Severe Hypothermia Induces Ferroptosis in Cerebral Cortical Nerve Cells.

Abnormal shifts in global climate, leading to extreme weather, significantly threaten the safety of individuals involved in outdoor activities. Hypothermia-induced coma or death frequently occurs in clinical and forensic settings. Despite this, the precise mechanism of central nervous system injury due to hypothermia remains unclear, hindering the development of targeted clinical treatments and specific forensic diagnostic indicators. The GEO database was searched to identify datasets related to hypothermia. Post-bioinformatics analyses, DEGs, and ferroptosis-related DEGs (FerrDEGs) were intersected. GSEA was then conducted to elucidate the functions of the Ferr-related genes. Animal experiments conducted in this study demonstrated that hypothermia, compared to the control treatment, can induce significant alterations in iron death-related genes such as PPARG, SCD, ADIPOQ, SAT1, EGR1, and HMOX1 in cerebral cortex nerve cells. These changes lead to iron ion accumulation, lipid peroxidation, and marked expression of iron death-related proteins. The application of the iron death inhibitor Ferrostatin-1 (Fer-1) effectively modulates the expression of these genes, reduces lipid peroxidation, and improves the expression of iron death-related proteins. Severe hypothermia disrupts the metabolism of cerebral cortex nerve cells, causing significant alterations in ferroptosis-related genes. These genetic changes promote ferroptosis through multiple pathways.

Manipulation of Moiré Superlattice in Twisted Monolayer-multilayer Graphene by Moving Nanobubbles.

In the heterostructure of two-dimensional (2D) materials, many novel physics phenomena are strongly dependent on the Moiré superlattice. How to achieve the continuous manipulation of the Moiré superlattice in the same sample is very important to study the evolution of various physical properties. Here, in minimally twisted monolayer-multilayer graphene, we found that bubble-induced strain has a huge impact on the Moiré superlattice. By employing the AFM tip to dynamically and continuously move the nanobubble, we realized the modulation of the Moiré superlattice, like the evolution of regular triangular domains into long strip domain structures with single or double domain walls. We also achieved controllable modulation of the Moiré superlattice by moving multiple nanobubbles and establishing the coupling of nanobubbles. Our work presents a flexible method for continuous and controllable manipulation of Moiré superlattices, which will be widely used to study novel physical properties in 2D heterostructures.

Prevalence of Mycobacterium bovis in deer in mainland China: a systematic review and meta-analysis.

Background: Deer tuberculosis is a chronic zoonotic infectious disease, despite the existence of socio-economic and zoonotic risk factors, but at present, there has been no systematic review of deer tuberculosis prevalence in mainland China. The aim of this meta-analysis was to estimate the overall prevalence of deer TB in mainland China and to assess possible associations between potential risk factors and the prevalence of deer tuberculosis. Methodology: This study was searched in six databases in Chinese and English, respectively (1981 to December 2023). Four authors independently reviewed the titles and abstracts of all retrieved articles to establish the inclusion exclusion criteria. Using the meta-analysis package estimated the combined effects. Cochran's Q-statistic was used to analyze heterogeneity. Funnel plots (symmetry) and used the Egger's test identifying publication bias. Trim-and-fill analysis methods were used for validation and sensitivity analysis. we also performed subgroup and meta-regression analyses. Results: In this study, we obtained 4,400 studies, 20 cross-sectional studies were screened and conducted a systematic review and meta-analysis. Results show: The overall prevalence of tuberculosis in deer in mainland China was 16.1% (95% confidence interval (CI):10.5 24.6; (Deer tuberculosis infected 5,367 out of 22,215 deer in mainland China) 5,367/22215; 1981 to 2023). The prevalence in Central China was the highest 17.5% (95% CI:14.0-21.9; 63/362), and among provinces, the prevalence in Heilongjiang was the highest at 26.5% (95% CI:13.2-53.0; 1557/4291). Elaphurus davidianus was the most commonly infected species, with a prevalence of 35.3% (95% CI:18.5-67.2; 6/17). We also assessed the association between geographic risk factors and the incidence of deer tuberculosis. Conclusion: Deer tuberculosis is still present in some areas of China. Assessing the association between risk factors and the prevalence of deer tuberculosis showed that reasonable and scientific-based breeding methods, a suitable breeding environment, and rapid and accurate detection methods could effectively reduce the prevalence of deer tuberculosis. In addition, in the management and operation of the breeding base, improving the scientific feed nutrition standards and establishing comprehensive standards for disease prevention, immunization, quarantine, treatment, and disinfection according to the breeding varieties and scale, are suggested as ways to reduce the prevalence of deer tuberculosis.

MuSCs and IPCs: roles in skeletal muscle homeostasis, aging and injury.

Skeletal muscle is a highly specialized tissue composed of myofibres that performs crucial functions in movement and metabolism. In response to external stimuli and injuries, a range of stem/progenitor cells, with muscle stem cells or satellite cells (MuSCs) being the predominant cell type, are rapidly activated to repair and regenerate skeletal muscle within weeks. Under normal conditions, MuSCs remain in a quiescent state, but become proliferative and differentiate into new myofibres in response to injury. In addition to MuSCs, some interstitial progenitor cells (IPCs) such as fibro-adipogenic progenitors (FAPs), pericytes, interstitial stem cells expressing PW1 and negative for Pax7 (PICs), muscle side population cells (SPCs), CD133-positive cells and Twist2-positive cells have been identified as playing direct or indirect roles in regenerating muscle tissue. Here, we highlight the heterogeneity, molecular markers, and functional properties of these interstitial progenitor cells, and explore the role of muscle stem/progenitor cells in skeletal muscle homeostasis, aging, and muscle-related diseases. This review provides critical insights for future stem cell therapies aimed at treating muscle-related diseases.

[Mechanism of albiflorin in improvement of Alzheimer's disease based on network pharmacology and in vitro experiments].

This study aimed to explore the mechanism of albiflorin in the treatment of Alzheimer's disease(AD) based on network pharmacology, molecular docking, and in vitro experiments. Network pharmacology was used to predict the potential targets and pathways of albiflorin against AD, and molecular docking technology was used to verify the binding affinity of albiflorin to key target proteins. Finally, the AD cell model was induced by Aß_(25-35) in rat pheochromocytoma(PC12) cells and intervened by albiflorin to validate core targets and pathways. The results of network pharmacological analysis showed that albiflorin acted on key targets such as mitogen-activated protein kinase-1(MAPK1 or ERK2), albumin(ALB), epidermal growth factor receptor(EGFR), caspase-3(CASP3), and sodium-dependent serotonin transporter(SLC6A4), and signaling pathways such as MAPK, cAMP, and cGMP-PKG. The results of molecular docking showed that albiflorin had strong binding affinity to MAPK1(ERK2). In vitro experiments showed that compared with the blank group, the model group showed decreased cell viability, decreased expression level of B-cell lymphoma 2(Bcl-2), increased Bcl-2-associated X protein(Bax), and reduced phosphorylation level of extracellular signal-regulated kinase 1/2(ERK1/2) and the relative expression ratio of p-ERK1/2 to ERK1/2. Compared with the model group, the albiflorin group showed potentiated cell viability, up-regulated expression of Bcl-2, down-regulated Bax, and increased phosphorylation level of ERK1/2 and the relative expression ratio of p-ERK1/2 to ERK1/2. These results suggest that the mechanism of albiflorin against AD may be related to its activation of the MAPK/ERK signaling pathway and its inhibition of neuronal apoptosis.

Nitrogen-doped porous carbon encapsulates multivalent cobalt-nickel as oxygen reduction reaction catalyst for zinc-air battery.

In this study, we present a bimetallic ion coexistence encapsulation strategy employing hexadecyl trimethyl ammonium bromide (CTAB) as a mediator to anchor cobalt-nickel (CoNi) bimetals in nitrogen-doped porous carbon cubic nanoboxes (CoNi@NC). The fully encapsulated and uniformly dispersed CoNi nanoparticles with the improved density of active sites help to accelerate the oxygen reduction reaction (ORR) kinetics and provide an efficient charge/mass transport environment. Zinc-air battery (ZAB) equipped CoNi@NC as cathode exhibits an open-circuit voltage of 1.45 V, a specific capacity of 870.0 mAh g-1, and a power density of 168.8 mW cm-2. Moreover, the two CoNi@NC-based ZABs in series display a stable discharge specific capacity of 783.0 mAh g-1, as well as a large peak power density of 387.9 mW cm-2. This work provides an effective way to tune the dispersion of nanoparticles to boost active sites in nitrogen-doped carbon structure, and enhance the ORR activity of bimetallic catalysts.

Correlation between different endometrial preparation protocols and pregnancy outcome of frozen embryo transfer in patients with polycystic ovary syndrome: a retrospective study.

OBJECTIVE: We retrospectively analyzed the correlation between different endometrial preparation protocols and pregnancy outcomes in patients with polycystic ovary syndrome (PCOS) who underwent frozen embryo transfer (FET). METHODS: A total of 200 PCOS patients who underwent FET were divided into HRT group (n = 65), LE group (n = 65), GnRHa + HRT group (n = 70) according to different endometrial preparation protocols. The endometrial thickness on the day of endometrial transformation, the number of embryos transferred, and the number of high-quality embryos transferred were compared among the three groups. The pregnancy outcomes of FET in the three groups were compared and analyzed, and a further multivariate logistic regression model was used to analyze the factors influencing FET pregnancy outcomes in PCOS patients. RESULTS: Endometrial thickness on the day of endometrial transformation, clinical pregnancy rate and live birth rate in GnRHa + HRT group were higher than those in the HRT group and LE group. The results of multivariate regression analysis showed that the pregnancy outcome of PCOS patients undergoing FET was significantly associated with the patient's age, endometrial preparation protocols, number of embryos transferred, endometrial thickness, and duration of infertility. CONCLUSION: Compared with HRT or LE alone, GnRHa + HRT protocol results in higher levels of endometrial thickness on the day of endometrial transformation, clinical pregnancy rate, and live birth rate. Female age, endometrial preparation protocols, number of embryos transferred, endometrial thickness, and duration of infertility are determined as factors influencing pregnancy outcomes in PCOS patients undergoing FET.

A novel myeloid cell marker genes related signature can indicate immune infiltration and predict prognosis of hepatocellular carcinoma: Integrated analysis of bulk and single-cell RNA sequencing.

Myeloid cells are physiologically related to innate immunity and inflammation. Tumor-associated myeloid cells gained increasing interest because of their critical roles in tumor progression and anticancer immune responses in human malignancies. However, the associations between tumor-associated myeloid cell-related genes and hepatocellular carcinoma have yet to be revealed. Here, through the integrating analysis of bulk and single-cell RNA (scRNA) sequencing of public HCC samples, we developed a gene signature to investigate the role of HCC-specific myeloid signature genes in HCC patients. We firstly defined 317 myeloid cell marker genes through analyzing scRNA data of HCC from the GEO dataset. After selecting the differentially expressed genes, eleven genes were also proved prognostic. Then we built a gene signature from the TCGA cohort and verified further with the ICGC dataset by applying the LASSO Cox method. An eight genes signature (FABP5, C15orf48, PABPC1, TUBA1B, AKR1C3, NQO1, AKR1B10, SPP1) was achieved finally. Patients in the high risk group correlated with higher tumor stages and poor survival than those in the low-risk group. The risk score was proved to be an independent risk factor for prognosis. The high risk group had higher infiltrations of dendritic cells, macrophages and Tregs. And the APC co-inhibition, T cell co-inhibition pathways were also activated. Besides, the risk score positively correlated with multidrug resistance proteins. In conclusion, our myeloid cell marker genes related signature can predict patients' survival and may also indicate the levels of immune infiltration and drug resistance.

Transcriptome analysis reveals dysregulated gene expression networks in Sertoli cells of cattle-yak hybrids.

Cattle-yak, the hybrid offspring of yak and taurine cattle, exhibits male sterility with normal female fertility. Spermatogenesis is arrested in adult cattle-yak, and apoptosis is elevated in spermatogenic cells. Currently, the mechanisms underlying these defects remain elusive. Sertoli cells are the only somatic cells that directly interact with spermatogenic cells in the seminiferous tubules and play essential roles in spermatogenesis. The present study was designed to investigate gene expression signatures and potential roles of Sertoli cells in hybrid sterility in cattle-yak. Immunohistochemical analysis showed that the 5 mC and 5hmC signals in Sertoli cells of cattle-yaks were significantly different from those of age-matched yaks (P < 0.05). Transcriptome profiling of isolated Sertoli cells identified 402 differentially expressed genes (DEGs) between cattle-yaks and yaks. Notably, niche factor glial cell derived neurotrophic factor (GDNF) was upregulated, and genes involved in retinoic acid (RA) biogenesis were changed in Sertoli cells of cattle-yak, suggesting possible impairments of spermatogonial fate decisions. Further studies showed that the numbers of proliferative gonocytes and undifferentiated spermatogonia in cattle-yak were significantly higher than those in yak (P < 0.01). Exogenous GDNF significantly promoted the proliferation of UCHL1-positive spermatogonia in yaks. Therefore, we concluded that altered GDNF expression and RA signaling impacted the fate decisions of undifferentiated spermatogonia in cattle-yak. Together, these findings highlight the role of Sertoli cells and their derived factors in hybrid sterility.

Causal relationship between serum uric acid and abnormal blood pressure based on the panel model study: A 5-year cohort study.

BACKGROUND AND AIMS: To investigate the relationship between elevated serum uric acid (SUA) levels and blood pressure (BP). METHODS AND RESULTS: Based on the Beijing Health Management Cohort, 5276 health examination people were enrolled. Cross-lagged model was used to explore the relationship between SUA levels and blood pressure. The results showed: (1) increased SUA and increased systolic blood pressure (SBP): ① The path coefficients from baseline SUA to follow-up SBP were statistically significant in both the general population (ß = 0.034, P < 0.05) and men (ß = 0.048, P < 0.05). The path coefficients from baseline SBP to follow-up SUA were not statistically significant in either the general population (ß = 0.010, P > 0.05) or men (ß = 0.011, P > 0.05). ② The path coefficients from baseline SUA to follow-up SBP and from baseline SBP to follow-up SUA were not statistically significant in women with BMI ≥ 25 kg/m2 and BMI < 25 kg/m2. (2) Increased SUA and diastolic blood pressure (DBP): ① There was no statistical significance between the path coefficients from baseline DBP to follow-up SUA and the path coefficients from baseline SUA to follow-up DBP. ② In men and women, BMI ≥ 25 kg/m2 and BMI < 25 kg/m2, the path coefficients from baseline DBP to follow-up SUA and from baseline SUA to follow-up DBP were not statistically significant. CONCLUSIONS: SUA can increase blood pressure in the general male population; no reverse time sequence relationship was found. The temporal relationships between SUA levels and SBP abnormalities were different in the sex and BMI subgroups. No bidirectional causal temporal relationship was found between SUA elevation and DBP abnormality.

Investigation on the mechanisms of human sperm DNA damage based on the proteomics analysis by SWATH-MS.

BACKGROUND: Spermatozoa have the task of delivering an intact paternal genome to the oocyte and supporting successful embryo development. The detection of sperm DNA fragmentation (SDF) has been emerging as a complementary test to conventional semen analysis for male infertility evaluation, but the mechanism leading to SDF and its impact on assisted reproduction remain unclear. Therefore, the study identified and analyzed the differentially expressed proteins of sperm with high and low SDF. METHODS: Semen samples from men attended the infertility clinic during June 2020 and August 2020 were analyzed, and sperm DNA fragmentation index (DFI) was detected by the sperm chromatin structure assay. Semen samples with low DFI (< 30%, control group) and high DFI (≥ 30%, experimental group) were optimized by density gradient centrifugation (DGC), and the differentially expressed proteins of obtained sperm were identified by the Sequential Window Acquisition of All Theoretical Mass Spectra Mass Spectrometry (SWATH-MS) and performed GO and KEGG analysis. RESULTS: A total of 2186 proteins were identified and 1591 proteins were quantified, of which 252 proteins were identified as differentially expressed proteins, including 124 upregulated and 128 downregulated. These differentially expressed proteins were involved in metabolic pathways, replication/recombination/repair, acrosomal vesicles, kinase regulators, fertilization, tyrosine metabolism, etc. Western blotting results showed that the expression levels of RAD23B and DFFA proteins and the levels of posttranslational ubiquitination and acetylation modifications in the experimental group were significantly higher than those in the control group, which was consistent with the results of proteomics analysis. CONCLUSIONS: Proteomic markers of sperm with high DNA fragmentation can be identified by the SWATH-MS and bioinformatic analysis, and new protein markers and posttranslational modifications related to sperm DNA damage are expected to be intensively explored. Our findings may improve our understanding of the basic molecular mechanism of sperm DNA damage.

Cerebellar injury induced by cadmium via disrupting the heat-shock response.

Cadmium (Cd) is a food contaminant that poses serious threats to animal health, including birds. It is also an air pollutant with well-known neurotoxic effects on humans. However, knowledge on the neurotoxic effects of chronic Cd exposure on chicken is limited. Thus, this study assessed the neurotoxic effects of chronic Cd on chicken cerebellum. Chicks were exposed to 0 (control), 35 (low), and 70 (high) mg/kg of Cd for 90 days, and the expression of genes related to the heat-shock response was investigated. The chickens showed clinical symptoms of ataxia, and histopathology revealed that Cd exposure decreased the number of Purkinje cells and induced degeneration of Purkinje cells with pyknosis, and some dendrites were missing. Moreover, Cd exposure increased the expression of heat-shock factors, HSF1, HSF2, and HSF3, and heat-shock proteins, HSP60, HSP70, HSP90, and HSP110. These changes indicate that HSPs improve the tolerance of the cerebellum to Cd. Conversely, the expressions of HSP10, HSP25, and HSP40 were decreased significantly, which indicated that Cd inhibits the expression of small heat-shock proteins. However, HSP27 and HSP47 were upregulated following low-dose Cd exposure, but downregulated under high-dose Cd exposure. This work sheds light on the toxic effects of Cd on the cerebellum, and it may provide evidence for health risks posed by Cd. Additionally, this work also identified a novel target of Cd exposure in that Cd induces cerebellar injury by disrupting the heat-shock response. Cd can be absorbed into chicken's cerebellum through the food chain, which eventually caused cerebellar injury. This study provided a new insight that chronic Cd-induced neurotoxicity in the cerebellum is associated with alterations in heat-shock response-related genes, which indicated that Cd through disturbing heat-shock response induced cerebellar injury.

Pyrrolidine Dithiocarbamate-loaded Electrospun Membranes for Peritendinous Anti-adhesion through Inhibition of the Nuclear Factor-κB Pathway.

Peritendinous adhesion is a major cause of limb dysfunction and disability in clinical practice. Numerous studies suggest that activation of nuclear factor-κB (NF-κB) pathway in macrophages could be the pivotal figure in excessive collagen synthesis and thus peritendinous adhesion formation. In this study, we assumed this pathological process could be suppressed by inhibiting NF-κB phosphorylation and nuclear translocation using pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor with the ability to penetrate cell membranes, in macrophages. Then, we conducted electrospinning process to incorporate PDTC into poly(L-lactic) acid (PLA) electrospinning membranes, that is, the PDTC-PLA membranes. Further, with integral film quality and stable drug release property, the PDTC-PLA membranes were subsequently analyzed in the capability and mechanism of preventing adhesion formation both in vitro and in vivo. Our results showed inhibition of macrophage proliferation as well as NF-κB pathway activation from in vitro assays and outstanding promotion in inhibiting NF-κB p65 phosphorylation and reducing adhesion formation from in vivo assays of PDTC-PLA compared to PLA membranes. In conclusion, our findings suggested that PDTC-PLA as an alternative therapeutic approach alleviated inflammation and peritendinous adhesion formation through NF-κB signaling pathway. STATEMENT OF SIGNIFICANCE: Pyrrolidine dithiocarbamate (PDTC) can be blended into poly-L-lactic acid (PLA) fibrous membranes by electrospinning process. This incorporation of PDTC into PLA is an effective way to inhibit proinflammatory activation of macrophages and to achieve advanced anti-adhesion outcome after tendon repair.

Portal vein tumor thrombosis in hepatocellular carcinoma: molecular mechanism and therapy.

Portal vein tumor thrombosis (PVTT), a common complication of advanced hepatocellular carcinoma (HCC), remains the bottleneck of the treatments. Liver cancer cells potentially experienced multi-steps during PVTT process, including cancer cells leave from cancer nest, migrate in extracellular matrix, invade the vascular barrier, and colonize in the portal vein. Accumulated evidences have revealed numerous of molecular mechanisms including genetic and epigenetic regulation, cancer stem cells, immunosuppressive microenvironment, hypoxia, et al. contributed to the PVTT formation. In this review, we discuss state-of-the-art PVTT research on the potential molecular mechanisms and experimental models. In addition, we summarize PVTT-associated clinical trials and current treatments for PVTT and suppose perspectives exploring the molecular mechanisms and improving PVTT-related treatment for the future.

Investigation of the mechanisms leading to human sperm DNA damage based on transcriptome analysis by RNA-seq techniques.

RESEARCH QUESTION: What are the molecular mechanisms leading to human sperm DNA damage? DESIGN: Semen samples were collected and the sperm DNA fragmentation index (DFI) was assessed. Differentially expressed RNA in spermatozoa with a high (DFI ≥30%, experimental group) or normal (DFI <30%, control group) DFI were identified by RNA-sequencing (RNA-seq) technology, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed. Three differentially expressed RNA related to sperm DNA damage and repair, namely PMS1, TP53BP1 and TLK2, were validated using real-time quantitative (RT-qPCR). RESULTS: A total of 19,970 expressed RNA were detected in the two groups. Compared with the control group, the expression levels of 189 RNA in the experimental group were significantly increased and those of 163 genes decreased. Gene Ontology enrichment analysis showed that these RNA were mainly concentrated in the ATPase-dependent transmembrane transport complex, extracellular exosome, somatic cell DNA recombination, protein binding, cytoplasm and regulation of localization. KEGG pathway analysis showed that these RNA were mainly related to the PI3K-Akt signalling pathway, endocytosis, p53 signalling pathway and cGMP-PKG signalling pathway. The RT-qPCR results showed that the expression levels of PMS1, TP53BP1 and TLK2 in the experimental group were significantly lower than in the control group (P = 0.01, 0.015 and 0.004, respectively), which was identical to the results of RNA sequencing. CONCLUSIONS: Differentially expressed RNA related to sperm DNA damage and repair may be identified by RNA-seq technology, which provides new insights into the understanding of sperm DNA damage and repair, and will help to discover new biomarkers related to sperm DNA damage.

A Virtual Reality Platform for Context-Dependent Cognitive Research in Rodents.

Animal survival necessitates adaptive behaviors in volatile environmental contexts. Virtual reality (VR) technology is instrumental to study the neural mechanisms underlying behaviors modulated by environmental context by simulating the real world with maximized control of contextual elements. Yet current VR tools for rodents have limited flexibility and performance (e.g., frame rate) for context-dependent cognitive research. Here, we describe a high-performance VR platform with which to study contextual behaviors immersed in editable virtual contexts. This platform was assembled from modular hardware and custom-written software with flexibility and upgradability. Using this platform, we trained mice to perform context-dependent cognitive tasks with rules ranging from discrimination to delayed-sample-to-match while recording from thousands of hippocampal place cells. By precise manipulations of context elements, we found that the context recognition was intact with partial context elements, but impaired by exchanges of context elements. Collectively, our work establishes a configurable VR platform with which to investigate context-dependent cognition with large-scale neural recording.

Histone methyltransferase Setdb1 mediates osteogenic differentiation by suppressing the expression of miR-212-3p under mechanical unloading.

Emerging evidence indicates that multiple mechanisms are involved in bone loss induced by mechanical unloading. Thus far, few study has established the pathophysiological role of histone modification for osteogenic differentiation under mechanical unloading. Here we demonstrated that the histone H3 lysine 9 (H3K9) methyltransferase Setdb1, which was sensitive to mechanical unloading, was increased during osteogenic differentiation of MC3T3-E1 cells for the first time. Knockdown of Setdb1 significantly blocked osteoblast function in vivo and in vitro. Through bioinformatics analysis of candidate miRNAs regulated by H3K9me3, we further identified that Setdb1 inhibited the expression of miR-212-3p by regulating the formation of H3K9me3 in the promoter region. Mechanically, we revealed that miR-212-3p was upregulated under mechanical unloading and suppressed osteogenic differentiation by directly downregulating High mobility group box 1 protein (Hmgb1) expression. Furthermore, we verified the molecular mechanism of the SETDB1/miR-212-3p/HMGB1 pathway in hFOB cells under mechanical unloading. In summary, these data demonstrate the essential function of the Setdb1/miR-212-3p/Hmgb1 pathway in osteogenic differentiation under mechanical unloading, and present a potential protective strategies against bone loss induced by mechanical unloading.

Short- and medium-chain chlorinated paraffins in urban road dust of Shanghai, China: concentrations, source apportionment and human exposure assessment.

Chlorinated paraffins (CPs) are ubiquitous anthropogenic contaminants that have been found in various environmental media. The objective of this study was to determine concentrations, spatial distribution, possible sources and potential health risk of SCCPs and MCCPs in urban road dust collected from Shanghai, China. The concentrations ranged from 9.74 to 11,400 ng g-1 for ΣSCCPs, 44.1 to 49,900 ng g-1 for ΣMCCPs and 53.9 to 61,400 ng g-1 for total CPs, respectively. MCCPs were the dominant component in all road dust, averagely accounting for 82.8% of total CPs. The concentrations of CPs in dust collected from traffic and commercial areas were significantly higher than those from campus, industrial, park and residential areas (p < 0.01), which could be attributed to tire wear in heavy traffic. All dust samples were divided into two groups by hierarchical cluster analysis for both SCCPs and MCCPs, and the most abundant homologue groups in most samples were C10Cl7-10 and C13Cl7-9 for SCCPs, and C14Cl7-9 and C15Cl8-9 for MCCPs. Correlation analysis showed that all carbon homologues in road dusts were highly correlated each other, suggesting SCCPs and MCCPs in dust maybe came from similar sources. Three sources for CPs in dust samples were apportioned by the PMF model; their relative contributions to the total CPs burden in dust were 25.6% for factor 1 (commercial CP mixture), 13.7% for factor 2 (long-distance transport) and 60.7% for factor 3 (commercial CP mixture). The median estimated daily intakes of total CPs via road dust were 1.78 × 10-5 for children and 3.0 × 10-6 mg kg-1 day-1 for adults, respectively. Quantitative risk assessment using non-cancer hazard index and total margin of exposure of total CPs indicated that total CPs at the present level in road dust pose no significant risk for both children and adults in Shanghai.

The default mode network is affected in the early stage of simian immunodeficiency virus infection: a longitudinal study.

Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network. Most recent studies have been cross-sectional and thus have not revealed dynamic changes in the default mode network following acquired immune deficiency syndrome infection and antiretroviral therapy. Specifically, when brain imaging data at only one time point are analyzed, determining the duration at which the default mode network is the most effective following antiretroviral therapy after the occurrence of acquired immune deficiency syndrome. However, because infection times and other factors are often uncertain, longitudinal studies cannot be conducted directly in the clinic. Therefore, in this study, we performed a longitudinal study on the dynamic changes in the default mode network over time in a rhesus monkey model of simian immunodeficiency virus infection. We found marked changes in default mode network connectivity in 11 pairs of regions of interest at baseline and 10 days and 4 weeks after virus inoculation. Significant interactions between treatment and time were observed in the default mode network connectivity of regions of interest pairs area 31/V6.R and area 8/frontal eye field (FEF). L, area 8/FEF.L and caudal temporal parietal occipital area (TPOC).R, and area 31/V6.R and TPOC.L. ART administered 4 weeks after infection not only interrupted the progress of simian immunodeficiency virus infection but also preserved brain function to a large extent. These findings suggest that the default mode network is affected in the early stage of simian immunodeficiency virus infection and that it may serve as a potential biomarker for early changes in brain function and an objective indicator for making early clinical intervention decisions.

Exosomes from Microvascular Endothelial Cells under Mechanical Unloading Inhibit Osteogenic Differentiation via miR-92b-3p/ELK4 Axis.

Mechanical unloading-related bone loss adversely harms astronauts' health. Nevertheless, the specific molecular basis underlying the phenomenon has not been completely elucidated. Although the bone microvasculature contributes significantly to bone homeostasis, the pathophysiological role of microvascular endothelial cells (MVECs) in bone loss induced by mechanical unloading is not apparent. Here, we discovered that MC3T3-E1 cells could take up exosomes produced by MVECs under clinorotation-unloading conditions (Clino Exos), which then prevented MC3T3-E1 cells from differentiating into mature osteoblasts. Moreover, miR-92b-3p was found to be highly expressed in both unloaded MVECs and derived exosomes. Further experiments demonstrated that miR-92b-3p was transferred into MC3T3-E1 cells by exosomes, resulting in the suppression of osteogenic differentiation, and that encapsulating miR-92b-3p inhibitor into the Clino Exos blocked their inhibitory effects. Furthermore, miR-92b-3p targeted ELK4 and the expression of ELK4 was lessened when cocultured with Clino Exos. The inhibitor-92b-3p-promoted osteoblast differentiation was partially reduced by siRNA-ELK4. Exosomal miR-92b-3p secreted from MVECs under mechanical unloading has been shown for the first time to partially attenuate the function of osteoblasts through downregulation of ELK4, suggesting a potential strategy to protect against the mechanical unloading-induced bone loss and disuse osteoporosis.