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BackgroundCognitive function impairment (CFI) and the Composite Dietary Antioxidant Index (CDAI) were investigated in this study.MethodsParticipants from the 2011–2014 cycles of the National Health and Nutrition Examination Survey were chosen to assess cognitive function using the Consortium to Establish a Registry for Alzheimer’s Disease Word Learning Test, the Animal Fluency Test, and the Digit Symbol Substitution Test. Participants scored below the 25% percentile of any of the three tests were defined as having cognitive function impairment. 24-h recalls of diet were collected to calculate CDAI.Results2,424 participants were included. The fully adjusted multivariate logistic regression model showed an increase of one CDAI unit reduced CFI risk by 5% (95% CI: 0.92 ~ 0.98, p = 0.004). When comparing individuals with the lowest CDAI in the first quartile (

Functional gastrointestinal disorders (FGIDs) are characterized by complex interactions between the gut and brain, leading to altered brain function and symptom manifestation. We used neuroimaging meta-analytic techniques in order to analyze the correlation between FGIDs and aberrant brain activity. A systematic review was performed to ascertain resting-state functional magnetic resonance imaging (rs-fMRI) studies examining brain function in FGIDs. Pooled meta-analyses by seed-based d mapping with permutation of subject images (SDM-PSI) were performed to assess variations in regional brain activity, and sensitivity analyses were applied to evaluate the robustness of findings. Meta-regression analyses were then carried out to examine possible links between demographic factors and neuroimaging changes. Our meta-analysis revealed significant changes in regional brain activities among FGIDs patients compared to healthy controls (HC). Increased brain activation was observed in several regions including the postcentral gyrus, calcarine fissure/surrounding cortex, superior frontal gyrus, and insula, while decreased activity was noted in the left posterior cingulate gyrus, right median cingulate/paracingulate gyri, and the left caudate nucleus. Furthermore, meta-regression analyses indicated negative associations between disease duration and alterations in specific brain regions. These findings underscored the intricate interplay between gut dysfunction and aberrant brain activity in FGIDs. Early intervention and multidisciplinary approaches addressing both gastrointestinal symptoms and associated emotional distress are crucial for improving the quality of life of the patients.

The agglomeration of nano carbon black (NCB), driven by its high specific surface energy, limits the fundamental performance of cementitious materials and hinders the broader application of functional cementitious materials in engineering domains. NCB-modified cement (NC) has a low snow-melting efficiency, resulting in high energy consumption and excessive CO2 emissions. Herein, this study innovatively proposed a method of using dispersants to overcome the above issue and systematically introduced the effects of three dispersants, polycarboxylic acid superplasticizer (PCE), tannic acid (TA), and sodium dodecyl sulfate (SDS), on NC. The dispersity of dispersant-NCB suspension was analyzed firstly, and then the performance of fresh paste, mechanical properties, resistivity, snow-melting speed and LCA of NC were explored. Experimental results indicated that, in terms of suspension stability, SDS was the most effective, followed by TA, while PCE exhibited the least efficacy. Furthermore, all three dispersants improved the fluidity of NC to varying degrees. However, PCE and TA demonstrated a retardation effect on the setting time, whereas SDS facilitated a reduction in the setting time of NC. From the point of view of mechanical properties, the use of these dispersants not only augmented the mechanical strength of the NC but also decreased its electrical resistivity. The uniform dispersion of SDS at the microstructural level of NCB had also been found. When the PCE content is 0.2%, TA content is 0.4%, and SDS content is 0.4%, the mechanical strength and resistivity of NC were the best. NC with dispersant TA melted snow three times faster than the control group, reducing snow-melting energy consumption. Moreover, LCA analysis showed that the addition of dispersants also reduced carbon emissions.

IntroductionIschemic stroke is a leading cause of morbidity and mortality in older adults. Therefore, in this study, we sought to understand the interplay between the microbiota, gut, and brain in the context of stroke in older adults.ObjectiveTo determine whether gut microbiota from younger individuals promotes recovery through angiogenesis in both elderly stroke patients and aged stroke mice, we explored the changes in gut microbiota and the correlation between short-chain fatty acids (SCFAs) and angiogenesis in the aged stroke population. Then, we altered the gut microbiome in aged mice by transplanting microbiota from younger donors before inducing experimental stroke to explore the mechanism by which gut microbiota-derived SCFAs promote angiogenesis.MethodsPart I: We conducted a single-center, double-blind trial to compare gut microbiota diversity and SCFA levels in fecal samples from older stroke patients with those from younger stroke patients. Additionally, we measured levels of vascular endothelial growth factor (VEGF) and VEGFC levels in plasma to assess their correlation with SCFA levels. Part II: We performed fecal microbiota transplantation (FMT) 3 days before inducing ischemic stroke in aged male mice (16–18) via distal middle cerebral artery occlusion (dMCAO). The FMT was conducted using gut microbiomes from either young donors (2–3 months) or aged donors (16–18 months).ResultsIn older stroke patients, gut microbiota diversity was significantly reduced compared to that in younger stroke patients. Furthermore, levels of acetate, a bacterially derived SCFA, were lower and positively correlated with angiogenesis markers (VEGF and VEGF-C). In aged stroke mice, transplantation of young microbiota improved stroke outcomes by promoting angiogenesis, which was facilitated by lymphatic ingrowth into the cortex. This protective effect was linked to gut microbiota-derived acetate, which enhanced lymphangiogenesis by replenishing acetyl coenzyme A.Conclusions(a) Gut microbiota-derived acetate promotes angiogenesis post-stroke and (b) lymphatic ingrowth into the cerebral cortex was observed in post-dMCAO mice. These findings suggest that selectively promoting SCFA-producing bacteria, particularly acetate-producers, could be a promising therapeutic strategy to reduce functional impairments in older stroke subjects.

IntroductionThe successful outcome of a pregnancy depends on the proper functioning uterine epithelium. DNA damage binding protein 1 and cullin 4-associated factor 2 (DCAF2), a conserved substrate receptor for the cullin 4-RING E3 ubiquitin ligase (CRL4) complex, is essential for maintaining genome stability by facilitating ubiquitin-mediated degradation of substrates.MethodsTo better understand the physiological role of DCAF2 in female reproduction, we conducted a study using mice with conditional knockout (cKO) of DCAF2 in the uterus using the progesterone receptor Cre (PgrCre/+) mouse model.ResultsOur results showed the cKO mice were completely infertile, despite having ovarian function. The cKO mice exhibited severely thin uteri, demonstrating notable defects in both the uterine epithelium and a lack of glands. In addition, there were impaired proliferation and differentiation of epithelial cells in the cKO mice, ultimately resulting in failed implantation. Moreover, through deciphering the uterine transcriptome of cKO mice, we revealed crucial differentially expressed genes associated with steroid signaling. Further experiments have demonstrated cKO mice exhibit elevated uterine PGR signaling and reduced estrogen receptor signaling, although the levels of progesterone and estrogen remained unaltered. These alterations may contribute to defects in epithelium.DiscussionOverall, our findings highlight a previously unrecognized but indispensable role for DCAF2 in the development of uterine luminal and glandular epithelium by orchestrating PGR and estrogen receptor responses. Its deficiency in the uterus leads to mouse infertility.

BackgroundThe overall understanding of the correlations between mortality risk and phytoestrogens in general population remains limited. We examined the association between urinary phytoestrogen levels and all-cause and cardiovascular mortality based on the National Health and Nutrition Examination Survey (NHANES).MethodsWeighted Cox proportional hazard regression models were employed to calculate adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs). Nonlinear relationships were assessed using multivariable-adjusted restricted cubic splines (RCS).ResultsIn the fully adjusted model, the highest quartiles of urinary genistein levels were correlated with significantly elevated all-cause (HR = 1.36, 95%CI: 1.16–1.59) and cardiovascular (HR = 1.58, 95%CI: 1.20–2.09) mortality. Urinary enterolactone levels in the third quartile were associated with reduced all-cause (HR = 0.77, 95%CI: 0.65–0.90) and cardiovascular (HR = 0.74, 95%CI: 0.55–0.99) mortality. In the highest quartiles of urinary daidzein levels, the cardiovascular mortality was significantly increased (HR = 1.44, 95%CI: 1.09–1.90). RCS showed an non-linear relationship between urinary daidzein levels and all-cause mortality (P = 0.04).ConclusionIn the context of a nationally representative sample, genistein exhibited associations with elevated all-cause and cardiovascular mortality, whereas enterolactone showed an association with reduced mortality. The dose–response relationship between urinary daidzein levels and all-cause mortality as well as sex-specific disparities in the impact of phytoestrogen levels should be considered.

BackgroundAcute pancreatitis (AP) is an extraintestinal manifestation of inflammatory bowel disease (IBD). Numerous observational studies have reported an increased risk of AP in patients diagnosed with IBD. However, the causal association and directionality between IBD or its subtypes and the development of AP remains unclear due to the limitations of observational research. This study aims to explore the relationship between IBD or its subtypes and AP risk using Mendelian Randomization (MR) method.MethodsA two-sample bidirectional MR study was conducted, selecting genetic variants associated with IBD and AP as instrumental variables from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) and FinnGen databases, respectively. The inverse-variance weighted (IVW) method used as the primary approach for causal inference. The Cochran Q test was employed for heterogeneity assessment. Sensitivity analyses were performed using the MR Egger intercept test, MR-Presso, and Leave-one-out method.ResultsThe results revealed that IBD (OR = 1.049, 95% CI = 1.010–1.090, p = 0.013) and ulcerative colitis (UC) (OR = 1.057, 95% CI = 1.013–1.102, p = 0.011) were significantly associated with an increased risk of AP. However, Crohn’s disease (CD) (OR = 1.023, 95% CI = 0.993-1.055, p = 0.134) did not show a causal association with the risk of AP. Interestingly, AP was suggestively associated with a decreased risk of CD (OR = 0.797, 95% CI = 0.637-0.997, p = 0.047). Furthermore, there was no causal association between AP and the risk of IBD (OR = 0.886, 95% CI = 0.753-1.042, p = 0.144) or UC (OR = 0.947, 95% CI = 0.773-1.159, p = 0.595).ConclusionIn conclusion, this study provides genetic evidence supporting the causal influence of IBD (specifically UC) on AP, while CD does not appear to have a causal impact on AP.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a lethal lung disease characterized by progressive fibrosis, leading to impaired gas exchange and high mortality. The etiology of IPF is complex, with potential links to autoimmune disorders such as hypothyroidism. This study explores the relationship between hypothyroidism and IPF, focusing on the mediating role of plasma proteins.MethodsA two-sample Mendelian randomization (MR) approach was employed to determine the impact of hypothyroidism on IPF and the mediating role of 4,907 plasma proteins, all in individuals of European ancestry. Sensitivity analyses, external validation, and reverse causality tests were conducted to ensure the robustness of the findings. Additionally, the function of causal SNPs was evaluated through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.ConclusionThe findings suggest that hypothyroidism, through altered plasma protein expression, particularly CXCL10, may contribute to the pathogenesis of IPF. This novel insight highlights the potential of CXCL10 as a therapeutic target in IPF, especially in patients with hypothyroidism. The study emphasizes the need for further research into the complex interplay between autoimmune disorders and IPF, with a view towards developing targeted interventions for IPF management.

Background: Bevacizumab (BV) is widely used in routine cancer treatment and clinical therapy in combination with many other agents. This study aims to describe and analyse post-market cases of pulmonary haemorrhage and haemoptysis reported with different BV treatment regimens by mining data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.Methods: Data were collected from the FAERS database between 2004 Q1 and 2023 Q1. Disproportionality analysis including the reporting odds ratio (ROR) was employed to quantify the signals of disproportionate reporting of pulmonary haemorrhage and haemoptysis adverse events (AEs) associated with BV-related treatment regimens. The demographic characteristics, time to onset and outcomes were further clarified.Results: A total of 55,184 BV-associated reports were extracted from the FAERS database, of which 497 reports related to pulmonary haemorrhage and haemoptysis. Overall, the median onset time of pulmonary haemorrhage and haemoptysis AEs was 43 days (interquartile range (IQR) 15-117 days). In the subgroup analysis, BV plus targeted therapy had the longest median onset time of 90.5 days (IQR 34-178.5 days), while BV plus chemotherapy had the shortest of 40.5 days (IQR 14–90.25). BV plus chemotherapy disproportionately reported the highest percentage of death (148 deaths out of 292 cases, 50.68%). Moreover, the BV-related treatments including four subgroups in our study demonstrated the positive signals with the association of disproportionate reporting of pulmonary haemorrhage and haemoptysis. Notably, BV plus chemotherapy showed a significant higher reporting risk in pulmonary haemorrhage and haemoptysis signals of disproportionate reporting in comparison to BV monotherapy (ROR 5.35 [95% CI, 4.78–6.02] vs. ROR 4.19 [95% CI, 3.56–4.91], p = 0.0147).Conclusion: This study characterized the reporting of pulmonary haemorrhage and haemoptysis, along with the time to onset and demographic characteristics among different BV-related treatment options. It could provide valuable evidence for further studies and clinical practice of BV.

Background and purposeNutrition is associated with tuberculosis drug-induced liver injury (TBLI). How dietary patterns relate to tuberculosis drug-induced liver injury is still unknown. The objective of this study is to explore the relation between dietary patterns and the risk of tuberculosis drug-induced liver injury.MethodsThis cohort study was conducted at two hospitals in Shandong Province, China, between 2011 and 2013. A total of 605 tuberculosis patients were included in the final analysis. The blood aspartate aminotransferase or alanine aminotransferase level was monitored through the 6-month tuberculosis treatment. The semi-quantitative food frequency questionnaires were used to survey dietary intake in the second month of the tuberculosis treatment. The China Healthy Diet Index (CHDI), which was previously validated in the Chinese population, was used as an a priori dietary pattern. A posteriori dietary patterns were extracted by principal component analysis (PCA).ResultsThe CHDI was negatively associated with the risk of liver injury [adjusted odds ratio (aOR) per standard deviation (SD) (95% CI): 0.61 (0.40–0.94)] and liver dysfunction [aOR per SD (95% CI): 0.47 (0.35–0.64)] in the multivariate logistic model. A positive association between “Organ meat, poultry, and vegetable oil” dietary pattern scores (extracted by PCA) and the risk of liver injury [aOR (95% CI): 3.02 (1.42–6.41)] and liver dysfunction [aOR (95% CI): 1.83 (1.09–3.05)] was observed.ConclusionIn conclusion, a high CHDI score was a protective factor for tuberculosis drug-induced liver injury, while the “Organ meat, poultry, and vegetable oil” dietary pattern, which was rich in organ meat, poultry, and vegetable oil and low in vegetables, was an independent risk factor for tuberculosis drug-induced liver injury.

Background: Immune checkpoint inhibitors (ICIs), including anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies, have become a standard treatment for multiple cancer types. However, ICIs can induce immune-related adverse events, with hepatitis-related adverse events (HRAEs) being of particular concern. Our objective is to identify and characterize HRAEs that exhibit a significant association with ICIs using real-world data.Methods: In this observational and retrospective pharmacovigilance study, we extracted real-world adverse events reports from the FDA Adverse Event Reporting System database spanning from the first quarter of 2004 to the first quarter of 2023. We conducted both Frequentist and Bayesian methodologies in the framework of disproportionality analysis, which included the reporting odds ratios (ROR) and information components (IC) to explore the intricate relationship between ICIs and HRAEs.Results: Through disproportionality analysis, we identified three categories of HRAEs as being significantly related with ICIs, including autoimmune hepatitis (634 cases, ROR 19.34 [95% CI 17.80–21.02]; IC025 2.43), immune-mediated hepatitis (546 cases, ROR 217.24 [189.95–248.45]; IC025 4.75), and hepatitis fulminant (80 cases, ROR 4.56 [3.65–5.70]; IC025 0.49). The median age of patients who report ICI-related HRAEs was 63 years (interquartile range [IQR] 53.8–72), with a fatal outcome observed in 24.9% (313/1,260) of these reports. Cases pertaining to skin cancer, lung cancer, and kidney cancer constituted the majority of these occurrences. Patients treated with anti-PD-1 or anti-PD-L1 antibodies exhibited a higher frequency of immune-mediated hepatitis in comparison to those undergoing anti-CTLA-4 monotherapy, with a ROR of 3.59 (95% CI 1.78–6.18). Moreover, the dual ICI therapy demonstrated higher reporting rates of ICI-related HRAEs compared to ICI monotherapy.Conclusion: Our findings confirm that ICI treatment carries a significant risk of severe HRAEs, in particular autoimmune hepatitis, immune-mediated hepatitis, and hepatitis fulminant. Healthcare providers should exercise heightened vigilance regarding these risks when managing patients receiving ICIs.

BackgroundST-segment elevation myocardial infarction (STEMI) persists to be prevalent in the elderly with a dismal prognosis. The capacity of endothelial progenitor cells (EPCs) is reduced with aging. Nevertheless, the influence of aging on the functionality of EPCs in STEMI is not fully understood.MethodThis study enrolled 20 younger STEMI patients and 21 older STEMI patients. We assessed the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events Risk (GRACE) scores in two groups. Then, we detected EPC migration, proliferation, adhesion, and plasma interleukin (IL)-18 and IL-23 concentrations in two groups. In addition, we analyzed the interconnection between age, EPC function, plasma IL-18 and IL-23 concentrations, and GRACE or TIMI scores in STEMI patients.ResultGRACE and TIMI scores in older STEMI patients were higher than in younger STEMI patients, whereas EPC function declined. GRACE and TIMI scores were found to have an inverse relationship with the EPC function. In older STEMI patients, plasma concentrations of IL-18 and IL-23 increased. Plasma IL-18 and IL-23 concentrations were adversely connected to EPC capacity and positively related to GRACE and TIMI scores. Moreover, age was positively correlated with plasma IL-18 or IL-23 concentrations, as well as GRACE or TIMI scores. However, age was adversely correlated with EPC function.ConclusionIn patients with STEMI, aging results in declined EPC function, which may be associated with inflammatory cytokines. The current investigation may offer new perception about mechanism and therapeutic targets of aging STEMI.

BackgroundCytochrome P450 2E1 (CYP2E1) converts isoniazid (INH) to toxic metabolites and is critical in INH-induced liver injury. The aim is to investigate the effect of folic acid (FA) on CYP2E1 and INH-induced liver injury.MethodsMale Balb/c mice were used. The mice in the control group only received an AIN-93M diet. The AIN-93M diet was supplemented with 0.66 g INH/kg diet for the mice in the INH and FA groups. The mice in the FA group were treated with additional 0.01 g FA/kg diet. The one-carbon cycle metabolites, the expressions of CYP2E1 and the DNA and RNA methylation levels were detected to reveal the potential mechanism.ResultsFA treatment significantly reduced the alanine aminotransferase level and alleviated the liver necrosis. The mRNA and protein expressions of CYP2E1 were significantly lower in the FA group than those in the INH group. The N6-methyladenosine RNA methylation level of Cyp2e1 significantly increased in the FA group compared with the INH group, while the DNA methylation levels of Cyp2e1 were similar between groups. Additionally, the liver S-adenosyl methionine (SAM)/S-adenosyl homocysteine (SAH) was elevated in the FA group and tended to be positively correlated with the RNA methylation level of Cyp2e1.ConclusionFA alleviated INH-induced liver injury which was potentially attributed to its inhibitory effect on CYP2E1 expressions through enhancing liver SAM/SAH and RNA methylation.

Purpose:Thalassemia is a severe hereditary blood disorder that poses a significant threat to human health and leads to mortality and disability. It is one of the most prevalent monogenic diseases worldwide. The aim of this study was to analyze the molecular epidemiological data of individuals of childbearing age from the Han ethnic group with thalassemia in Southwest China and to explore the application of next-generation sequencing (NGS) technology in screening thalassemia carriers.Methods:The participants were Han males and females of childbearing age who sought medical advice at the West China Second University Hospital, Sichuan University from June 2022 to June 2023. We detected α- and β-thalassemia mutations using full-length capture of the thalassemia genes and NGS technology.Results:In a cohort of 1,093 participants, 130 thalassemia carriers were identified, with an overall detection rate of 11.89% (130/1,093). Among these, 0.91% (10/1,093) had mutations that could not be detected using traditional PCR techniques. The proportions of carriers with α-, β-, and α-complexed β-thalassemia gene mutations were 7.68% (84/1,093), 3.93% (43/1,093), and 0.27% (3/1,093), respectively. We identified a novel HBA2 c.166del variant that has not been previously reported.Conclusion:Using NGS technology, we found that the mutation-carrying rate of thalassemia genes was 11.89% in the Han population of childbearing age in Southwest China. Compared with the results of traditional PCR techniques, NGS detected an additional 0.91% (10/1,093) rare genetic variants. NGS technology should be utilized as the primary screening method for thalassemia carriers among Han nationality people of childbearing age in Southwest China.

In aquaculture, good germplasm resources are nearly decisive for its development. The hard clam (Mercenaria mercenaria), a significant marine aquaculture bivalve in China, has flourished quickly since being introduced from North America in 1997. However, for numerous reasons, it has suffered from germplasm deterioration and uncertain origins. To address these issues, seven microsatellite DNA loci (SSRs) and mtCOI were employed to evaluate germplasm and trace the origins of various Chinese populations. The results of these two molecular genetic markers revealed weak genetic differentiation among all Chinese populations, with high genetic diversity observed across most individuals, except for a few outliers. This suggests an alarming situation regarding germplasm resources in China. Based on results of traceability analysis, the most likely areas of origin for the Chinese populations are Chesapeake Bay and the southern region of Cape Hatteras. This study provides a crucial theoretical foundation for the cultivation, conservation, and subsequent introduction of hard clam populations in China, thereby ensuring the sustainable growth of the hard clam breeding sector.

Plant diversity and productivity, two crucial properties that sustain ecosystem structures, functions, and services, are intrinsically linked to numerous ecological fields, making productivity–richness relationships (PRR) a central ecological concern. Despite extensive research from the Darwinian era to the 21st century, the various shapes of PRR and their underlying theories have sparked ongoing debates. While several processes, theories, and integrative models have been proposed to explain PRR, a comprehensive understanding of the types of PRR, the effects of these processes on plant productivity and richness, and the relationships between PRR shapes remains elusive. This paper proposes a new integrative framework that focuses on these aspects, aiming to elucidate the diverse shapes of PRR and their interconnections. We review recent integrative methods that explain the roles of processes and the varying shapes in PRR to support this new framework. The paper traces the distinct phases in PRR research, including the discovery of PRR shapes, tests of influencing processes, and integrative research. We discuss the application of the Structural Equation Model (SEM), Statistical Dynamical Model (SDM), and Differential Dynamical Model (DDM) in integrative research. This integrative framework can guide theoretical and applied ecologists in identifying, deriving, explaining, and predicting the interconnected but distinct shapes of PRR. The humped, asymptotic, positive, negative, and irregular shapes of PRR are interconnected, with one shape potentially transforming into another. The balance between the positive and negative effects of different processes determines the different shapes of PRR, ultimately leading to a globally positive effect of plant diversity on plant productivity and other ecosystem functions.

Gastrointestinal cancers account for approximately one-third of the total global cancer incidence and mortality with a poor prognosis. It is one of the leading causes of cancer-related deaths worldwide. Most of these diseases lack effective treatment, occurring as a result of inappropriate models to develop safe and potent therapies. As a novel preclinical model, tumor patient-derived organoids (PDOs), can be established from patients’ tumor tissue and cultured in the laboratory in 3D architectures. This 3D model can not only highly simulate and preserve key biological characteristics of the source tumor tissue in vitro but also reproduce the in vivo tumor microenvironment through co-culture. Our review provided an overview of the different in vitro models in current tumor research, the derivation of cells in PDO models, and the application of PDO model technology in gastrointestinal cancers, particularly the applications in combination with CRISPR/Cas9 gene editing technology, tumor microenvironment simulation, drug screening, drug development, and personalized medicine. It also elucidates the ethical status quo of organoid research and the current challenges encountered in clinical research, and offers a forward-looking assessment of the potential paths for clinical organoid research advancement.

IntroductionNight-shift workers often face various health issues stemming from circadian rhythm shift and the consequent poor sleep quality. We aimed to study nurses working night shifts, evaluate the electroencephalogram (EEG) pattern of daytime sleep, and explore possible pattern changes due to ambient light exposure (30 lux) compared to dim conditions (

BackgroundCarotid Intima-Media Thickness (CIMT) is a key marker for atherosclerosis, with its modulation being crucial for cardiovascular disease (CVD) risk assessment. While thyroid function’s impact on cardiovascular health is recognized, the causal relationship and underlying mechanisms influencing CIMT remain to be elucidated.MethodsIn this study, Mendelian Randomization (MR) was employed to assess the causal relationship between thyroid function and CIMT. Thyroid hormone data were sourced from the Thyroidomics Consortium, while lipid traits and CIMT measurements were obtained from the UK Biobank. The primary analysis method was a two-sample MR using multiplicative random effects inverse variance weighting (IVW-MRE). Additionally, the study explored the influence of thyroid hormones on lipid profiles and assessed their potential mediating role in the thyroid function-CIMT relationship through multivariate MR analysis.ResultsThe study revealed that lower levels of Free Thyroxine (FT4) within the normal range are significantly associated with increased CIMT. This association was not observed with free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), or TPOAb. Additionally, mediation analysis suggested that apolipoprotein A-I and B are involved in the relationship between thyroid function and CIMT. The findings indicate a potential U-shaped curve relationship between FT4 levels and CIMT, with thyroid hormone supplementation in hypothyroid patients showing benefits in reducing CIMT.ConclusionThis research establishes a causal link between thyroid function and CIMT using MR methods, underscoring the importance of monitoring thyroid function for early cardiovascular risk assessment. The results advocate for the consideration of thyroid hormone supplementation in hypothyroid patients as a strategy to mitigate the risk of carotid atherosclerosis. These insights pave the way for more targeted approaches in managing patients with thyroid dysfunction to prevent cardiovascular complications.

The brown planthopper (BPH) is the most destructive insect pest that threatens rice production globally. Developing rice varieties incorporating BPH-resistant genes has proven to be an effective control measure against BPH. In this study, we assessed the resistance of a core collection consisting of 502 rice germplasms by evaluating resistance scores, weight gain rates and honeydew excretions. A total of 117 rice varieties (23.31%) exhibited resistance to BPH. Genome-wide association studies (GWAS) were performed on both the entire panel of 502 rice varieties and its subspecies, and 6 loci were significantly associated with resistance scores (P value < 1.0e-8). Within these loci, we identified eight candidate genes encoding receptor-like protein kinase (RLK), nucleotide-binding and leucine-rich repeat (NB-LRR), or LRR proteins. Two loci had not been detected in previous study and were entirely novel. Furthermore, we evaluated the predictive ability of genomic selection for resistance to BPH. The results revealed that the highest prediction accuracy for BPH resistance reached 0.633. As expected, the prediction accuracy increased progressively with an increasing number of SNPs, and a total of 6.7K SNPs displayed comparable accuracy to 268K SNPs. Among various statistical models tested, the random forest model exhibited superior predictive accuracy. Moreover, increasing the size of training population improved prediction accuracy; however, there was no significant difference in prediction accuracy between a training population size of 737 and 1179. Additionally, when there existed close genetic relatedness between the training and validation populations, higher prediction accuracies were observed compared to scenarios when they were genetically distant. These findings provide valuable resistance candidate genes and germplasm resources and are crucial for the application of genomic selection for breeding durable BPH-resistant rice varieties.

Objective: A biomechanical comparative analysis was conducted to evaluate the retrograde tibial nailing (RTN) and distal tibia plate techniques for the treatment of distal tibia fractures.Methods: Fourteen fresh adult tibia specimens were selected, consisting of seven males and seven females aged 34–55 years. The specimens were randomly divided into two groups (Group A and Group B) using a numerical table method, with seven specimens in each group. Group A underwent internal fixation of distal tibial fractures using RTN, while Group B received internal fixation using a plate. The axial compression properties of the specimens were tested in the neutral positions under pressures of 100, 200, 300, 400, and 500 N. Additionally, the torsional resistance of the two groups was assessed by subjecting the specimens to torques of 1.0, 2.0, 3.0, 4.0, and 5.0 N m.Results: At pressures of 400 and 500 N, the axial compression displacement in Group A (1.11 ± 0.06, 1.24 ± 0.05) mm was significantly smaller than that in Group B (1.21 ± 0.08, 1.37 ± 0.11) mm (p = 0.023, 0.019). Moreover, at a pressure of 500 N, the axial compression stiffness in Group A (389.24 ± 17.79) N/mm was significantly higher than that of the control group (362.37 ± 14.44) N/mm (p = 0.010). When subjected to torques of 4 and 5 N m, the torsion angle in Group A (2.97° ± 0.23°, 3.41° ± 0.17°) was significantly smaller compared to Group B (3.31° ± 0.28°, 3.76° ± 0.20°) (p = 0.035, 0.004). Furthermore, at a torque of 5 N m, the torsional stiffness in Group A (1.48 ± 0.07) N m/° was significantly higher than that in Group B (1.36 ± 0.06) N·m/° (p = 0.003).Conclusion: The results obtained from the study demonstrate that the biomechanical performance of RTN outperforms that of the distal tibial plate, providing valuable biomechanical data to support the clinical implementation of RTN.

ObjectivesRecent studies pointed out that gut microbiome dysbiosis in HIV infection was possibly confounded in men who have sex with men (MSM), but there is a lack of evidence. It also remained unclear how MSM-associated gut microbiome dysbiosis affected human health. This study aimed to compare the differences in gut microbiome changes between HIV and MSM and reveal the potential impacts of MSM-associated gut microbiome dysbiosis on the immune system.MethodsWe searched available studies based on the PubMed database, and all gut microbiome changes associated with HIV infection and MSM were extracted from the enrolled studies. The gutMgene database was used to identify the target genes and metabolites of the gut microbiome. Bioinformatic technology and single-cell RNA sequencing data analysis were utilized to explore the impacts of these gut microbiome changes on human immunity.ResultsThe results showed significant overlaps between the gut microbiome associated with HIV and that of MSM. Moreover, bioinformatic analysis revealed that gut microbiome dysbiosis in MSM had an impact on several pathways related to immunity, including the IL-17 signaling pathway and Th17 cell differentiation. Additionally, target genes of MSM-associated gut microbiome were found to be highly expressed in monocytes and lymphocytes, suggesting their potential regulatory role in immune cells. Furthermore, we found that MSM-associated gut microbiome could produce acetate and butyrate which were reported to increase the level of inflammatory factors.ConclusionIn conclusion, this study highlighted that MSM-associated gut microbiome dysbiosis might increase the risk of HIV acquisition by activating the immune system. Further studies are expected to elucidate the mechanism by which gut microbiome dysbiosis in MSM modulates HIV susceptibility.

IntroductionThe lower respiratory tract microbiome is widely studied to pinpoint microbial dysbiosis of diversity or abundance that is linked to a number of chronic respiratory illnesses. However, it is vital to clarify how the microbiome, through the release of microbial metabolites, impacts lung health and oncogenesis.MethodsIn order to discover the powerful correlations between microbial metabolites and disease, we collected, under electronic bronchoscopy examinations, samples of paired bronchoalveolar lavage fluids (BALFs) from tumor-burden lung segments and ipsilateral non-tumor sites from 28 lung cancer participants, further performing metagenomic sequencing, short-chain fatty acid (SCFA) metabolomics, and multiomics analysis to uncover the potential correlations of the microbiome and SCFAs in lung cancer.ResultsIn comparison to BALFs from normal lung segments of the same participant, those from lung cancer burden lung segments had slightly decreased microbial diversity in the lower respiratory tract. With 18 differentially prevalent microbial species, including the well-known carcinogens Campylobacter jejuni and Nesseria polysaccharea, the relative species abundance in the lower respiratory tract microbiome did not significantly differ between the two groups. Additionally, a collection of commonly recognized probiotic metabolites called short-chain fatty acids showed little significance in either group independently but revealed a strong predictive value when using an integrated model by machine learning. Multiomics also discovered particular species related to SCFAs, showing a positive correlation with Brachyspira hydrosenteriae and a negative one with Pseudomonas at the genus level, despite limited detection in lower airways. Of note, these distinct microbiota and metabolites corresponded with clinical traits that still required confirmation.ConclusionsFurther analysis of metagenome functional capacity revealed that genes encoding environmental information processing and metabolism pathways were enriched in the lower respiratory tract metagenomes of lung cancer patients, further supporting the oncogenesis function of various microbial species by different metabolites. These findings point to a potent relationship between particular components of the integrated microbiota-metabolites network and lung cancer, with implications for screening and diagnosis in clinical settings.

Dissolved organic matter (DOM) in seawater, consisted of a complex mixture of compounds and accounted for about 90% of marine organic carbon, is an important part of the global carbon cycle and also a part of absolute salinity of seawater. As the components of DOM are non-ionized in seawater, electric conductivity measurement cannot observe its contribution to salinity, which could lead to measurement error in salinity. Salinity measurement based on optic refractive index could reveal contribution of all dissolved matters in seawater including both non-ionized and ionized components. In this paper, a comparative study of DOM contribution to the salinity measurement by optic refractive index method and electric conductivity method was carried out for the first time. Adding DOM, extracted from Aoshan Bay, Qingdao, China, into Chinese Standard Seawater, our experimental results showed an increase of optic refractive index at 1.19×10-4 ± 4×10-6 per 1g/kg of DOM, which corresponds to a practical salinity increase of 0.697 ± 0.036 PSU per 1 g/kg of DOM. While, the conductivity of seawater measured by a conductivity-temperature sensor showed a decrease of 0.00065 ± 0.00008 mS/cm per 1 g/kg of DOM, which corresponded to a decrease of salinity at 0.00052 ± 0.00007 PSU per 1 g/kg of DOM. By comparing the optic and electric measurement results, the contribution of non-conductive components in the dissolved organic matters to salinity could be distinguished, which has great significance for the measurement of absolute salinity, global carbon cycle etc.

Pancreatic neuroendocrine neoplasms (pNENs) are relatively rare epithelial malignancies originating from pancreatic neuroendocrine cells, pathologically classified into well-differentiated pancreatic neuroendocrine tumors (pNETs) and poorly-differentiated pancreatic neuroendocrine carcinoma (pNECs). Although they also fall under the category of pNENs, the almost entirely distinct biological characteristics and survival prognosis have caused debate among surgeons when it comes to the development of surgical intervention options, particularly for locally advanced G3 pNETs and pNECs. We present a case of 66-year-old male with nonfunctional G3 pNET, invasion of five nearby pancreatic organs and type II liver metastases. The patient achieved good outcomes after undergoing multivisceral resection and postoperative adjuvant chemotherapy. This finding helps surgeons better understand locally advanced pNENs, formulate treatment decisions systematically and confidently, and balance patient benefits and risks of surgery.

BackgroundMigraine is a prevalent neurovascular headache disorder. The link between dietary potassium and blood pressure has been established. We sought to delineate the relationship between dietary potassium intake and the prevalence of migraines.MethodsWe conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999–2004, comprising 10,254 participants aged ≥20 years. Participants who reported severe headaches or migraine in the self-report questionnaire were identified as migraineurs. A 24-h dietary recall methodology was used to assess dietary potassium intake. Multivariate regression analysis and restricted cubic spline (RCS) modeling were utilized to elucidate the relationship between dietary potassium and migraines.ResultsAmong the 10,254 participants, 20.1% were identified with migraine or severe headaches. The adjusted odds ratio (OR) for migraine occurrence in the Q2 dietary potassium intake (1771–2,476 mg/d) was 0.84 (95% CI: 0.73–0.97, p = 0.021) compared to the lowest quartile (Q1, ≤ 1771 mg/d). The relationship between dietary potassium and migraine exhibited an L-shaped pattern (non-linear, p = 0.016) with an inflection at approximately 1439.3 mg/d. In the subgroup analysis, when compared to Q1, who had the lowest dietary potassium intake, the adjusted OR for Q2 in females, those in the medium-high household income group, and with a Body Mass Index (BMI) ≥ 25 kg/m2 were as follows: (OR, 0.82; 95% CI, 0.69–0.98), (OR, 0.79; 95% CI, 0.66–0.95), and (OR, 0.78; 95% CI, 0.66–0.93), respectively. No significant interaction was observed across groups after adjusting for all possible covariates.ConclusionThe relationship between dietary potassium intake and migraine prevalence among US adults appears to follow an L-shaped curve.

IntroductionSpeech breathing is a term usually used to refer to the manner in which expired air and lung mechanics are utilized for the production of the airflow necessary for phonation. Neurologically, speech breathing overrides the normal rhythms of alveolar ventilation. Speech breathing is generated using the diaphragm, glottis, and tongue. The glottis is the opening between the vocal folds in the larynx; it is the primary valve between the lungs and the mouth, and by varying its degree of opening, the sound can be varied. The use of voice as an indicator of health has been widely reported. Chronic obstructive pulmonary disease (COPD) is the most common long-term respiratory disease. The main symptoms of COPD are increasing breathlessness, a persistent chesty cough with phlegm, frequent chest infections, and persistent wheezing. There is no cure for COPD, and it is one of the leading causes of death worldwide. The principal cause of COPD is tobacco smoking, and estimates indicate that COPD will become the third leading cause of death worldwide by 2030. The long-term aim of this research program is to understand how speech generation, breathing, and lung function are linked in people with chronic respiratory diseases such as COPD.MethodsThis pilot study was designed to test an articulatory speech task that uses a single word (“helicopter”), repeated multiple times, to challenge speech-generated breathing and breathlessness. Specifically, a single-word articulation task was used to challenge respiratory system endurance in people with healthy lungs by asking participants to rapidly repeat the word “helicopter” for three 20-s runs interspersed with two 20-s rest periods of silent relaxed breathing. Acoustic and prosodic features were then extracted from the audio recordings of each adult participant.Results and discussionThe pause ratio increased from the first run to the third, representing an increasing demand for breath. These data show that the repeated articulation task challenges speech articulation in a quantifiable manner, which may prove useful in defining respiratory ill-health.

Inflammation primarily influences the initiation, progression, and deterioration of many human diseases, and immune cells are the principal forces that modulate the balance of inflammation by generating cytokines and chemokines to maintain physiological homeostasis or accelerate disease development. S100A8/A9, a heterodimer protein mainly generated by neutrophils, triggers many signal transduction pathways to mediate microtubule constitution and pathogen defense, as well as intricate procedures of cancer growth, metastasis, drug resistance, and prognosis. Its paired receptors, such as receptor for advanced glycation ends (RAGEs) and toll-like receptor 4 (TLR4), also have roles and effects within tumor cells, mainly involved with mitogen-activated protein kinases (MAPKs), NF-κB, phosphoinositide 3-kinase (PI3K)/Akt, mammalian target of rapamycin (mTOR) and protein kinase C (PKC) activation. In the clinical setting, S100A8/A9 and its receptors can be used complementarily as efficient biomarkers for cancer diagnosis and treatment. This review comprehensively summarizes the biological functions of S100A8/A9 and its various receptors in tumor cells, in order to provide new insights and strategies targeting S100A8/A9 to promote novel diagnostic and therapeutic methods in cancers.

Nowadays, people have relaxed their vigilance against COVID-19 due to its declining infection numbers and attenuated virulence. However, COVID-19 still needs to be concern due to its emerging variants, the relaxation of restrictions as well as breakthrough infections. During the period of the COVID-19 infection, the imbalanced and hyper-responsive immune system plays a critical role in its pathogenesis. Macrophage Activation Syndrome (MAS) is a fatal complication of immune system disease, which is caused by the excessive activation and proliferation of macrophages and cytotoxic T cells (CTL). COVID-19-related hyperinflammation shares common clinical features with the above MAS symptoms, such as hypercytokinemia, hyperferritinemia, and coagulopathy. In MAS, immune exhaustion or defective anti-viral responses leads to the inadequate cytolytic capacity of CTL which contributes to prolonged interaction between CTL, APCs and macrophages. It is possible that the same process also occurred in COVID-19 patients, and further led to a cytokine storm confined to the lungs. It is associated with the poor prognosis of severe patients such as multiple organ failure and even death. The main difference of cytokine storm is that in COVID-19 pneumonia is mainly the specific damage of the lung, while in MAS is easy to develop into a systemic. The attractive therapeutic approach to prevent MAS in COVID-19 mainly includes antiviral, antibiotics, convalescent plasma (CP) therapy and hemadsorption, extensive immunosuppressive agents, and cytokine-targeted therapies. Here, we discuss the role of the therapeutic approaches mentioned above in the two diseases. And we found that the treatment effect of the same therapeutic approach is different.

Multi-layered drug delivery (MLDD) system has promising potential to achieve controlled release. However, existing technologies face difficulties in regulating the number of layers and layer-thickness ratio. In our previous works, layer-multiplying co-extrusion (LMCE) technology was applied to regulate the number of layers. Herein, we utilized layer-multiplying co-extrusion technology to modulate the layer-thickness ratio to expand the application of LMCE technology. Four-layered poly (ε-caprolactone)-metoprolol tartrate/poly (ε-caprolactone)-polyethylene oxide (PCL-MPT/PEO) composites were continuously prepared by LMCE technology, and the layer-thickness ratios for PCL-PEO layer and PCL-MPT layer were set to be 1:1, 2:1, and 3:1 just by controlling the screw conveying speed. The in vitro release test indicated that the rate of MPT release increased with decreasing the thickness of the PCL-MPT layer. Additionally, when PCL-MPT/PEO composite was sealed by epoxy resin to eliminate the edge effect, sustained release of MPT was achieved. The compression test confirmed the potential of PCL-MPT/PEO composites as bone scaffolds.

Ocean warming is suggested to exert profound effects on phytoplankton physiology and growth. Here, we investigated how the coccolithophore Emiliania huxleyi (BOF 92, a non-calcifying strain) responded to changes in temperature in short- and long-term thermal treatments. The specific growth rate after 10 days of acclimation increased gradually with increasing temperatures (14, 17, 21, 24, 28°C) and peaked at ~23°C, followed by a significant decrease to 28°C. Chlorophyll a content, cell size, photosynthetic rate, and respiratory rate increased significantly from 14°C to 24°C, but the cellular particulate organic carbon (POC) and nitrogen (PON) showed the lowest values at the optimal temperature. In contrast, during long-term thermal treatments at 17°C and 21°C for 656 days (~790 generations for 17°C treatment; ~830 generations for 21°C treatment), the warming significantly stimulated the growth in the first 34 days and the last 162 days, but there was no significant difference in specific growth rate from Day 35 to Day 493. Chlorophyll a content, cell size, cellular POC/PON, and the ratio of POC to PON, showed no significant difference between the warming and control for most of the duration of the long-term exposure. The warming-selected population did not acquire persistent traits in terms of growth and cell quotas of POC and PON, which resumed to the levels in the control temperature treatment after about 9 generations in the shift test. In summary, our results indicate that warming by 4°C (17°C and 21°C) enhanced the growth, but did not result in adaptative changes in E. huxleyi (BOF 92) over a growth period of about 800 generations, reflecting that mild or non-stressful warming treatment to E. huxleyi isolated from cold seas does not alter its phenotypic plasticity.

Background: Bone giant cell tumor (BGCT) is one of the world’s major disease types of locally aggressive bone tumors. In recent years, denosumab treatment has been introduced before curettage surgery. However, the current therapeutic was practical only sometimes, given the local recurrence effects after discontinuation of denosumab. Due to the complex nature of BGCT, this study aims to use bioinformatics to identify potential genes and drugs associated with BGCT.Methods: The genes that integrate BGCT and fracture healing were determined by text mining. The gene was obtained from the pubmed2ensembl website. We filtered out common genes for the function, and signal pathway enrichment analyses were implemented. The protein–protein interaction (PPI) networks and the hub genes were screened by MCODE built-in Cytoscape software. Lastly, the confirmed genes were queried in the Drug Gene Interaction Database to determine potential genes and drugs.Results: Our study finally identified 123 common specific genes in bone giant cell tumors and fracture healing text mining concepts. The GO enrichment analysis finally analyzed 115 characteristic genes in BP, CC, and MF. We selected 10 KEGG pathways and identified 68 characteristic genes. We performed protein–protein interaction analysis (PPI) on 68 selected genes and finally identified seven central genes. In this study, these seven genes were substituted into drug–gene interactions, and there were 15 antineoplastic drugs, 1 anti-involving drug, and 1 anti-influenza drug.Conclusion: The 7 genes (including ANGPT2, COL1A1, COL1A2, CTSK, FGFR1, NTRK2, and PDGFB) and 17 drugs, which have not been used in BGCT, but 6 of them approved by the FDA for other diseases, could be potential genes and drugs, respectively, to improve BGCT treatment. In addition, the correlation study and analysis of potential drugs through genes provide great opportunities to promote the repositioning of drugs and the study of pharmacology in the pharmaceutical industry.

BackgroundThe causal relationship between hypertension, antihypertensive drugs and the risk of erectile dysfunction is still uncertain. We performed a univariable and multivariable Mendelian randomization study to investigate whether they are causally related to erectile dysfunction.MethodsGenetic variants associated with blood pressure were derived from the genome-wide association study meta-analysis of the UK Biobank and International Consortium of Blood Pressure (N = 757,601). Summary association data for hypertension were obtained from the UK Biobank (N = 463,010) and the FinnGen study (N = 356,077). The summary statistics of erectile dysfunction were obtained from the European ancestry with 223,805 subjects. The SNP instruments used to assess the effect of the protein targets of antihypertensive drugs on erectile dysfunction were obtained from previous studys. Causal effects were estimated using the univariate Mendelian randomization method (inverse variance weighted, MR-Egger, weighted median, MR-PRESSO and Wald ratios) and the multivariate Mendelian randomization method. Sensitivity analyses were implemented with the Cochran's Q-test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis.ResultsUnivariate MR found that elevated diastolic blood pressure may increase the occurrence of erectile dysfunction (odds ratio [OR] = 1.012; 95% confidence interval [CI]: 1.000–1.024; P = 0.047). Genetically predicted hypertension is also associated with ED (For the FinnGen, OR = 1.106; 95% CI: 1.027–1.191; P = 0.008. For the UK Biobank, OR = 3.832; 95% CI: 1.410–10.414; P = 0.008). However, after adjusting for systolic blood pressure, diastolic blood pressure and hypertension using multivariate Mendelian randomization, only hypertension was causally associated with ED occurrence (For the FinnGen, OR = 1.103; 95% CI: 1.018–1.195; P = 0.017. For the UK Biobank, OR = 5.037; 95% CI: 1.601–15.846; P = 0.006). We found no evidence that the use of angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and thiazide diuretic increased the risk of erectile dysfunction.ConclusionsGenetically predicted hypertension increases the risk of erectile dysfunction, but we found no causal relationship between elevated systolic/diastolic blood pressure and erectile dysfunction. We speculate that the relationship between elevated blood pressure and erectile dysfunction risk may be nonlinear. We found little evidence that antihypertensive drugs increase the risk of erectile dysfunction.

BackgroundIntellectual developmental disorder 7 (also named DYRK1A syndrome) is an autosomal dominant disease. The main clinical features of DYRK1A syndrome include intellectual disability, microcephaly, and developmental delay. This study aimed to identify pathogenic variants in a Chinese girl with developmental delay, impaired social interaction, and autistic behavior.Case presentationThe case was a 6-year-old girl. Clinical symptoms of the patient mainly included developmental delay, seizures, autistic behavior and impaired social interaction. The patient presented with microcephaly, bushy eyebrows, a short lingual frenum, binocular esotropia, bilateral valgus and external rotation, and walked with an abnormal gait. Using whole-exome sequencing, we identified a 9,424 bp de novo heterozygous deletion (containing coding exons 10, 11, and 12, and partial sequences of non-coding exon 12) in DYRK1A, which is responsible for DYRK1A syndrome. The DYRK1A variant is classified as pathogenic according to the criteria of the American College of Medical Genetics and Genomics.ConclusionsThe findings of this study augment the data regarding the pathogenic variants of DYRK1A and provide important information for molecular diagnosis.

IntroductionFood web is an important basis for identifying trophodynamic processes, and evaluating the structural and functional characteristics of ecosystems. The trophodynamics and system function of artificial reef (AR) ecosystems have rarely been examined.MethodsStable isotope analysis was used to investigate the food web structure and functions of an artificial reef (AR) ecosystem in this study.Results and DiscussionThe δ13C and δ15N values of particulate organic matter (POM) in AR showed noticeable seasonal changes, and the δ13C value of POM in autumn was significantly higher than that in other seasons (p

Hepatectomy is an effective surgical method for the treatment of liver diseases, but intraoperative bleeding and postoperative liver function recovery are still key issues. This study aims to develop a composite hydrogel dressing with excellent hemostatic properties, biocompatibility, and ability to promote liver cell regeneration. The modified gelatin matrix (GelMA, 10%) was mixed with equal volumes of sodium alginate-dopamine (Alg-DA) at concentrations of 0.5%, 1%, and 2%. Then a cross-linking agent (0.1%) was added to prepare different composite hydrogels under UV light, named GelMA/Alg-DA-0.5, GelMA/Alg-DA-1 and GelMA/Alg-DA-2, respectively. All the prepared hydrogel has a porous structure with a porosity greater than 65%, and could be stabilized in a gel state after being cross-linked by ultraviolet light. Physicochemical characterization showed that the elastic modulus, water absorption, adhesion, and compressibility of the composite hydrogels were improved with increasing Alg-DA content. Furthermore, the prepared hydrogel exhibits in vitro degradability, excellent biocompatibility, and good hemostatic function. Among all tested groups, the group of GelMA/Alg-DA-1 hydrogel performed the best. To further enhance its application potential in the field of liver regeneration, adipose-derived mesenchymal stem cell exosomes (AD-MSC-Exo) were loaded into GelMA/Alg-DA-1 hydrogel. Under the same conditions, GelMA/Alg-DA-1/Exo promoted cell proliferation and migration more effectively than hydrogels without extracellular vesicles. In conclusion, the prepared GelMA/Alg-DA-1 composite hydrogel loaded with AD-MSC-Exo has great application potential in liver wound hemostasis and liver regeneration.

IntroductionMalonyl coenzyme A decarboxylase deficiency is caused by an abnormality in the MLYCD gene. The clinical manifestations of the disease involve multisystem and multiorgan.MethodsWe collected and analyzed a patient's clinical characteristics, genetic chain of evidence and RNA-seq. We use the search term “Malonyl-CoA Decarboxylase Deficiency” on Pubmed to collect cases reported.ResultsWe report a 3-year-old girl who is presented with developmental retardation, myocardial damage and elevated C3DC. High-throughput sequencing identified heterozygous mutation (c.798G>A, p.Q266?) in the patient inherited from her father. The other heterozygous mutation (c.641+5G>C) was found in the patient inherited from her mother. RNA-seq showed that there were 254 differential genes in this child, among which 153 genes were up-regulated and 101 genes were down-regulated. Exon jumping events occurred in exons encoding PRMT2 on the positive chain of chromosome 21, which led to abnormal splicing of PRMT2. (P

Humic acids (HAs) are natural polymers with diverse functional groups that have been documented and utilized in traditional Chinese medicine. Dextran sulfate sodium (DSS)-induced colitis has been used as a model to study inflammatory bowel disease. In this research, we investigate the effect of HAs on ameliorating DSS-induced colitis in mice. Our aim here was to investigate if HAs could be a remedy against colitis and the mechanisms involved. The results show that HAs facilitated a regain of body weight and restoration of intestinal morphology after DSS-induced colitis. HAs treatment alters the community of gut microbiota with more Lactobacillus and Bifidobacterium. Changes in bacterial community result in lower amounts of lipopolysaccharides in mouse sera, as well as lower levels of inflammatory cytokines through the Toll-like receptor 4 (TLR4)-NF-κB pathway. HAs also promoted the expression of tight junction proteins, which protect the intestinal barrier from DSS damage. Cell experiments show that HAs display an inhibitory effect on DSS growth as well. These results suggest that HAs can alleviate colitis by regulating intestinal microbiota, reducing inflammation, maintaining mucosal barriers, and inhibiting pathogen growth. Thus, HAs offer great potential for the prevention and treatment of colitis.

Non-invasive prenatal diagnosis for single-gene disorders (NIPD) is still in development and deserves further study. The advent of next-generation sequencing technology significantly improved the detection of multiple mutations for non-invasive prenatal diagnosis for single-gene disorder purposes. However, bespoke amplicon-based NGS assays are costly. In this study, we developed a new strategy for non-invasive prenatal screening for single-gene disorders based on a capillary electrophoresis (CE) platform using an amplification refractory mutation system (ARMS)-PCR technique. Allele-specific primers for several disease-correlated mutations were designed, and subsequently, sensitivity and specificity assays were conducted. Assays on simulated two-person DNA mixtures showed that three primers targeting the mutant allele could detect minor DNA components in 1:500 mixtures. All primers showed positive results at 0.01 ng of the template DNA. Cell-free fetal DNA was extracted from a pregnant woman’s peripheral blood for the detection of paternally inherited mutations. Our results showed that one primer successfully amplified the mutant allele of fetal DNA in maternal plasma, which was confirmed by genotyping the genomic DNA extracted from amniotic fluid. This study suggested that the ARMS-PCR technique, a fast and cost-effective method, might be a promising method used to target de novo or paternally inherited pathogenic mutations in maternal plasma.

Aquaporins (AQPs) are highly-selective transmembrane water transporters that are involved in the adaptation to environmental challenges. However, the structure, function, and evolution of AQPs in bivalves remain largely unknown. In this study, AQP gene family members were identified in nine bivalve species, and their abundance rangs from 7 to 15. Nine AQPs (MmAQPs) were identified in the genome of hard clam (Mercenaria mercenaria), which is a euryhaline bivalve that has evolved sophisticated osmoregulatory mechanisms and salinity adaptation. Structurally, all MmAQPs contain 6 or 12 transmembrane α-helices, a major intrinsic protein (MIP) domain, and 2 asparagine-proline-alanine (NPA) motifs. MmAQPs were classified into three subfamilies based on phylogenetic analysis: AQP1-like, AQP3-like, and AQP8-like. No AQP11-like subfamily member was identified in the genome of hard clam. Tandem duplication resulted in a lineage-specific expansion in AQP8-like subfamily in hard clams. MmAQP8 genes showed different expression sensitivity to different environmental stressors. The gene expression patterns of three MmAQP8 were similar under heat, hypoxia, and air exposure stress, but differed greatly under salinity stress, indicating that tandem duplication events may accelerate the functional divergence of AQP8 genes in hard clams. AQP3-like members may have undergone gene loss during evolution, resulting in weakened glycerol and urea penetration in hard clams. Three orthologs of MmAQPs were detected in the genomes of Cyclina sinensis and Archivesica marissinica through synteny analyses. Tissue expression profiles showed that MmAQP genes were highly expressed in the foot and hepatopancreas. Under environmental stress, the expression levels of most of the MmAQP genes changed significantly to maintain metabolic homeostasis. Several MmAQP genes were downregulated to reduce water permeability under salinity and air exposure stress. Several MmAQP genes were significantly upregulated to promote the transmembrane transport of ammonia and reactive oxygen species and activate anti-apoptotic responses to resist stress. This study provides a comprehensive understanding of the AQP gene family in hard clams, and lays a foundation for further studies to explore the functions of AQPs in bivalves.

With the increasing number of electric vehicles, a large number of charging loads connected to the power system will have an impact on the economic and safe operation of the power system. In this paper a day-ahead optimal dispatching method for distribution network (DN) with fast charging station (FCS) integrated with photovoltaic (PV) and energy storage (ES) is proposed to deal with the negative impact of FCS on DN. By adjusting the load distribution of DN through the optimization decision of ES and soft open points (SOP), the operation level of DN is improved. Firstly, based on the historical vehicle travel data, Monte Carlo simulation method (MCSM) is applied to realize the simulation of fast charging load. Secondly, the uncertainties of PV power is addressed via a robust optimization model of the economic operation level of DN. Based on the second order cone relaxation and duality theory, a two-stage optimal dispatching model of DN is proposed. The optimization model is divided into main problem (MP) and sub problem (SP). For MP, the access position of FCS is adjusted based on SOP. And the charging and discharging power of ES is adjusted. The load distribution is optimized. For SP, based on the uncertainty of PV, the worst scenario of DN is calculated. The robustness of the proposed strategy is guaranteed. Finally, the proposed is verified based on the IEEE 33 bus system and a road network with 34 nodes. The simulation results show that the proposed method can effectively relieve line congestion of DN. The operating range of the voltage is better optimized. And the operation cost of DN is reduced significantly.

English private tutoring, a.k.a. “shadow education” has been an important way that international students rely on for overseas test preparation. Despite the plethora of research on private tutoring in various countries and regions, scarce research focuses on the type of EPT that prepares students for overseas tests. Therefore, this study investigated the experience and perceptions of EPT in preparing for overseas writing tests of 187 Chinese students through retrospective interviews and questionnaires. The present study investigated Chinese students’ experience in and perceptions of EPT for study abroad writing test preparation. The results showed that most students received EPT in writing in various ways at cram schools and they devoted themselves to EPT in cram schools intensively. They favored EPT in cram schools mainly because the test-taking strategies taught there could help them obtain a higher grade on the writing section in overseas tests. With respect to writing teaching in cram schools, the most frequent teaching activities included teaching test-taking strategies and providing writing templates. Although most students acknowledged the usefulness of EPT in writing in terms of preparing themselves for the writing test, it was not necessarily the case for improving their general writing abilities. The students believed that the writing instruction was test-oriented and had a ceiling effect in improving their general writing abilities. However, with enough long time in EPT, the cramming nature of cram schools can be less obvious.

As a vital developmental event, metamorphosis controls the population dynamics of most marine invertebrates and affects the breeding of economic shellfish. Rapana venosa is an economically important species in China, but artificial aquaculture has hampered its metamorphosis process. Previous studies have found that juvenile oysters can effectively induce the metamorphosis of R. venosa, but the specific induction mechanism is not clear. Here, we investigated the mechanism underlying the response of R. venosa to juvenile oysters through the RNA-seq analysis. In this study, the gene set responses to metamorphosis cues (juvenile oysters) in R. venosa were identified, and GO and KEGG enrichment analyses were further performed on these gene sets. The results showed that the expression of the prototype of the class of immediate early genes, the transcription factor AP-1, was rapidly and significantly increased, and the molecular chaperone of NOS, HSP90, exhibited lower expression in the M12 group than in the control group. In contrast, the expression of inhibitors of apoptosis (IAPs) was significantly increased upon exposure to juvenile oysters. Additionally, the Wnt signaling pathway and MAPK signaling pathway were enriched in the trend analysis. These pathways may also play critical regulatory roles in the response to juvenile oysters. Taken together, the results show that competent larvae rapidly respond to the inducing effects of oysters via some immediate early genes, such as the transcription factor AP-1, which may further regulate downstream pathways such as the MAPK signaling pathway to cause subsequent changes, including a decrease in HSP90 and an increase in IAPs. These changes together may regulate the metamorphosis of R. venosa. This study provides further evidence that juvenile oysters are the metamorphosis cues of R. venosa, which may enhance our understanding of the metamorphosis mechanism in this marine invertebrate.

Yucca has abundant amounts of polyphenolics, steroidal saponins, and resveratrol and its extract can be used as a feed additive in the animal husbandry, which might contribute to the improvement in the growth and productivity in rabbit production. Hence, the current study aimed to examine the effects of yucca extract alone and in combination with Clostridium butyricum (C. butyricum) on growth performance, nutrient digestibility, muscle quality, and intestinal development of weaned rabbits. A total of 400 40-day-old male rabbits were randomly divided into 4 treatment groups for 40 days: (1) basal diet group, (2) basal diet contained 300 mg/kg of yucca extract, (3) basal diet supplemented with 0.4 × 1010 colony-forming units (CFU)/kg of C. butyricum, and (4) the blend of 0.4 × 1010/kg CFU of C. butyricum and 300 mg/kg of yucca extract. The supplementation of yucca extract or C. butyricum increased body weight (BW) of rabbits depending on the age, the combined addition of yucca extract and C. butyricum significantly increased BW, weight gain, and feed intake, companying with increased the digestibility of crud protein, fiber, phosphorous, and calcium as compared to control diet (P < 0.05). Furthermore, yucca extract and C. butyricum treatment alone and in combination notably increased the villus high and the ratio of villus high to crypt depth of rabbits (P < 0.05). The combined supplementation of yucca extract and C. butyricum altered the intestinal microbiota of rabbits, as demonstrated by increased the abundance of beneficial bacteria Ruminococcaceae and decreased the proportion of pathogenic bacteria such as Pseudomonadaceae and S24-7. In addition, the rabbits fed the diet with yucca extract and the blend of yucca extract and C. butyricum had significantly increased pH45min, decreased pressing loss, drip loss, and shears force when compared with rabbits received control diet (P < 0.05). Diet with C. butyricum or its mixture with yucca extract increased the fat content of meat, while the combined addition of yucca extract and C. butyricum declined the content of fiber in meat (P < 0.05). Collectively, the combined use of yucca extract and C. butyricum showed better results on growth performance and meat quality, which might be closely associated with the improved intestinal development and cecal microflora of the rabbits.

Marine protected areas (MPAs) are important tools for maintaining biodiversity, mitigating climate change, and conserving and restoring natural ecosystems. Management effectiveness assessment is an important component of conservation management in protected areas. In this study, we constructed a management effectiveness assessment tool based on publicly available information for China, with a total score of 126. We used the tool to systematically assess 27 national MPAs in the East China Sea. Our results showed that marine nature reserves (MNRs) and marine special reserves (MSRs) could be classified into two and three classifications, respectively, including MNRs I (n = 4, scores = 88-100), MNRs II (n = 6, scores = 75-81), MSRs I (n = 8, scores = 75-90), MSRs II (n = 6, scores = 59-75) and MSRs III (n = 3, scores = 53-56). Factors influencing the management effectiveness of nature reserves were the length of establishment and general public budget revenue, while for special reserves they were the length of establishment and total agricultural output value. Furthermore, protected areas with high management effectiveness scores tend to have a longer establishment time, dedicated management departments, adequate management staff and financial investment compared to those with low scores. In addition, the low-score MPAs require more communication with stakeholders. The study provides an objective and comprehensive systematic scoring of MPAs’ management using METT-based framework and multi-source data. It overcomes the challenge of the general lack of data on MPAs and provides a new approach to management effectiveness assessment.

As a crucial coastal wetland habitat in the transition zone between land and sea, global tidal flats have severely declined by 16% over the last two decades under the dual threats of intense human activities and climate change. The Yangtze River Delta of China, the largest estuary in the western Pacific Ocean, has abundant mudflat resources and a dense human population. It also has some of the most prominent conflicts between economic development and ecological conservation. The current lack of understanding of landscape patterns and influencing factors of the Yangtze River Delta mudflats has severely hampered the region’s ecological conservation and restoration efforts. Based on Landsat time-series images, this study generated a 30-m spatial resolution map of mudflats in the Yangtze River Delta, which shrank by 47% during 1990–2020, with a higher density of mudflat loss in Yancheng and Nantong cities of the Jiangsu province and Hangzhou, Shaoxing, and Ningbo cities of the Zhejiang province. Landscape indices, such as the patch density of tidal flats, have gradually changed since 2000, with most of them showing significant changes in 2010. Mudflats in Lianyungang, northwestern Yancheng, Nanhui, Jiaxing, and Hangzhou showed sharp negative changes in landscape characteristics. Natural and anthropogenic factors had synergistic effects on the above changes in mudflat landscape patterns in the Yangtze River Delta. Mudflat landscape features were mainly influenced by population growth, economic development, reclamation, sediment discharge, and air temperature. Based on the evolving characteristics of mudflat landscape patterns, we recommend improving mudflat landscape management and planning by strengthening mudflat policies, laws, and regulations, developing countermeasures against threats from major stressors, and enhancing the effectiveness of nature reserves for mudflat protection.

BackgroundTrauma-induced immune dysfunction has been a major barrier to achieving reduced mortality, which is poorly understood. Autophagy is a crucial catabolic mechanism of immune cells during times of stress. Few studies have investigated the immune regulatory effects induced by autophagy after trauma. Here, we use single-cell transcriptomics analysis in a major trauma cohort to demonstrate the dominant role of autophagy in innate immune cells during the early stages of major trauma.MethodSingle-cell transcriptional profiling of peripheral blood mononuclear cells (PBMCs) was performed, which were sampled from three control participants and five major trauma patients within 6 hours of injury. In detail, after single-cell RNA-sequence data processing, cell type annotation and cluster marker identification were performed. A genetic toolbox with 604 autophagy-related genes was used to monitor the autophagy levels in immune cells. In addition, all transcriptome RNA sequencing data obtained from PBMCs in a cohort of 167 major trauma patients were downloaded from gene expression omnibus (GEO) datasets (GSE36809). Key deregulated biological processes and important autophagic hub genes involved in immune cells were identified by weighted gene co-expression network analysis and gene ontology enrichment analysis.ResultsA total of 20,445 differentially expressed genes were identified and five co-expression modules were constructed. Enrichment analysis indicated that activated autophagy is the most important biological process during the early stages of major trauma, and JMY (autophagy-related genes) were identified as hub genes. The single-cell transcriptional profiling of PBMCs demonstrated that all components of adaptive immune cells were significantly decreased, whereas components of innate immune cells (monocytes and neutrophils) were significantly increased in major trauma patients compared with control participants. Activated autophagy was detected in monocytes and neutrophils by monitoring the dynamic transcriptional signature of the autophagy-related genetic toolbox. Biological process analysis shows that antigen uptake, processing presentation, and major histocompatibility complex (MHC) class II protein complex assembly pathways were up-regulated in autophagy-positive monocytes, whereas antigen processing and presentation of endogenous antigen and type I interferon signaling pathways were up-regulated in autophagy-positive neutrophils during the early stages of major trauma.ConclusionOur study demonstrated that autophagy is a biological process crucial to the development of immune disorders in the early stages of major trauma. Furthermore, the results of our study generated a comprehensive single-cell immune landscape for major trauma patients, in which we determined that autophagy profoundly affects the main functions of innate immune cells and provides insight into the cellular basis of immune dysregulation after major trauma.

BackgroundThe sustainable development of the agricultural product supply chain (APSC) is the key to protecting public health.MethodsThis paper explores the sustainable development status of the APSC in three northeast provinces of China from 2007 to 2020 and the development trend in the next 5 years by using the entropy weight—matter-element extension model (MEEM) and autoregressive integrated moving average model (ARIMA), taking into account the background of relatively backward development and the high proportion of agricultural output in these three provinces.ResultsAccording to the research results, the sustainable development of the APSC in Jilin Province is relatively stable, Heilongjiang Province has made considerable progress in the sustainable development of the APSC in recent years, while Liaoning Province has shown a significant downward trend in recent years in the sustainable development of the APSC, despite a strong development momentum in previous years.ConclusionsThe findings of this paper can be applied to the governance of APSC in other rural areas with uneven development. The assessment also provides guidance on the quality and safety of agricultural products and public health, and raises the awareness of policymakers on the importance of the APSC.