effective loading and gradual release of TC. MSN-TC demonstrated significant bacteriostatic activity against P. gingivalis. MSN-TC-treated rats showed significantly reduced cranial bone tissue destruction compared to MSN or TC-treated rats. Additionally, both MSN and MSN-TC exhibited inhibitory effects on the receptor activator of nuclear factor kappa-Β ligand-mediated osteoclast differentiation. The MSN-TC complex synthesized in this study demonstrated dual efficacy by exerting antibacterial effects on P. gingivalis and by resisting osteoclast differentiation, thereby mitigating bone resorption induced by P. gingivalis. Graphical Abstract

Abstract Electrosynthesis, a viable path to decarbonize the chemical industry, has been harnessed to generate valuable chemicals under ambient conditions. Here, we present a membrane-free flow electrolyzer for paired electrocatalytic upcycling of nitrate (NO3 −) and chloride (Cl−) to ammonia (NH3) and chlorine (Cl2) gases by utilizing waste streams as substitutes for traditional electrolytes. The electrolyzer concurrently couples electrosynthesis and gaseous-product separation, which minimizes the undesired redox reaction between NH3 and Cl2 and thus prevents products loss. Using a three-stacked-modules electrolyzer system, we efficiently processed a reverse osmosis retentate waste stream. This yielded high concentrations of (NH4)2SO4 (83.8 mM) and NaClO (243.4 mM) at an electrical cost of 7.1 kWh per kilogram of solid products, while residual NH3/NH4 + (0.3 mM), NO2 − (0.2 mM), and Cl2/HClO/ClO− (0.1 mM) pollutants in the waste stream could meet the wastewater discharge regulations for nitrogen- and chlorine-species. This study underscores the value of pairing appropriate half-reactions, utilizing waste streams to replace traditional electrolytes, and merging product synthesis with separation to refine electrosynthesis platforms.

Introduction: Immune checkpoint inhibitors can cause immune-related adverse events in various organ systems, with myocarditis being the most serious and life-threatening. This article reports three cases of immune myocarditis induced by camrelizumab, detailing the diagnostic and treatment process. Case Report: Three cases of immune-related myocarditis caused by the use of camrelizumab are reported. Three patients (case 1, male, 44 years old; case 2, male, 69 years old; and case 3, male, 53 years old) were treated with the immune checkpoint inhibitor, camrelizumab 200 mg, intravenously for nasopharyngeal and esophageal cancers. In case 1, 18 days after the 3rd cycle of immunotherapy, the patient’s troponin levels were elevated. In case 2, 1 day after the 1st cycle of treatment, troponin levels were elevated. The electrocardiogram showed right bundle branch block with left anterior branch block and abnormal ST-T segments in the lower wall, and the echocardiogram showed segmental ventricular dyskinesia and thickening of the myocardium of the left and right ventricles. In case 3, 12 days after the 3rd cycle of treatment, the patient developed chest tightness and breathlessness, and cardiac biomarkers were elevated. The electrocardiogram showed borderline QT interval prolongation and extensive ST-T segment changes, and cardiac ultrasound showed thinning of the myocardium in the middle and lower left ventricular anterior and lower posterior walls and loss of motility. All 3 patients were diagnosed with immune-associated cardiomyositis induced by camrelizumab, and camrelizumab was discontinued. In case 1, methylprednisolone succinate was administered as an intravenous infusion of 500 mg once a day for 4 days, and the patient’s troponin levels gradually decreased. In case 2, following the administration of intravenous methylprednisolone succinate sodium (500 mg) once daily for 5 consecutive days, the patient experienced gastrointestinal bleeding. The hormone dose was then reduced, and intravenous immune globulin (IVIG) 10 g/day was added. Treatment continued for 3 days after the patient’s death due to immune myocarditis and heart failure combined with gastrointestinal bleeding. Case 3 underwent a tracheotomy and received methylprednisolone sodium succinate (240 mg) intravenous drip daily for 7 days. Camrelizumab was discontinued. Although troponin and NT-proBNP levels remained elevated with an upward trend 7 days after starting treatment, they decreased after adding IVIG 20 g/day for 3 days. Treatment continued for another 3 days after improvement in cardiac biomarkers. After gradually reducing the hormone dose over 5 days following the stabilization of the patient’s condition, he was discharged from the hospital. The patient’s follow-up status is good. Conclusion: Emphasizing the importance of baseline assessment, early detection and timely intervention, standardized use of glucocorticosteroids, and the addition of immunosuppressants where necessary, these measures can be effective in reducing mortality and ultimately improving prognosis.

Abstract Aconiti Lateralis Radix Praeparata (Fuzi in Chinese) is widely used in the clinical treatment of tumors. This study aims to explore the active fractions and underlying mechanisms of Fuzi in the treatment of non-small cell lung cancer (NSCLC). Fuzi alkaloids (FZA) is prepared and found to inhibit the growth of NSCLC both in vitro and in vivo significantly. A total of 53 alkaloids are identified in FZA by UPLC-Q-TOF-MS. Proteomics experiment show that 238 differentially expressed proteins regulated by FZA are involved in amino acid anabolism, pyrimidine metabolism and PI3K/Akt-mTOR signaling pathway. Metabolomics analyses identify 32 significant differential metabolites which are mainly involved in amino acid metabolism, TCA cycle and other pathways. Multi-omics research combined with molecular biological assays suggest that FZA might regulate glycolysis through PI3K/Akt-mTOR pathway to treat NSCLC. The study lays a foundation for the anti-cancer investigation of Fuzi and provides a possible scientific basis for its clinical application.

Abstract This study was aimed to investigate the impact of intracytoplasmic sperm injection (ICSI) on reproductive outcomes in couples with non-male factor infertility and frozen-thawed embryo transfer (FET) treatment. This retrospective cohort study involved a total of 10,143 cycles from 6206 couples who underwent FET at the Third Affiliated Hospital of Zhengzhou University between January 2016 and September 2022. Patients were categorized into two groups based on the insemination methods of transferred embryos. Clinical and neonatal outcomes were compared between ICSI and conventional in vitro fertilization (cIVF) groups. The results showed that ICSI was not associated with improved clinical outcomes compared to cIVF. However, ICSI was associated with lower birthweight when twins were born. In conclusion, although subgroup analysis showed that ICSI was associated with slightly improved live birth rate for infertile couples with non-male factor infertility compared to cIVF, the regression analysis showed that ICSI did not demonstrate any improvement of the reproductive outcomes. The infertile women with twin pregnancies should be further informed of the lower birthweight and lower birth length when their oocytes were inseminated with ICSI. The findings of this study provide valuable insights for clinicians when discussing the benefits and risks of ICSI in patients with non-male factor infertility.

Abstract The Qinghai-Tibet Plateau (QTP), renowned for its exceptional biological diversity, is home to numerous endemic species. However, research on the virology of vulnerable vertebrates like yaks remains limited. In this study, our objective was to use metagenomics to provide a comprehensive understanding of the diversity and evolution of the gut virome in yak populations across different regions of the QTP. Our findings revealed a remarkably diverse array of viruses in the gut of yaks, including those associated with vertebrates and bacteriophages. Notably, some vertebrate-associated viruses, such as astrovirus and picornavirus, showed significant sequence identity across diverse yak populations. Additionally, we observed differences in the functional profiles of genes carried by the yak gut virome across different regions. Moreover, the virus-bacterium symbiotic network that we discovered holds potential significance in maintaining the health of yaks. Overall, this research expands our understanding of the viral communities in the gut of yaks and highlights the importance of further investigating the interactions between viruses and their hosts. These data will be beneficial for revealing the crucial role that viruses play in the yak gut ecology in future studies.

ABSTRACT: Spermatogenesis is a continuous process in which functional sperm are produced through a series of mitotic and meiotic divisions and morphological changes in germ cells. The aberrant development and fate transitions of spermatogenic cells cause hybrid sterility in mammals. Cattle-yak, a hybrid animal between taurine cattle (Bos taurus) and yak (Bos grunniens), exhibits male-specific sterility due to spermatogenic failure. In the present study, we performed single-cell RNA sequencing analysis to identify differences in testicular cell composition and the developmental trajectory of spermatogenic cells between yak and cattle-yak. The composition and molecular signatures of spermatogonial subtypes were dramatically different between these 2 animals, and the expression of genes associated with stem cell maintenance, cell differentiation and meiotic entry was altered in cattle-yak, indicating the impairment of undifferentiated spermatogonial fate decisions. Cell communication analysis revealed that signaling within different spermatogenic cell subpopulations was weakened, and progenitor spermatogonia were unable to or delayed receiving and sending signals for transformation to the next stage in cattle-yak. Simultaneously, the communication between niche cells and germ cells was also abnormal. Collectively, we obtained the expression profiles of transcriptome signatures of different germ cells and testicular somatic cell populations at the single-cell level and identified critical regulators of spermatogonial differentiation and meiosis in yak and sterile cattle-yak. The findings of this study shed light on the genetic mechanisms that lead to hybrid sterility and speciation in bovid species.

Abstract Background China has made remarkable achievements in tuberculosis (TB) prevention and control, but it still takes long way to achieve the End TB goal especially in underdeveloped Southwest China. TB healthcare workers (HCWs) are core forces in TB prevention and control but often face job burnout. This study aimed to explore the burden and associated factors of job burnout among TB HCWs in Southwest China. Methods This cross-sectional study used both survey questionnaires and semi-structured interviews, to assess job burnout among TB HCWs based on Malasch Model and explore the associated factors based on Herzberg’s two-factor theory (different hygiene and motivation factors). Quantitative data analysis adopts multiple linear regression to in SPSS 22.0, and qualitative data were analyzed through a framework approach. Results A total of 1140 TB HCWs were included in questionnaire surveys. The overall job burnout rates of TB HCWs in Centers for Disease Control and Prevention (CDC), designated hospitals and Primary Health Care (PHC) sectors were 55%, 70.1% and 67.5%, respectively. TB HCWs in CDC who scored lower in interpersonal factors had a higher risk of depersonalization (DP) [B(95%CI): -0.89 (-1.71 to -0.80)]. TB HCWs in designated hospitals who scored lower in doctor-patient relationship factors [B (95%CI): 6.63 (-12.06 to -1.20)] were more likely to have emotional exhaustion (EE). TB HCWs who were less satisfied with training, supervision and assessment in PHC sectors [B(95%CI): 0.65 (0.03 to 1.26)] had less personal accomplishment (PA). Interviews with nine TB HCWs showed that poor environment could lead to high infection and heavy workload could lead to work pressure among TB HCWs in Chongqing. It is also found that performance assessment and management of TB HCWs, communication and cooperation and so on are related to job burnout. Conclusions TB HCWs had different levels of job burnout in CDC, designated hospitals, and PHC sectors of Chongqing, which were affected by different hygiene and motivation factors. Governments, organizations and individuals should take cooperative measures such as strengthening communication to deal with job burnout among TB HCWs.

Abstract The separation and purification of chemical raw materials, particularly neutral compounds with similar physical and chemical properties, represents an ongoing challenge. In this study, we introduce a class of water-soluble macrocycle compound, calix[2]azolium[2]benzimidazolone (H), comprising two azolium and two benzimidazolone subunits. The heterocycle subunits form a hydrophobic binding pocket that enables H1 to encapsulate a series of neutral guests in water with 1:1 or 2:1 stoichiometry, including aldehydes, ketones, and nitrile compounds. The host-guest complexation in the solid state was further confirmed through X-ray crystallography. Remarkably, H1 was shown to be a nonporous adaptive crystal material to separate valeraldehyde from the mixture of valeraldehyde/2-methylbutanal/pentanol with high selectivity and recyclability in the solid states. This work not only demonstrates that azolium-based macrocycles are promising candidates for the encapsulation of organic molecules but also shows the potential application in separation science.

Abstract We design a quantum method for classical information compression that exploits the hidden subgroup quantum algorithm. We consider sequence data in a database with a priori unknown symmetries of the hidden subgroup type. We prove that data with a given group structure can be compressed with the same query complexity as the hidden subgroup problem, which is exponentially faster than the best-known classical algorithms. We moreover design a quantum algorithm that variationally finds the group structure and uses it to compress the data. There is an encoder and a decoder, along the paradigm of quantum autoencoders. After the training, the encoder outputs a compressed data string and a description of the hidden subgroup symmetry, from which the input data can be recovered by the decoder. In illustrative examples, our algorithm outperforms the classical autoencoder on the mean squared value of test data. This classical-quantum separation in information compression capability has thermodynamical significance: the free energy assigned by a quantum agent to a system can be much higher than that of a classical agent. Taken together, our results show that a possible application of quantum computers is to efficiently compress certain types of data that cannot be efficiently compressed by current methods using classical computers.

Drug discovery is a sophisticated process that incorporates scientific innovations and cutting-edge technologies. Compared to traditional bioactivity-based screening methods, encoding and display technologies for combinatorial libraries have recently advanced from proof-of-principle experiments to promising tools for pharmaceutical hit discovery due to their high screening efficiency, throughput, and resource minimization. This review systematically summarizes the development history, typology, and prospective applications of encoding and displayed technologies, including phage display, ribosomal display, mRNA display, yeast cell display, one-bead one-compound, DNA-encoded, peptide nucleic acid-encoded, and new peptide-encoded technologies, and examples of preclinical and clinical translation. We discuss the progress of novel targeted therapeutic agents, covering a spectrum from small-molecule inhibitors and nonpeptidic macrocycles to linear, monocyclic, and bicyclic peptides, in addition to antibodies. We also address the pending challenges and future prospects of drug discovery, including the size of screening libraries, advantages and disadvantages of the technology, clinical translational potential, and market space. This review is intended to establish a comprehensive high-throughput drug discovery strategy for scientific researchers and clinical drug developers.

Abstract The migratory insertion of metal-hydride into alkene has allowed regioselective access to organometallics, readily participating in subsequent functionalization as one conventional pathway of hydroalkylation, whereas analogous process with feedstock alkyne is drastically less explored. Among few examples, the regioselectivity of metal-hydride insertion is mostly governed by electronic bias of alkynes. To alter the regioselectivity and drastically expand the intermediate pools that we can access, one aspirational design is through alternative nickel-alkyl insertion, providing opposite regioselectivity induced by steric demand. Leveraging in situ formed nickel-alkyl species, we herein report the regio- and enantioselective hydroalkylation of alkynes with broad functional group tolerance, excellent regio- and enantioselectivity, enabling efficient route to diverse valuable chiral allylic amines motifs. Preliminary mechanistic studies indicate the aminoalkyl radical species can participate in metal-capture and lead to formation of nickel-alkyl, of which the migratory insertion is key to reverse regioselectivity observed in metal-hydride insertion.

Abstract Background The fruit of Phyllanthus emblica L., a traditional medicine in China and India, is used to treat diabetes mellitus. Its water extract (WEPE) has demonstrated hypoglycemic effects in diabetic rats, but its mechanisms on glucose utilization and insulin resistance in skeletal muscle remain unclear. Therefore, this study aims to investigate the effects and underlying mechanisms of WEPE on glucose utilization and insulin resistance using C2C12 myotubes. Methods Effects of WEPE on glucose uptake, GLUT4 translocation, and AMPK and AKT phosphorylation were investigated in C2C12 myotubes and palmitate-treated myotubes. An AMPK inhibitor and siRNA were used to explore the mechanisms of WEPE. Glucose uptake was determined using a 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake assay, and protein expression and GLUT4 translocation were assessed via western blotting. Results In normal myotubes, WEPE significantly stimulated glucose uptake and GLUT4 translocation to the plasma membrane at concentrations of 125 and 250 µg/mL. This was accompanied by an increase in the phosphorylation of AMPK and its downstream targets. However, both compound C and AMPK siRNA blocked the WEPE-induced GLUT4 translocation and glucose uptake. Moreover, pretreatment with STO-609, a calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor, inhibited WEPE-induced AMPK phosphorylation and attenuated the WEPE-stimulated glucose uptake and GLUT4 translocation. In myotubes treated with palmitate, WEPE prevented palmitate-induced insulin resistance by enhancing insulin-mediated glucose uptake and AKT phosphorylation. It also restored the insulin-mediated translocation of GLUT4 from cytoplasm to membrane. However, these effects of WEPE on glucose uptake and GLUT4 translocation were blocked by pretreatment with compound C. Conclusions WEPE significantly stimulated basal glucose uptake though CaMKKβ/AMPK pathway and markedly ameliorated palmitate-induced insulin resistance by activating the AMPK pathway in C2C12 myotubes.

The adiabatic shear band is a common dynamic failure mechanism in metal materials at high strain rates. In this work, a new approach was proposed to improve mechanical properties and inhibit the formation and propagation of the adiabatic shear band in the pure Mo single crystal. The microstructure evolution of the pure Mo and Mo-Nb single crystals subjected to the dynamic load was investigated by EBSD and TEM. At a strain rate of 2500 s−1, the developed adiabatic shear band was totally distributed in the pure Mo single crystal, and the slip is the main deformation mechanism. A thinner adiabatic shear band was distributed in the Mo-3Nb single crystal accompanied by a few bands of deformation twins and then disappeared in the Mo-6Nb single crystal, replaced by the {112} deformation twinning. At high strain rates, the dynamic deformation mechanism of the Mo single crystal is sensitive to the Nb element, which attributes to the reduction of the generalized stacking fault energy.

This study examines the hot deformation behavior of Mo-14Re alloy at various true strains (15%, 35%, 65%) and strain rates (0.01 s−1, 10 s−1) at a temperature of 1400K. The findings indicate that dynamic recovery (DRV) and dynamic recrystallization (DRX) occur concomitantly as strain increases at a low strain rate of 0.01 s−1, with DRV being the predominant softening mechanism. At a strain of 65%, DRX emerges as the primary softening process. Conversely, under high strain rates of 10 s−1, DRX is inhibited, and the Mo-14Re alloy experiences work hardening due to an increase in dislocation density. Microscopic analysis shows that the high-density dislocations facilitate the continued nucleation and growth of recrystallized grains at low strain rates. At high strain rates, tangled dislocations hinder dislocation motion and recrystallization. Regarding texture evolution, stronger {100}//CD and weaker {111}//CD fiber texture is observed at low strain rates of 0.01 s−1, while stronger {111}//CD and weaker {100}//CD fiber texture forms at high strain rates of 10 s−1, with enhanced texture intensity. Mechanistic analysis confirms the activation of the {110}, {112}, and {123} dislocation slip systems at elevated temperatures, with the {123} system being the most dominant.

Abstract There is no reliable causal evidence for the effect of statins on diabetic nephropathy (DN) and diabetic retinopathy (DR), and the results of previous observational studies are contradictory. Genetic variants linked to low-density lipoprotein cholesterol (LDL-C) from a UK biobank genome-wide association study and located within a 100kb window around HMGCR were used to proxy statins, comparing with PCSK9 inhibitors (control). DN and DR genome-wide association study summary statistics were obtained from the FinnGen study. Secondary MR analyses and NHANES cross-sectional data were used for validation. Drug-target Mendelian randomization (MR) was applied to investigate the association between the genetically proxied inhibition of HMGCR and PCSK9 with DN and DR, p

Abstract To investigate the effect mechanism of electroacupuncture based on the AMP-activated protein kinase (AMPK) /acetyl-CoA carboxylase (ACC) signaling pathway to improve glycolipid metabolism disorders in db/db mice. 10 db/m mice with normal genotype were used as the normal control group without diabetes (Con), and 30 db/db mice were divided randomly into three groups: Pathological model mice (Mod), Acupuncture + ACC antagonist group (Acu + ACC), and Acupuncture + AMPK antagonist group (Acu + AMPK). Con and Mod did not receive any special treatment, only as a control observation. The latter two groups of mice received electroacupuncture treatment for 4 weeks. Mouse triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol(LDL-C), and cholesterin(CHO) levels were detected by colorimetric assay. Enzyme-linked immunoassay (ELISA) was used to detect insulin(INS) levels. Liver histopathologic changes and hepatic glycogen synthesis were observed by HE and PAS staining. The mRNA and protein expression of insulin receptor substrate-1(IRS1), Phosphatidylinositol 3-kinase(PI3K), protein kinase B (AKT), AMPK, and ACC were detected by Western blot and qRT-PCR.The results show that compared with Mod, TG, LDL, CHO, and INS levels of Acu + AMPK and Acu + ACC mice were significantly reduced (P

Abstract Background The heart can be involved in immunoglobulin (Ig)-G4-related disease (IgG4-RD). This study aimed to summarize the clinical features and efficacy of treatment for IgG4-RD patients with heart involvement. Methods We conducted a retrospective study enrolling 42 IgG4-RD patients with heart involvement from the IgG4-RD cohorts of the Peking Union Medical College Hospital and Beijing An Zhen Hospital, from 2010 to 2022. Clinical, laboratory, radiological data were collected, and treatment responses to glucocorticoids and immunosuppressants were analyzed. Results IgG4-related cardiac involvement is a rare part of the IgG4-RD spectrum. The incidences of coronary periarteritis and pericarditis were 1.2%(13/1075) and 3.1%(33/1075), respectively in our cohort. Valvular disease possibly related to IgG4-RD was detected in two patients. None of the patients with myocardial involvement were identified. The average age was 58.2 ± 12.8 years, with a male predominance (76.7%). Coronary artery CT revealed that mass-like and diffuse wall-thickening lesions were the most frequently observed type of coronary periarteritis. Pericarditis presented as pericardial effusion, localized thickening, calcification and mass. After treatment with glucocorticoid and immunosuppressants, all patients achieved a reduced IgG4-RD responder index score and achieved radiological remission. Two patients with coronary peri-arteritis experienced clinical relapses during the maintenance period. Conclusions Cardiac involvement in IgG4-RD is rare and easily overlooked since many patients are asymptomatic, and the diagnosis relies on imaging. Patients showed a satisfactory response to glucocorticoid based treatment.

Abstract This study focuses on the prediction and management of carbon emissions (CE) under the backdrop of global warming, with a particular emphasis on developing spatial planning strategies for urban clusters. In this context, we integrate artificial intelligence technologies to devise an optimized spatial analysis method based on the attributes of multi-source, urban-level spatio-temporal big data on CE. This method enhances both the accuracy and interpretability of CE data processing. Our objectives are to accurately analyze the current status of CE, predict the future spatial distribution of urban CE in the Yangtze River Delta (YRD), and identify key driving factors. We aim to provide pragmatic recommendations for sustainable urban carbon management planning. The findings indicate that: (1) the algorithm designed by us demonstrates excellent fitting capabilities in the analysis of CE data in the YRD, achieving a fitting accuracy of 0.93; (2) it is predicted that from 2025 to 2030, areas with higher CE in the YRD will be primarily concentrated in the 'Provincial Capital Belt' and the 'Heavy Industry Belt'; (3) the economic foundation has been identified as the most significant factor influencing CE in the YRD; (4) projections suggest that CE in the YRD are likely to peak by 2030.

Current cytotoxic T lymphocyte (CTL) activating immunotherapy requires a major histocompatibility complex I (MHC-I)-mediated presentation of tumor-associated antigens, which malfunctions in around half of patients with triple-negative breast cancer (TNBC). Here, we create a LCL161-loaded macrophage membrane decorated nanoparticle (LMN) for immunotherapy of MHC-I-deficient TNBC. SIRPα on the macrophage membrane helps LMNs recognize CD47-expressing cancer cells for targeted delivery of LCL161, which induces the release of high mobility group protein 1 and proinflammatory cytokines from cancer cells. The released cytokines and high mobility group protein 1 activate antitumor immunity by increasing the intratumoral density of the phagocytic macrophage subtype by 15 times and elevating the intratumoral concentration of CTL lymphotoxin by 4.6 folds. LMNs also block CD47-mediated phagocytosis suppression. LMNs inhibit the growth of MHC-I-deficient TNBC tumors, as well as those resistant to combined therapy of anti-PDL1 antibody and albumin-bound paclitaxel, and prolong the survival of animals, during which process CTLs also play important roles. This macrophage membrane-decorated nanoparticle presents a generalizable platform for increasing macrophage-mediated antitumor immunity for effective immunotherapy of MHC-I-deficient cancers.

As a universal computational model in quantum computing, the quantum walk is employed in secure communication, quick query, similar calculation, graph mining, etc. At present, researchers have paid limited attention to the design, development, and relationship between models and algorithms of the quantum walk. Further, the theoreticals advantages of the quantum walk on graphs in graph computing are neglected. Aiming at the quantum walk model and algorithms for graph data, firstly, the core design strategy and theoretical advantages of quantum walks are analyzed, the construction form of significant operators and spatial dimension characteristics of relevant algorithms are summarized, and the logical relationship between model and algorithm is clarified. Secondly, according to the classification of discrete-time and continuous-time, the research advances and design difficulties of the quantum walk model are summarized, and the evolutionary trend of quantum walk extending from regular graphs to irregular graphs is concluded. Furthermore, around the similarity calculation of graphs, spatial search, and graph mining, the research progress of quantum walk algorithms is reviewed, and the technical characteristics, advantages and shortcomings of relevant algorithms are analyzed. Finally, from the perspectives of efficiency optimization, accuracy improvement, unitary constraints, and graph reconstruction, the future research directions of the quantum walk models and algorithms are prospected.

The maintenance and restoration of wetland habitat is a priority conservation action for most waterfowl and other wetland-dependent species in North America. Despite much progress in targeting habitat management in staging and wintering areas, methods to identify and target high-quality breeding habitats that result in the greatest potential for wildlife are still required. This is particularly true for species that breed in remote, inaccessible areas such as the American black duck, an intensively managed game bird in Eastern North America. Although evidence suggests that black ducks prefer productive, nutrient-rich waterbodies, such as beaver ponds, information about the distribution and quality of these habitats across the vast boreal forest is lacking with accurate identification remaining a challenge. Continuing advancements in remote sensing technologies that provide spatially extensive and temporally repeated information are particularly useful in meeting this information gap. In this study, we used multi-source remotely sensed information and a fuzzy analytical hierarchy process to map the spatial distribution of beaver ponds in Ontario. The use of multi-source data, including a Digital Elevation Model, a Sentinel-2 Multi-Spectral Image, and RadarSat 2 Polarimetric data, enabled us to identify individual beaver ponds on the landscape. Our model correctly identified an average of 83.0% of the known beaver dams and 72.5% of the known beaver ponds based on validation with an independent dataset. This study demonstrates that remote sensing is an effective approach for identifying beaver-modified wetland features and can be applied to map these and other wetland habitat features of interest across large spatial extents. Furthermore, the systematic acquisition strategy of the remote sensors employed is well suited for monitoring changes in wetland conditions that affect the availability of habitats important to waterfowl and other wildlife.

Eutrophication caused by excessive nitrogen and phosphorus is an important factor affecting water quality in drinking water sources. Convenient monitoring of eutrophication in water bodies can reduce the use of pesticides and reduce energy consumption, helping to promote ecological and economic development. This study examined the relationship between water eutrophication and the oxidation-reduction potential (ORP). The results showed that various parameters related to eutrophication, such as ammonia nitrogen, total nitrogen, total phosphorus, chlorophyll-a, and cyanobacteria, had correlations with ORP. There is a close relationship between eutrophication and the concentration of cyanobacteria. When cyanobacteria blooms occur in the drinking water source, it may contaminate the drinking water. Because the conventional eutrophication index does not include the concentration of cyanobacteria, principal component analysis (PCA) was utilized to comprehensively analyze these eutrophication-related parameters and obtain the eutrophication-related index, with the cumulative contribution of principal components reaching 81.8%. Different mathematical methods such as neural network model and mathematical fitting were used to study the relationship between ORP and the eutrophication-related index. A three-segment relationship between the ORP and the index was established. This three-stage relationship was confirmed in different reservoirs.

Background : Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indices of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction. Methods : This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed. Results : Distribution of the TyAG and TyAG-BMI indices shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P

Abstract Network analysis provides an innovative approach to examining symptom-to-symptom interactions in mental health, and adverse external conditions may change the network structures. This study compared the networks of common risk factors and mental health problems (loneliness, depressive symptoms, and anxiety symptoms) in community-dwelling older people before and during COVID-19. Older adults (aged ≥ 60) at risk for depression were recruited through non-governmental organizations. Loneliness, depressive symptoms and anxiety symptoms were measured using the three-item Loneliness Scale (UCLA-3), nine-item Patient Health Questionnaire (PHQ-9), and seven-item Generalized Anxiety Disorder Scale (GAD-7), respectively. Data from 2549 (before) and 3506 (during COVID-19) respondents were included using propensity score matching. Being restless (GAD-7-item5) was most central, indicated by Expected Influence, in both pre and during COVID-19 networks despite low severity (mean score). The network during COVID-19 had higher global strength and edge variability than the pre-pandemic network, suggesting easier symptom spread and potentially more complex symptom presentation. In addition, feeling isolated from others (UCLA-3-item3) had stronger connections with feeling worthless/guilty (PHQ-9-item6) and anticipatory anxiety (GAD-7-item7) during COVID-19 than before. These findings may enhance our knowledge of the symptom structure of common mental health problems and the impacts of the pandemic. Targeting central symptoms may offer novel preventive strategies for older people.

The forecast of the global numerical weather prediction model is often used as the background field to drive the regional mesoscale weather models, and its forecast quality has an important impact on the prediction skill of regional models. The mesoscale operational model in Central China uses the Global Forecast Field (NCEP GFS) of the US Center for Environmental Prediction as the background field, and its forecast accuracy needs to be improved. This paper proposes a method to improve the initial field of the model by using the three-dimensional variational method to assimilate the high-quality European Centre for Medium-range Weather Forecasts (ECMWF) fine-grid forecast field to improve the short-term forecasting ability of the model. At first, the error characters of the 12 h forecast products of NCEP GFS and ECMWF were analyzed by using sounding observations. The RMSE (root mean square error) of temperature, horizontal wind field and relative humidity of ECMWF 12 h forecast are smaller than those of NCEP GFS forecast. Second, sensitivity experiments of ECMWF forecast field assimilation with different resolutions were conducted. Finally, 1°×1° resolution was selected based on the sensitivity experiments and a series of the data assimilation experiments with 1°×1° resolution was performed for August 2021. The results are as follows. (1) The assimilation forecast of heavy rain from 11 to 13 August 2021 shows that after 12 hours of spin-up, the forecast error of the element field has been significantly improved, especially at the bottom of the model. The TS score of 12-36 h, 36-60 h and 60-84 h cumulative precipitation has a certain improvement, especially the forecast of rainstorm magnitude. (2) ECMWF forecast field assimilation sensitivity experiments with different resolutions show that the forecast effect of ECMWF forecast field with 1°×1° resolution is better than 0.5°×0.5° and 0.25°×0.25°. (3) A series of the data assimilation experiments for August 2021 shows that the assimilation of ECMWF 12 h 1°×1° predicted variables has a lower RMSE of the 12 h, 36 h and 60 h forecasted temperature, humidity and wind field in the vertical direction than the control experiments, and the TS score was significantly improved, especially for 50 mm heavy rain precipitation, with an increase of 13.33%, which can effectively improve the forecast skills of the Wuhan Mesoscale Model.

Abstract Background This study sought to elucidate the associations of cardiometabolic index (CMI), as a metabolism-related index, with all-cause and cardiovascular mortality among the older population. Utilizing data from the National Health and Nutrition Examination Survey (NHANES), we further explored the potential mediating effect of inflammation within these associations. Methods A cohort of 3029 participants aged over 65 years old, spanning six NHANES cycles from 2005 to 2016, was enrolled and assessed. The primary endpoints of the study included all-cause mortality and cardiovascular mortality utilizing data from National Center for Health Statistics (NCHS). Cox regression model and subgroup analysis were conducted to assess the associations of CMI with all-cause and cardiovascular mortality. The mediating effect of inflammation-related indicators including leukocyte, neutrophil, lymphocyte, systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR) were evaluated to investigate the potential mechanism of the associations between CMI and mortality through mediation package in R 4.2.2. Results The mean CMI among the enrolled participants was 0.74±0.66, with an average age of 73.28±5.50 years. After an average follow-up period of 89.20 months, there were 1,015 instances of all-cause deaths and 348 cardiovascular deaths documented. In the multivariable-adjusted model, CMI was positively related to all-cause mortality (Hazard Ratio (HR)=1.11, 95% CI=1.01-1.21). Mediation analysis indicated that leukocytes and neutrophils mediated 6.6% and 13.9% of the association of CMI with all-cause mortality. Conclusion Elevated CMI is positively associated with all-cause mortality in the older adults. The association appeared to be partially mediated through inflammatory pathways, indicating that CMI may serve as a valuable indicator for poor prognosis among the older population.

Abstract Background Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. Methods and results A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P

Introduction: Although programmed death ligand 1 (PD-L1) inhibitor plus chemotherapy regimen is a promising strategy for malignant tumors, it can induce significant immune-related adverse events, such as immune-related pneumonitis. Here, we report the first case of lethal immune-related pneumonitis in an Asian patient receiving anti-PD-L1 treatment. Case Presentation: A 68-year-old man was diagnosed with small cell lung cancer and interstitial pneumonia. After his pulmonary infection was relieved by comprehensive treatment, the patient received first-line treatment with durvalumab plus etoposide and carboplatin. Two weeks after starting durvalumab treatment, the patient had chest pain and shortness of breath. He was diagnosed with immune-induced pneumonia and treated with methylprednisolone, cefoperazone, and sulbactam, followed by oxygen and pirfenidone. Oxygen partial pressure decreased to 58 mm Hg within next the 4 days and laboratory assessment suggested cytokine storm. The patient underwent 2 plasma exchanges, one double filtration plasmapheresis and oxygen saturation decreased continuously. The patient died 1 month after durvalumab treatment. Conclusion: Immune-related pneumonitis induced by PD-L1 inhibitors is rare but life-threatening. Infection should be ruled out before starting immunotherapy.

Natural slopes usually display complicated exposed rock surfaces that are characterized by complex and substantial terrain undulation and ubiquitous undesirable phenomena such as vegetation cover and rockfalls. This study presents a systematic outcrop research of fracture pattern variations in a complicated rock slope, and the qualitative and quantitative study of the complex phenomena impact on three-dimensional (3D) discrete fracture network (DFN) modeling. As the studies of the outcrop fracture pattern have been so far focused on local variations, thus, we put forward a statistical analysis of global variations. The entire outcrop is partitioned into several subzones, and the subzone-scale variability of fracture geometric properties is analyzed (including the orientation, the density, and the trace length). The results reveal significant variations in fracture characteristics (such as the concentrative degree, the average orientation, the density, and the trace length) among different subzones. Moreover, the density of fracture sets, which is approximately parallel to the slope surface, exhibits a notably higher value compared to other fracture sets across all subzones. To improve the accuracy of the DFN modeling, the effects of three common phenomena resulting from vegetation and rockfalls are qualitatively analyzed and the corresponding quantitative data processing solutions are proposed. Subsequently, the 3D fracture geometric parameters are determined for different areas of the high-steep rock slope in terms of the subzone dimensions. The results show significant variations in the same set of 3D fracture parameters across different regions with density differing by up to tenfold and mean trace length exhibiting differences of 3–4 times. The study results present precise geological structural information, improve modeling accuracy, and provide practical solutions for addressing complex outcrop issues.

AIM: To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity. METHODS: A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited. Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals. Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery. The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software. Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2 (EPHA2). Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins. The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assay, respectively. The cell migration was analyzed by wound healing assay. Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo. RESULTS: A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif (SAM) domain of EPHA2. Functional studies demonstrated the variant's impact: reduced EPHA2 protein expression, altered subcellular localization, and disrupted interactions with other lens membrane proteins. This mutant notably enhanced human lens epithelial cell migration, and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast (DIC) optics. CONCLUSION: Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.

Single event transient (SET) induced by high energy single particle radiation is the main threat to space application electronic system reliability. The evaluation and measurement of SET is the key to improve the performance of radiation hardened intergrated circuit. In view of the single event transient generated by the combined circuit, an improved circuit-level simulation method combining charge collection sensitive volume (SV) and bipolar diffusion mechanism for SET with heavy ion incidence was presented. The physics based multi-node charge collection model was built by analyzing layout characteristics such as active region geometry and heavy ion incidence angle. As the charge sharing effect and parasitic bipolar amplification effect considered, the established method which was integrated in the developed TREES software was used for evaluating SET in the 65 nm commercial cell library. The results show that the SET cross sections and pulse width distribution can be calculated and compared, which offer reference data for SET filter design.