Aging-induced Alternation in the Gut Microbiota Impairs Host Antibacterial Defense.

Older individuals experience increased susceptibility and mortality to bacterial infections, but the underlying etiology remains unclear. Herein, it is shown that aging-associated reduction of commensal Parabacteroides goldsteinii (P. goldsteinii) in both aged mice and humans critically contributes to worse outcomes of bacterial infection.

Activating Sig-1R inhibits microvascular permeability by reducing LRRK2 expression in lipopolysaccharide-induced acute lung injury.

Background: Endothelial cells are the first and most damaged target cells during acute lung injury (ALI). Endothelial dysfunction increases pulmonary microvascular permeability, subsequently leading to pulmonary oedema and organ dysfunction; however, clinical treatments against microvascular permeability show poor efficacy. Herein, we aimed to explore the role of the Sigma-1 receptor (Sig-1R) in pulmonary microvascular permeability by constructing ALI animal and cell models, and further investigated the specific mechanisms.

The cardio-protective effect of cardiomyopeptidin in critically ill patients with myocardial injury: a retrospective cohort study.

In order to investigate the association between the use of cardiomyopeptidin (CMP) and outcomes in critically ill patients with myocardial injury, we conducted a retrospective cohort study in Nanfang hospital, Southern Medical University. Clinical data of patients with myocardial injury were collected retrospectively and adjusted for possible confounders by propensity score weighting. The main outcome was the in-hospital mortality.

A prediction model for nonresponsive outcomes in critically ill patients with acute respiratory distress syndrome undergoing prone position ventilation: A retrospective cohort study.

Objective: This study aimed to develop a reliable and effective nomogram model to identify high-risk populations with non-response to prone position ventilation (PPV) in acute respiratory distress syndrome (ARDS) patients.

Methods: This retrospective cohort study included 175 patients with ARDS undergoing PPV. An improvement of ≥ 20 mmHg in the PaO/FiO after the first PPV was defined as a 'response'.

Effects of tibolone combined with zoledronic acid on bone density, bone metabolism, and pain in postmenopausal patients with osteoporosis.

Objective: To explore the efficacy and safety of tibolone combined with zoledronic acid in the treatment of postmenopausal osteoporosis (PMO).

Methods: We conducted a retrospective analysis of 121 PMO patients from March 2019 to July 2021. Patients were divided into two groups based on treatment regimen: an observation group (n=62) receiving zoledronic acid combined with tibolone and a control group (n=59) receiving tibolone monotherapy.

TREM-1 inhibition or ondansetron administration ameliorates NLRP3 inflammasome and pyroptosis in traumatic brain injury-induced acute lung injury.

Introduction: Recently, NLR family pyrin domain containing 3 (NLRP3) and pyroptosis have been reported to be involved in traumatic brain injury-induced acute lung injury (TBI-ALI). Studies have shown that triggering receptor expressed on myeloid cells-1 (TREM-1) may be one of the upstream molecules regulating NLRP3/pyroptosis, and 5-hydroxytryptamine type 3-receptor (5-HT3R) antagonists can inhibit NLRP3/pyroptosis. However, the role of TRME-1 in TBI-ALI, the therapeutic effect of 5-HT3R inhibition on TBI-ALI and its mechanism are still unclear.

Gut commensal metabolite rhamnose promotes macrophages phagocytosis by activating SLC12A4 and protects against sepsis in mice.

Sepsis progression is significantly associated with the disruption of gut eubiosis. However, the modulatory mechanisms of gut microbiota operating during sepsis are still unclear. Herein, we investigated how gut commensals impact sepsis development in a pre-clinical model.

SIRTUIN 5 ALLEVIATES EXCESSIVE MITOCHONDRIAL FISSION VIA DESUCCINYLATION OF ATPASE INHIBITORY FACTOR 1 IN SEPSIS-INDUCED ACUTE KIDNEY INJURY.

Sepsis-induced acute kidney injury (SAKI) poses a significant clinical challenge with high morbidity and mortality. Excessive mitochondrial fission has been identified as the central pathogenesis of sepsis-associated organ damage, which is also implicated in the early stages of SAKI. Sirtuin 5 (SIRT5) has emerged as a central regulator of cellular mitochondrial function; however, its role in the regulation of sepsis-induced excessive mitochondrial fission in kidney and the underlying mechanism remains unclear.

Sandwich-type electrochemical immunosensing of CA125 by using nanoribbon-like TiCT MXenes and toluidine blue/UIO-66-NH.

CA125 (carbohydrate antigen 125) is an important biomarker of ovarian cancer, so developing effective method for its detection is of great significance. In the present work, a novel sandwich-like electrochemical immunosensor (STEM) of CA125 was constructed by preparing nanoribbon-like TiCT MXenes (TiCTNR) to immobilize primary antibody (PAb) of CA125 and UIO-66-NH MOFs structure to immobilize second antibody (SAb) and electroactive toluidine blue (Tb) probe. In this designed STEM assay, the as-prepared TiCTNR nanohybrid offers the advantages in large surface area and conductivity as carrier, and UIO-66-NH provided an ideal platform to accommodate SAb and a large number of Tb molecules as signal amplifier.

Effects of an Early Intensive Blood Pressure-lowering Strategy Using Remifentanil and Dexmedetomidine in Patients with Spontaneous Intracerebral Hemorrhage: A Multicenter, Prospective, Superiority, Randomized Controlled Trial.

Background: Although it has been established that elevated blood pressure and its variability worsen outcomes in spontaneous intracerebral hemorrhage, antihypertensives use during the acute phase still lacks robust evidence. A blood pressure-lowering regimen using remifentanil and dexmedetomidine might be a reasonable therapeutic option given their analgesic and antisympathetic effects. The objective of this superiority trial was to validate the efficacy and safety of this blood pressure-lowering strategy that uses remifentanil and dexmedetomidine in patients with acute intracerebral hemorrhage.

Site-specific reactivity of stepped Pt surfaces driven by stress release.

Heterogeneous catalysts are widely used to promote chemical reactions. Although it is known that chemical reactions usually happen on catalyst surfaces, only specific surface sites have high catalytic activity. Thus, identifying active sites and maximizing their presence lies at the heart of catalysis research, in which the classic model is to categorize active sites in terms of distinct surface motifs, such as terraces and steps.

Short-Chain Acyl-CoA Dehydrogenase as a Therapeutic Target for Cardiac Fibrosis.

Cardiac fibrosis is considered as unbalanced extracellular matrix production and degradation, contributing to heart failure. Short-chain acyl-CoA dehydrogenase (SCAD) negatively regulates pathological cardiac hypertrophy. The purpose of this study was to investigate the possible role of SCAD in cardiac fibrosis.

Discovery of Novel Potent and Fast BTK PROTACs for the Treatment of Osteoclasts-Related Inflammatory Diseases.

Bruton's tyrosine kinase (BTK) is an attractive target in inflammatory and autoimmune diseases. However, the effectiveness of BTK inhibitors is limited by side effects and drug resistance. In this study, we report the development of novel BTK proteolysis targeting chimeras (PROTACs) with different classes of BTK-targeting ligands (e.

Origin of Stability and Activity Enhancements in Pt-based Oxygen Reduction Reaction Catalysts via Defect-Mediated Dopant Adsorption.

Platinum alloys are highly efficient electrocatalysts for the oxygen reduction reaction (ORR) in acidic conditions. However, these alloys are susceptible to metal loss through leaching and degradation, leading to reduced catalyst stability and activity. Recently, it has been shown that doping with oxophilic elements can significantly alleviate these problems, with a prominent example being Mo-doped Pt alloys.

A first principles analysis of potential-dependent structural evolution of active sites in Fe-N-C catalysts.

Fe-N-C (iron-nitrogen-carbon) electrocatalysts have emerged as potential alternatives to precious metal-based materials for the oxygen reduction reaction (ORR). However, the structure of these materials under electrochemical conditions is not well understood, and their poor stability in acidic environments poses a formidable challenge for successful adoption in commercial fuel cells. To provide molecular-level insights into these complex phenomena, we combine periodic density functional theory (DFT) calculations, exhaustive treatment of coadsorption effects for ORR reaction intermediates, including O and OH, and comprehensive analysis of solvation stabilization effects to construct voltage-dependent ab initio thermodynamic phase diagrams that describe the in situ structure of the active sites.

PVB exerts anti-inflammatory effects by inhibiting the activation of MAPK and NF-κB signaling pathways and ROS generation in neutrophils.

Pinaverium bromide (PVB) has been shown to protect mice against sepsis, which is predominantly attributed to PVB-mediated anti-inflammatory effects by inhibiting primed neutrophils to produce proinflammatory cytokines. However, the underlying mechanism(s) by which PVB affects neutrophils remains unknown. In this study, we report that treatment with PVB either before or after LPS stimulation attenuated IL-1β and TNF-α expression at both mRNA and protein levels in LPS-activated murine neutrophils.

Gut-derived 4-hydroxyphenylacetic acid attenuates sepsis-induced acute kidney injury by upregulating ARC to inhibit necroptosis.

Background: Studies have found that the plasma content of gut-derived 4-hydroxyphenylacetic acid (4-HPA) was significantly increased in septic patients. However, the mechanism of 4-HPA elevation during sepsis and its relationship with sepsis-induced acute kidney injury (SAKI) remain unclear.

Methods: Cecal ligation and puncture (CLP) was performed in C57BL/6 mice to establish the SAKI animal model.

Self-adaptive amorphous CoOCl electrocatalyst for sustainable chlorine evolution in acidic brine.

Electrochemical chlorine evolution reaction is of central importance in the chlor-alkali industry, but the chlorine evolution anode is largely limited by water oxidation side reaction and corrosion-induced performance decay in strong acids. Here we present an amorphous CoOCl catalyst that has been deposited in situ in an acidic saline electrolyte containing Co and Cl ions to adapt to the given electrochemical condition and exhibits ~100% chlorine evolution selectivity with an overpotential of ~0.1 V at 10 mA cm and high stability over 500 h.

Melatonin attenuates sepsis-induced acute kidney injury by promoting mitophagy through SIRT3-mediated TFAM deacetylation.

AKI: acute kidney injury; ATP: adenosine triphosphate; BUN: blood urea nitrogen; CLP: cecal ligation and puncture; eGFR: estimated glomerular filtration rate; H&E: hematoxylin and eosin staining; LCN2/NGAL: lipocalin 2; LPS: lipopolysaccharide; LTL: lotus tetragonolobus lectin; mKeima: mitochondria-targeted Keima; mtDNA: mitochondrial DNA; PAS: periodic acid - Schiff staining; RTECs: renal tubular epithelial cells; SAKI: sepsis-induced acute kidney injury; Scr: serum creatinine; SIRT3: sirtuin 3; TFAM: transcription factor A, mitochondrial; TMRE: tetramethylrhodamine.