Huanglian-Jiedu decoction promotes adipose thermogenesis in obese mice by suppressing the expression of HDAC3.

ETHNOPHARMACOLOGICAL RELEVANCE: Huanglian Jiedu Decoction (HLJDD) is an ancient formula of traditional Chinese medicine that is commonly utilized in a range of disorders, and it has been shown to have pharmacological effects on glucose and lipid metabolism. However, the specific mechanism of HLJDD for the treatment of obesity and related metabolic disorders remains to be further investigated. AIM OF THE STUDY: It has been thought that encouraging adipose thermogenesis to raise the body's energy expenditure is a useful tactic for improving metabolic abnormalities and losing weight. In this study, we investigated the ability and underlying mechanisms of HLJDD to regulate fat cell thermogenesis to improve energy expenditure in obesity. METHODS: The obese mouse model was established on a high-fat diet for 12 weeks. All mice were divided into NC, HFD, HFD with HLJDD of a low dose (2.25 g/kg/d), and HFD with HLJDD of a high dose (4.5 g/kg/d) groups and kept for 4 weeks. In vitro experiments were conducted to evaluate the effects of 5% and 10% HLJDD-containing serum on differentiated 3T3-L1 cells and HDAC3-knocking-down 3T3-L1 cells. RESULTS: The results showed that HLJDD treatment significantly improved glucose and insulin tolerance and decreased the adipocyte radius of WATs, as well as increased energy consumption in obese mice. Besides, HLJDD treatment dramatically increased the levels of thermogenic genes UCP-1 and PGC-1α while suppressing HDAC3 levels in WATs and 3T3-L1 adipocytes. Importantly, the effects of HLJDD on PGC-1α and UCP-1 were blocked in HDAC3 knockdown adipocytes. CONCLUSIONS: Therefore, these results suggest that HLJDD enhanced adipose thermogenesis and improved energy expenditure by inhibiting HDAC3, thereby increasing UCP-1 and PGC-1α expression. These findings amplified the mechanisms of HLJDD and its potential to treat obesity and related metabolic disorders.

Urban-Rural Differences in the Association of eHealth Literacy With Medication Adherence Among Older People With Frailty and Prefrailty: Cross-Sectional Study.

Background: With advances in science and technology and improvements in health literacy, more studies have focused on frailty prevention by promoting medication adherence, emphasizing the role of eHealth literacy. However, the association between eHealth literacy and medication adherence in frail older adults has not been well studied, and it is unknown whether urban-rural differences exist in this relationship. Objective: This study aims to examine the relationship between eHealth literacy and medication adherence in older people with different frailty statuses, emphasizing variations between rural and urban areas. Methods: Between November and December 2020, a total of 4218 urban and rural community members (aged ≥60 years) in China were recruited as participants using a multistage random sampling method. A face-to-face structured questionnaire survey was conducted to collect information on demographic characteristics, eHealth literacy (consisting of application, evaluation, and decision dimensions), and medication adherence. eHealth literacy was assessed using the Chinese version of the eHealth Literacy Scale developed by Norman and Skinner, and medication adherence was measured using the 4-item Morisky scale. We used a general descriptive analysis and stratified logistic regression models to examine how eHealth literacy is linked to medication adherence and urban-rural differences. Results: There were 4218 respondents, of which 2316 (54.9%) lived in urban areas and 1902 (45.1%) in rural areas, respectively. After adjusting for potential confounders, among participants with prefrailty, eHealth literacy was associated with medication adherence in urban areas in terms of less application (adjusted odds ratio [AOR] 1.16, 95% CI 0.82-1.63), less evaluation (AOR 1.29, 95% CI 0.92-1.81), and less decision ability (AOR 1.20, 95% CI 0.86-1.68); eHealth literacy was linked with medication adherence in the rural areas in terms of less application (AOR 1.10, 95% CI 0.56-2.13), less evaluation (AOR 1.05, 95% CI 0.61-1.79), and less decision ability (AOR 1.10, 95% CI 0.64-1.90). Among frail participants, less eHealth literacy (AOR 0.85, 95% CI 0.48-1.51), along with its dimensions, including less application (AOR 0.85, 95% CI 0.47-1.54), evaluation (AOR 0.89, 95% CI 0.50-1.57), and decision ability (AOR 0.99, 95% CI 0.55-1.76), were associated with medication adherence in urban areas; less eHealth literacy (AOR 0.89, 95% CI 0.48-1.65), along with its dimensions, including less application (AOR 1.23, 95% CI 0.62-2.44), evaluation (AOR 0.98, 95% CI 0.53-1.82), and decision ability (AOR 0.90, 95% CI 0.49-1.67), were associated with medication adherence in rural areas. Conclusions: The results of this study suggest that there is an association between eHealth literacy and medication adherence among older people with frailty and prefrailty. To promote medication adherence, eHealth literacy can be helpful in tailoring interventions.

Novel hypothalamic pathways for metabolic effects of spexin.

One of the main underlying etiologies of type 2 diabetes (T2DM) is insulin resistance, which is most frequently caused by obesity. Notably, the deregulation of adipokine secretion from visceral adiposity has been identified as a crucial characteristic of type 2 diabetes and obesity. Spexin is an adipokine that is released by many different tissues, including white adipocytes and the glandular stomach, and is negatively connected with the state of energy storage. This peptide acts through GALR2/3 receptors to control a wide range of metabolic processes, including inflammation, browning, lipolysis, energy expenditure, and eating behavior. Specifically, spexin can enter the hypothalamus and regulate the hypothalamic melanocortin system, which in turn balances energy expenditure and food intake. This review examines recent advances and the underlying mechanisms of spexin in obesity and T2DM. In particular, we address a range of topics from basic research to clinical findings, such as an analysis of the possible function of spexin in the hypothalamic melanocortin response, which involves reducing energy intake and increasing energy expenditure while also enhancing insulin sensitivity and glucose tolerance. Gaining more insight into the mechanisms that underlie the spexin system's control over energy metabolism and homeostasis may facilitate the development of innovative treatment approaches that focus on combating obesity and diabetes.

18F-Fluorodeoxyglucose positron emission tomography/computed tomography imaging reveals the protective effect of docosahexaenoic acid on glucose metabolism by reducing brain 27-hydroxycholesterol.

Total cholesterol (TC) and the cholesterol oxidation product 27-hydroxycholesterol (27-OHC) are both increased in the elderly. Accumulating evidence has linked 27-OHC to glucose metabolism in the brain, while docosahexaenoic acid (DHA) has been shown to positively regulate the 27-OHC levels. However, it is unclear whether DHA may affect glucose metabolism in the brain by regulating 27-OHC levels. In this study, we hypothesized that DHA supplementation would modulate TC levels and reduce 27-OHC levels, thereby improving brain glucose metabolism in SAMP8 mice. The mice were assigned into the Control group and DHA dietary supplementation group. The study evaluated cholesterol levels, 27-OHC levels, and glucose metabolism in the brain. The results showed that DHA supplementation decreased serum levels of TC, low-density lipoprotein cholesterol (LDL-C), and increased levels of high-density lipoprotein cholesterol (HDL-C); and improved the glucose-corrected standardized uptake value of cortex, hippocampus, and whole brain regions in SAMP8 mice. In conclusion, supplementation of DHA could regulate the cholesterol composition and reduce the level of 27-OHC, thereby improving brain glucose metabolism in SAMP8 mice.

Effects of a food supplement containing phosphatidylserine on cognitive function in Chinese older adults with mild cognitive impairment: A randomized double-blind, placebo-controlled trial.

BACKGROUND: Phosphatidylserine (PS) and α-Linolenic acid (ALA), are positively associated with cognitive function, but their combination effects and possible mechanisms remain unclear. We aimed to explore the effects on cognition and potential mechanism of the supplements. METHODS: This randomized, double-blind, placebo-controlled trial recruited 190 MCI patients in Tianjin, China, and randomly assigned in intervention group and placebo group. Each group consumed two capsules every day for 12 months. Each capsule for intervention group contains 144 mg ALA, 31.5 mg PS and 3.6 mg Ginkgo total flavonoids as main functional components, with 0.48 mg Vitamin B1 (as thiamine hydrochloride), 0.48 mg Vitamin B6 (as pyridoxine hydrochloride) and 90 µg folic acid as supplement. Capsules for placebo group were identical but contain no active ingredients. Cognitive function, serum n-3 polyunsaturated fatty acids (PUFAs) and neurotransmitters were assessed at baseline and 12 months. Linear mixed effects model and causal mediation analysis were conducted to explore the effects and potential mechanism of the intervention. RESULTS: A total of 190 participants (mean [SD] age, 67.95 [5.62] years; 70 (36.8 %) male and 120 (63.2 %) female) were randomized to the placebo group (n = 95) and intervention group (n = 95). Compared with placebo group, the intervention group had statistically significant improvements in arithmetic testing (ß, 0.688; 95 % CI, 0.103-1.274), the similarity test (ß, 1.070; 95 % CI, 0.472-1.667) and short-term memory (ß, 0.600; 95 % CI, 0.399-0.800). Besides, the intervention group had statistically significant increases in serum ALA (ß, 1.620; 95 % CI, 0.967-2.265), DHA (ß, 2.797; 95 % CI, 1.075-4.532), EPA (ß, 1.472; 95 % CI, 0.296-2.643), acetylcholine (ß, 0.441; 95 % CI, 0.415-0.468), GABA (ß, 0.009; 95 % CI, 0.001-0.016) and 5-HT (ß, 0.160; 95 % CI, 0.081-0.238) compared to the placebo group. And the intervention may improve short-term memory by increasing serum ALA levels (average causal mediation effect = 0.132, 95 % CI, 0.053-0.225) with 19.7 % mediation proportion. CONCLUSIONS: This food supplement containing phosphatidylserine could improve different cognitive functions of MCI patients, especially short-term memory, and increase serum n-3 PUFAs and neurotransmitters levels. Serum ALA level might play a mediation role.

External-beam radiotherapy after transarterial chemoembolization (TACE) versus TACE alone for treatment of inoperable HCC: A randomized phase III trial.

PURPOSE: To compare the outcomes of transarterial chemoembolization (TACE) alone with those of TACE combined with external-beam radiotherapy (EBRT) in patients with hepatocellular carcinoma (HCC) in a multicenter randomized study. METHODS AND MATERIALS: From 2017 to 2022, 74 HCC patients with tumors confined to the liver without vascular invasion were treated with either TACE only (TACE group, 39 patients) or TACE combined with EBRT (TACE+EBRT group, 35 patients). The primary outcome measured was overall survival (OS). Secondary outcomes included progression-free survival (PFS), local tumor control (LC), and the assessment of treatment-related toxicity. RESULTS: Due to slow accrual, the trial was closed prematurely after enrolling 74 patients. All patients received two cycles of TACE before randomization. The TACE and TACE+EBRT groups showed comparable patient and tumor characteristics. The TACE group underwent an median of 3 TACE cycles, and the TACE+EBRT group received two cycles of TACE and a median of 5,500 cGy in 15 fractions. For the TACE group, the median LC duration was 13.1 months, while for the TACE+EBRT group, the median LC was not achieved (P<0.001). The PFS was recorded at 11.6 months in the TACE group compared to 15.4 months in the TACE+EBRT group (P=0.072). The median OS reached 36.8 months for the TACE group and extended to 47.1 months for the TACE+EBRT group (P=0.654). The incidence of toxicity was comparable between both groups. CONCLUSIONS: Although the number of patients enrolled in this clinical trial did not meet expectations. TACE combined with EBRT was shown to be more effective than TACE alone in improving local control (LC) without increasing toxicity, while PFS and OS was slightly improved. TACE+EBRT can be used as a standard treatment option for patients with inoperable but confined intrahepatic HCC.

Exploring the impact of metabolites function on heart failure and coronary heart disease: insights from a Mendelian randomization (MR) study.

BACKGROUND: Heart failure (HF) and coronary heart disease (CHD) are major causes of morbidity and mortality worldwide. While traditional risk factors such as hypertension, diabetes, and smoking have been extensively studied, the role of metabolite functions in the development of these cardiovascular conditions has been less explored. This study employed a Mendelian randomization (MR) approach to investigate the impact of metabolite functions on HF and CHD. METHODS: To assess the causal impacts of specific metabolite risk factors on HF and CHD, this study utilized genetic variants associated with these factors as instrumental variables. Comprehensive genetic and phenotypic data from diverse cohorts, including genome-wide association studies (GWAS) and cardiovascular disease registries, were incorporated into the research. RESULTS: Our results encompass 61 metabolic cell phenotypes, with ten providing strong evidence of the influence of metabolite functions on the occurrence of HF and CHD. We found that elevated levels of erucate (22:1n9), lower levels of α-tocopherol, an imbalanced citrulline-to-ornithine ratio, elevated γ-glutamyl glycine levels, and elevated 7-methylguanine levels independently increased the risk of these cardiovascular conditions. These findings were consistent across different populations and robust to sensitivity analyses. CONCLUSION: This MR study provides valuable insights into the influence of metabolite functions on HF and CHD. However, further investigation is needed to fully understand the precise mechanisms by which these metabolite factors contribute to the onset of these conditions. Such research could pave the way for the development of targeted therapeutic strategies.

Combination of circulating tumor cells, lncRNAs and DNA methylation for the diagnosis of endometrial carcinoma.

Endometrial carcinoma (EC) is one of the most common gynecological malignant neoplasms, the prognosis of which is strongly related to the time of diagnosis, with an earlier diagnosis leading to a better prognosis. Therefore, effective diagnostic indicators and methods are needed to ensure early detection. The present study explored the following in EC: Circulating tumor cells (CTCs); the long noncoding RNAs (lncRNAs) RP4-616B8.5, RP11-389G6.3 and carboxy-terminal domain (CTD)-2377D24.6; and the methylation of cysteine dioxygenase type 1 (CDO1) and CUGBP Elav-like family member 4 (CELF4). In total, 85 patients, including 71 with EC, and 14 without EC (NO-EC) but with uterine fibroids or polyps, were included in the present study. In total, 46 patients with EC and 8 NO-EC patients underwent CTC detection. In the evaluation of the EC vs. NO-EC groups, the results showed that the CTC-positive rate of the EC group was 80.43% and that the area under the curve (AUC) value of CTCs was 0.8872 (P=0.0098). A total of 35 patients with EC and 14 NO-EC patients underwent detection of the RP4-616B8.5, RP11-389G6.3 and CTD-2377D24.6 lncRNAs. When the levels of the three lncRNAs RP4-616B8.5, RP11-389G6.3 and CTD-2377D24.6 were compared between the EC and NO-EC groups, they were higher in the EC group; the P-values were 0.0002, 0.0001 and <0.0001, respectively, and the AUC values were 0.8184, 0.8347 and 0.8265, respectively. In addition, a total of 35 patients with EC and 8 NO-EC patients underwent CDO1 and CELF4 DNA methylation analysis. The positive rates of the methylated genes CDO1 and CELF4 were 20% (7/35) and 5.71% (2/35), and the P-values of the comparisons between the EC and NO-EC groups were 0.1748 and 0.5004, respectively; the AUC values were 0.6000 and 0.5286. Furthermore, the combination of CTCs, and lncRNAs RP4-616B8.5, RP11-389G6.3 and CTD-2377D24.6 exhibited high performance in the detection of EC (AUC=0.9375).

Research on the Stability and Response of Food Packaging Polystyrene Resin Materials to γ-ray Irradiation.

Radiation stability of food packaging materials is the key to ensuring food quality. In this study, 60Co γ-ray was selected to investigate the radiation resistance of food packaging polystyrene (PS) resin material, although the FTIR analysis showed that the intensity of several peaks decreased slightly. The gel permeation chromatography (GPC) results displayed that the value of peak molecular weight (Mp) of PS went from 2.68 × 105 g/mol down to 2.22 × 105 g/mol. Moreover, the residual mass (Res) of PS increased from 7.208 to 30.23%, indicating that the tendency of coking of PS was stronger after irradiation. In addition, the peak intensities of the three main pyrolysis products -CH2-, CH4, and CH2=CH2 increased by more than 30% compared to unirradiated PS, and a large number of them were detected in the whole pyrolysis process. Moreover, mechanical property analysis finds that both breaking strength and elongation data increased before irradiation dose of 50 kGy, then, decreased sharply with further increase of irradiation dose. The theoretical bond order analysis confirmed that the tertiary carbon bond attaching the benzene ring had the lowest bond energy. This study can give helpful guidance when using PS for food packing materials.

Novel α-glucosidase Inhibitors Designed as Type 2 Diabetes Drugs by QSAR, Molecular Docking and Molecular Dynamics Simulation Methods.

Diabetes mellitus is a globally prevalent disease of significant concern. Alpha-glucosidase has emerged as a prominent target for the treatment of type 2 diabetes. In this study, 39 α-glucosidase inhibitors (AGIs) of tetrahydrobenzo[b]thiophene-2-ylurea derivatives to establish a stable and valid Topomer CoMFA model, with a cross-validation coefficient (q²) of 0.766 and a non-cross-validation coefficient (r²) of 0.960. Subsequently, the ZINC15 database was used to screen the fragments, based on which 13 novel inhibitor molecules with theoretically potentially high activity were designed. Molecular docking and molecular dynamics simulations to understand the binding status of the inhibitor molecules to the target proteins showed that amino acids ASP215, GLN279 and ARG442 may form hydrogen bonds with the ligands and therefore enhance the inhibitory effect of the small molecules. Additionally, MM/PBSA calculations suggest that the newly designed molecules demonstrate more stable binding modes, and these newly designed molecules showed good ADMET properties with potential as AGIs. The findings would provide valuable guidance and a theoretical foundation for the design and development of novel AGIs.

Effect of aberrant fructose metabolism following SARS-CoV-2 infection on colorectal cancer patients' poor prognosis.

Most COVID-19 patients have a positive prognosis, but patients with additional underlying diseases are more likely to have severe illness and increased fatality rates. Numerous studies indicate that cancer patients are more prone to contract SARS-CoV-2 and develop severe COVID-19 or even dying. In the recent transcriptome investigations, it is demonstrated that the fructose metabolism is altered in patients with SARS-CoV-2 infection. However, cancer cells can use fructose as an extra source of energy for growth and metastasis. Furthermore, enhanced living conditions have resulted in a notable rise in fructose consumption in individuals' daily dietary habits. We therefore hypothesize that the poor prognosis of cancer patients caused by SARS-CoV-2 may therefore be mediated through fructose metabolism. Using CRC cases from four distinct cohorts, we built and validated a predictive model based on SARS-CoV-2 producing fructose metabolic anomalies by coupling Cox univariate regression and lasso regression feature selection algorithms to identify hallmark genes in colorectal cancer. We also developed a composite prognostic nomogram to improve clinical practice by integrating the characteristics of aberrant fructose metabolism produced by this novel coronavirus with age and tumor stage. To obtain the genes with the greatest potential prognostic values, LASSO regression analysis was performed, In the TCGA training cohort, patients were randomly separated into training and validation sets in the ratio of 4: 1, and the best risk score value for each sample was acquired by lasso regression analysis for further analysis, and the fifteen genes CLEC4A, FDFT1, CTNNB1, GPI, PMM2, PTPRD, IL7, ALDH3B1, AASS, AOC3, SEPINE1, PFKFB1, FTCD, TIMP1 and GATM were finally selected. In order to validate the model's accuracy, ROC curve analysis was performed on an external dataset, and the results indicated that the model had a high predictive power for the prognosis prediction of patients. Our study provides a theoretical foundation for the future targeted regulation of fructose metabolism in colorectal cancer patients, while simultaneously optimizing dietary guidance and therapeutic care for colorectal cancer patients in the context of the COVID-19 pandemic.

Anti-bacterial effects, and metabolites derived from bifidobacterial fermentation of an exopolysaccharide of Cs-HK1 medicinal fungus.

This study was to investigate the antibacterial effects and metabolites derived from bifidobacterial fermentation of an exopolysaccharide EPS-LM produced by a medicinal fungus Cordyceps sinensis, Cs-HK1. EPS-LM was a partially purified polysaccharide fraction which was mainly composed of Man, Glc and Gal at 7.31:12.95:1.00 mol ratio with a maximum molecular weight of 360 kDa. After fermentation of EPS-LM in two bifidobacterial cultures, B. breve and B. longum, the culture digesta showed significant antibacterial activities, inhibiting the proliferation and biofilm formation of Escherichia coli. Based on untargeted metabolomic profiling of the digesta, the levels of short chain fatty acids, carboxylic acids, benzenoids and their derivatives were all increased significantly (p < 0.01), which probably contributed to the enhanced antibacterial activity by EPS-LM. Since EPS-LM was only slightly consumed for the bifidobacterial growth, it mainly stimulated the biosynthesis of bioactive metabolites in the bifidobacterial cells. The results also suggested that EPS-LM polysaccharide may have a regulatory function on the bifidobacterial metabolism leading to production of antibacterial metabolites, which may be of significance for further exploration.

A retrospective study of the anterolateral thigh perforator flap in the treatment of chronic osteomyelitis of the leg with skin defects.

Background: As a chronic inflammatory process, chronic osteomyelitis is caused by bacterial infections that lead to bone destruction. This disease is more common in patients with open fractures and those undergoing multiple surgical procedures after trauma. We aimed to provide a comprehensive overview and critical assessment of the therapeutic efficacy of the anterolateral thigh (ALT) perforator flap in the management of chronic osteomyelitis with dermatologic and soft tissue imperfections localized in the lower extremity. Methods: A retrospective analysis involving a cohort of 16 patients who underwent ALT perforator flap reconstruction for the management of chronic osteomyelitis in the calf region that manifested with integumentary deficiencies was conducted. Results: During the follow-up period spanning from 4 months to 2 years, all 16 patients who underwent ALT perforator flap transplantation exhibited flap viability. Among these cases, 15 patients made a full recovery from the infection and 1 patient had partial survival. Among the 15 cases, 2 patients developed vascular crisis (owing to venous thrombosis during surgical exploration). One patient had a relapse of the disease 1-year post-surgery. The success rate of this surgical method was 15/16, and the surgical complications included flap crisis, flap necrosis, delayed wound healing, and recurrence of infection. Conclusion: The ALT perforator flap, which can cover bone and soft tissues and effectively control infections, can be applied to the treatment of chronic osteomyelitis of the lower limbs with skin defects. Overall, the muscle flap fills the dead space and medullary cavity and skin flap covers the skin defect.

Recent Advances in Immunotherapy for Breast Cancer: A Review.

Breast cancer is one of the most common malignant tumors in women in the world, and its incidence is increasing year by year, which seriously threatens the physical and mental health of women. Triple negative breast cancer (TNBC) is a special molecular type of breast cancer in which estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 are negative. Compared with other molecular types of breast cancer, triple-negative breast cancer (TNBC) has high aggressiveness and metastasis, high recurrence rate, lack of effective therapeutic targets, and usually poor clinical treatment effect. Chemotherapy was the main therapeutic means used in the past. With the advent of the immune era, immunotherapy has made a lot of progress in the treatment of triple-negative breast cancer (TNBC), bringing new therapeutic hope for the treatment of triple-negative breast cancer. This review combines the results of cutting-edge medical research, mainly summarizes the research progress of immunotherapy, and summarizes the main treatment methods of triple-negative breast cancer (TNBC) immunotherapy, including immune checkpoint inhibitors, tumor vaccines, adoptive immunotherapy and the application of traditional Chinese and western medicine. It provides a new idea for the treatment of triple negative breast cancer (TNBC).

[Predictive value of plasma exosome count for the prognosis in septic patients].

OBJECTIVE: To investigate the predictive value of plasma exosome count for the prognosis of patients with sepsis. METHODS: A prospective observational study was conducted. The patients with sepsis admitted to intensive care unit (ICU) of Zhejiang Hospital from November 2020 to December 2021 were enrolled as the study subjects. On the 1st day of admission to the ICU, the patient's gender, age, underlying disease, infection site, mean arterial pressure (MAP) and severity scores were recorded, and venous blood was taken for detecting the blood routine, blood biochemistry, and procalcitonin (PCT), and arterial blood was taken for blood gas analysis, simultaneously, the patient's noradrenaline (NA) dosage was recorded. On the 1st, 3rd, 5th, and 7th day of ICU admission, plasma exosomes were extracted, and the number of exosomes was detected by nanoparticle tracking analyzer. The endpoint of observation was the death of the patient 28 days after admission to the ICU. The differences in baseline data and plasma exosome counts of patients with different 28-day prognosis were analyzed and compared. The Spearman correlation method was used to analyze the correlation between plasma exosome counts and other clinical indicators. Binary multivariate Logistic regression analysis was used to screen the 28-day death risk factors of septic patients. The receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive value of each index on the 28-day death of septic patients. The Kaplan-Meier method was used to analyze the 28-day survival curve. RESULTS: A total of 26 patients with sepsis were enrolled, of whom 21 survived and 5 died on the 28th day. Compared with the survival group, the patients in the death group had lower MAP, higher sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score, white blood cell count (WBC), cardiac troponin I (cTnI), and worse oxygenation. The plasma exosome count on the 1st day of ICU admission in the death group was significantly higher than that in the survival group (×1015/L: 16.96±9.11 vs. 5.20±2.42, P < 0.05). Subsequently, the plasma exosome counts in both groups continued to decrease, and there was no statistically significant difference between the two groups. Spearman correlation analysis showed that the plasma exosome count on the 1st day of ICU admission in septic patients was significantly positively correlated with SOFA score, APACHE II score, blood lactic acid (Lac), alanine aminotransferase (ALT) and NA dosage (r values were 0.572, 0.585, 0.463, 0.411, 0.696, all P < 0.05), and it significantly negatively correlated with MAP and oxygenation index (PaO2/FiO2; r values were -0.392 and -0.496, both P < 0.05). Multivariate Logistic regression analysis showed that plasma exosome count on the 1st day of ICU admission was an independent risk factor for 28-day death in septic patients [odds ratio (OR) = 1.385, 95% confidence interval (95%CI) was 1.075-1.785, P = 0.012]. ROC curve analysis showed that the area under the ROC curve (AUC) of plasma exosome count on the 1st day of ICU admission for predicting 28-day death in septic patients was 0.800 (95%CI was 0.449-1.000); when the optimal cut-off value was 14.50×1015/L, the sensitivity was 80.0% and the specificity was 100%. According to the optimal cut-off value of 1-day plasma exosome count, the patients were divided into two groups for Kaplan-Meier survival curve analysis, and the results showed that the cumulative survival rate of patients with plasma exosome count < 14.50×1015/L was significantly higher than that of patients with plasma exosome count ≥ 14.50×1015/L (Log-Rank test: χ 2 = 19.100, P < 0.001). CONCLUSIONS: The plasma exosome count of septic patients is significantly increased on the 1st day of admission to the ICU, which is related to the severity, and can predict the risk of death at 28 days.

ß-hydroxybutyrate and mitochondria mediate the association between medium-chain fatty acids, DHA and mild cognitive impairment: a nested case-control study.

BACKGROUND: Medium-chain fatty acids (MCFAs) and docosahexaenoic acid (DHA) could affect the occurrence of mild cognitive impairment (MCI). ß-hydroxybutyrate (BHB), mitochondrial DNA copy number (mtDNAcn) and mitochondrial DNA (mtDNA) deletions might be their potential mechanisms. This study aimed to explore the relationship between MCFAs, DHA and MCI, and potential mechanisms. METHODS: This study used data from Tianjin Elderly Nutrition and Cognition (TENC) cohort study, 120 individuals were identified with new onset MCI during follow-up, 120 individuals without MCI were selected by 1:1 matching sex, age, and education levels as the control group from TENC. Conditional logistic regression analysis and mediation effect analysis were used to explore their relationship. RESULTS: Higher serum octanoic acid levels (OR: 0.633, 95% CI: 0.520, 0.769), higher serum DHA levels (OR: 0.962, 95% CI: 0.942, 0.981), and more mtDNAcn (OR: 0.436, 95% CI: 0.240, 0.794) were associated with lower MCI risk, while more mtDNA deletions was associated with higher MCI risk (OR: 8.833, 95% CI: 3.909, 19.960). Mediation analysis suggested that BHB and mtDNAcn, in series, have mediation roles in the association between octanoic acid and MCI risk, and mtDNA deletions have mediation roles in the association between DHA and MCI risk. CONCLUSION: Higher serum octanoic acid and DHA levels were associated with lower MCI risk. Octanoic acid could affect the incidence of MCI through BHB, then mitochondria function, or through mitochondria function, or directly. Serum DHA level could affect the incidence of MCI through mitochondria function, or directly.

TwinF interface inhibitor FP802 prevents retinal ganglion cell loss in a mouse model of amyotrophic lateral sclerosis.

Motor neuron loss is well recognized in amyotrophic lateral sclerosis (ALS), but research on retinal ganglion cells (RGCs) is limited. Ocular symptoms are generally not considered classic ALS symptoms, although RGCs and spinal motor neurons share certain cell pathologies, including hallmark signs of glutamate neurotoxicity, which may be triggered by activation of extrasynaptic NMDA receptors (NMDARs). To explore potential novel strategies to prevent ALS-associated death of RGCs, we utilized inhibition of the TwinF interface, a new pharmacological principle that detoxifies extrasynaptic NMDARs by disrupting the NMDAR/TRPM4 death signaling complex. Using the ALS mouse model SOD1G93A, we found that the small molecule TwinF interface inhibitor FP802 prevents the loss of RGCs, improves pattern electroretinogram (pERG) performance, increases the retinal expression of Bdnf, and restores the retinal expression of the immediate early genes, Inhibin beta A and Npas4. Thus, FP802 not only prevents, as recently described, death of spinal motor neurons in SOD1G93A mice, but it also mitigates ALS-associated retinal damage. TwinF interface inhibitors have great potential for alleviating neuro-ophthalmologic symptoms in ALS patients and offer a promising new avenue for therapeutic intervention.

Characterization of the flavor profile of Hulatang using GC-IMS coupled with sensory analysis.

Background: Hulatang is a traditional specialty snack in Henan, China, and is well known for its unique flavor. Methods: In this study, the volatile organic compounds (VOCs) in four kinds of Hulatang from two representative regions in Henan Province (Xiaoyaozhen and Beiwudu) were evaluated using headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS). Results: The results showed that Xiaoyaozhen Hulatang exhibited more ethers, fewer terpenes and ketones than Beiwudu Hulatang. Additionally, Hulatang from different regions were classified using the orthogonal partial least squares-discriminant analysis (OPLS-DA) based on GC-IMS data. Twenty aroma substances were selected as the potential markers using the variable importance in the projection (VIP) variable selection method. Additionally, fifteen aroma components significantly contributing to the aroma of Hulatang were screened using the relative odor activity value (ROAV) (ROAV > 1). Combined with the sensory score results, twelve key substances with significant correlation with odor perception were selected. The flavor characteristics of the key substances revealed that the flavor of Hulatang was mainly composed of volatile components with camphor, green, almond, fatty, spicy, herbal, vegetable, fruity, floral, musty, and solvent aromas. Conclusion: Overall, the experimental results provide a theoretical basis for evaluating the flavor characteristics of Hulatang from different regions using GC-IMS.

His bundle pacing combined with atrioventricular node ablation for atrial fibrillation: a systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVE: His bundle pacing (HBP) could replace failed biventricular pacing (BVP) in guidelines (IIa Indication), but the high capture thresholds and backup lead pacing requirements limit its development. We assessed the efficacy and safety of HBP combined with atrioventricular node ablation (AVNA) for atrial fibrillation (AF) and compared with BVP and left bundle branch pacing (LBBP). METHODS: We reviewed PubMed, Embase, Web of Science, and Cochrane Library databases on left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) score, QRS duration (QRSd), and pacing threshold. RESULTS: Thirteen studies included 1115 patients (639 with HBP, 338 with BVP, and 221 with LBBP). Compared with baseline, HBP improved LVEF (mean difference [MD]: 9.24 [6.10, 12.37]; p < 0.01), reduced NYHA score (MD: -1.12 [-1.34, -0.91]; p < 0.01), increased QRSd (MD: 10.08 [4.45, 15.70]; p < 0.01), and rose pacing threshold (MD: 0.16 [0.05, 0.26]; p < 0.01). HBP had comparable efficacy to BVP and LBBP and lower QRSd (p < 0.05). HBP had a lower success rate (85.97%) and more complications (16.1%). CONCLUSION: HBP combined with AVNA is effective for AF, despite having a lower success rate and more complications. Further trials are required to determine whether HBP is superior to BVP and LBBP.

Soil organic carbon fractions and their stability under different land uses in wind erosion area of Northeast China.

Exploring the physical fractions of organic carbon and influencing mechanisms in grassland, forest, and farmland soils in wind erosion area can provide scientific basis for carbon sequestration, land utilization, wind prevention measure making, and fertility restoration of sloping farmland in the region. We examined the differentiation of aggregate organic carbon and density fractionation organic carbon in 0-15 cm soil layer across grassland, forest, and sloping farmland with 350 m long and 5° slope gradient in the wind erosion area of Meilisi District, Qiqihar, Heilongjiang, as well as the sloping farmland in the downhill section, middle section, and uphill section with every 100 m apart from the bottom to the top. The results showed that soil aggregates >2 mm were all destroyed across grassland, forest, and farmland soils, while the percentage of aggregates <0.053 mm was significantly higher than that of other sizes. The percentage of various soil aggregates, organic carbon content from density fractionations, and the proportion of organic carbon in the heavy fraction aggregates in farmland were significantly lower than that in grassland and forest soils. Soil aggregates in the uphill section of farmland were completely destroyed, and organic carbon content in various size aggregates and density fractionations gradually decreased with increasing slope. The proportion of organic carbon in the heavy fraction aggregates decreased, but that in light fraction aggregates increased gradually. Soil organic carbon and available potassium were key factors affecting aggregate stability, aggregate organic carbon content, and organic carbon content in density fractionations, while the loss of organic carbon in aggregate led to a decrease in aggregate stability. In summary, compared with grassland and forest soils, the stability of soil aggregates, the aggregate organic carbon content, the organic carbon content in density fractionations, and the proportion of organic carbon in heavy fraction aggregates in farmland all decreased in the wind erosion area of Northeast China. With the increases of slope, the aggregate organic carbon content, the organic carbon content in density fractionations, and the proportion of organic carbon in the heavy fraction aggregates in sloping farmland all decreased. Planting trees, conserving and expanding grassland area, and increasing the application of organic materials in sloping farmland in wind erosion area are effective approaches to stabilize and increase carbon storage, improve soil structure, and enhance soil quality.