WTAP-mediated N6-methyladenosine modification promotes the inflammation, mitochondrial damage and ferroptosis of kidney tubular epithelial cells in acute kidney injury by regulating LMNB1 expression and activating NF-κB and JAK2/STAT3 pathways.

Acute kidney injury (AKI) is a serious complication of sepsis patients, but the pathogenic mechanisms underlying AKI are still largely unclear. In this view, the roles of the key component of N6-methyladenosine (m6A)-wilms tumor 1 associated protein (WTAP) in AKI progression were investigated. AKI mice model was established by using cecal ligation and puncture (CLP). AKI cell model was established by treating HK-2 cells with LPS. Cell apoptosis was analyzed by TdT-mediated dUTP Nick-End Labeling (TUNEL) staining and flow cytometry analysis. Cell viability was analyzed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The concentrations of inflammatory factors were examined with ELISA kits. Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and Fe2+ levels were detected with related kits. Gene expression was detected by western blot assay or quantitative real-time polymerase chain reaction (qRT-PCR) assay. The relation between WTAP and lamin B1 (LMNB1) was verified by Methylated RNA Immunoprecipitation (meRIP) assay, RIP assay, dual-luciferase reporter assay and Actinomycin D assay. CLP induced significant pathological changes in kidney tissues in mice and promoted inflammation, mitochondrial damage and ferroptosis. LMNB1 level was induced in HK-2 cells by LPS. LMNB1 knockdown promoted LPS-mediated HK-2 cell viability and inhibited LPS-mediated HK-2 cell apoptosis, inflammation, mitochondrial damage and ferroptosis. Then, WTAP was demonstrated to promote LMNB1 expression by m6A Methylation modification. Moreover, WTAP knockdown repressed LPS-treated HK-2 cell apoptosis, inflammation, mitochondrial damage and ferroptosis, while LMNB1 overexpression reversed the effects. Additionally, WTAP affected the pathways of NF-κB and JAK2/STAT3 by LMNB1. WTAP-mediated m6A promoted the inflammation, mitochondrial damage and ferroptosis in LPS-induced HK-2 cells by regulating LMNB1 expression and activating NF-κB and JAK2/STAT3 pathways.

Expression levels of ADAMTS 5, 9, and 12 in endometrial polyps and their predictive value for the diagnosis and recurrence of endometrial polyps.

PURPOSE: Endometrial polyps (EPs) are common gynecological disorders for which no clear etiology has been found. ADAMTS have been associated with a variety of diseases. This study aimed to investigate the potential correlation between serologic levels of ADAMTS 5, 9, and 12 in patients with EPs. METHODS: A total of 88 patients were categorized into two groups: the EPs group, consisting of recurrent EPs and first occurrence EPs, and a control group. The study compared the general information and serum levels of ADAMTS 5, 9, and 12 between the groups. RESULTS: Regarding the general data, a statistically significant age difference (p < 0.05) was observed, while no significant differences were found in the other variables. After considering age as a confounding factor, the previously observed statistical significance in the differences of ADAMTS5 and 9 between the groups diminished. However, it was found that the concentrations of ADAMTS12 in both the EPs group and the recurrent EPs group were significantly higher compared to the control group and the first occurrence EPs group (p < 0.05). ROC curves were generated to determine the critical values of ADAMTS12 for predicting EPs and recurrent EPs, which were found to be 0.6962 ng/ml (sensitivity: 100 %, specificity: 39.5 %) and 0.8768 ng/ml (sensitivity: 75.0 %, specificity: 76.3 %), respectively. CONCLUSION: Our findings revealed elevated serologic levels of ADAMTS12 in the EPs group, particularly in the recurrent EPs group. Furthermore, ADAMTS-12 was identified as a valuable biomarker for assisting in the diagnosis and prediction of EPs recurrence.

Advances in the ocular complications after hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) has benefited an increasing number of patients with hematological disease in the clinic. It is a curative therapy for malignant and nonmalignant hematological diseases. With the advancement and further clinical application of HSCT in recent years, the life expectancy of patients has increased, but complications have become more common. The occurrence of ocular complications is receiving increasing attention because they can seriously affect the quality of life of patients. Ocular complications require increased attention from clinicians because of their negative impact on patients and increasing incidence. Most of recent reports on posttransplant ocular complications involve ocular manifestations of graft-versus-host disease (GVHD), and a few ocular complications that do not originate from GVHD have also been reported. This review summarizes the diagnosis, scoring criteria, pathophysiology, and clinical manifestations of and common therapies for ocular graft-versus-host disease(oGVHD) after HSCT, and includes a description of some rare cases and novel therapies.

The mir-199b-5p encapsulated in adipocyte-derived exosomes mediates radioresistance of colorectal cancer cells by targeting JAG1.

Radiotherapy is a key treatment option for colorectal cancer, but its efficacy varies among patients. Our previous studies suggested that adipose tissue may confer the radioresistance of several abdominal tumors, such as pancreatic cancer, biliary cancer, and others. In the present work, the effects of adipocytes in regulating the radiosensitivity of colorectal cancer are explored for the first time. It was found that colony formation was increased and radiation-induced apoptosis decreased in colorectal cancer cells HCT8 and HCT116 co-cultured with adipocytes, which verified the mediation of adipocyte-driven radioresistance in colorectal cancer in vitro. Next, the colorectal cancer cells were incubated with adipocyte-derived exosomes, and a perceptible reduction in radiosensitivity was detected. Furthermore, to investigate the possible mechanisms involved, the exosomes were isolated, the encapsulated microRNAs were extracted and analyzed by small RNA sequencing. Based on bioinformatics analysis and qRT-PCR verification, miR-199b-5p was chosen for functional annotation. It was shown that miR-199b-5p expression was significantly upregulated after 6 Gy irradiation, and overexpressed miR-199b-5p significantly suppressed the radiosensitivity of HCT8 and HCT116 cells. In addition, jagged canonical Notch ligand 1(JAG1) was identified as the target gene of miR-199b-5p by using bioinformatics prediction and dual luciferase reporter gene assay. It was demonstrated that JAG1 conferred the radioresistance of colorectal cancer cells both in vivo and in vitro. Taken together, the present study demonstrates that adipocytes trigger the radioresistance of colorectal cancer cells, probably by targeting JAG1 through an adipocyte-derived exosomal miR-199b-5p.

Multifunctional electrospun polycaprolactone/chitosan/hEGF/lidocaine nanofibers for the treatment of 2 stage pressure ulcers.

In this study, a multifunctional nanofiber dressing that can promote antibacterial, analgesic and healing was prepared by electrospinning technology. Hydrophobic polycaprolactone (PCL)/chitosan (CS)/lidocaine hydrochloride (LID) and epidermal growth factor (EGF) were used as scaffold materials and dissolved in trifluoroacetic acid to prepare spinning solution. The morphology of PCEL dressing was observed by scanning electron microscopy. The fiber structure was dense and the average diameter was 297.0 nm. The water absorption capacity test and water contact angle measurement showed that the fiber had good water absorption and hydrophilicity (1302 %, 139.258°). Drug release was 84 % within 60 h. In the results of antibacterial experiment, the dressing showed certain antibacterial properties. The results of cell experiments show that the dressing can promote cell proliferation. In addition, coagulation experiments showed that the dressing could quickly coagulate the blood within 4 min. In addition, PCEL dressing promoted collagen deposition and vascularization through animal models of pressure sores. Therefore, multifunctional dressing can be used as an ideal auxiliary means for the treatment of pressure sores, and it is a promising alternative to chronic wound healing.

Animal models of chemotherapy-induced peripheral neuropathy for hematological malignancies: A review.

Chemotherapy is one of the main treatments for hematologic malignancies. However, chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxic reactions in chemotherapy, and the occurrence of CIPN affects patients' quality of life and can cause interruption of chemotherapy in severe cases, thus reducing the efficacy of chemotherapy. We currently summarize the existing CIPN animal models, including the characteristics of several common animal models such as bortezomib-induced peripheral neuropathy, vincristine-induced peripheral neuropathy, and oxaliplatin-induced peripheral neuropathy. It was found that CIPN may lead to behavioral, histopathological, and neurophysiological changes inducing peripheral neuropathy. However, the mechanism of CIPN has not been fully elucidated, especially the prevention and treatment protocols need to be improved. Therefore, this review article summarizes the progress of research on CIPN animal models and the possible mechanisms and treatment of CIPN.

Sex-differential association of suicide attempts with thyroid dysfunction in first-episode and drug-naïve young major depressive disorder patients with comorbid anxiety.

This study aimed to explore sex differences in the relationship between thyroid function indicators and suicide attempts in first-episode and drug-naïve young major depressive disorder (MDD) patients with comorbid anxiety (MDA). A total of 917 MDD patients (aged 18-35 years) were recruited. The Hamilton depression rating scale (HAMD-17), Hamilton anxiety rating scale (HAMA), positive and negative syndrome scale (PANSS) positive subscale and clinical global impression of severity scale (CGI-S) were used. 467 patients were classified as MDA. The prevalence of suicide attempts was 31.3% in MDA patients, which was significantly higher than that (7.3%) in MDD patients without anxiety. Compared with MDA patients without suicide attempts, MDA patients with suicide attempts were older, had a later age of onset, higher HAMD-17, HAMA, and PANSS positive symptom subscale scores, as well as higher TSH, TgAb and TPOAb levels. For male patients, TSH and TPOAb levels were independently associated with suicide attempts. For female patients, HAMA, PANSS positive symptom scores, CGI-S score and TPOAb levels were independently associated with suicide attempts. Our results suggest that the indicators of thyroid function which can predict suicide attempts in male and female MDA patients have sex differences.

Research progress in intelligent control of intrapartum oxytocin (unrevised version).

With the development of precision medicine and artificial intelligence, the infusion of many drugs has been intelligently controlled according to patients' conditions. However, the infusion of oxytocin (OT) still relies on medical staff responsible for implementing artificial regulation based on observation of fetal electronic monitoring and other maternal and fetal conditions. In this review, we discussed recent trends in intelligent infusion systems, the development status and dilemma of intelligent control of OT infusion, the drug intelligent feedback control system principle, and current risks and challenges to further promote obstetric informatization.

Benzo(a)pyrene regulates chaperone-mediated autophagy via heat shock protein 90.

AIMS: Some studies have shown that the Benzo(a)pyrene (BaP) exposure induced oxidative damage, DNA damage and autophagy, but the molecular mechanism is not clear. Heat shock protein 90 (HSP90) is regarded as an important target in cancer therapy and a key factor in autophagy. Therefore, this study aims to clarify the new mechanism of BaP regulating CMA through HSP90. MAIN METHODS: C57BL mice were fed with BaP at a dose of 25.3 mg/kg. A549 cells were treated with different concerntrations of BaP, and MTT assay was used to observe the effect of BaP on the proliferation of A549 cells. DNA damage was detected by alkaline comet assay. Focus experiment for detection of γ-H2AX by immunofluorescence. The mRNA expression of HSP90, HSC70 and Lamp-2a was detected by qPCR. The protein expressions of HSP90, HSC70 and Lamp-2a were detected by Western blot. Next, we knocked down HSP90 expression by the HSP90 Inhibitor, NVP-AUY 922, exposed or HSP90α shRNA lentivirus transduction in A549 cells. KEY FINDINGS: In these studies, we first found that heat shock protein 90 (HSP90), heat shock cognate 70 (HSC70) and lysosomal-associated membrane protein type 2 receptor (Lamp-2a) expressions of C57BL mice lung tissue and A549 cells exposed to BaP were significant increase, as well as BaP induced DNA double-strand breaks (DSBs) and activated DNA damage responses, as evidenced by comet assay and γ-H2AX foci analysis in A549 cells. Our results demonstrated BaP induced CMA and caused DNA damage. Next, we knocked down HSP90 expression by the HSP90 Inhibitor, NVP-AUY 922, exposed or HSP90α shRNA lentivirus transduction in A549 cells. HSC70 and Lamp-2a expressions of these cells exposed to BaP were not significant increase, which showed that BaP inducted CMA was mediated by HSP90. Further, HSP90α shRNA prevented BaP induced of BaP which suggested BaP regulated CMA and caused DNA damage by HSP90. Our results elucidated a new mechanism of BaP regulated CMA through HSP90. SIGNIFICANCE: BaP regulated CMA through HSP90. HSP90 is involved in the regulation of gene instability induced by DNA damage by BaP, which promotes CMA. Our study also revealed that BaP regulates CMA through HSP90. This study fills the gap of the effect of BaP on autophagy and its mechanism, which will lead to a more comprehensive understanding of the action mechanism of BaP.

Multiple iodide autocatalysis paths of chemo-hydrodynamical patterns in the Briggs-Rauscher reaction.

Autocatalytic feedback is often regarded as the core step for the chemo-hydrodynamical patterns in the nonlinear reaction system. The Briggs-Rauscher (BR) reaction shows sequential chemo-hydrodynamical patterns with three states, i.e. labyrinth, high iodine state, and rotating dendritic patterns. The short-lived labyrinth patterns, depending on [Mn2+]0, the ratio of [CH2(COOH)2]0 and [KIO3]0 and light intensities, result from iodide autocatalytic loop, which has three paths (involving Mn2+-induced radical reactions, the oxidation of iodomalonic compounds, and light-induced radical reactions, respectively). The high iodine state appears in a high ratio of [CH2(COOH)2]0 and [KIO3]0, relating to the autocatalytic path involving the oxidation of iodomalonic compounds. The light-induced radical autocatalytic path can act as a convenient control parameter to modulate the patterns in the first stage by increasing the iodine radicals. The dendritic patterns in the third stage result from the Marangoni effect caused by the evaporation of the solutions and reactions between H2O2 and iodine-containing species, which is independent of [CH2(COOH)2]0 and [Mn2+]0. This work contributes to a better understanding of the complex spatiotemporal patterns in the chemo-hydrodynamical system.

Rapid and quantitative detection of the inflammatory marker neopterin based on a visible luminescent Zn(II)-Eu(III) nanocluster.

A high-nuclearity Zn(II)-Eu(III) nanocluster was synthesized for the rapid and quantitative luminescence detection of neopterin as an inflammatory marker.

Delayed improvements in visual memory task performance among chronic schizophrenia patients after high-frequency repetitive transcranial magnetic stimulation.

BACKGROUND: Cognitive impairments are core characteristics of schizophrenia, but are largely resistant to current treatments. Several recent studies have shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dor-solateral prefrontal cortex (DLPFC) can reduce negative symptoms and improve certain cognitive deficits in schizophrenia patients. However, results are inconsistent across studies. AIM: To examine if high-frequency rTMS of the DLPFC can improve visual memory deficits in patients with schizophrenia. METHODS: Forty-seven chronic schizophrenia patients with severe negative symptoms on stable treatment regimens were randomly assigned to receive active rTMS to the DLPFC (n = 25) or sham stimulation (n = 22) on weekdays for four consecutive weeks. Patients performed the pattern recognition memory (PRM) task from the Cambridge Neuropsychological Test Automated Battery at baseline, at the end of rTMS treatment (week 4), and 4 wk after rTMS treatment (week 8). Clinical symptoms were also measured at these same time points using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS). RESULTS: There were no significant differences in PRM performance metrics, SANS total score, SANS subscores, PANSS total score, and PANSS subscores between active and sham rTMS groups at the end of the 4-wk treatment period, but PRM performance metrics (percent correct and number correct) and changes in these metrics from baseline were significantly greater in the active rTMS group at week 8 compared to the sham group (all P < 0.05). Active rTMS treatment also significantly reduced SANS score at week 8 compared to sham treatment. Moreover, the improvement in visual memory was correlated with the reduction in negative symptoms at week 8. In contrast, there were no between-group differences in PANSS total score and subscale scores at either week 4 or week 8 (all P > 0.05). CONCLUSION: High-frequency transcranial magnetic stimulation improves visual memory and reduces negative symptoms in schizophrenia, but these effects are delayed, potentially due to the requirement for extensive neuroplastic changes within DLPFC networks.

The absence of CsdA in Escherichia coli increases DNA replication and cell size but decreases growth rate at low temperature.

The CsdA protein is a highly conserved, DEAD-box RNA helicase and assists RNA structural remodeling at low temperature. We show that the fast-growing wild-type (WT) cells contain higher number of replication origins per cell with bigger cell size and the slowly growing cells possess less number of replication origins per cell with smaller cell size. The absence of CsdA leads to production of larger cells with higher number of origins per cell but slower growth at low temperature in an independent-manner of growth media. The phenotypes in ΔcsdA mutant are reversed by ectopic expression of CsdA or RNase R. A global transcription analysis shows that the absence of CsdA leads to significant decreases in transcription of about 200 genes at low temperature. These genes are associated with essential metabolic pathways, flagger assembly and cell division (minDE). It is likely that the slow growth of ΔcsdA cell results from the decreased transcription of essential metabolic genes, and the larger ΔcsdA cell could be a result of decreased transcription of minDE. The increased transcription of the nrdHIEF genes in ΔcsdA mutant is a likely reason that promotes DNA replication. We conclude that CsdA coordinates the cell cycle to growth by stabilizing mRNA of essential metabolic and cell division genes and degrading mRNA for nucleotide metabolic genes at low temperature.

Suicide attempt rate and the risk factors in young, first-episode and drug-naïve Chinese Han patients with major depressive disorder.

BACKGROUND: In recent years, the rates of suicide among young people have been increasing, and major depressive disorder (MDD) is regarded to be its main cause. Many factors such as thyroid dysfunction and metabolic abnormalities are thought to mediate this process, but the conclusions are inconsistent. This study investigated the rate of suicide attempts and associated risk factors among young, first-episode and drug-naïve Chinese Han patients with MDD. METHODS: A total of 917 patients with MDD (aged 18 ~ 35 years) were recruited. Demographic and clinical data were collected and thyroid function, fasting blood glucose and lipid profiles were measured. The Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), positive symptom subscale of Positive and Negative Syndrome Scale (PANSS) and clinical global impression of severity scale (CGI-S) were adopted to assess depression, anxiety, psychotic symptoms and disease severity respectively. RESULTS: The rate of suicide attempts was 19.5% in young MDD patients. There were significant differences in age (p = 0.003), education level (p = 0.001), age of onset (p = 0.004) and disease duration (p = 0.001) between patients with and without suicide attempts. Compared with patients without suicide attempts, patients with suicide attempts had significantly higher scores on the HAMD-17, HAMA, PANSS positive symptom subscale and CGI-S (all p < 0.001). Patients with suicide attempts had significantly higher levels of TSH (p < 0.001), TgAb (p = 0.004), TPOAb (p < 0.001), TG (p = 0.016), TC (p < 0.001), LDL (p < 0.001), and fasting glucose (p < 0.001), but significantly lower levels of HDL (p < 0.001). Logistic regression analysis showed that marital status (OR = 0.515, 95%CI: 0.280-0.950, p = 0.515), disease duration (OR = 1.100, 95%CI: 1.013-1.194, p = 0.024), HAMA score (OR = 1.313, 95%CI: 1.205-1.430, p < 0.001), CGI-S score (OR = 1.875, 95%CI: 1.339-2.624, p < 0.001), levels of FT3(OR = 0.717, 95%CI: 0.536-0.959, p = 0.025), TPOAb (OR = 1.004, 95%CI: 1.002-1.006, p < 0.001), TC (OR = 1.330, 95%CI: 1.011-1.750, p = 0.042) and LDL (OR = 0.736, 95%CI: 0.558-0.971, p = 0.030) were all independently associated with suicide attempts in young MDD patients. CONCLUSIONS: In China, the rate of suicide attempts in young patients with MDD is quite high and thyroid dysfunction and metabolic abnormalities may be implicated in its pathogenesis.

The Mediating Role of Coping Style in the Relationship Between Sleep Quality and Burnout: A Cross-Sectional Study Among Psychiatric Nurses.

Background: Although sleep quality is clearly associated with job burnout as shown in the existing research, the mechanism underpinning such relationship remains undefined. This work, thus, aimed to assess the current situation of sleep quality and burnout in Chinese psychiatric nurses, and to analyze the relationships between sleep quality, burnout and coping style, in order to provide possible targets to enhance mental health and wellbeing among psychiatric nurses. Method: This cross-sectional study was carried out in seven rehabilitation centers located in four different regions of China. The Pittsburgh Sleep Quality Index, the Epworth Sleeping Scale, the Maslach Burnout Inventory General Survey, and the Coping Style Questionnaire were distributed to 853 nurses in various mental hospitals, with a total of 664 participants being recruited in the final research. Results: The results of this current study showed a high prevalence of sleep disorders and burnout in Chinese psychiatric nurses. Moreover, emotional exhaustion (r = 0.456), cynicism (r = 0.323) and negative coping style (r = 0.191) in nurses were all positively correlated with total Pittsburgh Sleep Quality Index (PSQI) score, while professional efficacy (r = -0.079) and positive coping style (r = -0.140) were negatively correlated with total PSQI score. More interestingly, of all negative coping strategies, we found that self-blame had the most significant effect (ß = 0.156). Conclusions: The above results showed that coping style mediates the association of poor sleep quality with job burnout in Chinese psychiatric nurses. This study claimed that there is an urgent need to development the coping skills to sustain a healthy work life for nurses.

Mechanical forces on trophoblast motility and its potential role in spiral artery remodeling during pregnancy.

During the first trimester of pregnancy, cytotrophoblasts (CTBs) differentiate into extravillous trophoblasts (EVTs). EVTs migrate from villus to decidua, invade maternal spiral arteries (SAs) and more strikingly, they migrate against blood flow along the vessels and replace endothelial cells (ECs), completing SA remodeling. Studies have indicated that trophoblast cells are mechanosensitive. They assemble ECs, which can align in the direction of fluid flow. However, how they sense blood flow and transform mechanical stimulations into chemical signals remain largely unexplored. What factors trigger their motility? what are the potential and major factors that guide them to find their path and empower them to migrate against flow? To answer these intricate questions, this review provides some of the novel aspects and sheds new insights into clinical applications.

Interaction between AhR and HIF-1 signaling pathways mediated by ARNT/HIF-1ß.

BACKGROUND: The main causes of lung cancer are smoking, environmental pollution and genetic susceptibility. It is an indisputable fact that PAHs are related to lung cancer, and benzo(a) pyrene is a representative of PAHs. The purpose of the current investigation was to investigate the interaction between AhR and HIF-1 signaling pathways in A549 cells, which provide some experimental basis for scientists to find drugs that block AhR and HIF-1 signaling pathway to prevent and treat cancer. METHODS: This project adopts the CYP1A1 signaling pathways and the expression of CYP1B1 is expressed as a measure of AhR strength index. The expression of VEGF and CAIX volume as a measure of the strength of the signal path HIF-1 indicators. Through the construction of plasmid vector, fluorescence resonance energy transfer, real-time quantitative PCR, western blotting and immunoprecipitation, the interaction between AhR signaling pathway and HIF-1 signaling pathway was observed. RESULTS: BaP can enhance the binding ability of HIF-1α protein to HIF-1ß/ARNT in a dose-dependent manner without CoCl2. However, the binding ability of AhR protein to HIF-1ß/ARNT is inhibited by HIF-1α signaling pathway in a dose-dependent manner with CoCl2. CONCLUSION: It is shown that activation of the AhR signaling pathway does not inhibit the HIF-1α signaling pathway, but activation of the HIF-1α signaling pathway inhibits the AhR signaling pathway.

Molecular mechanism of benzo [a] pyrene regulating lipid metabolism via aryl hydrocarbon receptor.

BACKGROUND: Benzo [a] pyrene (BaP), a potent carcinogen, has been proved that it has toxicological effects via activation the aryl hydrocarbon receptor (AhR) pathway. AhR can participate in regulating lipogenesis and lipolysis. This topic will verify whether BaP regulates lipid metabolism via AhR. METHODS: (1) C57BL/6 mice were gavaged with BaP for 12 weeks to detect serum lipids, glucose tolerance, and insulin resistance. Morphological changes in white adipose tissue (WAT) were detected by Hematoxylin and Eosin staining. The mRNA expression levels of adipogenesis-related factors included recombinant human CCAAT/enhancer binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), and fatty acid binding protein 4 (FABP4) and inflammatory factors included nuclear factor kappa-B (NF-κB), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α) were detected using PCR. (2) Neutral lipid content changes in differentiated 3 T3-L1 adipocytes treated with BaP with and w/o AhR inhibitor were detected by Oil red staining. The protein expression levels of adipogenesis- and decomposition-related factors included PPARγ coactivator-1 alpha (PGC-1α), and peroxisome proliferation-activated receptor alpha (PPARα) were detected using western blotting. The mRNA expression levels of inflammatory factors were detected using PCR. RESULTS: (1) BaP inhibited body weight gain, decreased lipid content, increased lipid levels, and decreased glucose tolerance and insulin tolerance in mice; (2) BaP reduced the expressions of C/EBPα, PPARγ, FABP4, PGC-1α, and PPARα and increased the expressions of NF-κB, MCP-1, and TNF-α by activating AhR. CONCLUSION: BaP inhibit fat synthesis and oxidation while inducing inflammation by activating AhR, leading to WAT dysfunction and causing metabolic complications.

The Impact of the SARS-COV-2 Pandemic on the Mental Health and Employment Decisions of Medical Students in North China.

Background: The outbreak of severe respiratory syndrome coronavirus 2 (SARS-COV-2) has led to long periods of social isolation for individuals across the world. Although medical students generally have a high prevalence of mental health problems, they have received less attention than other groups concerning the impact of SARS-COV-2. Therefore, the present study investigated the mental health status, risk factors, and protective factors for mental health problems in medical students in North China during the SARS-COV-2 pandemic. Methods: A WeChat-based survey, which included the Depression Anxiety Stress Scale-21 and measures of social demographics, was performed twice. Risk and protective factors were identified by binary logistic regression analysis. Results: A total of 702 effective questionnaires were collected in two separate surveys. In total, 24.55% of medical students were suffering anxiety to different degrees of severity, 13.18% were suffering depression in the first survey, and 3.71% wanted to give up working in primary medical care during the SARS-COV-2 pandemic in the second survey. In contrast, during the SARS-COV-2 pandemic, a risk factor for anxiety and depression was gender which is male, while being knowledgeable about the SARS-COV-2 pandemic and having a lower academic burden were both protective factors. Conclusions: Measures are required to prevent increases in mental health problems in medical students. Our findings suggest that increasing knowledge about the SARS-COV-2 pandemic and reducing academic burden in medical students is extremely important during the SARS-COV-2 pandemic.

RNA Demethylase FTO Mediated RNA m6A Modification Is Involved in Maintaining Maternal-Fetal Interface in Spontaneous Abortion.

The N6-methyladenosine (m6A) RNA modification regulates the expression of genes associated with various biological and pathological processes, including spontaneous abortion (SA). The aim of this study was to determine the role of the m6A demethylase fat mass and obesity (FTO)- associated protein in SA. The FTO,IGF2BP1 and IGF2BP2 mRNA levels were significantly lower in the chorionic villi obtained from spontaneously aborted pregnancies compared to that of normal pregnancies, while the expression levels of METTL3 and WTAP were significantly elevated. However, ALKBH5, YTHDF2, and IGF2BP3 were elevated with no statistical significance between groups. In addition, MDA was elevated and SOD levels were decreased in the villi tissues of the SA group compared to the normal group, which was indicative of placental oxidative stress in the former. Furthermore, the expression of FTO and HLA-G were significantly decreased in the trophoblasts of the SA patients compared to that of normal pregnant women, while that of m6A was markedly higher in the former. In addition, the HLA-G and VEGFR mRNA levels were downregulated in the SA versus the control group, and that of MMP2, MMP7, MMP9 and VEGFA were upregulated. Finally, The RIP assay showed significantly decreased levels of FTO-bound HLA-G, VEGFR and MMP9 RNA in SA patients (P < 0.05), which corresponded to an increase in transcripts enriched with the m6A antibody (P < 0.05). However, compared with normal pregnant women, the levels of HLA-G, VEGFA, VEGFR, and MMP2 mRNA bound by YTHDF2 were significantly decreased in SA patients. Compared to the normal pregnant women, both FTO- and m6A-bound MMP7 were significantly increased in SA patients (P < 0.05), but YTHDF2 almost unbound to MMP7 mRNA. In summary, the downregulation of FTO in the chorionic villi disrupts immune tolerance and angiogenesis at the maternal-fetal interface, resulting in aberrant methylation and oxidative stress that eventually leads to SA.