Forkhead box O(FOXO)transcription factors serve as critical signaling hubs,initiating downstream autophagy-related gene expression in response to various growth factors and participating in mito-chondrial autophagy,thereby influencing cellular damage and repairing processes in acute and chronic kidney diseases.This article reviews the regulatory mechanisms of FOXO transcription factors and their impacts on au-tophagy and mitochondrial autophagy,aiming to explore the prospects of FOXO-induced mitochondrial autophagy in the treatment of renal diseases.

Small urban wetlands are widely distributed and susceptible to human activities, serving as important sources and sinks of carbon. Microorganisms play a crucial role in carbon cycle, while limited studies have been conducted on the microbial diversity in small urban wetlands and the functions of microbiome in carbon fixation and metabolism. To probe into the microbiome-driven carbon cycling in small urban wetlands and dissect the composition and functional groups of microbiome, we analyzed the relationships between the microbiome structure, element metabolism pathways, and habitat physicochemical properties in sediment samples across three small wetlands in Huzhou City, and compared them with natural wetlands in the Zoige wetland. High-throughput sequencing of 16S rRNA gene amplicons and metagenomics was employed to determine the species and functional groups. Sixty medium to high-quality metagenome-assembled genomes (MAGs) were constructed, including 55 bacterial and 5 archaeal taxa, and their potential in driving elemental cycles were analyzed, with a focus on carbon fixation. Several bacterial species were found to encode a nearly complete carbon fixation pathway, including the Calvin cycle, the reductive tricarboxylic acid cycle, the Wood-Ljungdahl pathway, and the reductive glycine pathway. There were several potential novel carbon-fixing bacterial members, such as those belonging to Syntrophorhabdus (Desulfobacterota) and UBA4417 (Bacteroidetes), which had high relative abundance in the wetland microbiome. Unveiling the genetic potential of these functional groups to facilitate element cycling is of great scientific importance for enhancing the carbon sequestration capacity of small urban wetlands.
Wetlands ; Microbiota/genetics* ; Carbon Cycle/genetics* ; Bacteria/classification* ; RNA, Ribosomal, 16S/genetics* ; China ; Cities ; Geologic Sediments/microbiology* ; Archaea/classification* ; Metagenomics ; Metagenome

OBJECTIVE: To identify early potential risk factors for hospital-acquired pneumonia (HAP) in patients with mild traumatic brain injury (mTBI), construct a risk prediction model, and evaluate its predictive efficacy. METHODS: A case-control study was conducted using clinical data from mTBI patients admitted to the neurosurgery department of Changzhou Second People's Hospital from September 2021 to September 2023. The patients were divided into two groups based on whether they developed HAP. Clinical data within 48 hours of admission were statistically analyzed to identify factors influencing HAP occurrence through univariate analysis. Least absolute shrinkage and selection operator (LASSO) regression analysis was employed for feature selection to identify the most influential variables. The dataset was divided into training and validation sets in a 7:3 ratio. A multivariate Logistic regression analysis was then performed using the training set to construct the prediction model, exploring the risk factors for HAP in mTBI patients and conducting internal validation in the validation set. Receiver operator characteristic curve (ROC curve), decision curve analysis (DCA), and calibration curve were utilized to assess the sensitivity, specificity, decision value, and predictive accuracy of the prediction model. RESULTS: A total of 677 mTBI patients were included, with 257 in the HAP group and 420 in the non-HAP group. The significant differences were found between the two groups in terms of age, maximum body temperature (MaxT), maximum heart rate (MaxHR), maximum systolic blood pressure (MaxSBP), minimum systolic blood pressure (MinSBP), maximum respiratory rate (MaxRR), cause of injury, and laboratory indicators [C-reactive protein (CRP), procalcitonin (PCT), neutrophil count (NEUT), erythrocyte sedimentation rate (ESR), fibrinogen (FBG), fibrinogen equivalent units (FEU), prothrombin time (PT), activated partial thromboplastin time (APTT), total cholesterol (TC), lactate dehydrogenase (LDH), prealbumin (PAB), albumin (Alb), blood urea nitrogen (BUN), serum creatinine (SCr), hematocrit (HCT), hemoglobin (Hb), platelet count (PLT), glucose (Glu), K⁺, Na⁺], suggesting they could be potential risk factors for HAP in mTBI patients. After LASSO regression analysis, the key risk factors were enrolled in the multivariate Logistic regression analysis. The results revealed that the cause of injury being a traffic accident [odds ratio (OR) = 2.199, 95% confidence interval (95%CI) was 1.124-4.398, P = 0.023], NEUT (OR = 1.330, 95%CI was 1.214-1.469, P < 0.001), ESR (OR = 1.053, 95%CI was 1.019-1.090, P = 0.003), FBG (OR = 0.272, 95%CI was 0.158-0.445, P < 0.001), PT (OR = 0.253, 95%CI was 0.144-0.422, P < 0.001), APTT (OR = 0.689, 95%CI was 0.578-0.811, P < 0.001), Alb (OR = 0.734, 95%CI was 0.654-0.815, P < 0.001), BUN (OR = 0.720, 95%CI was 0.547-0.934, P = 0.016), and Na⁺ (OR = 0.756, 95%CI was 0.670-0.843, P < 0.001) could serve as main risk factors for constructing the prediction model. Calibration curves demonstrated good calibration of the prediction model in both training and validation sets with no evident over fitting. ROC curve analysis showed that the area under the ROC curve (AUC) of the prediction model in the training set was 0.943 (95%CI was 0.921-0.965, P < 0.001), with a sensitivity of 83.6% and a specificity of 91.5%. In the validation set, the AUC was 0.917 (95%CI was 0.878-0.957, P < 0.001), with a sensitivity of 90.1% and a specificity of 85.0%. DCA indicated that the prediction model had a high net benefit, suggesting practical clinical applicability. CONCLUSIONS The cause of injury being a traffic accident, NEUT, ESR, FBG, PT, APTT, Alb, BUN, and Na⁺ are identified as major risk factors influencing the occurrence of HAP in mTBI patients. The prediction model constructed using these parameters effectively assesses the likelihood of HAP in mTBI patients.
Humans ; Risk Factors ; Case-Control Studies ; Logistic Models ; Healthcare-Associated Pneumonia/epidemiology* ; Brain Injuries, Traumatic/complications* ; Male ; Female ; ROC Curve ; Pneumonia/etiology* ; Middle Aged ; Adult

Objective To observe the effects of Yuebi Decoction on adriamycin-induced nephrotic syndrome(NS)and adhesion molecule levels in rats;To explore the possible mechanism of its inhibition of NS edema.Methods A NS rat model was established by a one-time tail vein injection of 6.5 mg/kg adriamycin.The rats were randomly divided into normal group,model group,prednisone group and Yuebi Decoction group.The prednisone group and Yuebi Decoction group were given 5 mg/kg prednisone and 22.2 g/kg Yuebi Decoction by gavage,respectively.The normal group and the model group were given an equal amount of normal saline by gavage,once a day for 2 consecutive weeks.The wet and dry weight ratios of skin and kidney were detected,24 hour urine total protein quantification(24 hUTP)and the contents of blood urea nitrogen(BUN),serum creatinine(SCr),total cholesterol(TC),albumin(ALB),hemoglobin(HB)were detected,HE and PAS staining was used to observe the morphology of renal tissue,ELISA was used to detect vascular cell adhesion molecule-1(VCAM-1)and intercellular adhesion molecule-1(ICAM-1)contents in renal tissue,the positive expressions of VCAM-1 and ICAM-1 were detected by immunohistochemistry,the expressions of VCAM-1,Rac1,signal transducer and activator of transcription 3(STAT3)and p-STAT3 proteins were detected by Western blot.Results Compared with the normal group,the wet dry weight ratio of the skin and kidney of the model group rats significantly increased(P<0.01),and the 24 hUTP,SCr,BUN and TC contents significantly increased(P<0.01),while the ALB and HB contents significantly decreased(P<0.01);with glomerular balloon atrophy,the renal tubules exhibit protein casts,inflammatory cell infiltration in renal interstitium,and significant increase in the contents of VCAM-1,ICAM-1 and protein expressions of VCAM-1,Rac1,p-STAT3 in renal tissue(P<0.01).Compared with the model group,the wet dry weight ratio of the skin and kidneys of rats in the prednisone group and Yuebi Decoction group was significantly reduced(P<0.05,P<0.01),and the 24 hUTP,SCr,BUN and TC were significantly reduced(P<0.01),while the contents of ALB and HB significantly increased(P<0.01);the infiltration of inflammatory cells in renal tissue was reduced,the protein casts decreased,and the contents of VCAM-1 and ICAM-1 in renal tissue,as well as the expressions of VCAM-1,Rac1 and p-STAT3 proteins significantly decreased(P<0.05,P<0.01).Conclusion Yuebi Decoction can alleviate edema,reduce urine protein,and improve capillary permeability in NS rats.Its mechanism is related to inhibiting the Rac1/STAT3 signaling pathway and reducing the expression of renal tissue adhesion molecules.

Forkhead box O(FOXO)transcription factors serve as critical signaling hubs,initiating downstream autophagy-related gene expression in response to various growth factors and participating in mito-chondrial autophagy,thereby influencing cellular damage and repairing processes in acute and chronic kidney diseases.This article reviews the regulatory mechanisms of FOXO transcription factors and their impacts on au-tophagy and mitochondrial autophagy,aiming to explore the prospects of FOXO-induced mitochondrial autophagy in the treatment of renal diseases.

Objective To observe the protective effect of Yuebi Decoction on adriamycin(ADR)-induced mouse glomerular endothelial cells(MGEC),and to explore the possible mechanism of action.Methods MGEC were stimulated with ADR at a concentration of 1.25 μmol·L-1 for 12 h.MGEC were divided into five groups:normal group,model group,and Yuebi Decoction low,medium,and high dosage groups(5%,10%,and 20%of drug-containing serum);the viability of cells was detected by CCK-8 assay,the cell mobility was detected by Transwell assay.The relative expression levels of MGEC VCAM-1,Rac1,STAT3,and p-STAT3 were detected by Western blot.The expression of endothelial marker CD31,VCAM-1 and ICAM-1 was detected by immunofluorescence.Results Compared with the normal group,the endothelial cell migration rate was decreased in the model group(P<0.01),the protein expression levels of VCAM-1,ICAM-1,Rac1 and p-STAT 3 were significantly increased(P<0.05,P<0.01).The endothelial cell migration rate of the high-dose group of Yuebi Decoction was significantly increased compared with that of the model group(P<0.05).VCAM-1,ICAM-1,Rac1 and p-STAT3 protein expression levels of the drug-containing serum of Yuebi Decoction each group were significantly reduced(P<0.05,P<0.01).Conclusion Yuebi Decoction inhibited ADR-induced adhesion molecule expression in MGEC,alleviated endothelial injury,and improved endothelial cell migration rate.Its mechanism may be related to the inhibition of the Rac1/STAT3 signaling pathway.

Objective To observe the effects of Yuebi Decoction on adriamycin-induced nephrotic syndrome(NS)and adhesion molecule levels in rats;To explore the possible mechanism of its inhibition of NS edema.Methods A NS rat model was established by a one-time tail vein injection of 6.5 mg/kg adriamycin.The rats were randomly divided into normal group,model group,prednisone group and Yuebi Decoction group.The prednisone group and Yuebi Decoction group were given 5 mg/kg prednisone and 22.2 g/kg Yuebi Decoction by gavage,respectively.The normal group and the model group were given an equal amount of normal saline by gavage,once a day for 2 consecutive weeks.The wet and dry weight ratios of skin and kidney were detected,24 hour urine total protein quantification(24 hUTP)and the contents of blood urea nitrogen(BUN),serum creatinine(SCr),total cholesterol(TC),albumin(ALB),hemoglobin(HB)were detected,HE and PAS staining was used to observe the morphology of renal tissue,ELISA was used to detect vascular cell adhesion molecule-1(VCAM-1)and intercellular adhesion molecule-1(ICAM-1)contents in renal tissue,the positive expressions of VCAM-1 and ICAM-1 were detected by immunohistochemistry,the expressions of VCAM-1,Rac1,signal transducer and activator of transcription 3(STAT3)and p-STAT3 proteins were detected by Western blot.Results Compared with the normal group,the wet dry weight ratio of the skin and kidney of the model group rats significantly increased(P<0.01),and the 24 hUTP,SCr,BUN and TC contents significantly increased(P<0.01),while the ALB and HB contents significantly decreased(P<0.01);with glomerular balloon atrophy,the renal tubules exhibit protein casts,inflammatory cell infiltration in renal interstitium,and significant increase in the contents of VCAM-1,ICAM-1 and protein expressions of VCAM-1,Rac1,p-STAT3 in renal tissue(P<0.01).Compared with the model group,the wet dry weight ratio of the skin and kidneys of rats in the prednisone group and Yuebi Decoction group was significantly reduced(P<0.05,P<0.01),and the 24 hUTP,SCr,BUN and TC were significantly reduced(P<0.01),while the contents of ALB and HB significantly increased(P<0.01);the infiltration of inflammatory cells in renal tissue was reduced,the protein casts decreased,and the contents of VCAM-1 and ICAM-1 in renal tissue,as well as the expressions of VCAM-1,Rac1 and p-STAT3 proteins significantly decreased(P<0.05,P<0.01).Conclusion Yuebi Decoction can alleviate edema,reduce urine protein,and improve capillary permeability in NS rats.Its mechanism is related to inhibiting the Rac1/STAT3 signaling pathway and reducing the expression of renal tissue adhesion molecules.

Objective To observe the protective effect of Yuebi Decoction on adriamycin(ADR)-induced mouse glomerular endothelial cells(MGEC),and to explore the possible mechanism of action.Methods MGEC were stimulated with ADR at a concentration of 1.25 μmol·L-1 for 12 h.MGEC were divided into five groups:normal group,model group,and Yuebi Decoction low,medium,and high dosage groups(5%,10%,and 20%of drug-containing serum);the viability of cells was detected by CCK-8 assay,the cell mobility was detected by Transwell assay.The relative expression levels of MGEC VCAM-1,Rac1,STAT3,and p-STAT3 were detected by Western blot.The expression of endothelial marker CD31,VCAM-1 and ICAM-1 was detected by immunofluorescence.Results Compared with the normal group,the endothelial cell migration rate was decreased in the model group(P<0.01),the protein expression levels of VCAM-1,ICAM-1,Rac1 and p-STAT 3 were significantly increased(P<0.05,P<0.01).The endothelial cell migration rate of the high-dose group of Yuebi Decoction was significantly increased compared with that of the model group(P<0.05).VCAM-1,ICAM-1,Rac1 and p-STAT3 protein expression levels of the drug-containing serum of Yuebi Decoction each group were significantly reduced(P<0.05,P<0.01).Conclusion Yuebi Decoction inhibited ADR-induced adhesion molecule expression in MGEC,alleviated endothelial injury,and improved endothelial cell migration rate.Its mechanism may be related to the inhibition of the Rac1/STAT3 signaling pathway.

Objective To observe the clinical efficacy of Shen Shuai Ⅱ Granules combined with integrated Western medicine therapy in patients with primary chronic kidney disease(CKD)in stages 3-4 with the syndrome of spleen and kidney qi deficiency,dampness turbidity and blood stasis,and its effects on expression of serum autophagy related proteins.Methods Totally 88 patients were randomly divided into treatment group and control group,with 44 cases in each group.Both groups were given an integrated Western medicine therapy.On this basis,the treatment group was given Shen Shuai Ⅱ Granules,while the control group was given Shen Shuai Ⅱ placebo,1 bag at a time,twice a day,orally.The treatment for both groups lasted for 24 weeks.The clinical efficacy of the two groups was observed.The TCM symptom scores,serum creatinine(Scr),blood urea nitrogen(BUN),uric acid(UA),blood calcium(Ca2+),blood phosphorus(P3-),parathyroid hormone(PTH),and 24-hour urinary protein quantification(24 UPro)before and after treatment were compared in the two groups.The serum levels of autophagy related protein Beclin-1,Atg7,and LC3-Ⅱ were detected by ELISA before and after treatment in the two groups.Safety indexes of both groups were monitored.Results During the treatment,4 cases fell off in the treatment group and 4 cases in the control group.The total effective rate in the treatment group was 55％(22/40),while that in the control group was 30％(12/40).The therapeutic effect in the treatment group was better than that in the control group(P<0.01).Compared with before treatment,the TCM symptom scores in the treatment group decreased after treatment(P<0.01),the levels of Scr,BUN,UA,P3-,PTH,and 24 UPro decreased(P<0.05,P<0.01),while eGFR increased(P<0.01).The levels of Scr in the control group increased(P<0.05),while eGFR decreased(P<0.01).After treatment,the treatment group had lower various TCM symptom scores,Scr,BUN,UA,P3-,PTH,and 24 UPro levels than the control group(P<0.01,P<0.05),and higher eGFR than the control group(P<0.01).Compared with before treatment,the serum levels of Beclin-1,Atg7,and LC3-Ⅱ increased in the treatment group after treatment(P<0.01,P<0.05),while the serum level of Beclin-1 decreased in the control group after treatment(P<0.01).After treatment,the improvement of the above indicators in the treatment group were better than those in the control group(P<0.01,P<0.05).Correlation analysis showed that Beclin-1,Atg7,and LC3-Ⅱ were negatively correlated with Scr and BUN(P<0.05),and positively correlated with eGFR(P<0.05).There was no obvious adverse reaction in both groups.Conclusion The combination of Shen Shuai Ⅱ Granules and integrated Western medicine therapy for the treatment of primary CKD in stages 3-4 with the syndrome of spleen and kidney qi deficiency,dampness turbidity and blood stasis has confirmed efficacy,which can effectively alleviate clinical symptoms,improve renal function,and delay the progression of CKD.The mechanism may be related to improving the level of autophagy in renal.

Science and technological advancements drive human progress, with laboratory animals serving as essential resources for developments in life sciences and medicine. However, the waste generated by these animals presents new challenges for urban management. Issues such as classification, recycling, effective utilization, and biohazard elimination must be addressed, necessitating the development of regulations, standards, and norms to keep pace with advancements. The construction of quality management system is the foundation and framework for the management of inspection and testing organizations. It should have strong operability and inspectability, enabling continuous improvement of the management level and enhancing the stability of basic management. However, current quality management systems often lack clarity in managing laboratory animal waste, including undefined disposal processes for non-medical institutions, inaccurate waste classification, and inadequate disposal methods for different waste categories. This paper addresses these challenges by identifying necessary processes to be added or removed in the quality management system of National Institutes for Food and Drug Control, developing effective SOPs, proposing practical measures to strengthen supervision and management, and integrating 6S management principles into our quality management system. In conclusion, effective management of laboratory animal waste should be centered on improving the quality management system, emphasizing waste classification and management at the source, controlling biological hazards, minimizing environmental pollution and promoting conditions for sustainable development.