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Abstract Background The prevalence of chronic conditions increases rapidly among older population. However, it is unclear how different chronic conditions progression contributes to the health care utilization, and whether intergenerational support modified this relationship. This study aimed to explore the longitudinal link between chronic condition progression and health care utilization, and examine whether intergenerational financial support is a moderator in this relationship among Chinese rural older people. Methods Data was derived from the Shandong Rural Elderly Health Cohort (SREHC), which was conducted from 2019 to 2020. A total of 2,785 participants were included in this study. Kruskal-Wallis rank tests and generalized estimating equation (GEE) models were employed to analyze the association between chronic condition progression and health care utilization. Moderating effect analysis was performed using GEE model and margins plot. Results Older people with progressive chronic conditions used more outpatient (no chronic condition to emerging multimorbidity: OR = 1.83; p = 0.028; one chronic condition to emerging multimorbidity: OR = 2.17; p

Abstract Background Exposure to indoor air pollution from solid cooking fuel use may increase mental disorders risk through pathways such as oroxidative stress, neuroinflammation, or cerebrovascular damage. However, few studies have explored the underlying mechanism between solid cooking fuel use and psychological distress. The present study aims to investigate the mediating role of sleep quality on the relationship between solid cooking fuel use and psychological distress among older adults in rural Shandong, China. Methods This study used the cross-sectional data from the second follow-up survey of the Shandong Rural Elderly Health Cohort (SREHC). A total of 3,240 rural older adults were included in the analysis. Logistic regression and the Karlson, Holm, and Breen (KHB) mediation analyses were performed to investigate the relationship between solid cooking fuel use and psychological distress, as well as the mediating role of sleep quality in this association. Results This study found that solid cooking fuel use was significantly and positively associated with psychological distress among older adults in rural Shandong, China (OR = 1.38, 95% CI: 1.12,1.70). Mediation analysis revealed that sleep quality mediated the association between solid cooking fuel use and psychological distress among older adults (β = 0.06, P = 0.011). The mediation effect accounted for 16.18% of the total effect. Conclusions Our study showed that solid cooking fuel use was associated with psychological distress among rural older adults, and sleep quality mediated this association. Interventions should focus on addressing cooking fuel types and poor sleep quality to reduce psychological distress. In the future, more aggressive environmental protection policies would be needed to lessen the adverse effects of indoor air pollution on the health of older adults in rural China.

Abstract Abdominal aortic aneurysms (AAA) are a significant health concern in developed countries due to their considerable mortality rate. The crucial factor of the progression of AAA is the release of neutrophils and neutrophil extracellular traps (NETs). Magnetic particle imaging (MPI) is a new imaging technique that offers the capability to detect superparamagnetic iron oxide nanoparticles (SPION) with exceptional sensitivity. We aimed to investigate the functional imaging of MPI for the detection and monitoring of neutrophil infiltration within AAA. A novel multimodal imaging agent targeting neutrophils, PEG-Fe3O4-Ly6G–Cy7 nanoparticles (Ly6G NPs), were designed by coupling Fe3O4 nanoparticles with Ly6G antibodies and Cy7. The targeting and sensitivity of Ly6G NPs were assessed using MPI and fluorescence imaging (FLI) in the AAA mouse model. After the inhibition of NETosis, the degree of neutrophil infiltration and AAA severity were assessed using MPI with Ly6G NPs. Ly6G NPs accurately localized and quantitatively analyzed AAA lesion sites in mice using MPI/FLI/CT. Compared to the control group, elevated MPI and FLI signal intensities were detected at the abdominal aortic lesion site, and neutrophil infiltration and NETs accumulation were detected by histological analysis in the AAA models. After the inhibition of NETs accumulation in vivo, pathological damage in the abdominal aorta was significantly reduced, along with a decrease in the accumulation of Ly6G NPs and MPI signals. This multimodal MPI strategy revealed that nanoparticles targeting Ly6G can be used to detect neutrophil infiltration within AAA and monitor AAA severity.

Despite the advanced technologies and global attention on cancer treatment strategies, cancer continues to claim lives and adversely affects socio-economic development. Although combination therapies were anticipated to eradicate this disease, the resilient and restorative nature of cancers allows them to proliferate at the expense of host immune cells energetically. This proliferation is driven by metabolic profiles specific to the cancer type and the patient. An emerging field is exploring the metabolic reprogramming (MR) of cancers to predict effective treatments. This mini-review discusses the recent advancements in cancer MR that have contributed to predictive, preventive, and precision medicine. Current perspectives on the mechanisms of various cancer types and prospects for MR and personalized cancer medicine are essential for optimizing metabolic outputs necessary for personalized treatments.

Infertility has become one of the most common chronic diseases among reproductive- aged individuals, and male factors account for about 50 %. Zinc is a trace element that is essential for sperm quality and male reproductive system. Although several current studies with small sample sizes have investigated this relationship, the conclusions have been still controversial. Here, using a large population sample involved 25,915 participants from Changzhou Maternity and Child Health Care Hospital, we revealed an inverted “U”-shaped trend between seminal plasma zinc concentrations and sperm motility PR/PR + NP (PR, progressive motility; NP, non-progressive motility). The results showed that the highest values of sperm PR/PR + NP observed in the group with intermediate concentrations of zinc (Group 2, 0.25–2.11 mmol/L). The mean values were 43.17 ± 19.03 % and 56.64 ± 20.28 %, respectively. And the lowest values came out in the highest zinc levels group (Group 4, > 3.04 mmol/L). In vitro cell experiments also showed that zinc caused dose-dependent cytotoxicity for GC-2 cells at a threshold value. Furthermore, RNA-seq analysis demonstrated that high concentrations of zinc exerted toxic effects on GC-2 cells through immune injury. Taken together, our findings suggested that moderate amounts of zinc are crucial for human reproduction and excessive concentrations may have adverse effects on male fertility.

Lower extremity peripheral artery disease (PAD) is a growing global health problem. New methods to diagnose PAD have been explored in recent years. At present, the majority of imaging methods for PAD focus on the macrovascular blood flow, and the exploration of microcirculation and tissue perfusion of PAD remains largely insufficient. In this report, we applied three new imaging technologies, i.e., second near-infrared region (NIR-II, 900–1,880 nm wavelengths) imaging, optical coherence tomography angiography (OCTA), and laser speckle flowgraphy (LSFG), in a PAD patient with a healthy human subject as control. Our results showed that the PAD patient had poorer tissue perfusion than the control without observed adverse effects. Moreover, compared with the first near-infrared region (NIR-I, 700–900 nm wavelengths) imaging results, NIR-II imaging had a higher signal-to-background ratio and resolution than NIR-I imaging and detected microvessels that were not detected by NIR-I imaging. These observations suggested that NIR-II imaging, OCTA, and LSFG are potentially safe and effective methods for diagnosing PAD.

Abstract Background This study aimed to explore the association between hypertension follow-up management and family doctor contract services, as well as to examine whether socioeconomic status (SES) had an interaction effect on this relationship among older adults in China. Methods We used data from the sixth National Health Service Survey of Shandong Province, China, including 3,112 older adults (age ≥ 60 years) with hypertension in 2018. Logistic regression models and a margins plot were used to analyze the role of SES in the relationship between hypertension follow-up management and family doctor contract services. Results The regular hypertension follow-up management rate and family doctor contracting rate were 81.8% and 70.9%, respectively, among older adults with hypertension. We found that participants with regular hypertension follow-up management were more likely to sign family doctor contract services (OR=1.28, 95%CI: 1.04, 1.58, P=0.018). The interaction effect occurred in the groups who lived in rural areas (OR=1.55, 95%CI: 1.02, 2.35), with high education level (OR=0.53, 95%CI: 0.32, 0.88) and had high incomes (OR=0.53, 95%CI: 0.35, 0.81). Conclusions Our findings suggested that regular hypertension follow-up management was associated with family doctor contract services and SES influenced this relationship. Primary health care should improve the contracting rate of family doctors by strengthening follow-up management of chronic diseases. Family doctors should focus on improving services quality and enriching the content of service packages especially for older adults with higher income and education level.

Abstract Background Catastrophic health expenditure (CHE) has a considerable impact on older people in later life, but little is known about the relationship between catastrophic health expenditure and health-related quality of life (HRQOL). The aim of this study was to examine the relationship between catastrophic health expenditure and health-related quality of life in older people, and to explore whether the daily care provided by adult children is a moderator in this relationship. Methods Data from the sixth National Health Services Survey in Shandong Province, China. The sample consisted of 8599 elderly people (age ≥ 60 years; 51.7% of female). Health-related quality of life was measured by the health utility value of EQ-5D-3 L. Interaction effects were analyzed using Tobit regression models and marginal effects analysis. Results The catastrophic health expenditure prevalence was 60.5% among older people in Shandong, China. catastrophic health expenditure was significantly associated with lower health-related quality of life (β= − 0.142, P

Abstract Background Atherosclerosis (AS) is a persistent inflammatory condition triggered and exacerbated by several factors including lipid accumulation, endothelial dysfunction and macrophages infiltration. Nobiletin (NOB) has been reported to alleviate atherosclerosis; however, the underlying mechanism remains incompletely understood. Methods This study involved comprehensive bioinformatic analysis, including multidatabase target prediction; GO and KEGG enrichment analyses for function and pathway exploration; DeepSite and AutoDock for drug binding site prediction; and CIBERSORT for immune cell involvement. In addition, target intervention was verified via cell scratch assays, oil red O staining, ELISA, flow cytometry, qRT‒PCR and Western blotting. In addition, by establishing a mouse model of AS, it was demonstrated that NOB attenuated lipid accumulation and the extent of atherosclerotic lesions. Results (1) Altogether, 141 potentially targetable genes were identified through which NOB could intervene in atherosclerosis. (2) Lipid and atherosclerosis, fluid shear stress and atherosclerosis may be the dominant pathways and potential mechanisms. (3) ALB, AKT1, CASP3 and 7 other genes were identified as the top 10 target genes. (4) Six genes, including PPARG, MMP9, SRC and 3 other genes, were related to the M0 fraction. (5) CD36 and PPARG were upregulated in atherosclerosis samples compared to the normal control. (6) By inhibiting lipid uptake in RAW264.7 cells, NOB prevents the formation of foam cell. (7) In RAW264.7 cells, the inhibitory effect of oxidized low-density lipoprotein on foam cells formation and lipid accumulation was closely associated with the PPARG signaling pathway. (8) In vivo validation showed that NOB significantly attenuated intra-arterial lipid accumulation and macrophage infiltration and reduced CD36 expression. Conclusions Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

With the growing interest to harness cancer metabolism and energy reprogramming, this mini review aimed to explain the metabolic programming revealing the mechanisms regarding the treatment resistance. This mini review summarized the prominent cancer metabolic reprogramming on macromolecules. In addition, metabolic reprogramming explaining immune response and treatment resistance as well as energy reprogramming mechanisms are briefly discussed. Finally, some prospects in MR for reversing cancer drug resistance are highlighted.

BackgroundAtherosclerosis (AS) is a chronic arterial pathology and a leading cause of vascular disease-related mortality. Fatty streaks in the arterial wall develop into atherosclerosis and characteristic plaques. Clinical interventions typically involve lipid-lowering medications and drugs for stabilizing vulnerable plaques, but no direct therapeutic agent specifically targets atherosclerosis. Garlic, also locally known as DASUAN, is recognized as a widely sold herbal dietary supplement esteemed for its cardiovascular benefits. However, the specific mechanisms of garlic’s anti-atherosclerotic effects remain unclear.AimsThis study aims to elucidate the pharmacological mechanisms through which garlic ameliorates atherosclerosis.MethodsThe study identified the major active components and targets of garlic by screening the TCMSP, TCM-ID, and, ETCM databases. Atherosclerosis-associated targets were obtained from the DisGeNET, GeneCards, and DiGSeE databases, and garlic intervention targets were determined through intersection. Utilizing the intersected genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using R software. A garlic component-disease target network was constructed using Cytoscape. RNA-seq datasets from the GEO database were utilized to identify differentially expressed genes (DEGs) associated with atherosclerosis. The target genes were intersected with DEGs and the FerrDb (ferroptosis database). Molecular docking predicted the binding interactions between active components and the core targets. In vitro and in vivo experiments validated the identified core targets.ResultsThe integration of garlic drug targets with atherosclerotic disease targets identified 230 target genes. Intersection with RNA-seq DEGs revealed 15 upregulated genes, including 8 target genes related to ferroptosis. Molecular docking indicated favorable affinities between garlic active components [Sobrol A, (+)-L-Alliin, Benzaldoxime, Allicin] and target genes (DPP4, ALOX5, GPX4). Experimental validation showed that GARLIC reduces the expression of ferroptosis-related genes in AS, suggesting its therapeutic potential through the regulation of ferroptosis.ConclusionGarlic ameliorates atherosclerosis by targeting intra-plaque ferroptosis and reducing lipid peroxidation. These findings provide novel insights into the pharmacological mechanisms underlying the efficacy of garlic in treating AS.

BackgroundBile acids (BAs), products of gut microbiota metabolism, have long been implicated in atherosclerotic disease pathogenesis. Characterizing the serum bile acid profile and exploring its potential role in carotid atherosclerosis (CAS) development are crucial tasks.MethodsIn this study, we recruited 73 patients with CAS as the disease group and 77 healthy individuals as the control group. We systematically measured the serum concentrations of 15 bile acids using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression were applied to analyze the impact of bile acids on the disease and select the key BAs. The possible molecular mechanism was elucidated by network pharmacology.Results(1) The BA profile of patients with CAS significantly differed. (2) Multifactorial logistic regression analysis identified elevated levels of GCDCA (OR: 1.01, P < 0.001), DCA (OR: 1.01, P = 0.005), and TDCA (OR: 1.05, P = 0.002) as independent risk factors for CAS development. Conversely, GCA (OR: 0.99, P = 0.020), LCA (OR: 0.83, P = 0.002), and GUDCA (OR: 0.99, P = 0.003) were associated with protective effects against the disease. GCA, DCA, LCA, and TDCA were identified as the four key BAs. (3) TNF, FXR, GPBAR1, ESR1 and ACE were predicted to be targets of BAs against AS. These four BAs potentially impact AS progression by triggering signaling pathways, including cAMP, PPAR, and PI3K-AKT pathways, via their targets.ConclusionThis study offers valuable insights into potential therapeutic strategies for atherosclerosis that target bile acids.

Abstract Background This study investigated the relationship between activities of daily living (ADL) limitations and the use of physical examination among older adults receiving informal care, and to further examine whether this relationship varies by gender and urban-rural areas. Methods The data in this study were obtained from the sixth Health Service of Shandong province, China. In total, 8,358 older adults aged 60 years or older who received informal care were included in the analysis. Binary logistic regression models were conducted to explore the association between ADL limitations and the use of physical examination and examine the differences between gender and urban-rural areas. Results The prevalence of limitations in ADL and physical examination utilization rate among older adults receiving informal care in Shandong Province were 14.12% and 72.31%, respectively. After adjusting for confounders, ADL limitations were negatively correlated with the utilization of physical examination services among older adults receiving informal care (OR = 0.74, 95% CI: 0.64, 0.87, P

Abstract Background Single-nucleotide polymorphisms (SNPs) are the most widely used form of molecular genetic variation studies. As reference genomes and resequencing data sets expand exponentially, tools must be in place to call SNPs at a similar pace. The genome analysis toolkit (GATK) is one of the most widely used SNP calling software tools publicly available, but unfortunately, high-performance computing versions of this tool have yet to become widely available and affordable. Results Here we report an open-source high-performance computing genome variant calling workflow (HPC-GVCW) for GATK that can run on multiple computing platforms from supercomputers to desktop machines. We benchmarked HPC-GVCW on multiple crop species for performance and accuracy with comparable results with previously published reports (using GATK alone). Finally, we used HPC-GVCW in production mode to call SNPs on a “subpopulation aware” 16-genome rice reference panel with ~ 3000 resequenced rice accessions. The entire process took ~ 16 weeks and resulted in the identification of an average of 27.3 M SNPs/genome and the discovery of ~ 2.3 million novel SNPs that were not present in the flagship reference genome for rice (i.e., IRGSP RefSeq). Conclusions This study developed an open-source pipeline (HPC-GVCW) to run GATK on HPC platforms, which significantly improved the speed at which SNPs can be called. The workflow is widely applicable as demonstrated successfully for four major crop species with genomes ranging in size from 400 Mb to 2.4 Gb. Using HPC-GVCW in production mode to call SNPs on a 25 multi-crop-reference genome data set produced over 1.1 billion SNPs that were publicly released for functional and breeding studies. For rice, many novel SNPs were identified and were found to reside within genes and open chromatin regions that are predicted to have functional consequences. Combined, our results demonstrate the usefulness of combining a high-performance SNP calling architecture solution with a subpopulation-aware reference genome panel for rapid SNP discovery and public deployment.

To develop a national reference panel for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen detection kit and establish a quality standard. The cultures of SARS-CoV-2 and other pathogens were collected to establish a national reference panel for SARS-CoV-2 antigen detection. The stability and homogeneity of the reference panel were evaluated. Based on World Health Organization (WHO) guidance and nucleic acid quantitative results, a quality standard reference panel was established. Currently, three generations of SARS-CoV-2 antigen national reference materials with batch numbers 370095–202001, 370095–202202, and 370095–202203 have been successfully established. These national reference panels comprised 8 positive samples, 20 negative samples, 1 repetitive sample, and 1 lower detection limit sample. The stability and homogeneity of the reference panel meet the requirements. The quality standards are as follows: the positive and negative coincidence rates are 8/8 and 20/20, respectively. The 10 test results of the medium and low-concentration repetitive reference materials should be positive, and the color rendering should be uniform (or the coefficient of variance should not be higher than 20.0%). The lower detection limit should be at least 5 × 105 U/mL (equivalent to copies/mL), and higher concentrations above the lower detection limit must be positive. A national reference panel for the SARS-CoV-2 antigen detection kit has been established. As the standard of SARS-CoV-2 antigen reagents, the reference panel has played a crucial role in the pre-marketing quality evaluation and post-marketing quality supervision in China.

Abstract Immunity-and-matrix-regulatory cells (IMRCs) derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix, which could be mass-produced with stable biological properties. Despite resemblance to mesenchymal stem cells (MSCs) in terms of self-renew and tri-lineage differentiation, the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined. Here, we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury. Following injection into the knees of rabbits with meniscal injury, IMRCs enhanced endogenous fibrocartilage regeneration. In the dose-escalating phase I clinical trial (NCT03839238) with eighteen patients recruited, we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting. Furthermore, the effective results of magnetic resonance imaging (MRI) of meniscus repair and knee functional scores suggested that 5 × 107 cells are optimal for meniscus injury treatment. In summary, we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury. Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

Based on the factor endowment theory and the agriculture-induced technological innovation theory, this study examines the impact of high-standard farmland construction (HFC) on agricultural ecological efficiency (AEE) and sustainable agricultural development. Using empirical data from 30 provinces in China between 2005 and 2022, it explores how high-standard farmland construction techniques can enhance AEE, considering factor endowment preferences and geographical characteristics. Empirical research indicates that high-standard farmland significantly enhances AEE, particularly in the eastern region, the main grain-producing areas, and the regions with less geographical fluctuation. Additionally, agricultural innovations, capital accumulation, and land circulation reinforce the benefits of such construction, whereas labor mobility has a moderating effect. Quantile regression analyses show that the impact of HFC on AEE initially increases and then diminishes, potentially due to inadequate post-management and maintenance. Consequently, the study recommends that the government enhance policy support and supervision for high-standard farmland projects, integrate agricultural technology with capital accumulation, optimize human resource allocation, guide labor mobility, and reform land transfer systems to boost AEE and sustainability.

Leaf width is a key determinant of planting density and photosynthetic efficiency. In an effort to determine which genes regulate maize plant leaf width, we performed a genome-wide association study (GWAS) of 1.49 × 106 single nucleotide polymorphisms (SNPs) in 80 sequenced backbone inbred maize lines in Jilin Province, China, based upon phenotypic leaf width data from two years. In total, 14 SNPs were identified as being significantly related to leaf width (p < 0.000001), with these SNPs being located on chromosomes 1, 2, 3, 5, 6, 7, 8, and 9. A total of five candidate genes were identified within a mean linkage disequilibrium (LD) distance of 9.7 kb, with a significant SNP being identified within the Zm00001d044327 candidate gene. RNA was then isolated from 12 different inbred maize lines from this GWAS study cohort and was used to conduct qPCR analyses which revealed significant differences in Zm00001d044327 expression among strains exhibiting significant differences in leaf width. Based on an assessment of EMS mutant lines harboring a conserved amino acid stop mutation and two non-synonymous mutations in Zm00001d044327 that exhibited a narrow leaf width, these data suggested that Zm00001d044327 is a key regulator of maize leaf width.

Background: Allergen immunotherapy (AIT) is still the only treatment that may affect the natural cause of allergic disease. This study is to investigate whether an accelerated up-dosing scheme for subcutaneous allergen immunotherapy (SCIT) using a native house dust mite (HDM) allergen extract is as safe as the standard 3-strengths dose-escalation scheme in children with moderate to severe allergic rhinitis or rhinoconjunctivitis with or without asthma in China. Methods: In this multicenter, open label, randomized controlled trial, the children aged 5–14 years were randomized 1:1 either to One Strength group or the Standard group. The dose escalation scheme for patients in the One Strength group included 6 injections of strength 3, whereas the Standard group comprised 14 injections using strength 1, 2, and 3. All treatment-emergent adverse events (TEAEs) were recorded and analyzed. The 5-point Likert scale was used to assess tolerability (ChiCTR2100050311). Results: Overall, 101 children were included in the Safety Set (One Strength group: 50 vs. Standard group: 51). A total of 26 TEAEs were reported for 15 children. TEAEs related to AIT occurred in 10 % of the children in the One Strength group and 11.8 % of the Standard group. The number of systemic adverse reactions was comparable in both groups (One Strength: 5 vs. Standard: 4). No serious TEAEs was recorded for either group. 90.0 % of patients in the One Strength group reached the maintenance dose without an interventional dose adjustment due to adverse events, compared to 78.4 % in the Standard group. All patients who completed the dose-escalation phase reached the recommended maintenance dose of 1.0 ml of strength 3.Investigators and patients rated the tolerability of the One Strength regimen slightly better than the Standard scheme. Conclusions: This exploratory study suggests that the accelerated One Strength dose-escalation scheme is comparable in safety and tolerability to the Standard regimen. However, due to the preliminary nature and small sample size, further research with larger sample sizes and robust study designs is necessary for confirmation.

Tibet orbivirus (TIBOV) was first isolated from Anopheles maculatus mosquitoes in Xizang, China, in 2009. In recent years, more TIBOV strains have been isolated in several provinces across China, Japan, East Asia, and Nepal, South Asia. Furthermore, TIBOVs have also been isolated from Culex mosquitoes, and several midge species. Additionally, TIBOV neutralizing antibodies have been detected in serum specimens from several mammals, including cattle, sheep, and pigs. All of the evidence suggests that the geographical distribution of TIBOVs has significantly expanded in recent years, with an increased number of vector species involved in its transmission. Moreover, the virus demonstrated infectivity towards a variety of animals. Although TIBOV is considered an emerging orbivirus, detailed reports on its genome and molecular evolution are currently lacking. Thus, this study performed the whole-genome nucleotide sequencing of three TIBOV isolates from mosquitoes and midges collected in China in 2009, 2011, and 2019. Furthermore, the genome and molecular genetic evolution of TIBOVs isolated from different countries, periods, and hosts (mosquitoes, midges, and cattle) was systematically analyzed. The results revealed no molecular specificity among TIBOVs isolated from different countries, periods, and vectors. Meanwhile, the time-scaled phylogenetic analysis demonstrated that the most recent common ancestor (TMRCA) of TIBOV appeared approximately 797 years ago (95% HPD: 16-2347) and subsequently differentiated at least three times, resulting in three distinct genotypes. The evolutionary rate of TIBOVs was about 2.12 × 10-3 nucleotide substitutions per site per year (s/s/y) (95% HPD: 3.07 × 10-5, 9.63 × 10-3), which is similar to that of the bluetongue virus (BTV), also in the Orbivirus genus. Structural analyses of the viral proteins revealed that the three-dimensional structures of the outer capsid proteins of TIBOV and BTV were similar. These results suggest that TIBOV is a newly discovered and rapidly evolving virus transmitted by various blood-sucking insects. Given the potential public health burden of this virus and its high infectious rate in a wide range of animals, it is significant to strengthen research on the genetic variation of TIBOVs in blood-feeding insects and mammals in the natural environment and the infection status in animals.

Abstract Endogenous essential metal ions play an important role in many life processes, especially in tumor development and immune response. The approval of various metallodrugs for tumor therapy brings more attention to the antitumor effect of metal ions. With the deepening understanding of the regulation mechanisms of metal ion homeostasis in vivo, breaking intracellular metal ion homeostasis becomes a new means to inhibit the proliferation of tumor cells and activate antitumor immune response. Diverse nanomedicines with the loading of small molecular ion regulators or metal ions have been developed to disrupt metal ion homeostasis in tumor cells, with higher safety and efficiency than free small molecular ion regulators or metal compounds. This comprehensive review focuses on the latest progress of various intracellular metal ion homeostasis regulation‐based nanomedicines in tumor therapy including calcium ion (Ca2+), ferrous ion (Fe2+), cuprous ion (Cu+), managanese ion (Mn2+), and zinc ion (Zn2+). The physiological functions and homeostasis regulation processes of ions are summarized to guide the design of metal ion regulation‐based nanomedicines. Then the antitumor mechanisms of various ions‐based nanomedicines and some efficient synergistic therapies are highlighted. Finally, the challenges and future developments of ion regulation‐based antitumor therapy are also discussed, hoping to provide a reference for finding more effective metal ions and synergistic therapies.

Abstract Background The purpose of this study was to evaluate the relationship between activities of daily living (ADL) limitations and family doctor contract services among overweight and obese older adults, as well as to examine whether this association varies by urban-rural residence. Methods Data for the present study were obtained from the sixth Health Service of Shandong province, China. A total of 4,249 overweight and obese older adults were included in this study. Binary logistic regression models were used to evaluate the relationship between ADL limitations and family doctor contract services, to examine the potential differences between urban and rural areas. Results Of 4,249 overweight and obese older adults, the prevalence of limitations in ADL and family doctor service contracting rate in Shandong province were 12.47% and 66.46%, respectively. The results of the regression analyses revealed that overweight and obese older adults with ADL limitations were more likely to sign up for family doctor services than those without ADL limitations (OR = 1.27, 95%CI: 1.02–1.58, P = 0.033). Only among rural overweight and obese older adults, the relationship between ADL limitations and family doctor contract services was statistically significant (OR = 1.50, 95%CI: 1.13–1.99, P = 0.005). Conclusions Our study found a significant association between ADL limitations and family doctor contract services among overweight and obese older adults in Shandong, China. This relationship differed by urban-rural residence. To promote the positive development of the family doctor contract service system, the government should increase publicity, provide personalized contracted services, and prioritize the healthcare needs of overweight and obese older adults with ADL limitations, with special attention to rural areas.

Abstract Background Non‐small cell lung cancer (NSCLC) is the most common type of lung cancer with high morbidity and mortality. The role of dysregulated circular RNAs (circRNAs) in human diseases are receiving more and more attention. In this study, we focused on the role and mechanism of circPKM2 in the progression of NSCLC. Methods The expression levels of circPKM2, microRNA‐1298‐5p (miR‐1298‐5p) and metadherin (MTDH) in NSCLC were measured by real‐time quantitative PCR (qRT‐PCR) or Western blot. Cell counting kit‐8 (CCK‐8), colony formation, 5‐ethynyl‐2′‐deoxyuridine (EdU) staining, flow cytometry, transwell and tube formation assays were conducted to evaluate the effects of circPKM2 on malignant phenotypes of NSCLC. Western blot was used to measure related marker protein levels. Results CircPKM2 and MTDH were highly expressed in NSCLC tissues and cells, while miR‐1298‐5p was downregulated. CircPKM2 knockdown effectively suppressed cell proliferation, migration, invasion and tube formation whereas induced apoptosis in vitro. CircPKM2 had a potential targeting site with miR‐1298‐5p and negatively regulated the expression of miR‐1298‐5p. MiR‐1298‐5p inhibitor reversed the effect of circPKM2 knockdown on the progression of NSCLC. CircPKM2 induced MTDH expression via sponging miR‐1298‐5p to promote the progression of NSCLC. MiR‐1298‐5p directly targeted MTDH, and the addition of MTDH partially attenuated the inhibition of miR‐1298‐5p on the progression of NSCLC. In addition, the downregulation of circPKM2 significantly slowed down the growth of xenograft tumors in vivo. Conclusion Our findings demonstrated that circPKM2 mediated NSCLC progression via regulating miR‐1298‐5p/MTDH axis, providing a novel therapeutic target for NSCLC.

Abstract Background Studies have proven that the risk of acute kidney injury (AKI) increased in patients with malnutrition. Prognostic nutritional index (PNI) and geriatric nutritional risk index (GNRI) were general tools to predict the risk of mortality, but the prognostic value of them for in-hospital mortality among patients with AKI have not been validated yet. Herein, this study aims to explore the association between PNI and GNRI and 30-day mortality in patients with AKI. Methods Demographic and clinical data of 863 adult patients with AKI were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database in 2001–2012 in this retrospective cohort study. Univariate and multivariate Cox proportional regression analyses were used to explore the association between PNI and GNRI and 30-day mortality. The evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses of age, Sequential Organ Failure Assessment (SOFA) score and Simplified Acute Physiology (SAPS-II) score were also performed. Results Totally, 222 (26.71%) patients died within 30 days. After adjusting for covariates, PNI ≥ 28.5 [HR = 0.71, 95%CI: (0.51–0.98)] and GNRI ≥ 83.25 [HR = 0.63, 95%CI: (0.47–0.86)] were both associated with low risk of 30-day mortality. These relationships were also found in patients who aged ≥ 65 years old. Differently, high PNI level was associated with low risk of 30-day mortality among patients with SOFA score

Objective: Necrotizing enterocolitis (NEC) is characterized by a rich infiltration of macrophages in the intestines, which is derived from monocytes in the blood. The authors aimed to explore the changing trend of absolute monocyte counts (AMC) over time in NEC infants and to verify whether the reduction of AMC correlates with the severity of NEC and whether it can be used to identify infants who need surgery. Method: The authors collected the clinical data of 66 control and 222 NEC infants. The NEC infants were divided into medical NEC (M-NEC) and surgical NEC (S-NEC). The counting of monocyte and their percentage change were compared at the time of birth, before NEC (baseline), the onset of NEC and after NEC (recovery). In addition, the same comparison was made among stages 1, 2 and 3 of Bell's staging, respectively. Results: The authors found that the AMC in NEC infants decreased sharply at the onset. Further comparison was made between 172 cases of M-NEC and 50 cases of S-NEC. It was discovered that the AMC reduced more in S-NEC infants at onset, but it increased more at recovery. In addition, the authors found that among stage 1,2 and 3, stage 3 had the lowest AMC and the largest percentage decrease at the onset. Conclusion: The AMC decreases sharply in NEC infants at onset, and the degree of decline is associated with the severity of NEC. AMC is expected to be a marker of NEC and provide a reference for clinicians in the diagnosis and treatment of NEC.

Abstract Background The objective of this study was to investigate the association between white blood cell count to hemoglobin ratio (WHR) and risk of in-hospital mortality in patients with lung cancer. Methods In this retrospective cohort study, the medical records of patients with lung cancer were retrieved from the electronic ICU (eICU) Collaborative Research Database between 2014 and 2015. The primary outcome was in-hospital mortality. The secondary outcome was the length of stay in intensive care unit (ICU). The cut-off value for the WHR was calculated by the X-tile software. The Cox model was applied to assess the association between WHR and in-hospital mortality among patients with lung cancer and the linear regression model was used to investigate the association between WHR and length of ICU stay. Subgroup analyses of age ( = 65 years), Acute Physiology and Chronic Health Evaluation (APACHE) score ( = 59), gender, ventilation (yes or no), and vasopressor (yes or no) in patients with lung cancer were conducted. Results Of the 768 included patients with lung cancer, 153 patients (19.92%) died in the hospital. The median total follow-up time was 6.88 (4.17, 11.23) days. The optimal cut-off value for WHR was 1.4. ICU lung cancer patients with WHR > = 1.4 had a significantly higher risk of in-hospital mortality [Hazard ratio: (HR): 1.65, 95% confidence interval (CI): 1.15 to 2.38, P = 0.007) and length of stay in ICU (HR: 0.63, 0.01, 95% CI: 1.24 to 0.045, P = 0.045). According to the subgroup analysis, WHR was found to be associated with in-hospital mortality in patients with higher APACHE score (HR: 1.60, 95% CI: 1.06 to 2.41, P = 0.024), in male patients (HR: 1.87, 95% CI: 1.15 to 3.04, P = 0.012), and in patients with the treatment of ventilation (HR: 2.33, 95% CI: 1.49 to 3.64, P

bZIP transcription factors play important roles in regulating plant development and stress responses. Although bZIPs have been identified in many plant species, there is little information on the bZIPs in Chrysanthemum. In this study, bZIP TFs were identified from the leaf transcriptome of C. mongolicum, a plant naturally tolerant to drought. A total of 28 full-length bZIP family members were identified from the leaf transcriptome of C. mongolicum and were divided into five subfamilies based on their phylogenetic relationships with the bZIPs from Arabidopsis. Ten conserved motifs were detected among the bZIP proteins of C. mongolicum. Subcellular localization assays revealed that most of the CmbZIPs were predicted to be localized in the nucleus. A novel bZIP gene, designated as CmbZIP9, was cloned based on a sequence of the data of the C. mongolicum transcriptome and was overexpressed in tobacco. The results indicated that the overexpression of CmbZIP9 reduced the malondialdehyde (MDA) content and increased the peroxidase (POD) and superoxide dismutase (SOD) activities as well as the expression levels of stress-related genes under drought stress, thus enhancing the drought tolerance of transgenic tobacco lines. These results provide a theoretical basis for further exploring the functions of the bZIP family genes and lay a foundation for stress resistance improvement in chrysanthemums in the future.

This study examines the effects of digital financial inclusion on non-farm employment of rural labor and the mediating mechanism of innovation and entrepreneurship activity using China Family Panel Studies (CFPS) and the provincial index of digital financial inclusion. Through the empirical test of the Probit model and mediation effect model, we found that: firstly, digital financial inclusion can promote non-farm employment of rural labor, with the level of digitalization having the most significant impact; secondly, by encouraging innovation and entrepreneurial activity, digital financial inclusion can promote non-farm employment of rural labor; thirdly, the driving effect of digital financial inclusion on non-farm employment of rural labor is more pronounced among the unmarried, eastern region, and male labor. Therefore, we should improve the construction of rural digital infrastructure and accelerate the development of inclusive rural finance to promote more diversified non-farm employment options for “disadvantaged groups”; encourage and support innovation at the government level, and create a favorable atmosphere for innovation and entrepreneurship. Simultaneously, farmers’ digital literacy and financial knowledge should be improved so that more can adopt and take advantage of digital financial inclusion.

Abstract Neuroblastoma (NB) is a kind of typical life-threatening extracranial tumor in children. N6-methyladenosine (m6A) modification is closely related to multiple cancer pathological processes. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) is a top-ranked prognostic risk gene in NB; however, its function is uncertain. The expression of m6A-associated enzymes in patients with NB was analyzed using the Gene Expression Omnibus (GEO) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. The IGF2BP3 level in NB cell lines and primary samples was tested using quantitative real-time polymerase chain reaction (qRT-PCR), western blot method, and immunohistochemical analysis. The IGF2BP3 function in cell proliferation was clarified based on many functional in vitro and in vivo experiments. The interaction between IGF2BP3 and N-myc was researched via RNA immunoprecipitation (RIP), m6A RNA immunoprecipitation (MeRIP), and chromatin immunoprecipitation (ChIP) assays. The 16 m6A-regulated enzymes in NB were researched, and the result indicated that IGF2BP3 overexpression was related to cancer progression, COG risk, and survival based on the GEO and TARGET databases. Besides, the IGF2BP3 and MYCN levels were positively correlated. IGF2BP3 expression levels increased in MYCN-amplified NB clinical samples and cells. Knockdown of IGF2BP3 inhibited N-myc expression and NB cell proliferation in vitro and in vivo. IGF2BP3 regulates MYCN RNA stability by modifying m6A. In addition, we demonstrated that N-myc is a transcription factor that directly promotes IGF2BP3 expression in NB cells. IGF2BP3 regulates the proliferation of NB cells via m6A modification of MYCN. N-myc also acts as a transcription factor that regulates IGF2BP3 expression. A positive feedback loop between IGF2BP3 and N-myc facilitates NB cell proliferation.

AbstractContrast-induced acute kidney injury (CI-AKI) has become the third leading cause of hospital-acquired kidney injury. A comprehensive analysis of the current state of research in the field of CI-AKI will help to reveal trends and hot topics in the field. To date, there are no published bibliometric analyses related to CI-AKI studies. Here, we analyze the relevant literature since the emergence of the concept and provide valuable insights. The literature was collected from the Web of Science Core Collection. The data were analyzed visually using CiteSpace and VOSviewer software. We collected a total of 4775 papers, with the United States and Guangdong Acad Med Sci as the major publishing powers in terms of country/region and institution. J AM COLL CARDIOL was the journal with the most published and cocited articles. Cluster analysis showed that clinical trials are the current research hotspot. The areas of risk assessment, prevention strategies, risk factors, and vascular lesions have been popular in recent years. Research on the mechanism of injury in CI-AKI will be the focus of future research, which will be crucial to reduce the clinical incidence of CI-AKI. In summary, this study provides a comprehensive analysis of the development process in the field of CI-AKI and discusses future research directions based on the analysis of objective data from many studies on CI-AKI.

Wastewater containing organic dyes has become one of the important challenges in water treatment due to its high salt content and resistance to natural degradation. In this work, a novelty adsorbent, PEI-SMA, was prepared by grafting polyethyleneimine (PEI) onto styrene-maleic anhydride copolymer (SMA) through an amidation reaction. The various factors, such as pH, adsorbent dosage, contact time, dye concentration, and temperature, which may affect the adsorption of PEI-SMA for Reactive Black 5 (RB5), were systematically investigated by static adsorption experiments. The adsorption process of PEI-SMA for RB5 was more consistent with the Langmuir isotherm model and the pseudo-second-order model, suggesting a single-layer chemisorption. PEI-SMA exhibits excellent adsorption performance for RB5 dye, with a maximum adsorption capacity of 1749.19 mg g–1 at pH = 2. Additionally, PEI-SMA exhibited highly efficient RB5 competitive adsorption against coexisting Cl− and SO42− ions and cationic dyes. The adsorption mechanism was explored, and it can be explained as the synergistic effect of electrostatic interaction, hydrogen bonding and π–π interaction. This study demonstrates that PEI-SMA could act as a high performance and promising candidate for the effective adsorption of anionic dyes from aqueous solutions.

Nanotheranostic agents capable of simultaneously enabling real-time tracking and precise treatment at tumor sites play an increasingly pivotal role in the field of medicine. In this article, we report a novel near-infrared-II window (NIR-II) emitting downconversion rare-earth nanoparticles (RENPs) to improve image-guided therapy for breast cancer. The developed α-NaErF4@NaYF4 nanoparticles (α-Er NPs) have a diameter of approximately 24.1 nm and exhibit superior biocompatibility and negligible toxicity. RENPs exhibit superior imaging quality and photothermal conversion efficiency in the NIR-II range compared to clinically approved indocyanine green (ICG). Under 808 nm laser irradiation, the α-Er NPs achieve significant tumor imaging performance and photothermal effects in vivo in a mouse model of breast cancer. Simultaneously, it combines X-ray computed tomography (CT) and ultrasound (US) tri-modal imaging to guide therapy for cancer. The integration of NIR-II imaging technology and RENPs establishes a promising foundation for future medical applications.

Summary: Epigenetic alterations are especially important in necrotizing enterocolitis (NEC). Here, we reported that histone deacetylase 8 (HDAC8) plays a previously unknown role in modulating arginine metabolism via acetylation of histone 3 lysine 9 (acetyl-H3K9) regulation during the pathogenesis of NEC. We found that HDAC8 was upregulated in humans and mice intestinal samples with NEC, while selective inhibition of HDAC8 expression ameliorated NEC. HDAC8 regulates enzymes involved in the metabolic conversion of proline to arginine (PRODH, PRODH2, OAT, and OTC) and arginine to ornithine (ARG1). The results showed that H3K9ac signal in the PRODH/PRODH2 promoter region was mediated by HDAC8. Additionally, the decreased concentration of butyric acid was strongly correlated with elevated HDAC8 levels and circulating arginine, which may result from an unbalanced Firmicutes/Bacteroidetes ratio. These results reveal previously underappreciated roles of microbial metabolites and HDAC8 to coordinate the arginine metabolism during NEC development.

Mesenchymal stromal cells (MSCs) derived from human embryonic stem cells (hESCs) are a desirable cell source for cell therapy owing to their capacity to be produced stably and homogeneously in large quantities. However, a scalable culture system for hPSC-derived MSCs is urgently needed to meet the cell quantity and quality requirements of practical clinical applications. In this study, we developed a new microcarrier with hyaluronic acid (HA) as the core material, which allowed scalable serum-free suspension culture of hESC-derived MSCs (IMRCs). We used optimal microcarriers with a coating collagen concentration of 100 ​μg/mL or concave-structured surface (cHAMCs) for IMRC amplification in a stirred bioreactor, expanding IMRCs within six days with the highest yield of over one million cells per milliliter. In addition, the harvested cells exhibited high viability, immunomodulatory and regenerative therapeutic promise comparable to monolayer cultured MSCs while showing more increased secretion of extracellular matrix (ECM), particularly collagen-related proteins. In summary, we have established a scalable culture system for hESC-MSCs, providing novel approaches for future cell therapies.

BackgroundAccumulating research provides evidence that the psychological health of older people deteriorated from before to during the COVID-19 pandemic. Unlike robust individuals, coexisting frailty and multimorbidity expose older adults to more complicated and wide-ranging stressors. Community-level social support (CSS) is also an important impetus for age-friendly interventions, and it is 1 of the components of social capital that is seen as an ecological-level property. To date, we have not found research that examines whether CSS buffered the adverse impacts of combined frailty and multimorbidity on psychological distress in a rural setting during COVID-19 in China. ObjectiveThis study explores the combined effect of frailty and multimorbidity on psychological distress in rural Chinese older adults during the COVID-19 pandemic and examines whether CSS would buffer the aforementioned association. MethodsData used in this study were extracted from 2 waves of the Shandong Rural Elderly Health Cohort (SREHC), and the final analytic sample included 2785 respondents who participated in both baseline and follow-up surveys. Multilevel linear mixed effects models were used to quantify the strength of the longitudinal association between frailty and multimorbidity combinations and psychological distress using 2 waves of data for each participant, and then, cross-level interactions between CSS and combined frailty and multimorbidity were included to test whether CSS would buffer the adverse impact of coexisting frailty and multimorbidity on psychological distress. ResultsFrail older adults with multimorbidity reported the most psychological distress compared to individuals with only 1 or none of the conditions (β=.68, 95% CI 0.60-0.77, P

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. Whether extracellular vesicles are effective in treating IPF and what is the optimal administrative route is not clear. Our previous studies have shown that immunity and matrix regulatory cells (IMRCs) derived from human embryonic stem cells can safely treat lung injury and fibrosis in mouse models, and its mechanism of action is related to the paracrine effect. In this study, we investigated the therapeutic effects of IMRC-derived extracellular vesicles (IMRC-EVs) on a bleomycin-induced pulmonary fibrosis mouse model and explored the optimal route of administration. Methods To study the biodistribution of IMRC-EVs after administration via different routes, NIR labeled-IMRC-EVs were delivered by intratracheal (IT) or intravenous (IV) route, and in vivo imaging was acquired at different time points. The therapeutic effects of IMRC-EVs delivered by different routes were analyzed by assessing histology, lung function, cytokines levels, and transcriptome profiling. RNA-seq of lung tissues was performed to investigate the mechanisms of EV treatment through IT or IV administrations. Results IMRC-EVs mainly reserved in the liver and spleen when administrated via IV route; and mainly retained in the lungs via the IT route. IMRC-EVs administrated via both routes demonstrated a therapeutic effect as attenuated pulmonary fibrosis, improved lung function, and histological parameters. Based on our RNA-seq results, different pathways may be affected by IMRC-EVs administrated via IT or IV routes. In addition, in vitro experiments showed that IMRC-EVs inhibited epithelial-to-mesenchymal transition induced by TGF-β. Conclusion IMRC-EVs administrated via IT or IV routes generate different biodistributions, but are both effective for the treatment of bleomycin-induced pulmonary fibrosis. The therapeutic mechanisms of IMRC-EVs administrated via different routes may be different.

Abstract Background Population ageing and social transformation present tremendous challenges to the informal support system of older adults, which engendered institutional care in China. This study aimed to examine the association between multimorbidity and institutional care willingness, and investigate whether there is an interaction effects between multimorbidity and functional limitations on institutional care willingness among Chinese older adults. Methods Data were obtained from the sixth National Health Service Survey of Shandong province, China. The sample included 8583 older adults (age ≥ 60 years; 51.7% women), 44.8% without chronic diseases, 34.8% and 20.4% with one chronic condition and multimorbidity, respectively. Multivariable logistic regression models and marginal effects analysis were used to the interaction effects analysis. Results A total of 666 (7.8%) participants had institutional care willingness in Shandong, China. Participants with multimorbidity were more likely to have institutional care willingness than their peers without chronic condition (OR = 1.25, 95% CI = 1.06, 1.55) after adjusted for confounders. Marginal effect analysis showed that under the condition that other variables remain unchanged, the probability of them with multimorbidity choosing institutional care for older adults with functional limitations was 6.9% lower than those without multimorbidity (95% CI = -0.128, -0.010, P = 0.023). The interaction effect between chronic health conditions and functional limitation for older adults to choose institutional care was statistically significant, and the average interaction effect was 4.83% (Z = -2.70, $${S}_{\overline{x} }$$ S x ¯ = 0.0189, P

In this study, starch ferulate was synthesized employing a mechanoenzymatic method, specifically based on the twin screw extrusion technique and lipase catalysis. The research then primarily centered on optimizing process parameters and conducting structural analysis. Optimal conditions were determined to be 8.2% ferulic acid addition, 66 °C extrusion temperature, and 3.2% lipase (N435) addition. The enzyme-catalyzed time was 30 s. The degree of substitution for starch ferulate was quantified at 0.005581 under these specific conditions. The presence of C=O bonds in the synthesized starch ferulate proved that the synthesis process was efficient. Additionally, the crystal structure underwent reconstruction. Observations through Scanning Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM) demonstrated that the mechanoenzymatic method led to an augmentation in the specific surface area of starch molecules, thereby facilitating the exposure of active sites. This breakthrough underscores the vast potential of mechanoenzymatic techniques to revolutionize the rapid and sustainable synthesis of starch ferulate, marking a pioneering stride in ester synthesis. The insights garnered from this study transcend theory, offering a visionary roadmap for the development and real-world deployment of advanced modified starch esters.

IntroductionAsthenozoospermia (AZS) is a leading cause of male infertility, affecting an estimated 18% of infertile patients. Kinesin proteins function as molecular motors capable of moving along microtubules. The highly conserved kinesin family member 9 (KIF9) localizes to the central microtubule pair in the flagella of Chlamydomonas cells. The loss of KIF9 expression in mice has been linked to AZS phenotypes.MethodsVariant screening was performed by whole exome sequencing from 92 Chinese infertile patients with AZS. Western blot was used to was used for analyzing of candidate proteins expression. Patients’ sperm samples were stained with immunofluorescent to visualise proteins localization and were visualised by transmission electron microscopy (TEM) to determine axoneme structures. Co-immunoprecipitation assay was used to verify the binding proteins of KIF9. In vitro fertilization (IVF) was used to evaluate the efficiency of clinical treatment.ResultsBi-allelic KIF9 loss-of-function variants were identified in two unrelated Chinese males exhibiting atypical sperm motility phenotypes. Both of these men exhibited typical AZS and suffered from infertility together with the complete absence of KIF9 expression. In contrast to these KIF9-deficient patients, positive KIF9 staining was evident throughout the flagella of sperm from normal control individuals. KIF9 was able to interact with the microtubule central pair (CP) component hydrocephalus-inducing protein homolog (HYDIN) in human samples. And KIF9 was undetectable in spermatozoa harboring CP deletions. The morphologicy of KIF9-deficient spermatozoa appeared normal under gross examination and TEM. Like in mice, in vitro fertilization was sufficient to overcome the fertility issues for these two patientsDiscussionThese findings indicate that KIF9 associates with the central microtubules in human sperm and that it functions to specifically regulate flagellar swinging. Overall, these results offer greater insight into the biological functions of KIF9 in the assembly of the human flagella and its role in male fertility.

ObjectiveThis study aimed to investigate the efficacy and safety of belimumab for treating children with refractory childhood-onset systemic lupus erythematosus (cSLE).MethodsTwenty-six cSLE patients who received belimumab treatment in our hospital from January 2020 to September 2021 (23 of them for more than 52 weeks) were enrolled in this study. Their clinical and laboratory data, assessment of disease activity, glucocorticoid dosage, and treatment-emergent adverse events (TEAEs) were retrieved for analysis. The paired samples t-test and the nonparametric test were used to compare the baseline and post-treatment data.ResultsThe mean age of onset was 10.3 ± 2.4 years old; the mean disease duration was 41.6 ± 37.4 months; the median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 10 (P25, P75: 3, 17); and the mean Physician’s Global Assessment (PGA) score at baseline was 1.9 ± 1.0. Compared with the baseline values, there was a significant decrease in the 24-h urine protein quantifications at 24 and 52 weeks of treatment (P

This study aimed to explore the latent profiles across perceived parental marital conflict and family cohesion, as well as the transition patterns within-person and within-sample profiles over time. We conducted a 1-year follow-up study with a sample of first-year high school students from China. A total of 453 participants were included in the present analysis. We identified the following three latent profiles: high parental conflict and poor family cohesion profile, moderate parental conflict and family cohesion profile, and low parental conflict and good family cohesion profile. Female students and those who not lived with parents together were more likely to perceive more parental marital conflict and less cohesion in the family. The majority of students with high transition probability remained in the same profiles over time. The counts of latent transition pattern also demonstrated that students remaining in the primary profile over time accounted for the large proportion. The present study advances empirical bases for confirming the family system theory’s notion that the family is not static, but dynamic. Findings provide the optimal timing of interventions toward healthy transition.

BackgroundRecent studies have shown that in-stent neoatherosclerosis (ISNA/NA) is an important cause of late stent failure. A comprehensive understanding of the current state of research in this field will facilitate the analysis of its development trends and hot frontiers. However, no bibliometric correlation has been reported yet. Here, we analyze the relevant literature since the emergence of the concept and provide valuable insights.MethodsPublications were collected from the Web of Science Core Collection (WoSCC) and PubMed. Microsoft Excel, SPSS and CiteSpace were used to analyze and present the data.ResultsA total of 498 articles were collected, with Japan and Cardiovasc Res Fdn being the main publishing forces in all country/region and institutions. J AM COLL CARDIOL is the journal with the most published and co-cited articles. According to co-citation analysis, optical coherence tomography, thrombosis, implantation, restenosis, drug-eluting stent, and bare metal stent have become more and more popular recently.ConclusionISNA is a niche and emerging field. How to reduce the incidence of ISNA and improve the late patency rate of coronary stents may remain a hot spot for future research. The pathogenesis of ISNA also needs to be explored in more depth.

Depression is a common mood disorder that has exhibited an increased incidence rate worldwide, but the overall clinical efficacy of antidepressants remains unsatisfactory. In traditional Ayurveda and Tibetan medicines, β-HgS-containing medicines have been used to treat neurological diseases for thousands of years, and our previous study found that β-HgS ameliorated depression-like behaviors in chronic restraint stress (CRS)-treated or chronic unpredictable mild stress (CUMS)-treated mice. Hence, present study investigated the effects of β-HgS combined with the clinical first-line antidepressants, imipramine (IMI) and sertraline (SER), on depression-like symptoms in CRS- and CUMS-co-treated mice. Our results revealed that β-HgS promoted the antidepressant effect of SER on depression-like behavior in mice, and enhanced its effects on promoting glucocorticoid receptor (GR) expression and neuronal proliferation in key hippocampal subregions, as well as increasing interleukin 10 (IL-10) levels and decreasing malondialdehyde levels in the sera of stress-stimulated mice. As for IMI, β-HgS enhanced its effects on preventing atrophy and severe structural damage in the hippocampus, as well as in promoting hippocampal GR levels and neuronal proliferation and serum IL-10 and superoxide dismutase (SOD) levels. Additionally, combination therapy resulted in the increased diversity of important intestinal microbiota compared to that of monotherapy, which may help sustain the health of the digestive tract and reduce inflammation to further enhance the antidepressant effects of IMI and SER in mice.

ObjectiveThis study aimed to assess the prognostic value of the Nutritional Risk Score 2002 (NRS2002) and patient-generated subjective global assessment (PG-SGA) for post-operative infections in patients with gastric cancer (GC) and colorectal cancer (CRC) who underwent curative surgery.MethodsThis prospective study included 1,493 GC patients and 879 CRC patients who underwent curative surgery at 18 hospitals in China between April 2017 and March 2020. The NRS2002 and PG-SGA were performed on the day of admission. The relationship between the nutritional status of patients before surgery and post-surgical incidence of infection was analyzed using univariate and multiple logistic regression analyses.ResultsAccording to NRS2002, the prevalence of nutritional risk was 51.1% in GC patients and 63.9% in CRC patients. According to the PG-SGA, 38.9% of GC patients and 54.2% of CRC patients had malnutrition. Approximately 4.4% of the GC patients and 9.9% of the CRC patients developed infectious complications after surgery. The univariate and multiple logistic regression analyses showed that the risk of infections was significantly higher in GC patients with a high nutritional risk score (NRS2002 ≥5) than in those with a low score (NRS2002

Aiming at facial expression recognition, the recognition rate is not high due to noise and occlusion. A hybrid approach of facial expression has been presented by combining local and global features. First, feature extraction is performed to fuse the histogram of oriented gradients (HOG) descriptor with the compounded local ternary pattern (C-LTP) descriptor. Second, features extracted by HOG and C-LTP are fused into a single feature vector. Third, the feature vector is sent to a multi-class support vector machine classifier for facial classification. Finally, the proposed method is compared with the existing facial expression recognition methods in three public facial expression image databases, and the results show that the recognition rates of the proposed method in MMI, JAFFE and CK[KG-*2]+ databases are 98.28%, 95.75% and 99.64%, respectively. The average recognition rate is 10% higher than other methods, which is better than other existing methods. The results of this study provide a reference for the research of facial expression recognition in many situations. The method of facial expression recognition proposed can effectively promote the development of human-computer interaction system and the study of computer image understanding. It is of great significance to realize the fusion of human language and natural language, as well as the establishment and implementation of the connection model between language and expression.

An outbreak of viral encephalitis caused by a Japanese encephalitis virus (JEV) genotype IV infection occurred in Australia between 2021 and 2022. A total of 47 cases and seven deaths were reported as of November 2022. This is the first outbreak of human viral encephalitis caused by JEV GIV since it was first isolated in Indonesia in the late 1970s. Here, a comprehensive phylogenetic analysis based on the whole genome sequences of JEVs revealed it emerged 1037 years ago (95% HPD: 463 to 2100 years). The evolutionary order of JEV genotypes is as follows: GV, GIII, GII, GI, and GIV. The JEV GIV emerged 122 years ago (95% HPD: 57–233) and is the youngest viral lineage. The mean substitution rate of the JEV GIV lineage was 1.145 × 10−3 (95% HPD values, 9.55 × 10−4, 1.35 × 10−3), belonging to rapidly evolving viruses. A series of amino acid mutations with the changes of physico-chemical properties located in the functional important domains within the core and E proteins distinguished emerging GIV isolates from old ones. These results demonstrate the JEV GIV is the youngest JEV genotype at a rapid evolution stage and has good host/vector adaptability for introduction to non-endemic areas. Thus, surveillance of JEVs is highly recommended.

LCL filter is widely used in grid-connected converters for good harmonic mitigation performance. However, resonance poles of LCL filter challenge system stability, especially in a digital control system. This paper studies the suppression method of the active power filter output LCL filter resonance. Because of the defect that the traditional active damping based on the filter capacitor current or capacitor voltage feedback needs to add additional sensors, a novel active damping with grid-side current component feedback is proposed. And analysis and design of the feedback function, the resonance suppression characteristics, and the impact on harmonic compensation performance are analyzed in detail respectively and proposes a novel active damping control method based on a quasi-resonant controller grid-side current feedback. On this basis, a mathematical model of the SAPF system with the proposed novel active damping was established, and the resonance characteristics were analyzed. Finally, the proposed method was verified through relevant experiments.

Abstract Background Clinically, skeletal muscle ischemia/reperfusion injury is a life-threatening syndrome that is often caused by skeletal muscle damage and is characterized by oxidative stress and inflammatory responses. Bilobalide has been found to have antioxidative and anti-inflammatory effects. However, it is unclear whether bilobalide can protect skeletal muscle from ischemia/reperfusion injury. Methods The effects of bilobalide on ischemia/reperfusion-injured skeletal muscle were investigated by performing hematoxylin and eosin staining and assessing the wet weight/dry weight ratio of muscle tissue. Then, we measured lipid peroxidation, antioxidant activity and inflammatory cytokine levels. Moreover, Western blotting was conducted to examine the protein levels of MAPK/NF-휅B pathway members. Results Bilobalide treatment could protected hind limb skeletal muscle from ischemia/reperfusion injury by alleviating oxidative stress and inflammatory responses via the MAPK/NF-휅B pathways. Conclusions Bilobalide may be a promising drug for I/R-injured muscle tissue. However, the specific mechanisms for the protective effects still need further study.

The green synthesis of silver nanoparticles (AgNPs) using a water extract of Ginger (Zingiber officinale) root by microwave irradiation and its antibacterial activities have been reported. However, AgNPs prepared from different parts of ginger root water or ethanol extract by ultrasound synthesis and their antioxidant activity and whether the biogenic could be used to catalyze the reduction of hazardous dye are unknown. This study concentrated on the facile green synthesis of AgNPs prepared from different parts (unpeeled ginger, peeled ginger, and ginger peel) of ginger root water or ethanol extract by the ultrasound-assisted method. We studied their antioxidant activity and catalytic degradation of hazardous dye Direct Orange 26 (DO26) and Direct Blue 15 (DB15). The surface plasmon resonance (SPR) peak of AgNPs was at 428-443 nm. The biogenic AgNPs were approximately 2 nm in size with a regular spherical shape identified from TEM analysis. The ethanol extracts of dried unpeeled ginger and peeled ginger, fresh peeled ginger and ginger peel. The Z. officinale AgNPs synthesized by dried unpeeled ginger ethanol extract showed the best antioxidant activity. Their scavenging activities were significantly better than BHT (p

BackgroundTo determine whether the embryo developmental stage affects biochemical or clinical pregnancy loss in young women undergoing frozen-thawed embryo transfer (FET) and to investigate the underlying mechanism.MethodsThis was a retrospective study including a total of 18,34 β-HCG (human chorionic gonadotropin)-positive FET cycles. According to the morphological appearance (MA) of transferred blastocysts, FET cycles with blastocysts were divided into two groups: Group A: morphologically good (MG) blastocysts only, and Group B: at least one morphologically non-good (MNG) blastocyst. FET cycles with day 3 cleavage embryos were assigned as Group C. Biochemical and clinical pregnancy loss were the main outcome measures.Result(s)We predicted 78% in vivo-formed MG and 53.9% in vivo-formed day 5 blastocysts in Group C. (a) Including cases in Group A and Group B for binary logistic regression, we showed that Group B and day 6 blastocysts had significantly higher rates of BPL and CPL than Group A and day 5 blastocysts, respectively. (b) Including cases in Group A, Group B, and Group C for binary logistic regression, we showed that Group C had a significantly higher rate of BPL than Group A and day 5 blastocysts and a similar rate of BPL as Group B and day 6 blastocysts. Group C had a higher rate of CPL than Group A (p=0.071) and day 5 blastocysts (p=0.039), and a lower rate of CPL than Group B (p=0.199) and day 6 blastocysts (p=0.234).Conclusion(s)(1) MA and days of usable blastocysts could serve as independent factors affecting the occurrence of BPL and CPL. (2) Transfer of day 3 cleavage embryos may produce “unusable blastocysts” in vivo, which significantly increased the rate of BPL. (3) The rate of CPL resulting from the transfer of day 3 embryos may depend on the rate of in vivo-formed MG or day 5 blastocysts. Our study indicated that the difference in the BPL or CPL between transfer of blastocysts and day 3 cleavage embryos may largely depend on the quality of embryos transferred.