Alginate-based injectable probiotic/squid ink composite hydrogels for accelerated wound healing of MRSA infected abscess through photothermally synergized probiotic therapy.

Methicillin-resistant Staphylococcus aureus (MRSA) infections pose great challenges to skin wound care due to the severe drug resistance developed in the clinic. There is an urgent need to exploit next-generation bactericidal therapeutics that are both antibiotic-free and multifunctional for enhanced wound healing. Herein, we designed a Ca2+-crosslinked alginate hydrogel (EcNSIN@Alg) containing two naturally derived bioactive components, probiotics Escherichia coli Nissle1917 (EcN) and Squid ink nanoparticles (SIN), to treat MRSA-infected wounds. The injectable composite hydrogel displayed excellent biocompatibility, photothermal antibacterial activity, and reactive oxygen species (ROS) scavenging property. Importantly, the probiotic EcN can enhance the photothermal SIN to promote immune regulatory activities, shifting pro-inflammatory macrophages (M1) to anti-inflammatory macrophages (M2). In an MRSA-infected abscess model, EcNSIN@Alg can reduce the expression level of wound inflammatory factors and ROS, increase the number of anti-inflammatory macrophages, accelerate collagen deposition and promote wound healing. This work offers a new perspective on developing safe, antibiotic-free, multifunctional bactericides using fully bioderived materials, with potential applications in clinical practice.

A novel prognosis evaluation indicator of patients with sepsis created by integrating six microfluidic-based neutrophil chemotactic migration parameters.

Impaired neutrophil migration in sepsis is associated with a poor prognosis. The potential of utilizing neutrophil chemotaxis to assess immune function, disease severity, and patient prognosis in sepsis remains underexplored. This study employed an innovative approach by integrating a multi-tip pipette with a Six-Unit microfluidic chip (SU6-chip) to establish gradients in six microchannels, thereby analyzing neutrophil chemotaxis in sepsis patients. We compared chemotactic parameters between healthy controls (NH = 20) and sepsis patients (NS1 = 25), observing significant differences in gradient perception time (GP), migration distance (MD), peak velocity (Vmax), chemotactic index (CI), reverse migration rate (RM), and stop migration number (SM). A novel composite indicator, the Sepsis Neutrophil Migration Evaluation (SNME) index, was developed by integrating these six chemotactic migration parameters. The SNME index and individual chemotaxis parameters showed significant correlations with the Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE II) score, hypersensitivity C-reactive protein (hs-CRP), and heparin-binding protein (HBP). Moreover, the SNME index demonstrated potential for monitoring sepsis progression, with ROC analysis confirming its predictive accuracy (area under the curve [AUC] = 0.895, cutoff value = 31.5, specificity = 86.73 %, sensitivity = 86.71 %), outperforming individual neutrophil chemotactic parameters. In conclusion, the SNME index represents a promising new tool for adjunctive diagnosis and prognosis assessment in patients with sepsis.

Continuous Disentangled Joint Space Learning for Domain Generalization.

Domain generalization (DG) aims to learn a model on one or multiple observed source domains that can generalize to unseen target test domains. Previous approaches have focused on extracting domain-invariant information from multiple source domains, but domain-specific information is also closely tied to semantics in individual domains and is not well-suited for generalization to the target domain. In this article, we propose a novel DG method called continuous disentangled joint space learning (CJSL), which leverages both domain-invariant and domain-specific information for more effective DG. The key idea behind CJSL is to formulate and learn a continuous joint space (CJS) for domain-specific representations from source domains through iterative feature disentanglement. This learned CJS can then be used to simulate domain-specific representations for test samples from a mixture of multiple domains via Monte Carlo sampling during the inference stage. Unlike existing approaches, which exploit domain-invariant feature vectors only or aim to learn a universal domain-specific feature extractor, we simulate domain-specific representations via sampling the latent vectors in the learned CJS for the test sample to fully use the power of multiple domain-specific classifiers for robust prediction. Empirical results demonstrate that CJSL outperforms 19 state-of-the-art (SOTA) methods on seven benchmarks, indicating the effectiveness of our proposed method.

Nano silver oxide-modified activated carbon as a novel catalyst for efficient removal of bacteria and micropollutants in aquatic environment.

Heterogeneous Fenton process is a promising water treatment technology for sterilization and degradation of organic pollutants, due to the strong oxidation of hydroxyl radicals (OH˙) generated. However, the low H2O2 activation efficiency and the instability of catalyst leading to low OH˙ production restricted development of this technology. Herein, we synthesized a novel porous activated carbon-loaded nano silver oxide (nAg2O/AC) catalyst to enhance the activation of H2O2 for removing bacteria (E. coli) and micropollutants (Tetracycline, TC) from water. In the nAg2O/AC Fenton system, reductive hydroxyl groups on AC accelerated Ag(i)/Ag cycle through mediated electron transfer, which markedly increased H2O2 activation efficiency to 73.7% (About 2.9 times that of traditional Fenton). Hence, nAg2O/AC Fenton achieved up to 6.0 log and 100% removal efficiency for E. coli and TC, respectively. The OH˙ as the major oxidizing species in nAg2O/AC Fenton system was detected and verified by radical scavenging tests and electron spin resonance (ESR) measurement. After 4 and 5 cycles of experiments, the removal of E. coli and TC still reached 5.2 log and 96%, respectively, confirming good stability of nAg2O/AC for considerable application prospects. This study concluded that nAg2O/AC is a promising H2O2 catalyst for simultaneous removal of bacteria and micropollutants in aqueous environment.

Effects of mindfulness-based music listening on conflict control in young adults with insomnia disorder: behavioral and event-related potential evidence.

Introduction: Insomnia Disorder (ID) has become the second most prevalent mental disorder, with significant negative effects on daytime cognitive functions. Previous studies suggested that mindfulness-based music listening (MBML) can effectively improve conflict control and attentional processing in healthy adults. However, the behavioral and neurophysiological characteristics of MBML in young adults with ID remain unclear. Methods: To explore the behavioral and neurophysiological characteristics of MBML in regulating negative emotions among young Chinese adults with ID, 60 young adults with ID were asked to complete an emotion-word Stroop task under three mood states while recording event-related potentials (ERPs). Results: Task and questionnaire results showed that (1) negative emotion induced by the negative simulated video significantly suppressed the attentional processing of emotional faces and words in the conflict control task among young people with ID, (2) MBML reduced cognitive and physical arousal levels, enhanced positive mood, and improved attentional control abilities in young adults with ID. The ERP results showed that a greater N3 effect and the smaller P3 and late positive component (LPC) effects reflected that MBML effectively regulated negative emotions induced by the negative simulated video and attentional processing abilities for conflict control in young adults with ID. Discussion: Maintaining mindfulness while listening to music may enhance positive emotional experiences and improve cognitive ability, and exhibit larger N3 effects and smaller P3 and LPC effects in the electrophysiology mechanism, with a reduction in the hyperarousal level in young adults with insomnia disorders.

An integrated machine learning model enhances delayed graft function prediction in pediatric renal transplantation from deceased donors.

BACKGROUND: Kidney transplantation is the optimal renal replacement therapy for children with end-stage renal disease; however, delayed graft function (DGF), a common post-operative complication, may negatively impact the long-term outcomes of both the graft and the pediatric recipient. However, there is limited research on DGF in pediatric kidney transplant recipients. This study aims to develop a predictive model for the risk of DGF occurrence after pediatric kidney transplantation by integrating donor and recipient characteristics and utilizing machine learning algorithms, ultimately providing guidance for clinical decision-making. METHODS: This single-center retrospective cohort study includes all recipients under 18 years of age who underwent single-donor kidney transplantation at our hospital between 2016 and 2023, along with their corresponding donors. Demographic, clinical, and laboratory examination data were collected from both donors and recipients. Univariate logistic regression models and differential analysis were employed to identify features associated with DGF. Subsequently, a risk score for predicting DGF occurrence (DGF-RS) was constructed based on machine learning combinations. Model performance was evaluated using the receiver operating characteristic curves, decision curve analysis (DCA), and other methods. RESULTS: The study included a total of 140 pediatric kidney transplant recipients, among whom 37 (26.4%) developed DGF. Univariate analysis revealed that high-density lipoprotein cholesterol (HDLC), donor after circulatory death (DCD), warm ischemia time (WIT), cold ischemia time (CIT), gender match, and donor creatinine were significantly associated with DGF (P < 0.05). Based on these six features, the random forest model (mtry = 5, 75%p) exhibited the best predictive performance among 97 machine learning models, with the area under the curve values reaching 0.983, 1, and 0.905 for the entire cohort, training set, and validation set, respectively. This model significantly outperformed single indicators. The DCA curve confirmed the clinical utility of this model. CONCLUSIONS: In this study, we developed a machine learning-based predictive model for DGF following pediatric kidney transplantation, termed DGF-RS, which integrates both donor and recipient characteristics. The model demonstrated excellent predictive accuracy and provides essential guidance for clinical decision-making. These findings contribute to our understanding of the pathogenesis of DGF.

Effect of isomeric polysaccharides on heteroaggregation of nanoplastics in high ionic strength conditions: Synergies of morphology and molecular conformation.

Polysaccharides with various molecular structures and morphology may influence the aggregation kinetics of nanoplastics. This study used various characterization methods to elucidate the heteroaggregation mechanism of polystyrene nanoplastics (PSNPs) in the presence of polysaccharides (ionic strength (IS) 1-800 mM NaCl and 0.01-60 mM CaCl2). The results showed that under high IS, cellulose (CL) accelerated the heteroaggregation of PSNPs, and the aggregation rate of PSNPs increased by approximately 62.05 %, while amylose (AM) had little effect (10.38 %). Compared with AM (43.2 nm), the morphology of the CL (78.4 nm) gully had improved surface roughness, leading to its decisive role in the heteroaggregation of PSNPs. Quantum chemistry calculations indicated that van der Waals forces of PSNPs-CL systems (-217.28 kJ mol-1) were stronger than those of PSNPs-AM systems (-184.62 kJ mol-1) based on the subtle molecular conformation differences between CL and AM (opposite and same sides of OH groups in CL and AM, respectively). The morphology and molecular conformation of polysaccharides collaboratively controlled the heteroaggregation of PSNPs. Because the morphology of polysaccharides was based on their molecular conformation, the latter is the most critical factor. These findings provide new insights into the effects of PSNPs stability in the environment.

Uncovering the spatial characteristics of global net anthropogenic nitrogen input at high resolution and across 1.42 million lake basins.

Global Net Anthropogenic Nitrogen Input (NANI) at high resolution is crucial for assessing the impact of human activities on aquatic environments. Insufficient global high-resolution data sources and methods have hindered the effective examination of the global characteristics and driving forces of NANI. This study presents a general framework for calculating global NANI, providing estimates at a 5-arc-minute resolution and over 1.42 million lake basins in 2015. The results highlight the region near the Tropic of Cancer as a concentration area for high NANI and an inflection point for latitude-based accumulation variation. It also emphasizes the uneven distribution of NANI among continents, with Asia and Africa having the highest proportions, yet their high and low values are notably lower than those of Europe and South America. A similar pattern is observed in global lakes, where Asia has the smallest quantity and volume, but the highest NANI intensity. In contrast, North America and Europe have larger quantities and volumes but the lowest NANI intensity. The global distribution characteristics reveal a clustering pattern in high and low values, with 1.25 % of the area having a sum of NANI exceeding 20 %. The uncertainty analysis regarding model parameters indicates that continents with the highest NANI do not always exhibit the highest uncertainty. These results bridge the gap between global nitrogen sustainable management and anthropogenic nitrogen input. They support research on spatiotemporal changes and controlling factors of global river nutrient loads, as well as the impact of climatic factors on basin nitrogen loss and its variability.

Cellular and molecular biology of posttranslational modifications in cardiovascular disease.

Cardiovascular disease (CVD) has now become the leading cause of death worldwide, and its high morbidity and mortality rates pose a great threat to society. Although numerous studies have reported the pathophysiology of CVD, the exact pathogenesis of all types of CVD is not fully understood. Therefore, much more research is still needed to explore the pathogenesis of CVD. With the development of proteomics, many studies have successfully identified the role of posttranslational modifications in the pathogenesis of CVD, including key processes such as apoptosis, cell metabolism, and oxidative stress. In this review, we summarize the progress in the understanding of posttranslational modifications in cardiovascular diseases, including novel protein posttranslational modifications such as succinylation and nitrosylation. Furthermore, we summarize the currently identified histone deacetylase (HDAC) inhibitors used to treat CVD, providing new perspectives on CVD treatment modalities. We critically analyze the roles of posttranslational modifications in the pathogenesis of CVD-related diseases and explore future research directions related to posttranslational modifications in cardiovascular diseases.

Superconductivity in Diamond-Like BC15.

Advancing the compositional space of a compound class can result in intriguing superconductors, such as LaH10. Herein, we performed a comprehensive first-principles structural search on a binary B-C system with various chemical compositions. The identified diamond-like BC15, named d-BC15, is thermodynamically superior to the synthesized BC3 and BC5. Interestingly, d-BC15 shows anisotropic superconductivity resulting from three distinct Fermi surfaces. Its predicted critical temperature (Tc) is 43.6 K at ambient pressure, beyond the McMillan limit. d-BC15 reaches a maximum of around 75 K at 0.43% hole doping due to the substantially enhanced density of states at the Fermi level. Additionally, d-BC15 demonstrates superhard characteristics with a Vickers hardness of 75 GPa. The calculated tensile and shear stresses are 72 and 73 GPa, respectively. The combination of high superconductivity and superhardness in d-BC15 offers new insights into the design of multifunctional materials.

Motor impulsivity and spicy food craving: A mediation analysis of insula-based resting state functional connectivity.

In China, the rate of spicy food consumption is rising, and chili pepper is among the most popular spicy foods consumed nationwide. However, little effort has been made to understand the mechanism behind spicy food craving. This exploratory study aimed to investigate differences in insula-based resting state functional connectivity (rsFC) between spicy food cravers and non-cravers, and the association between rsFC, impulsivity and spicy food craving. A group of extreme cravers (n = 49) and a group of age- and sex-matched non-cravers (n = 46) completed a resting-state fMRI scan, during which participants were instructed to keep their eyes closed, to not think of anything in particular, and to remain awake. Participants completed the Spicy Food Craving Questionnaire, Barratt Impulsiveness Scale, Sensation Seeking Scale and Positive and Negative Affect Schedule, and rated the frequency of spicy food intake. Results revealed increased insula-occipital lobe resting-state functional connectivity in individuals with spicy food cravings, and the positive correlations between insula-middle occipital gyrus rsFC, impulsivity and spicy food craving. Specifically, the insula-middle occipital gyrus rsFC strength mediated the relationship between the motor impulsivity and spicy food craving. It is hoped that our exploratory findings may shed new insights into the neural mechanisms of spicy food craving and motivate further exploration of spicy food craving in diverse contexts and cultures.

Multicentre evaluation of in vitro activity of contezolid against drug-resistant Staphylococcus and Enterococcus.

BACKGROUND: To investigate susceptibility to contezolid, a novel oxazolidinone, multicentre surveillance was conducted involving 2449 strains of Staphylococcus and Enterococcus collected from 65 hospitals across China. METHODS: The MICs of contezolid, linezolid and other clinically significant antibiotics were determined by the broth microdilution method. Consistency with the broth microdilution method for contezolid was assessed using agar dilution method, as well as disc diffusion and ETEST for linezolid, respectively. WGS was conducted on all 20 linezolid-resistant and 30 randomly non-resistant strains to analyse linezolid resistance genes (optrA, poxtA, cfr) and 23S rRNA mutation sites. RESULTS: All strains exhibited WT susceptibility to contezolid, while resistance proportions to daptomycin, vancomycin, teicoplanin, tigecycline and eravacycline ranged from 0% to 5.2% in Staphylococcus, and from 0% to 7.8% in Enterococcus. Linezolid resistance was higher in Enterococcus faecalis (4.4%) compared with Enterococcus faecium (0.2%). Contezolid showed a lower MIC50 (0.5 mg/L) than linezolid (2 mg/L) for methicillin-resistant Staphylococcus. Against Enterococcus, contezolid demonstrated a cumulative MIC percentage of 70% for VRE and 39.1% for E. faecalis (at MIC = 1 mg/L), whereas linezolid showed 0% and 1.1%, respectively. Among the 20 linezolid-resistant Enterococcus strains, all carried the optrA gene without 23S rRNA mutations. For contezolid, MICs were 4 mg/L for 19 strains and 2 mg/L for 1 strain. The ETEST, agar dilution and disc diffusion methods showed essential and categorical agreements of >90% for linezolid, with no major errors or very major errors. CONCLUSIONS: Contezolid demonstrated significant in vitro antibacterial activity against methicillin-resistant Staphylococcus, VRE and linezolid-resistant E. faecalis.

High-Performance Bimetallic Electrocatalysts for Hydrogen Evolution Reaction Using N-Doped Graphene-Supported N-Co6Mo6C.

Hydrogen has garnered considerable attention as a promising energy source for addressing contemporary environmental degradation and energy scarcity challenges. Electrocatalytic water splitting for hydrogen production has emerged as an environmentally friendly and versatile method, offering high purity. However, the development of cost-effective electrocatalytic catalysts using abundant and inexpensive materials is crucial. In this study, we successfully synthesized nitrogen-doped Co6Mo6C supported on nitrogen-doped graphene (N-Co6Mo6C/NC). The catalyst exhibited high performance and durability in alkaline electrolytes (1.0 M KOH) for hydrogen evolution, showcasing an overpotential of 185 mV at a current density of 100 mA cm-2 and a Tafel slope of 80 mV dec-1. These findings present a novel avenue for the fabrication of efficient bimetallic carbide catalysts.

Clinical application of the free superficial palmar branch of radial artery flap for soft-tissue reconstruction of distal digital injury.

PURPOSE: The purpose of this study is to retrospect and summarize clinical efficiency and experience of the free superficial palmar branch of radial artery (SPBRA) flap for soft-tissue reconstruction in distal digital injury. METHOD: 13 patients with soft-tissue defect of finger, reconstructed by the free superficial palmar branch of radial artery (SPBRA) flap in our department from January 2020 to January 2022, were reviewed. After 6-12 months of follow-up, evaluated the treatment effect of the fingers reconstructed by SPBRA flap. RESULTS: All the flaps in our series application were survival uneventful, and all the donor sites were closed primarily without complications or obvious scarring. The flaps were soft in texture and satisfactory in appearance and function. The flaps with the median nerve palmar cutaneous branch had a good sensation recovery. Measurement of two-point discrimination (TPD) ranged from 6 to 10 mm. All patients were satisfied with the aesthetic appearance. According to the Evaluation Trial Standards of Upper Limb Partial Function of Hand Surgery of Chinese Medical Association, the results were graded as excellent in 11 cases and good in 2 cases. CONCLUSION: The SPBRA perforator flap has the advantages of simple operation, soft texture, good appearance and function, and is credible and useful for reconstructing various finger injuries.

Synergistic Enhancement of Biaxial Stretching and Multilayer Composites in All-Solid-State Polymer Electrolytes.

As an important component of lithium-ion batteries, all-solid-state electrolytes should possess high ionic conductivity, excellent flexibility, and relatively high mechanical strength. All-solid-state polymer electrolytes (ASSPEs) based on polymers seem to be able to meet these requirements. However, pure ASSPEs have relatively low ionic conductivity, and the addition of inorganic fillers such as lithium salts will reduce their flexibility and mechanical strength. To address the above issues, in this paper, the solvent-free method was used to prepare a poly(vinylidenefluoride-co-hexafluoropropylene)/lithium bis(trifluoromethanesulfonyl) imide/poly(ethylene oxide) all-solid-state polymer electrolyte, which was then subjected to 4 × 4 magnification synchronous bidirectional stretching. Subsequently, it was multilayered with PEO-based composite polymer electrolytes to obtain multilayered composite polymer electrolytes (MCPEs). Bidirectional stretching provides superior in-plane and out-of-plane mechanical properties to MCPEs by inducing molecular chain orientation, which suppresses the growth of lithium dendrites. Concurrently, it facilitates the formation of the ß-crystal form of PVDF-HFP, thereby weakening the ion solvation effect and reducing the lithium-ion migration energy barrier. Multilayered compounding improves the interfacial contact between MCPEs and electrodes, thereby reducing the interfacial impedance. Experiments have demonstrated that the MCPEs prepared in this paper exhibit high ionic conductivity at room temperature (1.83 × 10-4 S cm-1), low interfacial resistance (547 Ω cm-2), excellent mechanical properties (26 MPa), and excellent cycling rate performance (a capacity retention rate of 90% after 110 cycles at 0.1 C), which can meet the performance requirements of lithium-ion batteries for ASSPEs.

Loss of Nrf2 aggravates ionizing radiation-induced intestinal injury by activating the cGAS/STING pathway via Pirin.

Ionizing radiation (IR)-induced intestinal injury remains a major limiting factor in abdominal radiation therapy, and its pathogenesis remains unclear. In this study, mouse models of IR-induced intestinal injury were established, and the effect of IR on nuclear factor erythroid 2-related factor 2 (Nrf2) was determined. More severe IR-induced intestinal damage was observed in Nrf2 knockout (KO) mice than in wild-type mice. Then, the negative regulation of cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) signaling by Nrf2 was examined both in vivo and in vitro after IR. This was accompanied by alterations in the intestinal neutrophil and macrophage populations in mice. Subsequently, the effect of the cGAS/STING pathway on the intestinal toxicity of IR was also investigated. Moreover, the downregulation of cGAS/STING by Nrf2 via its target gene, Pirin, was confirmed using transfection assays. A rescue experiment with Pirin was also conducted using adeno-associated virus in Nrf2 KO mice. Finally, the protective effect of calcitriol against IR-induced intestinal injury, along with increased Nrf2 and Pirin levels and decreased cGAS, pSTING, and interferon-beta levels, were observed. Taken together, our results suggest that Nrf2 alleviates IR-induced intestinal injury through Pirin-mediated inhibition of the innate immunity-related cGAS/STING pathway.

Healing mechanism of cotton bandages loaded with PNIPAM/GO-Ag hydrogel on deep second-degree burn wounds in a rat model.

Dressings play a crucial role in the management of burn wounds. In this study, cotton bandages were modified with poly (N-isopropylacrylamide)/graphite oxide/nano silver (PNIPAM/GO-Ag) hydrogel to obtain a novel dressing (PNIPAM/GO-Ag/COT). The healing effect of the PNIPAM/GO-Ag/COT dressing on deep second-degree burn wounds in rats and the changes of related inflammatory factors were explored and analyzed systematically. The deep second-degree burn model was established by the steam scald method in Sprague-Dawley (SD) rats. The granulation tissue, collagen deposition, the expression of tumor necrosis factor-α (TNF-α), and basic fibroblast growth factor (bFGF) in the wound were evaluated by means of HE staining, Masson staining, ELISA, and immunohistochemistry methods. The results showed that, compared with the blank group (rats without the dressing treatment), the PNIPAM/GO-Ag/COT dressing reduced the expression of TNF-α by approximately 18 % and promoted the bFGF expression in wound tissue. Compared to the control group (rats with the gauze treatment), the wound healing rate in the PNIPAM/GO-Ag/COT dressing group was 58 % on the 14th day, with an increase of 30 %. These results demonstrated that the PNIPAM/GO-Ag/COT dressing primarily promoted burn wound healing by reducing inflammatory reactions, promoting collagen deposition, and enhancing the expression of bFGF.

Monocyte/lymphocyte ratio as a risk factor of cardiovascular and all-cause mortality in coronary artery disease with low-density lipoprotein cholesterol levels below 1.4 mmol/L: A large longitudinal multicenter study.

BACKGROUND AND AIMS: The monocyte/lymphocyte ratio (MLR), an inflammatory marker, has an unclear relationship with the risk of residual inflammation in patients with coronary artery disease (CAD) and low-density lipoprotein cholesterol (LDL-C) below 1.4 mmol/L. This study aimed to assess the association between the MLR and cardiovascular and all-cause mortalities in these patients. METHODS: A total of 2747 patients diagnosed with CAD via coronary angiography (CAG) and presenting with LDL-C levels < 1.4 mmol/L were enrolled in this observational study conducted from January 2007 to December 2020. Patients were categorized into four groups based on the MLR quartiles. We used Kaplan-Meier analysis and Cox regression models to evaluate the relationship between baseline MLR and cardiovascular and all-cause mortalities. RESULTS: Among the 2747 participants followed up for a median duration of 6 years, there were 184 cardiovascular and 462 all-cause deaths. Elevated MLR levels were found to be associated with an increased risk of both cardiovascular and all-cause mortalities according to the Kaplan-Meier analysis. Multivariate Cox regression analysis demonstrated a significant association between higher MLR and an elevated risk of cardiovascular and all-cause mortality. Compared to the older group, with an increase in MLR levels, the younger group showed a higher hazard ratio for cardiovascular death. Similar results were obtained in the single-vessel disease group. CONCLUSIONS: In patients with CAD and LDL-C levels < 1.4 mmol/L, MLR can serve as a risk factor for both cardiovascular and all-cause mortalities owing to the risk of residual inflammation.

Chondrocyte Ferritinophagy as a Molecular Mechanism of Arthritis-A Narrative Review.

Osteoarthritis (OA) is a prevalent joint disease affecting orthopedic patients. Its incidence is steadily increasing, causing great economic hardship for individuals and society as a whole. OA is connected with risk factors such as genetics, obesity, and joint diseases; yet, its pathophysiology is still largely understood. At present, several cell death pathways govern the initiation and advancement of OA. It has been discovered that the onset and progression of OA are strongly associated with pyroptosis, senescence, apoptosis, ferroptosis, and autophagy. Ferroptosis and autophagy have not been well studied in OA, and elucidating their molecular mechanisms in chondrocytes is important for the diagnosis of OA. For this reason, we aim was reviewed recent national and international developments and provided an initial understanding of the molecular pathways underlying autophagy and ferroptosis in OA. We determined the reference period to be the last five years by searching for the keywords "osteoarthritis, mechanical stress, Pizeo1, ferroptosis, autophagy, ferritin autophagy" in the three databases of PUBMED, Web of Science, Google Scholar. We then screened irrelevant literature by reading the abstracts. Ferroptosis is a type of programmed cell death that is dependent on reactive oxygen species and Fe2+. It is primarily caused by processes linked to amino acid metabolism, lipid peroxidation, and iron metabolism. Furthermore, Piezoelectric mechanically sensitive ion channel assembly 1 (PIEZO1), which is triggered by mechanical stress, has been revealed to be intimately associated with ferroptosis events. It was found that mechanical injury triggers changes in the intracellular environment of articular chondrocytes (e.g., elevated levels of oxidative stress and increased inflammation) through PIEZO1, ultimately leading to iron death in chondrocytes. Therefore, we believe that PIEZO1 is a key initiator protein of iron death in chondrocytes. Widely present in eukaryotic cells, autophagy is a lysosome-dependent, evolutionarily conserved catabolic process that carries misfolded proteins, damaged organelles, and other macromolecules to lysosomes for breakdown and recycling. Throughout OA, autophagy is activated to differing degrees, indicating that autophagy may play a role in the development of OA. According to recent research, autophagy is a major factor in the process that leads cells to ferroptosis. Despite the notion of ferritinophagy being put forth, not much research has been done to clarify the connection between ferroptosis and autophagy in OA.

Association of ACEI/ARB therapy with total and cardiovascular death in coronary artery disease patients with advanced chronic kidney disease: a large multi-center longitudinal study.

INTRODUCTION: Advanced chronic kidney disease (CKD) is common among patients with coronary artery disease (CAD), and angiotensin­converting enzyme inhibitors (ACEI) or angiotensin­receptor blockers (ARB) can improve cardiac and renal function, but whether ACEI/ARB therapy improves long-term prognosis remains unclear among these high-risk patients. Therefore, this research aimed to investigate the relationship between ACEI/ARB therapy and long-term prognosis among CAD patients with advanced CKD. METHODS: CAD patients with advanced CKD were included in five hospitals. Advanced CKD was defined as estimated glomerular filtration rate (eGFR)<30 ml/min per 1.73 m2. Cox regression models and competing risk Fine and Gray models were used to examine the relationship between ACEI/ARB therapy and all-cause and cardiovascular death, respectively. RESULTS: Of 2527 patients, 47.6% population of our cohort was discharged on ACEI/ARB. The overall all-cause and cardiovascular mortality were 38.6% and 24.7%, respectively. Multivariate Cox regression analyses indicated that ACEI/ARB therapy was found to be associated with lower rates of both all-cause mortality (hazard ratio (HR)=0.836, 95% confidence interval (CI): 0.738-0.948, p = 0.005) and cardiovascular mortality (HR = 0.817, 95%CI: 0.699-0.956, p = 0.011). In the propensity-matched cohort, the survival benefit was consistent, and significantly better survival was observed for all-cause mortality (HR = 0.856, 95%CI: 0.752-0.974, p = 0.019) and cardiovascular mortality (HR = 0.830, 95%CI: 0.707-0.974, p = 0.023) among patients treated with ACEI/ARB. CONCLUSION: ACEI/ARB therapy showed a better survival benefit among high-risk CAD patients with advanced CKD at long-term follow-up, which manifested that strategies to maintain ACEI/ARB treatment may improve clinical outcomes among these high-risk populations.

What is the current knowledge on the topic? Advanced CKD is highly prevalent and strongly associated with higher mortality risk and worse outcomes among CAD patients, and patients with advanced CKD have often been excluded from randomized controlled trials, creating an evidence gap for these high-risk CAD patients. ACEI/ARB are beneficial for greater survival among CAD patients, but the effect of ACEI/ARB therapy on long-term prognosis is unclear among CAD patients with advanced CKD.What does this study add to our knowledge? ACEI/ARB treatment showed a better survival benefit among high-risk CAD patients with advanced CKD at long-term follow-up.How might this change clinical pharmacology or translational science? CAD patients with advanced CKD are not only have worse outcomes but also limited in their choice of therapy strategies. Our study may prompt an important reference for the subsequent improvement of long-term prognosis among these high-risk populations.