Esketamine alleviates ferroptosis-mediated acute lung injury by modulating the HIF-1α/HO-1 pathway.

BACKGROUND: Alveolar epithelial cell (AEC) ferroptosis contributes to the progression of acute lung injury (ALI). Esketamine (ESK) is a new clinical sedative, anesthetic, and analgesic drug that has attracted substantial attention in mental health research because of its antidepressant effects. However, the effects of ESK on ferroptosis-mediated ALI remain unclear. OBJECTIVE: This study aimed to explore the protective effect of ESK on AEC ferroptosis in ALI and its potential molecular mechanism in vivo and in vitro. METHODS: The antiferroptotic and anti-inflammatory effects of ESK were assessed in a mouse model of lipopolysaccharide (LPS)-induced ALI. In vitro, the epithelial cell lines MLE-12 and A549 were used to examine the underlying mechanism by which ESK regulates inflammation and ferroptosis. RESULTS: ESK protected mice against LPS-induced ALI, significantly attenuated pathological changes in the lungs and decreased inflammation and ferroptosis. In vitro, ESK inhibited LPS-induced inflammation and ferroptosis in MLE-12 and A549 cells. Moreover, ferroptosis mediated inflammation in LPS-induced ALI in vivo and in vitro, and ESK decreased the LPS-induced inflammatory response by suppressing ferroptosis. ESK promoted the HIF-1α/HO-1 pathway in LPS-treated AECs and in the lung tissues of mice with LPS-induced ALI. Moreover, pretreatment with ESK and the HIF-1α stabilizer dimethyloxaloylglycine (DMOG) substantially attenuated lung injury and prevented changes in ferroptosis-related biochemical indicators, including glutathione (GSH) depletion, malondialdehyde (MDA) production and glutathione peroxidase 4 (GPX4) downregulation, in untreated LPS-induced mice but not in LPS-induced mice treated with the HO-1 inhibitor zinc protoporphyrin (ZNPP). Similar effects were observed in vitro in HO-1 siRNA-transfected A549 cells after LPS incubation but not in control siRNA-transfected cells. CONCLUSION: ESK can inhibit ferroptosis-mediated lipid peroxidation by increasing the expression of HIF-1α/HO-1 pathway, highlighting the potential of ESK to treat LPS-induced ALI.

Probing spin hydrodynamics on a superconducting quantum simulator.

Characterizing the nature of hydrodynamical transport properties in quantum dynamics provides valuable insights into the fundamental understanding of exotic non-equilibrium phases of matter. Experimentally simulating infinite-temperature transport on large-scale complex quantum systems is of considerable interest. Here, using a controllable and coherent superconducting quantum simulator, we experimentally realize the analog quantum circuit, which can efficiently prepare the Haar-random states, and probe spin transport at infinite temperature. We observe diffusive spin transport during the unitary evolution of the ladder-type quantum simulator with ergodic dynamics. Moreover, we explore the transport properties of the systems subjected to strong disorder or a tilted potential, revealing signatures of anomalous subdiffusion in accompany with the breakdown of thermalization. Our work demonstrates a scalable method of probing infinite-temperature spin transport on analog quantum simulators, which paves the way to study other intriguing out-of-equilibrium phenomena from the perspective of transport.

Elimination of Intragrain Defect to Enhance the Performance of FAPbI3 Perovskite Solar Cells by Ionic Liquid.

Ionic liquids have been widely used to improve the efficiency and stability of perovskite solar cells (PSCs), and are generally believed to passivate defects on the grain boundaries of perovskites. However, few studies have focused on the relevant effects of ionic liquids on intragrain defects in perovskites which have been shown to be critical for the performance of PSCs. In this work, the effect of ionic liquid 1-hexyl-3-methylimidazolium iodide (HMII) on intragrain defects of formamidinium lead iodide (FAPbI3) perovskite is investigated. Abundant {111}c intragrain planar defects in pure FAPbI3 grains are found to be significantly reduced by the addition of the ionic liquid HMII, shown by using ultra-low-dose selected area electron diffraction. As a result, longer charge carrier lifetimes, higher photoluminescence quantum yield, better charge carrier transport properties, lower Urbach energy, and current-voltage hysteresis are achieved, and the champion power conversion efficiency of 24.09% is demonstrated. These observations suggest that ionic liquids significantly improve device performance resulting from the elimination of {111}c intragrain planar defects.

Comparison of the effect of tea shoots during different seasons in Arma chinensis (Hemiptera: Pentatomidae) reared on Ectropis grisescens (Lepidoptera: Geometridae) pupae.

In this study, we compared the growth, development, and fecundity of Arma chinensis (Fallou) reared on pupae of the geometrid Ectropis grisescens Warren fed on tea shoots during different seasons of the year. The raw data on life history were analyzed using the age-stage, 2-sex life table. When reared on spring or winter geometrid pupae, the duration of the immature stage of A. chinensis was significantly longer than in those produced during the summer or autumn. The survival rate of immature A. chinensis reared on autumn geometrid pupae was significantly lower compared to other treatments. Reproductive diapause was observed in adult A. chinensis reared on winter geometrid pupae. The adult preoviposition period (APOP), total preoviposition period (TPOP), and total longevity were significantly longer in A. chinensis reared on winter pupae than in the other treatments. The fecundity of A. chinensis reared on spring geometrid pupae was significantly lower than in the other treatments. The higher intrinsic rate of increase of the A. chinensis reared on summer pupae (r = 0.0966 day-1) and autumn pupae (r = 0.0983 day-1) resulted in higher fecundity, shorter immature duration, and shorter TPOP compared to the winter and spring populations. These findings can be utilized to enhance and sustain biological control of E. grisescens in tea plantations.

Effects of vitamin family members on insulin resistance and diabetes complications.

The following letter to the editor highlights the article "Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance" in World J Diabetes 2023 Oct 15; 14 (10): 1514-1523. It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.

Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats.

OBJECTIVE: This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats. METHODS: CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 µg/kg, and CP + Dex 25 µg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting. RESULTS: Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1. CONCLUSION: Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.

The dysfunction of CD8+ T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis.

Endometriosis is defined as an oestrogen-dependent and inflammatory gynaecological disease of which the pathogenesis remains unclear. This study aimed to investigate the cellular heterogeneity and reveal the effect of CD8+ T cells on the progress of endometriosis. Three ovarian endometriosis patients were collected, and single-cell RNA sequencing (scRNA-seq) progressed and delineated the cellular landscape of endometriosis containing five cell clusters. The endometrial cells (EMCs) were the major component, of which the mesenchymal cells were preponderant and characterized with increased inflammation and oestrogen synthesis in endometriosis. The proportion of T cells, mainly CD8+ T cells rather than CD4+, was reduced in endometriotic lesions, and the cytokines and cytotoxicity of ectopic T cells were depressed. CD8+ T cells depressed the proliferation of ESCs through inhibiting CDK1/CCNB1 pathway to arrest the cell cycle and triggered inflammation through activating STAT1 pathway. Correspondingly, the coculture with ESCs resulted in the dysfunction of CD8+ T cells through upregulating STAT1/PDCD1 pathway and glycolysis-promoted metabolism reprogramming. The endometriotic lesions were larger in nude mouse models with T-cell deficiency than the normal mouse models. The inhibition of T cells via CD90.2 or CD8A antibody increased the endometriotic lesions in mouse models, and the supplement of T cells to nude mouse models diminished the lesion sizes. In conclusion, this study revealed the global cellular variation of endometriosis among which the cellular count and physiology of EMCs and T cells were significantly changed. The depressed cytotoxicity and aberrant metabolism of CD8+ T cells were induced by ESCs with the activation of STAT1/PDCD1 pathway resulting in immune survival to promote endometriosis.

Transcriptomic analyses and machine-learning methods reveal dysregulated key genes and potential pathogenesis in human osteoarthritic cartilage.

Aims: This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Methods: Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization. Results: A total of 46 genes were obtained from the intersection of significantly upregulated genes in osteoarthritic cartilage and the key module genes screened by WGCNA. Functional annotation analysis revealed that these genes were closely related to pathological responses associated with OA, such as inflammation and immunity. Four key dysregulated genes (cartilage acidic protein 1 (CRTAC1), iodothyronine deiodinase 2 (DIO2), angiopoietin-related protein 2 (ANGPTL2), and MAGE family member D1 (MAGED1)) were identified after using machine-learning algorithms. These genes had high diagnostic value in both the training cohort and external validation cohort (receiver operating characteristic > 0.8). The upregulated expression of these hub genes in osteoarthritic cartilage signified higher levels of immune infiltration as well as the expression of metalloproteinases and mineralization markers, suggesting harmful biological alterations and indicating that these hub genes play an important role in the pathogenesis of OA. A competing endogenous RNA network was constructed to reveal the underlying post-transcriptional regulatory mechanisms. Conclusion: The current study explores and validates a dysregulated key gene set in osteoarthritic cartilage that is capable of accurately diagnosing OA and characterizing the biological alterations in osteoarthritic cartilage; this may become a promising indicator in clinical decision-making. This study indicates that dysregulated key genes play an important role in the development and progression of OA, and may be potential therapeutic targets.

The Function of Circular RNAs in Myocardial Ischemia-Reperfusion Injury: Underlying Mechanisms and Therapeutic Advancement.

Myocardial ischemia reperfusion injury (MIRI) represents a prevalent and severe cardiovascular condition that arises primarily after myocardial infarction recanalization, cardiopulmonary bypass surgery, and both stable and unstable angina pectoris. MIRI can induce malignant arrhythmias and heart failure, thereby increasing the morbidity and mortality rates associated with cardiovascular diseases. Hence, it is important to assess the potential pathological mechanisms of MIRI and develop effective treatments. The role of circular RNAs (circRNAs) in MIRI has increasingly become a topic of interest in recent years. Moreover, significant evidence suggests that circRNAs play a critical role in MIRI pathogenesis, thereby representing a promising therapeutic target. This review aimed to provide a comprehensive overview of the current understanding of the role of circRNAs in MIRI and discuss the mechanisms through which circRNAs contribute to MIRI development and progression, including their effects on apoptosis, inflammation, oxidative stress, and autophagy. Furthermore, the potential therapeutic applications of circRNAs in MIRI treatment, including the use of circRNA-based therapies and modulation of circRNA expression levels, have been explored. Overall, this paper highlights the importance of circRNAs in MIRI and underscores their potential as novel therapeutic targets.

Contamination and health risks brought by arsenic, lead and cadmium in a water-soil-plant system nearby a non-ferrous metal mining area.

Heavy metal(loid)s contamination prevails in the water-soil-plant system around non-ferrous metal mining areas. The present study aimed to evaluate the heavy metal(loid)s contamination in Nandan Pb-Zn mining area (Guangxi, China). A total of 36 river water samples, 75 paired paddy soil and rice samples, and 128 paired upland soil and plant samples were collected from this area. The concentrations of arsenic (As), lead (Pb), and cadmium (Cd) in these samples were measured. Results showed that the average water quality indexes (WQIs) at the 12 sampling sites along the main river ranged from 41 to 5008, indicating the water qualities decreasing from "Excellent" to "Undrinkable". The WQIs nearby tailings or industrial park were significantly higher than those at the other sites. 34.0% and 64.5% of soil samples exceeded the risk screening values for As and Cd. The Pb and Cd concentrations in all rice samples exceeded the Chinese food safety limits by 18.7% and 82.7%, respectively. Leafy vegetables had a higher concentration of As, Pb, and Cd than other vegetables, exceeding the maximum permissible limits by 14.1%, 61.2%, and 40.0%, respectively. The biological accumulation coefficient (BAC) of Cd was the highest in rice and lettuce leaves. The hazard quotients (HQs) of As and Cd, indicating non-carcinogenic risks, were 4.15 and 1.76 in adult males, and 3.40 and 1.45 in adult females, all higher than the permitted level (1.0). The carcinogenic probabilities of As and Cd from rice and leafy vegetables consumption were all higher than 1 × 10-4. We conclude that metal(loid)s contamination of the water-soil-plant system has posed great non-carcinogenic and carcinogenic risks to the local population.

The Correlation of Inflammation, Oxidative Stress, and Hippocampal Perfusion in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is closely related to abnormal cerebral blood flow. Inflammation and oxidative stress have always been important factors in the pathophysiology of AF. It remains unknown whether inflammation and oxidative stress are correlated to hippocampal perfusion in patients with AF.Sixty-three patients with AF with normal hippocampal blood perfusion (NHBP) were compared to 71 patients with AF with abnormal hippocampal blood perfusion (AHBP) using a case-control study design. The serum levels of inflammation and oxidative stress were measured. The hippocampal perfusion was detected. (1) The serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and oxidized low-density lipoprotein (ox-LDL) were statistically higher in the AHBP group than in the NHBP group. In the AHBP subgroup analysis, the serum levels of hs-CRP and IL-6 were statistically higher in patients with persistent AF than those with paroxysmal AF. (2) The relative cerebral blood volume (rCBV), mean transit time (MTT), and the time-to-peak (TTP) were statistically higher in the AHBP group than in the NHBP group. Moreover, cerebral blood flow (rCBF) was statistically lower in the AHBP group than in the NHBP group. (3) relative cerebral blood volume (rCBV), rCBF, MTT, and TTP were passively associated with serum hs-CRP and IL-6; rCBV, rCBF, and MTT were positively associated with ox-LDL. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF after multivariate logistic regression analysis.Oxidative stress and inflammatory biomarkers were increased in patients with AF with AHBP, in which the serum levels of hs-CRP and IL-6 in the persistent AF group were statistically higher than those in the paroxysmal AF group. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF.

Role of brain-derived neurotrophic factor in endotoxaemia-induced acute lung injury.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), which is a pulmonary manifestation of a systemic reactive inflammatory syndrome, is a serious disease with high mortality, and sepsis is an important risk factor in the development of ALI. Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family. It plays an essential role in the regulation of the modification of synaptic efficacy and brain metabolic activity and enhances neuronal survival. However, the role and underlying mechanism of BDNF in sepsis-induced ALI remain unclear. Here, we sought to observe the expression of BDNF in the lung tissues of mice. C57BL/6J mice were divided randomly into two groups: saline (n = 4) and lipopolysaccharide (LPS) (n = 4). We found that BDNF expression was elevated in the lung tissues of septic mice. Furthermore, we found that BDNF colocalized with aquaporin 5, a marker for type I alveolar epithelial cells, by immunofluorescence staining. In addition, we also found that tropomyosin-related kinase B, the specific receptor of BDNF, colocalized with surfactant protein C, a marker for type II alveolar epithelial cells, by immunofluorescence staining. Finally, the present study indicated that BDNF may alleviate excessive LPS-induced autophagy in alveolar epithelial cells. Overall, we hypothesize that BDNF expression increases in the lung tissues of septic mice as a compensatory mechanism to ameliorate sepsis-induced ALI by inhibiting excessive alveolar epithelial cell autophagy.

Simulating Chern insulators on a superconducting quantum processor.

The quantum Hall effect, fundamental in modern condensed matter physics, continuously inspires new theories and predicts emergent phases of matter. Here we experimentally demonstrate three types of Chern insulators with synthetic dimensions on a programable 30-qubit-ladder superconducting processor. We directly measure the band structures of the 2D Chern insulator along synthetic dimensions with various configurations of Aubry-André-Harper chains and observe dynamical localisation of edge excitations. With these two signatures of topology, our experiments implement the bulk-edge correspondence in the synthetic 2D Chern insulator. Moreover, we simulate two different bilayer Chern insulators on the ladder-type superconducting processor. With the same and opposite periodically modulated on-site potentials for two coupled chains, we simulate topologically nontrivial edge states with zero Hall conductivity and a Chern insulator with higher Chern numbers, respectively. Our work shows the potential of using superconducting qubits for investigating different intriguing topological phases of quantum matter.

Quantum Simulation of Topological Zero Modes on a 41-Qubit Superconducting Processor.

Quantum simulation of different exotic topological phases of quantum matter on a noisy intermediate-scale quantum (NISQ) processor is attracting growing interest. Here, we develop a one-dimensional 43-qubit superconducting quantum processor, named Chuang-tzu, to simulate and characterize emergent topological states. By engineering diagonal Aubry-André-Harper (AAH) models, we experimentally demonstrate the Hofstadter butterfly energy spectrum. Using Floquet engineering, we verify the existence of the topological zero modes in the commensurate off-diagonal AAH models, which have never been experimentally realized before. Remarkably, the qubit number over 40 in our quantum processor is large enough to capture the substantial topological features of a quantum system from its complex band structure, including Dirac points, the energy gap's closing, the difference between even and odd number of sites, and the distinction between edge and bulk states. Our results establish a versatile hybrid quantum simulation approach to exploring quantum topological systems in the NISQ era.

PDHA1 Alleviates Myocardial Ischemia-Reperfusion Injury by Improving Myocardial Insulin Resistance During Cardiopulmonary Bypass Surgery in Rats.

OBJECTIVE: Cardiopulmonary bypass (CPB) is a requisite technique for thoracotomy in advanced cardiovascular surgery. However, the consequent myocardial ischemia-reperfusion injury (MIRI) is the primary culprit behind cardiac dysfunction and fatal consequences post-operation. Prior research has posited that myocardial insulin resistance (IR) plays a vital role in exacerbating the progression of MIRI. Nonetheless, the exact mechanisms underlying this phenomenon remain obscure. METHODS: We constructed pyruvate dehydrogenase E1 α subunit (PDHA1) interference and overexpression rats and used ascending aorta occlusion in an in vivo model of CPB-MIRI. We devised an in vivo model of CPB-MIRI by constructing rat models with both pyruvate dehydrogenase E1α subunit (PDHA1) interference and overexpression through ascending aorta occlusion. We analyzed myocardial glucose metabolism and the degree of myocardial injury using functional monitoring, biochemical assays, and histological analysis. RESULTS: We discovered a clear downregulation of glucose transporter 4 (GLUT4) protein content expression in the CPB I/R model. In particular, cardiac-specific PDHA1 interference resulted in exacerbated cardiac dysfunction, significantly increased myocardial infarction area, more pronounced myocardial edema, and markedly increased cardiomyocyte apoptosis. Notably, the opposite effect was observed with PDHA1 overexpression, leading to a mitigated cardiac dysfunction and decreased incidence of myocardial infarction post-global ischemia. Mechanistically, PDHA1 plays a crucial role in regulating the protein content expression of GLUT4 on cardiomyocytes, thereby controlling the uptake and utilization of myocardial glucose, influencing the development of myocardial insulin resistance, and ultimately modulating MIRI. CONCLUSION: Overall, our study sheds new light on the pivotal role of PDHA1 in glucose metabolism and the development of myocardial insulin resistance. Our findings hold promising therapeutic potential for addressing the deleterious effects of MIRI in patients.

Integrated Proteomics and Metabolomics Analysis to Explore the Amelioration Mechanisms of Rosa roxburghii Tratt Fruit Polyphenols on Lipopolysaccharide-Induced Acute Lung Injury Mice.

Acute lung injury (ALI) is the main cause of death for the elderly and children due to its high morbidity and mortality rates. Plant-derived functional foods are becoming increasingly important to the healthcare and food industries for adjunctive and alternative treatments of ALI. Polyphenols have been regarded to be beneficial to the prevention and amelioration of ALI. Rosa roxburghii Tratt fruit polyphenols (RRTP) has potential to prevent ALI, but mechanism remains unclear. This study was set up to systematically analyze the RRTP extract active ingredients, comprehensively evaluate its protective effects via lung histopathological examination, protein concentration, and cytokines production in ALI mice induced by lipopolysaccharide (LPS), and finally revealed alleviation mechanisms of the regulatory effects of RRTP by proteomics and metabolomics approach. The results demonstrated RRTP could synergistically exert significant preventive effects against ALI by notably ameliorating lung histopathological damage and pulmonary capillary permeability in ALI mice, inhibiting lung tissue inflammatory response and acute phase proteins and S-100 calcium binding proteins, suppressing excessive activation of complement and coagulation cascades, and regulating disordered lipids metabolism and amino acid metabolism. This study illustrated that RRTP has obvious advantages in ALI adjunctive therapy and revealed the complicated amelioration mechanisms, which provides a breakthrough for the development and demonstration of RRTP as a nutritional compound additive for complementary therapy of ALI.

Risk factors for postoperative surgical site infections after anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

OBJECTIVES: The primary aim was to evaluate risk factors for surgical site infections after anterior cruciate ligament reconstruction (ACLR). The secondary aim was to investigate the surgical site infection incidence rate and the mean time to postoperative surgical site infection symptoms. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase and Web of Science were searched from database inception to September 2021 and updated in April 2022. ELIGIBILITY CRITERIA: Quantitative, original studies reporting potential risk factors for surgical site infections after ACLR were included. RESULTS: Twenty-three studies with 3871 infection events from 469 441 ACLRs met the inclusion criteria. Male sex (OR 1.78, p< 0.00001), obesity (OR 1.82, p=0.0005), tobacco use (OR 1.37, p=0.01), diabetes mellitus (OR 3.40, p=0.002), steroid use history (OR 4.80, p<0.00001), previous knee surgery history (OR 3.63, p=0.02), professional athlete (OR 4.56, p=0.02), revision surgery (OR 2.05, p=0.04), hamstring autografts (OR 2.83, p<0.00001), concomitant lateral extra-articular tenodesis (OR 3.92, p=0.0001) and a long operating time (weighted mean difference 8.12, p=0.005) were identified as factors that increased the risk of surgical site infections (superficial and deep) after ACLR. Age, outpatient or inpatient surgery, bone-patellar tendon-bone autografts or allografts and a concomitant meniscus suture did not increase the risk of surgical site infections. The incidence of surgical site infections after ACLR was approximately 1% (95% CI 0.7% to 1.2%). The mean time from surgery to the onset of surgical site infection symptoms was approximately 17.1 days (95% CI 13.2 to 21.0 days). CONCLUSION: Male sex, obesity, tobacco use, diabetes mellitus, steroid use history, previous knee surgery history, professional athletes, revision surgery, hamstring autografts, concomitant lateral extra-articular tenodesis and a long operation time may increase the risk of surgical site infections after ACLR. Although the risk of surgical site infections after ACLR is low, raising awareness and implementing effective preventions for risk factors are priorities for clinicians to reduce the incidence of surgical site infections due to its seriousness.

Insulin reduces pyroptosis-induced inflammation by PDHA1 dephosphorylation-mediated NLRP3 activation during myocardial ischemia-reperfusion injury.

BACKGROUND: Previous studies proved that pyrin domain-containing protein 3 (NLRP3)-induced pyroptosis plays an important role in Myocardial ischemia-reperfusion injury (MIRI). Insulin can inhibit the activation of NLRP3 inflammasome, although the exact mechanism remains unclear. The aim of this study was to determine whether insulin reduces NLRP3-induced pyroptosis by regulating pyruvate dehydrogenase E1alpha subunit (PDHA1) dephosphorylation during MIRI. METHODS: Rat hearts were subject to 30 min global ischemia followed by 60 min reperfusion, with or without 0.5 IU/L insulin. Myocardial ischemia-reperfusion injury was evaluated by measuring myocardial enzymes release, Cardiac hemodynamics, pathological changes, infarct size, and apoptosis rate. Cardiac aerobic glycolysis was evaluated by measuring ATP, lactic acid content, and pyruvate dehydrogenase complex (PDHc) activity in myocardial tissue. Recombinant adenoviral vectors for PDHA1 knockdown were constructed. Pyroptosis-related proteins were measured by Western blotting analysis, immunohistochemistry staining, and ELISA assay, respectively. RESULTS: It was found that insulin significantly reduced the area of myocardial infarction, apoptosis rate, and improved cardiac hemodynamics, pathological changes, energy metabolism. Insulin inhibits pyroptosis-induced inflammation during MIRI. Subsequently, Adeno-associated virus was used to knock down cardiac PDHA1 expression. Knockdown PDHA1 not only promoted the expression of NLRP3 but also blocked the inhibitory effect of insulin on NLRP3-mediated pyroptosis in MIRI. CONCLUSIONS: Results suggest that insulin protects against MIRI by regulating PDHA1 dephosphorylation, its mechanism is not only to improve myocardial energy metabolism but also to reduce the NLRP3-induced pyroptosis.

Risk Factors for Revision or Rerupture After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis.

BACKGROUND: The rerupture or need for revision after anterior cruciate ligament reconstruction (ACLR) is a serious complication. Preventive strategies that target the early identification of risk factors are important to reduce the incidence of additional surgery. PURPOSE: To perform a systematic review and meta-analysis to investigate risk factors for revision or rerupture after ACLR. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: Literature searches were performed in PubMed, Embase, and Web of Science from database inception to November 2021 and updated in January 2022. Quantitative, original studies reporting potential adjusted risk factors were included. Odds ratios (ORs) were calculated for potential risk factors. RESULTS: A total of 71 studies across 13 countries with a total sample size of 629,120 met the inclusion criteria. Fifteen factors were associated with an increase in the risk of revision or rerupture after ACLR: male sex (OR, 1.27; 95% CI, 1.14-1.41), younger age (OR, 1.07; 95% CI, 1.05-1.08), lower body mass index (BMI) (OR, 1.03; 95% CI, 1.00-1.06), family history (OR, 2.47; 95% CI, 1.50-4.08), White race (OR, 1.32; 95% CI, 1.08-1.60), higher posterolateral tibial slope (OR, 1.15; 95% CI, 1.05-1.26), preoperative high-grade anterior knee laxity (OR, 2.30; 95% CI, 1.46-3.64), higher baseline Marx activity level (OR, 1.07; 95% CI, 1.02-1.13), return to a high activity level/sport (OR, 2.03; 95% CI, 1.15-3.57), an ACLR within less than a year after injury (OR, 2.05; 95% CI, 1.81-2.32), a concomitant medial collateral ligament (MCL) injury (OR, 1.62; 95% CI, 1.31-2.00), an anteromedial portal or transportal technique (OR, 1.36; 95% CI, 1.22-1.51), hamstring tendon (HT) autografts (vs bone-patellar tendon-bone [BPTB] autografts) (OR, 1.60; 95% CI, 1.40-1.82), allografts (OR, 2.63; 95% CI, 1.65-4.19), and smaller graft diameter (OR, 1.21; 95% CI, 1.05-1.38). The other factors failed to show an association with an increased risk of revision or rerupture after ACLR. CONCLUSION: Male sex, younger age, lower BMI, family history, White race, higher posterolateral tibial slope, preoperative high-grade anterior knee laxity, higher baseline Marx activity level, return to a high activity level/sport, an ACLR within less than a year from injury, a concomitant MCL injury, an anteromedial portal or transportal technique, HT autografts (vs BPTB autografts), allografts, and smaller graft diameter may increase the risk of revision or rerupture after ACLR. Raising awareness and implementing effective preventions/interventions for risk factors are priorities for clinical practitioners to reduce the incidence of revision or rerupture after ACLR.

Analysis of protective effects of Rosa Roxburghii Tratt fruit polyphenols on lipopolysaccharide-induced acute lung injury through network pharmacology and metabolomics.

Acute lung injury (ALI) is a respiratory disease with high morbidity and mortality rates and is the primary cause of death in children and the elderly around the world. The use of Chinese foods in the complementary and alternative treatment of ALI has attracted more and more attention. This study aimed to explore the anti-ALI activity of Chinese functional foods Rosa roxburghii Tratt fruit polyphenols (RRTP). RRTP was administered to lipopolysaccharide-induced ALI mice, and its protective effects were comprehensively evaluated by lung histopathological examination, wet/dry (W/D) ratio, and cytokine production. Metabolomics analysis was used to identify the differential metabolites and metabolic pathways in plasma, and molecular docking and systemic biology-based network pharmacology assay were performed to explore the active components and potential therapeutic targets. The results indicated that RRTP significantly attenuated the severity of pathological changes and pulmonary capillary permeability. Furthermore, RRTP limited the increase in tumor necrosis factor alpha (TNF-α), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6) levels and the decrease in interleukin 10 (IL-10) levels in ALI mice. Metabolomics studies revealed that RRTP markedly affected 19 different metabolites, three amino acid metabolism pathways, and sphingolipid metabolism. Moreover, network pharmacology identified AKT1 (AKT serine/threonine kinase 1), TP53, IL-6, VEGFA (vascular endothelial growth factor A), and TNF (tumor necrosis factor) as the most promising target proteins, while quercetin, luteolin, and kaempferol were the core active components of RRTP. This study investigated the complex mechanisms of RRTP against ALI for the first time, and provided a foundation for the application of RRTP as a functional food, facilitating the research of nutritional food additives for the adjuvant treatment of ALI.