Highly Moisture-Resistant Flexible Thin-Film-Based Triboelectric Nanogenerator for Environmental Energy Harvesting and Self-Powered Tactile Sensing.

Triboelectric nanogenerator (TENG) has been demonstrated as a sustainable energy utilization method for waste mechanical energy and self-powered system. However, the charge dissipation of frictional layer materials in a humid environment severely limits their stable energy supply. In this work, a new method is reported for preparing polymer film as a hydrophobic negative friction material by solution blending poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and polyvinyl chloride (PVC), doping with titanium dioxide (TiO2) nanoparticles, and further surface patterning modification. The P-TENG composed of the PVDF-HFP/PVC/TiO2 composite film with optimized hydrophobic performance (WCA = 124°) achieved an output voltage of 235 V and a short-circuit current of 35 µA, which is approximately three times that of the bare PVDF-HFP-based TENG. Under charge excitation, the transferred charge of the P-TENG can reach 35 nC. When the external load resistance is 5.5 MΩ, the output peak power density can reach 1.4 W m-2. Meanwhile, the hydrophobic surface layer with a rough surface structure enables the device to overcome the influence of water molecules on charge transfer in a humid environment, quickly recover, and maintain a high output. The P-TENG can effectively monitor finger flexibility and strength and realize real-time evaluation of the exercise state and hand fatigue of the elderly and rehabilitation trainers. It has broad application prospects in self-powered intelligent motion sensing, soft robotics, human-machine interaction, and other fields.

Organic Iodine Improves the Growth Performance and Gut Health of Fujian Yellow Rabbits.

Organic iodine is a new trace element additive that is highly efficient in regulating cell growth, function, and metabolism. This study demonstrated that organic iodine improves the growth performance and gut health of Fujian yellow rabbits. A total of 160 healthy rabbits of similar weight were randomly divided into four groups, which were treated with organic iodine (0, 0.5, 1.0, and 1.5 mg/kg) for 60 days. Our results indicated that organic iodine improved the growth performance, including significantly increased BW, ADG, and ADFI, and decreased F/G notably. Organic iodine improved the content of T3, T4, IgM, IgA, and IgM in serum, and intestinal mucosal immunity (IL-1α, IL-2, and sIgA). Organic iodine supplementation ameliorated gut morphometry and morphology, such as higher villus height and lower crypt depth. Organic iodine increased the amount of goblet cells significantly. The 0.5 mg/kg organic iodine most increased the activities of amylase, cellulase, and trypsin in caecum. Organic iodine induced more active caecum fermentation, higher NH3-N, acetic acid, propionic acid, and butyric acid, while lowering PH. In conclusion, organic iodine improved the growth performance and gut morphometry and morphology, and increased caecum enzyme activities, active caecum fermentation, and intestinal immunity of Fujian yellow rabbits.

Ecotoxicological Effects of Microplastics Combined With Antibiotics in the Aquatic Environment: Recent Developments and Prospects.

Both microplastics and antibiotics are commonly found contaminants in aquatic ecosystems. Microplastics have the ability to absorb antibiotic pollutants in water, but the specific adsorption behavior and mechanism are not fully understood, particularly in relation to the impact of microplastics on toxicity in aquatic environments. We review the interaction, mechanism, and transport of microplastics and antibiotics in water environments, with a focus on the main physical characteristics and environmental factors affecting adsorption behavior in water. We also analyze the effects of microplastic carriers on antibiotic transport and long-distance transport in the water environment. The toxic effects of microplastics combined with antibiotics on aquatic organisms are systematically explained, as well as the effect of the adsorption behavior of microplastics on the spread of antibiotic resistance genes. Finally, the scientific knowledge gap and future research directions related to the interactions between microplastics and antibiotics in the water environment are summarized to provide basic information for preventing and treating environmental risks. Environ Toxicol Chem 2024;00:1-12. © 2024 SETAC.

PmHs1pro-1 monitors Bsursaphelenchus xylophilus infection and activates defensive response in resistant Pinus massoniana.

Plant resistance (R) genes play a crucial role in the detection of effector proteins secreted by pathogens, either directly or indirectly, as well as in the subsequent activation of downstream defence mechanisms. However, little is known about how R genes regulate the defence responses of conifers, particularly Pinus massoniana, against the destructive pine wood nematode (PWN; Bursaphelenchus xylophilus). Here, we isolated and characterised PmHs1pro-1, a nematode-resistance gene of P. massoniana, using bioinformatics, molecular biology, histochemistry and transgenesis. Tissue-specific expressional pattern and localisation of PmHs1pro-1 suggested that it was a crucial positive regulator in response to PWN attack in resistant P. massoniana. Meanwhile, overexpression of PmHs1pro-1 was found to activate reactive oxygen species (ROS) metabolism-related enzymes and the expressional level of their key genes, including superoxide dismutase, peroxidase and catalase. In addition, we showed that PmHs1pro-1 directly recognised the effector protein BxSCD1of PWN, and induced the ROS burst responding to PWN invasion in resistant P. massoniana. Our findings illustrated the molecular framework of R genes directly recognising the effector protein of pathology in pine, which offered a novel insight into the plant-pathogen arms race.

Local vascular Klotho mediates diabetes-induced atherosclerosis via ERK1/2 and PI3-kinase-dependent signaling pathways.

BACKGROUND AND AIMS: Diabetes is one of the major causes of cardiovascular disease (CVD). As high as 29 % of patients with diabetes develop atherosclerosis. Vascular Smooth Muscle Cells (VSMCs) are a key mediator in the pathogenesis of atherosclerosis, generating pro-inflammatory and proliferative characteristics in atherosclerotic lesions. METHODS: We used human atherosclerotic samples, developed diabetes-induced atherosclerotic mice, and generated loss of function and gain of function in Klotho human aortic smooth muscle cells to investigate the function of Klotho in atherosclerosis. RESULTS: We found that Klotho expression is decreased in smooth muscle actin-positive cells in patients with diabetes and atherosclerosis. Consistent with human data, we found that Apoe knockout mice with streptozotocin-induced diabetes fed on a high-fat diet showed decreased expression of Klotho in SMCs. Additionally, these mice showed increased expression of TGF-ß, MMP9, phosphorylation of ERK and Akt. Further, we utilized primary Human Aortic Smooth Muscle Cells (HASMCs) with d-glucose under dose-response and in time-dependent conditions to study the role of Klotho in these cells. Klotho gain of function and loss of function studies showed that Klotho inversely regulated the expression of atherosclerotic markers TGF-ß, MMP2, MMP9, and Fractalkine. Further, High Glucose (HG) induced Akt, and ERK1/2 phosphorylation were enhanced or mitigated by endogenous Klotho deficiency or its overexpression respectively. PI3K/Akt and MAPK/ERK inhibition partially abolished the HG-induced upregulation of TGF-ß, MMP2, MMP9, and Fractalkine. Additionally, Klotho knockdown increased the proliferation of HASMCs and enhanced α-SMA and TGF-ß expression. CONCLUSIONS: Taken together, these results indicate that local vascular Klotho is involved in diabetes-induced atherosclerosis, which is via PI3K/Akt and ERK1/2-dependent signaling pathways.

[Value of calprotectin S100 A8/A9 in predicting the severity of Mycoplasma pneumoniae pneumonia in children]. / 钙卫蛋白S100 A8/A9å¯¹è‚ºç‚Žæ”¯åŽŸä½“è‚ºç‚Žæ‚£å„¿ç— æƒ ä¸¥é‡ç¨‹åº¦çš„é¢„æµ‹ä»·å€¼.

OBJECTIVES: To investigate the role of calprotectin S100 A8/A9 complex in evaluating the condition of children with severe Mycoplasma pneumoniae pneumonia (SMPP). METHODS: A prospective study was conducted among 136 children with Mycoplasma pneumoniae pneumonia (MPP) and 30 healthy controls. According to the severity of the condition, the children with MPP were divided into mild subgroup (40 children) and SMPP subgroup (96 children). The levels of S100 A8/A9 complex and related inflammatory factors were compared between the MPP group and the healthy control group, as well as between the two subgroups of MPP. The role of S100 A8/A9 in assessing the severity of MPP was explored. RESULTS: The MPP group had a significantly higher level of S100 A8/A9 than the healthy control group, with a significantly greater increase in the SMPP subgroup (P<0.05). The multivariate logistic regression analysis showed that the increases in serum C reactive protein (CRP) and S100A8/A9 were closely associated with SMPP (P<0.05). The receiver operating characteristic (ROC) curve analysis showed that the combined measurement of serum S100 A8/A9 and CRP had an area under the ROC curve of 0.904 in predicting SMPP, which was significantly higher than the AUC of S100 A8/A9 or CRP alone (P<0.05), with a specificity of 0.718 and a sensitivity of 0.952. CONCLUSIONS: S100 A8/A9 is closely associated with the severity of MPP, and the combination of S100 A8/A9 with CRP is more advantageous for assessing the severity of MPP in children.

Electrocatalytic Coupling of Nitrate and Formaldehyde for Hexamethylenetetramine Synthesis via C-N Bond Construction and Ring Formation.

Hexamethylenetetramine (HMTA) is extensively used in the defense industry, medicines, food, plastics, rubber, and other applications. Traditional organic synthesis of HMTA relies on ammonia derived from the Haber process at high temperatures and pressures. In contrast, electrochemical methods enable a safe and green one-pot synthesis of HMTA from waste NO3-. However, HMTA synthesis through the electrochemical method is challenging owing to the complex reaction pathways involving C-N bond construction and ring formation. In this study, HMTA was efficiently synthesized over electrochemical oxidation-derived copper (e-OD-Cu), with a yield of 76.8% and a Faradaic efficiency of 74.9% at -0.30 VRHE. The catalytic mechanism and reaction pathway of HMTA synthesis on e-OD-Cu were investigated through a series of in situ characterization methods and density-functional theory calculations. The results demonstrated that the electrocatalytic synthesis of HMTA involved a tandem electrochemical-chemical reaction. Additionally, the results indicated that the presence of Cu vacancies enhanced substrate adsorption and inhibited the further hydrogenation of C═N. Overall, this study provides an electrocatalytic method for HMTA synthesis and an electrochemical strategy for constructing multiple C-N bonds.

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa in children diagnosed by echocardiography: Two case reports.

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is rare, particularly in children, and is potentially fatal. This article presents two cases of pediatric mitral-aortic intervalvular fibrosa pseudoaneurysm: one secondary to infective endocarditis and the other confirmed to be congenital in nature. The characteristic echocardiographic manifestations of mitral-aortic intervalvular fibrosa pseudoaneurysm demonstrated in this study will enhance diagnostic efficacy and guide early clinical intervention.

Predicting intraoperative blood loss during cesarean sections based on multi-modal information: a two-center study.

PURPOSE: To develop and validate a nomogram model that combines radiomics features, clinical factors, and coagulation function indexes (CFI) to predict intraoperative blood loss (IBL) during cesarean sections, and to explore its application in optimizing perioperative management and reducing maternal morbidity. METHODS: In this retrospective consecutive series study, a total of 346 patients who underwent magnetic resonance imaging (156 for training and 68 for internal test, center 1; 122 for external test, center 2) were included. IBL+ was defined as more than 1000 mL estimated blood loss during cesarean sections. The prediction models of IBL were developed based on machine-learning algorithms using CFI, radiomics features, and clinical factors. ROC analysis was performed to evaluate the performance for IBL diagnosis. RESULTS: The support vector machine model incorporating all three modalities achieved an AUC of 0.873 (95% CI 0.769-0.941) and a sensitivity of 1.000 (95% CI 0.846-1.000) in the internal test set, with an AUC of 0.806 (95% CI 0.725-0.872) and a sensitivity of 0.873 (95% CI 0.799-0.922) in the external test set. It was also scored significantly higher than the CFI model (P = 0.035) on the internal test set, and both the CFI (P = 0.002) and radiomics-CFI models (P = 0.007) on the external test set. Additionally, the nomogram constructed based on three modalities achieved an internal testing set AUC of 0.960 (95% CI 0.806-0.999) and an external testing set AUC of 0.869 (95% CI 0.684-0.967) in the pregnant population without a pernicious placenta previa. It is noteworthy that the AUC of the proposed model did not show a statistically significant improvement compared to the Clinical-CFI model in both internal (P = 0.115) and external test sets (P = 0.533). CONCLUSION: The proposed model demonstrated good performance in predicting intraoperative blood loss (IBL), exhibiting high sensitivity and robust generalizability, with potential applicability to other surgeries such as vaginal delivery and postpartum hysterectomy. However, the performance of the proposed model was not statistically significantly better than that of the Clinical-CFI model.

Nomogram incorporating preoperative pan-immune-inflammation value and monocyte to high-density lipoprotein ratio for survival prediction in patients with colorectal cancer: a retrospective study.

OBJECTIVE: Using the preoperative pan-immune-inflammation value (PIV) and the monocyte to high-density lipoprotein ratio (MHR) to reflect inflammation, immunity, and cholesterol metabolism, we aim to develop and visualize a novel nomogram model for predicting the survival outcomes in patients with colorectal cancer (CRC). METHODS: A total of 172 patients with CRC who underwent radical resection were retrospectively analyzed. Survival analysis was conducted after patients were grouped according to the optimal cut-off values of PIV and MHR. Univariate and multivariate analyses were performed using Cox proportional hazards regression to screen the independent prognostic factors. Based on these factors, a nomogram was constructed and validated. RESULTS: The PIV was significantly associated with tumor location (P < 0.001), tumor maximum diameter (P = 0.008), and T stage (P = 0.019). The MHR was closely related to gender (P = 0.016), tumor maximum diameter (P = 0.002), and T stage (P = 0.038). Multivariate analysis results showed that PIV (Hazard Ratio (HR) = 2.476, 95% Confidence Interval (CI) = 1.410-4.348, P = 0.002), MHR (HR = 3.803, 95%CI = 1.609-8.989, P = 0.002), CEA (HR = 1.977, 95%CI = 1.121-3.485, P = 0.019), and TNM stage (HR = 1.759, 95%CI = 1.010-3.063, P = 0.046) were independent prognostic indicators for overall survival (OS). A nomogram incorporating these variables was developed, demonstrating robust predictive accuracy for OS. The area under the curve (AUC) values of the predictive model for 1-, 2-, and 3- year are 0.791,0.768,0.811, respectively. The calibration curves for the probability of survival at 1-, 2-, and 3- year presented a high degree of credibility. Furthermore, Decision curve analysis (DCA) for the probability of survival at 1-, 2-, and 3- year demonstrate the significant clinical utility in predicting survival outcomes. CONCLUSION: Preoperative PIV and MHR are independent risk factors for CRC prognosis. The novel developed nomogram demonstrates a robust predictive ability, offering substantial utility in facilitating the clinical decision-making process.

Hydrophobic TPU/CNTs-ILs Ionogel as a Reliable Multimode and Flexible Wearable Sensor for Motion Monitoring, Information Transfer, and Underwater Sensing.

Ionogel-based sensors have gained widespread attention in recent years due to their excellent flexibility, biocompatibility, and multifunctionality. However, the adaptation of ionogel-based sensors in extreme environments (such as humid, acidic, alkaline, and salt environments) has rarely been studied. Here, thermoplastic polyurethane/carbon nanotubes-ionic liquids (TPU/CNTs-ILs) ionogels with a complementary sandpaper morphology on the surface were prepared by a solution-casting method with a simple sandpaper as the template, and the hydrophobic flexible TPU/CNTs-ILs ionogel-based sensor was obtained by modification using nanoparticles modified with cetyltrimethoxysilane. The hydrophobicity improves the environmental resistance of the sensor. The ionogel-based sensor exhibits multimode sensing performance and can accurately detect response signals from strain (0-150%), pressure (0.1-1 kPa), and temperature (30-100 °C) stimuli. Most importantly, the hydrophobic TPU/CNTs-ILs ionogel-based sensors can be used not only as wearable strain sensors to monitor human motion signals but also for information transfer, writing recognition systems, and underwater activity monitoring. Thus, the hydrophobic TPU/CNTs-ILs ionogel-based sensor offers a new strategy for wearable electronics, especially for applications in extreme environments.

A nomogram for predicting survival in patients with gastrointestinal stromal tumor: a study based on the surveillance, epidemiology, and end results database.

Purpose: The objective of this investigation was to construct and validate a nomogram for prognosticating cancer-specific survival (CSS) in patients afflicted with gastrointestinal stromal tumor (GIST) at 3-, 5-, and 8-years post-diagnosis. Methods: Data pertaining to patients diagnosed with GIST were acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Through random selection, a training cohort (70%) and a validation cohort (30%) were established from the patient population. Employing a backward stepwise Cox regression model, independent prognostic factors were identified. Subsequently, these factors were incorporated into the nomogram to forecast CSS rates at 3-, 5-, and 8-years following diagnosis. The nomogram's performance was assessed using indicators such as the consistency index (C-index), the area under the time-dependent receiver operating characteristic curve (AUC), the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), calibration curves, and decision-curve analysis (DCA). Results: This investigation encompassed a cohort of 3,062 GIST patients. By analyzing the Cox regression model within the training cohort, nine prognostic factors were identified: age, sex, race, marital status, AJCC (American Joint Committee on Cancer) stage, surgical status, chemotherapy status, radiation status, and income status. The nomogram was subsequently developed and subjected to both internal and external validation. The nomogram exhibited favorable discrimination abilities, as evidenced by notably high C-indices and AUC values. Calibration curves confirmed the nomogram's reliability. Moreover, the nomogram outperformed the AJCC model, as demonstrated by enhanced NRI and IDI values. The DCA curves validated the clinical utility of the nomogram. Conclusion: The present study has successfully constructed and validated the initial nomogram for predicting prognosis in GIST patients. The nomogram's performance and practicality suggest its potential utility in clinical settings. Nevertheless, further external validation is warranted.

Fluoroquinolone antibiotics in the aquatic environment: environmental distribution, the research status and eco-toxicity.

The increasing presence of fluoroquinolone (FQ) antibiotics in aquatic environments is a growing concern due to their widespread use, negatively impacting aquatic organisms. This paper provides an overview of the environmental distribution, sources, fate, and both single and mixed toxicity of FQ antibiotics in aquatic environments. It also examines the accumulation of FQ antibiotics in aquatic organisms and their transfer into the human body through the food chain. The study identifies critical factors such as metabolism characteristics, physiochemical characteristics, light, temperature, dissolved oxygen, and environmental compatibility that influence the presence of FQ antibiotics in aquatic environments. Mixed pollutants of FQ antibiotics pose significant risks to the ecological environment. Additionally, the paper critically discusses advanced treatment technologies designed to remove FQ antibiotics from wastewater, focusing on advanced oxidation processes (AOPs) and electrochemical advanced oxidation processes (EAOPs). The discussion also includes the benefits and limitations of these technologies in degrading FQ antibiotics in wastewater treatment plants. The paper concludes by proposing new approaches for regulating and controlling FQ antibiotics to aid in the development of ecological protection measures.

A case report of autosomal recessive polycystic kidney disease with noncompaction of ventricular myocardium: coincidence or different manifestations of ciliopathy?

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a rare inherited cystic disease characterized by bilateral renal cyst formation and congenital liver fibrosis. Cardiovascular disorders such as noncompaction of ventricular myocardium (NVM) have not been reported with ARPKD. CASE PRESENTATION: A 5-month-old girl was examined after presenting with a fever and turbid urine for one day and was diagnosed as urinary tract infection. Urinary ultrasound showed multiple round, small cysts varying in size in both kidneys. Genetic testing revealed two heterozygous mutations and one exon deletion in the polycystic kidney and hepatic disease 1 gene, indicating a diagnosis of ARPKD. During hospitalization, she was found to have chronic heart failure after respiratory tract infection, with an ejection fraction of 29% and fraction shortening of 13%. When the patient was 15 months old, it was found that she had prominent trabeculations and deep intertrabecular recesses with the appearance of blood flow from the ventricular cavity into the intertrabecular recesses by echocardiography. The noncompaction myocardium was 0.716 cm and compaction myocardium was 0.221 cm (N/C = 3.27), indicating a diagnosis of NVM. Liver and kidney function remained normal during four-year follow-up. CONCLUSIONS: This is the first report of NVM in a patient with ARPKD. It is unsure if the coexistence of NVM and ARPKD is a coincidence or they are different manifestations of ciliary dysfunction in the heart and kidneys.

Optical Molecular Probes for Imaging and Early Diagnosis of Acute Kidney Injury.

The kidneys play an irreplaceable role in metabolism and excretion. However, Acute Kidney Injury (AKI) often occurs due to high local concentrations of drugs, inflammation, and trauma. Activated optical probes with excellent detection performance can effectively identify biomarkers in the initial stage of AKI and play an important role in evaluating AKI and preventing the development of diseases. This article summarizes representative design strategies for molecular probes and special diagnostic applications. These molecular probes show great potential in basic research and clinical diagnosis, enabling enhanced images of tissue structure and biomarkers, as well as early diagnosis of AKI. In addition, the difficulties and challenges that optical probes may face in the development and application of AKI are also discussed in this article.

Effects of cell-free DNA on kidney disease and intervention strategies.

Kidney disease has become a global public health problem. Patients with end-stage kidney disease must rely on dialysis or undergo renal transplantation, placing heavy burdens on their families and society. Therefore, it is important to develop new therapeutic targets and intervention strategies during early stages of chronic kidney disease. The widespread application of liquid biopsy has led to an increasing number of studies concerning the roles of cell-free DNA (cfDNA) in kidney disease. In this review, we summarize relevant studies concerning the roles of cfDNA in kidney disease and describe various strategies for targeted removal of cfDNA, with the goal of establishing novel therapeutic approaches for kidney disease.

Application of biological agents in the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been traditionally treated using glucocorticoids and immunosuppressants. However, these treatment modes are associated with high recurrence AAV rates and adverse reactions. Therefore, treatment strategies for AAV need to be urgently optimized. The efficacy and safety of biological agents in the treatment of vasculitis have been clinically validated. This review comprehensively summarizes the evidence-based support for the clinical use of existing biological agents in AAV. The findings reveal that multiple biological agents not only effectively reduce the adverse reactions associated with glucocorticoids and immunosuppressants but also demonstrate significant therapeutic efficacy. Notably, rituximab, an anti-CD20 antibody, has emerged as a first-line treatment option for AAV. Mepolizumab has shown promising results in relapsed and refractory eosinophilic granulomatosis with polyangiitis. Other biological agents targeting cytokines, complement, and other pathways have also demonstrated clinical benefits in recent studies. The widespread application of biological agents provides new insights into the treatment of AAV and is expected to drive further clinical research. These advancements not only improve patient outcomes but also offer more possibilities and hope in the field of AAV treatment.

Oxymatrine attenuates sepsis-induced inflammation and organ injury via inhibition of HMGB1/RAGE/NF-κB signaling pathway.

Sepsis is a life-threatening organ dysfunction that endangers patient lives and is caused by an imbalance in the host defense against infection. Sepsis continues to be a significant cause of morbidity and mortality in critically sick patients. Oxymatrine (OMT), a quinolizidine alkaloid derived from the traditional Chinese herb Sophora flavescens Aiton, has been shown to have anti-inflammatory effects on a number of inflammatory illnesses according to research. In this study, we aimed to evaluate the therapeutic effects of OMT on sepsis and explore the underlying mechanisms. We differentiated THP-1 cells into THP-1 macrophages and studied the anti-inflammatory mechanism of OMT in a lipopolysaccharide (LPS)-induced THP-1 macrophage sepsis model. Activation of the receptor for advanced glycation end products (RAGE), as well as NF-κB, was assessed by Western blot analysis and immunofluorescence staining. ELISA was used to measure the levels of inflammatory factors. We found that OMT significantly inhibited HMGB1-mediated RAGE/NF-κB activation and downstream inflammatory cytokine production in response to LPS stimulation. Finally, an in vivo experiment was performed on septic mice to further study the effect of OMT on injured organs. The animal experiments showed that OMT significantly inhibited HMGB1-mediated RAGE/NF-κB activation, protected against the inflammatory response and organ injury induced by CLP, and prolonged the survival rate of septic mice. Herein, we provide evidence that OMT exerts a significant therapeutic effect on sepsis by inhibiting the HMGB1/RAGE/NF-κB signaling pathway.

The Spermine Oxidase/Spermine Axis Coordinates ATG5-Mediated Autophagy to Orchestrate Renal Senescence and Fibrosis.

Decreased plasma spermine levels are associated with kidney dysfunction. However, the role of spermine in kidney disease remains largely unknown. Herein, it is demonstrated that spermine oxidase (SMOX), a key enzyme governing polyamine metabolism, is predominantly induced in tubular epithelium of human and mouse fibrotic kidneys, alongside a reduction in renal spermine content in mice. Moreover, renal SMOX expression is positively correlated with kidney fibrosis and function decline in patients with chronic kidney disease. Importantly, supplementation with exogenous spermine or genetically deficient SMOX markedly improves autophagy, reduces senescence, and attenuates fibrosis in mouse kidneys. Further, downregulation of ATG5, a critical component of autophagy, in tubular epithelial cells enhances SMOX expression and reduces spermine in TGF-ß1-induced fibrogenesis in vitro and kidney fibrosis in vivo. Mechanically, ATG5 readily interacts with SMOX under physiological conditions and in TGF-ß1-induced fibrogenic responses to preserve cellular spermine levels. Collectively, the findings suggest SMOX/spermine axis is a potential novel therapy to antagonize renal fibrosis, possibly by coordinating autophagy and suppressing senescence.

[Activated phosphoinositide 3-kinase delta syndrome: report of seven cases]. / PI3Kδ过度活化综合征7例报道.

OBJECTIVES: To summarize the clinical data of 7 children with activated phosphoinositide 3-kinase delta syndrome (APDS) and enhance understanding of the disease. METHODS: A retrospective analysis was conducted on clinical data of 7 APDS children admitted to Hunan Provincial People's Hospital from January 2019 to August 2023. RESULTS: Among the 7 children (4 males, 3 females), the median age of onset was 30 months, and the median age at diagnosis was 101 months. Recurrent respiratory tract infections, hepatosplenomegaly, and multiple lymphadenopathy were observed in all 7 cases. Sepsis was observed in 5 cases, otitis media and multiple caries were observed in 3 cases, and diarrhea and joint pain were observed in 2 cases. Lymphoma and systemic lupus erythematosus were observed in 1 case each. Fiberoptic bronchoscopy was performed in 4 cases, revealing scattered nodular protrusions in the bronchial lumen. The most common respiratory pathogen was Streptococcus pneumoniae (4 cases). Six patients had a p.E1021K missense mutation, and one had a p.434-475del splice site mutation. CONCLUSIONS: p.E1021K is the most common mutation site in APDS children. Children who present with one or more of the following symptoms: recurrent respiratory tract infections, hepatosplenomegaly, multiple lymphadenopathy, otitis media, and caries, and exhibit scattered nodular protrusions on fiberoptic bronchoscopy, should be vigilant for APDS. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(5): 499-505.