Acute kidney injury in critical care: complications of hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is an immune dysfunction characterized by an exaggerated and pathological inflammatory response, potentially leading to systemic inflammatory reactions and multiple-organ failure, including renal involvement. HLH can be classified as primary or secondary, with primary HLH associated with genetic mutations affecting cell degranulation capacity, and secondary HLH often linked to infections, tumors, and autoimmune diseases. The pathogenesis of HLH is not fully understood, but primary HLH is typically driven by genetic defects, whereas secondary HLH involves the activation of CD8+ T cells and macrophages, leading to the release of inflammatory cytokines and systemic inflammatory response syndrome (SIRS). The clinical presentation of HLH includes non-specific manifestations, making it challenging to differentiate from severe sepsis, particularly secondary HLH due to infections. Shared features include prolonged fever, hepatosplenomegaly, hematopenia, hepatic dysfunction, hypertriglyceridemia, and hypofibrinogenemia, along with histiocytosis and hemophagocytosis. However, distinctive markers like dual hemocytopenia, hypertriglyceridemia, hypofibrinogenemia, and elevated sCD25 levels may aid in differentiating HLH from sepsis. Indeed, no singular biomarker effectively distinguishes between hemophagocytic lymphohistiocytosis and infection. However, research on combined biomarkers provides insights into the differential diagnosis. Renal impairment is frequently encountered in both HLH and sepsis. It can result from a systemic inflammatory response triggered by an influx of inflammatory mediators, from direct damage caused by these factors, or as a consequence of the primary disease process. For instance, macrophage infiltration of the kidney can lead to structural damage affecting various renal components, precipitating disease. Presently, tubular necrosis remains the predominant form of renal involvement in HLH-associated acute kidney injury (HLH-AKI). However, histopathological changes may also encompass interstitial inflammation, glomerular abnormalities, microscopic lesions, and thrombotic microangiopathy. Treatment approaches for HLH and sepsis diverge significantly. HLH is primarily managed with repeated chemotherapy to eliminate immune-activating stimuli and suppress hypercellularity. The treatment approach for sepsis primarily focuses on anti-infective therapy and intensive symptomatic supportive care. Renal function significantly influences clinical decision-making, particularly regarding the selection of chemotherapy and antibiotic dosages, which can profoundly impact patient prognosis. Conversely, renal function recovery is a complex process influenced by factors such as disease severity, timely diagnosis, and the intensity of treatment. A crucial aspect in managing HLH-AKI is the timely diagnosis, which plays a pivotal role in reversing renal impairment and creating a therapeutic window for intervention, may have opportunity to improve patient prognosis. Understanding the clinical characteristics, underlying causes, biomarkers, immunopathogenesis, and treatment options for hemophagocytic lymphohistiocytosis associated with acute kidney injury (HLH-AKI) is crucial for improving patient prognosis.

Establishment of microneurovascular units in alginate hydrogel microspheres to reveal the anti-hypoxic effect of salidroside.

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International Recommendations on Postoperative Management for Potentially Resectable Locally Recurrent Nasopharyngeal Carcinoma.

PURPOSE: Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. While postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. METHODS AND MATERIALS: A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. RESULTS: The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60Gy, and hyperfractionation has shown promise in reducing toxicity. CONCLUSION: These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for the clinical experts involved in the treatment of locally recurrent NPC. SUMMARY: This article provides international recommendations on postoperative management for potentially resectable locally recurrent nasopharyngeal carcinoma (NPC), with a special focus on postoperative re-irradiation (re-RT). The consensus guidelines highlight the importance of achieving clear surgical margins, suggest considering re-RT for patients with positive or close margins, recommend an optimal re-RT dose of around 60Gy, and propose the use of hyperfractionation to reduce toxicity. The aim is to improve patient outcomes in the management of resectable locally recurrent NPC.

The role of tissue-derived extracellular vesicles in tumor microenvironment.

The tumor microenvironment (TME) is a highly heterogeneous ecosystem that plays critical roles in the initiation, progression, invasion, and metastasis of cancers. Extracellular vesicles (EVs), as emerging components of the host-tumor communication, are lipid-bilayer membrane structures that are secreted by most cell types into TEM and increasingly recognized as critical elements that regulate the interaction between tumor cells and their surroundings. They contain a variety of bioactive molecules, such as proteins, nucleic acids, and lipids, and participate in various pathophysiological processes while regulating intercellular communication. While many studies have focused on the EVs derived from different body fluids or cell culture supernatants, the direct isolation of tissue-derived EVs (Ti-EVs) has garnered more attention due to the advantages of tissue specificity and accurate reflection of tissue microenvironment. In this review, we summarize the protocol for isolating Ti-EVs from different tissue interstitium, discuss the role of tumor-derived and adipose tissue-derived Ti-EVs in regulating TME. In addition, we sum up the latest application of Ti-EVs as potential biomarkers for cancer diseases.

Synthetic macrolides overcoming MLSBK-resistant pathogens.

Conventional macrolide-lincosamide-streptogramin B-ketolide (MLSBK) antibiotics are unable to counter the growing challenge of antibiotic resistance that is conferred by the constitutive methylation of rRNA base A2058 or its G2058 mutation, while the presence of unmodified A2058 is crucial for high selectivity of traditional MLSBK in targeting pathogens over human cells. The absence of effective modes of action reinforces the prevailing belief that constitutively antibiotic-resistant Staphylococcus aureus remains impervious to existing macrolides including telithromycin. Here, we report the design and synthesis of a novel series of macrolides, featuring the strategic fusion of ketolide and quinolone moieties. Our effort led to the discovery of two potent compounds, MCX-219 and MCX-190, demonstrating enhanced antibacterial efficacy against a broad spectrum of formidable pathogens, including A2058-methylated Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and notably, the clinical Mycoplasma pneumoniae isolates harboring A2058G mutations which are implicated in the recent pneumonia outbreak in China. Mechanistic studies reveal that the modified quinolone moiety of MCX-190 establishes a distinctive secondary binding site within the nascent peptide exit tunnel. Structure-activity relationship analysis underscores the importance of this secondary binding, maintained by a sandwich-like π-π stacking interaction and a water-magnesium bridge, for effective engagement with A2058-methylated ribosomes rather than topoisomerases targeted by quinolone antibiotics. Our findings not only highlight MCX-219 and MCX-190 as promising candidates for next-generation MLSBK antibiotics to combat antibiotic resistance, but also pave the way for the future rational design of the class of MLSBK antibiotics, offering a strategic framework to overcome the challenges posed by escalating antibiotic resistance.

Organelle Proximity Analysis for Enhanced Quantification of Mitochondria-Endoplasmic Reticulum Interactions in Single Cells via Super-Resolution Microscopy.

Mitochondria (MT) and the endoplasmic reticulum (ER) maintain lipid and calcium homeostasis through membrane contacts, particularly MT-ER contacts (MERCs), spanning distances from 10 to 50 nm. However, the variation of different distance ranges and the metabolic factors influencing this variation remain poorly understood. This study employed microfluidic chip-based super-resolution microscopy in conjunction with a Moore-Neighbor tracing-incorporated organelle proximity analysis algorithm. This approach enabled precise three-dimensional localization of single-fluorescence protein molecules within narrow and irregular membrane proximities. It achieved lateral localization precision of less than 20 nm, resulting in a minimum MERC distance of approximately 8 nm in spatial and mean distances across multiple threshold ranges. Additionally, we demonstrated that the MERC distance variation was correlated with MT size rather than ER width. The proportion of each distance range varied significantly after the stimuli. Free cholesterol showed a negative correlation with various distances, while distances of 10-30 nm were associated with glucose, glutamine, and pyruvic acid. Furthermore, the 30-40 nm range was influenced by citric acid. These results underscore the role of advanced subcellular organelle analysis in elucidating the single-molecule behavior and organelle morphology in single-cell studies.

Ultrasound findings and clinical characteristics in differentiating renal urothelial carcinoma from endophytic clear cell renal cell carcinoma.

OBJECTIVE: This study aimed to evaluate the clinical characteristics and features of conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) in differentiating between renal urothelial carcinomas (RUC) and endophytic clear cell renal cell carcinomas (EccRCC). METHODS: A total of 72 RUCs and 120 EccRCCs confirmed by pathology were assessed retrospectively. Both CUS and CEUS were performed within 4 weeks before the surgery. Logistic regression analyses were used to select statistically significant variables of clinical, CUS, and CEUS features for the differentiation of RUC and EccRCC. Sensitivity (SEN), specificity (SPE), and the area under the receiver-operating characteristic curve (AUC) were assessed for diagnostic performance. Inter- and intra-observer agreements of CUS and CEUS features were evaluated using the intra-class correlation coefficient(ICC). RESULTS: Multiple logistic regression analysis demonstrated that clinical (age >50 years old and hematuria), CUS (size <4.0 cm, hypo-echogenicity, irregular shape, hydronephrosis) and CEUS (absence of non-enhancement area, iso- /hypo-enhancement in cortical phase and absence of rim-like enhancement) features were independent factors for RUC diagnosis. When combining clinical characters with CUS and CEUS features into an integrated diagnostic criterion, the AUC reached 0.917 (95% CI 0.873-0.961), with a sensitivity of 95.8% and specificity of 87.5%. ICC ranged from 0.756 to 0.907 for inter-observer agreement and 0.791 to 0.934 for intra-observer agreement for CUS and CEUSfeatures. CONCLUSIONS: The combination of clinical features of age and hematuria with imaging features of CUS and CEUS can be useful for the differentiation between RUC and EccRCC.

Role of Trace Cadmium Exposure on the Development of Occlusal Traumatic Temporomandibular Arthritis.

OBJECTIVE: To investigate whether heavy metal cadmium acts as a risk factor for temporomandibular joint disorder disease and to study its pathogenic mechanism. METHODS: A total of 57 rats were allocated into 6 distinct groups, distinguished by 2 interventions: occlusal elevation and cadmium water gavage. These groups included a blank control group, occlusal elevation group, occlusal elevation + 0.42 mg/mL cadmium water gavage group, occlusal elevation + 4.2 mg/mL cadmium water gavage group, no occlusal elevation + 0.42 mg/mL cadmium water gavage group, and no occlusal elevation + 4.2 mg/mL cadmium water gavage group. The impact of cadmium exposure on cartilage oxidative stress was evaluated through the assessment of SOD, CAT, GST, and GSH-Px enzyme activities. In addition, the influence of cadmium exposure on alterations in the extracellular matrix and inflammatory mediators was examined by analyzing the expression levels of type II collagen, protein aggregation polysaccharide, glycosaminoglycan, IL1ß, IL-6, and TNF-α. Histologic examination of the condylar process cartilage of rats in the occlusal elevation + cadmium water gavage group was conducted to ascertain the occurrence of osteoarthritis. RESULTS: The variance in the expression levels of inflammatory factors did not demonstrate statistical significance between the occlusal elevation group and the blank control group; however, statistical significance was observed between the occlusal elevation + cadmium water gavage group and both the control and occlusal elevation groups. CONCLUSION: The severity of inflammation and condylar lesions correlates directly with the concentration of cadmium.

Desulfurization of Thiols for Nucleophilic Substitution.

Although the desulfurization of thiols is a topic of great importance and has received significant attention, most efforts have focused on the hydrodesulfurization of thiols. In this work, we describe the desulfurization of thiols for nucleophilic substitution. This process occurs rapidly, promoted by the Ph3P/ICH2CH2I system, and can be extended to a wide range of nucleophiles. Notably, free amines can be employed as nucleophiles to synthesize various secondary and tertiary amines. This method tolerates a wide array of functional groups, including hydroxyl groups in amination reactions. Benzyl thiols are particularly reactive and can be completely converted at room temperature within 15 min. Although alkyl thiols show lower reactivity, they can also be converted smoothly at a reaction temperature of 70 °C overnight.

iTRAQ proteomics analysis of placental tissue with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus is an endocrine and metabolic disorder that appears for the first time during pregnancy and causes varying degrees of short- and/or long-term effects on the mother and child. The etiology of the disease is currently unknown and isobaric tags for relative and absolute quantitation proteomics approach, the present study attempted to identify potential proteins in placental tissues that may be involved in the pathogenesis of GDM and adverse foetal pregnancy outcomes. METHODS: Pregnant women with GDM hospitalised were selected as the experimental group, and pregnant women with normal glucose metabolism as the control group. The iTRAQ protein quantification technology was used to screen the differentially expressed proteins between the GDM group and the normal control group, and the differentially expressed proteins were analysed by GO, KEGG, PPI, etc., and the key proteins were subsequently verified by western blot. RESULTS: Based on the proteomics of iTRAQ, we experimented with three different samples of placental tissues from GDM and normal pregnant women, and the total number of identified proteins were 5906, 5959, and 6017, respectively, which were similar in the three different samples, indicating that the results were reliable. Through the Wayne diagram, we found that the total number of proteins coexisting in the three groups was 4475, and 91 differential proteins that could meet the quantification criteria were strictly screened, of which 32 proteins were up-regulated and 59 proteins were down-regulated. By GO enrichment analysis, these differential proteins are widely distributed in extracellular membrane-bounded organelle, mainly in extracellular exosome, followed by intracellular vesicle, extracellular organelle. It not only undertakes protein binding, protein complex binding, macromolecular complex binding, but also involves molecular biological functions such as neutrophil degranulation, multicellular organismal process, developmental process, cellular component organization, secretion, regulated exocytosis. Through the analysis of the KEGG signaling pathway, it is found that these differential proteins are mainly involved in HIF-1 signaling pathway, Glycolysis/Gluconeogenesis, Central carbon metabolism in cancer, AMPK signaling pathway, Proteoglycans in cancer, Protein processing in endoplasmic reticulum, Thyroid cancer, Alcoholism, Glucagon signaling pathway. DISCUSSION: This preliminary study helps us to understand the changes in the placental proteome of GDM patients, and provides new insights into the pathophysiology of GDM.

Integrated Methylome and Transcriptome Analysis between Wizened and Normal Flower Buds in Pyrus pyrifolia Cultivar 'Sucui 1'.

Here, cytosine methylation in the whole genome of pear flower buds was mapped at a single-base resolution. There was 19.4% methylation across all sequenced C sites in the Pyrus pyrifolia cultivar 'Sucui 1' flower bud genome. Meantime, the CG, CHG, and CHH sequence contexts (where H = A, T or C) exhibited 47.4%, 33.3%, and 11.9% methylation, respectively. Methylation in different gene regions was revealed through combining methylome and transcriptome analysis, which presented various transcription trends. Genes with methylated promoters exhibited lower expression levels than genes with non-methylated promoters, while body-methylated genes displayed an obvious negative correlation with their transcription levels. The methylation profiles of auxin- and cytokinin-related genes were estimated. And some of them proved to be hypomethylated, with increased transcription levels, in wizened buds. More specifically, the expression of the genes PRXP73, CYP749A22, and CYP82A3 was upregulated as a result of methylation changes in their promoters. Finally, auxin and cytokinin concentrations were higher in wizened flower buds than in normal buds. The exogenous application of paclobutrazol (PP333) in the field influenced the DNA methylation status of some genes and changed their expression level, reducing the proportion of wizened flower buds in a concentration-dependent manner. Overall, our results demonstrated the relationship between DNA methylation and gene expression in wizened flower buds of P. pyrifolia cultivar 'Sucui 1', which was associated with changes in auxin and cytokinin concentrations.

Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis.

OBJECTIVE: To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis. METHODS: PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software. RESULTS: A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (ß2-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or ß2-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias. CONCLUSIONS: The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.

Renin-angiotensin-aldosterone system (RAAS) inhibitors are commonly used to treat diabetic neuropathy (DN) and Astragalus membranaceus components are known to improve DN symptoms.We aimed to establish the efficacy and safety of using Astragalus combined with RAAS inhibitors.Astragalus combined with RAAS inhibitors enhances the total effective rate of diabetic neuropathy response to treatment and reduces urinary protein excretion rate, serum creatinine, blood urea nitrogen and HbAlc.Sensitivity analysis affirms study stability, while publication bias was detected for total effective rate, serum creatinine, and 24 h urinary protein levels.

Prognostic impact of elective tracheotomy in resected oral cavity squamous cell carcinoma: A nationwide cohort study.

BACKGROUND: Elective tracheotomy is commonly performed in resected oral squamous cell carcinoma (OCSCC) to maintain airway patency. However, the indications for this procedure vary among surgeons. This nationwide study evaluated the impact of tracheotomy on both the duration of in-hospital stay and long-term survival outcomes in patients with OCSCC. METHODS: A total of 18,416 patients with OCSCC were included in the analysis, comprising 7981 patients who underwent elective tracheotomy and 10,435 who did not. The primary outcomes assessed were 5-year disease-specific survival (DSS) and overall survival (OS). To minimize potential confounding factors, a propensity score (PS)-matched analysis was performed on 4301 patients from each group. The duration of hospital stay was not included as a variable in the PS-matched analysis. RESULTS: Prior to PS matching, patients with tracheotomy had significantly lower 5-year DSS and OS rates compared to those without (71% vs. 82%, p < 0.0001; 62% vs. 75%, p < 0.0001, respectively). Multivariable analysis identified tracheotomy as an independent adverse prognostic factor for 5-year DSS (hazard ratio = 1.10 [1.03-1.18], p = 0.0063) and OS (hazard ratio = 1.10 [1.04-1.17], p = 0.0015). In the PS-matched cohort, the 5-year DSS was 75% for patients with tracheotomy and 76% for those without (p = 0.1488). Five-year OS rates were 66% and 67%, respectively (p = 0.0808). Prior to PS matching, patients with tracheotomy had a significantly longer mean hospital stay compared to those without (23.37 ± 10.56 days vs. 14.19 ± 8.34 days; p < 0.0001). Following PS matching, the difference in hospital stay duration between the two groups remained significant (22.34 ± 10.25 days vs. 17.59 ± 9.54 days; p < 0.0001). CONCLUSIONS: While elective tracheotomy in resected OCSCC patients may not significantly affect survival, it could be associated with prolonged hospital stays.

Anti-inflammatory in vitro activities of eleven selected caffeic acid derivatives based on a combination of pro-/anti-inflammatory cytokine secretions and principal component analysis - A comprehensive evaluation.

Eleven compounds including caffeic acid (CA), 4 kinds of caffeoylquinic acid (CQA) and 6 kinds of dicaffeoylquinic acid (DCQA), were selected to evaluate the anti-inflammatory effectiveness using mouse primary peritoneal macrophages in the absence or presence of lipopolysaccharide (LPS). The optimal non-cytotoxic doses of each individual compound were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Pro-inflammatory (TNF-α, IL-1ß, IL-6) and anti-inflammatory (IL-10) cytokines secreted by treated macrophages were analyzed using the enzyme-linked immunosorbent assay. Cytokine secretion profiles of each individual test sample at optimal non-cytotoxic doses were further analyzed using Principal Component Analysis (PCA). The results showed that CA and all selected CQAs exhibited lower cytotoxicity (IC50: >50 µmol/l). Both CA and 5-CQA were found to have the most significant contributions for inhibiting pro-inflammatory cytokines, but increasing anti-inflammatory cytokine secretions, evidencing that CA at 10 µmol/l and 5-CQA at 25 µmol/l can be qualified as potent anti-inflammatory agents for treating inflammation-related diseases.

Neutrophil-to-lymphocyte ratio as a predictor for outcomes in patients with short-term emergency department revisits.

BACKGROUND: Analysis of short-term emergency department (ED) revisits is a common emergency care quality assurance practice. Previous studies have explored various risk factors of ED revisits; however, laboratory data were usually omitted. This study aimed to evaluate the prognostic significance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), and systemic immune-inflammation index (SII) in predicting outcomes of patients revisiting the ED. METHODS: This retrospective observational cohort study investigated short-term ED revisit patients. The primary outcome measure was high-risk ED revisit, a composite of in-hospital mortality or intensive care unit (ICU) admission after 72-h ED revisit. The NLR, PLR, and SII were investigated as potential prognostic predictors of ED revisit outcomes. RESULTS: A total of 1916 encounters with short-term ED revisit patients were included in the study; among these, 132 (6.9%) encounters, comprising 57 in-hospital mortalities and 95 ICU admissions, were high-risk revisits. High-risk revisit patients had significantly higher NLR, PLR, and SII (11.6 vs. 6.6, p<0.001; 26.2 vs. 18.9, p=0.004; 2209 vs. 1486, p=0.002, respectively). Multiple regression analysis revealed revisit-NLR as an independent factor for predicting poor outcomes post-ED revisits (Odds Ratio: 1.031, 95% Confidence Interval: 1.017-1.045, p<0.001); an optimal cut-off value of 7.9 was proven for predicting high-risk ED revisit. CONCLUSION: The intensity of the inflammatory response expressed by NLR was an independent predictor for poor outcomes of ED revisits and should be considered when ED revisits occur. Future prediction models for ED revisit outcomes can include revisit-NLR as a potential predictor to reflect the progressive conditions in ED patients.

Sub-inhibitory concentrations of tetrabromobisphenol A induce the biofilm formation of methicillin-resistant Staphylococcus aureus.

Biofilm formation by methicillin-resistant Staphylococcus aureus (MRSA) on indwelling medical devices complicates the treatment of infection. Tetrabromobisphenol A (TBBPA), a synthetic, lipophilic, halogenated aromatic compound widely used as an additive in plastics and electronic products, has raised environmental concerns due to its potential for bioaccumulation. This study investigated the impact of sub-inhibitory concentrations of TBBPA on MRSA biofilm formation. Crystal violet staining and confocal laser scanning microscopy analysis demonstrated that 1/8 MIC (0.5 µg/mL) of TBBPA significantly stimulated MRSA biofilm formation (P < 0.0001). MTT assays indicated that the metabolic activity within the biofilms increased by 15.60-40.85% compared to untreated controls. Dot blot immunoassay, autolysis assay, and extracellular DNA (eDNA) quantification further revealed TBBPA enhanced the production of polysaccharide intercellular adhesin (PIA) and eDNA, which are key biofilm components. Additionally, TBBPA was found to enhance the production of staphyloxanthin, facilitating MRSA survival under oxidative conditions and in human whole blood. RT-qPCR analysis showed that TBBPA significantly upregulated genes associated with biofilm formation (icaA, atlA, sarA), staphyloxanthin biosynthesis (crtM and sigB), and oxidative stress responses (sodA and katA). These findings suggest that TBBPA promotes MRSA biofilm development and enhances bacterial resistance to adverse conditions, thereby potentially exacerbating risks to human health.

Ruthenium Complexes with NNN-Pincer Ligands for N-Methylation of Amines Using Methanol.

A series of ruthenium complexes (Ru1-Ru4) bearing new NNN-pincer ligands were synthesized in 58-78% yields. All of the complexes are air and moisture stable and were characterized by IR, NMR, and high-resolution mass spectra (HRMS). In addition, the structures of Ru1-Ru3 were confirmed by X-ray crystallographic analysis. These Ru(II) complexes exhibited high catalytic efficiency and broad functional group tolerance in the N-methylation reaction of amines using CH3OH as both the C1 source and solvent. Experimental results indicated that the electronic effect of the substituents on the ligands considerably affects the catalytic reactivity of the complexes in which Ru3 bearing an electron-donating OMe group showed the highest activity. Deuterium labeling and control experiments suggested that the dehydrogenation of methanol to generate ruthenium hydride species was the rate-determining step in the reaction. Furthermore, this protocol also provided a ready approach to versatile trideuterated N-methylamines under mild conditions using CD3OD as a deuterated methylating agent.

Development and validation of a machine-learning model for predicting the risk of death in sepsis patients with acute kidney injury.

The mortality rate of patients with sepsis-induced acute kidney injury (S-AKI) is notably elevated. The initial categorization of prognostic indicators has a beneficial impact on elucidating and enhancing disease outcomes. This study aimed to predict the mortality risk of S-AKI patients by employing machine learning techniques. The sample size determined by a four-step procedure yielded 1508 samples. The research design necessitated the inclusion of individuals with S-AKI from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The patients were initially admitted to the Intensive Care Unit (ICU) for their hospital stay. Additionally, these patients (aged from 18 to 89 years old) had encountered S-AKI on the day of their admittance. Forty-two predictive factors were analyzed, with hospitalization death as the outcome variable. The training set (4001 cases) consisted of 70 % of the participants, and the remaining (1714 cases) participants were allocated to the validation set. Furthermore, an additional validation set (MIMIC-III) consisted of 1757 patients from the MIMIC-III database. Moreover, an external validation set from the Intensive Care Department of Beijing Friendship Hospital (BFH) comprised 72 patients. Six machine learning models were employed in the prediction, namely the logistic, lasso, rpart, random forest, xgboost, and artificial neural network models. The comparative efficacy of the newly developed model in relation to the APACHE II model for predicting mortality risk was also assessed. The XGBoost model exhibited a superior performance with the training set. With the internal validation set and the two external validation sets (MIMIC-III and BFH), the xgboost algorithm demonstrated the highest performance. Meanwhile, APACHE II performed poorly at predicting the mortality risk with the BFH validation set. The mortality risk was influenced by three primary clinical parameters: urine volume, lactate, and Glasgow Coma Scale (GCS) score. Thus, we developed a prediction model for the risk of death among S-AKI patients that has an improved performance compared to previous models and is a potentially valuable tool for S-AKI prediction and treatment in the clinic.