Associations of sex-related and thyroid-related hormones with risk of metabolic dysfunction-associated fatty liver disease in T2DM patients.

BACKGROUND: We aimed to examine sex-specific associations between sex- and thyroid-related hormones and the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS: Cross-sectional analyses of baseline information from an ongoing cohort of 432 T2DM patients (185 women and 247 men) in Xiamen, China were conducted. Plasma sex-related hormones, including estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone, and total testosterone (TT), and thyroid-related hormones, including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and parathyroid hormone (PTH), were measured using chemiluminescent immunoassays. MAFLD was defined as the presence of hepatic steatosis (diagnosed by either hepatic ultrasonography scanning or fatty liver index (FLI) score > 60) since all subjects had T2DM in the present study. RESULTS: Prevalence of MAFLD was 65.6% in men and 61.1% in women with T2DM (P = 0.335). For men, those with MAFLD showed significantly decreased levels of FSH (median (interquartile range (IQR)):7.2 (4.9-11.1) vs. 9.8 (7.1-12.4) mIU/ml) and TT (13.2 (10.4-16.5) vs. 16.7 (12.8-21.6) nmol/L) as well as increased level of FT3 (mean ± standard deviation (SD):4.63 ± 0.68 vs. 4.39 ± 0.85 pmol/L) than those without MAFLD (all p-values < 0.05). After adjusting for potential confounding factors, FSH and LH were negative, while progesterone was positively associated with the risk of MAFLD in men, and the adjusted odds ratios (ORs) (95% confidence intervals (CIs)) were 0.919 (0.856-0.986), 0.888 (0.802-0.983), and 8.069 (2.019-32.258) (all p-values < 0.05), respectively. In women, there was no statistically significant association between sex- or thyroid-related hormones and the risk of MAFLD. CONCLUSION: FSH and LH levels were negative, whereas progesterone was positively associated with the risk of MAFLD in men with T2DM. Screening for MAFLD and monitoring sex-related hormones are important for T2DM patients, especially in men.

Association of Pro-Inflammatory Diet, Smoking, and Alcohol Consumption with Bladder Cancer: Evidence from Case-Control and NHANES Studies from 1999 to 2020.

BACKGROUND AND PURPOSE: Diet might be a modifiable factor in preventing cancer by modulating inflammation. This study aims to explore the association between the dietary inflammatory index (DII) score and the risk of bladder cancer (BC). METHODS: A total of 112 BC patients and 292 control subjects were enrolled in a case-control trial. Additionally, we tracked a total of 109 BC patients and 319 controls, whose propensity scores were obtained from the Nutrition Examination Survey (NHANES) database spanning from 1999 to 2020. The baseline index and dietary intake data were assessed using a food frequency questionnaire (FFQ). DII scores were calculated based on the dietary intake of 20 nutrients obtained from participants and categorized into four groups. The association between the inflammatory potential of the diet and BC risk was investigated using multivariate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: High DII scores were associated with a pro-inflammatory diet and a higher risk of BC, with higher DII scores positively associated with a higher risk of BC (quartiles 4 vs. 1, ORs 4.89, 95% CIs 2.09-11.25 p < 0.001). Specifically, this might promote BC development by inducing oxidative stress and affecting DNA repair mechanisms. This result was consistent with the NHANES findings (quartiles 4 vs. 1, ORs 2.69, 95% CIs 1.25-5.77, p = 0.006) and further supported the association of pro-inflammatory diet and lifestyle factors with the risk of BC. CONCLUSIONS: Diets with the highest pro-inflammatory potential were associated with an increased risk of BC. By adjusting lifestyle factors, individuals might effectively lower their DII, thereby reducing the risk of developing BC. The results are consistent with the NHANES cohort.

Ultra-Fast Selenol-Yne Click (SYC) Reaction Enables Poly(selenoacetal) Covalent Adaptable Network Formation.

The emergence of covalent adaptable networks (CANs) based on dynamic covalent bonds (DCBs) presents a promising avenue for achieving resource recovery and utilization. In this study, we discovered a novel dynamic covalent bond called selenacetal, which is obtained through a double click reaction between selenol and activated alkynes. Density functional theory (DFT) calculations demonstrated that the ΔG for the formation of selenoacetals ranges from 12 to 18 kJ mol-1, suggesting its potential for dynamic reversibility. Dynamic exchange experiments involving small molecules and polymers provide substantial evidence supporting the dynamic exchange properties of selenoacetals. By utilizing this highly efficient click reaction, we successfully synthesized dynamic materials based on selenoacetal with remarkable reprocessing capabilities without any catalysts. These materials exhibit chemical recycling under alkaline conditions, wherein selenoacetal (SA) can decompose into active enone selenide (ES) and diselenides. Reintroducing selenol initiates a renewed reaction with the enone selenide, facilitating material recycling and yielding a newly developed dynamic material exhibiting both photo- and thermal responsiveness. The results underscore the potential of selenoacetal polymers in terms of recyclability and selective degradation, making them a valuable addition to conventional covalent adaptable networks.

Matrine exhibits antiviral activities against PEDV by directly targeting Spike protein of the virus and inducing apoptosis via the MAPK signaling pathway.

Porcine Epidemic Diarrhea Virus (PEDV) is a highly contagious virus that causes Porcine Epidemic Diarrhea (PED). This enteric disease results in high mortality rates in piglets, leading to significant financial losses in the pig industry. However, vaccines cannot provide sufficient protection against epidemic strains. Spike (S) protein exposed on the surface of virion mediates PEDV entry into cells. Our findings imply that matrine (MT), a naturally occurring alkaloid, inhibits PEDV infection targeting S protein of virions and biological process of cells. The GLY434 residue in the autodocking site of the S protein and MT conserved based on sequence comparison. This study provides a comprehensive analysis of viral attachment, entry, and virucidal effects to investigate how that MT inhibits virus replication. MT inhibits PEDV attachment and entry by targeting S protein. MT was added to cells before, during, or after infection, it exhibits anti-PEDV activities and viricidal effects. Network pharmacology focuses on addressing causal mechanisms rather than just treating symptoms. We identified the key genes and screened the cell apoptosis involved in the inhibition of MT on PEDV infection in network pharmacology. MT significantly promotes cell apoptosis in PEDV-infected cells to inhibit PEDV infection by activating the MAPK signaling pathway. Collectively, we provide the biological foundations for the development of single components of traditional Chinese medicine to inhibit PEDV infection and spread.

Predictive value of bronchoscopy combined with CT score for refractory mycoplasma pneumoniae pneumonia in children.

INTRODUCTION: Mycoplasma pneumoniae pneumonia (MPP) is prevalent in paediatric patients and can progress to refractory mycoplasma pneumoniae pneumonia (RMPP). OBJECTIVE: To assess the predictive value of bronchoscopy combined with computed tomography (CT) score in identifying RMPP in children. METHODS: A retrospective analysis was conducted on 244 paediatric patients with MP, categorising them into RMPP and general mycoplasma pneumoniae pneumonia (GMPP) groups. A paired t-test compared the bronchitis score (BS) and CT score before and after treatment, supplemented by receiver operating characteristic (ROC) analysis. RESULTS: The RMPP group showed higher incidences of extrapulmonary complications and pleural effusion (58.10% and 40%, respectively) compared with the GMPP group (44.60%, p = 0.037 and 18.71%, p < 0.001, respectively). The CT scores for each lung lobe were statistically significant between the groups, except for the right upper lobe (p < 0.05). Correlation analysis between the total CT score and total BS yielded r = 0.346 and p < 0.001. The ROC for BS combined with CT score, including area under the curve, sensitivity, specificity, and cut-off values, were 0.82, 0.89, 0.64, and 0.53, respectively. CONCLUSION: The combined BS and CT score method is highly valuable in identifying RMPP in children.

Advanced Multifunctional Hydrogels for Enhanced Wound Healing through Ultra-Fast Selenol-SNAr Chemistry.

Fabrication of versatile hydrogels in a facile and effective manner represents a pivotal challenge in the field of biomaterials. Herein, a novel strategy is presented for preparing on-demand degradable hydrogels with multilevel responsiveness. By employing selenol-dichlorotetrazine nucleophilic aromatic substitution (SNAr) to synthesize hydrogels under mild conditions in a buffer solution, the necessity of additives or posttreatments can be obviated. The nucleophilic and redox reactions between selenol and tetrazine culminate in the formation of three degradable chemical bonds-diselenide, aryl selenide, and dearomatized selenide-in a single, expeditious step. The resultant hydrogel manifests exceptional adaptability to intricate environments in conjunction with self-healing and on-demand degradation properties. Furthermore, the resulting material demonstrated light-triggered antibacterial activity. Animal studies further underscore the potential of integrating metformin into Se-Tz hydrogels under green light irradiation, as it effectively stimulates angiogenesis and collagen deposition, thereby fostering efficient wound healing. In comparison to previously documented hydrogels, Se-Tz hydrogels exhibit controlled degradation and drug release, outstanding antibacterial activity, mechanical robustness, and bioactivity, all without the need for costly and intricate preparation procedures. These findings underscore Se-Tz hydrogels as a safe and effective therapeutic option for diabetic wound dressings.

Whole-transcriptome RNA sequencing reveals CeRNA regulatory network under long-term space composite stress in Rats.

To systematically evaluate the effect of simulated long-term spaceflight composite stress (LSCS) in hippocampus and gain more insights into the transcriptomic landscape and molecular mechanism, we performed whole-transcriptome sequencing based on the control group (Ctrl) and the simulated long-term spaceflight composite stress group (LSCS) from six hippocampus of rats. Subsequently, differential expression analysis was performed on the Ctrl and LSCS groups, followed by enrichment analysis and functional interaction prediction analysis to investigate gene-regulatory circuits in LSCS. In addition, competitive endogenous RNA (ceRNA) network was constructed to gain insights into genetic interaction. The result showed that 276 differentially expressed messenger RNAs (DEmRNAs), 139 differentially expressed long non-coding RNAs (DElncRNAs), 103 differentially expressed circular RNAs (DEcircRNAs), and 52 differentially expressed microRNAs (DEmiRNAs) were found in LSCS samples compared with the controls, which were then subjected to enrichment analysis of Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways to find potential functions. PI3K-Akt signaling pathway and MAPK signaling pathway may play fundamental roles in the pathogenesis of LSCS. A ceRNA network was constructed with the predicted 340 DE pairs, which revealed the interaction roles of 220 DEmiRNA-DEmRNA pairs, 76 DEmiRNA-DElncRNA pairs, and 44 DEmiRNA-DEcircRNA pairs. Further, Thrombospondins2 was found to be a key target among those ceRNAs. Overall, we conducted for the first time a full transcriptomic analysis of the response of hippocampus to the LSCS that involved a potential ceRNA network, thus providing a basis to study the underlying mechanism of the LSCS.

Examining the wound healing potential of curcumin-infused electrospun nanofibers from polyglutamic acid and gum arabic.

Advancements in medicine have led to continuous enhancements and innovations in wound dressing materials, making them pivotal in medical care. We used natural biological macromolecules, γ-polyglutamic acid and gum arabic as primary raw materials to create nanofibers laden with curcumin by blending electrostatic spinning technology in the current investigation. These nanofibers were meticulously characterized using fluorescence microscopy, scanning electron microscopy, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Our comprehensive analyses confirmed the successful encapsulation of curcumin within the nanofiber carrier and it has uniform diameter, good water absorption and mechanical properties. Subsequently, we evaluated the antimicrobial effects of these curcumin-loaded nanofibers against Staphylococcus aureus through an oscillating flask method. We created a mouse model with acute full-thickness skin defects to further investigate the wound healing potential. We conducted various biochemical assays to elucidate the mechanism of action. The results revealed that curcumin nanofibers profoundly impacted wound healing. They bolstered the expression of TGF-ß1 and VEGF and reduced the expression of inflammatory factors, leading to an accelerated re-epithelialization process, enhanced wound contraction, and increased regeneration of new blood vessels and hair follicles. Furthermore, these nanofibers positively influenced the proportion of three different collagen types. This comprehensive study underscores the remarkable potential of curcumin-loaded nanofibers to facilitate wound healing and lays a robust experimental foundation for developing innovative, natural product-based wound dressings.

Differences in the activities of six soil enzymes in response to cadmium contamination of paddy soils in high geological background areas.

East Yunnan province in southwest China is a region with elevated natural abundance (high geological background levels) of Cd due to high metal (loid) contents in the soils. Enzyme activities are useful indicators of metal (loid) toxicity in contaminated soils and whether Cd inhibits enzyme activities in paddy soils in high geological background areas is of considerable public concern. A pot experiment combined with field investigation was conducted to assess the effects of Cd on six soil enzymes that are essential to the cycling of C, N, and P in soils. Inhibitory effects of Cd fractions on enzyme activities were assessed using ecological dose-response models. The impact of soil properties on the inhibition of sensitive soil enzymes by Cd were assessed using linear and structural equation models. Cadmium was enriched in the paddy soils with 72.2 % of soil samples from high geological background areas exceeding the Chinese threshold values (GB 15618-2018) of Cd. Enzyme responses to Cd contamination varied markedly with a negative response by catalase but a positive response by invertase. Urease, ß-glucosidase, and alkaline phosphatase activities were stimulated at low Cd concentrations and inhibited at high concentrations. The average inhibition ratios of ß-glucosidase, urease, and catalase in high Cd levels were 19.9, 38.9, and 51.9%, respectively. Ecological dose-response models indicate that catalase and urease were the most Cd-sensitive of the enzymes studied and were suitable indicators of soil quality in high geological background areas. Structural equation modeling (SEM) indicates that soil properties influenced sensitive enzymes through various pathways, indicating that soil properties were factors determining Cd inhibition of enzyme activities. This suggests that Cd concentrations and soil physicochemical properties under a range of environmental conditions should be considered in addressing soil Cd pollution.

Optimization of ultrasound-assisted extraction of Imperata cylindrica polysaccharides and evaluation of its anti-oxidant and amelioration of uric acid stimulated cell apoptosis.

An efficient, cost-effective and environmentally friendly ultrasound-assisted hot water method for Imperata cylindrica polysaccharide (ICPs) extraction was developed. According to the response surface results, the optimal ultrasonic time was 85 min, ultrasonic power was 192.75 W, temperature was 90.74 °C, liquid-solid ratio was 26.1, and polysaccharide yield was 28.50 %. The polysaccharide mainly consisted of arabinose (Ara), galactose (Gal), and glucose (Glc), with a molecular weight of 62.3 kDa. Ultrasound-assisted extraction of Imperata cylindrica polysaccharide (UICP) exhibited stronger anti-oxidant activity and ability to ameliorate cellular damage due to uric acid stimulation compared with traditional hot water extraction of Imperata cylindrica polysaccharide (ICPC-b). It also exhibited higher thermal stability, indicating its potential value for applications in the food industry.

Foodborne Carbon Dots Aggravate High-Fat-Diet-Induced Glucose Homeostasis Imbalance by Disrupting the Gut-Liver Axis.

Foodborne carbon dots (CDs) are generally produced during cooking and exist in food items. Generally, CDs are regarded as nontoxic materials, but several studies have gradually confirmed the cytotoxicity of CDs, such as oxidative stress, reduced cellular activity, apoptosis, etc. However, studies focusing on the health effects of long-term intake of food-borne CDs are scarce, especially in populations susceptible to metabolic disease. In this study, we reported that CDs in self-brewing beer had no effect on glucose metabolism in CHOW-fed mice but exacerbated high-fat-diet (HFD)-induced glucose metabolism disorders via the gut-liver axis. Chronic exposure to foodborne CDs increased fasting glucose levels and exacerbated liver and intestinal barrier damage in HFD-fed mice. The 16s rRNA sequencing analysis revealed that CDs significantly altered the gut microbiota composition and promoted lipopolysaccharide (LPS) synthesis-related KEGG pathways (superpathway of (Kdo)2-lipid A, Kdo transfer to lipid IVA Ill (Chlamydia), lipid IVA biosynthesis, and so on) in HFD-fed mice. Mechanically, CD exposure increased the abundance of Gram-negative bacteria (Proteobacteria and Desulfovibrionaceae), thus producing excessive endotoxin-LPS, and then LPS was transferred by the blood circulation to the liver due to the damaged intestinal barrier. In the liver, LPS promoted TLR4/NF-κB/P38 MAPK signaling, thus enhancing systemic inflammation and exacerbating HFD-induced insulin resistance. However, pretreating mice with antibiotics eliminated these effects, indicating a key role for gut microbiota in CDs exacerbating glucose metabolism disorders in HFD-fed mice. The finding herein provides new insight into the potential health risk of foodborne nanoparticles in susceptible populations by disturbing the gut-liver axis.

Protective effect of Baoyuan Jieyu formula on long-term spaceflight composite stress-induced depressive-like behavior and memory deficits through regulation of Ca2+ channel currents.

Long-term spaceflight composite stress (LSCS) can cause adverse effects on human systems, especially the central nervous system. This study aimed to identify the underlying mechanisms of the protective effect of Baoyuan Jieyu Formula (BYJYF) on LSCS-induced depressive-like behavior and memory deficits. In this experiment, we simulated the real space station environment for a period of 42 days. Novel object recognition test and forced swimming test were used to assess the memory abilities and depression level of rats as well as test the therapeutic effects of BYJYF treatment. Results showed LSCS could induce depressive-like behavior and damage short-term memory in the behavioral level, and BYJYF could enhance the ability to resist LSCS. Meanwhile, LSCS increased the levels of CRH, ACTH, and CORT and induced HPA axis hyperactivity, which can be relieved by BYJYF. Further, we predicted and verified the potential signaling pathways of BYJYF. Results showed BYJYF may reverse the inhibition of LSCS on Ca2+ channel currents. And we also found that BYJYF may exert its medicinal effects via four main active components including saikosaponin A. Overall, BYJYF exhibited protective effects against LSCS-induced depressive-like behavior and memory deficits, which might be ascribed to the regulation of Ca2+ channel currents and four active components. And it might become a promising candidate medicine for diseases induced by LSCS.

C15:0 and C17:0 partially mediate the association of milk and dairy products with bladder cancer risk.

The relationship between saturated fatty acids (SFA) and bladder cancer (BC) risk has been conflicting. Our aim was to investigate the relationship between erythrocyte membrane SFA and BC risk. A total of 404 participants were enrolled in the study (including 112 cases and 292 controls). A validated food frequency questionnaire was used to assess the food intake. The constitutive composition of fatty acids in the erythrocyte membrane was measured by gas chromatography. After adjustment for BC risk factors, SFA had no significant association with BC risk. However, C18:0 was positively linked with BC risk with an odds ratio (OR; 95% CI) of 2.99 (1.37-6.53). In contrast, very-long-chain saturated fatty acids (VLCSFA), especially C24:0, were negatively related to BC risk with an OR (95% CI) of 0.28 (0.12-0.65) for VLCSFA and 0.33 (0.15-0.75) for C24:0. Higher total odd-chain SFA (C15:0 and C17:0) were associated with a lower risk of BC with OR (95% CI) of 0.18 (0.076-0.44), 0.18 (0.068-0.47), 0.34 (0.14-0.81), respectively. After subgroup analysis, the protective effects C15:0 and C17:0 were still remained. Receiver operating characteristic analysis displayed that the combination of C15:0 and C17:0 indexes increased the accurate predictive rate of BC risk. Further mediation effect analysis showed that C15:0 and C17:0 could be used as partial mediation effectors for milk and dairy products and bladder carcinogenesis. Overall, the combination of odd-chain SFA (C15:0 and C17:0) in the erythrocyte membrane could serve as a reliable mediator and predictor, indicating a relationship between a high intake of milk and dairy products and a lower risk of BC.

A Self-Adaptive Biomimetic Periosteum Employing Nitric Oxide Release for Augmenting Angiogenesis in Bone Defect Regeneration.

The periosteum plays a vital role in the regeneration of critical-size bone defects and highly comminuted fractures, promoting the differentiation of osteoblasts, accelerating the reconstruction of the vascular network, and guiding bone tissue regeneration. However, the materials loaded with exogenous growth factors are limited by the release and activity of the elements. Therefore, the material structure must be carefully designed for the periosteal function. Here, a self-adaptive biomimetic periosteum strategy is proposed, which is a novel interpenetrating double network hydrogel consisting of diselenide-containing gelatin and calcium alginate (modified natural collagen and polysaccharide) to enhance the stability, anti-swelling, and delayed degradation of the hydrogel. The diselenide bond continuously releases nitric oxide (NO) by metabolizing endogenous nitrosated thiols (RSNO), activates the nitric oxide-cycle guanosine monophosphate (NO-cGMP) signal pathway, coordinates the coupling effect of angiogenesis and osteogenesis, and accelerates the repair of bone defects. This self-adaptive biomimetic periosteum with the interpenetrating double network structure formed by the diselenide-containing gelatin and calcium alginate has been proven to be safe and effective in repairing critical-size bone defects and is expected to provide a promising strategy for solving clinical problems.

Long-term spaceflight composite stress induces depressive behaviors in model rats through disrupting hippocampus synaptic plasticity.

INTRODUCTION: Long-term spaceflight composite stress (LSCS) can cause adverse effects on human systems, including the central nervous system, which could trigger anxiety and depression. AIMS: This study aimed to identify changes in hippocampus synaptic plasticity under LSCS. METHODS: The present study simulated the real long-term space station environment by conducting a 42-day experiment that involved simulating microgravity, isolation, noise, circadian rhythm disruptions, and low pressure. The mood and behavior of the rats were assessed by behavior test. Transmission electron microscopy and patch-clamp were used to detect the changes in synapse morphology and electrophysiology, and finally, the expression of NMDA receptor channel proteins was detected by western blotting. RESULTS: The results showed that significant weight loss, anxiety, and depressive behaviors in rats were observed after being exposed to LSCS environment for 42 days. The synaptic structure was severely damaged, manifested as an obvious decrease in postsynaptic density thickness and synaptic interface curvature (p < 0.05; p < 0.05, respectively). Meanwhile, LTP was significantly impaired (p < 0.0001), and currents in the NMDAR channel were also significantly reduced (p < 0.0001). Further analysis found that LSCS decreased the expression of two key subtype proteins on this channel. CONCLUSION: These results suggested that LSCS-induced depressive behaviors by impairing synaptic plasticity in rat hippocampus.

Mechanism of cryptotanshinone to improve endocrine and metabolic functions in the endometrium of PCOS rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cryptotanshinone is the main bioactive component of Salvia miltiorrhiza, with various mechanisms of action, including antioxidant, anti-inflammatory, cardiovascular protection, neuroprotection, and hepatoprotection. Salvia miltiorrhiza is used clinically by gynecologists in China. AIM OF THE STUDY: Polycystic ovary syndrome (PCOS) has a significant impact on women's quality of life, leading to infertility and reproductive disorders. Hence, this study aims to assess the pharmacological activity of cryptotanshinone in the treatment of PCOS and investigate its therapeutic mechanism. MATERIALS AND METHODS: Human chorionic gonadotropin (HCG) combined with insulin is used to simulate a PCOS-like rat model and attempt to discover the abnormal changes that occur and the means by which the pathway acts in this model. RESULTS: The transcriptome sequencing method is used to identify 292 differential genes that undergo significant changes, of which 219 were upregulated and 73 were downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the signaling pathways reveals that differential expressed genes are significantly enriched in 23 typical pathways. Estrogen signaling pathways are screened in the cryptotanshinone and model groups, and significant differential changes in Fos, ALOX12, and AQP8 are found. This suggests that these signaling pathways and molecules may be the main signaling targets for regulating the differences in endometrial tissue. CONCLUSION: These results indicate that cryptotanshinone has targets for regulating the proliferation of endometrial tissue via estrogen signaling pathways in PCOS-like rats, providing an experimental basis for the clinical application of cryptotanshinone in the treatment of PCOS.

RNASEH1-AS1 induced by H3K27ac stabilizes ANXA2 mRNA to promote the progression of colorectal cancer through recruiting BUD13.

Colorectal cancer (CRC) is a malignant tumor with high morbidity and mortality. It is well-accepted that dysregulated lncRNAs are closely related to the development of CRC. In this study, the function and mechanism of RNASEH1-AS1 in CRC were investigated. RT-qPCR and western blot detected the expression of targeted genes in tissues and cells. CCK-8, clone formation, wound healing assay, and Transwell were applied to evaluate CRC cell malignant behaviors. ChIP, RIP, and RNA pull-down validated interactions among RNASEH1-AS1, H3K27ac, CBP, BUD13, and ANXA2. Nucleoplasmic separation and FISH assay determined the location of RNASEH1-AS1 in CRC cells. IHC assay was used to detect Ki-67 expression in tumor tissues from mice. RNASEH1-AS1 was highly expressed in CRC tumor tissues and cells. RNASEH1-AS1 silencing effectively suppressed the viability, proliferation, migration, and invasion of CRC cells. In addition, CBP-mediated H3K27ac increased RNASEH1-AS1 expression in CRC cells and RNASEH1-AS1 could elevate ANXA2 expression through recruiting BUD13. Furthermore, RNASEH1-AS1 silencing inhibited malignant phenotypes of CRC cells and tumor growth in mice through decreasing ANXA2 expression and inactivating the Wnt/ß-catenin pathway. Our results revealed that RNASEH1-AS1 induced by CBP-mediated H3K27ac activated Wnt/ß-catenin pathway to promote CRC progression through recruiting BUD13 to stabilize ANXA2 mRNA, which provides substantial evidence of RNASEH1-AS1 in CRC. Targeting RNASEH1-AS1 might alleviate CRC progression.

Effect of atrazine on testicular toxicity involves accommodative disorder of xenobiotic metabolizing enzymes system and testosterone synthesis in European quail (Coturnix coturnix).

Due to the wide use of atrazine (ATR), the concern has increased regarding the negative impact of ATR on reproduction. Nevertheless, the reproductive effects caused by different exposure concentrations and the severity of toxic damage are poorly understood. In organisms, ATR is metabolized and degraded through phase II enzyme systems, and changes in cytochrome P450 (CYP) enzymes may have a regulatory role in the harm of ATR. However, less information is available on the induction of CYPs by ATR in avian organisms, and even less on its effects on the testis. Birds are exposed to ATR mainly through food residues and contaminated water, the purpose of this study was to examine reproductive toxicity by different exposure concentrations and elaborate metabolic disorders caused by ATR in European quail (Coturnix coturnix). In this study, the quail were given ATR at 50 mg/kg, 250 mg/kg and 500 mg/kg by oral gavage for 45 days, and the testicular weight coefficients, histopathology and ultrastructure of testes, primary biochemical functions, sex steroid hormones, critical protein levels in the testosterone synthesis pathway, the expression of genes involved CYPs, gonad axis and nuclear receptors expression were investigated. Altogether, testicular coefficient decreased significantly in the high-dose group (1.22%) compared with the control group (3.03%) after 45 days of ATR exposure, and ATR is a potent CYP disruptor that acts through the NXRs and steroid receptor subfamily (APND, CAR, ERND and ERα) without a dose-dependent manner. Notably, ATR interfered with the homeostasis of hormones by triggering the expression of hormones on the gonad axis (LH and E2). These results suggest that exposure to ATR can cause testicular toxicity involving accommodative disorder of phase II enzyme and testosterone synthesis in European quail.

Long-term spaceflight composite stress induces depression and cognitive impairment in astronauts-insights from neuroplasticity.

The environment on the space station is quite unique compared to Earth, which is a composite of multiple stressors, such as microgravity, isolation, confinement, noise, circadian rhythm disturbance, and so on. During prolonged space missions, astronauts have to stay in such extreme environments for long periods, which could induce adverse effects on both their physical and mental health. In some circumstances, this kind of long-term spaceflight composite stress (LSCS) could also induce depression and cognitive impairment in various ways, including dysregulating the neuroplasticity of the brains of astronauts, which should be attached to great importance. Here, we have comprehensively reviewed the impact of individual and combined stressors on depression and cognitive function during long-term spaceflight, explained the underlying mechanisms of those effects from the perspective of neuroplasticity, and current countermeasures for mitigating these challenges. This review provides insights into LSCS and potential neuroplasticity mechanisms, current with potentially great impact for understanding and mitigating the mental health risks and traumas of career astronauts and space tourists.

Optimization strategy for the early timing of bronchoalveolar lavage treatment for children with severe mycoplasma pneumoniae pneumonia.

BACKGROUND: Early evaluation of severe mycoplasma pneumoniae pneumonia (SMPP) and the prompt utilization of fiberoptic bronchoscopic manipulation can effectively alleviate complications and restrict the progression of sequelae. This study aim to establish a nomogram forecasting model for SMPP in children and explore an optimal early therapeutic bronchoalveolar lavage (TBAL) treatment strategy. METHODS: This retrospective study included children with mycoplasma pneumoniae pneumonia (MPP) from January 2019 to December 2021. Multivariate logistic regression analysis was used to screen independent risk factors for SMPP and establish a nomogram model. The bootstrap method was employed and a receiver operator characteristic (ROC) curve was drawn to evaluate the accuracy and robustness of the model. Kaplan-Meier analysis was used to assess the effect of lavage and hospitalization times. RESULTS: A total of 244 cases were enrolled in the study, among whom 68 with SMPP and 176 with non-SMPP (NSMPP). A prediction model with five independent risk factors: left upper lobe computed tomography (CT) score, sequential organ failure assessment (SOFA) score, acute physiology and chronic health assessment (APACHE) II score, bronchitis score (BS), and c-reactive protein (CRP) was established based on the multivariate logistic regression analysis. The ROC curve of the prediction model showed the area under ROC curve (AUC) was 0.985 (95% confidence interval (CI) 0.972-0.997). The Hosmer-Lemeshow goodness-of-fit test results showed that the nomogram model predicted the risk of SMPP well (χ2 = 2.127, P = 0.977). The log-rank result suggested that an early BAL treatment could shorten MPP hospitalization time (P = 0.0057). CONCLUSION: This nomogram model, based on the left upper lobe CT score, SOFA score, APACHE II score, BS, and CRP level, represents a valuable tool to predict the risk of SMPP in children and optimize the timing of TBAL.