Macrophage exosomes mediate palmitic acid-induced metainflammation by transferring miR-3064-5p to target IκBα and activate NF-κB signaling.

INTRODUCTION: High palmitic acid (PA) levels trigger metainflammation, facilitating the onset and progression of chronic metabolic diseases. Recently, exosomes were identified as new inflammation mediators. However, the mechanism by which macrophage exosomes mediate PA-induced inflammation remains unclear. OBJECTIVES: To explore how PA induces metainflammation through macrophage exosomes. METHODS: Exosomes secreted by RAW264.7 mouse macrophages stimulated with PA (ExosPA) or not (Exos) were prepared by ultracentrifugation. The differential miRNAs between ExosPA and Exos were identified by high-throughput sequencing, and their targeted mRNAs and proteins were bioinformatically analyzed and verified by qPCR and western blot. Mouse macrophages and metabolic cells (AML-12 hepatocytes, C2C12 myocytes or 3T3-L1 adipocytes) were treated with ExosPA or Exos. The verified miRNAs and its targeted molecules related to inflammation were analyzed in recipient cells. Furthers, exosomes were prepared from primary peritoneal macrophages isolated from AIN93G diet-fed (Control PM-Exos) or HPD-fed (PA PM-Exos) mice. Control or PA PM-Exos were then tail vein injected (30 µg) into mice (n = 10), once a week for 2 weeks. The verified miRNA and its targets in blood, blood exosomes, and metabolic tissues were detected. Finally, measured the levels of miRNA, inflammatory factors, and fatty acids in the blood of 20 obese/overweight individuals and 20 healthy individuals. RESULTS: ExoPA activate NF-κB signaling and enhance inflammatory enzyme/cytokine production in macrophages and metabolic cells. ExoPA enrich miR-3064-5p and target to inhibit IκBα as verified by exosome inhibitors and miR-3064-5p mimics and inhibitors. HPD elevates exosomal miR-3064-5p, macrophage exosomal miR-3064-5p, and inflammatory cytokine levels in mice circulation. PA PM-Exos from HPD-fed mice triggered inflammation in the circulation and metabolic tissues/organs of chow diet-fed mice. Overweight/obese individuals exhibit increased levels of circulating palmitoleic acid, exosomal miR-3064-5p, and high-sensitivity C-reactive proteins. CONCLUSIONS: Macrophage exosomes transferring miR-3064-5p to target IκBα and activate NF-κB signaling in metabolic cells is a mechanism of PA-induced metainflammation.

Gut Microbiota Plays Essential Roles in Soyasaponin's Preventive Bioactivities against Steatohepatitis in the Methionine and Choline Deficient (MCD) Diet-Induced Non-Alcoholic Steatohepatitis (NASH) Mice.

SCOPE: Gut microbiota (GM) is involved in nonalcoholic steatohepatitis (NASH) development. Phytochemicals soyasaponins can prevent NASH possibly by modulating GM. This study aims to investigate the preventive bioactivities of soyasaponin monomers (SS-A1 and SS-Bb) against NASH and explores the mechanisms by targeting GM. METHODS AND RESULTS: Male C57BL/6 mice are fed with methionine and choline deficient (MCD) diet containing SS-A1 , SS-Bb, or not for 16 weeks. Antibiotics-treated pseudo germ-free (PGF) mice are fed with MCD diet containing SS-A1 , SS-Bb, or not for 8 weeks. GM is determined by 16S rRNA amplicon sequencing. Bile acids (BAs) are measured by UPLC-MS/MS. In NASH mice, SS-A1 and SS-Bb alleviate steatohepatitis and fibrosis, reduce ALT, AST, and LPS in serum, decrease TNF-α, IL-6, α-SMA, triglycerides, and cholesterol in liver. SS-A1 and SS-Bb decrease Firmicutes, Erysipelotrichaceae, unidentified-Clostridiales, Eggerthellaceae, Atopobiaceae, Aerococcus, Jeotgalicoccus, Gemella, Rikenella, increase Proteobacteria, Verrucomicrobia, Akkermansiaceae, Romboutsia, and Roseburia. SS-A1 and SS-Bb alter BAs composition in liver, serum, and feces, activate farnesoid X receptor (FXR) in liver and ileum, increase occludin and ZO-1 in intestine. However, GM clearance abrogates the preventive bioactivities of SS-A1 and SS-Bb against NASH. CONCLUSION: GM plays essential roles in soyasaponin's preventive bioactivities against steatohepatitis in MCD diet-induced NASH mice.

Impact of propofol and sevoflurane anesthesia on cognition and emotion in gastric cancer patients undergoing radical resection.

BACKGROUND: Propofol and sevoflurane are commonly used anesthetic agents for maintenance anesthesia during radical resection of gastric cancer. However, there is a debate concerning their differential effects on cognitive function, anxiety, and depression in patients undergoing this procedure. AIM: To compare the effects of propofol and sevoflurane anesthesia on postoperative cognitive function, anxiety, depression, and organ function in patients undergoing radical resection of gastric cancer. METHODS: A total of 80 patients were involved in this research. The subjects were divided into two groups: Propofol group and sevoflurane group. The evaluation scale for cognitive function was the Loewenstein occupational therapy cognitive assessment (LOTCA), and anxiety and depression were assessed with the aid of the self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Hemodynamic indicators, oxidative stress levels, and pulmonary function were also measured. RESULTS: The LOTCA score at 1 d after surgery was significantly lower in the propofol group than in the sevoflurane group. Additionally, the SAS and SDS scores of the sevoflurane group were significantly lower than those of the propofol group. The sevoflurane group showed greater stability in heart rate as well as the mean arterial pressure compared to the propofol group. Moreover, the sevoflurane group displayed better pulmonary function and less lung injury than the propofol group. CONCLUSION: Both propofol and sevoflurane could be utilized as maintenance anesthesia during radical resection of gastric cancer. Propofol anesthesia has a minimal effect on patients' pulmonary function, consequently enhancing their postoperative recovery. Sevoflurane anesthesia causes less impairment on patients' cognitive function and mitigates negative emotions, leading to an improved postoperative mental state. Therefore, the selection of anesthetic agents should be based on the individual patient's specific circumstances.

Symptom experience in endocrine therapy for breast cancer patients: A qualitative systematic review and meta-synthesis.

Objective: The purpose of this study was to systematically integrate the experience of symptoms of breast cancer patients receiving endocrine therapy, analyze the patients' understanding and coping status of symptoms, and provide information for the development of targeted symptom management measures. Methods: We searched databases including PubMed/MEDLINE, MEDLINE (Ovid), Web of Science, EMBASE (Ovid), CINAHL (EBSCO), and ProQuest from inception to September 25, 2023. Literature was screened and analyzed using Endnote software, evaluated using the Joanna Briggs Institute Critical Appraisal Tool for Qualitative Research, and the results were integrated using JBI's Pooled Integration Methodology. Results: Three composite findings were derived from 10 studies: symptom distress during endocrine therapy; coping in symptom experience; and support needs. Conclusions: Emphasis should be placed on the symptomatic experience of breast cancer patients undergoing endocrine therapy, and effective interventions should be developed to improve patients' medication compliance and quality of life. Finally, the long-term survival rate of patients is improved. Systematic review registration: CRD42023466073.

Cognitive function and its associated factors among patients with cancer pain: a multicentre cross-sectional study in China.

OBJECTIVE: This research aimed to assess the levels of cognitive function and its contributing factors among individuals experiencing cancer pain (CP) in mainland China. DESIGN: A descriptive, cross-sectional study. SETTING: The investigation was undertaken within three tertiary oncology hospitals. PARTICIPANTS: We included 220 hospitalised individuals who reported experiencing cancer-related pain and consented to complete the research questionnaires. OUTCOME MEASURES: The collected data encompassed sociodemographic and clinical variables, augmented by results from validated questionnaires. Cognitive impairment (CI) was evaluated using the Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog) scale, with scores ranging from 0 to 148. Sleep quality, depression and anxiety were assessed through the Pittsburgh Sleep Quality Index, the Patient Health Questionnaire-9 and the Generalised Anxiety Disorder-7, respectively. A binary logistic regression model was used to identify factors associated with CI in individuals with CP. RESULTS: Of the 225 individuals approached, 220 (97.8%) participated in the study. The mean FACT-Cog score for those with CP was 101.29 (SD=25.24; range=25-148). The prevalence of CI among these individuals was 35.90%. Sleep quality was rated below medium in 45% of participants with CP. More than moderate pain was reported by 28.2%, with 64.6% experiencing depression and 38.6% experiencing anxiety. Increased odds of developing CI were observed in those with CP (OR 1.422, 95% CI 1.129 to 1.841), depression (OR 1.119, 95% CI 1.029 to 1.2117), anxiety (OR 1.107, 95% CI 1.005 to 1.220), advancing age (OR 1.042, 95% CI 1.013 to 1.073), poor sleep quality (OR 1.126, 95% CI 1.013 to 1.252) and a history of smoking (OR 3.811, 95% CI 1.668 to 8.707). CONCLUSIONS: CI associated with CP is notably prevalent in China. Those older, with a smoking history, inadequate sleep, more severe pain, depression and anxiety, have a heightened risk of CI. Consequently, interventions need to be personalised, addressing these key determinants.

Milk Exosomes from Gestational Diabetes Mellitus (GDM) and Healthy Parturient Exhibit Differential miRNAs Profiles and Distinct Regulatory Bioactivity on Hepatocyte Proliferation.

SCOPE: Exosomes, a novel type of bioactive component in human milk (HM), affect infant development, growth, and health. Recent studies indicate that HM exosomes and miRNAs relate to gestational diabetes mellitus (GDM). However, the miRNAs profiles and functionalities of HM exosomes from GDM parturient remain unclear. This study aims to compare the differential miRNAs in HM exosomes from GDM and healthy parturient, and investigate the HM exosomes bioactivities in regulating hepatocyte proliferation and insulin sensitivity. METHODS AND RESULTS: This study extracted HM exosomes from GDM (GDM-EXO) and healthy (NOR-EXO) parturient by ultracentrifugation, high-throughput sequenced and compared the exosomal miRNAs profiles, and explored the regulatory bioactivities on hepatocyte proliferation in HepG2 cells and Balb/c mice. As compared to NOR-EXO, GDM-EXO has similar morphology, size, concentration, and exosome-specific markers (CD9 and TSG101) expression. GDM-EXO and NOR-EXO specifically harbor 1299 and 8 miRNAs, respectively. Moreover, GDM-EXO had 176 upregulated and 47 downregulated miRNAs compared with NOR-EXO. Both GDM-EXO and NOR-EXO were absorbed in cultured HepG2 hepatocytes and mice liver. GDM-EXO inhibited hepatocytes proliferation by downregulating mammalian target of rapamycin (mTOR) possibly via exosomal miR-101-3p delivery. CONCLUSION: HM exosomes from GDM and healthy parturient exhibit differential miRNAs profiles and distinct regulatory bioactivity on hepatocyte proliferation.

Gold nanoclusters Cys-Au NCs as selective fluorescent probes for "on-off-on" detection of Fe3+ and ascorbic acid.

Gold nanoclusters exhibit attractive properties owing to their excellent biocompatibility and strong photostability in the biomedical domain. In this research, cysteine-protected fluorescent gold nanoclusters (Cys-Au NCs) were synthesized via decomposing Au(i)-thiolate complexes for the detection of Fe3+ and ascorbic acid in a bidirectional "on-off-on" mode. Meanwhile, the detailed characterization confirmed that the mean particle size of the prepared fluorescent probe was 2.43 nm and showed a fluorescence quantum yield of 3.31%. In addition, our results indicate that the fluorescence probe for ferric ions exhibited a broad detection scope ranging from 0.1 to 2000 µM and excellent selectivity. The as-prepared Cys-Au NCs/Fe3+ was demonstrated to be an ultrasensitive and selective nanoprobe for the detection of ascorbic acid. This study indicated that the "on-off-on" fluorescent probes Cys-Au NCs held a promising application for the bidirectional detection of Fe3+ and ascorbic acid. Furthermore, our novel "on-off-on" fluorescent probes provided insight into the rational design of thiolate-protected gold nanoclusters for biochemical analysis of high selectivity and sensitivity.

Advances in the Bioactivities of Phytochemical Saponins in the Prevention and Treatment of Atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory disease characterized by hardening and narrowing of arteries. AS leads to a number of arteriosclerotic vascular diseases including cardiovascular diseases, cerebrovascular disease and peripheral artery disease, which pose a big threat to human health. Phytochemicals are a variety of intermediate or terminal low molecular weight secondary metabolites produced during plant energy metabolism. Phytochemicals from plant foods (vegetables, fruits, whole grains) and traditional herb plants have been shown to exhibit multiple bioactivities which are beneficial for prevention and treatment against AS. Many types of phytochemicals including polyphenols, saponins, carotenoids, terpenoids, organic sulfur compounds, phytoestrogens, phytic acids and plant sterols have already been identified, among which saponins are a family of glycosidic compounds consisting of a hydrophobic aglycone (sapogenin) linked to hydrophilic sugar moieties. In recent years, studies have shown that saponins exhibit a number of biological activities such as anti-inflammation, anti-oxidation, cholesterol-lowering, immunomodulation, anti-platelet aggregation, etc., which are helpful in the prevention and treatment of AS. This review aims to summarize the recent advances in the anti-atherosclerotic bioactivities of saponins such as ginsenoside, soyasaponin, astra-galoside, glycyrrhizin, gypenoside, dioscin, saikosaponin, etc.

Willingness of patients with cancer pain to participate in end-of-life decisions: a multi-center cross-sectional study from three coastal provinces in southern China.

BACKGROUND: Little is known about patients' intention for participation in end-of-life decisions (EOLD) in three coastal provinces in southern China. This study aimed to explore the willingness of patients with cancer pain to participate in EOLD and potential influencing factors. METHODS: A multi-center cross-sectional study was performed in three coastal provinces in southern China. Two hundred and thirty patients with cancer pain were recruited and consented to fill out the questionnaires. The patients' willingness to participate in EOLD, demographic and disease-related data was surveyed. RESULTS: In total, 223 patients completed and returned the survey (response rate = 96.95%). One hundred four cases (46.64%) were willing to participate in EOLD. 119 (54.36%) cases not willing to participate in EOLD, respectively. Multivariate logistic regression analysis shows that educational level (OR: 0.683, 95% CI: 0.482-0.966), history of alcoholism (OR: 8.353, 95%CI: 2.535-27.525), Eastern Cooperative Oncology Group (ECOG) score (OR: 0.645, 95% CI: 0.450-0.925) and experience of explosive pain (OR: 6.367, 95% CI: 3.103-13.062) and clinical rescue (OR: 3.844, 95% CI: 1.722-8.577) had significant effects on EOLD intention (P <  0.05). Finally, a predictive model combined above five factors was established, which showed a good discrimination (area under receiver operating characteristic curve: 0.849, 95% CI: 0.796-0.899, P <  0.001) and calibration (Hosmer-Lemeshow Test: Chi-square = 10.103, P = 0.258) for which patients more willing to participate in EOLD. CONCLUSIONS: The willingness of patients with cancer pain to participate in EOLD is at a modest level in three coastal provinces in southern China. Patients with lower educational level, history of alcoholism, better health status and experience of explosive pain and clinical rescue may be more prone to participate in EOLD.

The Accelerated Progression of Atherosclerosis Correlates with Decreased miR-33a and miR-21 and Increased miR-122 and miR-3064-5p in Circulation and the Liver of ApoE-/- Mice with Streptozocin (STZ)-Induced Type 2 Diabetes.

Atherosclerosis is a major risk factor for type 2 diabetes (T2D) mortality. We aim to investigate the changes in miR-21, miR-122, miR-33a and miR-3064-5p in circulation and the liver of ApoE-/- mice with streptozocin (STZ)-induced T2D. Twenty 5-week-old male ApoE-/- mice were randomly assigned to the control (n = 10) and T2D group (n = 10) and intraperitoneally injected with a citrate buffer and streptozotocin (STZ) (40 mg/kg BW) once a day for three consecutive days. The successfully STZ-induced T2D mice (n = 5) and control mice (n = 5) were then fed with a high-fat diet (HFD) for 34 weeks. Compared to the control mice, ApoE-/- mice with STZ-induced T2D had slower (p < 0.05) growth, increased (p < 0.05) total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), decreased (p < 0.05) high-density lipoprotein cholesterol (HDL-C) in serum, reduced (p < 0.05) TC and sterol regulatory element-binding protein-2 (Srebp-2), elevated (p < 0.05) ATP-binding-cassette-transporter-A1 (Abca1) in the liver, aggravated (p < 0.05) atherosclerotic lesions in the aorta, downregulated (p < 0.05) miR-21 and miR-33a, and upregulated (p < 0.05) miR-122 and miR-3064-5p in serum and the liver. In addition, the aortic lesions showed a positive correlation with miR-122 (r = 1.000, p = 0.001) and a negative correlation with miR-21 (r = −1.000, p = 0.001) in ApoE-/- mice with T2D. In conclusion, T2D-accelerated atherosclerosis correlates with a reduction in miR-21 and miR-33a and an elevation in miR-122 and miR-3064-5p in circulation and the liver of ApoE-/- mice.

Inflammation Induced by Lipopolysaccharide and Palmitic Acid Increases Cholesterol Accumulation via Enhancing Myeloid Differentiation Factor 88 Expression in HepG2 Cells.

Recently, multiple studies have shown that chronic inflammation disturbs cholesterol homeostasis and promotes its accumulation in the liver. The underlying molecular mechanism remains to be revealed. The relationship between the toll-like receptor 4 (TLR4) inflammatory signaling pathway and cholesterol accumulation was investigated in HepG2 cells treated with lipopolysaccharide (LPS) or palmitic acid (PA) for different lengths of time. In addition, the effects of pretreatment with 20µmol/L ST2825 (MyD88 inhibitor) were also studied in LPS- or PA-treated HepG2 cells and myeloid differentiation factor 88 (MyD88)-overexpressing HEK293T cells. The intracellular total and free cholesterol levels were measured using a commercial kit and filipin staining, respectively. The expression levels of sterol regulatory element-binding protein-2 (SREBP-2) and components in the TLR4 signaling pathway were determined using Western blotting. The treatments with LPS for 12 h and with PA for 24 h significantly increased the contents of intracellular total and free cholesterol, as well as the expression levels of SREBP-2 and components in the TLR4 signaling pathway. The inhibition of MyD88 by ST2825 significantly decreased the cholesterol content and the expression levels of SREBP-2 and components of the TLR4/MyD88/NF-κB pathway in HepG2 cells, as well as MyD88-overexpressing HEK293T cells. These results indicated that LPS and PA treatments increase SREBP-2-mediated cholesterol accumulation via the activation of the TLR4/MyD88/NF-κB signaling pathway in HepG2 cells.

Isolation and identification of a new strain of nervous necrosis virus from the big-belly seahorse Hippocampus abdominalis.

BACKGROUND: Betanodaviruses, members of the Nodaviridae family, are the causative agents of viral nervous necrosis in fish, resulting in great economic losses worldwide. METHODS: In this study, we isolated a virus strain named seahorse nervous necrosis virus (SHNNV) from cultured big-belly seahorses Hippocampus abdominalis in Xiamen city, Fujian Province, China. Virus isolation, PCR detection, phylogenetic analysis, qRT-PCR, fluorescence in situ hybridization and histology were used for virus identification and analysis of virus histopathology. Furthermore, an artificial infection experiment was conducted for virulence testing. RESULTS: Brain and eye tissue homogenates of diseased big-belly seahorses were inoculated onto a grouper spleen (GS) cell monolayer at 28 °C. Tissue homogenates induced obvious cytopathic effects in GS cells. PCR and sequencing analyses revealed that the virus belonged to Betanodavirus and shared high sequence identity with red-spotted grouper nervous necrosis virus isolates. qRT-PCR and fluorescence in situ hybridization revealed that SHNNV mainly attacked the brain and eye. Histopathological examination revealed that the virus led to cytoplasmic vacuolation in the brain and retinal tissues. Infection experiments confirmed that SHNNV was highly infectious, causing massive death in big-belly seahorses. CONCLUSION: A novel seahorse betanodavirus from the big-belly seahorse cultured in China was discovered. This finding will contribute to the development of efficient strategies for disease management in aquaculture.

Melatonin Attenuates Ropivacaine-Induced Apoptosis by Inhibiting Excessive Mitophagy Through the Parkin/PINK1 Pathway in PC12 and HT22 Cells.

Melatonin, as an endogenous circadian indoleamine secreted by the pineal gland, executes extensive biological functions, including antioxidant, anti-inflammatory, anti-tumor, and neuroprotective effects. Although melatonin has been reported to serve as a potential therapeutic against many nerve injury diseases, its effect on ropivacaine-induced neurotoxicity remains obscure. Our research aimed to explore the impact and mechanism of melatonin on ropivacaine-induced neurotoxicity. Our results showed that melatonin pretreatment protected the cell viability, morphology, and apoptosis of PC12 and HT22 cells, and it also improved ropivacaine-induced mitochondrial dysfunction and the activation of mitophagy. In addition, we found that autophagy activation with rapamycin significantly weakened the protective effect of melatonin against ropivacaine-induced apoptosis, whereas autophagy inhibition with 3-MA enhanced the effect of melatonin. We also detected the activation of Parkin and PINK1, a canonical mechanism for mitophagy regulation, and results shown that melatonin downregulated the expression of Parkin and PINK1, and upregulated Tomm20 and COXIV proteins, so that those results indicated that melatonin protected ropivacaine-induced apoptosis through suppressing excessive mitophagy by inhibiting the Parkin/PINK1 pathway. Melatonin may be a useful potential therapeutic agent against ropivacaine-induced neurotoxicity.

Genome and gene evolution of seahorse species revealed by the chromosome-level genome of Hippocampus abdominalis.

Seahorses belong to the teleost family Syngnathidae that evolved a distinct body plan and unique male pregnancy compared to other teleosts. As a classic model for studying evolution of viviparity and sexual selection of teleosts, seahorse species still lack a publicly available high-quality reference genome. Here, we generated the genome assembly of the big-belly seahorse, Hippocampus abdominalis with long-read and Hi-C technologies. We managed to place over 99% of the total length of 444.7 Mb of assembled genome into 21 linkage groups with almost no gaps. We reconstructed a phylogenomic tree with the big-belly seahorse genome and other representative Syngnathidae and teleost species. We also reconstructed the historical population dynamics of four representative Syngnathidae species. We found the gene families that underwent expansion or contraction in the Syngnathidae ancestor were enriched for immune-related or ion transporter gene ontology terms. Many of these genes were also reported to show a dynamic expression pattern during the pregnancy stages of H. abdominalis. We also identified putative positively selected genes in the Syngnathidae ancestor or in H. abdominalis, whose mouse mutants are enriched for abnormal craniofacial and limb morphological phenotypes. Overall, our study provides an important genome resource for evolutionary and developmental studies of seahorse species, and candidate genes for future experimental works.

Development and assessment of a mental health preliminary screening questionnaire for cancer patients.

BACKGROUND: The mental health of cancer patients is attracting increasing attention. Thus, an efficient mental health preliminary screening questionnaire (MHPSQ) for cancer patients is required. This study sought to develop an MHPSQ, test its reliability and validity, and administer it among cancer patients. METHODS: A literature review and interviews with 8 patients were conducted to determine the questionnaire item pool, and experts were consulted to confirm the first draft. Next, 150 cancer patients were selected for the project analysis and validity assessment to develop the final document; 400 patients were then selected for the reliability and validity tests. After which, 1,000 patients were assessed using the Self-Rating Anxiety Scale, Self-Rating Depression Scale (SDS), and MHPSQ, and the completion times for each scale were evaluated. Finally, the specificity and sensitivity of the MHPSQ were then determined. RESULTS: Four factors (i.e., mood, sleep, social function, and interpersonal relationships) were ultimately retained as MHPSQ items. MHPSQ's Cronbach's α and test-retest reliability were 0.76 and 0.92, respectively. The time required to complete the MHPSQ was 83.90±19.00 s. Its sensitivity and specificity were 92.4% and 98.5%, respectively. CONCLUSIONS: The MHPSQ has good reliability and validity. Comprising only 4 items, it is easy to operate and effectively identifies patients with psychological abnormalities.

Ropivacaine Induces Cell Cycle Arrest in the G0/G1 Phase and Apoptosis of PC12 Cells via Inhibiting Mitochondrial STAT3 Translocation.

STAT3 has neuroprotective effect via non-canonical activation and mitochondrial translocation, but its effect on ropivacaine-induced neurotoxicity remains unclear. Our previous study revealed that apoptosis was an important mechanism of ropivacaine-induced neurotoxicity; this study is to illustrate the relationship between STAT3 with ropivacaine-induced apoptosis. Those results showed that ropivacaine treatment decreased cell viability, induced cell cycle arrest in the G0/G1 phase, apoptosis, oxidative stress, and mitochondrial dysfunction in PC12 cells. Moreover, ropivacaine decreased the phosphorylated levels of STAT3 at Ser727 and downregulated the expression of STAT3 upstream gene IL-6. The mitochondrial translocation of STAT3 was also hindered by ropivacaine. To further illustrate the connection of STAT3 protein structure with ropivacaine, the autodock-vina was used to examine the interaction between STAT3 and ropivacaine, and the results showed that ropivacaine could bind to STAT3's proline site and other sites. In addition, the activator and inhibitor of mitoSTAT3 translocation were used to demonstrate it was involved in ropivacaine-induced apoptosis; the results showed that enhancing the mitochondrial STAT3 translocation could prevent ropivacaine-induced apoptosis. Finally, the expression of p-STAT3 and the levels of apoptosis in the spinal cord were also detected; the results were consistent with the cell experiment; ropivacaine decreased the expression of p-STAT3 protein and increased the levels of apoptosis in the spinal cord. We demonstrated that ropivacaine induced apoptosis by inhibiting the phosphorylation of STAT3 at Ser727 and the mitochondrial STAT3 translocation. This effect was reversed by the activation of the mitochondrial STAT3 translocation.

P53 inhibitor pifithrin-α inhibits ropivacaine-induced neuronal apoptosis via the mitochondrial apoptosis pathway.

The neurotoxicity of local anesthetics (LAs) has attracted more and more attention, However, they lack preventive and therapeutic measures. Many studies have shown that apoptosis plays an important role in the process of LA-induced neurotoxicity. As an important signaling molecule to activate apoptosis, p53 has been proved to be involved in the neurotoxicity induced by LAs, but the mechanism is unclear. In this study, we explored the effect of pifithrin-α (PFT-α), a p53 inhibitor, on apoptosis by ropivacaine (Rop) in vivo and in vitro. Cell viability and apoptosis detected by CCK-8 and a JC-1 apoptosis detection kit, the changes of spinal cord structure observed after hematoxylin and eosin staining, apoptosis of the spinal cord measured by terminal deoxynucleotidyl transferase dUTP nick end labeling staining, behavioral assessment of the nerve Injury evaluated by the detection of sciatic nerve conduction velocity (SNCV) andmechanical withdrawal threshold (MWT), the expression of p53 and many apoptosis-related genes included Bax, Bcl-2, and caspase-3 detected by quantitative real-time polymerase chain reaction, Western blot analysis, immunofluorescence, and immunohistochemistry. Results showed that PC12 cell viability decreased because of Rop, but the pretreatment of PFT-α could protect it. And PFT-α reduced the injuries in the spinal cord by Rop included vacuoles or edema. The results of immunofluorescence and immunohistochemistry testing showed that PFT-α inhibited the p53 protein upregulated by Rop. Apoptosis rate and many proapoptotic genes include p53, Bax, caspase-3 messenger RNA, and proteins were increased by Rop, but PFT-α could decrease it. In conclusion, PFT-α inhibited cell apoptosis and spinal cord injuries induced by Rop.

Soyasaponin A2 Alleviates Steatohepatitis Possibly through Regulating Bile Acids and Gut Microbiota in the Methionine and Choline-Deficient (MCD) Diet-induced Nonalcoholic Steatohepatitis (NASH) Mice.

SCOPE: Nonalcoholic steatohepatitis (NASH) is a chronic progressive disease with complex pathogenesis of which the bile acids (BAs) and gut microbiota are involved. Soyasaponins (SS) exhibits many health-promoting effects including hepatoprotection, but its prevention against NASH is unclear. This study aims to investigate the preventive bioactivities of SS monomer (SS-A2 ) against NASH and further clarify its mechanism by targeting the BAs and gut microbiota. METHODS AND RESULTS: The methionine and choline deficient (MCD) diet-fed male C57BL/6 mice were intervened with obeticholic acid or SS-A2 for 16 weeks. Hepatic pathology is assessed by hematoxylin-eosin and Masson's trichrome staining. BAs in serum, liver, and colon are measured by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQMS). Gut microbiota in caecum are determined by 16S rDNA amplicon sequencing. In the MCD diet-induced NASH mice, SS-A2 significantly reduces hepatic steatosis, lobular inflammation, ballooning, nonalcoholic fatty liver disease activity score (NAS) scores, and fibrosis, decreases Erysipelotrichaceae (Faecalibaculum) and Lactobacillaceae (Lactobacillus) and increases Desulfovibrionaceae (Desulfovibrio). Moreover, SS-A2 reduces serum BAs accumulation and promotes fecal BAs excretion. SS-A2 changes the BAs profiles in both liver and serum and specifically increases the taurohyodeoxycholic acid (THDCA) level. Faecalibaculum is negatively correlated with serum THDCA. CONCLUSION: SS-A2 alleviates steatohepatitis possibly through regulating BAs and gut microbiota in the MCD diet-induced NASH mice.

Interpersonal Neural Synchronization During Cooperative Behavior of Basketball Players: A fNIRS-Based Hyperscanning Study.

Accumulating evidence has consistently shown that team-based sports (such as basketball) are beneficial to interpersonal cooperation. However, its neural correlate remains to be discovered, especially in the perspective of two-person neuroscience. In this study, 12 dyads of basketball players and 12 dyads of college students who had no experience of team-based sports training were asked to perform joint-drawing task and control task. During task performance, neural activities were recorded in frontal area by the functional near-infrared spectroscopy (fNIRS)-based hyperscanning approach. The results demonstrated that dyads of basketball players were faster to finish joint-drawing task and showed higher subjective cooperativeness than dyads of college students. Meanwhile, significant interpersonal neural synchronization (INS) was observed in the dorsolateral prefrontal area only when pairs of basketball players performed joint-drawing task, but not control task. Therefore, we provide the first piece of inter-brain evidence for enhanced cooperative behavior in the individuals with team-based sports training, which could make us deeply understand exact neural correlate for experience-dependent changes of cognitions in humans.

The complete mitochondrial genome of the Picasso clownfish: genomic comparisons and phylogenetic inference among Amphiprioninae.

Picasso clownfish belong to the subfamily Amphiprioninae and are considered a variant of the genus Amphiprion. In this study, we first sequenced the complete mitochondrial genome of the Picasso clownfish by Illumina next-generation sequencing technology. The length of the whole mitogenome is 16,727 bp long, with a gene arrangement and composition similar to those of two other Amphiprion species (Amphiprion ocellaris and Amphiprion percula). The topological structure of the phylogenetic tree shows that the Picasso clownfish is more closelyrelated to A. percula than it is to A. ocellaris, suggesting that the Picasso clownfish may be a variant of A. percula.