BACKGROUND Gastric cancer is the most common malignancy of the digestive system and surgical resection is the primary treatment.Advances in surgical technology have reduced the risk of complications after radical gast...BACKGROUND Gastric cancer is the most common malignancy of the digestive system and surgical resection is the primary treatment.Advances in surgical technology have reduced the risk of complications after radical gastrectomy;however,post-surgical pancreatic fistula remain a serious issue.These fistulas can lead to abdominal infections,anastomotic leakage,increased costs,and pain;thus,early diagnosis and prevention are crucial for a better prognosis.Currently,C-reactive protein(CRP),procalcitonin(PCT),and total bilirubin(TBil)levels are used to predict post-operative infections and anastomotic leakage.However,their predictive value for pancreatic fistula after radical gastrectomy for gastric cancer remains unclear.The present study was conducted to determine their predictive value.AIM To determine the predictive value of CRP,PCT,and TBil levels for pancreatic fistula after gastric cancer surgery.METHODS In total,158 patients who underwent radical gastrectomy for gastric cancer at our hospital between January 2019 and January 2023 were included.The patients were assigned to a pancreatic fistula group or a non-pancreatic fistula group.Multivariate logistic analysis was conducted to assess the factors influencing development of a fistula.Receiver operating characteristic(ROC)curves were used to determine the predictive value of serum CRP,PCT,and TBil levels on day 1 postsurgery.RESULTS On day 1 post-surgery,the CRP,PCT,and TBil levels were significantly higher in the pancreatic fistula group than in the non-pancreatic fistula group(P<0.05).A higher fistula grade was associated with higher levels of the indices.Univariate analysis revealed significant differences in the presence of diabetes,hyperlipidemia,pancreatic injury,splenectomy,and the biomarker levels(P<0.05).Logistic multivariate analysis identified diabetes,hyperlipidemia,pancreatic injury,CRP level,and PCT level as independent risk factors.ROC curves yielded predictive values for CRP,PCT,and TBil levels,with the PCT level having the highest area under the curve(AUC)of 0.80[95%confidence interval(CI):0.72-0.90].Combined indicators improved the predictive value,with an AUC of 0.86(95%CI:0.78-0.93).CONCLUSION Elevated CRP,PCT,and TBil levels predict risk of pancreatic fistula post-gastrectomy for gastric cancer.展开更多
Chronic low-grade inflammation is a major contributor to both the onset and advancement of type 2 diabetes mellitus(T2DM),and its associated microvascular complications,including diabetic nephropathy,retinopathy,and p...Chronic low-grade inflammation is a major contributor to both the onset and advancement of type 2 diabetes mellitus(T2DM),and its associated microvascular complications,including diabetic nephropathy,retinopathy,and peripheral neuropathy.This review aims to overview the roles of high sensitivity C-reactive protein(hs-CRP),C-reactive protein(CRP),CRP-to-lymphocyte count ratio(CLR),and the CRP-to-albumin ratio(CAR)as biomarkers for assessing systemic inflammation and predicting the development and severity of diabetic chronic microvascular complications.Elevated levels of CRP and hs-CRP have been consistently associated with increased risk of these complications,reflecting ongoing inflammatory processes that contribute to endothelial dysfunction and tissue damage.Furthermore,CAR and CLR,which combine CRP with albumin and lymphocyte counts respectively,offer a more nuanced understanding of the inflammatory and immune response in T2DM patients.While individual studies have demonstrated the clinical relevance of these biomarkers in predicting disease onset and progression,further investigation is needed to establish their utility in clinical practice.This review highlights the potential of these biomarkers for enhancing early detection,risk stratification,and personalized management of diabetic patients,ultimately aiming to improve outcomes and reduce the burden of diabetic chronic microvascular complications.展开更多
Background:Bacterial pneumonia continues to be a significant global health concern,particularly among high-risk groups,necessitating the development of precise and early diagnostic biomarkers.While the efficacy of pro...Background:Bacterial pneumonia continues to be a significant global health concern,particularly among high-risk groups,necessitating the development of precise and early diagnostic biomarkers.While the efficacy of procalcitonin(PCT)and C-reactive protein(CRP)as inflammatory markers is widely recognized,their relative diagnostic performance across different age groups remains debate.This meta-analysis was designed to assess the diagnostic accuracy of PCT and CRP in bacterial pneumonia.Methods:In this meta-analysis adhering to PRISMA guidelines,we searched PubMed,Web of Science,and the Cochrane Library for relevant diagnostic accuracy studies.From 19 included studies(n=2,603),data were extracted to construct tables.Study quality was assessed with the QUADAS-2 tool.The bivariate random-effects model was employed to derive pooled sensitivity,specificity,positive and negative likelihood ratios,and summary AUCs.To explore the substantial heterogeneity(I^(2)>80%),we performed pre-specified subgroup analyses based on age demographics.Results:Our findings indicate superior diagnostic performance for PCT,evidenced by a pooled sensitivity of 0.8841 and specificity of 0.8499,relative to CRP’s sensitivity of 0.8371 and specificity of 0.7185.The area under the ROC curve(AUC)for PCT was 0.992,a value significantly higher than that of CRP(0.987).Intriguingly,subgroup analyses revealed age-dependent variations:CRP demonstrated enhanced diagnostic utility in minors,while PCT proved substantially more effective in non-elderly adults.Conclusion:These results reinforce the clinical relevance of PCT as a more dependable biomarker for bacterial pneumonia,particularly in informing antibiotic treatment and mitigating misuse.This study uniquely includes age-stratified analyses based on predefined groups(minors and non-elderly adults),providing refined insights for individualized diagnostic approaches.We propose further multicenter research endeavors to confirm threshold optimization and explore combined biomarker strategies.展开更多
Background and Objective Inflammation plays a pivotal role in the progression of coronary artery disease(CAD).High-sensitivity C-reactive protein(hsCRP)serves as a well-established biomarker for assessing cardiovascul...Background and Objective Inflammation plays a pivotal role in the progression of coronary artery disease(CAD).High-sensitivity C-reactive protein(hsCRP)serves as a well-established biomarker for assessing cardiovascular inflammation risk.However,the specific intestinal microbiota alteration contributing to increased inflammation remains unclear.Therefore,the present study investigated the correlation between the intestinal microbiota and inflammation in patients with unstable angina(UA).Methods A cohort of 92 patients with UA was recruited for this study.The plasma hsCRP level was measured via a CardioPhase hsCRP assay,fecal samples were collected after admission,and 16S rRNA sequencing was conducted to identify the fecal microbial profile.The participants were classified into two groups according to the median hsCRP level(1.11 mg/L).The composition of the fecal microbiota was compared between patients with hsCRP≥1.11 mg/L and those with hsCRP<1.11 mg/L.Additionally,the correlations between the fecal microbiota and clinical characteristics were analyzed.Results A notable reduction in the relative abundance of Akkermansia was observed in patients with hsCRP≥1.11 mg/L,whereas the diversity of the fecal microbiota was not significantly different between patients with hsCRP≥1.11 mg/L and those with hsCRP<1.11 mg/L.Furthermore,the abundance of Akkermansia was negatively correlated with hsCRP levels.Conclusion This study suggested a significant association between decreased levels of Akkermansia and inflammatory risk in patients with UA.These findings underscore the potential role of the intestinal microbiota in contributing to inflammation in UA patients.Further work is needed on the mechanism by which the microbiota contributes to inflammatory risk.展开更多
AIM:To determine the differences in levels of systemic C-reactive protein(CRP)in patients with geographic atrophy(GA)and sex-based differences in CRP levels.METHODS:Blood samples from patients with GA and controls wer...AIM:To determine the differences in levels of systemic C-reactive protein(CRP)in patients with geographic atrophy(GA)and sex-based differences in CRP levels.METHODS:Blood samples from patients with GA and controls were collected in a prospective age-related macular degeneration(AMD)registry from August 2014 to June 2021.AMD was confirmed using multimodal imaging and the Beckman and Consensus of Atrophy Meeting criteria for GA.High-sensitivity serum CRP levels were measured using an automated nephelometer.A non-parametric(rank-based)linear regression model was fit with an interaction between sex and GA.RESULTS:There were 97 GA patients and 139 controls,with females comprising 55%and 66%of each cohort,respectively.There is no difference in CRP between cases and controls,with a median(interquartile range)of 1.2(0.6-2.6)mg/L in GA patients versus 1.3(0.8–2.9)mg/L in controls(P=0.52).Although females had higher CRP levels compared to males in both the GA and control groups,this difference did not reach statistical significance after adjustment for multiple comparisons.CONCLUSION:There is no significant difference in systemic CRP levels between GA cases and controls.展开更多
Objective:To analyze the diagnostic value of combined testing of C-reactive protein(CRP)and procalcitonin(PCT)in elderly patients with bacterial pneumonia.Methods:This study included 50 elderly patients with bacterial...Objective:To analyze the diagnostic value of combined testing of C-reactive protein(CRP)and procalcitonin(PCT)in elderly patients with bacterial pneumonia.Methods:This study included 50 elderly patients with bacterial pneumonia as the observation group and 50 patients with non-bacterial pneumonia as the control group,recruited from May 2022 to October 2023.Fasting venous blood samples were collected in the morning from all 100 participants.CRP levels were measured using a fully automated biochemical analyzer,while PCT levels were detected using the immunoturbidimetric luminescence method.Results:CRP and PCT levels were significantly higher in bacterial pneumonia patients[(98.25±11.59)mg/L and(3.57±1.35)μg/L,respectively]compared to the control group[(5.55±2.78)mg/L and(0.25±0.12)μg/L,respectively],with significant intergroup differences(P<0.05).Patients with severe bacterial pneumonia exhibited higher serum CRP and PCT levels compared to those with moderate or mild disease(P<0.05).The combined testing of CRP and PCT showed higher sensitivity and specificity than individual tests.In the observation group,CRP and PCT levels significantly decreased after treatment compared to pre-treatment levels.Conclusion:The combination of CRP and PCT testing provides high diagnostic accuracy for bacterial pneumonia in elderly patients.It effectively differentiates bacterial from non-bacterial infections,offering valuable data to guide clinical treatment.展开更多
The advancement of various types of fluorescent nanoparticles is crucial for enhancing the application of lateral flow immunoassays(LFIA)across multiple fields.Currently,the fluorescent nanoparticles utilized in LFIA ...The advancement of various types of fluorescent nanoparticles is crucial for enhancing the application of lateral flow immunoassays(LFIA)across multiple fields.Currently,the fluorescent nanoparticles utilized in LFIA predominantly consist of traditional dye-doped nanoparticles or aggregation-induced luminescence dye-doped nanoparticles.The reliance on specific types of nanoparticles limits the diversity of signal reporting groups available for LFIA.Herein,we developed a solid-state luminescent dye-doped nanoparticles(SLDNPs)-based LFIA system with exceptional stability for the detection of C-reactive protein(CRP)in serum.The synthesis of SLD_(520)NP_(S)was simplicity,efficient and eco-friendly,which was ideal for large-scale production of the LFIA test strip.And the SLD_(520)NP_(S)exhibits superior fluorescence quantum yield(49%),fully guarantees the performance of the LFIA test strip.The constructed SLD_(520)NPsm Ab1-based LFIA demonstrated a satisfactory linear relationship with CRP concentrations ranging from 0.5 ng/mL to 100 ng/mL,with limits of detection(LOD)of 0.78 ng/mL and a visible LOD of 1 ng/mL using a handheld 405 nm lamp.Furthermore,the developed LFIA exhibited excellent recoveries in serum,ranging from 94.45%to 102.5%.Overall,the outstanding performance of the SLD_(520)NPs-mAb1-based LFIA indicates that solid-state luminescent dyes have significant potential applications in the field of LFIA.展开更多
In this study,thyme essential oil(TEO)nanoemulsion(tPTNs)was constructed with transglutaminase(TGase)-modified potato protein,and its antibacterial activity and mechanism of action were evaluated and explored.Results ...In this study,thyme essential oil(TEO)nanoemulsion(tPTNs)was constructed with transglutaminase(TGase)-modified potato protein,and its antibacterial activity and mechanism of action were evaluated and explored.Results indicated that tPTNs exhibited great antibacterial activity against both Staphylococcus aureus and Escherichia coli,with minimal inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of 2.5 and 5.0 mg/mL,respectively.Also,the antibacterial effects of tPTNs were concentration-dependent.We observed a significant decrease in the absolute value of the zeta potential,and significant increases in particle size,cell membrane hydrophobicity,conductivity,the release of metal ions,and the leakage of nucleic acid as the concentration of tPTNs increased from 0 mg/mL to MBC.Furthermore,sodium dodecyl sulphate-polyacrylamide gel electrophoresis(SDS-PAGE)demonstrated that protein synthesis was inhibited or even disrupted.Analysis by liquid chromatography-mass spectrometry(LC-MS)indicated that treatment with tPTNs caused significant changes in bacterial metabolites,1117 and 692 differential metabolites being found for S.aureus and E.coli,respectively.The differential metabolites were involved in nucleotide metabolism,amino acid metabolism,tricarboxylic acid cycle and other metabolic pathways.These findings provide valuable insights for the application of thyme essential oil as an efficient antibacterial agent and for the understanding of its mechanism of action.展开更多
BACKGROUND Gastric cancer,a globally prevalent malignant tumor,continues to exhibit high incidence and mortality rates.Although radical gastrectomy remains the primary treatment for this disease,postoperative complica...BACKGROUND Gastric cancer,a globally prevalent malignant tumor,continues to exhibit high incidence and mortality rates.Although radical gastrectomy remains the primary treatment for this disease,postoperative complications frequently arise,negatively impacting short-term recovery and significantly reducing patients’quality of life.In this context,accurately predicting the risk of postoperative recurrence and metastasis,coupled with targeted interventions,could substantially improve patient outcomes.The C-reactive protein-triglyceride-glucose index(CTI),a composite biomarker that integrates metabolic disturbances and systemic inflammation,has garnered increasing attention in oncology.The prognostic nutritional index(PNI),a composite measure based on serum albumin and peripheral blood lymphocyte count,is used to evaluate both the nutritional status and systemic immune function of patients.In recent years,both the CTI and PNI have demonstrated significant prognostic value in predicting tumor outcomes,assessing treatment responses,and formulating personalized treatment strategies.AIM To investigate whether the combined inflammation and insulin resistance marker,the CTI,can serve as a prognostic indicator for patients undergoing radical gastrectomy for gastric cancer.Additionally,it seeks to develop a predictive model by incorporating the PNI alongside CTI.METHODS This retrospective study included a total of 300 patients who underwent radical gastrectomy.The patients were classified into high and low CTI groups based on their CTI index.Cox proportional hazards regression analysis was performed to identify independent prognostic factors influencing overall survival(OS)and disease-free survival(DFS),and two nomogram models were developed.RESULTS Of the included patients,131 had a high CTI and 169 had a low CTI.The DFS period of the low CTI group was significantly longer than that of the high CTI group.The number of postoperative adjuvant treatments,T stage,N stage,CTI,and PNI were identified as independent prognostic factors for DFS.The hazard ratio for CTI was 2.07(95%confidence interval:1.36-3.17,P<0.001).In terms of OS,the OS period of the low CTI group was significantly longer than that of the high CTI group.Whether adjuvant treatment was administered,T stage,CTI,and PNI were independent prognostic factors for OS.The hazard ratio for CTI was 2.47(95%confidence interval:1.44-4.23,P=0.001).The nomogram models for OS and DFS further emphasized the importance of CTI as a key predictor of patient prognosis.CONCLUSION CTI is a long-term prognostic indicator for the outcome of radical gastrectomy for gastric cancer.Patients with lower CTI values have a better prognosis.The prediction models constructed by combining CTI with PNI has good predictive ability for DFS and OS after radical gastrectomy.展开更多
Proteostasis,also known as protein homeostasis,is a tightly regulated cellular quality control process that ensures the balance of protein synthesis,folding,posttranslational modifications,and degradation.Maintaining ...Proteostasis,also known as protein homeostasis,is a tightly regulated cellular quality control process that ensures the balance of protein synthesis,folding,posttranslational modifications,and degradation.Maintaining proteostasis is vital for cellular function,organismal health,and longevity.The disru ption of proteostasis can lead to a range of detrimental effects,including accelerated aging,compromised cellular function,and even cell death,manifesting in numerous human diseases(Hipp et al.,2019).展开更多
Oat milk has gained widespread consumer acceptance for its creamy texture,β-glucan content,and environmental sustainability.However,its relatively low protein content(typically 2-3 g/serving)presents a nutritional li...Oat milk has gained widespread consumer acceptance for its creamy texture,β-glucan content,and environmental sustainability.However,its relatively low protein content(typically 2-3 g/serving)presents a nutritional limitation,largely due to poor protein solubility.This study investigated how processing conditions influence protein content and functional stability in oat-based systems by applying two treatments:(1)α-amylase enzymatic hydrolysis,and(2)pH-shifting(from pH 7 to 12 and back)with mild heating(50℃for 10 or 30 min).Oat protein solutions were formulated from two sources:oat flour(OF)and oat protein isolate(OPI).Results suggests that α-amylase pretreatment effectively reduced starch-driven viscosity in OF,facilitating better sample handling and centrifugation.Following pH-shifting and heat treatment,both OF and OPI solutions showed significantly improved protein solubility,with protein content increased from 2.0 to~6.5 g/serving.These changes were accompanied by reduced precipitation,smaller particle sizes,and more negative zeta potential values,indicating enhanced colloidal stability.SDS-PAGE analysis revealed the presence of low-molecular-weight protein fractions,supporting increased solubilization.Fluorescence microscopy confirmed the formation of smaller,more uniformly dispersed particles in treated samples compared to controls.However,noticeable darkening or browning occurred under high-pH heating,indicating potential challenges in color control.The findings provide useful information for future industrial applications and product innovation in the plant-based beverage sector.展开更多
CR Dhan 310(CRD310),a biofortified rice variety,contains a significantly higher level of grain protein compared with its recurrent parent Naveen(NV),as well as most adapted high-yielding rice varieties in India.Althou...CR Dhan 310(CRD310),a biofortified rice variety,contains a significantly higher level of grain protein compared with its recurrent parent Naveen(NV),as well as most adapted high-yielding rice varieties in India.Although a limited investigation depicted that CRD310 contained higher levels of glutelin and some essential amino acids,detailed biochemical,molecular,and cellular mechanisms remain to be studied.As one of the means to identify the proteins and understand the underlying mechanism of higher proteins accumulation in grains of CRD310,the comparative proteomics was undertaken on grains of CRD310 and NV at the yellow ripening stage.展开更多
Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,wi...Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.展开更多
Novel insights into complex biological processes very often critically depend on the establishment of new potent read-out tools and improved protocols.A lot has been learned over the past four decades on physiological...Novel insights into complex biological processes very often critically depend on the establishment of new potent read-out tools and improved protocols.A lot has been learned over the past four decades on physiological functions and,importantly,disease-related roles of the prion protein(PrP),a relatively broadly expressed membrane-anchored glycoprotein with high levels in several cell types of the nervous and immune system and with well-established key roles in different progressive and fatal neurodegenerative protein misfolding diseases(proteopathies).展开更多
BACKGROUND Inflammatory cytokines are associated with cancer prognosis,but their specific role in cholangiocarcinoma remains poorly understood.The lymphocyte to C-reactive protein ratio(LCR),a novel inflammatory-nutri...BACKGROUND Inflammatory cytokines are associated with cancer prognosis,but their specific role in cholangiocarcinoma remains poorly understood.The lymphocyte to C-reactive protein ratio(LCR),a novel inflammatory-nutritional biomarker,has demonstrated predictive value in gastrointestinal cancers;however,its clinical relevance in cholangiocarcinoma has not been investigated.AIM To validate the LCR as an independent prognostic factor for overall survival(OS),surgical site infection(SSI),and length of hospital stay in patients with resectable cholangiocarcinoma.METHODS We conducted a retrospective analysis of 76 patients with cholangiocarcinoma who underwent radical surgery between 2008 and 2013.The preoperative LCR was calculated as the lymphocyte count divided by C-reactive protein level,using a cutoff value of 180.Univariate and multivariate logistic regression analyses were performed to evaluate factors associated with SSI and hospitalization duration,while Kaplan-Meier survival curves and Cox proportional hazards models were used to assess predictors of OS.RESULTS Patients in the low LCR group was significantly associated with several adverse clinical outcomes:A shorter median OS(14.93 months vs 46.67 months;P=0.022);a 4.5-fold increased risk of prolonged hospitalization(P=0.007);and a higher incidence of SSI(odds ratio=4.41,P=0.045).Multivariate analysis confirmed that LCR was an independent predictor of OS[hazard ratio(HR)=3.204,P=0.002],SSI,and hospitalization duration.Additionally,R0 resection(HR=3.546,P=0.002)and advanced tumor-node-metastasis stage(HR=2.016,P=0.035)were identified as independent prognostic factors for OS.CONCLUSION In this retrospective study,preoperative LCR is a cost-effective and practical biomarker that independently predicts OS,postoperative complications,and hospitalization duration in patients with resectable cholangiocarcinoma,thereby facilitating more precise patient stratification.展开更多
Protein aggregation drives proteinopathies ranging from ALS to systemic amyloidosis,yet the multiscale determinants bridging sequence,structure,and kinetics remain elusive.We present SKALE,an interpretable machine lea...Protein aggregation drives proteinopathies ranging from ALS to systemic amyloidosis,yet the multiscale determinants bridging sequence,structure,and kinetics remain elusive.We present SKALE,an interpretable machine learning framework that integrates sequence motifs,AlphaFold-derived structural descriptors,and experimental kinetics to decode aggregation mechanisms.SKALE identifies latent hotspots that evade conventional tools and matches high-performing neural baselines while preserving computational efficiency.In ALS-linked SOD1 G86R,the model isolates a risk region at residues 72-91 where preserved β-sheet geometry coincides with weakened hydrogen bonding to drive nucleation.Similarly,analysis of TDP-43 S332N reveals that a locally unwound helix increases surface exposure,a prediction validated by showing that targeted deletion of model-identified regions significantly reduces cellular aggregation.The framework generalizes to Tau P301L and PRNP variants where it uncovers distal aggregation-prone regions to discriminate pathogenic drivers from neutral mutations.Interpretability analysis further disentangles global from mutation-local mechanisms to reveal that β-sheet propensity acts as a shared determinant while hydrogen bond dynamics define specific routes to nucleation.These findings establish SKALE as a scalable,disease-agnostic engine that combines high-fidelity prediction with biophysical resolution to decode the molecular logic of misfolding and guide therapeutic design.展开更多
BACKGROUND Acute-on-chronic liver failure(ACLF)is a life-threatening syndrome associated with high short-term mortality.Accurate risk stratification is crucial for the mana-gement of ACLF.AIM To evaluate the prognosti...BACKGROUND Acute-on-chronic liver failure(ACLF)is a life-threatening syndrome associated with high short-term mortality.Accurate risk stratification is crucial for the mana-gement of ACLF.AIM To evaluate the prognostic value of the C-reactive protein to albumin ratio(CAR)and its dynamic changes in patients with ACLF defined by the Chinese Group on Study of Severe Hepatitis B(COSSH)criteria.METHODS A total of 126 consecutive patients diagnosed with COSSH-ACLF were pros-pectively enrolled.CAR was calculated at admission and on days 4,7,and 14.The primary and secondary outcomes were 28-day and 90-day mortality,respectively.Multivariate Cox regression analysis was conducted to identify independent predictors of mortality.A novel prognostic model(COSSH-CAR),integrating baseline and dynamic variables,was developed and compared with established prognostic scoring systems.RESULTS The 28-day and 90-day mortality rates were 27.8%and 40.5%,respectively.Baseline CAR was significantly higher in 28-day non-survivors than in survivors(2.68 vs 1.42,P<0.001).The dynamic change in CAR from baseline to day 7(ΔCAR-7)showed stronger predictive power for 28-day mortality[area under the receiver operating characteristic curve(AUC)=0.765]than baseline CAR(AUC=0.698),ΔCAR-4(AUC=0.706)orΔCAR-14(AUC=0.712).Multivariate analysis identifiedΔCAR-7(HR=1.53),baseline Model for End-Stage Liver Disease-Sodium(MELD-Na)score(HR=1.08),and hepatic encephalopathy grade(HR=1.92)as independent predictors of 28-day mortality(all P<0.05).The COSSH-CAR model,which incorporated these parameters,showed superior predictive performance(AUC=0.832)for 28-day mortality compared with established prognostic scores,including Child-Pugh(AUC=0.721),MELD-Na(AUC=0.768)and COSSH-ACLF(AUC=0.786)and effectively stratified patients into three risk categories with significantly different survival rates(P<0.001).CONCLUSION Dynamic changes in CAR during the first week provide important prognostic information in patients with COSSH-ACLF,surpassing baseline values and conventional inflammatory markers.The novel COSSH-CAR model improves risk stratification and may support clinical decision-making in the management of ACLF,pending ex-ternal validation in diverse populations.展开更多
Ataxin-2 is a 140 kDa cytoplasmic multifunctional protein that plays fundamental roles in diverse cellular mechanisms(Costa et al.,2024).Although widely studied in the context of the neurodegenerative diseases spinoce...Ataxin-2 is a 140 kDa cytoplasmic multifunctional protein that plays fundamental roles in diverse cellular mechanisms(Costa et al.,2024).Although widely studied in the context of the neurodegenerative diseases spinocerebellar ataxia type 2(SCA2)and amyotrophic lateral sclerosis(ALS),ataxin-2 functions span far beyond its pathogenic properties in the disease context(Figure 1).In fact,it has a wide range of biological functions that include RNA metabolism,translation regulation,stress response,endocytosis,calcium signaling,and the control of circadian rhythm.In this perspective,we highlight the main roles of ataxin-2 protein,which are described in detail in Costa et al.(2024).展开更多
In an era of profound changes to global trade,food security,and industrial organization,the ChinaIndonesia“Two Countries,Twin Parks”initiative has emerged as a strategic experiment with farreaching implications.Anch...In an era of profound changes to global trade,food security,and industrial organization,the ChinaIndonesia“Two Countries,Twin Parks”initiative has emerged as a strategic experiment with farreaching implications.Anchored in marine protein processing and advanced food manufacturing,this collaboration reflects not only a convergence of economic interests but also a deliberate rethinking of how China engages with global resources,technology,and partners.展开更多
文摘BACKGROUND Gastric cancer is the most common malignancy of the digestive system and surgical resection is the primary treatment.Advances in surgical technology have reduced the risk of complications after radical gastrectomy;however,post-surgical pancreatic fistula remain a serious issue.These fistulas can lead to abdominal infections,anastomotic leakage,increased costs,and pain;thus,early diagnosis and prevention are crucial for a better prognosis.Currently,C-reactive protein(CRP),procalcitonin(PCT),and total bilirubin(TBil)levels are used to predict post-operative infections and anastomotic leakage.However,their predictive value for pancreatic fistula after radical gastrectomy for gastric cancer remains unclear.The present study was conducted to determine their predictive value.AIM To determine the predictive value of CRP,PCT,and TBil levels for pancreatic fistula after gastric cancer surgery.METHODS In total,158 patients who underwent radical gastrectomy for gastric cancer at our hospital between January 2019 and January 2023 were included.The patients were assigned to a pancreatic fistula group or a non-pancreatic fistula group.Multivariate logistic analysis was conducted to assess the factors influencing development of a fistula.Receiver operating characteristic(ROC)curves were used to determine the predictive value of serum CRP,PCT,and TBil levels on day 1 postsurgery.RESULTS On day 1 post-surgery,the CRP,PCT,and TBil levels were significantly higher in the pancreatic fistula group than in the non-pancreatic fistula group(P<0.05).A higher fistula grade was associated with higher levels of the indices.Univariate analysis revealed significant differences in the presence of diabetes,hyperlipidemia,pancreatic injury,splenectomy,and the biomarker levels(P<0.05).Logistic multivariate analysis identified diabetes,hyperlipidemia,pancreatic injury,CRP level,and PCT level as independent risk factors.ROC curves yielded predictive values for CRP,PCT,and TBil levels,with the PCT level having the highest area under the curve(AUC)of 0.80[95%confidence interval(CI):0.72-0.90].Combined indicators improved the predictive value,with an AUC of 0.86(95%CI:0.78-0.93).CONCLUSION Elevated CRP,PCT,and TBil levels predict risk of pancreatic fistula post-gastrectomy for gastric cancer.
文摘Chronic low-grade inflammation is a major contributor to both the onset and advancement of type 2 diabetes mellitus(T2DM),and its associated microvascular complications,including diabetic nephropathy,retinopathy,and peripheral neuropathy.This review aims to overview the roles of high sensitivity C-reactive protein(hs-CRP),C-reactive protein(CRP),CRP-to-lymphocyte count ratio(CLR),and the CRP-to-albumin ratio(CAR)as biomarkers for assessing systemic inflammation and predicting the development and severity of diabetic chronic microvascular complications.Elevated levels of CRP and hs-CRP have been consistently associated with increased risk of these complications,reflecting ongoing inflammatory processes that contribute to endothelial dysfunction and tissue damage.Furthermore,CAR and CLR,which combine CRP with albumin and lymphocyte counts respectively,offer a more nuanced understanding of the inflammatory and immune response in T2DM patients.While individual studies have demonstrated the clinical relevance of these biomarkers in predicting disease onset and progression,further investigation is needed to establish their utility in clinical practice.This review highlights the potential of these biomarkers for enhancing early detection,risk stratification,and personalized management of diabetic patients,ultimately aiming to improve outcomes and reduce the burden of diabetic chronic microvascular complications.
基金supported by the National Natural Science Foundation of China(82360801,82460822)Natural Science Foundation of Inner Mongolia Autonomous Region(2022LHQN08001,2023QN08050,2025LHMS08061)+4 种基金the Scientific Research Project of Higher Education Institutions in Inner Mongolia Autonomous Region(NJZY23135)the Laboratory Open Fund of Inner Mongolia Medical University(2024ZN23)and the General Project of Inner Mongolia Medical University(YKD2025MS047Inner Mongolia Medical University Undergraduate Science and Technology Innovation"Talent Cultivation"Project(YCPY2025028,YCPY2025024)Inner Mongolia Medical University Undergraduate Innovation and Entrepreneurship Training Program Project(101322025034).
文摘Background:Bacterial pneumonia continues to be a significant global health concern,particularly among high-risk groups,necessitating the development of precise and early diagnostic biomarkers.While the efficacy of procalcitonin(PCT)and C-reactive protein(CRP)as inflammatory markers is widely recognized,their relative diagnostic performance across different age groups remains debate.This meta-analysis was designed to assess the diagnostic accuracy of PCT and CRP in bacterial pneumonia.Methods:In this meta-analysis adhering to PRISMA guidelines,we searched PubMed,Web of Science,and the Cochrane Library for relevant diagnostic accuracy studies.From 19 included studies(n=2,603),data were extracted to construct tables.Study quality was assessed with the QUADAS-2 tool.The bivariate random-effects model was employed to derive pooled sensitivity,specificity,positive and negative likelihood ratios,and summary AUCs.To explore the substantial heterogeneity(I^(2)>80%),we performed pre-specified subgroup analyses based on age demographics.Results:Our findings indicate superior diagnostic performance for PCT,evidenced by a pooled sensitivity of 0.8841 and specificity of 0.8499,relative to CRP’s sensitivity of 0.8371 and specificity of 0.7185.The area under the ROC curve(AUC)for PCT was 0.992,a value significantly higher than that of CRP(0.987).Intriguingly,subgroup analyses revealed age-dependent variations:CRP demonstrated enhanced diagnostic utility in minors,while PCT proved substantially more effective in non-elderly adults.Conclusion:These results reinforce the clinical relevance of PCT as a more dependable biomarker for bacterial pneumonia,particularly in informing antibiotic treatment and mitigating misuse.This study uniquely includes age-stratified analyses based on predefined groups(minors and non-elderly adults),providing refined insights for individualized diagnostic approaches.We propose further multicenter research endeavors to confirm threshold optimization and explore combined biomarker strategies.
基金supported by the National Natural Science Foundation of China(No.82030016,No 82230011 and No.82200533).
文摘Background and Objective Inflammation plays a pivotal role in the progression of coronary artery disease(CAD).High-sensitivity C-reactive protein(hsCRP)serves as a well-established biomarker for assessing cardiovascular inflammation risk.However,the specific intestinal microbiota alteration contributing to increased inflammation remains unclear.Therefore,the present study investigated the correlation between the intestinal microbiota and inflammation in patients with unstable angina(UA).Methods A cohort of 92 patients with UA was recruited for this study.The plasma hsCRP level was measured via a CardioPhase hsCRP assay,fecal samples were collected after admission,and 16S rRNA sequencing was conducted to identify the fecal microbial profile.The participants were classified into two groups according to the median hsCRP level(1.11 mg/L).The composition of the fecal microbiota was compared between patients with hsCRP≥1.11 mg/L and those with hsCRP<1.11 mg/L.Additionally,the correlations between the fecal microbiota and clinical characteristics were analyzed.Results A notable reduction in the relative abundance of Akkermansia was observed in patients with hsCRP≥1.11 mg/L,whereas the diversity of the fecal microbiota was not significantly different between patients with hsCRP≥1.11 mg/L and those with hsCRP<1.11 mg/L.Furthermore,the abundance of Akkermansia was negatively correlated with hsCRP levels.Conclusion This study suggested a significant association between decreased levels of Akkermansia and inflammatory risk in patients with UA.These findings underscore the potential role of the intestinal microbiota in contributing to inflammation in UA patients.Further work is needed on the mechanism by which the microbiota contributes to inflammatory risk.
基金Supported by the Greenwald Family Research Fund,a Research to Prevent Blindness grant to the Department of Ophthalmology,University of Colorado,the Frederic C.Hamilton Macular Degeneration Center,Sue Anschutz-Rodgers Eye Center Research Fund,NIH/NCATS Colorado CTSA(No.UL1 TR002535)in part by the National Eye Institute of the National Institutes of Health[No.R01EY032456(AML)].
文摘AIM:To determine the differences in levels of systemic C-reactive protein(CRP)in patients with geographic atrophy(GA)and sex-based differences in CRP levels.METHODS:Blood samples from patients with GA and controls were collected in a prospective age-related macular degeneration(AMD)registry from August 2014 to June 2021.AMD was confirmed using multimodal imaging and the Beckman and Consensus of Atrophy Meeting criteria for GA.High-sensitivity serum CRP levels were measured using an automated nephelometer.A non-parametric(rank-based)linear regression model was fit with an interaction between sex and GA.RESULTS:There were 97 GA patients and 139 controls,with females comprising 55%and 66%of each cohort,respectively.There is no difference in CRP between cases and controls,with a median(interquartile range)of 1.2(0.6-2.6)mg/L in GA patients versus 1.3(0.8–2.9)mg/L in controls(P=0.52).Although females had higher CRP levels compared to males in both the GA and control groups,this difference did not reach statistical significance after adjustment for multiple comparisons.CONCLUSION:There is no significant difference in systemic CRP levels between GA cases and controls.
文摘Objective:To analyze the diagnostic value of combined testing of C-reactive protein(CRP)and procalcitonin(PCT)in elderly patients with bacterial pneumonia.Methods:This study included 50 elderly patients with bacterial pneumonia as the observation group and 50 patients with non-bacterial pneumonia as the control group,recruited from May 2022 to October 2023.Fasting venous blood samples were collected in the morning from all 100 participants.CRP levels were measured using a fully automated biochemical analyzer,while PCT levels were detected using the immunoturbidimetric luminescence method.Results:CRP and PCT levels were significantly higher in bacterial pneumonia patients[(98.25±11.59)mg/L and(3.57±1.35)μg/L,respectively]compared to the control group[(5.55±2.78)mg/L and(0.25±0.12)μg/L,respectively],with significant intergroup differences(P<0.05).Patients with severe bacterial pneumonia exhibited higher serum CRP and PCT levels compared to those with moderate or mild disease(P<0.05).The combined testing of CRP and PCT showed higher sensitivity and specificity than individual tests.In the observation group,CRP and PCT levels significantly decreased after treatment compared to pre-treatment levels.Conclusion:The combination of CRP and PCT testing provides high diagnostic accuracy for bacterial pneumonia in elderly patients.It effectively differentiates bacterial from non-bacterial infections,offering valuable data to guide clinical treatment.
基金supported by the National Natural Science Foundation of China(Nos.22064014,21765013)the Science and Technology Development Plan Project of Lanzhou(No.20211-146)+3 种基金the Science and Technology Project of Gansu Province(Nos.21YF5FA071,21JR7RA538)the Industrial Support Programme for Higher Education Institutions Project(Nos.2023CYZC-69,2024CYCZ-05)the 2023 Gansu Provincial Key Talent Project(No.2023RCXM26)a Gansu province postdoctoral grant(No.00247)。
文摘The advancement of various types of fluorescent nanoparticles is crucial for enhancing the application of lateral flow immunoassays(LFIA)across multiple fields.Currently,the fluorescent nanoparticles utilized in LFIA predominantly consist of traditional dye-doped nanoparticles or aggregation-induced luminescence dye-doped nanoparticles.The reliance on specific types of nanoparticles limits the diversity of signal reporting groups available for LFIA.Herein,we developed a solid-state luminescent dye-doped nanoparticles(SLDNPs)-based LFIA system with exceptional stability for the detection of C-reactive protein(CRP)in serum.The synthesis of SLD_(520)NP_(S)was simplicity,efficient and eco-friendly,which was ideal for large-scale production of the LFIA test strip.And the SLD_(520)NP_(S)exhibits superior fluorescence quantum yield(49%),fully guarantees the performance of the LFIA test strip.The constructed SLD_(520)NPsm Ab1-based LFIA demonstrated a satisfactory linear relationship with CRP concentrations ranging from 0.5 ng/mL to 100 ng/mL,with limits of detection(LOD)of 0.78 ng/mL and a visible LOD of 1 ng/mL using a handheld 405 nm lamp.Furthermore,the developed LFIA exhibited excellent recoveries in serum,ranging from 94.45%to 102.5%.Overall,the outstanding performance of the SLD_(520)NPs-mAb1-based LFIA indicates that solid-state luminescent dyes have significant potential applications in the field of LFIA.
文摘In this study,thyme essential oil(TEO)nanoemulsion(tPTNs)was constructed with transglutaminase(TGase)-modified potato protein,and its antibacterial activity and mechanism of action were evaluated and explored.Results indicated that tPTNs exhibited great antibacterial activity against both Staphylococcus aureus and Escherichia coli,with minimal inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of 2.5 and 5.0 mg/mL,respectively.Also,the antibacterial effects of tPTNs were concentration-dependent.We observed a significant decrease in the absolute value of the zeta potential,and significant increases in particle size,cell membrane hydrophobicity,conductivity,the release of metal ions,and the leakage of nucleic acid as the concentration of tPTNs increased from 0 mg/mL to MBC.Furthermore,sodium dodecyl sulphate-polyacrylamide gel electrophoresis(SDS-PAGE)demonstrated that protein synthesis was inhibited or even disrupted.Analysis by liquid chromatography-mass spectrometry(LC-MS)indicated that treatment with tPTNs caused significant changes in bacterial metabolites,1117 and 692 differential metabolites being found for S.aureus and E.coli,respectively.The differential metabolites were involved in nucleotide metabolism,amino acid metabolism,tricarboxylic acid cycle and other metabolic pathways.These findings provide valuable insights for the application of thyme essential oil as an efficient antibacterial agent and for the understanding of its mechanism of action.
文摘BACKGROUND Gastric cancer,a globally prevalent malignant tumor,continues to exhibit high incidence and mortality rates.Although radical gastrectomy remains the primary treatment for this disease,postoperative complications frequently arise,negatively impacting short-term recovery and significantly reducing patients’quality of life.In this context,accurately predicting the risk of postoperative recurrence and metastasis,coupled with targeted interventions,could substantially improve patient outcomes.The C-reactive protein-triglyceride-glucose index(CTI),a composite biomarker that integrates metabolic disturbances and systemic inflammation,has garnered increasing attention in oncology.The prognostic nutritional index(PNI),a composite measure based on serum albumin and peripheral blood lymphocyte count,is used to evaluate both the nutritional status and systemic immune function of patients.In recent years,both the CTI and PNI have demonstrated significant prognostic value in predicting tumor outcomes,assessing treatment responses,and formulating personalized treatment strategies.AIM To investigate whether the combined inflammation and insulin resistance marker,the CTI,can serve as a prognostic indicator for patients undergoing radical gastrectomy for gastric cancer.Additionally,it seeks to develop a predictive model by incorporating the PNI alongside CTI.METHODS This retrospective study included a total of 300 patients who underwent radical gastrectomy.The patients were classified into high and low CTI groups based on their CTI index.Cox proportional hazards regression analysis was performed to identify independent prognostic factors influencing overall survival(OS)and disease-free survival(DFS),and two nomogram models were developed.RESULTS Of the included patients,131 had a high CTI and 169 had a low CTI.The DFS period of the low CTI group was significantly longer than that of the high CTI group.The number of postoperative adjuvant treatments,T stage,N stage,CTI,and PNI were identified as independent prognostic factors for DFS.The hazard ratio for CTI was 2.07(95%confidence interval:1.36-3.17,P<0.001).In terms of OS,the OS period of the low CTI group was significantly longer than that of the high CTI group.Whether adjuvant treatment was administered,T stage,CTI,and PNI were independent prognostic factors for OS.The hazard ratio for CTI was 2.47(95%confidence interval:1.44-4.23,P=0.001).The nomogram models for OS and DFS further emphasized the importance of CTI as a key predictor of patient prognosis.CONCLUSION CTI is a long-term prognostic indicator for the outcome of radical gastrectomy for gastric cancer.Patients with lower CTI values have a better prognosis.The prediction models constructed by combining CTI with PNI has good predictive ability for DFS and OS after radical gastrectomy.
基金supported by a grant of the Korea Dementia Research Project through the Korea Dementia Research Center (RS-2022-KH126506 to JSL)the ABC-based Regenerative BioTherapeutics(ABC project) grant (RS-2024-00426031 to JSL)NRF Grant (2022R1A2C3013138 to HR,RS-2024-00449723 to JGL) funded by the Korea government (the Ministry of Health&Welfare,Ministry of Science and ICT,Ministry of Education)
文摘Proteostasis,also known as protein homeostasis,is a tightly regulated cellular quality control process that ensures the balance of protein synthesis,folding,posttranslational modifications,and degradation.Maintaining proteostasis is vital for cellular function,organismal health,and longevity.The disru ption of proteostasis can lead to a range of detrimental effects,including accelerated aging,compromised cellular function,and even cell death,manifesting in numerous human diseases(Hipp et al.,2019).
基金supported by the USDA National Institute of Food and Agriculture,Hatch project 7009323.
文摘Oat milk has gained widespread consumer acceptance for its creamy texture,β-glucan content,and environmental sustainability.However,its relatively low protein content(typically 2-3 g/serving)presents a nutritional limitation,largely due to poor protein solubility.This study investigated how processing conditions influence protein content and functional stability in oat-based systems by applying two treatments:(1)α-amylase enzymatic hydrolysis,and(2)pH-shifting(from pH 7 to 12 and back)with mild heating(50℃for 10 or 30 min).Oat protein solutions were formulated from two sources:oat flour(OF)and oat protein isolate(OPI).Results suggests that α-amylase pretreatment effectively reduced starch-driven viscosity in OF,facilitating better sample handling and centrifugation.Following pH-shifting and heat treatment,both OF and OPI solutions showed significantly improved protein solubility,with protein content increased from 2.0 to~6.5 g/serving.These changes were accompanied by reduced precipitation,smaller particle sizes,and more negative zeta potential values,indicating enhanced colloidal stability.SDS-PAGE analysis revealed the presence of low-molecular-weight protein fractions,supporting increased solubilization.Fluorescence microscopy confirmed the formation of smaller,more uniformly dispersed particles in treated samples compared to controls.However,noticeable darkening or browning occurred under high-pH heating,indicating potential challenges in color control.The findings provide useful information for future industrial applications and product innovation in the plant-based beverage sector.
基金supported by the director of Indian Council of Agricultural Research and International Rice Research Institute (ICAR-CRRI), Cuttack, Indiathe coordinator of the ICAR-sponsored project ‘C-reactive protein (CRP) in Biofortification in Selected Crops’, India
文摘CR Dhan 310(CRD310),a biofortified rice variety,contains a significantly higher level of grain protein compared with its recurrent parent Naveen(NV),as well as most adapted high-yielding rice varieties in India.Although a limited investigation depicted that CRD310 contained higher levels of glutelin and some essential amino acids,detailed biochemical,molecular,and cellular mechanisms remain to be studied.As one of the means to identify the proteins and understand the underlying mechanism of higher proteins accumulation in grains of CRD310,the comparative proteomics was undertaken on grains of CRD310 and NV at the yellow ripening stage.
基金supported by the National Natural Science Foundation of China,Nos.82371310(to YJ),82271306(to JP)the Sichuan Science and Technology Support Program,Nos.2023YFH0069(to JP),2023NSFSC0028(to YJ),2023NSFSC1559(to YJ),2022YFS0615(to JP),2022NSFSC1421(to JP)+1 种基金Scientific Research Project of Sichuan Provincial Health Commission,No.23LCYJ040(to YJ)Youth Foundation of Southwestern Medical University and Southwest Medical University Project,Nos.2020ZRQNA038(to JP),2021ZKZD013(to JP),2021LZXNYD-P01(to YJ),2023QN014(to JP).
文摘Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
基金financially supported by the Hainan Province Science and Technology Special Fund(Grant no:ZDYF2024XDNY187).
文摘Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.
基金supported by the CJD Foundation,USA,the Alzheimer Forschung Initiative(AFI)e.V.,Germany,and Werner-Otto-Stiftung,Germany(all to HCA),ChinaScholarship Council(grant#202108080249 to FS)Deutsche Forschungsgemeinschaft(DFG)CRC877“Proteolysis as a regulatory event in pathophysiology”(project A12 to MG),Slovene Research and InnovationAgency(grant number P4-0176 to VCS).
文摘Novel insights into complex biological processes very often critically depend on the establishment of new potent read-out tools and improved protocols.A lot has been learned over the past four decades on physiological functions and,importantly,disease-related roles of the prion protein(PrP),a relatively broadly expressed membrane-anchored glycoprotein with high levels in several cell types of the nervous and immune system and with well-established key roles in different progressive and fatal neurodegenerative protein misfolding diseases(proteopathies).
基金Supported by National Natural Science Foundation of China,No.82170412.
文摘BACKGROUND Inflammatory cytokines are associated with cancer prognosis,but their specific role in cholangiocarcinoma remains poorly understood.The lymphocyte to C-reactive protein ratio(LCR),a novel inflammatory-nutritional biomarker,has demonstrated predictive value in gastrointestinal cancers;however,its clinical relevance in cholangiocarcinoma has not been investigated.AIM To validate the LCR as an independent prognostic factor for overall survival(OS),surgical site infection(SSI),and length of hospital stay in patients with resectable cholangiocarcinoma.METHODS We conducted a retrospective analysis of 76 patients with cholangiocarcinoma who underwent radical surgery between 2008 and 2013.The preoperative LCR was calculated as the lymphocyte count divided by C-reactive protein level,using a cutoff value of 180.Univariate and multivariate logistic regression analyses were performed to evaluate factors associated with SSI and hospitalization duration,while Kaplan-Meier survival curves and Cox proportional hazards models were used to assess predictors of OS.RESULTS Patients in the low LCR group was significantly associated with several adverse clinical outcomes:A shorter median OS(14.93 months vs 46.67 months;P=0.022);a 4.5-fold increased risk of prolonged hospitalization(P=0.007);and a higher incidence of SSI(odds ratio=4.41,P=0.045).Multivariate analysis confirmed that LCR was an independent predictor of OS[hazard ratio(HR)=3.204,P=0.002],SSI,and hospitalization duration.Additionally,R0 resection(HR=3.546,P=0.002)and advanced tumor-node-metastasis stage(HR=2.016,P=0.035)were identified as independent prognostic factors for OS.CONCLUSION In this retrospective study,preoperative LCR is a cost-effective and practical biomarker that independently predicts OS,postoperative complications,and hospitalization duration in patients with resectable cholangiocarcinoma,thereby facilitating more precise patient stratification.
基金International Brain Research Organization(IBRO)Rising Star Awardee and received an IBRO Early Career Principal Investigator Grant(No.PM010CNI000148)supported by Sunway University internal grant(No.GRTIN-IGS[02]-CVVR-11-2023)+2 种基金supported by the Fundamental Research Funds from the Central of Public Welfare Research Institute,China Rehabilitation Institutesupported by the research initiation funding scheme provided by Henan University of Technology(No.0004/31401568)Shenzhen Vaccine Biopharmaceuticals Limited(No.0004/51100292).
文摘Protein aggregation drives proteinopathies ranging from ALS to systemic amyloidosis,yet the multiscale determinants bridging sequence,structure,and kinetics remain elusive.We present SKALE,an interpretable machine learning framework that integrates sequence motifs,AlphaFold-derived structural descriptors,and experimental kinetics to decode aggregation mechanisms.SKALE identifies latent hotspots that evade conventional tools and matches high-performing neural baselines while preserving computational efficiency.In ALS-linked SOD1 G86R,the model isolates a risk region at residues 72-91 where preserved β-sheet geometry coincides with weakened hydrogen bonding to drive nucleation.Similarly,analysis of TDP-43 S332N reveals that a locally unwound helix increases surface exposure,a prediction validated by showing that targeted deletion of model-identified regions significantly reduces cellular aggregation.The framework generalizes to Tau P301L and PRNP variants where it uncovers distal aggregation-prone regions to discriminate pathogenic drivers from neutral mutations.Interpretability analysis further disentangles global from mutation-local mechanisms to reveal that β-sheet propensity acts as a shared determinant while hydrogen bond dynamics define specific routes to nucleation.These findings establish SKALE as a scalable,disease-agnostic engine that combines high-fidelity prediction with biophysical resolution to decode the molecular logic of misfolding and guide therapeutic design.
文摘BACKGROUND Acute-on-chronic liver failure(ACLF)is a life-threatening syndrome associated with high short-term mortality.Accurate risk stratification is crucial for the mana-gement of ACLF.AIM To evaluate the prognostic value of the C-reactive protein to albumin ratio(CAR)and its dynamic changes in patients with ACLF defined by the Chinese Group on Study of Severe Hepatitis B(COSSH)criteria.METHODS A total of 126 consecutive patients diagnosed with COSSH-ACLF were pros-pectively enrolled.CAR was calculated at admission and on days 4,7,and 14.The primary and secondary outcomes were 28-day and 90-day mortality,respectively.Multivariate Cox regression analysis was conducted to identify independent predictors of mortality.A novel prognostic model(COSSH-CAR),integrating baseline and dynamic variables,was developed and compared with established prognostic scoring systems.RESULTS The 28-day and 90-day mortality rates were 27.8%and 40.5%,respectively.Baseline CAR was significantly higher in 28-day non-survivors than in survivors(2.68 vs 1.42,P<0.001).The dynamic change in CAR from baseline to day 7(ΔCAR-7)showed stronger predictive power for 28-day mortality[area under the receiver operating characteristic curve(AUC)=0.765]than baseline CAR(AUC=0.698),ΔCAR-4(AUC=0.706)orΔCAR-14(AUC=0.712).Multivariate analysis identifiedΔCAR-7(HR=1.53),baseline Model for End-Stage Liver Disease-Sodium(MELD-Na)score(HR=1.08),and hepatic encephalopathy grade(HR=1.92)as independent predictors of 28-day mortality(all P<0.05).The COSSH-CAR model,which incorporated these parameters,showed superior predictive performance(AUC=0.832)for 28-day mortality compared with established prognostic scores,including Child-Pugh(AUC=0.721),MELD-Na(AUC=0.768)and COSSH-ACLF(AUC=0.786)and effectively stratified patients into three risk categories with significantly different survival rates(P<0.001).CONCLUSION Dynamic changes in CAR during the first week provide important prognostic information in patients with COSSH-ACLF,surpassing baseline values and conventional inflammatory markers.The novel COSSH-CAR model improves risk stratification and may support clinical decision-making in the management of ACLF,pending ex-ternal validation in diverse populations.
基金Cure CSB ProjectViljem Julijan Association for Children with Rare Diseases(Slovenia)+1 种基金Algarve Biomedical Center Research Institute(ABC-Ri)AC received a PhD fellowship from the Portuguese Science and Technology Foundation(FCT)#2020.07892.BD.
文摘Ataxin-2 is a 140 kDa cytoplasmic multifunctional protein that plays fundamental roles in diverse cellular mechanisms(Costa et al.,2024).Although widely studied in the context of the neurodegenerative diseases spinocerebellar ataxia type 2(SCA2)and amyotrophic lateral sclerosis(ALS),ataxin-2 functions span far beyond its pathogenic properties in the disease context(Figure 1).In fact,it has a wide range of biological functions that include RNA metabolism,translation regulation,stress response,endocytosis,calcium signaling,and the control of circadian rhythm.In this perspective,we highlight the main roles of ataxin-2 protein,which are described in detail in Costa et al.(2024).
文摘In an era of profound changes to global trade,food security,and industrial organization,the ChinaIndonesia“Two Countries,Twin Parks”initiative has emerged as a strategic experiment with farreaching implications.Anchored in marine protein processing and advanced food manufacturing,this collaboration reflects not only a convergence of economic interests but also a deliberate rethinking of how China engages with global resources,technology,and partners.
