Protective role of the CD73-A2AR axis in cirrhotic cardiomyopathy through negative feedback regulation of the NF-κB pathway.

Background: Myocardial inflammation and apoptosis induced by cirrhosis are among the primary mechanisms of cirrhotic cardiomyopathy. CD73, a common extracellular nucleotidase also known as 5'-nucleotidase, is associated with the progression of inflammation and immunity in multiple organs. However, the mechanism by which CD73 contributes to myocardial inflammation and apoptosis in cirrhosis remains unclear. Methods: In this study, a cirrhotic cardiomyopathy model in mice was established by bile duct ligation. Myocardial-specific overexpression of CD73 was achieved by tail vein injection of AAV9 (adeno-associated virus)-cTNT-NT5E-mCherry, and cardiac function in mice was assessed using echocardiography. Myocardial inflammation infiltration and apoptosis were evaluated through pathological observation and ELISA assays. The expression of CD73, A2AR, apoptotic markers, and proteins related to the NF-κB pathway in myocardial tissue were measured. Results: In the myocardial tissue of the cirrhotic cardiomyopathy mouse model, the expression of CD73 and A2AR increased. Overexpression of CD73 in the myocardium via AAV9 injection and stimulation of A2AR with CGS 21680 inhibited myocardial inflammation and cardiomyocyte apoptosis induced by cirrhosis. Additionally, overexpression of CD73 suppressed the activation of the NF-κB pathway by upregulating the expression of the adenosine receptor A2A. Conclusion: Our study reveals that the CD73/A2AR signaling axis mitigates myocardial inflammation and apoptosis induced by cirrhosis through negative feedback regulation of the NF-κB pathway.

Prescribed performance adaptive neural event-triggered control for switched nonlinear cyber-physical systems under deception attacks.

In this paper, the design of an adaptive neural event-triggered control scheme for a class of switched nonlinear systems affected by external disturbances and deception attacks is presented. In order to address the effects caused by unknown disturbances, a switched nonlinear disturbance observer is used, and the error between the estimated signals and actual disturbances is small. Meanwhile, a prescribed performance function is introduced, which aims to ensure system output reaches the performance bounds within a predefined finite time. In addition, a dynamic event-triggered mechanism is designed to reduce the communication load. Based on the theoretical analysis, all signals within the closed-loop system are bounded, while simultaneously ensuring the complete elimination of Zeno behavior. Finally, the validity and efficacy of the scheme are proven by an example of numerical simulation.

Fecal microbiota transplantation alleviates mild-moderate COVID-19 associated diarrhoea and depression symptoms: A prospective study of a randomized, double-blind clinical trial.

Currently, the emergence of the endemic Coronavirus disease (COVID-19) situation still poses a serious threat to public health. However, it remains elusive about the role of fecal microbiota transplantation in treating COVID-19. We performed a randomized, double-blind, placebo-controlled clinical trial enrolling a cohort of 40 COVID-19 patients with mild-moderate symptoms. Our results showed that fecal microbiota transplantation provided an amelioration in diarrhoea (p = 0.026) of digestive system and depression (p = 0.006) of neuropsychiatric-related symptom in COVID-19 patients, respectively. Meanwhile, we found that the number of patients with diarrhoea decreased from 19 to 0 on day 7 after fecal microbiota transplantation treatment, and it was statistically changed compared to the placebo group (p = 0.047). Of note, the serum concentration of aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT, fecal microbiota transplantation, pre vs. post: 0.966 vs. 0.817), a biomarker for predicting long COVID-19, was significantly reduced by fecal microbiota transplantation. In all, our study supports that fecal microbiota transplantation could be a novel therapeutic strategy for COVID-19 patients with diarrhoea and depressive symptoms, which is potentially valuable in ameliorating long COVID-19 symptoms.

Predictive value of bile acids as metabolite biomarkers for gallstone disease: A systematic review and meta-analysis.

BACKGROUND: The profiles of bile acids (BAs) in patients with gallstone disease (GSD) have been found to be altered markedly though in an inconsistent pattern. This study aims to characterize the variation of the BA profiles in GSD patients, thereby to discover the potential metabolite biomarkers for earlier detection of GSD. METHODS: Literature search of eight electronic database in both English and Chinese was completed on May 11, 2023. The qualitative and quantitative reviews were performed to summarize the changes of BA profiles in GSD patients compared with healthy subjects. The concentrations of BAs were adopted as the primary outcomes and the weighted mean differences (WMDs) and 95% confidence interval (CI) were generated by random-effects meta-analysis models. RESULTS: A total of 30 studies were enrolled which included 2313 participants and reported the 39 BAs or their ratios. Qualitative review demonstrated serum Taurocholic Acid (TCA), Glycochenodeoxycholic acid (GCDCA), Glycocholic acid (GCA), Taurochenodeoxycholic acid (TCDCA), Glycodeoxycholic acid (GDCA) and Deoxycholic acid (DCA) were significantly increased in GSD patients compared with healthy subjects. Meta analysis was performed in 16 studies and showed that serum Total BAs (TBA) (WMD = 1.36µmol/L, 95%CI = 0.33; 2.4) was elevated however bile TBA (WMD = -36.96mmol/L, 95%CI = -52.32; -21.6) was declined in GSD patients. GCA (WMD = 0.83µmol/L, 95%CI = 0.06; 1.6) and TCA (WMD = 0.51µmol/L; 95%CI = 0.18; 0.85) were both increased in serum sample; TCDCA (WMD = 2.64mmol/L, 95%CI = 0.16; 5.12) was rising, however GCDCA (WMD = -13.82mmol/L, 95%CI = -21.86; -5.78) was falling in bile sample of GSD patients. The level of serum DCA in the GSD patients was found to be increased by using chromatography, yet decreased by chromatography mass spectrometry. CONCLUSION: The profiles of BAs demonstrated distinctive changes in GSD patients compared with healthy control subjects. Serum GCA, TCA and GCDCA, as the typically variant BAs, presented as a potential marker for earlier diagnosis of GSD, which could facilitate early prophylactic intervention. Yet, further validation of these biomarkers by longitudinal studies is still warranted in the future. PROSPERO registration number CRD42022339649.

Prediction of hepatic artery occlusion after liver transplantation by ultrasound characteristics and clinical risk factors.

BACKGROUND: Hepatic artery occlusion (HAO) after liver transplantation (LT) is a devastating complication, resulting in early graft loss and reduced overall survival. Ultrasound is an established assessment method for HAO in patients following LT, especially those with complex hepatic artery reconstruction. AIM: To investigate the ultrasound characteristics and analyze the risk factors associated with HAO in patients after LT. METHODS: We retrospectively analyzed the ultrasound characteristics and the clinic risk factors associated with HAO in 400 adult LT patients who were enrolled and treated at the Third People's Hospital of Shenzhen between November 2016 and July 2022. Fourteen patients diagnosed with acute HAO (A-HAO) by surgery and fifteen diagnosed with chronic HAO (C-HAO) were included. A control group of 33 patients without HAO complications during the same period were randomly selected using a random number table. All patients underwent an ultrasonography examination. Parameters including resistance index (RI), peak systolic velocity (PSV), and portal vein velocity (PVV) were compared across the groups. Additionally, basic clinical data were collected for all patients, including gender, age, primary diagnosis, D-dimer concentration, total operation time, cold ischemia time, hot ischemia time, intraoperative blood loss and transfusion, intraoperative urine volume, infusion, model for end-stage liver disease (MELD) score, and whether complex hepatic artery reconstructions were performed. Furthermore, risk factors influencing HAO formation after LT were analyzed. RESULTS: Compared to the non-HAO group, PVV and RI were higher in the A-HAO group, while PSV was lower. Conversely, both PSV and RI were lower in the C-HAO group compared to the non-HAO group. The proportion of patients undergoing complex hepatic artery reconstructions and the gamma-glutamyltransferase (GGT) level before occlusion were significantly higher in the A-HAO group compared to the non-HAO group. However, there were no distinct differences between the two groups in D-dimer, MELD score, pre-occlusion alanine transaminase and aspartate transaminase levels, or intraoperative conditions. CONCLUSION: Ultrasound features of the hepatic artery before occlusion are significantly associated with postoperative HAO development. Additionally, complex hepatic artery reconstructions, defined as revascularization of the graft requiring additional anastomosis between donor hepatic arteries, constitute a risk factor for A-HAO. Besides, abnormal pre-occlusion GGT elevation is an important biochemical indicator. Therefore, ultrasound examination serves as an important tool for screening HAO, especially in patients with the identified risk factors.

Pediatric femoral shaft fractures: the American Academy of Orthopaedic Surgeons clinical practice guidelines versus actual management in a teaching hospital.

Background: In 2009, the clinical practice guidelines (CPG) were released by the American Academy of Orthopaedic Surgeons (AAOS), which outline an age-based approach for treating pediatric femoral shaft fractures (PFSF), both nonoperatively and operatively. The aim of the current study was to investigate potential disparities between the recommended treatments for PFSF based on the AAOS-CPG and the actual treatments administered in The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University. Methods: A retrospective review was conducted on the medical charts and radiographs of all PFSF treated at The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University from January 2014 to January 2022. We identified 445 children who met our inclusion criteria and evaluated their treatments according to the AAOS-CPG. Actual treatments were then compared with the treatments recommended by the AAOS-CPG. Binomial and multivariate logistic regression was used to examine whether different factors could predict the choice between operative and nonoperative management. Results: Operative treatments were undertaken in 102 of 215 (47.4%) fractures in children younger than 6 years, in 102 of 122 (83.6%) fractures in those between 6 and 12 years of age, and in 107 of 108 (99.1%) fractures in those older than 12 years. Nonoperative management was conducted in 113 of 215 (52.6%) fractures in children younger than 6 years, in 20 of 122 (16.4%) fractures in those between 6 and 12 years of age, and in 1 of 108 (0.9%) fractures in those older than 12 years of age. Surgeon decisions for non-surgery were in agreement with the CPG 52.6% of the time, whereas agreement reached 90.9% for surgical choices. Predictors of actual operative management were age (P=0.01), patient weight (P<0.001), fracture pattern (P<0.001), presence of other orthopedic injuries requiring surgery (P=0.002), and polytrauma (P=0.02). Conclusions: There was limited concordance between actual treatments and CPG recommendations, particularly for the nonoperative management of fractures in children under 6 years old. Age, patient weight, fracture pattern, presence of other orthopedic injuries requiring surgery, and polytrauma were the main predictors of our operative decision-making process.

Identification of immune- and oxidative stress-related signature genes as potential targets for mRNA vaccines for pancreatic cancer patients.

Adenocarcinoma of the pancreas (PAAD) is one of the deadliest malignant tumors, and messenger ribonucleic acid vaccines, which constitute the latest generation of vaccine technology, are expected to lead to new ideas for the treatment of pancreatic cancer. The Cancer Genome Atlas-PAAD and Genotype-Tissue Expression data were merged and analyzed. Weighted gene coexpression network analysis was used to identify gene modules associated with tumor mutational burden among the genes related to both immunity and oxidative stress. Differentially expressed immune-related oxidative stress genes were screened via univariate Cox regression analysis, and these genes were analyzed via nonnegative matrix factorization. After immune infiltration analysis, least absolute shrinkage and selection operator regression combined with Cox regression was used to construct the model, and the usefulness of the model was predicted based on the receiver operating characteristic curve and decision curve analysis curves after model construction. Finally, metabolic pathway enrichment was analyzed using gene set enrichment analysis combined with Kyoto Encyclopedia of Genes and Genomes and gene ontology biological process analyses. This model consisting of the ERAP2, mesenchymal-epithelial transition factor (MET), CXCL9, and angiotensinogen (AGT) genes can be used to help predict the prognosis of pancreatic cancer patients more accurately than existing models. ERAP2 is involved in immune activation and is important in cancer immune evasion. MET binds to hepatocyte growth factor, leading to the dimerization and phosphorylation of c-MET. This activates various signaling pathways, including MAPK and PI3K, to regulate the proliferation, invasion, and migration of cancer cells. CXCL9 overexpression is associated with a poor patient prognosis and reduces the number of CD8 + cytotoxic T lymphocytes in the PAAD tumor microenvironment. AGT is cleaved by the renin enzyme to produce angiotensin 1, and AGT-converting enzyme cleaves angiotensin 1 to produce angiotensin 2. Exposure to AGT-converting enzyme inhibitors after pancreatic cancer diagnosis is associated with improved survival. The 4 genes identified in the present study - ERAP2, MET, CXCL9, and AGT - are expected to serve as targets for messenger ribonucleic acid vaccine development and need to be further investigated in depth.

Insights gained into the injury mechanism of drug and herb induced liver injury in the hepatic microenvironment.

Drug-Induced Liver Injury (DILI) and herb Induced Liver Injury (HILI) continues to pose a substantial challenge in both clinical practice and drug development, representing a grave threat to patient well-being. This comprehensive review introduces a novel perspective on DILI and HILI by thoroughly exploring the intricate microenvironment of the liver. The dynamic interplay among hepatocytes, sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, cholangiocytes, and the intricate vascular network assumes a central role in drug metabolism and detoxification. Significantly, this microenvironment is emerging as a critical determinant of susceptibility to DILI and HILI. The review delves into the multifaceted interactions within the liver microenvironment, providing valuable insights into the complex mechanisms that underlie DILI and HILI. Furthermore, we discuss potential strategies for mitigating drug-induced liver injury by targeting these influential factors, emphasizing their clinical relevance. By highlighting recent advances and future prospects, our aim is to shed light on the promising avenue of leveraging the liver microenvironment for the prevention and mitigation of DILI and HILI. This deeper understanding is crucial for advancing clinical practices and ensuring patient safety in the realm of DILI and HILI.

Comparative genomics illuminates karyotype and sex chromosome evolution of sharks.

Chondrichthyes is an important lineage to reconstruct the evolutionary history of vertebrates. Here, we analyzed genome synteny for six chondrichthyan chromosome-level genomes. Our comparative analysis reveals a slow evolutionary rate of chromosomal changes, with infrequent but independent fusions observed in sharks, skates, and chimaeras. The chondrichthyan common ancestor had a proto-vertebrate-like karyotype, including the presence of 18 microchromosome pairs. The X chromosome is a conversed microchromosome shared by all sharks, suggesting a likely common origin of the sex chromosome at least 181 million years ago. We characterized the Y chromosomes of two sharks that are highly differentiated from the X except for a small young evolutionary stratum and a small pseudoautosomal region. We found that shark sex chromosomes lack global dosage compensation but that dosage-sensitive genes are locally compensated. Our study on shark chromosome evolution enhances our understanding of shark sex chromosomes and vertebrate chromosome evolution.

Novel Systemic Inflammatory Markers Predict All-Cause Mortality in Patients Undergoing Endovascular Abdominal Aortic Aneurysm Repair.

Background: Clinically useful predictors for risk stratification of long-term survival may assist in selecting patients for endovascular abdominal aortic aneurysm (EVAR) procedures. This study aimed to analyze the prognostic significance of peroperative novel systemic inflammatory markers (SIMs), including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), hemoglobin-to-red cell distribution width ratio (HRR), systemic immune-inflammatory index (SIII), and systemic inflammatory response index (SIRI), for long-term mortality in EVAR. Methods: A retrospective analysis was performed on 147 consecutive patients who underwent their first EVAR procedure at the Department of Vascular Surgery, Beijing Hospital. The patients were divided into the mortality group (n = 37) and the survival group (n = 110). The receiver operating characteristic curves were used to ascertain the threshold value demonstrating the most robust connection with mortality. The Kaplan-Meier survival analysis was performed between each SIM and mortality. The relationship between SIMs and survival was investigated using restricted cubic splines and multivariate Cox regression analysis. Results: The study included 147 patients, with an average follow-up duration of 34.28 ± 22.95 months. Deceased patients showed significantly higher NLR (p < 0.001) and reduced HRR (p < 0.001). The Kaplan-Meier estimates of mortality were considerably greater in the higher-NLR group (NLR > 2.77) and lower-HRR group (HRR < 10.64). The hazard ratio (HR) of 0.833 (95% confidence interval (95% CI): 0.71-0.97, p < 0.021) was determined to be statistically significant in predicting death in the multivariable analysis. Conclusions: Preoperative higher-NLR and lower-HRR have been associated with a lower long-term survival rate in abdominal aortic aneurysm (AAA) patients undergoing elective EVAR. Multivariate Cox regression showed that decreased preoperative HRR is an independent risk factor that increases mortality risk following EVAR. SIMs, such as the NLR and HRR, could be used in future clinical risk prediction methodologies for AAA patients undergoing EVAR. However, additional prospective cohort studies are needed to identify these findings.

Contrast­associated acute kidney injury in myocardial infarction patients undergoing elective percutaneous coronary intervention: insight from the Iodixanol-AKI Registry.

Previous studies have reported a high occurrence of contrast-associated acute kidney injury (CA-AKI) in myocardial infarction (MI) patients undergoing primary percutaneous coronary intervention (PCI). However, the data on CA-AKI in MI patients who underwent elective PCI are limited. To evaluate the incidence of CA-AKI in MI patients undergoing elective PCI. The data were sourced from the Iodixanol-AKI Registry of MI patients scheduled to undergo elective PCI in 8 medical centers from May 2020 to November 2021. The participants were divided into three groups: acute, prior, and multiple MI. The outcomes measured were CA-AKI and the composite endpoint of major adverse renal and cardiovascular events (MARCE). The incidence of CA-AKI was 4.46% (37/830) in the MI patients, 4.40% (7/159) in the acute MI patients, 4.41% (22/499) in the prior MI patients, and 4.65% (8/172) in the multiple MI patients. Of note, 36 patients (97.30%) at AKI stage 1, and only 1 patient at AKI stage 2. There was no difference in the incidence of CA-AKI (P = 0.991) among the three groups. Multivariate regression analysis revealed that the independent risk factors for CA-AKI were diabetes and an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. MARCE occurred in 3.4% (28/830) of the total patients and was not associated with either any subgroup of patients with MI or AKI. The incidence of CA-AKI was low and mainly limited to mildly impaired renal function in MI patients undergoing elective PCI.

Case Report: Isolated Vertigo as the Sole Manifestation of Left Lateral Medullary Infarction Following Contralateral Varicella-Zoster Virus Infection.

Background: Cerebral infarct associated with varicella-zoster virus (VZV) has been reported in the literature, while isolated central dizziness due to lateral medullary infarct (LMI) following VZV infection is rarely reported. Case report: We report the case of a 65-year-old man who presented to the neurology department because of herpes zoster on the right trigeminal nerve distribution. At 12 hours after admission, he developed transient vertigo along with nausea and unsteady walking and left-sided spontaneous horizontal nystagmus, gaze-evoked nystagmus, and upbeat nystagmus. The other usual signs of LMI including Horner syndrome, dysarthria, swallowing difficulty, and hemibody sensory change were absent. Video head impulse indicated decreased head impulse gain of the vestibulo-ocular reflex for the bilateral horizontal, anterior, and posterior semicircular canals with abnormal saccade waves. Suppression head impulse paradigm showed few downward saccades reflecting anti-compensatory saccades after the end of the head impulse back to the head-fixed target and decreased vestibulo-ocular reflex gain values of bilateral semicircular canals. Brain magnetic resonance imaging (MRI) showed a small infarct in the far dorsolateral portion of the left rostral medulla. The cerebrospinal fluid was positive for VZV DNA. Conclusions: In patients with VZV infection who develop dizziness, the possibility of cerebral infarct should be considered. Patients with facial herpes zoster and neurological symptoms always be screened for stroke using MRI and lumbar puncture should be performed and acyclovir administered empirically.

Efficacy of submental island flap closing advanced mandibular MRONJ lesion in malignancy patients.

OBJECTIVE: This study evaluated the effectiveness of a submental island flap in closing advanced mandibular medication-related osteonecrosis of the jaw (MRONJ) wounds in patients with malignant tumors. SUBJECTS AND METHODS: A total of 85 patients with stage II and III MRONJ of mandible with malignant tumor as their primary disease were retrospectively analyzed. All patients underwent surgical treatment, and the soft tissue wound closure was performed either with a submental island flap (SIF) or mucoperiosteal flap (MF). Univariate and multifactorial models were applied to analyze the factors influencing patients' prognosis. RESULTS: Univariate analysis (p = 0.004, OR 0.075-0.575, 95% CI) and binary logistic regression (p = 0.017, OR 0.032-0.713, 95% CI) suggested that the surgical prognosis of SIF wound closure was significantly better than that of MF. CONCLUSION: Closure of wound after resection of mandibular MRONJ lesions in patients with malignant tumors using SIF had a better clinical prognosis compared with MF.

Transcriptome analysis of Kunming mice responses to the bite of Xenopsylla cheopis.

BACKGROUND: Flea bites could trigger a series of complex molecular responses in the host. However, our understanding of the responses at the molecular level is still relatively limited. This study quantifies the changes in gene expression in mice after flea bites by RNA sequencing (RNA-seq) from their spleens, revealing the potential biological effects of host response to flea bites. METHODS: RNA-seq was used for transcriptome analysis to screen for differentially expressed genes (DEGs) between the control mice group and the flea bite mice group. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on DEGs. Protein-protein interaction (PPI) network analysis on DEGs related to immune processes was performed. Finally, we randomly selected several genes from the screened DEGs to validate the results from the transcriptome data by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: A total of 521 DEGs were identified, including 277 upregulated and 244 downregulated. There were 258 GO terms significantly enriched by upregulated DEGs and 419 GO terms significantly enriched by downregulated DEGs. Among the upregulated DEGs, 22 GO terms were associated with immune cells (e.g., B cells and T cells) and immune regulatory processes, while among the downregulated DEGs, 58 GO terms were associated with immune cells and immune regulatory processes. Through PPI analysis, we found that CD40 molecules with significantly downregulated expression levels after flea bites may play an important role in host immune regulation. Through KEGG pathway enrichment analysis, a total of 26 significantly enriched KEGG pathways were identified. The RT-qPCR analysis results indicated that the transcriptome sequencing results were reliable. CONCLUSIONS: Through in-depth analysis of transcriptome changes in mice caused by flea bites, we revealed that flea bites could stimulate a series of biological and immunological responses in mice. These findings not only provided a deeper understanding of the impact of flea bites on the host but also provided a basis for further research on the interaction between ectoparasites and the host. We believe that digging deeper into the significance of these transcriptome changes will help reveal more about the adaptive response of the host to ectoparasites.

The landscape of programmed cell death-related lncRNAs in Alzheimer's disease and Parkinson's disease.

This study delivers a thorough analysis of long non-coding RNAs (lncRNAs) in regulating programmed cell death (PCD), vital for neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD). We propose a new framework PCDLnc, and identified 20 significant lncRNAs, including HEIH, SNHG15, and SNHG5, associated with PCD gene sets, which were known for roles in proliferation and apoptosis in neurodegenerative diseases. By using GREAT software, we identified regulatory functions of top lncRNAs in different neurodegenerative diseases. Moreover, lncRNAs cis-regulated mRNAs linked to neurodegeneration, including JAK2, AKT1, EGFR, CDC42, SNCA, and ADIPOQ, highlighting their therapeutic potential in neurodegenerative diseases. A further exploration into the differential expression of mRNA identified by PCDLnc revealed a role in apoptosis, ferroptosis and autophagy. Additionally, protein-protein interaction (PPI) network analysis exposed abnormal interactions among key genes, despite their consistent expression levels between disease and normal samples. The randomforest model effectively distinguished between disease samples, indicating a high level of accuracy. Shared gene subsets in AD and PD might serve as potential biomarkers, along with disease-specific gene sets. Besides, we also found the strong relationship between AD and immune infiltration. This research highlights the role of lncRNAs and their associated genes in PCD in neurodegenerative diseases, offering potential therapeutic targets and diagnostic markers for future study and clinical application.

Therapeutic effects of flavonoids on pulmonary fibrosis: A preclinical meta-analysis.

BACKGROUND: The efficacy of flavonoid supplementation in animal models of pulmonary fibrosis has been demonstrated. PURPOSE: We conducted a systematic review and meta-analysis to evaluate the efficacy and underlying mechanisms of flavonoids in animal models of bleomycin-induced pulmonary fibrosis. STUDY DESIGN: Relevant studies (n = 45) were identified from English- and Chinese-language databases from the inception of the database until October 2023. METHODS: Methodological quality was evaluated using the SYRCLE risk of bias tool. Statistical analyses were conducted using RevMan 5.3 and Stata 17.0. Lung inflammation and fibrosis score were the primary outcome indicators. RESULTS: Flavonoids can alleviate pathological changes in the lungs. The beneficial effects of flavonoids on pulmonary fibrosis likely relate to their inhibition of inflammatory responses, restoration of oxidative and antioxidant homeostasis, and regulation of fibroblast proliferation, migration, and activation by transforming growth factor ß1/mothers against the decapentaplegic homologue/AMP-activated protein kinase (TGF-ß1/Smad3/AMPK), inhibitor kappa B alpha/nuclear factor-kappa B (IκBα/NF-κB), phosphatidylinositol 3-kinase (PI3K)/AKT, interleukin 6/signal transducer/activator of transcription 3 (IL6/STAT3), and nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2-Keap1) pathways. CONCLUSION: Flavonoids are potential candidate compounds for the prevention and treatment of pulmonary fibrosis. However, extensive preclinical research is necessary to confirm the antifibrotic properties of natural flavonoids.

Elevating Discharge Voltage of Li2CO3-Routine Li-CO2 Battery over 2.9†V at an Ultra-Wide Temperature Window.

The Li-CO2 batteries utilizing greenhouse gas CO2 possess advantages of high energy density and environmental friendliness. However, these batteries following Li2CO3-product route typically exhibit low work voltage (<2.5 V) and energy efficiency. Herein, we have demonstrated for the first time that cobalt phthalocyanine (CoPc) as homogeneous catalyst can elevate the work plateau towards 2.98 V, which is higher than its theoretical discharge voltage without changing the Li2CO3-product route. This unprecedented discharge voltage is illustrated by mass spectrum and electrochemical analyses that CoPc has powerful adsorption capability with CO2 (-7.484 kJ mol-1) and forms discharge intermediate of C33H16CoN8O2. Besides high discharge capacity of 18724 mAh g-1 and robust cyclability over 1600 hours (1000 mAh g-1 cut-off) at a current density of 100 mA g-1, the batteries show high temperature adaptability (-30-80 °C). Our work is paving a promising avenue for the progress of high-efficiency Li-CO2 batteries.

P2X7 receptor deficiency attenuates cisplatin-induced kidney injury via inhibiting NLRP3 inflammasome activation.

Nephrotoxicity is a major constraint of cisplatin application in many solid tumors. Since the lack of preventive strategies, the necessity exists to identify critical molecular targets involved in cisplatin nephrotoxicity. The Purinergic ligand-gcotedion channel 7 receptor (P2X7R) is a ligand-gated ion channel that is predominantly implicated in inflammation and cell death. Our aim is to investigate the role P2X7R in cisplatin-induced acute and chronic kidney injury, as well as the underlying mechanism. In this study, we found that cisplatin can cause an increase in the expression of P2X7R in mouse kidney tissue, and P2X7R knockout can alleviate acute renal function damage caused by cisplatin, as well as the expression of kidney injury molecule 1 (KIM-1) and interleukin-18 (IL-18). Cisplatin can cause an increase in the expression of nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in mouse kidney tissue. Compared with wild-type mice, P2X7R -/- mice showed decreased expression of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved Caspase-1, and cleaved IL-1ß in kidney tissue after cisplatin administration, and the apoptosis of renal tubular epithelial cells were also decreased. In addition, we also found that NLRP3 knockout can improve cisplatin induced degeneration, detachment, and necrosis of renal tubular epithelial cells. Furthermore, P2X7R -/- mice also showed reduced renal fibrosis and better long-term renal prognosis. In conclusion, our study identified that P2X7R knockout can improve cisplatin induced acute renal injury and chronic renal fibrosis by inhibiting the activation of NLRP3 inflammasome.

S-scheme heterojunction phthalocyanine/TiO2 photoelectrochemical sensor for innovative glutathione detection.

A novel photoelectrochemical sensor, employing an S-scheme heterojunction of phthalocyanine and TiO2 nanoparticles, has been developed to enable highly sensitive determination of glutathione. By integrating the favorable stability, environmental benignity, and electronic properties of the TiO2 matrix with the unique photoactivity of phthalocyanine species, the designed sensor presents a substantial linear dynamic range and a low detection limit for the quantification of glutathione. The sensitivity is attributed to efficient charge transfer and separation across the staggered heterojunction energy levels, which generates measurable photocurrent signals. Systematic variation of phthalocyanine content reveals an optimal composition that balances light harvesting capacity and electron-hole recombination rates. The incorporation of phosphotungstic acid (PTA) in sample preparation effectively minimizes interference from compounds like L-cysteine and others. Consequently, this leads to an improvement in accuracy through the reduction of impurity levels. Appreciable photocurrent enhancements are observed upon introduction of both oxidized and reduced glutathione at the optimized composite photoanode. Coupled with advantageous features of photoelectrochemical transduction such as simplicity, cost-effectiveness, and resistance to fouling, this sensor holds great promise for practical applications in complex biological media.

Robust distributed fixed-time cooperative hunting control for multi-quadrotor with obstacles avoidance.

This paper addressed the robust distributed fixed-time cooperative hunting problem of multiple quadrotors subject to disturbances in obstacles environment. To handle the underactuated issue inherent in quadrotor dynamics, an inner-outer (attitude-position) loop cascade control configuration is proposed to achieve the cooperative flight control of quadrotors. For position subsystem, as the information of target cannot be accessible to all quadrotors, a distributed fixed-time observer is devised to estimate the target's information. To improve the system's robustness, a fixed-time extended state observer is designed to reject disturbances actively. Based on two observers, the sliding mode position encirclement control protocol with repulsive force is presented to avoid obstacles and encircle the target within a fixed time. For attitude subsystem, a sliding mode attitude tracking control protocol is proposed such that tracking errors can converge to zero even under disturbances. The stability analysis is performed to show the stabilization of the whole closed-loop system with fixed-time convergence. Finally, two sets of comparison simulation are provided to show the superiority of the developed control strategy.