Three new phenylpropanoids, namely (7'R,8'R) guaiacylglycerol 4'-O-ß-D-[6â³-O-(4-O-ß-D-glucopyranosyl)-p-hydroxyl-benzoyl]-glucopyranoside (1), (7 R,8R) guaiacylglycerol 8-O-1'-(2',6'-dimethoxy-4'-O-ß-D-glucopyranosyl)-benzene (2), (7'R,8'R) guaiacylglycerol 4'-O-ß-D-[6â³-O-3,5-dimethoxy-4-hydroxylbenzoyl]-gluco-pyranoside (3), along with one known phenylpropanoid (4) were isolated from the ethanol extract of Phyllostachys nigra var. henonis fresh culm. The structures of all compounds were determined by analysis of UV, 1D NMR, 2D NMR, HR-ESI-MS and CD data. All compounds were evaluated for their DPPH radical scavenging activity. Compound 2 (IC50 54.9 µM) and 3 (IC50 77.2 µM) exhibited moderate antioxidant activity compared with two positive control compounds L-ascorbic acid (IC50 15.5 µM) and 2,6-ditertbutyl-4-methyl phenol (IC50 19.1 µM).
Antibiotics release into the water environment through sewage discharge is a significant environmental concern. In the present study, we investigated the removal of ciprofloxacin (CIP) in simulated sewage by biological aeration filter (BAF) equipped with Fe3O4-modified zeolite (Fe3O4@ZF). Fe3O4@ZF were prepared with impregnation method, and the Fe3O4 particles were successfully deposited on the surface of ZF in an amorphous form according to the results of XPS and XRD analysis. The modification also increased the specific surface area (from 16.22 m²/g to 22 m²/g) and pore volume (from 0.0047 cm³/g to 0.0063 cm³/g), improving the adsorption efficiency of antibiotics. Fe3O4 modified ZF improved the treatment performance significantly, and the removal efficiency of CIP in BAF-Fe3O4@ZF was 79%±2.4%. At 10ml/L CIP, the BAF-Fe3O4@ZF reduced the relative abundances of antibiotics resistance genes (ARGs) int, mexA, qnrB and qnrS in the effluent by 57.16%, 39.59%, 60.22%, and 20.25%, respectively, which effectively mitigate the dissemination risk of ARGs. The modification of ZF increased CIP-degrading bacteria abundance, such as Rhizobium and Deinococcus-Thermus, and doubled bacterial ATP activity, promoting CIP degradation. This study offers a viable, efficient method to enhance antibiotic treatment and prevent leakage via sewage discharge.
Anti-Bacterial Agents , Ciprofloxacin , Wastewater , Water Pollutants, Chemical , Zeolites , Zeolites/chemistry , Ciprofloxacin/pharmacology , Ciprofloxacin/chemistry , Wastewater/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Filtration/methods , Water Purification/methods , Waste Disposal, Fluid/methods , Adsorption , Drug Resistance, Microbial/genetics , Genes, Bacterial , Drug Resistance, Bacterial/genetics
Berberrubine (BRB), a main metabolite of berberine, has stronger hypoglycemic and lipid-lowering activity than its parent form. We previously found that BRB could cause obvious nephrotoxicity, but the molecular mechanism involved remains unknown. In this study, we systematically integrated metabolomics and quantitative proteomics to reveal the potential mechanism of nephrotoxicity caused by BRB. Metabolomic analysis revealed that 103 significantly differentially metabolites were changed. Among the mentioned compounds, significantly upregulated metabolites were observed for phosphorylcholine, sn-glycerol-3-phosphoethanolamine, and phosphatidylcholine. The top three enriched KEGG pathways were the mTOR signaling pathway, central carbon metabolism in cancer, and choline metabolism in cancer. ERK1/2 plays key roles in all three metabolic pathways. To further confirm the main signaling pathways involved, a proteomic analysis was conducted to screen for key proteins (such as Mapk1, Mapk14, and Caspase), indicating the potential involvement of cellular growth and apoptosis. Moreover, combined metabolomics and proteomics analyses revealed the participation of ERK1/2 in multiple metabolic pathways. These findings indicated that ERK1/2 regulated the significantly differentially abundant metabolites determined via metabolomics analysis. Notably, through a cellular thermal shift assay (CETSA) and molecular docking, ERK1/2 were revealed to be the direct binding target involved in BRB-induced nephrotoxicity. To summarize, this study sheds light on the understanding of severe nephrotoxicity caused by BRB and provides scientific basis for its safe use and rational development.
Germinated soybean is one kind of food and a medicine. In the actual process of producing a large amount of naturally germinated soybean, it is difficult to strictly control the germination process conditions. However, sprout length may be more suitable as the terminal judgment indicator for naturally germinated soybean. An UPLC-DAD method was developed and validated to explore the transformation profiles of soybean isoflavones in germinated yellow or black soybean with different sprout lengths. Moreover, an LC - QTOF-MS/MS method was used to avoid false positive results. The contents of daidzein, glycitein, and genistein almost reached their corresponding maximum values when the sprout length ranged from 1.0 cm to 1.5 cm (P < 0.05). Therefore, yellow soybean is suggested to be the processing raw material with higher contents of those isoflavones, and the optimal sprout length for germinated soybean may be in the range of 1.0-1.5 cm.
The Sterculia genus is comprised of approximately 300 species, which have been widely used as traditional medicines to treat inflammation, snake bites, gastrointestinal diseases, skin diseases, microbial infections and many other diseases. To gain a comprehensive understanding of the therapeutic potential of Sterculia plants, an extensive literature search was conducted in CNKI, Bing, Wanfang Database, Springer Database, Elsevier Database, Google Scholar, Baidu Scholar, PubMed, and other similar websites from January 1971 to March 2024. The research indicated that Sterculia species predominantly contain flavonoids, terpenoids, phenylpropanoids, fatty acids, alkaloids and other chemical components. A wide range of pharmacologic activities such as anti-inflammatory, antioxidant, antibacterial and other biological activities have been reported. Nevertheless, there isn't much scholarly research on the therapeutic material basis of the genus Sterculia. This review reports the ethnobotany, phytochemicals, and biological activities of the plants in the Sterculia genus as herbal remedies.
While mitochondria are susceptible to environmental detriments, little is known about potential associations between arsenic metabolites and mitochondria DNA copy number (mtDNAcn). We attempted to examine whether maternal urinary arsenic metabolite levels in different trimesters were related to neonatal cord blood mtDNAcn. We included 819 mother-newborn pairs embedded in an in-progress birth cohort survey performed from April 2014 to October 2016 in Wuhan, China. We determined maternal urinary arsenic species concentrations in different trimesters. We determined cord blood mtDNAcn using quantitative real-time polymerase chain reaction. In covariate-adjusted models, each one-unit increment of dimethylated arsenic (DMA) and total arsenic (TAs) in the third trimester was related to 8.43% (95% CI 1.13%, 16.26%) and 12.15% (95% CI 4.35%, 20.53%) increases in mtDNAcn, respectively. The dose-response trend with statistical significance was observed across tertiles of DMA and TAs in the third trimester with mtDNAcn (DMA percent changes (%Δ) = 25.60 (95% CI 6.73, 47.82), for the highest vs the lowest tertile (P = 0.02); TAs %Δ = 40.31 (95% CI 19.25, 65.10), for the highest vs the lowest tertile (P = 0.0002)). These findings may prove the relationships between prenatal arsenic species levels and neonatal mitochondrial dysfunction.
ETHNOPHARMACOLOGICAL RELEVANCE: Berberine (BBR) is the main active component from Coptidis rhizome, a well-known Chinese herbal medicine used for metabolic diseases, especially diabetes for thousands of years. BBR has been reported to cure various metabolic disorders, such as nonalcoholic fatty liver disease (NAFLD). However, the direct proteomic targets and underlying molecular mechanism of BBR against NAFLD remain less understood. AIM OF THE STUDY: To investigate the direct target and corresponding molecular mechanism of BBR on NAFLD is the aim of the current study. MATERIALS AND METHODS: High-fat diet (HFD)-fed mice and oleic acid (OA) stimulated HepG2 cells were utilized to verify the beneficial impacts of BBR on glycolipid metabolism profiles. The click chemistry in proteomics, DARTS, CETSA, SPR and fluorescence co-localization analysis were conducted to identify the targets of BBR for NAFLD. RNA-seq and shRNA/siRNA were used to investigate the downstream pathways of the target. RESULTS: BBR improved hepatic steatosis, ameliorated insulin resistance, and reduced TG levels in the NAFLD models. Importantly, Aldo-keto reductase 1B10 (AKR1B10) was first proved as the target of BBR for NAFLD. The gene expression of AKR1B10 increased significantly in the NAFLD patients' liver tissue. We further demonstrated that HFD and OA increased AKR1B10 expression in the C57BL/6 mice's liver and HepG2 cells, respectively, whereas BBR decreased the expression and activities of AKR1B10. Moreover, the knockdown of AKR1B10 by applying shRNA/siRNA profoundly impacted the beneficial effects on the pathogenesis of NAFLD by BBR. Meanwhile, the changes in various proteins (ACC1, CPT-1, GLUT2, etc.) are responsible for hepatic lipogenesis, fatty acid oxidation, glucose uptake, etc. by BBR were reversed by the knockdown of AKR1B10. Additionally, RNA-seq was used to identify the downstream pathway of AKR1B10 by examining the gene expression of liver tissues from HFD-fed mice. Our findings revealed that BBR markedly increased the protein levels of PPARα while downregulating the expression of PPARγ. However, various proteins of PPAR signaling pathways remained unaffected post the knockdown of AKR1B10. CONCLUSIONS: BBR alleviated NAFLD via mediating PPAR signaling pathways through targeting AKR1B10. This study proved that AKR1B10 is a novel target of BBR for NAFLD treatment and helps to find new targets for the treatment of NAFLD by using active natural compounds isolated from traditional herbal medicines as the probe.
Transient receptor potential channels (TRPs) are widely recognized as a group of ion channels involved in various sensory perceptions, such as temperature, taste, pressure, and vision. While macroautophagy (hereafter referred to as autophagy) is primarily regulated by core machinery, the ion exchange mediated by TRPs between intracellular and extracellular compartments, as well as within organelles and the cytoplasm, plays a crucial role in autophagy regulation as an important signaling transduction mechanism. Moreover, certain TRPs can directly interact with autophagy regulatory proteins to participate in autophagy regulation. In this article, we provide an in-depth review of the current understanding of the regulatory mechanisms of autophagy, with a specific focus on TRPs. Furthermore, we highlight the potential prospects for drug development targeting TRPs in autophagy for the treatment of human diseases.
BACKGROUND: The effectiveness of high-flow nasal cannula (HFNC) therapy in patients with bronchiectasis experiencing hypercapnia remains unclear. Our aim was to retrospectively analyze the short-term outcomes of HFNC therapy in such patients, and to further explore the predictors of HFNC treatment failure in this particular patient population. METHODS: A retrospective review was conducted on patients with bronchiectasis who received HFNC (n = 70) for hypercapnia (arterial partial pressure of carbon dioxide, PaCO2 ≥ 45 mmHg) between September 2019 and September 2023. RESULTS: In the study population, 30% of patients presented with acidemia (arterial pH < 7.35) at baseline. Within 24 h of HFNC treatment, there was a significant reduction in PaCO2 levels by a mean of 4.0 ± 12.7 mmHg (95% CI -7.0 to -1.0 mmHg). Concurrently, arterial pH showed a statistically significant increase with a mean change of 0.03 ± 0.06 (95% CI 0.01 to 0.04). The overall hospital mortality rate in our study was 17.5%. The median length of hospital stay was 11.0 days (interquartile range [IQR] 8.0 to 16.0 days). Sub-analysis revealed no statistically significant differences in hospital mortality (19.0% vs. 20.4%, p = 0.896), length of hospital stay (median 14.0 days [IQR 9.0 to 18.0 days] vs. 10.0 days [IQR 7.0 to 16.0 days], p = 0.117) and duration of HFNC application (median 5.0 days [IQR 2.0 to 8.5 days] vs. 6.0 days [IQR 4.9 to 9.5 days], p = 0.076) between the acidemia group and the non-acidemia group (arterial pH ≥ 7.35). However, more patients in the non-acidemia group had do-not-intubate orders. The overall treatment failure rate for HFNC was 28.6%. Logistic regression analysis identified the APACHE II score (OR 1.24 per point) as the independent predictor of HFNC failure. CONCLUSIONS: In patients with bronchiectasis and hypercapnia, HFNC as an initial respiratory support can effectively reduce PaCO2 level within 24 h of treatment. A high APACHE II score has emerged as a prognostic indicator for HFNC treatment failure. These observations highlight randomized controlled trials to meticulously evaluate the efficacy of HFNC in this specific population.
Bronchiectasis , Cannula , Hypercapnia , Oxygen Inhalation Therapy , Humans , Retrospective Studies , Hypercapnia/therapy , Male , Female , Bronchiectasis/therapy , Oxygen Inhalation Therapy/methods , Middle Aged , Aged , Hospital Mortality , Length of Stay/statistics & numerical data , Carbon Dioxide , Treatment Outcome
A balance between the development and suppression of inflammation can always be found in the body. When this balance is disturbed, a strong inflammatory response can damage the body. It sometimes is necessary to use drugs with a significant anti-inflammatory effect, such as nonsteroidal anti-inflammatory drugs and steroid hormones, to control inflammation in the body. However, the existing anti-inflammatory drugs have many adverse effects, which can be deadly in severe cases, making research into new safer and more effective anti-inflammatory drugs necessary. Currently, numerous types of natural products with anti-inflammatory activity and distinct structural features are available, and these natural products have great potential for the development of novel anti-inflammatory drugs. This review summarizes 260 natural products and their derivatives with anti-inflammatory activities in the last two decades, classified by their active ingredients, and focuses on their structure-activity relationships in anti-inflammation to lay the foundation for subsequent new drug development. We also elucidate the mechanisms and pathways of natural products that exert anti-inflammatory effects via network pharmacology predictions, providing direction for identifying subsequent targets of anti-inflammatory natural products.
The intricate geometry and thin walls of the motor housing in new energy vehicles render it susceptible to casting defects during conventional casting processes. However, the lost-foam casting process holds a unique advantage in eliminating casting defects and ensuring the strength and air-tightness of thin-walled castings. In this paper, the lost-foam casting process of thin-walled A356 alloy motor housing was simulated using ProCAST software (2016.0). The results indicate that the filling process is stable and exhibits characteristics of diffusive filling. Solidification occurs gradually from thin to thick. Defect positions are accurately predicted. Through analysis of the defect volume range, the optimal process parameter combination is determined to be a pouring temperature of 700 °C, an interfacial heat transfer coefficient of 50, and a sand thermal conductivity coefficient of 0.5. Microscopic analysis of the motor housing fabricated using the process optimized through numerical simulations reveals the absence of defects such as shrinkage at critical locations.
Magnesium matrix composites are essential lightweight metal matrix composites, following aluminum matrix composites, with outstanding application prospects in automotive, aerospace lightweight and biomedical materials because of their high specific strength, low density and specific stiffness, good casting performance and rich resources. However, the inherent low plasticity and poor fatigue resistance of magnesium hamper its further application to a certain extent. Many researchers have tried many strengthening methods to improve the properties of magnesium alloys, while the relationship between wear resistance and plasticity still needs to be further improved. The nanoparticles added exhibit a good strengthening effect, especially the ceramic nanoparticles. Nanoparticle-reinforced magnesium matrix composites not only exhibit a high impact toughness, but also maintain the high strength and wear resistance of ceramic materials, effectively balancing the restriction between the strength and toughness. Therefore, this work aims to provide a review of the state of the art of research on the matrix, reinforcement, design, properties and potential applications of nano-reinforced phase-reinforced magnesium matrix composites (especially ceramic nanoparticle-reinforced ones). The conventional and potential matrices for the fabrication of magnesium matrix composites are introduced. The classification and influence of ceramic reinforcements are assessed, and the factors influencing interface bonding strength between reinforcements and matrix, regulation and design, performance and application are analyzed. Finally, the scope of future research in this field is discussed.
Objective: Late-onset myasthenia gravis (LOMG) often has comorbidities, and its initial symptoms may be ignored or misdiagnosed as other diseases. There were few large surveys on LOMG. Our study aimed to summarize clinical characteristics of LOMG to improve the rate of correct MG diagnosis. Methods: A retrospective cohort study included 240 LOMG patients with onset age ≥65 years old who were treated at PLA General Hospital from January 1, 2003 to January 1, 2023. Results: The male to female ratio was 1:1.2 (P = 0.699). MGFA clinical classification: Class I 31.3%, Class IIa 12.9%, Class IIb 51.3%, Class IIIa 0.8%, Class IIIb 0.8%, Class IV 0.4%, Class V2.5%. The onset symptom was ptosis in 78.8% and diplopia was in 18.8%. Swallowing dysfunction in the stage of LOMG was in 41.7%. The incidence of thymoma in LOMG was 14.2%. 85.4% of patients antibodies against the muscle acetylcholine receptor (AChR) are detected. The overall incidence of supramaximal repetitive nerve stimulation (Jolly test) was 57.1%, among which the highest positive rate (50.7%) was in the facial nerve. Jolly test of Class IIb was tested in the highest positive rate and Class I was in the lowest one (χ2 = 7.023, P = 0.030). Conclusion: There was no significant difference in the incidence of LOMG between males and females. The clinical manifestations were mainly Class I and Class II, and severe MG was rare. The most common onset symptom was ptosis. The incidence of LOMG with thymoma was low. Supramaximal repetitive nerve stimulation (Jolly test) of the facial nerve was the easiest to detect and Jolly test of Class IIb was tested in the highest positive rate and Class I was in the lowest one.
Volatile organic compounds (VOCs) are ubiquitous in both indoor and outdoor environments. Evidence on the associations of individual and joint VOC exposure with all-cause and cause-specific mortality is limited. Measurements of 15 urinary VOC metabolites were available to estimate exposure to 12 VOCs in the National Health and Nutritional Examination Survey (NHANES) 2005-2006 and 2011-2018. The environment risk score (ERS) was calculated using LASSO regression to reflect joint exposure to VOCs. Follow-up data on death were obtained from the NHANES Public-Use Linked Mortality File through December 31, 2019. Cox proportional hazard models and restricted cubic spline models were applied to evaluate the associations of individual and joint VOC exposures with all-cause and cause-specific mortality. Population attributable fractions were calculated to assess the death burden attributable to VOC exposure. During a median follow-up of 6.17 years, 734 (8.34 %) deaths occurred among 8799 adults. Urinary metabolites of acrolein, acrylonitrile, 1,3-butadiene, and ethylbenzene/styrene were significantly associated with all-cause, cardiovascular disease (CVD), respiratory disease (RD), and cancer mortality in a linear dose-response manner. Linear and robust dose-response relationships were also observed between ERS and all-cause and cause-specific mortality. Each 1-unit increase in ERS was associated with a 33.6 %, 39.1 %, 109.8 %, and 67.8 % increase for all-cause, CVD, RD, and cancer mortality risk, respectively. Moreover, joint exposure to VOCs contributed to 17.95 % of all-cause deaths, 13.49 % of CVD deaths, 35.65 % of RD deaths, and 33.85 % of cancer deaths. Individual and joint exposure to VOCs may enhance the risk of all-cause and cause-specific mortality. Reducing exposure to VOCs may alleviate the all-cause and cause-specific death burden.
Air Pollutants , Benzene Derivatives , Environmental Exposure , Volatile Organic Compounds , Humans , Prospective Studies , Male , United States/epidemiology , Adult , Environmental Exposure/statistics & numerical data , Female , Middle Aged , Air Pollutants/analysis , Nutrition Surveys , Cardiovascular Diseases/mortality , Butadienes , Neoplasms/mortality , Respiratory Tract Diseases/mortality , Mortality
Rationale: To meet the need of long-acting analgesia in postoperative pain management, slow-releasing formulations of local anesthetics (LAs) have been extensively investigated. However, challenges still remain in obtaining such formulations in a facile and cost-effective way, and a mechanism for controlling the release rate to achieve an optimal duration is still missing. Methods: In this study, nanosheets formed by a self-assembling peptide were used to encapsulate ropivacaine in a soft-coating manner. By adjusting the ratio between the peptide and ropivacaine, ropivacaine particles with different size were prepared. Releasing profile of particles with different size were studied in vitro and in vivo. The influence of particle size and ropivacaine concentration on effective duration and toxicity were evaluated in rat models. Results: Our results showed that drug release rate became slower as the particle size increased, with particles of medium size (2.96 ± 0.04 µm) exhibiting a moderate release rate and generating an optimal anesthetic duration. Based on this size, formulations at different ropivacaine concentrations generated anesthetic effect with different durations in rat sciatic nerve block model, with the 6% formulation generated anesthetic duration of over 35 h. Long-acting analgesia up to 48 h of this formulation was also confirmed in a rat total knee arthroplasty model. Conclusion: This study provided a facile strategy to prepare LA particles of different size and revealed the relationship between particle size, release rate and anesthetic duration, which provided both technical and theoretical supports for developing long-acting LA formulations with promising clinical application.
Anesthetics, Local , Nanoparticles , Particle Size , Peptides , Ropivacaine , Ropivacaine/administration & dosage , Ropivacaine/chemistry , Ropivacaine/pharmacokinetics , Animals , Anesthetics, Local/administration & dosage , Anesthetics, Local/chemistry , Rats , Nanoparticles/chemistry , Peptides/chemistry , Peptides/administration & dosage , Pain, Postoperative/drug therapy , Rats, Sprague-Dawley , Male , Analgesia/methods , Delayed-Action Preparations/chemistry , Drug Liberation , Amides/chemistry , Amides/administration & dosage , Sciatic Nerve/drug effects , Disease Models, Animal
BACKGROUND: Rhythm control is a cornerstone of atrial fibrillation (AF) management. Shorter time between diagnosis of AF and receipt of catheter ablation is associated with greater rates of therapy success. Previous work considered diagnosis-to-ablation time as a binary or categorical variable and did not consider the unique risk profile of patients after a referral for ablation was made. OBJECTIVE: The purpose of this study was to comprehensively assess the impact of diagnosis-to-ablation and referral-to-ablation time on postprocedural outcomes at a population level. METHODS: This observational cohort study included patients who received catheter ablation to treat AF in Ontario, Canada. Patient demographics, medical comorbidities, AF diagnosis date, ablation referral date, and ablation date were collected. The primary outcomes of interest included a composite of death and hospitalization/emergency department visit for AF, heart failure, or ischemic stroke. Multivariable Cox models assessed the impact of diagnosis-to-ablation and referral-to-ablation times on the primary outcome. RESULTS: Our cohort included 7472 patients who received ablation for de novo AF between April 1, 2016, and March 31, 2022. Median [interquartile range] diagnosis-to-ablation time was 718 [399-1274] days and median referral-to-ablation time was 221 [117-363] days. Overall, 911 patients (12.2%) had the composite endpoint within 1 year of ablation. Increasing diagnosis-to-ablation time was associated with a greater incidence for the primary outcome (hazard ratio [HR]1.02; 95% confidence interval [CI] 1.01-1.02 per month). Increasing referral-to-ablation time did not impact the primary outcome (HR 1.00; 95% CI 0.98-1.01 per month). CONCLUSION: Delays between AF diagnosis and ablation referral may contribute to adverse postprocedural outcomes and provide an opportunity for health system quality improvements.
BACKGROUND: Berberine is an isoquinoline alkaloid that is extensively applied in the clinic due to its potential therapeutic effects on dysentery and infectious diarrhoea. Its main metabolite, berberrubine, a promising candidate for ameliorating hyperlipidaemia, has garnered more attention than berberine. However, our study revealed that berberrubine induces severe kidney damage, while berberine was proven to be safe. PURPOSE: Herein, we explored the opposite biological effects of these two compounds on the kidney and elucidated their underlying mechanisms. METHODS: First, integrated metabolomic and proteomic analyses were conducted to identify relevant signalling pathways. Second, a click chemistry method combined with a cellular thermal shiftassay, a drug affinity responsive target stability assay, and microscale thermophoresis were used to identify the direct target proteins. Moreover, a mutation experiment was performed to study the specific binding sites. RESULTS: Animal studies showed that berberrubine, but not berberine, induced severe chronic, subchronic, and acute nephrotoxicity. More importantly, berberine reversed the berberrubine-reduced nephrotoxicity. The results indicated that the cPLA2 signalling pathway was highly involved in the nephrotoxicity induced by berberrubine. We further confirmed that the direct target of berberrubine is the BASP1 protein (an upstream factor of cPLA2 signalling). Moreover, berberine alleviated nephrotoxicity by binding cPLA2 and inhibiting cPLA2 activation. CONCLUSION: This study is the first to revel the opposite biological effects of berberine and its metabolite berberrubine in inducing kidney injury. Berberrubine, but not berberine, shows strong nephrotoxicity. The cPLA2 signalling pathway can be activated by berberrubine through targeting of BASP1, while berberine inhibits this pathway by directly binding with cPLA2. Our study paves the way for studies on the exact molecular targets of herbal ingredients. We also demonstrated that natural small molecules and their active metabolites can have opposite regulatory roles in vivo through the same signalling pathway.
Berberine , Kidney , Berberine/analogs & derivatives , Berberine/pharmacology , Animals , Kidney/drug effects , Male , Signal Transduction/drug effects , Humans , Proteomics , Kidney Diseases/chemically induced , Kidney Diseases/drug therapy , Rats, Sprague-Dawley , Mice , Rats
BACKGROUND: This retrospective study investigated the prognostic value of serum inflammatory markers in nasopharyngeal carcinoma (NPC) patients, focusing on their association with overall survival (OS) and liver metastasis-free survival (LMFS). METHODS: The study included 314 NPC patients treated between 2010 and 2020. Clinical characteristics, treatment methods, and serum inflammatory markers were assessed. Patients were categorized into two groups of with and without liver metastasis. Univariate and multivariate Cox regression and Kaplan-Meier survival analyses were performed to investigate the prognostic value of serum inflammatory markers in NPC patients with and without liver metastasis. RESULTS: In the whole cohort, univariate Cox regression analysis singled out tumor necrosis factor-α (TNF-α) (HR = 1.57, 95% CI 1.44-4.90, p = 0.004) and neutrophil-to-lymphocyte ratio (NLR) (HR = 2.13, 95% CI 1.33-3.99, p = 0.009), which were significantly associated with poorer OS. In patients with liver metastasis, TNF-α and NLR could not independently predict OS. However, high TNF-α levels were independently associated with worse OS in patients without liver metastasis (HR (95% CI) = 2.75 (1.67-8.68), p < 0.001). High NLR levels could independently predict poor OS in both groups with (HR (95% CI) = 1.94 (1.77-6.38), p = 0.010) and without liver metastasis (HR (95% CI) = 1.58 (1.19-7.54), p = 0.009). Ultimately, TNF-α and NLR could not significantly predict LMFS. CONCLUSION: This study highlights the prognostic significance of TNF-α and NLR in NPC patients, especially in those with liver metastasis. These inflammatory markers could serve as valuable indicators for assessing the prognosis of NPC patients. Further research is warranted to validate their clinical utility and explore potential therapeutic implications.
Modern medicine has produced large genetic datasets of high dimensions through advanced gene sequencing technology, and processing these data is of great significance for clinical decision-making. Gene selection (GS) is an important data preprocessing technique that aims to select a subset of feature information to improve performance and reduce data dimensionality. This study proposes an improved wrapper GS method based on forensic-based investigation (FBI). The method introduces the search mechanism of the slime mould algorithm in the FBI to improve the original FBI; the newly proposed algorithm is named SMA_FBI; then GS is performed by converting the continuous optimizer to a binary version of the optimizer through a transfer function. In order to verify the superiority of SMA_FBI, experiments are first executed on the 30-function test set of CEC2017 and compared with 10 original algorithms and 10 state-of-the-art algorithms. The experimental results show that SMA_FBI is better than other algorithms in terms of finding the optimal solution, convergence speed, and robustness. In addition, BSMA_FBI (binary version of SMA_FBI) is compared with 8 binary algorithms on 18 high-dimensional genetic data from the UCI repository. The results indicate that BSMA_FBI is able to obtain high classification accuracy with fewer features selected in GS applications. Therefore, SMA_FBI is considered an optimization tool with great potential for dealing with global optimization problems, and its binary version, BSMA_FBI, can be used for GS tasks.
Algorithms , Physarum polycephalum , Clinical Decision-Making , Genetic Techniques , Technology
Quasi-solid-state batteries (QSSBs) are gaining widespread attention as a promising solution to improve battery safety performance. However, the safety improvement and the underlying mechanisms of QSSBs remain elusive. Herein, a novel strategy combining high-safety ethylene carbonate-free liquid electrolyte and in situ polymerization technique is proposed to prepare practical QSSBs. The Ah-level QSSBs with LiNi0.83Co0.11Mn0.06O2 cathode and graphite-silicon anode demonstrate significantly improved safety features without sacrificing electrochemical performance. As evidenced by accelerating rate calorimetry tests, the QSSBs exhibit increased self-heating temperature and onset temperature (T2), and decreased temperature rise rate during thermal runaway (TR). The T2 has a maximum increase of 48.4 °C compared to the conventional liquid batteries. Moreover, the QSSBs do not undergo TR until 180 °C (even 200 °C) during the hot-box tests, presenting significant improvement compared to the liquid batteries that run into TR at 130 °C. Systematic investigations show that the in situ formed polymer skeleton effectively mitigates the exothermic reactions between lithium salts and lithiated anode, retards the oxygen release from cathode, and inhibits crosstalk reactions between cathode and anode at elevated temperatures. The findings offer an innovative solution for practical high-safety QSSBs and open up a new sight for building safer high-energy-density batteries.
