Roles of the tumor microenvironment in the resistance to programmed cell death protein 1 inhibitors in patients with gastric cancer.

Despite the continuous developments and advancements in the treatment of gastric cancer (GC), which is one of the most prevalent types of cancer in China, the overall survival is still poor for most patients with advanced GC. In recent years, with the progress in tumor immunology research, attention has shifted toward immunotherapy as a therapeutic approach for GC. Programmed cell death protein 1 (PD-1) inhibitors, as novel immunosuppressive medications, have been widely utilized in the treatment of GC. However, many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy. To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy, to maximize the clinical activity of immunosuppressive drugs, and to elicit a lasting immune response, it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients. This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment, aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.

Structural and property characterization of low-molecular-weight novel reuterans synthesized from pea starch by Limosilactobacillus reuteri N1 GtfB with 4,6-α-glucanotransferase II activity.

Promising novel α-glucanotransferases with starch-converting activity have recently emerged from the CAZy GH70 GtfB subfamily. In this study, we thoroughly investigated and elucidated the impact of the newly characterized 4,6-α-glucanotransferase II Limosilactobacillus reuteri N1 GtfB (LrN1 GtfB), which was capable of synthesizing linear (α1 → 6) and branched (α1 → 4,6) linkages, on the fine structure, rheology, and retrogradation properties of pea starch (PS). The results revealed that as the reaction time increased, the total (α1 → 6) linkages in linear chains and branching points of PS increased from 5.6 % to 18.7 %, the molecular weight decreased from 7.3 × 106 g/mol to 7.4 × 104 g/mol, and the percentage of short chains (DP ≤ 12) increased from 47.4 % to 92.7 %, thereby producing low-molecular-weight, short-clustered novel reuterans with new (α1 → 6) linkages in both linear chains and branches. Additionally, LrN1 GtfB-modified PS exhibited lower storage/loss modulus and weaker creep property, indicating a significant attenuation of the strength and rigidity of the modified gel structure. Moreover, products derived from pea starch and LrN1 GtfB exhibited notably low retrogradation properties. These findings provide insights into the potential application of GtfB-type α-glucanotransferases in starch-based products, thereby producing unique-structured α-glucans with versatile properties from starch.

In vitro digestion and functional properties of bovine ß-casein: A comparison between adults and infants.

Gastrointestinal digestibility behavior, structural and functional characteristics of bovine ß-casein (ß-CN) were studied in vitro under infant and adult conditions. This direct comparison helps reveal the effects of different physiological stages on the digestive behavior of ß-CN. Not only was the degree of hydrolysis (DH) of ß-CN analyzed, but also the changes in its digestive morphology, microstructure, and secondary structure during digestion were explored in depth. Meanwhile, we focused on the physicochemical properties of ß-CN digesta, including solubility, emulsifying and foaming properties, as well as their functional properties, such as antimicrobial and antioxidant activities. Key results showed that ß-CN underwent more extensive hydrolysis in the adult digestion model, with approximately twice the DH compared to the infant model. The adult model exhibited faster digestion kinetics, less protein flocculation, and a more loosened secondary structure, indicating a more efficient digestion process. Notably, the digesta from the adult model displayed significantly improved solubility and emulsifying properties, and also enhanced antioxidant capacities, with significantly better inhibition of two common pathogenic bacteria than the infant model, and an average increase in the diameter of the inhibition zone of approximately 2 mm. These findings underscore the differential digestive behavior and functional potential of ß-CN across physiological stages. This comprehensive assessment approach contributes to a more comprehensive insight into the digestive behavior of ß-CN. Therefore, we conclude that producing products from unmodified ß-CN may be more suitable for the adult population, and that the digesta in the adult model exhibit higher functional properties.

Wild Pepper (Piper laetispicum) Fruit Quality Traits at Different Developmental Stages.

High-quality Piper laetispicum (Piper laetispicum C. DC) is the key to the development of foods, natural medicines, and cosmetics. Its crude fat, ash, piperine, protein, and aroma compounds were determined in this experiment. Principal component (PCA) and hierarchical cluster analyses (HCA) were used to evaluate the aroma compounds at different developmental stages. The main aroma compounds identified using steam distillation combined with GC-MS were sabinene (34.83-76.14%), α-copaene (5.11-19.51%), linalool (2.42-15.70%), trans-caryophyllene (2.37-6.57%), α-pinene (1.51-4.31%), and germacrene D (1.30-4.10%). The aroma metabolites at different developmental stages were analysed using non-targeted metabolomes, and linalool was found to be the most abundant. Based on the experimental results, there were more nutrient compounds in young Piper laetispicum than in the last three developmental stages. The aromatic metabolites contributed the most to PC1. There were also more different metabolites of aroma between the young and expanding stages. Therefore, regarding quality, young fruits have great potential.

Fabrication of rGO/BiOI photocathode and its catalytic performance in the degradation of 4-Fluoroaniline.

Organic fluorine compounds are acute carcinogenic and mutagenic to humans. Photoelectrocatalysis (PEC) treatment is an innovative technology in the field of the removal of fluorine compounds, and thus current research focused on improving stability and catalytic ability of photoanode. In this study, it has been synthesized a rGO/BiOI photocathode for the efficient degradation of 4-Fluoroaniline (4-FA). The physical characterization and photoelectrochemical properties of the photocathode was determined. The results indicate that the PEC treatment with the rGO/BiOI photocathode was more efficient compared with individual processes. During the optimization experiments, the PEC treatment achieved 99.58 % and 72.12 % of 4-FA degradation and defluorination within 1 h. Cyclic stability experiments show that rGO/BiOI photocathode was efficient and stable, which reached 96.91 % and 67.64 % of 4-FA degradation and defluorination after five cycles. Mechanism analysis indicates that the PEC process was based on an electrochemical reaction and photo-induced processes. The degradation product of 4-FA was mainly 2,4-di-t-butylphenol, and trapping experiments indicates that h+ is the primary oxidizing species. Therefore, PEC treatment with rGO/BiOI photocathode is a competitive green approach to remove fluorine compounds pollutants and brings new insights into development of PEC treatment.

Genome-Wide Identification, Characterization, and Expression Analysis of the MYB-R2R3 Gene Family in Black Pepper (Piper nigrum L.).

Black pepper (Piper nigrum L.), a prominent spice crop, known as the "king of spices", originated from India. The growth and development of black pepper are influenced by various environmental conditions. MYB transcription factors play a crucial role in controlling metabolic processes, abiotic stress management, and plant growth and development. In this study, we identified 160 PnMYB transcription factors in the black pepper genome. Phylogenetic analysis was performed using 125 R2R3-MYB proteins from black pepper and Arabidopsis thaliana, resulting in the mapping of 20 groups on the phylogenetic tree, each containing members from both species. Most members of the PnMYB family possess two introns, and motif 3 and motif 4 are conserved in all members. The number of genes on each chromosome ranges from 1 to 10. Collinear analysis indicated the creation of new members through gene fragments and tandem replication. The Ka/Ks ratio indicated that purifying selection and positive selection acted on PnMYB of pepper. The majority of pepper PnMYB family members were in the nucleus. Significant differences in gene expression levels were observed between different species and infection periods when Piper nigrum L. and Piper flaviflorum were infected with Phytophthora capsici. These findings are valuable for future studies on the biological role and molecular mechanism of the PnMYB gene.

Prognostic aging gene-based score for colorectal cancer: unveiling links to drug resistance, mutation burden, and personalized treatment strategies.

OBJECTIVE: Colorectal cancer (CRC) is characterized by high incidence and mortality rates worldwide. In this study, we present a novel aging-related gene-based risk scoring system (Aging score) as a predictive tool for CRC prognosis. METHOD: We identified prognostic aging-related genes using univariate Cox regression analysis, revealing key biological processes in CRC progression. We then constructed a robust prognostic model using LASSO and multivariate Cox regression analyses, including four critical genes: CAV1, FOXM1, MAD2L1, and WT1. RESULT: The Aging score demonstrated high prognostic performance across the training, testing, and entire TCGA-CRC datasets, proving its reliability. High-risk patients identified by the Aging score had significantly shorter overall survival times than low-risk patients, indicating its potential for patient stratification and personalized treatment. The Aging score remained an independent prognostic factor compared to age, gender, and tumor stage. Additionally, the score was linked to tumor mutation burden and microsatellite instability, indicators of immune checkpoint inhibitor response. High-risk patients also showed higher estimated IC50 values for common chemotherapeutic drugs, suggesting possible treatment resistance. CONCLUSION: Our findings highlight the Aging score's potential to enhance clinical decision-making and pave the way for personalized CRC management.

Research status of polycystic ovary syndrome treatment: a mini review and a bibliometric analysis from 2010 to 2023.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in premenopausal women, often linked to abdominal obesity, insulin resistance, and metabolic issues. With its heterogeneous nature, PCOS treatment should be tailored to individual symptoms and patient preferences. This study examines collaboration networks among countries, institutions, authors, references, and journals related to PCOS treatment. METHODS: Web of Science data was analyzed using VOSviewer and CiteSpace for bibliometric visualization. Chinese and Western medicine treatments for PCOS were reviewed, emphasizing symptom-targeted solutions. RESULTS: Data from 4682 records authored by 400 individuals from 515 institutes in 62 countries revealed China as the leading contributor. Notable authors include Monash University and Richard S. Legro. Common research themes include adipocytes, inflammation, insulin sensitivity, oxidative stress, and the gut microbiome. Tailoring treatment to individual needs is essential, focusing on hyperandrogenism, ovulation, and insulin resistance, with lifestyle counseling to address obesity. CONCLUSION: This bibliometric analysis provides valuable insights into the research status of PCOS treatment. China has made significant contributions, and complementary and alternative therapies, such as traditional Chinese medicine and acupuncture, have also shown beneficial effects recently. The research on inflammation, oxidative stress, and the gut microbiome may provide new targets and strategies for the treatment of PCOS. The recognition of the metabolic problems in PCOS patients facilitates the formulation of more personalized treatment plans to improve the prognosis of patients.

Localized Cas12a-based cascade amplification for sensitive and robust detection of APE1.

APE1, an essential enzyme for DNA repair, is overexpressed in various cancers and has been identified as a potential biomarker for cancer diagnosis. However, detecting APE1 at low expression levels in the early stage of cancer presents a significant obstacle. Here, we introduced a novel localized Cas12a-based cascade amplification (LCas12a-CA) method. This method confined both the terminal deoxynucleotidyl transferase and the crRNA/Cas12a complex onto the surfaces of gold nanoparticles (AuNPs). This confinement not only boosts the stability of the multiple enzymes but also induces a substrate channeling effect. As a result, it significantly accelerates the reaction rate and enhances the sensitivity of APE1 detection. Upon the addition of APE1, the AP sites within the APE1 primer can be recognized and cleaved by APE1, exposing the 3'-OH ends. In the presence of LCas12a-CA, polyA sequences are generated at 3'-OH ends with the help of TdT and dATP. The sequences directly enter the Cas12a system, activating the trans-cleavage activity of Cas12a, thereby cutting the reporters on the surface of AuNPs and releasing fluorescence. Our platform demonstrates a detection limit (LOD) as low as 2.51 × 10-6 U/mL, which is more than 60 times lower than that of free Cas12a-CA. Furthermore, the LCas12a-CA exhibits enhanced resistance ability in extreme environments and has been proven effective for the detection of APE1 in clinical samples. Overall, this work offers a promising platform for robust biosensing in cancer diagnosis and prognosis.

Genome-wide identification of Glycyrrhiza uralensis Fisch. MAPK gene family and expression analysis under salt stress relieved by Bacillus subtilis.

Introduction: Research on Glycyrrhiza uralensis, a nonhalophyte that thrives in saline-alkaline soil and a traditional Chinese medicinal component, is focused on improving its ability to tolerate salt stress to increase its productivity and preserve its "Dao-di" characteristics. Furthermore, the inoculation of bioagents such as Bacillus subtilis to increase plant responses to abiotic stressors is currently a mainstream strategy. Mitogen-activated protein kinase (MAPK), a highly conserved protein kinase, plays a significant role in plant responses to various abiotic stress pathways. Methods: This investigation involved the identification of 21 members of the GuMAPK family from the genome of G. uralensis, with an analysis of their protein conserved domains, gene structures, evolutionary relationships, and phosphorylation sites using bioinformatics tools. Results: Systematic evolutionary analysis of the 21 GuMAPKs classified them into four distinct subgroups, revealing significant differences in gene structure and exon numbers. Collinearity analysis highlighted the crucial role of segmental duplication in expanding the GuMAPK gene family, which is particularly evident in G. uralensis and shows a close phylogenetic relationship with Arabidopsis thaliana, tomato, and cucumber. Additionally, the identification of phosphorylation sites suggests a strong correlation between GuMAPK and various physiological processes, including hormonal responses, stress resistance, and growth and development. Protein interaction analysis further supported the role of GuMAPK proteins in regulating essential downstream genes. Through examination of transcriptome expression patterns, GuMAPK16-2 emerged as a prospective pivotal regulatory factor in the context of salt stress and B. subtilis inoculation, a finding supported by its subcellular localization within the nucleus. Discussion: These discoveries offer compelling evidence for the involvement of GuMAPK in the salt stress response and for the exploration of the mechanisms underlying B. subtilis' enhancement of salt tolerance in G. uralensis.

Prognostic model of fibroblasts in idiopathic pulmonary fibrosis by combined bulk and single-cell RNA-sequencing.

Background: Fibroblasts play an important role in the development of idiopathic pulmonary fibrosis (IPF). Methods: We employed single-cell RNA-sequencing data obtained from the Gene Expression Omnibus database to perform cell clustering and annotation analyses. We then performed secondary clustering of fibroblasts and conducted functional enrichment and cell trajectory analyses of the two newly defined fibroblast subtypes. Bulk RNA-sequencing data were used to perform consensus clustering and weighted gene co-expression network analysis. We constructed a fibroblast-related prognostic model using least absolute shrinkage, selection operator regression, and Cox regression analysis. The prognostic model was validated using a validation dataset. Immune infiltration and functional enrichment analyses were conducted for patients in the high- and low-risk IPF groups. Results: We characterized two fibroblast subtypes that are active in IPF (F3+ and ROBO2+). Using fibroblast-related genes, we identified five genes (CXCL14, TM4SF1, CYTL1, SOD3, and MMP10) for the prognostic model. The area under the curve values of our prognostic model were 0.852, 0.859, and 0.844 at one, two, and three years in the training set, and 0.837, 0.758, and 0.821 at one, two, and three years in the validation set, respectively. Conclusion: This study annotates and characterizes different subtypes of fibroblasts in IPF.

Nickel(II)/BINOL-catalyzed enantioselective C-H activation via desymmetrization and kinetic resolution.

The field of nickel catalysis has witnessed remarkable growth in recent years. However, the use of nickel catalysts in enantioselective C-H activation remains a daunting challenge because of their variable oxidation states, intricate coordination chemistry, and unpredictable reactivity patterns. Herein, we report an enantioselective C-H activation reaction catalyzed by commercially available and air-stable nickel(II) catalyst. Readily available and simple (S)-BINOL is used as a chiral ligand. This operationally simple protocol enables the synthesis of planar chiral metallocenes in high yields with excellent enantioselectivity through desymmetrization and kinetic resolution. Air-stable planar chiral nickelacycle intermediates are first synthesized via enantioselective C-H nickelation and shown to be possible intermediates of the reaction. Deuterium-labeling studies, alongside the characterization and transformation of chiral nickel(II) species, suggest that C-H cleavage is the enantio-determining step. Moreover, the large-scale synthesis and diverse synthetic transformations underscore the practicality of this protocol.

The influence of adverse events on inpatient outcomes in a tertiary hospital using a diagnosis-related group database.

Adverse events (AEs) are a significant concern for healthcare systems. However, it is difficult to evaluate their influence because of the complexity of various medical services. This study aimed to assess the influence of AEs on the outcomes of hospitalized patients using a diagnosis-related group (DRG) database. We conducted a case-control study of hospitalized patients at a multi-district tertiary hospital with 2200 beds in China, using data from a DRG database. An AE refers to an unintended physical injury caused or contributed to by medical care that requires additional hospitalization, monitoring, treatment, or even death. Relative weight (RW), a specific indicator of DRG, was used to measure the difficulty of diagnosis and treatment, disease severity, and medical resources utilized. The primary outcomes were hospital length of stay (LOS) and hospitalization costs. The secondary outcome was discharge to home. This study applied DRG-based matching, Hodges-Lehmann estimate, regression analysis, and subgroup analysis to evaluate the influence of AEs on outcomes. Two sensitivity analyses by excluding short LOS and changing adjustment factors were performed to assess the robustness of the results. We identified 2690 hospitalized patients who had been divided into 329 DRGs, including 1345 patients who experienced AEs (case group) and 1345 DRG-matched normal controls. The Hodges-Lehmann estimate and generalized linear regression analysis showed AEs led to prolonged LOS (unadjusted difference, 7 days, 95% confidence interval [CI] 6-8 days; adjusted difference, 8.31 days, 95% CI 7.16-9.52 days) and excess hospitalization costs (unadjusted difference, $2186.40, 95% CI: $1836.87-$2559.16; adjusted difference, $2822.67, 95% CI: $2351.25-$3334.88). Logistic regression analysis showed AEs were associated with lower odds of discharge to home (unadjusted odds ratio [OR] 0.66, 95% CI 0.54-0.82; adjusted OR 0.75, 95% CI 0.61-0.93). The subgroup analyses showed that the results for each subgroup were largely consistent. LOS and hospitalization costs increased significantly after AEs in complex diseases (RW ≥ 2) and in relation to high degrees of harm subgroups (moderate harm and above groups). Similar results were obtained in sensitivity analyses. The burden of AEs, especially those related to complex diseases and severe harm, is significant in China. The DRG database serves as a valuable source of information that can be utilized for the evaluation and management of AEs.

[Effect of combined application of organic and chemical fertilizers on yield and quality of Epimedium pubescens].

To investigate the effects of different ratios of organic and chemical fertilizers on the yield and quality of Epimedium pubescens,so as to provide a scientific basis for the fertilization of high-yield and high-quality E. pubescens cultivation. In this experiment,a field plot test was conducted,and CK(without fertilizer) was set as the control group,with five treatment groups with different ratios of organic fertilizers and chemical fertilizers set up,namely OF0(100% chemical fertilizers),OF25(25% organic fertilizers),OF50(50% organic fertilizers),OF75(75% organic fertilizers),and OF100(100% organic fertilizers). The effects of different fertilization patterns on the agronomic traits,yield,effective component content,nutrient accumulation,and soil physicochemical properties of E. pubescens were determined,and the yield and quality of the medicinal herb were comprehensively evaluated by using the CRITIC weights method. It was found that the herb yield of each treatment group was significantly increased compared with the CK group,although the yield of the groups with both organic fertilizer and chemical fertilizer was slightly lower than that of OF0. However,there was no significant difference,which indicated that the organic fertilizer combined with chemical fertilizer could ensure the herb yield. With the increase in organic fertilizer ratios,the medicinal components epimedin A,epimedin B,and epimedin C showed a tendency of first increasing and then decreasing,with the highest content in the OF25,while icariin showed a rising trend,with the best in the OF100. However,overall,the total flavonol glycosides ABCI accumulated the most in the OF25. The results of the CRITIC method showed that the top three fertilization treatments in terms of the comprehensive scores of the medicinal herb were OF25,OF50,and OF75. Organic fertilizer combined with chemical fertilizer is conducive to improving the soil's fertilizer holding and supply capacity,and the soil indexes are optimal in OF100. The soil enzyme activity is the highest in OF75. Meanwhile,organic fertilizer combined with chemical fertilizer can help the plant's uptake and accumulation of nutrients,and OF25 shows the most obvious effect.By comprehensively considering the influence of different ratios of organic and chemical fertilizers on the yield,effective component content,nutrient accumulation,and other indexes of E. pubescens,it is recommended that a 25% ratio(7 500 kg·hm~(-2)) of organic fertilizers and chemical fertilizers should be used in E. pubescens production in the first year,so as to promote the E. pubescens industry to increase yield and improve quality.

Association of Definitive Radiotherapy for Esophageal Cancer and the Incidence of Secondary Head and Neck Cancers: A SEER Population-Based Study.

Background: Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC. Methods: This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis. Results: In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC. Conclusion: An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC.

Prediction of carbon emissions from public buildings in China's Coastal Provinces under different scenarios --A case study of Fujian Province.

With the rapid pace of industrialization and the increasing intensity of human activities, the global climate change and energy crisis have reached a heightened level of severity. Consequently, achieving an early peak in carbon emissions has become an imperative in addressing this pressing issue. Particularly, coastal provinces, known for their developed economies, high population density, and substantial building energy consumption, have emerged as significant contributors to carbon emissions. Notably, public buildings, serving as critical constituents of the construction industry, possess immense potential for both energy conservation and emissions reduction. In light of this, the present study focuses on Fujian Province, situated along the coast, and constructs a carbon emission estimation model for public buildings based on the Kaya identity. This model takes into account various factors specific to Fujian Province, including population characteristics, economic conditions, tertiary industry development, public building area, and energy consumption. Through scenario analysis, the study projects that the year of peak carbon emissions for public buildings in Fujian Province is estimated to be 2030, 2035, and 2040 under low-carbon, baseline, and high-carbon scenarios respectively. The corresponding peak carbon emission levels are anticipated to reach 23.62 million t, 24.18 million t, and 24.76 million t CO2. Lastly, based on local policies and actual conditions, the study proposes a set of policy measures and feasible approaches tailored to Fujian Province, aiming to achieve an early peak in carbon emissions.

Serum macroelements and microelements levels in periparturient dairy cows in relation to fatty liver diseases.

BACKGROUND: Fatty liver in dairy cows is a common metabolic disease defined by triglyceride (TG) buildup in the hepatocyte. Clinical diagnosis of fatty liver is usually done by liver biopsy, causing considerable economic losses in the dairy industry owing to the lack of more effective diagnostic methods. Therefore, this study aimed to investigate the potential utility of blood biomarkers for the diagnosis and early warning of fatty liver in dairy cows. RESULTS: A total of twenty-four lactating cows within 28 days after parturition were randomly selected as experimental animals and divided into healthy cows (liver biopsy tested, n = 12) and cows with fatty liver (liver biopsy tested, n = 12). Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the macroelements and microelements in the serum of two groups of cows. Compared to healthy cows (C), concentrations of calcium (Ca), potassium (K), magnesium (Mg), strontium (Sr), selenium (Se), manganese (Mn), boron (B) and molybdenum (Mo) were lower and copper (Cu) was higher in fatty liver cows (F). Meanwhile, the observed differences in macroelements and microelements were related to delivery time, with the greatest major disparity between C and F occurring 7 days after delivery. Multivariable analysis was used to test the correlation between nine serum macroelements, microelements and fatty liver. Based on variable importance projection and receiver operating characteristic (ROC) curve analysis, minerals Ca, Se, K, B and Mo were screened as the best diagnostic indicators of fatty liver in postpartum cows. CONCLUSIONS: Our data suggested that serum levels of Ca, K, Mg, Se, B, Mo, Mn, and Sr were lower in F than in C. The most suitable period for an early-warning identification of fatty liver in cows was 7 days after delivery, and Ca, Se, K, B and Mo were the best diagnostic indicators of fatty liver in postpartum cows.

Association of Methyl Donor Nutrients' Dietary Intake and Cognitive Impairment in the Elderly Based on the Intestinal Microbiome.

Globally, cognitive impairment (CI) is the leading cause of disability and dependency among the elderly, presenting a significant public health concern. However, there is currently a deficiency in pharmacological interventions that can effectively cure or significantly reverse the progression of cognitive impairment. Methyl donor nutrients (MDNs), including folic acid, choline, and vitamin B12, have been identified as potential enhancers of cognitive function. Nevertheless, there remains a dearth of comprehensive research investigating the connection between the dietary intake of MDNs and CI. In our study, we comprehensively assessed the relationship between MDNs' dietary intake and CI in older adults, utilizing 16S rRNA gene sequencing to investigate the potential underlying mechanisms. The results showed an obvious difference in the methyl-donor nutritional quality index (MNQI) between the dementia (D) group and the dementia-free (DF) group. Specifically, there was a lower MNQI in the D group than that in the DF group. For the gut microbiome, the beta diversity of gut flora exhibited higher levels in the high methyl-donor nutritional quality (HQ) group as opposed to the low methyl-donor nutritional quality (LQ) group, and lower levels in the D group in comparison to the DF group. Subsequently, we performed a correlation analysis to examine the relationship between the relative abundance of microbiota, the intake of MDNs, and Montreal Cognitive Assessment (MoCA) scores, ultimately identifying ten genera with potential regulatory functions. Additionally, KEGG pathway analyses suggested that the one-carbon metabolism, chronic inflammation, and DNA synthesis potentially serve as pathways through which MDNs may be promising for influencing cognitive function. These results implied that MDNs might have the potential to enhance cognitive function through the regulation of microbiota homeostasis. This study offers dietary recommendations for the prevention and management of CI in the elderly.

Analyzing embryo dormancy at single-cell resolution reveals dynamic transcriptional responses and activation of integrin-Yap/Taz prosurvival signaling.

Embryonic diapause is a reproductive adaptation that enables some mammalian species to halt the otherwise continuous pace of embryonic development. In this dormant state, the embryo exploits poorly understood regulatory mechanisms to preserve its developmental potential for prolonged periods of time. Here, using mouse embryos and single-cell RNA sequencing, we molecularly defined embryonic diapause at single-cell resolution, revealing transcriptional dynamics while the embryo seemingly resides in a state of suspended animation. Additionally, we found that the dormant pluripotent cells rely on integrin receptors to sense their microenvironment and preserve their viability via Yap/Taz-mediated prosurvival signaling.

Taraxasterol protects against acetaminophen-induced hepatotoxicity by reducing liver inflammatory response and ameliorating oxidative stress in mice.

Acute liver failure is mainly caused by the overdose of acetaminophen (APAP) globally. The traditional Chinese medicinal (TCM) herb, Taraxacum, contains Taraxasterol (TAX) as one of the active components. It is a pentacyclic-triterpene compound isolated from this herb. Present work aimed to investigate the in vitro and in vivo protection effect of TAX in APAP-induced acute liver injury, and determine the potential regulatory mechamisms. The liver injury caused by APAP is attenuated by TAX, as shown by the alleviated pathological changes of mice liver and the reduced serological indexes. TAX evidently controlled the oxidative stress and liver inflammation in mice liver. In vitro studies found that TAX reversed the decrease in LO2 cell viability induced by APAP, and protected LO2 cells from APAP-induced injury. In addition, TAX reduced the secretion of inflammatory factors in RAW264.7 macrophages as induced via APAP. Besides, TAX inhibited oxidative stress in LO2 cells induced by APAP in vitro. Noteworthy, TAX enhanced protein and mRNA expressions of Nrf2 in vivo, and knockdown of Nrf2 by using adeno-associated virus (AAV)-Nrf2-KO attenuated inhibitory impact of TAX in acute liver injury induced by APAP. Also, AAV-NRF2-KO weakened the inhibitory impact of TAX against APAP-triggered liver inflammation and oxidative stress of mice liver. Moreover, TAX activated the Nrf2 signaling in APAP-induced LO2 cells, as shown by the increased nuclear Nrf2 expression together with downstream HO-1 expression in vitro. Inhibition of Nrf2 by using ML-385, anNrf2inhibitor, weakened the inhibitory effect of TAX against APAP-induced oxidative stress and cell injury in LO2 cells. Moreover, inhibition of Nrf2 attenuated anti-inflammatory effect of TAX for APAP-induced RAW264.7 cells. Collectively, TAX could protect against APAP-triggered hepatotoxicitythrough suppression of liver oxidative stress and inflammatory response in mice.