Development and validation of a nomogram for predicting occurrence of severe case in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era.

Background: The significant rebound of influenza A (H1N1) virus activity, particularly among children, with rapidly growing number of hospitalized cases is of major concern in the post-COVID-19 era. The present study was performed to establish a prediction model of severe case in pediatric patients hospitalized with H1N1 infection during the post-COVID-19 era. Methods: This is a multicenter retrospective study across nine public tertiary hospitals in Yunnan, China, recruiting pediatric H1N1 inpatients hospitalized at five of these centers between February 1 and July 1, 2023, into the development dataset. Screening of 40 variables including demographic information, clinical features, and laboratory parameters were performed utilizing Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression to determine independent risk factors of severe H1N1 infection, thus constructing a prediction nomogram. Receiver operating characteristic (ROC) curve, calibration curve, as well as decision curve analysis (DCA) were employed to evaluate the model's performance. Data from four independent cohorts comprised of pediatric H1N1 inpatients from another four hospitals between July 25 and October 31, 2023, were utilized to externally validate this nomogram. Results: The development dataset included 527 subjects, 122 (23.1 %) of whom developed severe H1N1 infection. The external validation dataset included 352 subjects, 72 (20.5 %) of whom were eventually confirmed as severe H1N1 infection. The LASSO regression identified 19 candidate predictors, with logistic regression further narrowing down to 11 independent risk factors, including underlying conditions, prematurity, fever duration, wheezing, poor appetite, leukocyte count, neutrophil-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α). By integrating these 11 factors, a predictive nomogram was established. In terms of prediction of severe H1N1 infection, excellent discriminative capacity, favorable accuracy, and satisfactory clinical usefulness of this model were internally and externally validated via ROC curve, calibration curve, and DCA, respectively. Conclusion: Our study successfully established and validated a novel nomogram model integrating underlying conditions, prematurity, fever duration, wheezing, poor appetite, leukocyte count, NLR, ESR, LDH, IL-10, and TNF-α. This nomogram can effectively predict the occurrence of serious case in pediatric H1N1 inpatients during the post-COVID-19 era, facilitating the early recognition and more efficient clinical management of such patients.

Theoretical Insights of Curvature Effects of FeN4-Doped Carbon Nanotubes on ORR Activity.

The advancement of metal-air batteries is critically contingent on the progression of efficient catalysts for the oxygen reduction reaction (ORR). The potential applications of a series of FeN4-doped carbon nanotubes (Fe-N4CNTs) of varying diameters as ORR catalysts were examined using density functional theory. We explored the stability and electronic properties of Fe-N4CNTs by analyzing the energy and examining the density of states. A marked dependence of the catalytic performance on the nanotube diameter was observed: as the transition from (5, 5) to (10, 10) Fe-N4CNTs occurred, the catalytic activity on the outer surface of the carbon tubes enhanced progressively, with the overpotential reducing from 0.94 to 0.86 V. Conversely, the catalytic activity on the inner surface of the carbon tubes decreased progressively with the overpotential also increasing from 0.62 to 1.04 V. In addition, we found that curvature significantly affected the electronic structure and charge transfer at the FeN4 site, regulating the adsorption and desorption of reactants, intermediates, and products during electrocatalysis and thus influencing the catalytic activity of the Fe-N4CNTs. This investigation offers valuable guidance for the design of Fe-based single-atom catalysts and the practical application of Fe-N-C materials.

A novel combined nomogram for predicting severe acute lower respiratory tract infection in children hospitalized for RSV infection during the post-COVID-19 period.

Introduction: Off-season upsurge of respiratory syncytial virus (RSV) infection with changed characteristics and heightened clinical severity during the post-COVID-19 era are raising serious concerns. This study aimed to develop and validate a nomogram for predicting the risk of severe acute lower respiratory tract infection (SALRTI) in children hospitalized for RSV infection during the post-COVID-19 era using machine learning techniques. Methods: A multicenter retrospective study was performed in nine tertiary hospitals in Yunnan, China, enrolling children hospitalized for RSV infection at seven of the nine participating hospitals during January-December 2023 into the development dataset. Thirty-nine variables covering demographic, clinical, and laboratory characteristics were collected. Primary screening and dimension reduction of data were performed using Least Absolute Shrinkage and Selection Operator (LASSO) regression, followed by identification of independent risk factors for RSV-associated SALRTI using Logistic regression, thus finally establishing a predictive nomogram model. Performance of the nomogram was internally evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) based on the development dataset. External validation of our model was conducted using same methods based on two independent RSV cohorts comprising pediatric RSV inpatients from another two participating hospitals between January-March 2024. Results: The development dataset included 1102 patients, 239 (21.7%) of whom developed SALRTI; while the external validation dataset included 249 patients (142 in Lincang subset and 107 in Dali subset), 58 (23.3%) of whom were diagnosed as SALRTI. Nine variables, including age, preterm birth, underlying condition, seizures, neutrophil-lymphocyte ratio (NLR), interleukin-6 (IL-6), lactate dehydrogenase (LDH), D-dimer, and co-infection, were eventually confirmed as the independent risk factors of RSV-associated SALRTI. A predictive nomogram was established via integrating these nine predictors. In both internal and external validations, ROC curves indicated that the nomogram had satisfactory discrimination ability, calibration curves demonstrated good agreement between the nomogram-predicted and observed probabilities of outcome, and DCA showed that the nomogram possessed favorable clinical application potential. Conclusion: A novel nomogram combining several common clinical and inflammatory indicators was successfully developed to predict RSV-associated SALRTI. Good performance and clinical effectiveness of this model were confirmed by internal and external validations.

Blood and urine biomarkers of disease progression in IgA nephropathy.

The prognosis of patients with IgA nephropathy (IgAN) is variable but overall not good. Almost all patients with IgAN are at risk of developing end-stage renal disease within their expected lifetime. The models presently available for prediction of the risk of progression of IgAN, including the International IgA Nephropathy Prediction Tool, consist of traditional clinical, pathological, and therapeutic indicators. Finding biomarkers to improve the existing risk prediction models or replace pathological indicators is important for clinical practice. Many studies have attempted to identify biomarkers for prediction of progression of IgAN, such as galactose-deficient IgA1, complement, a spectrum of protein biomarkers, non-coding RNA, and shedding cells. This article reviews the biomarkers of progression of IgAN identified in recent years, with a focus on those with clinical value, in particular the combination of multiple biomarkers into a biomarker spectrum. Future research should focus on establishing a model based primarily on biomarkers that can predict progression of IgAN and testing it in various patient cohorts.

Low back pain in medical workers and its influencing factors.

PURPOSE: To investigate the prevalence of occupational lower back pain (OLBP) among medical workers and identify the contributing factors. METHODS: An electronic questionnaire was distributed to medical workers at Yuebei People's Hospital to gather information on various factors, including gender, age, body mass index (BMI), length of employment, job role, education level, professional title, marital status, fertility status, frequency of night shift, weight lifting daily, duration of daily standing at work, frequency of bending, work-related stress, experience with low back protection training, and frequency of waist exercises. Univariate and multivariate logistic regression analyses were conducted to identify the factors associated with OLBP in medical workers. RESULTS: Out of the 98 medical workers surveyed, 67 experienced OLBP (68.37%). The results of multivariate logistic regression analysis revealed that working for more than 5 years, holding a nursing position, and lacking training in low back protection were significant risk factors for developing OLBP in medical workers (all P<0.05). CONCLUSION: OLBP is a prevalent issue among medical workers, and various factors such as length of employment, job role, and training in low back protection can influence its occurrence.

p38 Signaling Mediates Naringin-Induced Osteogenic Differentiation of Porcine Metanephric Mesenchymal Cells.

OBJECTIVE: To explore the potential of metanephric mesenchymal cells (MMCs) for osteogenesis and naringin's ability to enhance this process and its molecular mechanism. METHODS: Porcine MMCs at 70 days of gestation were used as tool cells, cultured in osteogenic induction medium, identified by immunocytochemistry staining. Osteogenic potential of porcine MMCs and naringin's ability to enhance this process was tested by detecting changes in cell viability, alkaline phosphatase (ALP) activity, the expression of runt-related transcription factor 2 (Runx2), osteopontin (OPN) and osteocalcin (OCN), and the formation of mineralized nodules, and the application of the p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin. RESULTS: Immunocytochemical staining showed that the cells were Vimentin and Six2(+), E-cadherin and CK-18(-). Naringin can activate the p38 signaling pathway to enhance the osteogenesis of porcine MMCs by increasing cell viability, ALP activity, the expressions of Runx2, OPN and OCN, and the formation of mineralized nodules (P<0.05). The application of p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin, manifested by decreased ALP activity, the expressions of Runx2, OPN and OCN, and the formation of mineralized nodules (P<0.05). CONCLUSION: Naringin, the active ingredient of Chinese herbal medicine Rhizoma Drynariae for nourishing Shen (Kidney) and strengthening bone, enhances the osteogenic differentiation of renal MMCs through the p38 signaling pathway.

The Selectivity Origins in Ag-Catalyzed CO2 Electroreduction.

Ag exhibits high selectivity of electrochemical CO2 reduction (CO2R) toward C1 products, while the hydrogenation involving the concerted proton-electron transfer (CPET) or sequential electron-proton transfer (SEPT) mechanism is still in debate. Toward a better understanding of the Ag-catalyzed electrochemical CO2R, we employed a microkinetic model based on the Marcus electron transfer theory to thoroughly investigate the selectivity of C1 products of electrochemical CO2R over the Ag(111) surface. We found that at an acidic condition of pH = 1.94, formate is the main product when U < -0.94 V via the CPET mechanism, whereas CO becomes the primary product when U > -0.94 V via the SEPT mechanism. Conversely, at an alkaline condition of pH = 13.95, formate is the main product following the SEPT mechanism. Our findings provide novel insights into the influence of external factors (applied potential and pH) on the product selectivity and hydrogenation mechanism of electrochemical CO2R.

Ultrafast conformation-dependent charge transfer in N, N, N', N'-tetramethyl-1,3-propanediamine: Effect of flexible carbon skeleton on electron lone pair interactions.

Flexible three-carbon skeleton makes N, N, N', N'-tetramethyl-1,3-propanediamine (TMPDA) an important diamine system to investigate the conformation-dependent electron lone pair interactions and charge delocalization. The charge transfer process linked to structural motions of the three-carbon skeleton has been monitored in real time by the Rydberg electron binding energy (BE) spectra of TMPDA coupled with quantum chemical calculations. Optical excitation to the 3p state with a 200 nm pump pulse initially generated a localized charge on one of the two nitrogen atoms that may partially transfer to the other one. Rapid internal conversion (IC) from the 3p to 3s state occurred within 430 fs, resulting in an initial charge delocalized 3s_h/3s_l population ratio of 23.6 %/76.4 %. A final 3s_h/3s_l (51.9 %/48.1 %) equilibrium proceeded within about 2.64 ps. The 3s_h (TTTT+, GG'TG+ and G'GG'G+) and 3s_l (GG'GG'+ and GG'G'G+) (see text for structure definitions) are identified as the extended and folded conformers, respectively. Two types of electron lone pair interactions, i.e., through-space interaction (TSI) and through-bond interaction (TBI), are found to coexist in TMPDA to drive charge transfer. The GG'GG'+ and GG'G'G+ structures exhibit TSI, while the TTTT+ structure shows TBI. The GG'TG+ and G'GG'G+ structures exhibit both TSI and TBI. Flexible three-carbon skeleton provide more opportunities for the two N-electron lone pairs to overlap in space (i.e., TSI), making TMPDA to be favorable for the most stably folded conformation.

The novel HLA-B*15:02:15 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*15:02:15 differs from HLA-B*15:02:01:01 by one nucleotide in exon 2.

Combined lineage tracing and scRNA-seq reveal the activation of Sox9+ cells in renal regeneration with PGE2 treatment.

Uncovering mechanisms of endogenous regeneration and repair through resident stem cell activation will allow us to develop specific therapies for injuries and diseases by targeting resident stem cell lineages. Sox9+ stem cells have been reported to play an essential role in acute kidney injury (AKI). However, a complete view of the Sox9+ lineage was not well investigated to accurately elucidate the functional end state and the choice of cell fate during tissue repair after AKI. To identify the mechanisms of fate determination of Sox9+ stem cells, we set up an AKI model with prostaglandin E2 (PGE2) treatment in a Sox9 lineage tracing mouse model. Single-cell RNA sequencing (scRNA-seq) was performed to analyse the transcriptomic profile of the Sox9+ lineage. Our results revealed that PGE2 could activate renal Sox9+ cells and promote the differentiation of Sox9+ cells into renal proximal tubular epithelial cells and inhibit the development of fibrosis. Furthermore, single-cell transcriptome analysis demonstrated that PGE2 could regulate the restoration of lipid metabolism homeostasis in proximal tubular epithelial cells by participating in communication with different cell types. Our results highlight the prospects for the activation of endogenous renal Sox9+ stem cells with PGE2 for the regenerative therapy of AKI.

Bortezomib elevates intracellular free Fe2+ by enhancing NCOA4-mediated ferritinophagy and synergizes with RSL-3 to inhibit multiple myeloma cells.

Iron contributes to tumor initiation and progression; however, excessive intracellular free Fe2+ can be toxic to cancer cells. Our findings confirmed that multiple myeloma (MM) cells exhibited elevated intracellular iron levels and increased ferritin, a key protein for iron storage, compared with normal cells. Interestingly, Bortezomib (BTZ) was found to trigger ferritin degradation, increase free intracellular Fe2+, and promote ferroptosis in MM cells. Subsequent mechanistic investigation revealed that BTZ effectively increased NCOA4 levels by preventing proteasomal degradation in MM cells. When we knocked down NCOA4 or blocked autophagy using chloroquine, BTZ-induced ferritin degradation and the increase in intracellular free Fe2+ were significantly reduced in MM cells, confirming the role of BTZ in enhancing ferritinophagy. Furthermore, the combination of BTZ with RSL-3, a specific inhibitor of GPX4 and inducer of ferroptosis, synergistically promoted ferroptosis in MM cell lines and increased cell death in both MM cell lines and primary MM cells. The induction of ferroptosis inhibitor liproxstatin-1 successfully counteracted the synergistic effect of BTZ and RSL-3 in MM cells. Altogether, our findings reveal that BTZ elevates intracellular free Fe2+ by enhancing NCOA4-mediated ferritinophagy and synergizes with RSL-3 by increasing ferroptosisin MM cells.

Etching of Ag nanoparticles triggered bidirectional regulation for electrochemiluminescence ratiometric immunoassay.

A highly efficient ratiometric electrochemiluminescence (ECL) immunoassay was explored by bidirectionally regulating the ECL intensity of two luminophors. The immunoassay was conducted in a split-type mode consisting of an ECL detection procedure and a sandwich immunoreaction. The ECL detection was executed using a dual-disk glassy carbon electrode modified with two potential-resolved luminophors (g-C3N4-Ag and Ru-MOF-Ag nanocomposites), and the sandwich immunoreaction using glucose oxidase (GOx)-modified SiO2 nanospheres as labels was carried out in a 96-well plate. The Ag nanoparticles (NPs) acted as bifunctional units both for triggering the resonance energy transfer (RET) with g-C3N4 and for accelerating the electron transfer rate of the Ru-MOF-Ag ECL reaction. When the H2O2 catalyzed by GOx in the 96-well plate was transferred to the dual-disk glass carbon electrode, the doped Ag NPs in the two luminophors could be etched, thus destroying the RET between C3N4 and the accelerated reaction to Ru-MOF, resulting in an opposite trend in the ECL signal outputted from the dual disks. Using the ratio of the two signals for quantification, the constructed immunosensor for a model target, i.e. myoglobin, exhibited a low detection limit of 4.7 × 10-14 g/mL. The ingenious combination of ECL ratiometry, bifunctional Ag NPs, and a split-type strategy effectively reduces environmental and human errors, offering a more precise and sensitive analysis for complex samples.

Evaluation of disease severity and prediction of severe cases in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era: a multicenter retrospective study.

BACKGROUND: The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. METHODS: A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. RESULTS: After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3+ T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability. CONCLUSIONS: Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.

A radical 1,4-aryl migration enables nickel-catalysed remote cross-electrophile coupling of ß-bromo amino acid esters with vinyl triflates.

A radical 1,4-aryl migration enabling a cross-electrophile coupling reaction toward remote transalkylation of N-benzyl alanine has been developed. In this strategy, with the occurrence of a radical-mediated Turce-Smiles rearrangement, key α-aminoalkyl radicals are generated. The as-formed α-aminoalkyl radical serves as a robust coupling partner for cross-electrophilic coupling with vinyl triflates, affording a series of olefin-tethered amino acid motifs.

Urinary miR-185-5p is a biomarker of renal tubulointerstitial fibrosis in IgA nephropathy.

Background: For IgA nephropathy (IgAN), tubular atrophy/interstitial fibrosis is the most important prognostic pathological indicator in the mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and presence of crescents (MEST-C) score. The identification of non-invasive biomarkers for tubular atrophy/interstitial fibrosis would aid clinical monitoring of IgAN progression and improve patient prognosis. Methods: The study included 188 patients with primary IgAN in separate confirmation and validation cohorts. The associations of miR-92a-3p, miR-425-5p, and miR-185-5p with renal histopathological lesions and prognosis were explored using Spearman correlation analysis and Kaplan-Meier survival curves. Bioinformatics analysis and dual luciferase experiments were used to identify hub genes for miR-185-5p. The fibrotic phenotypes of tubular epithelial cells were evaluated in vivo and in HK-2 cells. Results: miRNA sequencing and cohort validation revealed that the expression levels of miR-92a-3p, miR-425-5p, and miR-185-5p in urine were significantly increased among patients with IgAN; these levels could predict the extent of tubular atrophy/interstitial fibrosis in such patients. The combination of the three biomarkers resulted in an area under the receiver operating characteristic curve of 0.742. The renal prognosis was significantly worse in the miR-185-5p high expression group than in the low expression group (P=0.003). Renal tissue in situ hybridization, bioinformatics analysis, and dual luciferase experiments confirmed that miR-185-5p affects prognosis in patients with IgAN mainly by influencing expression of the target gene tight junction protein 1 (TJP1) in renal tubular epithelial cells. In vitro experiment revealed that an miR-185-5p mimic could reduce TJP1 expression in HK-2 cells, while increasing the levels of α-smooth muscle actin, fibronectin, collagen I, and collagen III; these changes promoted the transformation of renal tubular epithelial cells to a fibrotic phenotype. An miR-185-5p inhibitor can reverse the fibrotic phenotype in renal tubular epithelial cells. In a unilateral ureteral obstruction model, the inhibition of miR-185-5p expression alleviated tubular atrophy/interstitial fibrosis. Conclusion: Urinary miR-185-5p, a non-invasive biomarker of tubular atrophy/interstitial fibrosis in IgAN, may promote the transformation of renal tubular epithelial cells to a fibrotic phenotype via TJP1.

Comprehensive HRMS Screening and Risk Assessments of Aristolochic Acid Analogues in Asari Radix et Rhizoma and Related Commercial Health Products.

Aristolochic acid analogues (AAAs) are well-known toxins. We performed the first comprehensive screening on AAAs in Asari Radix et Rhizoma (underground part of Asarum heterotropoides Schmidt), the only Aristolochiaceae plant widely used in clinical practice. LC-HRMS revealed 70 trace AAAs using polygonal mass defect filtering and precursor ion list strategies, 38 of which were newly discovered in A. heterotropoides. UHPLC-QTrap-MS/MS was then utilized for quantitative/semiquantitative analysis of 26 abundant compounds. Seventeen AAAs were detected from 91 batches of A. heterotropoides and 20 AAAs from 166 consumable products. For 141 Asari-containing proprietary products, aristolactam I and aristolactam II-glucoside exhibited the widest distribution, present in 98% products. AA IVa was the most abundant, detected in 91%. Notably, 60% of the products contained AA I (0.03-0.79 ppm). The safety was assessed using linear extrapolation, permitted daily exposure, cumulative amount, and the margin of exposure. It is recommended that AA I content be limited to 3 ppm.

Assessment of the causal relationship between gut microbiota and cardiovascular diseases: a bidirectional Mendelian randomization analysis.

BACKGROUND: Previous studies have shown an association between gut microbiota and cardiovascular diseases (CVDs). However, the underlying causal relationship remains unclear. This study aims to elucidate the causal relationship between gut microbiota and CVDs and to explore the pathogenic role of gut microbiota in CVDs. METHODS: In this two-sample Mendelian randomization study, we used genetic instruments from publicly available genome-wide association studies, including single-nucleotide polymorphisms (SNPs) associated with gut microbiota (n = 14,306) and CVDs (n = 2,207,591). We employed multiple statistical analysis methods, including inverse variance weighting, MR Egger, weighted median, MR pleiotropic residuals and outliers, and the leave-one-out method, to estimate the causal relationship between gut microbiota and CVDs. Additionally, we conducted multiple analyses to assess horizontal pleiotropy and heterogeneity. RESULTS: GWAS summary data were available from a pooled sample of 2,221,897 adult and adolescent participants. Our findings indicated that specific gut microbiota had either protective or detrimental effects on CVDs. Notably, Howardella (OR = 0.955, 95% CI: 0.913-0.999, P = .05), Intestinibacter (OR = 0.908, 95% CI:0.831-0.993, P = .03), Lachnospiraceae (NK4A136 group) (OR = 0.904, 95% CI:0.841-0.973, P = .007), Turicibacter (OR = 0.904, 95% CI: 0.838-0.976, P = .01), Holdemania (OR, 0.898; 95% CI: 0.810-0.995, P = .04) and Odoribacter (OR, 0.835; 95% CI: 0.710-0.993, P = .04) exhibited a protective causal effect on atrial fibrillation, while other microbiota had adverse causal effects. Similar effects were observed with respect to coronary artery disease, myocardial infarction, ischemic stroke, and hypertension. Furthermore, reversed Mendelian randomization analyses revealed that atrial fibrillation and ischemic stroke had causal effects on certain gut microbiotas. CONCLUSION: Our study underscored the importance of gut microbiota in the context of CVDs and lent support to the hypothesis that increasing the abundance of probiotics or decreasing the abundance of harmful bacterial populations may offer protection against specific CVDs. Nevertheless, further research is essential to translate these findings into clinical practice.

Proteomic analysis of multiple organ dysfunction induced by rhabdomyolysis.

Rhabdomyolysis (RM) leads to dysfunction in the core organs of kidney, lung and heart, which is an important reason for the high mortality and disability rate of this disease. However, there is a lack of systematic research on the characteristics of rhabdomyolysis-induced injury in various organs and the underlying pathogenetic mechanisms, and especially the interaction between organs. We established a rhabdomyolysis model, observed the structural and functional changes in kidney, heart, and lung. It is observed that rhabdomyolysis results in significant damage in kidney, lung and heart of rats, among which the pathological damage of kidney and lung was significant, and of heart was relatively light. Meanwhile, we analyzed the differentially expressed proteins (DEPs) in the kidney, heart and lung between the RM group and the sham group based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). In our study, Serpina3n was significantly up-regulated in the kidney, heart and lung. Serpina3n is a secreted protein and specifically inhibits a variety of proteases and participates in multiple physiological processes such as complement activation, inflammatory responses, apoptosis pathways, and extracellular matrix metabolism. It is inferred that Serpina3n may play an important role in multiple organ damage caused by rhabdomyolysis and could be used as a potential biomarker. This study comprehensively describes the functional and structural changes of kidney, heart and lung in rats after rhabdomyolysis, analyzes the DEPs of kidney, heart and lung, and determines the key role of Serpina3n in multiple organ injury caused by rhabdomyolysis. SIGNIFICANCE: This study comprehensively describes the functional and structural changes of kidney, heart and lung in rats after rhabdomyolysis, analyzes the DEPs of kidney, heart and lung, and determines the key role of Serpina3n in multiple organ injury caused by rhabdomyolysis.

Local Renal Treatments for Acute Kidney Injury: A Review of Current Progress and Future Translational Opportunities.

Acute kidney injury (AKI) constitutes a significant public health concern, with limited therapeutic options to mitigate injury or expedite recovery. A novel therapeutic approach, local renal treatment, encompassing pharmacotherapy and surgical interventions, has exhibited positive outcomes in AKI management. Peri-renal administration, employing various delivery routes, such as the renal artery, intrarenal, and subcapsular sites, has demonstrated superiority over peripheral intravenous infusion. This review evaluates different drug delivery methods, analyzing their benefits and limitations, and proposes potential improvements. Renal decapsulation, particularly with the availability of minimally invasive techniques, emerges as an effective procedure warranting renewed consideration for AKI treatment. The potential synergistic effects of combined drug delivery and renal decapsulation could further advance AKI therapies. Clinical studies have already begun to leverage the benefits of local renal treatments, and with ongoing technological advancements, these modalities are expected to increasingly outperform systemic intravenous therapy.

Role of amorphous engineering and cerium doping in NiFe oxyhydroxide for electrocatalytic water oxidation.

Amorphous engineering and atomistic doping provide an effective way to improve the catalytic activity in the oxygen evolution reaction (OER) of transition metal layered double hydroxides. Herein, Cerium (Ce) was introduced into NiFe-based oxyhydroxide using a modified aqueous sol-gel procedure. Ce as an electron acceptor promoted the coupling oxidation of Ni2+/3+ in NiFe oxyhydroxide, and the activated oxyhydroxide showed excellent catalytic activity in OER. The amorphous NiFeCe oxyhydroxide electrocatalyst demonstrated great modified OER catalytic activity under alkaline conditions and excellent cyclic stability, with an overpotential of only 284 mV at 50 mA cm-2, which was significantly better than amorphous NiFe oxyhydroxide and crystalline NiFeCe oxyhydroxide. Theoretical investigations further indicated that the overpotential of the rate-determining step (*OOH deprotonation) decreased from 0.66 to 0.41 V after Ce doping and strong electron interaction, effectively reducing the dependence of proton activity in the solution of OER, and optimizing the adsorption/desorption process of related oxygen-containing species in the reaction. This work also provides a good reference for optimizing OER activity by using rare-earth-metal induced electronic regulation strategies.