[Impact of cecal ligation and puncture-induced sepsis on the proliferation and differentiation of intestinal stem cells].

OBJECTIVE: To analyze the impact of cecal ligation and puncture (CLP)-induced sepsis on the proliferation and differentiation of intestinal epithelial cells. METHODS: (1) Animal experiment: sixteen male C57BL/6 mice were divided into sham operation group (Sham group) and CLP-induced sepsis model group (CLP group) by random number table method, with 8 mice in each group. After 5 days of operation, the jejunal tissues were taken for determination of leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) and intestinal alkaline phosphatase (IAP) by polymerase chain reaction (PCR). The translation of LGR5 was detected by Western blotting. The expression of proliferating cell nuclear antigen (Ki67) was analyzed by immunohistochemistry. IAP level was detected by modified calcium cobalt staining and colorimetry. Immunofluorescence staining was used to detect the expression of Paneth cell marker molecule lysozyme 1 (LYZ1) and goblet cell marker molecule mucin 2 (MUC2). (2) Cell experiment: IEC6 cells in logarithmic growth stage were divided into blank control group and lipopolysaccharide (LPS) group (LPS 5 µg/mL). Twenty-four hours after treatment, PCR and Western blotting were used to analyze the transcription and translation of LGR5. The proliferation of IEC6 cells were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining. The transcription and translation of IAP were detected by PCR and colorimetric method respectively. RESULTS: (1) Animal experiment: the immunohistochemical results showed that the positive rate of Ki67 staining in the jejunal tissue of CLP group was lower than that of Sham group [(41.7±2.5)% vs. (48.7±1.4)%, P = 0.01]. PCR and Western blotting results showed that there were no statistical differences in the mRNA and protein expressions of LGR5 in the jejunal tissue between the CLP group and Sham group (Lgr5 mRNA: 0.7±0.1 vs. 1.0±0.2, P = 0.11; LGR5/ß-actin: 0.83±0.17 vs. 0.68±0.19, P = 0.24). The mRNA (0.4±0.1 vs. 1.0±0.1, P < 0.01) and protein (U/g: 47.3±6.0 vs. 73.1±15.3, P < 0.01) levels of IAP in the jejunal tissue were lower in CLP group. Immunofluorescence saining analysis showed that the expressions of LYZ1 and MUC2 in the CLP group were lower than those in the Sham group. (2) Cell experiment: PCR and Western blotting results showed that there was no significant difference in the expression of LGR5 between the LPS group and the blank control group (Lgr5 mRNA: 0.9±0.1 vs. 1.0±0.2, P = 0.33; LGR5/ß-actin: 0.71±0.18 vs. 0.69±0.04, P = 0.81). The proliferation rate of IEC6 cells in the LPS group was lower than that in the blank control group, but there was no significant difference [positivity rate of EdU: (40.5±3.8)% vs. (46.5±3.6)%, P = 0.11]. The mRNA (0.5±0.1 vs. 1.0±0.2, P < 0.01) and protein (U/g: 15.0±4.0 vs. 41.2±10.4, P < 0.01) of IAP in the LPS group were lower than those in the blank control group. CONCLUSIONS: CLP-induced sepsis inhibits the proliferation and differentiation of intestinal epithelial cells, impairing the self-renewal ability of intestinal epithelium.

Comparative efficacy of six programmed cell death Protein-1 inhibitors as first-line treatment for advanced non-small cell lung cancer: a multicenter retrospective cohort study.

The purpose of this study was to assess the comparative efficacy of six programmed cell death-1 inhibitors (nivolumab, pembrolizumab, sintilimab, tislelizumab, toripalimab, and camrelizumab) that have been used as first-line therapy for Chinese patients with advanced non-small cell lung cancer (NSCLC), which remains unclear. We determined the differences in efficacy by observing patient survival data, with the goal of informing future treatment options. Retrospective data analysis from June 2015 to April 2023 included 913 patients across six groups: nivolumab (123%, 13.5%), pembrolizumab (421%, 46.1%), sintilimab (239%, 26.1%), tislelizumab (64%, 7.0%), toripalimab (39%, 4.3%), and camrelizumab (27%, 3.0%). The median progression-free survival (PFS) for each group was 16.0, 16.1, 18.4, 16.9, 23.7, and 12.8 months, and the median overall survival (OS) was 33.7, 36.1, 32.5, not reached, 30.9 and 46.0 months for the nivolumab, sintilimab, pembrolizumab, tislelizumab, toripalimab, and camrelizumab groups, respectively. While differences existed in the objective response rates among groups (p < 0.05), there were no significant differences (all p > 0.05) in PFS or OS. The findings suggest comparable efficacy among these PD-1 inhibitors for NSCLC treatment, underscoring their collective suitability and aiding treatment decisions.

Prevalence and viral suppression of hepatitis B virus infection among people living with HIV on antiretroviral therapy in Sierra Leone.

OBJECTIVE: Sub-Saharan Africa is one of the regions with the highest burdens of HIV and hepatitis B virus (HBV), but data on the impact of antiretroviral therapy (ART) on HBV DNA suppression is limited. In this study, we aimed to determine the prevalence and associated factors of a positive hepatitis B surface antigen (HBsAg) among people living with HIV, and assess the suppression of ART on HBV replication in people living with HIV in Sierra Leone. METHODS: A cross-sectional study was designed to recruit people living with HIV aged 18 years or older in ten public hospitals in Sierra Leone between August 2022 and January 2023. Statistical analyses were performed using R software. Logistic regression analysis was used to assess factors independently associated with positive HBsAg and HBV DNA suppression. RESULTS: Of the 3106 people living with HIV recruited in this study, 2311 (74.4%) were women. The median age was 36 years, 166 (5.3%) had serological evidence of HBV vaccination. The overall prevalence of HBsAg positivity was 12.0% (95% CI: 10.9% to 13.2%). Male sex (adjusted OR (aOR) 2.11, 95% CI: 1.67 to 2.68; p<0.001) and being separated (aOR 1.83, 95% CI: 1.06 to 3.16, p=0.031; reference group: being married) were independent predictors of HBsAg seropositivity. Among 331 people living with HIV and HBV receiving ART, 242 (73.1%) achieved HBV DNA suppression (below 20 IU/mL). HBV suppression rate was higher in HIV-virally suppressed patients than those with unsuppressed HIV viral load (p<0.001). In addition, the male sex was more likely to have unsuppressed HBV DNA (aOR 1.17, 95% CI: 1.17 to 3.21; p=0.010). CONCLUSIONS: We reported a high prevalence of HBsAg seropositivity and low HBV immunisation coverage in people living with HIV in Sierra Leone. In addition, we observed that ART can efficiently result in a viral suppression rate of HBV infection. Therefore, achieving the global target of eliminating HBV infection by 2030 requires accelerated access to care for people living with HIV and HBV, including HBV testing, antiviral treatment and hepatitis B vaccination.

Single-nucleus transcriptome analysis identifies a novel FKBP5+ endothelial cell subtype involved in endothelial-to-mesenchymal transition in adipose tissue during aging.

Age-associated adipose tissue (AT) dysfunction is multifactorial and often leads to detrimental health consequences. AT is highly vascularized and endothelial cells (ECs) has been recently identified as a key regulator in the homeostasis of AT. However, the alteration of cell composition in AT during aging and the communication between endothelial cells and adipocytes remain poorly understood. In this study, we take advantage of single nucleus RNA sequencing analysis, and discovered a group of FKBP5+ ECs specifically resident in aged AT. Of interest, FKBP5+ ECs exhibited the potential for endothelial-to-mesenchymal transition (EndoMT) and exhibited a critical role in regulating adipocytes. Furthermore, lineage tracing experiments demonstrated that ECs in aged AT tend to express FKBP5 and undergo EndoMT with progressive loss of endothelial marker. This study may provide a basis for a new mechanism of microvascular ECs-induced AT dysfunction during aging.

Impact of high-altitude acclimatization and de-acclimatization on the intestinal microbiota of rats in a natural high-altitude environment.

Introduction: Intestinal microorganisms play an important role in the health of both humans and animals, with their composition being influenced by changes in the host's environment. Methods: We evaluated the longitudinal changes in the fecal microbial community of rats at different altitudes across various time points. Rats were airlifted to high altitude (3,650 m) and acclimatized for 42 days (HAC), before being by airlifted back to low altitude (500 m) and de-acclimatized for 28 days (HADA); meanwhile, the control group included rats living at low altitude (500 m; LA). We investigated changes in the gut microbiota at 12 time points during high-altitude acclimatization and de-acclimatization, employing 16S rRNA gene sequencing technology alongside physiological indices, such as weight and daily autonomous activity time. Results: A significant increase in the Chao1 index was observed on day 14 in the HAC and HADA groups compared to that in the LA group, indicating clear differences in species richness. Moreover, the principal coordinate analysis revealed that the bacterial community structures of HAC and HADA differed from those in LA. Long-term high-altitude acclimatization and de- acclimatization resulted in the reduced abundance of the probiotic Lactobacillus. Altitude and age significantly influenced intestinal microbiota composition, with changes in ambient oxygen content and atmospheric partial pressure being considered key causal factors of altitude-dependent alterations in microbiota composition. High-altitude may be linked to an increase in anaerobic bacterial abundance and a decrease in non-anaerobic bacterial abundance. Discussion: In this study, the hypobaric hypoxic conditions at high-altitude increased the abundance of anaerobes, while reducing the abundance of probiotics; these changes in bacterial community structure may, ultimately, affect host health. Overall, gaining a comprehensive understanding of the intestinal microbiota alterations during high-altitude acclimatization and de-acclimatization is essential for the development of effective prevention and treatment strategies to better protect the health of individuals traveling between high- and low-altitude areas.

KaryoXpert: An accurate chromosome segmentation and classification framework for karyotyping analysis without training with manually labeled metaphase-image mask annotations.

Automated karyotyping is of great importance for cytogenetic research, as it speeds up the process for cytogeneticists through incorporating AI-driven automated segmentation and classification techniques. Existing frameworks confront two primary issues: Firstly the necessity for instance-level data annotation with either detection bounding boxes or semantic masks for training, and secondly, its poor robustness particularly when confronted with domain shifts. In this work, we first propose an accurate segmentation framework, namely KaryoXpert. This framework leverages the strengths of both morphology algorithms and deep learning models, allowing for efficient training that breaks the limit for the acquirement of manually labeled ground-truth mask annotations. Additionally, we present an accurate classification model based on metric learning, designed to overcome the challenges posed by inter-class similarity and batch effects. Our framework exhibits state-of-the-art performance with exceptional robustness in both chromosome segmentation and classification. The proposed KaryoXpert framework showcases its capacity for instance-level chromosome segmentation even in the absence of annotated data, offering novel insights into the research for automated chromosome segmentation. The proposed method has been successfully deployed to support clinical karyotype diagnosis.

Quantitative morphological analysis framework of infant cranial sutures and fontanelles based on CT images.

Characterizing the suture morphological variation is a crucial step to investigate the influence of sutures on infant head biomechanics. This study aimed to establish a comprehensive quantitative framework for accurately capturing the cranial suture and fontanelle morphologies in infants. A total of 69 CT scans of 2-4 month-old infant heads were segmented to identify semilandmarks at the borders of cranial sutures and fontanelles. Morphological characteristics, including length, width, sinuosity index (SI), and surface area, were measured. For this, an automatic method was developed to determine the junction points between sutures and fontanelles, and thin-plate-spline (TPS) was utilized for area calculation. Different dimensionality reduction methods were compared, including nonlinear and linear principal component analysis (PCA), as well as deep-learning-based variational autoencoder (VAE). Finally, the significance of various covariates was analyzed, and regression analysis was performed to establish a statistical model relating morphological parameters with global parameters. This study successfully developed a quantitative morphological framework and demonstrate its application in quantifying morphologies of infant sutures and fontanelles, which were shown to significantly relate to global parameters of cranial size, suture SI, and surface area for infants aged 2-4 months. The developed framework proved to be reliable and applicable in extracting infant suture morphology features from CT scans. The demonstrated application highlighted its potential to provide valuable insights into the morphologies of infant cranial sutures and fontanelles, aiding in the diagnosis of suture-related skull fractures. Infant suture, Infant fontanelle, Morphological variation, Morphology analysis framework, Statistical model.

Polygenic risk scores for autoimmune related diseases are significantly different in cancer exceptional responders.

A small number of cancer patients respond exceptionally well to therapies and survive significantly longer than patients with similar diagnoses. Profiling the germline genetic backgrounds of exceptional responder (ER) patients, with extreme survival times, can yield insights into the germline polymorphisms that influence response to therapy. As ERs showed a high incidence in autoimmune diseases, we hypothesized the differences in autoimmune disease risk could reflect the immune background of ERs and contribute to better cancer treatment responses. We analyzed the germline variants of 51 ERs using polygenic risk score (PRS) analysis. Compared to typical cancer patients, the ERs had significantly elevated PRSs for several autoimmune-related diseases: type 1 diabetes, hypothyroidism, and psoriasis. This indicates that an increased genetic predisposition towards these autoimmune diseases is more prevalent among the ERs. In contrast, ERs had significantly lower PRSs for developing inflammatory bowel disease. The left-skew of type 1 diabetes score was significant for exceptional responders. Variants on genes involved in the T1D PRS model associated with cancer drug response are more likely to co-occur with other variants among ERs. In conclusion, ERs exhibited different risks for autoimmune diseases compared to typical cancer patients, which suggests that changes in a patient's immune set point or immune surveillance specificity could be a potential mechanistic link to their exceptional response. These findings expand upon previous research on immune checkpoint inhibitor-treated patients to include those who received chemotherapy or radiotherapy.

ProNet DB: a proteome-wise database for protein surface property representations and RNA-binding profiles.

The rapid growth in the number of experimental and predicted protein structures and more complicated protein structures poses a significant challenge for computational biology in leveraging structural information and accurate representation of protein surface properties. Recently, AlphaFold2 released the comprehensive proteomes of various species, and protein surface property representation plays a crucial role in protein-molecule interaction predictions, including those involving proteins, nucleic acids and compounds. Here, we proposed the first extensive database, namely ProNet DB, that integrates multiple protein surface representations and RNA-binding landscape for 326 175 protein structures. This collection encompasses the 16 model organism proteomes from the AlphaFold Protein Structure Database and experimentally validated structures from the Protein Data Bank. For each protein, ProNet DB provides access to the original protein structures along with the detailed surface property representations encompassing hydrophobicity, charge distribution and hydrogen bonding potential as well as interactive features such as the interacting face and RNA-binding sites and preferences. To facilitate an intuitive interpretation of these properties and the RNA-binding landscape, ProNet DB incorporates visualization tools like Mol* and an Online 3D Viewer, allowing for the direct observation and analysis of these representations on protein surfaces. The availability of pre-computed features enables instantaneous access for users, significantly advancing computational biology research in areas such as molecular mechanism elucidation, geometry-based drug discovery and the development of novel therapeutic approaches. Database URL:  https://proj.cse.cuhk.edu.hk/aihlab/pronet/.

Differences in physicochemical properties of pectin extracted from pomelo peel with different extraction techniques.

In order to obtain high yield pomelo peel pectin with better physicochemical properties, four pectin extraction methods, including hot acid extraction (HAE), microwave-assisted extraction (MAE), ultrasound-assisted extraction, and enzymatic assisted extraction (EAE) were compared. MAE led to the highest pectin yield (20.43%), and the lowest pectin recovery was found for EAE (11.94%). The physicochemical properties of pomelo peel pectin obtained by different methods were also significantly different. Pectin samples obtained by MAE had the highest methoxyl content (8.35%), galacturonic acid content (71.36%), and showed a higher apparent viscosity, thermal and emulsion stability. The pectin extracted by EAE showed the highest total phenolic content (12.86%) and lowest particle size (843.69 nm), showing higher DPPH and ABTS scavenging activities than other extract methods. The pectin extracted by HAE had the highest particle size (966.12 nm) and degree of esterification (55.67%). However, Fourier-transform infrared spectroscopy showed that no significant difference occurred among the different methods in the chemical structure of the extracted pectin. This study provides a theoretical basis for the industrial production of pomelo peel pectin.

Chitosan modified with PAP as a promising delivery system for melatonin in the treatment of osteoporosis: targeting the divalent metal transporter 1.

The demands for novel and efficient therapies have gradually increased with the rising concerns of osteoporosis (OP). The most popular method in promoting bone regeneration during osteoporotic conditions consists of loading bioactive materials with different drugs to treat osteoporotic bones by either promoting the process of osteogenesis, or by inhibiting the activity of osteoclasts. By analyzing single cell sequencing results, we found that divalent metal transporter 1 (DMT1) played a role in OP. Based on our previous results, we found that melatonin (MT) suppressed expression of DMT1 induced by high glucose during OP, so we determined the efficacy of MT for the treatment of OP. However, the clinical effects of MT on OP were unsatisfactory. To enhance its biological efficacy, we combined MT with porous gelatin chitosan (chitosan) and the conductive material, PLA-b-AP-b-PLA (PAP), then determined how MT incorporation in chitosan@PAP nanoparticles affected the ability to promote MC3T3-E1 osteogenesis and mineralization, both in vitro and in vivo. The results confirmed the effect of MT on DMT1. We then prepared and characterized composites prepared as nanofibers, and determined the efficacy of MT combined with chitosan-PAP modified hydrogels as a slow-release system in a femur model of osteoporosis mice, with associated properties suitable for bone tissue engineering. The results indicated that MT-loaded chitosan@PAP nanospheres showed favorable osteogenic functions, both in vivo and in vitro, providing a practical solution for bone regeneration for OP patients.

A tempo-spatial controllable microfluidic shear-stress generator for in-vitro mimicking of the thrombus.

Pathological conditions linked to shear stress have been identified in hematological diseases, cardiovascular diseases, and cancer. These conditions often exhibit significantly elevated shear stress levels, surpassing 1000 dyn/cm2 in severely stenotic arteries. Heightened shear stress can induce mechanical harm to endothelial cells, potentially leading to bleeding and fatal consequences. However, current technology still grapples with limitations, including inadequate flexibility in simulating bodily shear stress environments, limited range of shear stress generation, and spatial and temporal adaptability. Consequently, a comprehensive understanding of the mechanisms underlying the impact of shear stress on physiological and pathological conditions, like thrombosis, remains inadequate. To address these limitations, this study presents a microfluidic-based shear stress generation chip as a proposed solution. The chip achieves a substantial 929-fold variation in shear stress solely by adjusting the degree of constriction in branch channels after PDMS fabrication. Experiments demonstrated that a rapid increase in shear stress up to 1000 dyn/cm2 significantly detached 88.2% cells from the substrate. Long-term exposure (24 h) to shear stress levels below 8.3 dyn/cm2 did not significantly impact cell growth. Furthermore, cells exposed to shear stress levels equal to or greater than 8.3 dyn/cm2 exhibited significant alterations in aspect ratio and orientation, following a normal distribution. This microfluidic chip provides a reliable tool for investigating cellular responses to the wide-ranging shear stress existing in both physiological and pathological flow conditions.

The discovery of regional neurotoxicity-associated metabolic alterations induced by carbon quantum dots in brain of mice using a spatial metabolomics analysis.

BACKGROUND: Recently, carbon quantum dots (CQDs) have been widely used in various fields, especially in the diagnosis and therapy of neurological disorders, due to their excellent prospects. However, the associated inevitable exposure of CQDs to the environment and the public could have serious severe consequences limiting their safe application and sustainable development. RESULTS: In this study, we found that intranasal treatment of 5 mg/kg BW (20 µL/nose of 0.5 mg/mL) CQDs affected the distribution of multiple metabolites and associated pathways in the brain of mice through the airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) technique, which proved effective in discovery has proven to be significantly alerted and research into tissue-specific toxic biomarkers and molecular toxicity analysis. The neurotoxic biomarkers of CQDs identified by MSI analysis mainly contained aminos, lipids and lipid-like molecules which are involved in arginine and proline metabolism, biosynthesis of unsaturated fatty acids, and glutamine and glutamate metabolism, etc. as well as related metabolic enzymes. The levels or expressions of these metabolites and enzymes changed by CQDs in different brain regions would induce neuroinflammation, organelle damage, oxidative stress and multiple programmed cell deaths (PCDs), leading to neurodegeneration, such as Parkinson's disease-like symptoms. This study enlightened risk assessments and interventions of QD-type or carbon-based nanoparticles on the nervous system based on toxic biomarkers regarding region-specific profiling of altered metabolic signatures. CONCLUSION: These findings provide information to advance knowledge of neurotoxic effects of CQDs and guide their further safety evaluation.

Spatial spillovers of violent conflict amplify the impacts of climate variability on malaria risk in sub-Saharan Africa.

Africa carries a disproportionately high share of the global malaria burden, accounting for 94% of malaria cases and deaths worldwide in 2019. It is also a politically unstable region and the most vulnerable continent to climate change in recent decades. Knowledge about the modifying impacts of violent conflict on climate-malaria relationships remains limited. Here, we quantify the associations between violent conflict, climate variability, and malaria risk in sub-Saharan Africa using health surveys from 128,326 individuals, historical climate data, and 17,429 recorded violent conflicts from 2006 to 2017. We observe that spatial spillovers of violent conflict (SSVCs) have spatially distant effects on malaria risk. Malaria risk induced by SSVCs within 50 to 100 km from the households gradually increases from 0.1% (not significant, P>0.05) to 6.5% (95% CI: 0 to 13.0%). SSVCs significantly promote malaria risk within the average 20.1 to 26.9 °C range. At the 12-mo mean temperature of 22.5 °C, conflict deaths have the largest impact on malaria risk, with an approximately 5.8% increase (95% CI: 1.0 to 11.0%). Additionally, a pronounced association between SSVCs and malaria risk exists in the regions with 9.2 wet days per month. The results reveal that SSVCs increase population exposure to harsh environments, amplifying the effect of warm temperature and persistent precipitation on malaria transmission. Violent conflict therefore poses a substantial barrier to mosquito control and malaria elimination efforts in sub-Saharan Africa. Our findings support effective targeting of treatment programs and vector control activities in conflict-affected regions with a high malaria risk.

Prognosis of immune checkpoint inhibitor-induced myasthenia gravis: a single center experience and systematic review.

Background: Immune checkpoint inhibitors (ICI)-induced myasthenia gravis (MG) is an uncommon but potentially fatal neurotoxicity. We aim to help physicians familiarize themselves with the clinical characteristics of ICI-induced MG, facilitating early diagnosis and prompt intervention. Methods: We searched the Chinese People's Liberation Army General Hospital medical record system from January 2017 to August 2023 for patients diagnosed with ICI-induced MG. We systematically reviewed the literature until August 2023 to identify all similar patients. We collected clinical information on these patients. Results: 110 patients were identified, 9 from our institution and 101 from case reports. In our institution, Median age was 66 years (range: 49-79 years). 6 were males. The most common was lung cancer (n = 4). All patients had no previous history of MG and received PD-1 or PD-L1 inhibitors. The median time from ICI initiation to first MG symptoms was 4 weeks (range: 2-15 weeks). ICIs were discontinued in all patients. Most patients initially received high-dose corticosteroids, and their symptoms improved. Some patients are discharged with corticosteroids maintenance therapy. In addition, 55 patients (50%) with concomitant myositis and/or myocarditis and MG-induced mortality were more common in the myositis and/or myocarditis group (10.9% vs. 34.5%, p = 0.016). Overlap of myositis with MG (OR = 3.148, p = 0.009) and anti-AChR antibody positivity (OR = 3.364, p = 0.005) were both significantly associated with poor outcomes. Conclusion: Our study reveals the prognosis of ICI-induced MG and suggests that myositis and/or myocarditis are severe comorbidities of ICI-induced MG, emphasizing the importance of early diagnosis and clinical intervention.

Lymphocyte antigen 96: A new potential biomarker and immune target in Parkinson's disease.

BACKGROUND: Lymphocyte antigen 96 (LY96) plays an important role in innate immunity and has been reported to be associated with various neurological diseases. However, its role in Parkinson's disease (PD) remains unclear. METHODS: Transcriptome data from a total of 49 patients with PD and 34 healthy controls were downloaded from the Gene Expression Omnibus (GEO) database to analyse the expression pattern of LY96 and its relationship with gene function and immune-related markers. In addition, peripheral blood samples were collected from clinical patients to validate LY96 mRNA expression levels. Finally, an in vitro cell model of PD based on highly differentiated SH-SY5Y cells was constructed, with small interfering RNA-silenced LY96 expression, and LY96 mRNA level, cell viability, flow cytometry, and mitochondrial membrane potential assays were performed. RESULTS: The results of the analyses of the GEO database and clinical samples revealed significantly abnormally high LY96 expression in patients with PD compared with healthy controls. The results of cell experiments showed that inhibiting LY96 expression alleviated adverse cellular effects by increasing cell viability, reducing apoptosis, and reducing oxidative stress. Gene set enrichment analysis showed that LY96 was positively correlated with T1 helper cells, T2 helper cells, neutrophils, natural killer T cells, myeloid-derived suppressor cells, macrophages, and activated CD4 cells, and may participate in PD through natural killer cell-mediated cytotoxicity pathways and extracellular matrix receptor interaction pathways. CONCLUSION: These findings suggested that LY96 might be a novel potential biomarker for PD, and offer insights into its immunoregulatory role.

Hypothermia protects the integrity of corticospinal tracts and alleviates mitochondria injury after intracerebral hemorrhage in mice.

Disruption of corticospinal tracts (CST) is a leading factor for motor impairments following intracerebral hemorrhage (ICH) in the striatum. Previous studies have shown that therapeutic hypothermia (HT) improves outcomes of ICH patients. However, whether HT has a direct protection effect on the CST integrity and the underlying mechanisms remain largely unknown. In this study, we employed a chemogenetics approach to selectively activate bilateral warm-sensitive neurons in the preoptic areas to induce a hypothermia-like state. We then assessed effects of HT treatment on the integrity of CST and motor functional recovery after ICH. Our results showed that HT treatment significantly alleviated axonal degeneration around the hematoma and the CST axons at remote midbrain region, ultimately promoted skilled motor function recovery. Anterograde and retrograde tracing revealed that HT treatment protected the integrity of the CST over an extended period. Mechanistically, HT treatment prevented mitochondrial swelling in degenerated axons around the hematoma, alleviated mitochondrial impairment by reducing mitochondrial ROS accumulation and improving mitochondrial membrane potential in primarily cultured cortical neurons with oxyhemoglobin treatment. Serving as a proof of principle, our study provided novel insights into the application of HT to improve functional recovery after ICH.

Coexistence of kaposiform hemangioendothelioma and capillary malformation: More than a coincidence? Two case reports.

The coexistence of kaposiform hemangioendothelioma (KHE) and capillary malformation (CM) is quite rare, and few relevant studies can be found to confirm whether this phenomenon is accidental. We diagnosed and treated two such patients, revealing interesting phenomena associated with the development of vascular diseases. These cases offer the possibility that the coexistence of KHE and CM is not accidental and open up a new field of research related to pediatric vascular tumors and vascular malformations. Personalization and precision are required in the diagnosis and treatment of such patients, and the present findings provide a reliable theoretical and practical basis for further research on the pathogenesis and therapy of patients with multiple vascular diseases.

DNA methylation remodeling and the functional implication during male gametogenesis in rice.

BACKGROUND: Epigenetic marks are reprogrammed during sexual reproduction. In flowering plants, DNA methylation is only partially remodeled in the gametes and the zygote. However, the timing and functional significance of the remodeling during plant gametogenesis remain obscure. RESULTS: Here we show that DNA methylation remodeling starts after male meiosis in rice, with non-CG methylation, particularly at CHG sites, being first enhanced in the microspore and subsequently decreased in sperm. Functional analysis of rice CHG methyltransferase genes CMT3a and CMT3b indicates that CMT3a functions as the major CHG methyltransferase in rice meiocyte, while CMT3b is responsible for the increase of CHG methylation in microspore. The function of the two histone demethylases JMJ706 and JMJ707 that remove H3K9me2 may contribute to the decreased CHG methylation in sperm. During male gametogenesis CMT3a mainly silences TE and TE-related genes while CMT3b is required for repression of genes encoding factors involved in transcriptional and translational activities. In addition, CMT3b functions to repress zygotic gene expression in egg and participates in establishing the zygotic epigenome upon fertilization. CONCLUSION: Collectively, the results indicate that DNA methylation is dynamically remodeled during male gametogenesis, distinguish the function of CMT3a and CMT3b in sex cells, and underpin the functional significance of DNA methylation remodeling during rice reproduction.

Synergistic detoxification efficiency and mechanism of triclocarban degradation by a bacterial consortium in the liver-gut-microbiota axis of zebrafish (Danio rerio).

Triclocarban (TCC), an emerging organic contaminant, poses a potential threat to human health with long-term exposure. Here, Rhodococcus rhodochrous BX2 and Pseudomonas sp. LY-1 were utilized to degrade TCC at environmental related concentrations for enhancing TCC biodegradation and investigating whether the toxicity of intermediate metabolites is lower than that of the parent compound. The results demonstrated that the bacterial consortium could degrade TCC by 82.0% within 7 days. The calculated 96 h LC50 for TCC, as well as its main degradation product 3,4-Dichloroaniline (DCA) were 0.134 mg/L and 1.318 mg/L respectively. Biodegradation also alleviated histopathological lesions induced by TCC in zebrafish liver and gut tissues. Liver transcriptome analysis revealed that biodegradation weakened differential expression of genes involved in disrupted immune regulation and lipid metabolism caused by TCC, verified through RT-qPCR analysis and measurement of related enzyme activities and protein contents. 16 S rRNA sequencing indicated that exposure to TCC led to gut microbial dysbiosis, which was efficiently improved through TCC biodegradation, resulting in decreased relative abundances of major pathogens. Overall, this study evaluated potential environmental risks associated with biodegradation of TCC and explored possible biodetoxification mechanisms, providing a theoretical foundation for efficient and harmless bioremediation of environmental pollutants.