Dissolved organic matter characteristics linked to bacterial community succession and nitrogen removal performance in woodchip bioreactors.

Woodchip bioreactors are an eco-friendly technology for removing nitrogen (N) pollution. However, there needs to be more clarity regarding the dissolved organic matter (DOM) characteristics and bacterial community succession mechanisms and their association with the N removal performance of bioreactors. The laboratory woodchip bioreactors were continuously operated for 360 days under three influent N level treatments, and the results showed that the average removal rate of TN was 45.80 g N/(m3·day) when the influent N level was 100 mg N/L, which was better than 10 mg N/L and 50 mg N/L. Dynamic succession of bacterial communities in response to influent N levels and DOM characteristics was an important driver of TN removal rates. Medium to high N levels enriched a copiotroph bacterial module (Module 1) detected by network analysis, including Phenylobacterium, Xanthobacteraceae, Burkholderiaceae, Pseudomonas, and Magnetospirillaceae, carrying N-cycle related genes for denitrification and ammonia assimilation by the rapid consumption of DOM. Such a process can increase carbon limitation to stimulate local organic carbon decomposition to enrich oligotrophs with fewer N-cycle potentials (Module 2). Together, this study reveals that the compositional change of DOM and bacterial community succession are closely related to N removal performance, providing an ecological basis for developing techniques for N-rich effluent treatment.

Cultivating Innovative Employees: The Influence of Regulatory Focus and Institutional Empowerment.

The relationship between regulatory focus, a pivotal trait, and innovative behavior has been long recognized, with previous scholars often emphasizing the reluctance of individuals possessing a prevention focus to engage in innovation due to their risk-averse tendencies. This study introduces a research model proposing that the relationship between promotion focus, prevention focus, and innovation behavior, is positively mediated by knowledge sharing. Additionally, institutional empowerment is posited as a moderating variable that enhances the positive relationship between regulatory focus and knowledge sharing. Empirical investigation of a moderated-mediation model reveals that the impact of regulatory focus on innovation behaviors is mediated by knowledge sharing, with this mediation being more pronounced under conditions of elevated perceptions of institutional empowerment. This research significantly advances the understanding of regulatory focus and its implications for innovation behavior. In addition, it highlights the significance of institutional empowerment as a boundary condition that encourages individuals with diverse regulatory focus to expand their behavioral boundaries. It specifically emphasizes the managerial capacity to leverage the needs and motivations of individuals with a pronounced prevention focus through institutional empowerment, resulting in transformative outcomes even in unfavorable situations.

m6A-mediated HDAC9 upregulation promotes particulate matter-induced airway inflammation via epigenetic control of DUSP9-MAPK axis and acts as an inhaled nanotherapeutic target.

Exposure to particulate matter (PM) can cause airway inflammation and worsen various airway diseases. However, the underlying molecular mechanism by which PM triggers airway inflammation has not been completely elucidated, and effective interventions are lacking. Our study revealed that PM exposure increased the expression of histone deacetylase 9 (HDAC9) in human bronchial epithelial cells and mouse airway epithelium through the METTL3/m6A methylation/IGF2BP3 pathway. Functional assays showed that HDAC9 upregulation promoted PM-induced airway inflammation and activation of MAPK signaling pathway in vitro and in vivo. Mechanistically, HDAC9 modulated the deacetylation of histone 4 acetylation at K12 (H4K12) in the promoter region of dual specificity phosphatase 9 (DUSP9) to repress the expression of DUSP9 and resulting in the activation of MAPK signaling pathway, thereby promoting PM-induced airway inflammation. Additionally, HDAC9 bound to MEF2A to weaken its anti-inflammatory effect on PM-induced airway inflammation. Then, we developed a novel inhaled lipid nanoparticle system for delivering HDAC9 siRNA to the airway, offering an effective treatment for PM-induced airway inflammation. Collectively, we elucidated the crucial regulatory mechanism of HDAC9 in PM-induced airway inflammation and introduced an inhaled therapeutic approach targeting HDAC9. These findings contribute to alleviating the burden of various airway diseases caused by PM exposure.

Organocatalytic enantioselective construction of Si-stereocenters: recent advances and perspectives.

Silicon-stereogenic chiral organosilanes have found increasing applications in synthetic chemistry, medicinal chemistry, and materials science. In this context, various asymmetric catalytic methods have been established for the diverse synthesis of silicon-stereogenic silanes. In particular, asymmetric organocatalysis is emerging as an important and complementary synthetic tool for the enantioselective construction of silicon-stereocenters, along with the rapid development of chiral-metal catalyzed protocols. Its advent provides a powerful platform to achieve functionalized silicon-stereogenic organosilanes with structural diversity, and should lead to great development in chiral organosilicon chemistry. In this Tutorial Review, we highlight these latest achievements from two aspects: desymmetrizations of prochiral tetraorganosilanes and dynamic kinetic asymmetric transformations of racemic organosilanes by employing five organocatalytic activation modes. The advantages, limitations and synthetic value of each protocol, as well as the synthetic opportunities still open for further exploration, are also discussed.

Specialized Metabolites From the Husks of Rice Oryza sativa L. and Their Biological Activities.

Rice (Oryza sativa L.) husk harbors a substantial proportion of biological metabolites, as one of the most plentiful agriculture by-products in rice milling process, rice husk remains poorly utilized. As a continuing search for potential bioactive molecules from the husk of rice, a totally of twelve conponents (1-12), including six sterol ferulates (1-6), one flavonoid (7), one dipeptide (8), and four phenylpropanoid derivatives (9-12) were obtained. All the chemical structures were elucidated based on comprehensive spectroscopic data. Wherein, compounds 1 and 2 were yield as previous undescribed metabolites, and the comprehensive NMR data for compounds 3 and 4 were first presented in its entirety. Motivated by the similarity of the structural motifs of components 1-6 to that of reported sterol ferulates, the antioxidant and anti-inflammatory effects for compounds 1-6 were evaluated in vitro. Among them, compounds 5/6 had a significant antioxidant activity compare to that of vitamin E in both DPPH and reducing power assay up to the concentration 40 µg/ml; while compounds 1 and 2 exhibited weak suppressive effect on the production of nitric oxide, with the IC50 values of 53.27 ± 1.37 µM.

Bioenzymatic detoxification of mycotoxins.

Mycotoxins are secondary metabolites produced during the growth, storage, and transportation of crops contaminated by fungi and are physiologically toxic to humans and animals. Aflatoxin, zearalenone, deoxynivalenol, ochratoxin, patulin, and fumonisin are the most common mycotoxins and can cause liver and nervous system damage, immune system suppression, and produce carcinogenic effects in humans and animals that have consumed contaminated food. Physical, chemical, and biological methods are generally used to detoxify mycotoxins. Although physical methods, such as heat treatment, irradiation, and adsorption, are fast and simple, they have associated problems including incomplete detoxification, limited applicability, and cause changes in food characteristics (e.g., nutritive value, organoleptic properties, and palatability). Chemical detoxification methods, such as ammonification, ozonation, and peroxidation, pollute the environment and produce food safety risks. In contrast, bioenzymatic methods are advantageous as they achieve selective detoxification and are environmentally friendly and reusable; thus, these methods are the most promising options for the detoxification of mycotoxins. This paper reviews recent research progress on common mycotoxins and the enzymatic principles and mechanisms for their detoxification, analyzes the toxicity of the degradation products and describes the challenges faced by researchers in carrying out enzymatic detoxification. In addition, the application of enzymatic detoxification in food and feed is discussed and future directions for the development of enzymatic detoxification methods are proposed for future in-depth study of enzymatic detoxification methods.

Survey of mosquito species in intensive pig farms in Hunan province, China.

Mosquitoes (Diptera: Culicidae) are one of the most studied groups of arthropods worldwide due to their high transmission capacity for pathogens, including viruses and parasites. During June to October 2022, the prevalence of mosquito species in 12 intensive pig farms from 12 representative administrative regions in Hunan province of China was investigated using traps with ultraviolet light. All collected mosquitoes were counted and identified to species according to morphological and molecular methods. A total of 4,443 mosquito specimens were collected in the pig farms, and they represented one family, four genera and nine species. Culex pipiens pipiens (24%) was the most common mosquito species, followed by Armigeres subalbatus (23.4%) and Culex tritaeniorhynchus (20.6%). Phylogenetic analyses based on mitochondrial cox1 sequences revealed all mosquito species from present study grouping into distinct monophyletic groups corresponding to nine known mosquito species with strongly supported. The results of the present investigation have implications for the ongoing control of mosquito infestation in pig farms in Hunan province, China. This is the first report of mosquito populations in intensive pig farms in Hunan province, China.

Proteomics analysis of immune response-related proteins in Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP).

The objective is to characterize differentially expressed proteins (DEPs) in Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) through high-throughput analysis. Sera from 11 healthy controls (HCs), 21 GBS and 19 CIDP patients were subjected to Olink Proteomics Analysis. In the comparison between CIDP and GBS groups, up-regulation of ITM2A and down-regulation of NTF4 were observed. Comparing GBS with HCs revealed 18 up-regulated and 4 down-regulated proteins. Comparing CIDP with the HCs identified 15 up-regulated and 4 down-regulated proteins. Additionally, the correlation between clinical characteristics and DEPs were uncovered. In conclusion, the DEPs have significant potential to advance our understanding of the pathogenesis in these debilitating neurological disorders.

Tmem39b promotes tumor progression and sorafenib resistance by inhibiting ferroptosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) poses a significant threat to human health. Resistance to sorafenib in the chemotherapy of HCC is a common and significant issue that profoundly impacts clinical treatment. While several members of the transmembrane (TMEM) protein family have been implicated in the occurrence and progression of HCC, the association between TMEM39b and HCC remains unexplored. This study revealed a significant overexpression of TMEM39b in HCC, which correlated with a poor prognosis. Subsequent investigation revealed that RAS-selective lethal 3 (RSL3) induced pronounced ferroptosis in HCC, and knocking down the expression of TMEM39b significantly decreased its severity. Similarly, following the induction of ferroptosis in HCC by sorafenib, knocking down the expression of TMEM39b also decreased the severity of ferroptosis, enhancing HCC tolerance to sorafenib. In conclusion, we propose that TMEM39b promotes tumor progression and resistance to sorafenib by inhibiting ferroptosis in HCC.

Development of the CRISPR-Cas12a system for editing of Pseudomonas aeruginosa phages.

Pseudomonas aeruginosa is a common opportunistic pathogen. The potential efficacy of phage therapy has attracted the attention of researchers, but efficient gene-editing tools are lacking, limiting the study of their biological properties. Here, we designed a type V CRISPR-Cas12a system for the gene editing of P. aeruginosa phages. We first evaluated the active cutting function of the CRISPR-Cas12a system in vitro and discovered that it had a higher gene-cutting efficiency than the type II CRISPR-Cas9 system in three different P. aeruginosa phages. We also demonstrated the system's ability to precisely edit genes in Escherichia coli phages, Salmonella phages, and P. aeruginosa phages. Using the aforementioned strategies, non-essential P. aeruginosa phage genes can be efficiently deleted, resulting in a reduction of up to 5,215 bp (7.05%). Our study has provided a rapid, efficient, and time-saving tool that accelerates progress in phage engineering.

Long-term Durability Between Parent and Child Patient Reported Outcomes in Eosinophilic Esophagitis.

BACKGROUND: Because young children cannot self-report symptoms, there is a need for parent surrogate reports. While early work suggested parent child alignment for eosinophil esophagitis (EoE) patient reported outcomes (PROs), the longitudinal alignment is unclear. OBJECTIVE: To assess the agreement and longitudinal stability of PROs between children with EoE and their parents. METHODS: 292 parent-child respondents completed 723 completed questionnaires over 5 years in an observational trial in the Consortium of Eosinophilic Gastrointestinal Disease Researchers. The change in and agreement between parent and child Pediatric Eosinophilic Esophagitis Symptom Score version 2 (PEESSv2.0) and Pediatric Quality of Life Eosinophilic Esophagitis Module (PedsQL-EoE) PROs over time were assessed using Pearson correlation and Bland-Altman analyses. Clinical factors influencing PROs and their agreement were evaluated using linear mixed models. RESULTS: The cohort had a median disease duration equalling 3.7 years and was predominantly male (73.6%) and white (85.3%). Child and parent PEESSv2.0 response groups were identified and were stable over time. There was strong correlation between child and parent report (PEESSv2.0 0.83, PedsQL-EoE 0.74) with minimal pairwise differences for symptoms. Longitudinally, parent-reported PedsQL-EoE scores were stable (p ≥ 0.32), whereas child-reported PedsQL-EoE scores improved (p = 0.026). A larger difference in parent and child PedsQL-EoE reports was associated with younger age (p < 0.001) and differences were driven by psychosocial PRO domains. CONCLUSION: There is strong longitudinal alignment between child and parent report using EoE PROs. These data provide evidence that parent report is a stable proxy for objective EoE symptoms in their children.

Losartan Treatment Reduces Esophageal Eosinophilic Inflammation in a Subset of Eosinophilic Esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven esophageal disorder. Connective tissue disorders (CTDs) and esophageal connective tissue alterations are associated with EoE, therefore angiotensin II type 1 receptor (AT1R) blockade with losartan, an accepted CTD treatment, is a potential EoE treatment. OBJECTIVE: We evaluated losartan's effects on esophageal pathology, symptoms, and safety in patients with EoE with and without a CTD in an open-label, non-placebo controlled multi-site study. METHODS: Fifteen participants, 5-23 years old, with EoE underwent treatment with a per-protocol titrated doses of losartan in an open-label, 16-week pilot trial. Losartan was added to standard-of-care therapy and 14 patients completed the study. Eosinophil counts served as the primary endpoint, while EoE Histology Scoring System (EoEHSS), Endoscopic Reference Scores (EREFS), EoE Diagnostic Panel (EDP), and patient-reported outcomes (PROs) were also assessed. RESULTS: Esophageal eosinophilia was not reduced following losartan. The peak eosinophil count was not reduced for the proximal (median (IQR): -3 (-22 to 3), p = 0.49) and distal esophagus (median (IQR): -18 (-39 to -1), p = 0.23). There were no differences in losartan response in EoE with or without CTD (n = 7 and 8, respectively). Regardless, a small subset of 4 participants resolved esophageal eosinophilia with concomitant reduction in EoEHSS and EREFS scores. Across all subjects, the Pediatric EoE Symptom Score and Pediatric Quality of Life Inventory EoE Module and EDP improved following losartan (p < 0.05). CONCLUSION: Losartan treatment associated with improved PRO scores and EDP biomarkers albeit without reducing esophageal eosinophilia overall. A subset of patients demonstrated improved histopathological and endoscopic features which could not be tied to a specific feature which could predict response to treatment.

Chemoenzymatic Synthesis of Fluorinated Mycocyclosin Enabled by the Engineered Cytochrome P450-Catalyzed Biaryl Coupling Reaction.

Installing fluorine atoms onto natural products holds great promise for the generation of fluorinated molecules with improved or novel pharmacological properties. The enzymatic oxidative carbon-carbon coupling reaction represents a straightforward strategy for synthesizing biaryl architectures, but the exploration of this method for producing fluorine-substituted derivatives of natural products remains elusive. Here, in this study, we report the protein engineering of cytochrome P450 from Mycobacterium tuberculosis (MtCYP121) for the construction of a series of new-to-nature fluorine-substituted Mycocyclosin derivatives. This protocol takes advantage of a "hybrid" chemoenzymatic procedure consisting of tyrosine phenol lyase-catalyzed fluorotyrosine preparation from commercially available fluorophenols, intermolecular chemical condensation to give cyclodityrosines, and an engineered MtCYP121-catalyzed intramolecular biphenol coupling reaction to complete the strained macrocyclic structure. Computational mechanistic studies reveal that MtCYP121 employs Cpd I to abstract a hydrogen atom from the proximal phenolic hydroxyl group of the substrate to trigger the reaction. Then, conformational change makes the two phenolic hydroxyl groups close enough to undergo intramolecular hydrogen atom transfer with the assistance of a pocket water molecule. The final diradical coupling process completes the intramolecular C-C bond formation. The efficiency of the biaryl coupling reaction was found to be influenced by various fluorine substitutions, primarily due to the presence of distinct binding conformations.

MiR362-3p Alleviates Osteosarcoma by Regulating the IL6ST/JAK2/STAT3 Pathway in Vivo and in Vitro.

Objectives: To investigate the effects and the related signaling pathway of miR-362-3p on OS. Methods: The bioinformatics analysis approaches were employed to investigate the target pathway of miR-362-3p. After the 143B and U2OS cells and nu/nu male mice were randomly divided into blank control (BC) group, normal control (NC) group, and overexpression group (OG), the CCK-8, EdU staining, wound healing assay, Transwell assay, and TUNEL staining were adopted to respectively determine the effects of overexpressed miR-362-3p on the cell viability, proliferation, migration, invasion, and apoptosis of 143B and U2OS cells in vitro, tumor area assay and hematoxylin and eosin staining were employed to respectively determine the effects of overexpressed miR-362-3p on the growth and pathological injury of OS tissue in vivo. The qRT-PCR, Western blot, and immunohistochemical staining were applied to respectively investigate the effects of overexpressed miR-362-3p on the IL6ST/JAK2/STAT3 pathway in OS in vivo and in vitro. Results: The bioinformatics analysis approaches combined qRT-PCR indicated that the IL6ST/JAK2/STAT3 is one of the target pathways of miR-362-3p. Compared with NC, the cell viability, proliferation, migration, and invasion of 143B and U2OS cells were dramatically (P < 0.01) inhibited but the apoptosis was prominently (P <0 .0001) promoted in OG. Compared with NC, the growth of OS tissue was significantly (P < 0.05) suppressed and the pathological injury of OS tissue was substantially aggravated in OG. The gene expression levels of IL6ST, JAK2, and STAT3 and the protein expression levels of IL6ST, JAK2, p-JAK2, STAT3, and p-STAT3 in 143B and U2OS cells were memorably (P < 0.0001) lower in OG than those in NC. In addition, the positively stained areas of proteins of IL6ST, JAK2, p-JAK2, STAT3, and p-STAT3 of OS tissue in OG were markedly (P < 0.01) reduced compared with those in NC. Conclusion: The overexpression of miR362-3p alleviates OS by inhibiting the IL6ST/JAK2/STAT3 pathway in vivo and in vitro.

Application of Natural Antibacterial Plants in the Extraction of Uranium from Seawater.

Marine biofouling directly affects the performance and efficiency of uranium (U(VI)) extraction from seawater. Compared to traditional chemical methods, natural plant extracts are generally biodegradable and nontoxic, making them an environmentally friendly alternative to synthetic chemicals in solving the marine biofouling problem. The effectiveness of natural antibacterial plants (i.e., pine needle, peppermint, Acorus gramineus Soland, Cacumen platycladi, and wormwood) in solving the marine biofouling problem was evaluated in this work. Experimental results showed that natural antibacterial plants could kill Vibrio alginolyticus in solution and effectively solve the marine biofouling problem of U(VI) extraction. To improve the adsorption capacity of natural plants for U(VI) in seawater, poly(vinylphosphonic acid) (PVPA) was modified on natural antibacterial plant surfaces by irradiation grafting technology. PVPA and natural antibacterial plants work as active sites and base materials for the U(VI) extraction material, respectively. The recovery performance of PVPA/pine needle for U(VI) was preliminarily studied. Results show that the adsorption of U(VI) on PVPA/pine needle follows pseudo-second-order and Langmuir models, and the maximum adsorption capacity is 111 mg/g at 298 K and pH 8.2.

The HD-ZIP IV transcription factor GLABRA2 acts as an activator for proanthocyanidin biosynthesis in Medicago truncatula seed coat.

Proanthocyanidins (PAs), a group of flavonoids, are found in leaves, flowers, fruits, and seed coats of many plant species. PAs are primarily composed of epicatechin units in the seed coats of the model legume species, Medicago truncatula. It can be synthesized from two separate pathways, the leucoanthocyanidin reductase (MtLAR) pathway and the anthocyanidin synthase (MtANS) pathway, which produce epicatechin through anthocyanidin reductase (MtANR). These pathways are mainly controlled by the MYB-bHLH-WD40 (MBW) ternary complex. Here, we characterize a class IV homeodomain-leucine zipper (HD-ZIP IV) transcription factor, GLABRA2 (MtGL2), which contributes to PA biosynthesis in the seed coat of M. truncatula. Null mutation of MtGL2 results in dark brown seed coat, which is accompanied by reduced PAs accumulation and increased anthocyanins content. The MtGL2 gene is predominantly expressed in the seed coat during the early stages of seed development. Genetic and molecular analyses indicate that MtGL2 positively regulates PA biosynthesis by directly activating the expression of MtANR. Additionally, our results show that MtGL2 is strongly induced by the MBW activator complexes that are involved in PA biosynthesis. Taken together, our results suggest that MtGL2 acts as a novel positive regulator in PA biosynthesis, expanding the regulatory network and providing insights for genetic engineering of PA production.

Evaluation of the FPMC respiratory panel for detection of respiratory tract pathogens in nasopharyngeal swab and sputum specimens.

OBJECTIVES: The performance of the new Respiratory Pathogen panel (fluorescent probe melting curve, FPMC) for the qualitative detection of 12 organisms (chlamydia pneumoniae, mycoplasma pneumoniae, adenovirus, influenza A virus, influenza B virus, parainfluenza virus, rhinovirus, etc.) was assessed. METHODS: Prospectively collected nasopharyngeal swab (NPS) and sputum specimens (n = 635) were detected by using the FPMC panel, with the Sanger sequencing method as the comparative method. RESULTS: The overall percent concordance between the FPMC analysis method and the Sanger sequencing method was 100% and 99.66% for NPS and sputum specimens, respectively. The FPMC testified an overall positive percent concordance of 100% for both NPS and sputum specimens. The FPMC analysis method also testified an overall negative percent concordance of 100% and 99.38% for NPS and sputum specimens, respectively. CONCLUSIONS: The FPMC analysis method is a stable and accurate assay for rapid, comprehensive detecting for respiratory pathogens.

The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development.

Malformations of cortical development (MCD) are a group of developmental disorders characterized by abnormal cortical structures caused by genetic or harmful environmental factors. Many kinds of MCD are caused by genetic variation. MCD is the common cause of intellectual disability and intractable epilepsy. With rapid advances in imaging and sequencing technologies, the diagnostic rate of MCD has been increasing, and many potential genes causing MCD have been successively identified. However, the high genetic heterogeneity of MCD makes it challenging to understand the molecular pathogenesis of MCD and to identify effective targeted drugs. Thus, in this review, we outline important events of cortical development. Then we illustrate the progress of molecular genetic studies about MCD focusing on the PI3K/PTEN/AKT/mTOR pathway. Finally, we briefly discuss the diagnostic methods, disease models, and therapeutic strategies for MCD. The information will facilitate further research on MCD. Understanding the role of the PI3K/PTEN/AKT/mTOR pathway in MCD could lead to a novel strategy for treating MCD-related diseases.

Self-Sulfhydrated, Nitro-Fixed Albumin Nanoparticles as a Potent Therapeutic Agent for the Treatment of Acute Liver Injury.

Exogenous polysulfhydryls (R-SH) supplementation and nitric oxide (NO) gas molecules delivery provide essential antioxidant buffering pool components and anti-inflammatory species in cellular defense against injury, respectively. Herein, the intermolecular disulfide bonds in bovine serum albumin (BSA) molecules were reductively cleaved under native and mild conditions to expose multiple sulfhydryl groups (BSA-SH), then sulfhydryl-nitrosylated (R-SNO), and nanoprecipitated to form injectable self-sulfhydrated, nitro-fixed albumin nanoparticles (BSA-SNO NPs), allowing albumin to act as a NO donor reservoir and multiple sulfhydryl group transporter while also preventing unfavorable oxidation and self-cross-linking of polysulfhydryl groups. In two mouse models of ischemia/reperfusion-induced and endotoxin-induced acute liver injury (ALI), a single low dosage of BSA-SNO NPs (S-nitrosothiols: 4 µmol·kg-1) effectively attenuated oxidative stress and systemic inflammation cascades in the upstream pathophysiology of disease progression, thus rescuing dying hepatocytes, regulating host defense, repairing microcirculation, and restoring liver function. By mechanistically upregulating the antioxidative signaling pathway (Nrf-2/HO-1/NOQ1) and inhibiting the inflammatory cytokine storm (NF-κB/p-IκBα/TNF-α/IL-ß), BSA-SNO NPs blocked the initiation of the mitochondrial apoptotic signaling pathway (Cyto C/Bcl-2 family/caspase-3) and downregulated the cell pyroptosis pathway (NLRP3/ASC/IL-1ß), resulting in an increased survival rate from 26.7 to 73.3%. This self-sulfhydrated, nitro-fixed functionalized BSA nanoformulation proposes a potential drug-free treatment strategy for ALI.

Preadmission metformin use increased the incidence of hyperlactatemia at admission and 30-day in-hospital mortality among T2D patients with heart disease at high risk of hypoxia.

BACKGROUND: Surprisingly, despite the high prevalence of metformin use in type 2 diabetes (T2D) patients with heart disease, limited safety data is available regarding metformin use in patients with acute and critical heart disease. METHODS: In this single-center retrospective study, patients admitted to the cardiology department for heart failure (HF) or acute coronary syndrome (ACS) between December 2013 and December 2021 and who underwent arterial blood gas analysis at admission with an estimated glomerular clearance rate of ≥45 ml/min/1.73 m2 were identified. The incidences of hyperlactatemia, acidosis, and 30-day in-hospital mortality were compared between preadmission metformin users and nonusers. RESULTS: Of 526 admissions, 193/193 metformin users/nonusers were selected in a propensity score-matched model. Metformin users had greater lactate levels (2.55 ± 2.07 mmol/l vs. 2.00 ± 1.80 mmol/l P < 0.01), a greater incidence of hyperlactatemia [odds ratio (OR) = 2.55; 95% confidence interval (CI), 1.63-3.98; P < 0.01] and acidosis (OR = 1.78; 95% CI, 1.00-3.16; P < 0.05) at admission and a greater incidence of in-hospital mortality (OR = 3.83; 95% CI, 1.05-13.94; P < 0.05), especially those with HF/acute myocardial infarction, elderly age, or without preadmission insulin use. CONCLUSIONS: Our results suggest that, compared to metformin nonusers, preadmission use of metformin may be associated with a greater incidence of hyperlactatemia and acidosis at admission and greater 30-day in-hospital mortality among T2D patients with HF or ACS at high risk of hypoxia, particularly those without preadmission insulin use. The safety of metformin in this population needs to be confirmed in prospective controlled trials.