The impact of intracytoplasmic sperm injection versus conventional in vitro fertilization on the reproductive outcomes of couples with non-male factor infertility and frozen-thawed embryo transfer cycles.

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

Theoretical study of excited state dynamics of a ratiometric fluorescent probe for detection of SO2 derivatives.

Sulfur dioxide (SO2), a toxic air pollutant, can have harmful effects on human health when inhaled or when it forms bisulfite in the body. In the present work, a ratiometric fluorescent probe, 2-(2'-hydroxyphenyl)benzothiazole-3-ethyl-1,1,2-trimethyl-1H-benzo[e]indolium (HBT-EMBI), was selected to study the mechanism of SO2 derivatives detection. This study provides insights into the attributions of ratiometric fluorescence through hydrogen bond dynamics, electronic excitation properties, radiation rates, and excited state intramolecular proton transfer (ESIPT) processes using the density functional theory (DFT) and the time-dependent density functional theory (TDDFT) level. The results confirm that the large Stokes shifts and broad emission spectra of the HBT-EMBI probe are associated with its intramolecular charge transfer (ICT) characteristics and hydrogen bonding-driven ESIPT processes, respectively. After the addition reaction between the probe and HSO3-/SO32-, the conformational populations of HBT-EMBI-HSO3- transfer abnormally from enol configurations to more stable keto configurations, which leads to a distinguished change in the visible color and the ratiometric fluorescence signal, and is not due to the blockage of the ICT process of HBT-EMBI-HSO3-, as previously reported. This work provides a new perspective on the mechanism of detection of SO2 derivatives by ESIPT fluorescent probes.

Exploring the predictive values of CRP and lymphocytes in coronary artery disease based on a machine learning and Mendelian randomization.

Purpose: To investigate the predictive value of leukocyte subsets and C-reactive protein (CRP) in coronary artery disease (CAD). Methods: We conducted a Mendelian randomization analysis (MR) on leukocyte subsets, C-reactive protein (CRP) and CAD, incorporating data from 68,624 patients who underwent coronary angiography from 2010 to 2022. After initial screening, clinical data from 46,664 patients were analyzed. Techniques employed included propensity score matching (PSM), logistic regression, lasso regression, and random forest algorithms (RF). Risk factors were assessed, and the sensitivity and specificity of the models were evaluated using receiver operating characteristic (ROC) curves. Additionally, survival analysis was conducted based on a 36-month follow-up period. Results: The inverse variance weight (IVW) analysis showed that basophil count (OR 0.92, 95% CI: 0.84-1.00, P = 0.048), CRP levels (OR 0.87, 95% CI: 0.73-1.00, P = 0.040), and lymphocyte count (OR 1.10, 95% CI: 1.04-1.16, P = 0.001) are significant risk factors for CAD. Using LASSO regression, logistic regression, and RF analysis, both CRP and lymphocyte counts were consistently identified as risk factors for CAD, prior to and following PSM. The ROC curve analysis indicated that the combination of lymphocyte and CRP levels after PSM achieves a higher diagnostic value (0.85). Survival analysis revealed that high lymphocyte counts and low CRP levels are associated with a decreased risk of Major Adverse Cardiovascular Events (MACE) (P < 0.001). Conversely, a higher CRP level combined with lymphocyte counts correlates with a poorer prognosis. Conclusion: There is a causal relationship between lymphocytes, CRP and CAD. The combined assessment of CRP and lymphocytes offers diagnostic value for CAD. Furthermore, high CRP levels coupled with low lymphocyte counts are associated with a poor prognosis.

Matrix Viscoelasticity Tunes the Mechanobiological Behavior of Chondrocytes.

In articular cartilage, the pericellular matrix acting as a specialized mechanical microenvironment modulates environmental signals to chondrocytes through mechanotransduction. Matrix viscoelastic alterations during cartilage development and osteoarthritis (OA) degeneration play an important role in regulating chondrocyte fate and cartilage matrix homeostasis. In recent years, scientists are gradually realizing the importance of matrix viscoelasticity in regulating chondrocyte function and phenotype. Notably, this is an emerging field, and this review summarizes the existing literatures to the best of our knowledge. This review provides an overview of the viscoelastic properties of hydrogels and the role of matrix viscoelasticity in directing chondrocyte behavior. In this review, we elaborated the mechanotransuction mechanisms by which cells sense and respond to the viscoelastic environment and also discussed the underlying signaling pathways. Moreover, emerging insights into the role of matrix viscoelasticity in regulating chondrocyte function and cartilage formation shed light into designing cell-instructive biomaterial. We also describe the potential use of viscoelastic biomaterials in cartilage tissue engineering and regenerative medicine. Future perspectives on mechanobiological comprehension of the viscoelastic behaviors involved in tissue homeostasis, cellular responses, and biomaterial design are highlighted. Finally, this review also highlights recent strategies utilizing viscoelastic hydrogels for designing cartilage-on-a-chip.

The posttraumatic growth of fathers of preterm infants: protocol for a qualitative study in China.

Background: Prematurity presents a significant life crisis for families, often exceeding their expectations. Fathers of premature infants face the burden of multiple caregiving roles and undergo psychological changes. When confronted with such crises, individuals often engage in self-evaluation and may experience positive transformations. This study aims to employ a qualitative research methodology to explore the experiences of fathers of preterm infants. Materials and methods: A phenomenological approach design will be utilized, drawing upon semi-structured in-depth interviews informed by existing literature. Thematic analysis will be employed, adhering to the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. In-depth individual interviews, lasting 40-60 minutes, will be conducted with fathers of preterm infants to understand their experiences. The thematic analysis process will facilitate a comprehensive understanding of the factors contributing to post-traumatic growth among these fathers. This methodology provides a structured approach to investigating the experiences and influences on post-traumatic growth in fathers of preterm infants. Results: This study will highlight changes in post-traumatic growth among fathers of preterm infants. Discussion: Research on the post-traumatic growth (PTG) of fathers of preterm infants is crucial to understanding the unique challenges and psychological transformations they experience. This study aims to explore the factors contributing to PTG in these fathers and how cultural contexts in China influence this process. By elucidating these aspects, the findings can inform targeted interventions and support systems tailored to the needs of fathers of preterm infants. The results may also contribute to developing guidelines and policies to promote psychological well-being and resilience among this population in the healthcare system. Ethics and dissemination: This study adheres to the International Ethical Guidelines for Biomedical Research and the Declaration of Helsinki. Approval has been obtained from the People's Hospital of Deyang Human Research Ethics Committee (No: 2019-04-150-K01). The research follows the principles of open science, and the findings will be published while ensuring participants' confidentiality.

Combating coal-burning-borne endemic arsenism in Shaanxi Province, Northwest China: The impact of high-arsenic coal ban, improved cook-stoves, and health education.

To eliminate the epidemic of coal-burning-borne endemic arsenism (CBBA), our study organized and implemented comprehensive measures including high-arsenic coal ban, improved cook-stoves, and health education. We also aimed to promote the application value of these measures in preventing and controlling CBBA to the world. From 2004 to 2005, through a stratified random sampling method, we selected 58,256 individuals to investigate the prevalence of CBBA and the arsenic levels in 1287 environmental and biological specimens. The prevalence of CBBA was 19.26 % and significantly associated with the arsenic levels in coal, pepper, corn and hair, which were at or exceeded national upper limits. To timely prevent and control the disease, the comprehensive measures have been implemented since 2005 to present. Comparison and correlation analyses were utilized to evaluate the effectiveness of these measures in reducing the prevalence of CBBA. According to statistics, 73 high-arsenic coal mines were banned and over 99 % households in endemic areas accepted stove improvements and diversified health education. Monitoring studies during 2010-2019 has confirmed that these measures led to a decrease in urine arsenic levels among endemic residents, and they developed novel dietary practices, such as properly drying, storage, and washing of food. Additionally, the awareness rate of CBBA increased from less than 70 % to over 95 %. Finally, the prevalence of CBBA has decreased to 0.153 % investigated by a census involving 2.076 million endemic residents in 2019. In summary, CBBA in northwest China has been successfully controlled through banning on high-arsenic coal, introducing improved cook-stoves, and providing health education.

Butyric acid reduced lipid deposition in immortalized chicken preadipocyte by inhibiting cell proliferation and differentiation.

The hyperplasia and hypertrophy of preadipocytes were closely related to lipid deposition in animals. Butyric acid was reported to be involved in lipid metabolism. The aim of the current study was to investigate the effect of butyric acid on the proliferation and differentiation of the immortalized chicken preadipocyte 2 (ICP2). ICP2 were treated respectively with 12mM butyric acid for 48h in proliferation trial and 4mM butyric acid plus 200 µM oleic acid for 3 d in differentiation trial. For the proliferation trial, RNA-seq analysis revealed that 2039 genes were significantly up-regulated and 780 genes were significantly down-regulated with 12 mM butyric acid after 48 h treatment. Concurrently, Cell cycle, DNA replication and p53 signaling pathways were down-regulated in Butyric acid group. More importantly, 12 mM butyric acid restrained the expression of cell proliferation genes such as PCNA, CDK1 and CDK2 in Butyric acid group (P < 0.05), and the protein expression levels of PCNA and CDK1 were also significantly decreased (P < 0.05). The Oil red staining revealed a fewer presence of red fat droplets in ICP2 following treatment with 4 mM butyric acid, accompanied by decreased levels of total cholesterol (TC) and triglycerides (TG). RNA-seq analysis shown that the number of up and down-regulated genes were 2095 and 1042 respectively in OAB group (oleic acid+butyric acid) when compared with OA group (oleic acid). Meanwhile the AMPK signaling pathway, FOXO signaling pathway and focal adhesion were significantly enriched in OAB group. Additionally, 4 mM butyric acid inhibited the expression of lipid differentiation genes including FABP4, C/EBPα, PPARγ and LPL in OAB group (P < 0.05), as well as lipogenesis proteins such as FABP4, C/EBP-α and PPARγ (P < 0.05). In conclusion, 12 mM butyric acid effectively inhibited the proliferation of ICP2 by slowing down cell cycle progression, while 4 mM butyric acid alleviated lipid deposition by reducing the production of lipid droplets through inhibiting the expression of lipid differentiation marker genes and proteins.

Unveiling an anoikis-related risk model and the role of RAD9A in colon cancer.

OBJECTIVE: Colorectal cancer (CRC), specifically colon adenocarcinoma, is the third most prevalent and the second most lethal form of cancer. Anoikis is found to be specialized form of programmed cell death (PCD), which plays a pivotal role in tumor progression. This study aimed to investigate the role of the anoikis related genes (ARGs) in colon cancer. METHODS: Consensus unsupervised clustering, differential expression analysis, tumor mutational burden analysis, and analysis of immune cell infiltration were utilized in the study. For the analysis of RNA sequences and clinical data of COAD patients, data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were obtained. A prognostic scoring system for overall survival (OS) prediction was developed using Cox regression and LASSO regression analysis. Furthermore, loss-of-function assay was utilized to explore the role of RAD9A played in the progression of colon cancer. RESULTS: The prognostic value of a risk score composed of NTRK2, EPHA2, RAD9A, CDC25C, and SNAI1 genes was significant. Furthermore, these findings suggested potential mechanisms that may influence prognosis, supporting the development of individualized treatment plans and management of patient outcomes. Further experiments confirmed that RAD9A could promote proliferation and metastasis of colon cancer cells. These effects may be achieved by affecting the phosphorylation of AKT. CONCLUSION: Differences in survival time and the tumor immune microenvironment (TIME) were observed between two gene clusters associated with ARGs. In addition, a prognostic risk model was established and confirmed as an independent risk factor. Furthermore, our data indicated that RAD9A promoted tumorigenicityby activating AKT in colon cancer.

Role of Excessive Mitochondrial Fission in Seawater Immersion Aggravated Hemorrhagic Shock-Induced Cardiac Dysfunction and the Protective Effect of Mitochondrial Division Inhibitor-1.

Aims: Seawater immersion significantly aggravated organ dysfunction following hemorrhagic shock, leading to higher mortality rate. However, the effective treatment is still unavailable in clinic. Mitochondria were involved in the onset and development of multiple organ function disorders; whether mitochondria participate in the cardiac dysfunction following seawater immersion combined with hemorrhagic shock remains poorly understood. Hence, we investigated the role and possible mechanism of mitochondria in seawater immersion combined with hemorrhage shock-induced cardiac dysfunction. Results: Mitochondrial fission protein dynamin-related protein 1 (Drp1) was activated and translocated from the cytoplasm to mitochondria in the heart following seawater immersion combined with hemorrhagic shock, leading to excessive mitochondrial fission. Excessive mitochondrial fission disrupted mitochondrial function and structure and activated mitophagy and apoptosis. At the same time, excessive mitochondrial fission resulted in disturbance of myocardial structure and hemodynamic disorders and ultimately provoked multiple organ dysfunction and high mortality. Further studies showed that the mitochondrial division inhibitor mitochondrial division inhibitor-1 can significantly reverse Drp1 mitochondrial translocation and inhibit mitochondrial fragmentation, reactive oxygen species (ROS) accumulation, mitophagy, and apoptosis and then protect circulation and vital organ functions, prolonging animal survival. Innovation: Our findings indicate that Drp1-mediated mitochondrial fission could be a novel therapeutic targets for the treatment of seawater immersion combined with hemorrhagic shock. Conclusion: Drp1 mitochondrial translocation played an important role in the cardiac dysfunction after seawater immersion combined with hemorrhage shock. Drp1-mediated excessive mitochondrial fission leads to cardiac dysfunction due to the mitochondrial structure and bioenergetics impairment.

Npc1 deficiency impairs microglia function via TREM2-mTOR signaling in Niemann-Pick disease type C.

Niemann-Pick disease Type C (NPC) is a neurodegenerative disease mainly caused by the mutation in NPC1 gene, leading to massive accumulation of unesterified cholesterol in the late endosome/lysosome of cells. Impaired phenotype of microglia is a hallmark in Npc1 mutant mice (Npc1-/- mice). However, the mechanism of Npc1 in regulating microglial function is still unclear. Here, we showed that the reactive microglia in the neonatal Npc1-/- mice indicated by the increased lysosome protein CD68 and phagocytic activity were associated with disrupted TREM2-mTOR signaling in microglia. Furthermore, in Npc1-deficient BV2 cells, genetic deletion of Trem2 partially restored microglial function, probably via restored mTOR signaling. Taken together, our findings indicated that loss of Npc1 in microglia caused changes of their morphologies and the impairment of lysosomal function, which were linked to the TREM2-mTOR signaling pathway.

CD34+ stromal cells/telocytes and their role in mouse lung development: Light microscopy, immunofluorescence, ultrastructural and scanning electron microscopy evidence.

Telocytes (TCs), a novel type of mesenchymal or interstitial cell with specific, very long and thin cellular prolongations, have been found in various mammalian organs and have potential biological functions. However, their existence during lung development is poorly understood. This study aimed to investigate the existence, morphological features, and role of CD34+ SCs/TCs in mouse lungs from foetal to postnatal life using primary cell culture, double immunofluorescence, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The immunofluorescence double staining profiles revealed positive expression of CD34 and PDGFR-α, Sca-1 or VEGFR-3, and the expression of these markers differed among the age groups during lung development. Intriguingly, in the E18.5 stage of development, along with the CD34+ SCs/TCs, haematopoietic stem cells and angiogenic factors were also significantly increased in number compared with those in the E14.5, E16.5, P0 and P7. Subsequently, TEM confirmed that CD34+ SCs/TCs consisted of a small cell body with long telopodes (Tps) that projected from the cytoplasm. Tps consisted of alternating thin and thick segments known as podomers and podoms. TCs contain abundant endoplasmic reticulum, mitochondria and secretory vesicles and establish close connections with neighbouring cells. Furthermore, SEM revealed characteristic features, including triangular, oval, spherical, or fusiform cell bodies with extensive cellular prolongations, depending on the number of Tps. Our findings provide evidence for the existence of CD34+ SCs/TCs, which contribute to vasculogenesis, the formation of the air‒blood barrier, tissue organization during lung development and homoeostasis.

Synergistic collaboration between AMPs and non-direct antimicrobial cationic peptides.

Non-direct antimicrobial cationic peptides (NDACPs) are components of the animal innate immune system. But their functions and association with antimicrobial peptides (AMPs) are incompletely understood. Here, we reveal a synergistic interaction between the AMP AW1 and the NDACP AW2, which are co-expressed in the frog Amolops wuyiensis. AW2 enhances the antibacterial activity of AW1 both in vitro and in vivo, while mitigating the development of bacterial resistance and eradicating biofilms. AW1 and AW2 synergistically damage bacterial membranes, facilitating cellular uptake and interaction of AW2 with the intracellular target bacterial genomic DNA. Simultaneously, they trigger the generation of ROS in bacteria, contributing to cell death upon reaching a threshold level. Moreover, we demonstrate that this synergistic antibacterial effect between AMPs and NDACPs is prevalent across diverse animal species. These findings unveil a robust and previously unknown correlation between AMPs and NDACPs as a widespread antibacterial immune defense strategy in animals.

Dietary betaine supplementation improved egg quality and gut microbes of laying hens under dexamethasone-induced oxidative stress.

Oxidative stress is a frequent concern in the breeding of laying hens, and limit the healthy development of poultry. Dexamethasone (DXM) has been demonstrated to induce oxidative stress. Conversely, betaine is an alkaloid with a potent antioxidant activity. The study was designed to investigate the ameliorative effect of betaine on DXM-induced oxidative stress in laying hens. The results revealed that DXM treatment significantly decreased laying rate, shell strength, albumen height, Haugh unit, egg weight, folk weight and albumen weight, alongside increased malondialdehyde (MDA) and decreased total antioxidant capacity (T-AOC) in serum and liver (P < 0.05). In contrast, dietary betaine addition reversed those parameters mentioned above (P < 0.05). Hepatic RNA-seq analysis showed that there existed 110 up- and 88 down-regulated genes in DXM group when compared with the control. Meanwhile there were 117 upregulation and 169 downregulation genes in BT group when compared with DXM group. Besides, we found that dietary betaine addition significantly down-regulated cell adhesion molecules, glycerolipid metabolism and glycolysis gluconeogenesis pathways. In addition, a total of 44 and 94 differential metabolites were identified respectively from Con vs. DXM and DXM vs BT. More importantly, dietary betaine addition significantly increased the levels of pantothenic acid, gamma-Aminobutyric acid, equol and choline, all of which were related to antioxidant and anti-inflammatory properties. Furthermore, gut microbiota analysis indicated that the Chao and Observed_species indexes were remarkably higher in BT group (P<0.05). Heatmap analysis revealed that Subdoligranulum, Prevotella, Blautia, YRC22, Bacteroides, Ruminococcus and Coprococcus were notably restored in BT group (P<0.05). Taken together, our findings collectively illustrate that dietary betaine addition could attenuate DXM-induced oxidative stress, improve egg quality and gut microbes of laying hens.

Novel manufacturing process of pneumococcal capsular polysaccharides using advanced sterilization methods.

Pneumococcal disease is caused by Streptococcus pneumoniae, including pneumonia, meningitis and sepsis. Capsular polysaccharides (CPSs) have been shown as effective antigens to stimulate protective immunity against pneumococcal disease. A major step in the production of pneumococcal vaccines is to prepare CPSs that meet strict quality standards in immunogenicity and safety. The major impurities come from bacterial proteins, nucleic acids and cell wall polysaccharides. Traditionally, the impurity level of refined CPSs is reduced by optimization of purification process. In this study, we investigated new aeration strategy and advanced sterilization methods by formaldehyde or ß-propiolactone (BPL) to increase the amount of soluble polysaccharide in fermentation supernatant and to prevent bacterial lysis during inactivation. Furthermore, we developed a simplified process for the CPS purification, which involves ultrafiltration and diafiltration, followed by acid and alcohol precipitation, and finally diafiltration and lyophilization to obtain pure polysaccharide. The CPSs prepared from formaldehyde and BPL sterilization contained significantly lower level of residual impurities compared to the refined CPSs obtained from traditional deoxycholate sterilization. Finally, we showed that this novel approach of CPS preparation can be scaled up for polysaccharide vaccine production.

Exogenous Application of Amino Acids Alleviates Toxicity in Two Chinese Cabbage Cultivars by Modulating Cadmium Distribution and Reducing Its Translocation.

Plants communicate underground by secreting multiple amino acids (AAs) through their roots, triggering defense mechanisms against cadmium (Cd) stress. However, the specific roles of the individual AAs in Cd translocation and detoxification remain unclear. This study investigated how exogenous AAs influence Cd movement from the roots to the shoots in Cd-resistant and Cd-sensitive Chinese cabbage cultivars (Jingcui 60 and 16-7 cultivars). The results showed that methionine (Met) and cysteine (Cys) reduced Cd concentrations in the shoots of Jingcui 60 by approximately 44% and 52%, and in 16-7 by approximately 43% and 32%, respectively, compared to plants treated with Cd alone. However, threonine (Thr) and aspartic acid (Asp) did not show similar effects. Subcellular Cd distribution analysis revealed that AA supplementation increased Cd uptake in the roots, with Jingcui 60 preferentially storing more Cd in the cell wall, whereas the 16-7 cultivar exhibited higher Cd concentrations in the organelles. Moreover, Met and Cys promoted the formation of Cd-phosphate in the roots of Jingcui 60 and Cd-oxalate in the 16-7 cultivar, respectively. Further analysis showed that exogenous Cys inhibited Cd transport to the xylem by downregulating the expression of HMA2 in the roots of both cultivars, and HMA4 in the 16-7 cultivar. These findings provide insights into the influence of exogenous AAs on Cd partitioning and detoxification in Chinese cabbage plants.

Intelligent drugs based on notch protein remodeling: a defensive targeting strategy for tumor therapy.

In the process of tumor treatment, systemic drug administration is hindered by biological barriers, leading to the retention of a large number of drug molecules in healthy tissues and causing unavoidable side effects. The precise deployment of drugs at the tumor site is expected to alleviate this phenomenon. Here, we take endostatin and Her2 (+) tumors as examples and develop an intelligent drug with simple "wisdom" by endowing mesenchymal stem cells (MSCs) with an intelligent response program (iMSCEndostatin). It can autonomously perceive and distinguish tumor cells from non-tumor cells, establishing a logical connection between tumor signals and drug release. Enable it to selectively deploy drugs at the tumor site, thereby locking the toxicity of drugs at the tumor site. Unlike traditional aggressive targeting strategies that aim to increase drug concentration at the lesion, intelligent drugs are more inclined to be defensive strategies that prevent the presence of drugs in healthy tissues.

Th1 cells reduce the osteoblast-like phenotype in valvular interstitial cells by inhibiting NLRP3 inflammasome activation in macrophages.

BACKGROUND AND AIMS: Inflammation is initiates the propagation phase of aortic valve calcification. The activation of NLRP3 signaling in macrophages plays a crucial role in the progression of calcific aortic valve stenosis (CAVS). IFN-γ regulates NLRP3 activity in macrophages. This study aimed to explore the mechanism of IFN-γ regulation and its impact on CAVS progression and valve interstitial cell transdifferentiation. METHODS AND RESULTS: The number of Th1 cells and the expression of IFN-γ and STAT1 in the aortic valve, spleen and peripheral blood increased significantly as CAVS progressed. To explore the mechanisms underlying the roles of Th1 cells and IFN-γ, we treated CAVS mice with IFN-γ-AAV9 or an anti-IFN-γ neutralizing antibody. While IFN-γ promoted aortic valve calcification and dysfunction, it significantly decreased NLRP3 signaling in splenic macrophages and Ly6C+ monocytes. In vitro coculture showed that Th1 cells inhibited NLPR3 activation in ox-LDL-treated macrophages through the IFN-γR1/IFN-γR2-STAT1 pathway. Compared with untreated medium, conditioned medium from Th1-treated bone marrow-derived macrophages reduced the osteogenic calcification of valvular interstitial cells. CONCLUSION: Inhibition of the NLRP3 inflammasome by Th1 cells protects against valvular interstitial cell calcification as a negative feedback mechanism of adaptive immunity toward innate immunity. This study provides a precision medicine strategy for CAVS based on the targeting of anti-inflammatory mechanisms.

BHBA attenuates endoplasmic reticulum stress-dependent neuroinflammation via the gut-brain axis in a mouse model of heat stress.

BACKGROUND: Heat stress (HS) commonly occurs as a severe pathological response when the body's sensible temperature exceeds its thermoregulatory capacity, leading to the development of chronic brain inflammation, known as neuroinflammation. Emerging evidence suggests that HS leads to the disruption of the gut microbiota, whereas abnormalities in the gut microbiota have been demonstrated to affect neuroinflammation. However, the mechanisms underlying the effects of HS on neuroinflammation are poorly studied. Meanwhile, effective interventions have been unclear. ß-Hydroxybutyric acid (BHBA) has been found to have neuroprotective and anti-inflammatory properties in previous studies. This study aims to explore the modulatory effects of BHBA on neuroinflammation induced by HS and elucidate the underlying molecular mechanisms. METHODS: An in vivo and in vitro model of HS was constructed under the precondition of BHBA pretreatment. The modulatory effects of BHBA on HS-induced neuroinflammation were explored and the underlying molecular mechanisms were elucidated by flow cytometry, WB, qPCR, immunofluorescence staining, DCFH-DA fluorescent probe assay, and 16S rRNA gene sequencing of colonic contents. RESULTS: Heat stress was found to cause gut microbiota disruption in HS mouse models, and TM7 and [Previotella] spp. may be the best potential biomarkers for assessing the occurrence of HS. Fecal microbiota transplantation associated with BHBA effectively reversed the disruption of gut microbiota in HS mice. Moreover, BHBA may inhibit microglia hyperactivation, suppress neuroinflammation (TNF-α, IL-1ß, and IL-6), and reduce the expression of cortical endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP) mainly through its modulatory effects on the gut microbiota (TM7, Lactobacillus spp., Ruminalococcus spp., and Prevotella spp.). In vitro experiments revealed that BHBA (1 mM) raised the expression of the ERS marker GRP78, enhanced cellular activity, and increased the generation of reactive oxygen species (ROS) and anti-inflammatory cytokines (IL-10), while also inhibiting HS-induced apoptosis, ROS production, and excessive release of inflammatory cytokines (TNF-α and IL-1ß) in mouse BV2 cells. CONCLUSION: ß-Hydroxybutyric acid may be an effective agent for preventing neuroinflammation in HS mice, possibly due to its ability to inhibit ERS and subsequent microglia neuroinflammation via the gut-brain axis. These findings lay the groundwork for future research and development of BHBA as a preventive drug for HS and provide fresh insights into techniques for treating neurological illnesses by modifying the gut microbiota.

Predictive value of total cholesterol to high-density lipoprotein cholesterol ratio for chronic kidney disease among adult male and female in Northwest China.

Background: Studies have found that the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) was associated with the development of chronic kidney disease (CKD). However, the relationship in different genders was rarely discussed. The aim of this study was to explore this relationship and assess its predictive power for both males and females. Methods: Based on a prospective cohort platform in northwest China, 32,351 participants without CKD were collected in the baseline and followed up for approximately 5 years. Cox proportional hazard model and restricted cubic spline regression analysis were performed to investigate the association between TC, HDL-C, TC/HDL-C and CKD in adult female and male. The clinical application value of the indicators in predicting CKD was evaluated by the receiver operator characteristic curve. Results: During a mean follow-up of 2.2 years, 484 males and 164 females developed CKD. After adjusted for relevant confounders, for every one standard deviation increase in TC, HDL-C and TC/HDL-C, the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for CKD were 1.17 (1.05-1.31), 0.84 (0.71-0.99), and 1.15 (1.06-1.25) for males, 0.94 (0.78-1.13), 0.58 (0.35-0.95), and 1.19 (1.01-1.40) for females, respectively. The results also showed that TC, HDL-C, and TC/HDL-C were associated with CKD in a linear dose-response relationship. The TC/HDL-C had the largest area under the curve (AUC) compared to TC and HDL-C, and the AUC among the females was larger than that among males. Conclusions: The TC/HDL-C was significantly associated with CKD in adult males and females and has better clinical value in predicting CKD than TC and HDL-C, especially in females.

Water body extraction from high spatial resolution remote sensing images based on enhanced U-Net and multi-scale information fusion.

Employing deep learning techniques for the semantic segmentation of remote sensing images has emerged as a prevalent approach for acquiring information about water bodies. Yet, current models frequently fall short in accurately extracting water bodies from high-resolution remote sensing images, as these images often present intricate details of terrestrial objects and complex backgrounds. Vegetation, shadows, and other objects close to water boundaries have increased similarity to water bodies. Moreover, water bodies in high-resolution images have different boundary complexities, shapes, and sizes. This situation makes it somewhat challenging to accurately distinguish water bodies in high-resolution images. To overcome these difficulties, this paper presents a novel network model named EU-Net, specifically designed to extract water bodies from high-resolution remote sensing images. The proposed EU-Net model, with U-net as the backbone network, incorporates improved residual connections and attention mechanisms, and designs multi-scale dilated convolution and multi-scale feature fusion modules to enhance water body extraction performance in complex scenarios. Specifically, in the proposed model, improved residual connections are introduced to enable the learning of more complex features; the attention mechanism is employed to improve the model's discriminative ability by focusing on important channels and spatial areas. The implemented multi-scale dilated convolution technique enhances the model's receptive field while maintaining the same number of parameters. The designed multi-scale feature fusion module is capable of processing both small-scale details and large-scale structures in images, while simultaneously modeling the spatial context relationships of features at different scales. Experimental results validate the superior performance of EU-Net in accurately identifying water bodies from high-resolution remote sensing images, outperforming current models in terms of water extraction accuracy.