Natural products reverse cancer multidrug resistance.

Cancer stands as a prominent global cause of death. One of the key reasons why clinical tumor chemotherapy fails is multidrug resistance (MDR). In recent decades, accumulated studies have shown how Natural Product-Derived Compounds can reverse tumor MDR. Discovering novel potential modulators to reduce tumor MDR by Natural Product-Derived Compounds has become a popular research area across the globe. Numerous studies mainly focus on natural products including flavonoids, alkaloids, terpenoids, polyphenols and coumarins for their MDR modulatory activity. Natural products reverse MDR by regulating signaling pathways or the relevant expressed protein or gene. Here we perform a deep review of the previous achievements, recent advances in the development of natural products as a treatment for MDR. This review aims to provide some insights for the study of multidrug resistance of natural products.

Cascade Microbial Metabolism of Ferulic Acid In Vitro Fermented by the Human Fecal Inoculum.

Ferulic acid (FA), predominantly existing in most cereals, can modulate the gut microbiome, but the influences of its metabolites on the microbial population and FA-transforming microorganisms are still unclear. In this study, FA and its potential phenolic metabolites were fermented in vitro for 24 h with the human fecal inoculum. A comparable short chain fatty acid (SCFA) production trend was observed in the presence and absence of substrates, suggesting limited contribution of FA mechanism to SCFA formation. Dihydroferulic acid, 3-(3,4-dihydroxyphenyl)propionic acid, and 3-(3-hydroxyphenyl)propionic acid were ascertained to be successive metabolites of FA, by tracking the intermediate variation. FA remarkably promoted the absolute abundances of total bacteria, while different metabolites affected bacterial growth of selective genera. Specific genera were identified as quantitatively correlating to the content of FA and its metabolites. Ultimately, FA-mediated gut microbiota modulation involves both the action of metabolizing microbes and the regulation effects of metabolites on bacterial growth.

Chloroplast genomes of Caragana tibetica and Caragana turkestanica: structures and comparative analysis.

BACKGROUND: The genus Caragana encompasses multiple plant species that possess medicinal and ecological value. However, some species of Caragana are quite similar in morphology, so identifying species in this genus based on their morphological characteristics is considerably complex. In our research, illumina paired-end sequencing was employed to investigate the genetic organization and structure of Caragana tibetica and Caragana turkestanica, including the previously published chloroplast genome sequence of 7 Caragana plants. RESULTS: The lengths of C. tibetica and C. turkestanica chloroplast genomes were 128,433 bp and 129,453 bp, respectively. The absence of inverted repeat sequences in these two species categorizes them under the inverted repeat loss clade (IRLC). They encode 110 and 111 genes (4 /4 rRNA genes, 30 /31tRNA genes, and 76 /76 protein-coding genes), respectively. Comparison of the chloroplast genomes of C. tibetica and C. turkestanica with 7 other Caragana species revealed a high overall sequence similarity. However, some divergence was observed between certain intergenic regions (matK-rbcL, psbD-psbM, atpA-psbI, and etc.). Nucleotide diversity (π) analysis revealed the detection of five highly likely variable regions, namely rps2-atpI, accD-psaI-ycf4, cemA-petA, psbN-psbH and rpoA-rps11. Phylogenetic analysis revealed that C. tibetica's sister species is Caragana jubata, whereas C. turkestanica's closest relative is Caragana arborescens. CONCLUSIONS: The present study provides worthwhile information about the chloroplast genomes of C. tibetica and C. turkestanica, which aids in the identification and classification of Caragana species.

Distribution of oxygen-containing functional groups on defective graphene: properties engineering and Li adsorption.

In this study, the distribution of oxygen-containing functional groups on graphene with vacancies and topological defects was systematically investigated using advanced computational methods and the structure models for multi-defect graphene oxides (GOs) were proposed. All potential adsorption sites were considered through an automated structure generation program to identify energetically favorable structures. Unlike the pristine graphene surface where oxygen-containing functional groups always aggregate with each other, we observed a tendency for them to preferentially adsorb near defects. Furthermore, they may also be distributed on the same side or both sides of the defective graphene. These multi-defect GOs can exhibit either metallic or semiconducting properties. Notably, upon adsorbing the same oxygen-containing functional groups onto the surface of defective graphene, their electronic characteristics become homogeneous. The coexistence of vacancy/topological defects and oxygen-containing functional groups within the graphene lattice introduces intriguing mechanical anisotropic properties to graphene, including the uncommon negative Poisson's ratio. Additionally, these materials exhibit anisotropic optical behavior, displaying heightened absorption within the infrared and visible regions compared to pristine graphene. Finally, it is found that Li atoms are adsorbed stably on the surfaces of multi-defect GOs via the formation of LinO/LimOH clusters. The research findings presented in this paper, encompassing the development of structural models for multi-defect GOs, could provide crucial insights into the properties and potential applications of graphene oxides.

Betaine improves appetite regulation and glucose-lipid metabolism in mandarin fish (Siniperca chuatsi) fed a high-carbohydrate-diet by regulating the AMPK/mTOR signaling.

Diets with high carbohydrate (HC) was reported to have influence on appetite and intermediary metabolism in fish. To illustrate whether betaine could improve appetite and glucose-lipid metabolism in aquatic animals, mandarin fish (Siniperca chuatsi) were fed with the HC diets with or without betaine for 8 weeks. The results suggested that betaine enhanced feed intake by regulating the hypothalamic appetite genes. The HC diet-induced downregulation of AMPK and appetite genes was also positively correlated with the decreased autophagy genes, suggesting a possible mechanism that AMPK/mTOR signaling might regulate appetite through autophagy. The HC diet remarkably elevated transcriptional levels of genes related to lipogenesis, while betaine alleviated the HC-induced hepatic lipid deposition. Additionally, betaine supplementation tended to store the energy storage as hepatic glycogen. Our findings proposed the possible mechanism for appetite regulation through autophagy via AMPK/mTOR, and demonstrated the feasibility of betaine as an aquafeed additive to regulate appetite and intermediary metabolism in fish.

Prediction of high-level fear of cancer recurrence in breast cancer survivors: An integrative approach utilizing random forest algorithm and visual nomogram.

PURPOSE: This study is the first attempt to use a combination of regression analysis and random forest algorithm to predict the risk factors for high-level fear of cancer recurrence and develop a predictive nomogram to guide clinicians and nurses in identifying high-risk populations for high-level fear of cancer recurrence. METHODS: After receiving various recruitment strategies, a total of 781 survivors who had undergone breast cancer resection within 5 years in four Grade-A hospitals in China were included. Besides demographic and clinical characteristics, variables were also selected from the perspectives of somatic, cognitive, psychological, social and economic factors, all of which were measured using a scale with high reliability and validity. This study established univariate regression analysis and random forest model to screen for risk factors for high-level fear of cancer recurrence. Based on the results of the multi-variable regression model, a nomogram was constructed to visualize risk prediction. RESULTS: Fatigue, social constraints, maladaptive cognitive emotion regulation strategies, meta-cognition and age were identified as risk factors. Based on the predictive model, a nomogram was constructed, and the area under the curve was 0.949, indicating strong discrimination and calibration. CONCLUSIONS: The integration of two models enhances the credibility of the prediction outcomes. The nomogram effectively transformed intricate regression equations into a visual representation, enhancing the readability and accessibility of the prediction model's results. It aids clinicians and nurses in swiftly and precisely identifying high-risk individuals for high-level fear of cancer recurrence, enabling the development of timely, predictable, and personalized intervention programs for high-risk patients.

Integration of metalloproteome and immunoproteome reveals a tight link of iron-related proteins with COVID-19 pathogenesis and immunity.

Increasing clinical data show that the imbalance of host metallome is closely associated with different kinds of disease, however, the intrinsic mechanisms of action of metals in immunity and pathogenesis of disease remain largely undefined. There is lack of multiplexed profiling system to integrate the metalloproteome-immunoproteome information at systemic level for exploring the roles of metals in immunity and disease pathogenesis. In this study, we build up a metal-coding assisted multiplexed proteome assay platform for serum metalloproteomic and immunoproteomic profiling. By taking COVID-19 as a showcase, we unbiasedly uncovered the most evident modulation of iron-related proteins, i.e., Ft and Tf, in serum of severe COVID-19 patients, and the value of Ft/Tf could work as a robust biomarker for COVID-19 severity stratification, which overtakes the well-established clinical risk factors (cytokines). We further uncovered a tight association of transferrin with inflammation mediator IL-10 in COVID-19 patients, which was proved to be mainly governed by the monocyte/macrophage of liver, shedding light on new pathophysiological and immune regulatory mechanisms of COVID-19 disease. We finally validated the beneficial effects of iron chelators as anti-viral agents in SARS-CoV-2-infected K18-hACE2 mice through modulation of iron dyshomeostasis and alleviating inflammation response. Our findings highlight the critical role of liver-mediated iron dysregulation in COVID-19 disease severity, providing solid evidence on the involvement of iron-related proteins in COVID-19 pathophysiology and immunity.

Tumorigenesis driven by the BRAF V600E oncoprotein requires secondary mutations that overcome its feedback inhibition of migration and invasion.

BRAF V600E mutation occurs in 46% of melanomas and drives high levels of ERK activity and ERK-dependent proliferation. However, BRAF V600E is insufficient to drive melanoma in GEMM models, and 82% of human benign nevi harbor BRAF V600E mutations. We show here that BRAF V600E inhibits mesenchymal migration by causing feedback inhibition of RAC1 activity. ERK pathway inhibition induces RAC1 activation and restores migration and invasion. In cells with BRAF V600E , mutant RAC1, overexpression of PREX1, PREX2, or PTEN inactivation restore RAC1 activity and cell motility. Together, these lesions occur in 48% of BRAF V600E melanomas. Thus, although BRAF V600E activation of ERK deregulates cell proliferation, it prevents full malignant transformation by causing feedback inhibition of cell migration. Secondary mutations are, therefore, required for tumorigenesis. One mechanism underlying tumor evolution may be the selection of lesions that rescue the deleterious effects of oncogenic drivers. Statement of significance: BRAF V600E activation of ERK causes feedback inhibition of cell migration and invasion and thus blocks tumorigenesis. Secondary genetic lesions are required to rescue these processes and enable tumor development. Thus, oncogenic feedback can shape the details of tumor progression and, in doing so, selects for new mutations that may be therapeutic targets.

Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial.

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180-365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients' improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).

Molecularly Imprinted Electrochemical Sensor Based on α-Cyclodextrin Inclusion Complex and MXene Modification for Highly Sensitive and Selective Detection of Alkylresorcinols in Whole Wheat Foods.

Authenticating whole wheat foods poses a significant challenge for both the grain industry and consumers. Alkylresorcinols (ARs), serving as biomarkers of whole wheat, play a crucial role in assessing the authenticity of whole wheat foods. Herein, we introduce a novel molecularly imprinted electrochemical sensor with modifications involving a molecularly imprinted polymer (MIP) and MXene nanosheets, enabling highly sensitive and selective detection of ARs. Notably, we specifically chose 5-heneicosylresorcinol (AR21), the predominant homologue in whole wheat, as the template molecule. α-Cyclodextrin and acrylamide served as dual functional monomers, establishing a robust multiple interaction between the MIP and AR21. As a result, the sensor exhibited a wide linear range of 0.005 to 100 µg·mL-1 and a low detection limit of 2.52 ng·mL-1, demonstrating exceptional selectivity and stability. When applied to commercial whole wheat foods, the assay achieved satisfactory recoveries and accuracy, strongly validating the practicality and effectiveness of this analytical technique.

Stable dispersion of carbon nanotubes in a molten salt of KNO3-NaNO3-NaNO2-LiNO3-LiOH.

Carbon nanotubes (CNTs) have excellent mechanical and electrical properties; however, they suffer from dispersion problems in various applications. Traditional dispersing strategies of CNTs mostly use oxidation with strong acids or mechanical milling with high energy, which causes serious damage to the intrinsic structures and properties of CNTs. Therefore, it is important to develop new methods for dispersing CNTs without destroying their structures. This paper proposes to disperse CNTs in low-temperature molten salts composed of KNO3-NaNO3-NaNO2-LiNO3-LiOH. By adjusting the composition ratio of molten salts and alkaline, the interaction between charged ions and CNT electrons in the molten salt is studied. The alkaline molten salts can stably disperse CNTs and do not destroy their lengths, thereby offering better electric conductivity. This work will provide a new yet effective method for dispersing CNTs with high aspect ratios, which are important for the application of CNTs and other nanocarbons.

Health risks and sources of trace elements and black carbon in PM2.5 from 2019 to 2021 in Beijing.

A comprehensive health risk assessment of PM2.5 is meaningful to understand the current status and directions regarding further improving air quality from the perspective of human health. In this study, we evaluated the health risks of PM2.5 as well as highly toxic inorganic components, including heavy metals (HMs) and black carbon (BC) based on long-term observations in Beijing from 2019 to 2021. Our results showed that the relative risks of chronic obstructive pulmonary disease, lung cancer, acute lower respiratory tract infection, ischemic heart disease, and stroke decreased by 4.07%-9.30% in 2020 and 2.12%-6.70% in 2021 compared with 2019. However, they were still at high levels ranging from 1.26 to 1.77, in particular, stroke showed the highest value in 2021. Mn had the highest hazard quotient (HQ, from 2.18 to 2.56) for adults from 2019 to 2021, while Ni, Cr, Pb, As, and BC showed high carcinogenic risks (CR > 1.0×10-6) for adults. The HQ values of Mn and As and the CR values of Pb and As showed constant or slight upwards trends during our observations, which is in contrast to the downward trends of other HMs and PM2.5. Mn, Cr, and BC are crucial toxicants in PM2.5. A significant shrink of southern region sourcesof HMs and BCshrank suggests the increased importance of local sources. Industry, dust, and biomass burning are the major contributors to the non-carcinogenic risks, while traffic emissions and industry are the dominant contributors to the carcinogenic risks in Beijing.

Integration of Multi-Omics, Histological, and Biochemical Analysis Reveals the Toxic Responses of Nile Tilapia Liver to Chronic Microcystin-LR Exposure.

Microcystin-LR (MC-LR) is a cyanobacterial metabolite produced during cyanobacterial blooms and is toxic to aquatic animals, and the liver is the main targeted organ of MC-LR. To comprehensively understand the toxicity mechanism of chronic exposure to environmental levels of MC-LR on the liver of fish, juvenile Nile tilapia were exposed to 0 µg/L (control), 1 µg/L (M1), 3 µg/L (M3), 10 µg/L (M10), and 30 µg/L (M30) MC-LR for 60 days. Then, the liver hepatotoxicity induced by MC-LR exposure was systematically evaluated via histological and biochemical determinations, and the underlying mechanisms were explored through combining analysis of biochemical parameters, multi-omics (transcriptome and metabolome), and gene expression. The results exhibited that chronic MC-LR exposure caused slight liver minor structural damage and lipid accumulation in the M10 group, while resulting in serious histological damage and lipid accumulation in the M30 group, indicating obvious hepatotoxicity, which was confirmed by increased toxicity indexes (i.e., AST, ALT, and AKP). Transcriptomic and metabolomic analysis revealed that chronic MC-LR exposure induced extensive changes in gene expression and metabolites in six typical pathways, including oxidative stress, apoptosis, autophagy, amino acid metabolism, primary bile acid biosynthesis, and lipid metabolism. Taken together, chronic MC-LR exposure induced oxidative stress, apoptosis, and autophagy, inhibited primary bile acid biosynthesis, and caused fatty deposition in the liver of Nile tilapia.

A novel breast cancer image classification model based on multiscale texture feature analysis and dynamic learning.

Assistive medical image classifiers can greatly reduce the workload of medical personnel. However, traditional machine learning methods require large amounts of well-labeled data and long learning times to solve medical image classification problems, which can lead to high training costs and poor applicability. To address this problem, a novel unsupervised breast cancer image classification model based on multiscale texture analysis and a dynamic learning strategy for mammograms is proposed in this paper. First, a gray-level cooccurrence matrix and Tamura coarseness are used to transfer images to multiscale texture feature vectors. Then, an unsupervised dynamic learning mechanism is used to classify these vectors. In the simulation experiments with a resolution of 40 pixels, the accuracy, precision, F1-score and AUC of the proposed method reach 91.500%, 92.780%, 91.370%, and 91.500%, respectively. The experimental results show that the proposed method can provide an effective reference for breast cancer diagnosis.

Effects of different wall-breaking methods on the nutrient release of Ganoderma lucidum spore powder during in vitro digestion.

BACKGROUND: The hard double-walled structure of Ganoderma lucidum spore powder (GLSP) is difficult for the human body to digest, so it is very important to break the wall of GLSP. In this study, the wall of GLSP was broken by mechanical milling at room temperature (MM-R) and ultra-fine grinding at low temperature (UFG-L), respectively. RESULTS: Compared with MM-R, UFG-L could better retain the sporangium powder's morphological and structural integrity. During in vitro digestion, compared with unbroken GLSP, the released amounts of polysaccharides and triterpenes from broken GLSP were significantly increased, and they increased with the increase of specific surface area. The bioaccessibility of polysaccharide and triterpene from unbroken GLSP after the intestinal stage were 29.52% and 5.37%, respectively. The bioaccessibility of polysaccharides and triterpene from broken GLSP by MM-R after the intestinal phase were 39.73-72.45% and 16.44-24.97%, while those by UFG-L were 44.53-104.18% and 12.96-32.90%, respectively. CONCLUSION: The active ingredients of broken GLSP showed better digestion and absorption abilities than unbroken GLSP. Moreover, the specific surface area of GLSP by UFG-L was lower than that by MM-R, and the bioaccessibility of GLSP by UFG-L was higher than that by MM-R. © 2024 Society of Chemical Industry.

Comprehensive analysis of vulnerability status and associated affect factors among prehospital emergency patients: a single-center descriptive cross-sectional study.

Background: Prehospital emergency care is a critical but often understudied aspect of healthcare. Patient vulnerability in this setting can significantly impact outcomes. The aim of this study was to investigate the vulnerability status and to determine associated affect factors among prehospital emergency patients in China. Methods: In this cross-sectional study conducted in China, from April 2023 to July 2023, we assessed the vulnerability of prehospital emergency patients using the Safety in Prehospital Emergency Care Index (SPECI) scale. We conducted a detailed questionnaire-based survey to gather demographic and disease-related information. We employed the SPECI scale, consisting of two subscales, to evaluate patient vulnerability. Statistical analyses, including t-tests, ANOVA, and multiple linear regression, were used to identify factors associated with vulnerability. Results: The study included a total of 973 prehospital emergency patients, with a response rate of 81.9%. These patients exhibited a low-to-moderate level of vulnerability, with an average SPECI score of 14.46 out of 40. Vulnerability was significantly associated with age (particularly those aged 60 and above), disease severity (severe conditions increased vulnerability), disease type (circulatory diseases correlated with higher vulnerability), alterations in consciousness, and chronic diseases. Unexpectedly, digestive system diseases were negatively correlated with vulnerability. Conclusion: Addressing patient vulnerability in prehospital care is essential. Tailored interventions, EMS provider training, and interdisciplinary collaboration can mitigate vulnerability, especially in older patients and those with severe conditions.

Nanopore-based metagenomics analysis reveals microbial presence in amniotic fluid: A prospective study.

Background: Current research on amniotic fluid (AF) microbiota yields contradictory data, necessitating an accurate, comprehensive, and scientifically rigorous evaluation. Objective: This study aimed to characterise the microbial features of AF and explore the correlation between microbial information and clinical parameters. Methods: 76 AF samples were collected in this prospective cohort study. Fourteen samples were utilised to establish the nanopore metagenomic sequencing methodology, whereas the remaining 62 samples underwent a final statistical analysis along with clinical information. Negative controls included the operating room environment (OE), surgical instruments (SI), and laboratory experimental processes (EP) to elucidate the background contamination at each step. Simultaneously, levels of five cytokines (IL-1ß, IL-6, IL-8, TNF-α, MMP-8) in AF were assessed. Results: Among the 62 AF samples, microbial analysis identified seven without microbes and 55 with low microbial diversity and abundance. No significant clinical differences were observed between AF samples with and without microbes. The correlation between microbes and clinical parameters in AF with normal chromosomal structure revealed noteworthy findings. In particular, the third trimester exhibited richer microbial diversity. Pseudomonas demonstrated higher detection rates and relative abundance in the second trimester and Preterm Birth (PTB) groups. S. yanoikuyae in the PTB group exhibited elevated detection frequencies and relative abundance. Notably, Pseudomonas negatively correlated with activated partial thromboplastin time (APTT) (r = -0.329, P = 0.016), while Staphylococcus showed positive correlations with APTT (r = 0.395, P = 0.003). Furthermore, Staphylococcus negatively correlated with birth weight (r = -0.297, P = 0.034). Conclusion: Most AF samples exhibited low microbial diversity and abundance. Certain microbes in AF may correlate with clinical parameters such as gestational age and PTB. However, these associations require further investigation. It is essential to expand the sample size and undertake more comprehensive research to elucidate the clinical implications of microbial presence in AF.

Does transanal drainage tubes placement have an impact on the incidence of anastomotic leakage after rectal cancer surgery? a systematic review and meta-analysis.

BACKGROUND: Whether Transanal drainage tubes (TDTs) placement reduces the occurrence of anastomotic leakage (AL) after rectal cancer (RC) surgery remains controversial. Most existing meta-analyses rely on retrospective studies, while the prospective studies present an inadequate level of evidence. METHODS: A systematic review and meta-analysis of prospective studies on TDTs placement in RC patients after surgery was conducted. The main analysis index was the incidence of AL, Grade B AL, and Grade C AL, while secondary analysis index was the incidence of anastomotic bleeding, incision infection, and anastomotic stenosis. A comprehensive literature search was performed utilizing the databases Cochrane Library, Embase, PubMed, and Web of Science. We recorded Risk ratios (RRs) and 95% confidence intervals (CI) for each included study, and a fixed-effect model or random-effect model was used to investigate the correlation between TDTs placement and four outcomes after RC surgery. RESULTS: Seven studies (1774 participants, TDT 890 vs non-TDT 884) were considered eligible for quantitative synthesis and meta-analysis. The meta-analysis revealed that the incidence of AL was 9.3% (83/890) in the TDT group and 10.2% (90/884) in the non-TDT group. These disparities were found to lack statistical significance (P = 0.58). A comprehensive meta-analysis, comprising four studies involving a cumulative sample size of 1259 participants, revealed no discernible disparity in the occurrence of Grade B AL or Grade C AL between the TDT group and the non-TDT group (Grade B AL: TDT 34/631 vs non-TDT 26/628, P = 0.30; Grade C AL: TDT 11/631 vs non-TDT 27/628, P = 0.30). Similarly, the incidences of anastomotic bleeding (4 studies, 876 participants), incision infection (3studies, 713 participants), and anastomotic stenosis (2studies, 561 participants) were 5.5% (24/440), 8.1% (29/360), and 2.9% (8/280), respectively, in the TDT group, and 3.0% (13/436), 6.5% (23/353), and 3.9% (11/281), respectively, in the non-TDT group. These differences were also determined to lack statistical significance (P = 0.08, P = 0.43, P = 0.48, respectively). CONCLUSION: The placement of TDTs does not significantly affect the occurrence of AL, Grade B AL, and Grade C AL following surgery for rectal cancer. Additionally, TDTs placement does not be associated with increased complications such as anastomotic bleeding, incision infection, or anastomotic stenosis. TRIAL REGISTRATION: PROSPERO: CRD42023427914.

Protective Effect of Dihydromyricetin Against Exercise-Induced Muscle Damage and Its Mechanism.

Objective To investigate the protective effect of dihydromyricetin (DHM) against exercise-induced muscle damage (EIMD) in mice and its potential mechanism.Methods Adult male C57BL/6J mice were randomly divided into control group (CG), exercise group (EG), and exercise + 100 mg/kg weight ·d DHM (DHM) group. The intervention lasted for four weeks, during which the animals in the EG and DHM groups were subjected to exercise training for 1 h per day. The day after the training, a 90-min treadmill exercise (slope: 0 and speed: 18 m/min) was conducted in both EG and DHM groups. Samples of blood and gastrocnemius muscles were harvested from the three groups 24 h after the exercise, followed by the measurement of serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA), and skeletal muscle mitochondrial enzyme complex I and II activities. Histological changes in the skeletal muscle were observed by transmission electron microscopy, and the protein expressions of mitochondrial function-related pathways were detected by Western blotting.Results Skeletal muscle morphological changes and mitochondrial damage were alleviated in the DHM group compared to those in the EG. The activities of EIMD markers CK and LDH and the level of lipid peroxidation were notably repressed and the serum T-SOD activity was enhanced after DHM intervention. Western blotting demonstrated that the expressions of sirtuin type 3 (SIRT3), estrogen-related receptor alpha, and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha in the skeletal muscle of mice increased after the DHM intervention.Conclusion DHM can relieve EIMD in mice, possibly by promoting the recovery of the mitochondrial structure and function in the skeletal muscle of mice after high-intensity exercise via the activation of the SIRT3 signaling pathway.