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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.

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.

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.

Abstract Exposure to cigarette smoke directly damages the lungs and causes lung inflammation. The anti‐inflammatory properties of edible bird's nest (EBN) have been reported. We aimed to determine the effect of EBN on pneumonia in a mouse model exposed to cigarette smoke. Fifty BALB/c mice were randomly divided into control, model, positive drug, low‐dose EBN, and high‐dose EBN groups (n = 10 each). Except for the control group, the mice in each group were exposed to four cigarettes once a day for 8 days. In addition, we validated the effects of EBN on A549 cells and investigated the mechanism by which EBN alleviates lung inflammation. Edible bird's nest (EBN) could alleviate the structural damage of lung tissue and the smoke‐induced inflammatory response in mice. The best effect was observed at the high dose of EBN (0.019 g). The mice treated with EBN had a stronger ability than those in the model group to resist cigarette smoke stimulation, as indicated by a decrease in serum and lung inflammatory markers (interleukin 6 [IL‐6], tumor necrosis factor‐α [TNF‐α], and interleukin 8 [IL‐8]), an increase in serum interleukin 10 (IL‐10) levels, and a decrease in the expression of inflammasome NOD‐like receptor pyrin 3 (NLRP3). In addition, our cell experiments showed that EBN attenuated cigarette smoke‐induced pulmonary inflammation mainly by inhibiting the tumor necrosis factor receptor 1 (TNFR1)/nuclear factor‐kappa B (NF‐κB)/NLRP3 pathway. These findings provide theoretical evidence for the positive nutritional qualities of EBN for the lung by demonstrating that it inhibits the TNFR1/NF‐κB/NLRP3 signaling pathway, which prevents the development of cigarette smoke‐induced pulmonary inflammation.

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.

Abstract Background Ischemia and no obstructive coronary artery disease (INOCA) is increasingly recognized and associated with poor outcomes. The triglyceride-glucose (TyG) index is a reliable alternative measure of insulin resistance significantly linked to cardiovascular disease and adverse prognosis. We investigated the association between the TyG index and myocardial ischemia and the prognosis in INOCA patients. Methods INOCA patients who underwent both coronary angiography and myocardial perfusion imaging (MPI) were included consecutively. All participants were divided into three groups according to TyG tertiles (T1, T2, and T3). Abnormal MPI for myocardial ischemia in individual coronary territories was defined as summed stress score (SSS) ≥ 4 and summed difference score (SDS) ≥ 2. SSS refers to the sum of all defects in the stress images, and SDS is the difference of the sum of all defects between the rest images and stress images. All patients were followed up for major adverse cardiac events (MACE). Results Among 332 INOCA patients, 113 (34.0%) had abnormal MPI. Patients with higher TyG index had a higher rate of abnormal MPI (25.5% vs. 32.4% vs. 44.1%; p = 0.012). Multivariate logistic analysis showed that a high TyG index was significantly correlated with abnormal MPI in INOCA patients (OR, 1.901; 95% CI, 1.045–3.458; P = 0.035). During the median 35 months of follow-up, 83 (25%) MACE were recorded, and a higher incidence of MACE was observed in the T3 group (T3 vs. T2 vs. T1: 36.9% vs. 21.6% vs. 16.4%, respectively; p = 0.001). In multivariate Cox regression analysis, the T3 group was significantly associated with the risk of MACE compared to the T1 group (HR, 2.338; 95% CI 1.253–4.364, P = 0.008). Conclusion This study indicates for the first time that the TyG index is significantly associated with myocardial ischemia and poor prognosis among INOCA patients.

Abstract Background Like all other species, fungi are susceptible to infection by viruses. The diversity of fungal viruses has been rapidly expanding in recent years due to the availability of advanced sequencing technologies. However, compared to other virome studies, the research on fungi-associated viruses remains limited. Results In this study, we downloaded and analyzed over 200 public datasets from approximately 40 different Bioprojects to explore potential fungal-associated viral dark matter. A total of 12 novel viral sequences were identified, all of which are RNA viruses, with lengths ranging from 1,769 to 9,516 nucleotides. The amino acid sequence identity of all these viruses with any known virus is below 70%. Through phylogenetic analysis, these RNA viruses were classified into different orders or families, such as Mitoviridae, Benyviridae, Botourmiaviridae, Deltaflexiviridae, Mymonaviridae, Bunyavirales, and Partitiviridae. It is possible that these sequences represent new taxa at the level of family, genus, or species. Furthermore, a co-evolution analysis indicated that the evolutionary history of these viruses within their groups is largely driven by cross-species transmission events. Conclusions These findings are of significant importance for understanding the diversity, evolution, and relationships between genome structure and function of fungal viruses. However, further investigation is needed to study their interactions.

Objective To investigate associations between three-dimensional(3D) morphology of cervical vertebrae and skeletal maturation by cone-beam computed tomography(CBCT) and establish corresponding regression models for quantitatively evaluating cervical vertebral maturation(CVM). Methods The analyzed sample consisted of 358 CBCT images (175 male, 183 female), of which 277 images were randomly selected as the model development group and 81 as the performance test group. Twenty-one 3D morphological parameters were defined and measured, incorporating all parts of the cervical vertebrae, including the cervical vertebral bodies, transverse processes, spinous processes, pedicles, lamina, and articular processes. The cervical vertebral maturation index (CVMI) was determined by experienced orthodontists as reference standard. Spearman’s rank correlation coefficient and multivariable stepwise regression analysis were used to identify the associations and build regression models. The performance test group was employed to examine each model’s reliability. Paired-samples Wilcoxon signed-rank test compared the CVMI of the model prediction with the reference standard. Results Three-dimensional morphological changes in various parts of the cervical vertebrae correlated with CVMI (P0.05). Conclusion New associations were found between 3D morphology of cervical vertebrae and skeletal maturation. The 3D-driven morphometric CVM assessment method and corresponding regression models exhibited good credibility and high consistency with experts.