Abnormal intrinsic functional hubs and connectivity in patients with post-stroke depression.

OBJECTIVE: The present study aimed to investigate the specific alterations of brain networks in patients with post-stroke depression (PSD), and further assist in elucidating the brain mechanisms underlying the PSD which would provide supporting evidence for early diagnosis and interventions for the disease. METHODS: Resting-state functional magnetic resonace imaging data were acquired from 82 nondepressed stroke patients (Stroke), 39 PSD patients, and 74 healthy controls (HC). Voxel-wise degree centrality (DC) conjoined with seed-based functional connectivity (FC) analyses were performed to investigate the PSD-related connectivity alterations. The relationship between these alterations and depression severity was further examined in PSD patients. RESULTS: Relative to both Stroke and HC groups, (1) PSD showed increased centrality in regions within the default mode network (DMN), including contralesional angular gyrus (ANG), posterior cingulate cortex (PCC), and hippocampus (HIP). DC values in contralesional ANG positively correlated with the Patient Health Questionnaire-9 (PHQ-9) scores in PSD group. (2) PSD exhibited increased connectivity between these three seeds showing altered DC and regions within the DMN: bilateral medial prefrontal cortex and middle temporal gyrus and ipsilesional superior parietal gyrus, and regions outside the DMN: bilateral calcarine, ipsilesional inferior occipital gyrus and contralesional lingual gyrus, while decreased connectivity between contralesional ANG and contralesional supramarginal gyrus. Moreover, these FC alterations could predict PHQ-9 scores in PSD group. INTERPRETATION: These findings highlight that PSD was related with increased functional connectivity strength in some areas within the DMN, which might be attribute to the specific alterations of connectivity between within DMN and outside DMN regions in PSD.

Changes in proteomic cargo of circulating extracellular vesicles in response to lifestyle intervention in adolescents with hepatic steatosis.

BACKGROUND: Recent studies suggest that proteomic cargo of extracellular vesicles (EVs) may play a role in metabolic improvements following lifestyle interventions. However, the relationship between changes in liver fat and circulating EV-derived protein cargo following intervention remains unexplored. METHODS: The study cohort comprised 18 Latino adolescents with obesity and hepatic steatosis (12 males/6 females; average age 13.3 ± 1.2 y) who underwent a six-month lifestyle intervention. EV size distribution and concentration were determined by light scattering intensity; EV protein composition was characterized by liquid chromatography tandem-mass spectrometry. RESULTS: Average hepatic fat fraction (HFF) decreased 23% by the end of the intervention (12.5% [5.5] to 9.6% [4.9]; P = 0.0077). Mean EV size was smaller post-intervention compared to baseline (120.2 ± 16.4 nm to 128.4 ± 16.5 nm; P = 0.031), although the difference in mean EV concentration (1.1E+09 ± 4.1E+08 particles/mL to 1.1E+09 ± 1.8E+08 particles/mL; P = 0.656)) remained unchanged. A total of 462 proteins were identified by proteomic analysis of plasma-derived EVs from participants pre- and post-intervention, with 113 proteins showing differential abundance (56 higher and 57 lower) between the two timepoints (adj-p <0.05). Pathway analysis revealed enrichment in complement cascade, initial triggering of complement, creation of C4 and C2 activators, and regulation of complement cascade. Hepatocyte-specific EV affinity purification identified 40 proteins with suggestive (p < 0.05) differential abundance between pre- and post-intervention samples. CONCLUSIONS: Circulating EV-derived proteins, particularly those associated with the complement cascade, may contribute to improvements in liver fat in response to lifestyle intervention.

TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase.

Nonalcoholic fatty liver disease (NAFLD) encompasses a disease continuum from simple steatosis to nonalcoholic steatohepatitis (NASH). However, there are currently no approved pharmacotherapies for NAFLD, although several drugs are in advanced stages of clinical development. Because of the complex pathophysiology and heterogeneity of NAFLD, the identification of potential therapeutic targets is clinically important. Here, we demonstrated that tripartite motif 56 (TRIM56) protein abundance was markedly downregulated in the livers of individuals with NAFLD and of mice fed a high-fat diet. Hepatocyte-specific ablation of TRIM56 exacerbated the progression of NAFLD, while hepatic TRIM56 overexpression suppressed it. Integrative analyses of interactome and transcriptome profiling revealed a pivotal role of TRIM56 in lipid metabolism and identified the lipogenesis factor fatty acid synthase (FASN) as a direct binding partner of TRIM56. TRIM56 directly interacted with FASN and triggered its K48-linked ubiquitination-dependent degradation. Finally, using artificial intelligence-based virtual screening, we discovered an orally bioavailable small-molecule inhibitor of FASN (named FASstatin) that potentiates TRIM56-mediated FASN ubiquitination. Therapeutic administration of FASstatin improved NAFLD and NASH pathologies in mice with an optimal safety, tolerability, and pharmacokinetics profile. Our findings provide proof of concept that targeting the TRIM56/FASN axis in hepatocytes may offer potential therapeutic avenues to treat NAFLD.

Ento-A alleviates DSS-induced experimental colitis in mice by remolding intestinal microbiota to regulate SCFAs metabolism and the Th17 signaling pathway.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by changes in the metabolism of short chain fatty acids (SCFAs), dysregulation of gut microbiota, and an imbalance of Treg/Th17. Herein, we explore the effects of the Ento-A (an alcohol extract of Periplaneta americana L.) on a mouse model of UC. First, a chronic and recurrent UC model was constructed in BALB/c mice by 2.2% DSS administration. UC mice were continuously treated for 14 days with Ento-A (50, 100, 200 mg/kg, i.g.) or a negative control. Ento-A alleviated many of the pathological changes observed in UC mice, such as body weight loss, disease activity index, changes in colon length, and colonic mucosal damage index. Ento-A also decreased levels of proinflammatory cytokines (IL-1ß, IL-6, IL-17A, and TNF-α), increased levels of anti-inflammatory cytokines (IL-10 and TGF-ß1) and repaired the intestinal mucosal barrier. Additionally, Ento-A regulated the proportions of Th17 cells, and Treg cells in mesenteric lymph nodes harvested from treated mice (as assessed by Flow cytometry), and the expression levels of IL-17A and Foxp3 in colon (as assessed by immunohistochemistry). 16 S rRNA gene sequencing revealed that Ento-A regulated gut microbiota. GC-MS analysis demonstrated that Ento-A also restored SCFAs content in the intestinal tract. Finally, transcriptomic analysis revealed that Ento-A regulated the IL-17 signaling pathway. In summary, Ento-A regulates the diversity and abundance of intestinal flora in UC mice, enhancing the secretion of SCFAs, subsequently regulating the IL-17 signaling pathway, and ultimately repairing the intestinal mucosal barrier.

High-frequency rTMS of the left dorsolateral prefrontal cortex for post-stroke depression: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis investigated the therapeutic efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) for treatment of post-stroke depression (PSD). METHODS: Ten articles with 266 patients in rTMS group and 258 patients in control group were included. The primary outcome was performed to examine the efficacy of rTMS for PSD. Secondary outcomes of response rates and remission rates and subgroup analyses were further explored. RESULTS: Our meta-analysis revealed a significant pooled effect size (the standard mean difference (SMD) was -1.45 points (95% CI, -2.04 to -0.86; p < 0.00001)). The odds ratio (OR) of the response rate and remission rate were 8.41 (95% CI, 2.52-28.12, p = 0.0005) and 6.04 (95% CI, 1.5-24.39, p = 0.01). Moreover, rTMS treatment for PSD patients in subacute phase and targeting the left DLPFC at 5-cm anterior to the left motor hotspot or the midpoint of the middle frontal gyrus showed significant antidepressant effect. In addition, the Hamilton Depression Rating Scale (HAMD) was sensitive to detect depressive changes in patients. CONCLUSIONS: Our meta-analysis elucidated that the application of high-frequency rTMS over the left DLPFC was an effective treatment alternative for PSD. SIGNIFICANCE: Our meta-analysis may help to develop more reasonable treatment strategies in clinical practice for PSD patients.

Effect of in situ simulation training for emergency caesarean section on maternal and infant outcomes.

BACKGROUND: Emergency caesarean section (ECS) is an effective method for rapid termination of pregnancy and for saving maternal and foetal life in emergencies. Experts recommend that the interval from decision of operation to the decision to delivery interval (DDI) should be shortened as much as possible. Studies have shown that improving communication skills among staff by performing simulation drills shortens DDI, thus reducing the occurrence of adverse obstetric events and protecting maternal and child safety. In situ simulation (ISS) training is a simulation-based training approach for clinical team members conducted in a real-world clinical setting. In August 2020, Anhui Maternal and Child Health Hospital began ISS training on the rapid obstetric response team (RRT) in our hospital area for emergency caesarean section. This study aimed to investigate the effect of implementing in situ simulation training for emergency caesarean section on maternal and child outcomes by comparing maternal and child-related data on emergency caesarean section in two hospital areas. METHODS: Data on cases of emergency caesarean delivery implemented in two hospital districts from August 2020 to August 2022 were collected: 19 in the untrained group and 26 in the training group. The two groups were compared concerning the interval from the decision of operation to the decision to delivery interval (DDI), the interval from the decision of operation to the initiation of skin incision, the interval from skin incision to the decision to delivery interval, and the neonatal situation. RESULTS: Primary outcome comparison: The training group had a significantly shorter interval between the DDI compared to the untrained group (8.14 ± 3.13 vs. 11.03 ± 3.52, P = 0.006). Secondary outcomes comparison: The training group had a significantly shorter interval between the decision to cut skin compared to the untrained group (6.45 ± 2.21 vs. 9.95 ± 4.02, P = 0.001). However, there was no significant difference in the interval between cutting skin and infant delivery between the two groups (2.24 ± 0.08 vs. 2.18 ± 0.13, P > 0.05). Additionally, the Apgar score at 1 min after birth was higher in the training group compared to the untrained group (7.29 ± 2.38 vs. 6.04 ± 1.46, P < 0.05). CONCLUSIONS: The DDI for emergency caesarean section procedures can be significantly shortened, and neonatal Apgar scores at 1 min improved by implementing in situ simulation training for emergency caesarean section in obstetric rapid response teams. In situ simulation training is an effective tool for training in emergency caesarean section procedures and is worth promoting.

Effect of Kangfuxiaomi suppository on pelvic inflammatory disease in rats.

Pelvic inflammatory disease (PID) is commonly encountered in gynecological practice. Kangfuxiaomi suppository, made from the compound extract of Periplaneta Americana, is a Traditional Chinese Medicine remedy widely used for the treatment of gynecological disorders. This study aimed to preliminarily explore the therapeutic effect of Kangfuxiaomi suppository in a rat model of PID established by chemical injury and pathogen infection. The key parameters assessed were vulvar inflammation score, vaginal + uterine organ index, and serum levels of interleukin (IL)- 8; tumor necrosis factor (TNF)-α; C-reactive protein (CRP); superoxide dismutase (SOD); and malondialdehyde (MDA). In addition, levels of IL-6, cyclooxygenase (COX)- 2, and IL-2 in cervical tissues as well as that of IL-1ß and prostaglandin E-2 (PGE2) in uterine tissues were measured. The expression levels of nuclear factor-kappa B (NF-κB) p65 and Toll-like receptor 4 (TLR4) in uterine tissues were detected by immunohistochemical method. After Kangfuxiaomi suppository treatment, the vulva inflammation score and histopathological score of PID rats showed a tendency to decrease. Serum IL-8, TNF-α, CRP, and MDA levels were reduced, while SOD levels were significantly increased. Levels of IL-6, IL-2, and COX-2 in cervical tissues were somewhat decreased, and PGE2 and IL-1ß levels in uterine tissue were significantly decreased. Moreover, the levels of NF-κB p65 and TLR4 protein expression were also decreased. These findings demonstrated the therapeutic effect of Kangfuxiaomi suppository in PID rats. The underlying mechanism may involve enhanced antioxidant capacity and decreased secretion of proinflammatory factors via the NF-κB/TLR4 signaling pathway.

Harnessing the Therapeutic Potential of Ginsenoside Rd for Activating SIRT6 in Treating a Mouse Model of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent global condition and a common precursor to liver cancer, yet there is currently no specific medication available for its treatment. Ginseng, renowned for its medicinal and dietary properties, has been utilized in NAFLD management, although the precise underlying mechanism remains elusive. To investigate the effectiveness of ginsenoside Rd, we employed mouse and cell models to induce NAFLD using high-fat diets, oleic acid, and palmitic acid. We explored and confirmed the specific mechanism of ginsenoside Rd-induced hepatic steatosis through experiments involving mice with a liver-specific knockout of SIRT6, a crucial protein involved in metabolic regulation. Our findings revealed that administration of ginsenoside Rd significantly reduced the inflammatory response, reactive oxygen species (ROS) levels, lipid peroxide levels, and mitochondrial stress induced by oleic acid and palmitic acid in primary hepatocytes, thereby mitigating excessive lipid accumulation. Moreover, ginsenoside Rd administration effectively enhanced the mRNA content of key proteins involved in fatty acid oxidation, with a particular emphasis on SIRT6 and its target proteins. We further validated that ginsenoside Rd directly binds to SIRT6, augmenting its deacetylase activity. Notably, we made a significant observation that the protective effect of ginsenoside Rd against hepatic disorders induced by a fatty diet was almost entirely reversed in mice with a liver-specific SIRT6 knockout. Our findings highlight the potential therapeutic impact of Ginsenoside Rd in NAFLD treatment by activating SIRT6. These results warrant further investigation into the development of Ginsenoside Rd as a promising agent for managing this prevalent liver disease.

Antioxidative effect of Periplaneta americana extract on dextran sulfate sodium-induced ulcerative colitis through activation of the Nrf2 signal.

CONTEXT: Periplaneta americana L. (Blattariae) is used as a treatment for ulcerative colitis (UC) in Chinese traditional medicine. OBJECTIVE: To evaluate the antioxidative activity of P. americana whole body ethanol extract (PAE) on UC mice and whether glycine and proline could be used for quality control and identification of active PAE components. MATERIALS AND METHODS: NCM460 cells were pre-incubated in PAE, AA-L, AA-M, and AA-H (low, high and medium doses of proline and glycine), then treated with recombinant human TNF-α. The glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen (ROS) levels were determined. UC mice were fed with water containing 2.5% dextran sulfate sodium (w/v) after pre-treatment with different doses of PAE once a day for 7 days. ELISA was used to detect the concentrations of inflammation-related factors. Colon tissues of mice were used to detect the activity of myeloperoxidase (MPO), GSH, MDA, and SOD. Histological changes were observed using H&E staining. The expression of target proteins was determined by western blotting. RESULTS: In vivo, PAE treatment reduced the DAI score more than in the model group, restoring the weight and colonic length. It also reduced the severity of colitis, and inflammatory and oxidative stress intensity. Additionally, western blotting showed that the Nrf2 pathway was activated by PAE. In vitro PAE significantly alleviated TNF-α-induced cell damage and oxidative stress, which is relevant to the activation of the Nrf2 pathway. CONCLUSIONS: PAE may relieve oxidative stress through the Nrf2 signaling pathway, and proline and glycine may be used as active components of its antioxidative stress activity.

Frequency-dependent and time-variant alterations of neural activity in post-stroke depression: A resting-state fMRI study.

BACKGROUND: Post-stroke depression (PSD) is one of the most frequent psychiatric disorders after stroke. However, the underlying brain mechanism of PSD remains unclarified. Using the amplitude of low-frequency fluctuation (ALFF) approach, we aimed to investigate the abnormalities of neural activity in PSD patients, and further explored the frequency and time properties of ALFF changes in PSD. METHODS: Resting-state fMRI data and clinical data were collected from 39 PSD patients (PSD), 82 S patients without depression (Stroke), and 74 age- and sex-matched healthy controls (HC). ALFF across three frequency bands (ALFF-Classic: 0.01-0.08 Hz; ALFF-Slow4: 0.027-0.073 Hz; ALFF-Slow5: 0.01-0.027 Hz) and dynamic ALFF (dALFF) were computed and compared among three groups. Ridge regression analyses and spearman's correlation analyses were further applied to explore the relationship between PSD-specific alterations and depression severity in PSD. RESULTS: We found that PSD-specific alterations of ALFF were frequency-dependent and time-variant. Specially, compared to both Stroke and HC groups, PSD exhibited increased ALFF in the contralesional dorsolateral prefrontal cortex (DLPFC) and insula in all three frequency bands. Increased ALFF in ipsilesional DLPFC were observed in both slow-4 and classic frequency bands which were positively correlated with depression scales in PSD, while increased ALFF in the bilateral hippocampus and contralesional rolandic operculum were only found in slow-5 frequency band. These PSD-specific alterations in different frequency bands could predict depression severity. Moreover, decreased dALFF in contralesional superior temporal gyrus were observed in PSD group. LIMITATIONS: Longitudinal studies are required to explore the alterations of ALFF in PSD as the disease progress. CONCLUSIONS: The frequency-dependent and time-variant properties of ALFF could reflect the PSD-specific alterations in complementary ways, which may assist to elucidate underlying neural mechanisms and be helpful for early diagnosis and interventions for the disease.

Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies.

The ever-increasing prevalence of noncommunicable diseases (NCDs) represents a major public health burden worldwide. The most common form of NCD is metabolic diseases, which affect people of all ages and usually manifest their pathobiology through life-threatening cardiovascular complications. A comprehensive understanding of the pathobiology of metabolic diseases will generate novel targets for improved therapies across the common metabolic spectrum. Protein posttranslational modification (PTM) is an important term that refers to biochemical modification of specific amino acid residues in target proteins, which immensely increases the functional diversity of the proteome. The range of PTMs includes phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, glycosylation, palmitoylation, myristoylation, prenylation, cholesterylation, glutathionylation, S-nitrosylation, sulfhydration, citrullination, ADP ribosylation, and several novel PTMs. Here, we offer a comprehensive review of PTMs and their roles in common metabolic diseases and pathological consequences, including diabetes, obesity, fatty liver diseases, hyperlipidemia, and atherosclerosis. Building upon this framework, we afford a through description of proteins and pathways involved in metabolic diseases by focusing on PTM-based protein modifications, showcase the pharmaceutical intervention of PTMs in preclinical studies and clinical trials, and offer future perspectives. Fundamental research defining the mechanisms whereby PTMs of proteins regulate metabolic diseases will open new avenues for therapeutic intervention.

Uterine torsion complicated by severe placental abruption in the second trimester: a case report and literature review.

BACKGROUND: Uterine torsion is a rare obstetric event that can occur during pregnancy and is difficult to diagnose. Its occurrence may lead to serious adverse pregnancy outcomes. CASE INTRODUCTION: The patient was a 33-year-old woman at 30+ 5 weeks' gestation with a singleton pregnancy. The pregnancy course, including fetal growth, and prenatal examinations were regular. Except for a small amount of vaginal bleeding in early pregnancy and treatment with progesterone, there were no prenatal abnormalities, and the patient denied any trauma or sexual history. The patient was admitted to the emergency department with persistent severe pain in the lower abdomen and slight vaginal bleeding during night sleep. Abdominal pain started two hours prior to admission and was accompanied by nausea, vomiting, and dizziness. Examination revealed positive abdominal tenderness, high uterine tone, and no significant intermittent period of uterine contractions, and measurement of the fetal heart rate by means of the nonstress test revealed a rate of 60 beats per minute. Therefore, placental abruption was highly suspected. Subsequently, an emergency cesarean section was performed under general anesthesia. The newborn boy, with Apgar scores of 0-3-4 after birth and weighing 1880 g, was transferred to the neonatal intensive care unit (NICU) and died two days later due to ineffective rescue. After the uterine incision was sutured, the examination revealed that the uterine incision was located on the posterior wall of the uterus, and the uterus was twisted 180° to the right. The diagnosis after cesarean section was 180° uterine torsion to the right, severe placental abruption, and severe neonatal asphyxia. On the fifth day after surgery, the patient recovered and was discharged from the hospital. CONCLUSIONS: Posterior uterine incision cesarean section may be performed in unexpected circumstances and is also feasible as a safe option for resetting if torsion is not complete. Abdominal pain during pregnancy is less likely to be diagnosed as uterine torsion, which often leads to premature birth, fetal asphyxia, placental abruption, and even perinatal death. Therefore, for abdominal pain during pregnancy, obstetricians should consider the possibility of uterine torsion.

Deterioration in glycemic control on schooldays among children and adolescents with type 1 diabetes: A continuous glucose monitoring-based study.

Background: To investigate the effect of school life by comparing the glycemic control between holidays and schooldays in children and adolescents with type 1 diabetes (T1D). Methods: This observational study enrolled school-aged students with T1D (aged 6-19) from September 2019 to July 2021. Continuous glucose monitoring (CGM) records were processed and divided into holidays and schooldays. Other information was collected via questionnaires. We compared the results using paired T-test, Wilcoxon paired test and logistic regression analysis. Results: 78 paticipants were included (40 boys, mean age 9.95 years). A total of 142,945 h of CGM data were analyzed. Overall, TIR (3.9-7.8 mmol/L) during holidays was better than schooldays [56.97 (SD 15.03) vs. 55.87 (15.06), %, p = 0.039]. On nocturnal (0-6 am) glycemic fluctuation, TIR was longer in children aged 6-10 [60.54 (17.40) vs. 56.98 (SD 16.32), %, p = 0.012] during holiday and TAR (7.8 mmol/L) was shorter [31.54 (17.54) vs. 35.54 (16.95), %, p = 0.013], compared with schooldays. In adolescents aged 10-19 years, TAR was also significantly shorter during holidays. Stratified analysis showed that girls, patients with longer duration, and insulin pump users had more pronounced worsening of nighttime glycemia on schooldays. Logistic regression analysis showed that girls had higher risk of worse nocturnal glycemic control [3.26, 95% CI: (1.17, 9.72), p = 0.027] and nocturnal hyperglycemia [OR = 2.95, 95% CI: (1.08, 8.56), p = 0.039], compared to boys. Conclusions: Children and adolescents with T1D were found to have worse glycemic control in nighttime during schooldays.

CCRT and aerobic exercise: a randomised controlled study of processing speed, cognitive flexibility, and serum BDNF expression in schizophrenia.

Computerised cognitive remediation therapy (CCRT) and aerobic exercise are often used to rehabilitate social functioning in patients with schizophrenia. However, there is limited knowledge regarding the effects of CCRT combined with aerobic exercise on cognitive function and brain-derived neurotrophic factor (BDNF) levels in patients with schizophrenia and cognitive impairment. Ninety-six patients with schizophrenia and cognitive impairment were included in this study and randomly divided into control, aerobic exercise (AE), and CCRT combined with aerobic exercise (CAE) groups. Changes in processing speed and cognitive flexibility at week 8 were evaluated as primary and secondary cognitive outcomes using the Trail Making Test: Part A, the Brief Assessment of Cognition in Schizophrenia: Symbol Coding Test, and the Stroop Colour-Word Test. Positive and Negative Syndrome Scale (PANSS) scores and serum BDNF expression were determined as other secondary outcomes. The CAE group showed significantly better performance in terms of changes in processing speed and cognitive flexibility than the control and AE groups at week 8 (p < 0.05); however, no significant improvements in processing speed and cognitive flexibility were found between the control and AE groups. The CAE group showed significant improvements in the PANSS negative symptoms than the control group at week 8 (p < 0.05), but the AE group showed no significant difference in the changes of PANSS negative symptoms when compared with the other two groups. The CAE group and AE group showed a greater increase in serum BDNF levels than the control group (p < 0.01), but there was no significant difference in serum BDNF expression between the CAE group and AE group. In conclusion, 8-week CCRT combined with aerobic exercise may improve some cognitive performance and negative symptoms in patients with schizophrenia. Aerobic exercise may have an immediate effect on serum BDNF levels rather than cognitive function.

Ginsenoside Rc Modulates SIRT6-NRF2 Interaction to Alleviate Alcoholic Liver Disease.

Alcoholic liver disease (ALD) is a serious worldwide health problem. Ginsenoside Rc is a major active ingredient isolated from Panax ginseng, whose pharmacological effects counteract oxidative stress, inflammation, and lipid accumulation. However, it is still unclear whether ginsenoside Rc might exert beneficial effects on alcohol-induced liver injury. To this aim, mice primary hepatocytes (MPHs) were challenged with alcohol to test ginsenoside Rc's effects on their intracellular alcohol metabolism. C57BL/6J mice or SIRT6alb-/- mice were chronically fed a diet with added alcohol or given a single gavage of alcohol with or without ginsenoside Rc. Analyses of alcohol metabolism, oxidative stress, inflammation, lipid metabolism, and RNaseq expression were conducted to explore potential targets exploited by ginsenoside Rc to protect against ALD. Our results showed that ginsenoside Rc attenuated alcohol-induced liver injury by regulating oxidative stress, inflammation, and lipid accumulation both in vivo and in vitro. Ginsenoside Rc did increase the deacetylase activity of SIRT6, thereby lowering acetylated NRF2 levels, which elevated NRF2's stability, and subsequently exerting an antioxidant effect. In keeping with this, the hepatic knockout of SIRT6 almost abolished the hepatoprotective effects of ginsenoside Rc against ALD. Therefore, our results suggest that ginsenoside Rc attenuated hepatocytes' damage and oxidative stress in ALD by up-regulating the SIRT6/NRF2 pathway. Hence, ginsenoside Rc may be a promising drug to treat or relieve ALD.

Comparison of machine learning models for predicting the risk of breast cancer-related lymphedema in Chinese women.

Objective: Predictive models for the occurrence of cancer symptoms by using machine learning (ML) algorithms could be used to aid clinical decision-making in order to enhance the quality of cancer care. This study aimed to develop and validate a selection of classification models that used ML algorithms to predict the occurrence of breast cancer-related lymphedema (BCRL) among Chinese women. Methods: This was a retrospective cohort study of consecutive cases that had been diagnosed with breast cancer, stages I-IV. Forty-eight variables were grouped into five feature sets. Five classification models with ML algorithms were developed, and the models' performance and the variables' relative importance were assessed accordingly. Results: Of 370 eligible female participants, 91 had BCRL (24.6%). The mean age of this study sample was 49.89 (SD â€‹= â€‹7.45). All participants had had breast cancer surgery, and more than half of them had had a modified radical mastectomy (n â€‹= â€‹206, 55.5%). The mean follow-up time after breast cancer surgery was 28.73 months (SD â€‹= â€‹11.71). Most of the tumors were either stage I (n â€‹= â€‹49, 31.2%) or stage II (n â€‹= â€‹252, 68.1%). More than half of the sample had had postoperative chemotherapy (n â€‹= â€‹227, 61.4%). Overall, the logistic regression model achieved the best performance in terms of accuracy (91.6%), precision (82.1%), and recall (91.4%) for BCRL. Although this study included 48 predicting variables, we found that the five models required only 22 variables to achieve predictive performance. The most important variable was the number of positive lymph nodes, followed in descending order by the BCRL occurring on the same side as the surgery, a history of sentinel lymph node biopsy, a dietary preference for meat and fried food, and an exercise frequency of less than three times per week. These factors were the most influential predictors for enhancing the ML models' performance. Conclusions: This study found that in the ML training dataset, the multilayer perceptron model and the logistic regression model were the best discrimination models for predicting the outcome of BCRL, and the k-nearest neighbors and support vector machine models demonstrated good calibration performance in the ML validation dataset. Future research will need to use large-sample datasets to establish a more robust ML model for predicting BCRL deeply and reliably.

Comparative Proteomic Analysis of Liver Tissues and Serum in db/db Mice.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) affects one-quarter of individuals worldwide. Liver biopsy, as the current reliable method for NAFLD evaluation, causes low patient acceptance because of the nature of invasive sampling. Therefore, sensitive non-invasive serum biomarkers are urgently needed. RESULTS: The serum gene ontology (GO) classification and Kyoto encyclopedia of genes and genomes (KEGG) analysis revealed the DEPs enriched in pathways including JAK-STAT and FoxO. GO analysis indicated that serum DEPs were mainly involved in the cellular process, metabolic process, response to stimulus, and biological regulation. Hepatic proteomic KEGG analysis revealed the DEPs were mainly enriched in the PPAR signaling pathway, retinol metabolism, glycine, serine, and threonine metabolism, fatty acid elongation, biosynthesis of unsaturated fatty acids, glutathione metabolism, and steroid hormone biosynthesis. GO analysis revealed that DEPs predominantly participated in cellular, biological regulation, multicellular organismal, localization, signaling, multi-organism, and immune system processes. Protein-protein interaction (PPI) implied diverse clusters of the DEPs. Besides, the paralleled changes of the common upregulated and downregulated DEPs existed in both the liver and serum were validated in the mRNA expression of NRP1, MUP3, SERPINA1E, ALPL, and ALDOB as observed in our proteomic screening. METHODS: We conducted hepatic and serum proteomic analysis based on the leptin-receptor-deficient mouse (db/db), a well-established diabetic mouse model with overt obesity and NAFLD. The results show differentially expressed proteins (DEPs) in hepatic and serum proteomic analysis. A parallel reaction monitor (PRM) confirmed the authenticity of the selected DEPs. CONCLUSION: These results are supposed to offer sensitive non-invasive serum biomarkers for diabetes and NAFLD.

Piezo-Photocatalytic Synergy in BiFeO3 @COF Z-Scheme Heterostructures for High-Efficiency Overall Water Splitting.

Solar-driven overall water splitting is an ideal way to generate renewable energy while still challenging. For the first time, this work combined covalent organic frameworks (COFs) and piezoelectric material by covalent linkages to form Z-scheme core@shell heterostructure for overall water splitting. Benefiting from the synergistic effect between the polarized electric field and photo-generated charges, as well as the precise adjustment of shell thickness, the carrier separation and utilization efficiency is greatly improved. The optimal BiFeO3 @TpPa-1-COF photocatalyst revealed hydrogen (H2 ) and oxygen (O2 ) production rates of 1416.4 and 708.2 µmol h-1 g-1 under the excitation of ultrasonication coupled with light irradiation, which is the best performance among various piezo- and COF-based photocatalysts. This provides a new sight for the practical application of highly efficient photocatalytic overall water splitting.

Effects of wasp venom on venous thrombosis in rats.

Objectives: This study aimed to investigate the potential effects of wasp venom (WV) from Vespa magnifica on antithrombosis in rats with inferior vena cava (IVC) thrombosis. Materials and Methods: The thrombosis rat model was established by improving the IVC stenosis, in which rats were subjected to IVC ligation for 75 min. Rats were administered argatroban (IP) or WV (s.c.) for 4 hr after IVC thrombosis. The weight, inhibition rate, and pathological morphology of the thrombosis induced by IVC ligation and the variation in four coagulation parameters, coagulation factors, and CD61+CD62P+ were simultaneously determined in IVC rats. Results: The thrombus formed as a result of IVC ligation was stable. Compared with the control group, the weight of the thrombus was significantly reduced in the argatroban group. Thrombus weight was reduced by treatment with 0.6, 0.2, and 0.05 mg/kg WV, with inhibition rates of 52.19%, 35.32%, and 28.98%, respectively. Inflammatory cells adhered to and infiltrated the vessel wall in the IVC group more than in the sham group. However, the pathological morphology and CD61+CD62P+ of the WV treatment groups tended to be normal. Conclusion: We improved the model of IVC thrombosis to be suitable for evaluation of antithrombotic drugs. Our findings demonstrated that WV could inhibit IVC thrombosis associated with reducing coagulation factors V and CD61+CD62p expression in rats.