Risk factors for acute kidney injury in preterm neonates after noncardiac surgery: a single-center retrospective cohort study.

Postoperative acute kidney injury (AKI) is a common complication that is associated with chronic kidney disease, early postsurgical mortality, and prolonged hospital stays. Preterm neonates who undergo surgery are at risk factors for AKI due to underdeveloped kidneys. To date, little is known about the incidence and perioperative risk factors for AKI in preterm neonates undergoing noncardiac surgery. Preterm neonates who underwent noncardiac surgery between January May 1, 2020, and February 28, 2023, were enrolled in the trial according to the inclusion criteria. Both multivariable and logistic regression analyses were used to analyze the associations between characteristic data and AKI. In total, 106 preterm neonates met the inclusion criteria, and 25 preterm neonates (23.6%) developed postoperative AKI. Multivariate analysis revealed that the factors associated with AKI were gestational age < 32 weeks [OR: 4.88; 95% CI (1.23-19.42)], preoperative sepsis [OR: 3.98; 95% CI (1.29-12.28)], and intraoperative hypotension [OR: 3.75; 95% CI (1.26-11.15)]. Preterm neonates who developed AKI were more likely to have longer hospital length of stays (38 [18,69] days vs. 21[12,46]) and higher medical costs (93,181.6 [620450.0,173,219.0] ï¿¥ vs. 58,134.6 [31015.1,97,224,1) ï¿¥ than neonates who did not develop AKI. Preterm neonates who underwent noncardiac surgery had a high incidence of AKI. Independent risk factors for AKI in preterm neonates who underwent noncardiac surgery were low gestational age, preoperative sepsis, and intraoperative hypotension. Preterm neonates who developed AKI were more likely to have longer hospital stays and higher medical costs.

Integrative catalytic pairs for efficient multi-intermediate catalysis.

Single-atom catalysts (SACs) have attracted considerable research interest owing to their combined merits of homogeneous and heterogeneous catalysts. However, the uniform and isolated active sites of SACs fall short in catalysing complex chemical processes that simultaneously involve multiple intermediates. In this Review, we highlight an emerging class of catalysts with adjacent binary active centres, which is called integrative catalytic pairs (ICPs), showing not only atomic-scale site-to-site electronic interactions but also synergistic catalytic effects. Compared with SACs or their derivative dual-atom catalysts (DACs), multi-interactive intermediates on ICPs can overcome kinetic barriers, adjust reaction pathways and break the universal linear scaling relations as the smallest active units. Starting from this active-site design principle, each single active atom can be considered as a brick to further build integrative catalytic clusters (ICCs) with desirable configurations, towards trimer or even larger multi-atom units depending on the requirement of a given reaction.

Oxidation Mechanism and Toxicity Evolution of Linalool, a Typical Indoor Volatile Chemical Product.

Linalool, a high-reactivity volatile chemical product (VCP) commonly found in cleaning products and disinfectants, is increasingly recognized as an emerging contaminant, especially in indoor air. Understanding the gas-phase oxidation mechanism of linalool is crucial for assessing its impact on atmospheric chemistry and human health. Using quantum chemical calculations and computational toxicology simulations, we investigated the atmospheric transformation and toxicity evolution of linalool under low and high NO/HO2· levels, representing indoor and outdoor environments. Our findings reveal that linalool can undergo the novel mechanisms involving concerted peroxy (RO2·) and alkoxy radical (RO·) modulated autoxidation, particularly emphasizing the importance of cyclization reactions indoors. This expands the widely known RO2·-dominated H-shift-driven autoxidation and proposes a generalized autoxidation mechanism that leads to the formation of low-volatility secondary organic aerosol (SOA) precursors. Toxicological analysis shows that over half of transformation products (TPs) exhibited higher carcinogenicity and respiratory toxicity compared to linalool. We also propose time-dependent toxic effects of TPs to assess their long-term toxicity. Our results indicate that the strong indoor emission coupled with slow consumption rates lead to significant health risks under an indoor environment. The results highlight complex indoor air chemistry and health concerns regarding persistent toxic products during indoor cleaning, which involves the use of linalool or other VCPs.

The HPE1 RNA-binding protein modulates chloroplast RNA editing to promote photosynthesis under cold stress in Arabidopsis.

Cold stress has severe negative consequences for plant growth and crop yield. Here, we report that an Arabidopsis thaliana mutant that lacks the HPE1 gene, which encodes an RNA-binding protein, maintains higher photosynthetic activity under cold stress, together with higher accumulation of thylakoid proteins. We showed that HPE1 interacts with MORF2 and MORF9 and thereby mediates RNA editing in chloroplasts. Loss of HPE1 function increased the editing efficiency at four RNA editing sites, rpoC-488, ndhB-149, ndhB-746 and matK-706, under cold stress and altered the expression of nuclear photosynthesis-related genes and cold-responsive genes. We propose that HPE1-mediated RNA editing acts as a trigger for retrograde signaling that affects photosynthesis under cold stress.

Anerobic ammonium oxidation coupled to iron(III) reduction catalyzed by a lithoautotrophic nitrate-reducing iron(II) oxidizing enrichment culture.

The last two decades have seen nitrogen/iron-transforming bacteria at the forefront of new biogeochemical discoveries, such as anaerobic ammonium oxidation coupled to ferric iron reduction (feammox) and lithoautotrophic nitrate-reducing ferrous iron-oxidation (NRFeOx). These emerging findings continue to expand our knowledge of the nitrogen/iron cycle in nature, and also highlight the need to re-understand the functional traits of the microorganisms involved. Here, as a proof-of-principle, we report compelling evidence for the capability of a NRFeOx enrichment culture to catalyze the feammox process. Our results demonstrate that the NRFeOx culture predominantly oxidizes NH4+ to nitrogen gas, by reducing both chelated NTA-Fe(III) and poorly soluble Fe(III)-bearing minerals (γ-FeOOH) at pH 4.0 and 8.0, respectively. In the NRFeOx culture, Fe(II)-oxidizing bacteria of Rhodanobacter and Fe(III)-reducing bacteria of unclassified_Acidobacteriota coexisted. Their relative abundances were dynamically regulated by the supplemented iron sources. Metagenomic analysis revealed that the NRFeOx culture contained a complete set of denitrifying genes along with hao genes for ammonium oxidation. Additionally, numerous genes encoding extracellular electron transport-associated proteins or their homologs were identified, which facilitated the reduction of extracellular iron by this culture. More broadly, this work lightens the unexplored potential of specific microbial groups in driving nitrogen transformation through multiple pathways, and highlights the essential role of microbial iron metabolism in the integral biogeochemical nitrogen cycle.

The Microbiological Characteristics of Acinetobacter Baumannii Associated With Early Mortality in Patients With Bloodstream Infection.

Background: Despite rapid deaths resulting from Acinetobacter baumannii bacteremia, the clinical impact of the microbiological characteristics of A baumannii strains on early mortality (EM) is unclear. We aimed to identify the microbiological characteristics of A baumannii strains associated with EM. Methods: Clinical information and isolates from patients with A baumannii bacteremia from January 2015 to December 2021 were collected. EM was defined as death within 3 days of the initial positive blood culture, whereas late mortality meant death within 5-30 days. The microbiological characteristics of A baumannii were analyzed using multilocus sequence typing, polymerase chain reactions, and a Galleria mellonella in vivo infection model. Results: Among 130 patients, 69 (53.1%) died within 30 days and EM occurred in 38 (55.1% of 30-day deaths). Sequence type 191 (ST191) strain was more prevalent in patients with EM than in 30-day survivors (31.6% vs 6.6%). Regarding virulence genes, bfmS was more frequent (92.1% vs 47.5%), whereas bauA was less frequent (13.2% vs 52.5%) in patients with EM than in 30-day survivors. Higher clinical severity, pneumonia, and ST191 infection were identified as independent risk factors for EM. In the G mellonella infection model, ST191, bfmS+, and bauA- isolates showed higher virulence than non-ST191, bfmS-, and bauA+ isolates, respectively. Conclusions: ST191 and bfmS were more frequently found in the EM group. ST191 infection was also an independent risk factor for EM and highly virulent in the in vivo model. Tailored infection control measures based on these characteristics are necessary for A baumannii bacteremia management.

Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial.

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation. Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method. Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed. Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.

A novel prognostic signature related to programmed cell death in osteosarcoma.

Background: Osteosarcoma primarily affects children and adolescents, with current clinical treatments often resulting in poor prognosis. There has been growing evidence linking programmed cell death (PCD) to the occurrence and progression of tumors. This study aims to enhance the accuracy of OS prognosis assessment by identifying PCD-related prognostic risk genes, constructing a PCD-based OS prognostic risk model, and characterizing the function of genes within this model. Method: We retrieved osteosarcoma patient samples from TARGET and GEO databases, and manually curated literature to summarize 15 forms of programmed cell death. We collated 1621 PCD genes from literature sources as well as databases such as KEGG and GSEA. To construct our model, we integrated ten machine learning methods including Enet, Ridge, RSF, CoxBoost, plsRcox, survivalSVM, Lasso, SuperPC, StepCox, and GBM. The optimal model was chosen based on the average C-index, and named Osteosarcoma Programmed Cell Death Score (OS-PCDS). To validate the predictive performance of our model across different datasets, we employed three independent GEO validation sets. Moreover, we assessed mRNA and protein expression levels of the genes included in our model, and investigated their impact on proliferation, migration, and apoptosis of osteosarcoma cells by gene knockdown experiments. Result: In our extensive analysis, we identified 30 prognostic risk genes associated with programmed cell death (PCD) in osteosarcoma (OS). To assess the predictive power of these genes, we computed the C-index for various combinations. The model that employed the random survival forest (RSF) algorithm demonstrated superior predictive performance, significantly outperforming traditional approaches. This optimal model included five key genes: MTM1, MLH1, CLTCL1, EDIL3, and SQLE. To validate the relevance of these genes, we analyzed their mRNA and protein expression levels, revealing significant disparities between osteosarcoma cells and normal tissue cells. Specifically, the expression levels of these genes were markedly altered in OS cells, suggesting their critical role in tumor progression. Further functional validation was performed through gene knockdown experiments in U2OS cells. Knockdown of three of these genes-CLTCL1, EDIL3, and SQLE-resulted in substantial changes in proliferation rate, migration capacity, and apoptosis rate of osteosarcoma cells. These findings underscore the pivotal roles of these genes in the pathophysiology of osteosarcoma and highlight their potential as therapeutic targets. Conclusion: The five genes constituting the OS-PCDS model-CLTCL1, MTM1, MLH1, EDIL3, and SQLE-were found to significantly impact the proliferation, migration, and apoptosis of osteosarcoma cells, highlighting their potential as key prognostic markers and therapeutic targets. OS-PCDS enables accurate evaluation of the prognosis in patients with osteosarcoma.

Iodine(III)-Mediated Trifluoroacetylation of a C(sp2)-H or C(sp)-H Bond with Masked Trifluoroacyl Reagents.

A novel strategy for incorporating a trifluoroacetyl functionality into a range of structurally varied unsaturated bonds was developed by using PhI(OCOMe)2 as an oxidant with a masked trifluoroacyl reagent as a trifluoroacetyl radical precursor. The oxidative decarboxylation of the masked trifluoroacyl precursor followed by a tandem radical process provides versatile access to 5-exo-trig cyclization of N-arylacrylamides, direct C(sp2)-H trifluoroacetylation of quinolines, isoquinoline, 2H-indazole, and quinoxalin-2(1H)-ones, and C(sp)-H trifluoroacetylation of alkynes. This protocol is characterized by mild reaction conditions, operational simplicity, and broad functional group compatibility.

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Nitrate pollution in groundwater has become a global concern. One of the most important issues in controlling the nitrate pollution of groundwater is to identify the pollution source quickly and accurately. In this review, we firstly summarized the isotopic background values of potential sources of nitrate pollution in groundwater in 17 provinces (cities, autonomous regions) and 29 study areas in China, which could provide the fundamental database for subsequent research. Secondly, we reviewed the research progress of nitrate isotopes combined with multiple tracers for tracing nitrate in groundwater, and discussed their applicable conditions, advantages, and disadvantages. We found that halides and microorganisms combined with nitrate isotopes could accurately trace the pollution sources of domestic sewage, excrement and agricultural activities. The combination of Δ17O and nitrate isotopes could effectively distinguish the source of atmospheric deposition of nitrate in groundwater. The combination of groundwater age and nitrate isotopes could further determine the time scale of nitrate pollution. In addition, we summarized the application cases and compared the characteristics of mass balance mixing model, IsoSource model, Bayesian isotope mixing model, and EMMTE model for quantitative identification of nitrate pollution in groundwater. For the complexity and concealment of groundwater pollution sources, the coupling of nitrate isotopes with other chemical and biological tracing methods, as well as the application of nitrate isotope quantitative models, are effective tools for reliably identifying groundwater nitrate sources and transformation processes.

Autoclaving-treated germinated brown rice relieves hyperlipidemia by modulating gut microbiota in humans.

Introduction: Germinated brown rice is a functional food with a promising potential for alleviating metabolic diseases. This study aimed to explore the hypolipidemic effects of autoclaving-treated germinated brown rice (AGBR) and the underlying mechanisms involving gut microbiota. Methods: Dietary intervention with AGBR or polished rice (PR) was implemented in patients with hyperlipidemia for 3 months, and blood lipids were analyzed. Nutritional characteristics of AGBR and PR were measured and compared. Additionally, 16S rDNA sequencing was performed to reveal the differences in gut microbiota between the AGBR and PR groups. Results: AGBR relieves hyperlipidemia in patients, as evidenced by reduced levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein-B, and elevated levels of high-density lipoprotein cholesterol and apolipoprotein-A1. In terms of nutrition, AGBR had significantly higher concentrations of free amino acids (10/16 species), γ-aminobutyric acid, resistant starch, soluble dietary fiber, and flavonoids (11/13 species) than PR. In addition, higher microbial abundance, diversity, and uniformity were observed in the AGBR group than in the PR group. At the phylum level, AGBR reduced Firmicutes, Proteobacteria, Desulfobacterota, and Synergistota, and elevated Bacteroidota and Verrucomicrobiota. At the genus level, AGBR elevated Bacteroides, Faecalibacterium, Dialister, Prevotella, and Bifidobacterium, and reduced Escherichia-Shigella, Blautia, Romboutsia, and Turicibacter. Discussion: AGBR contributes to the remission of hyperlipidemia by modulating the gut microbiota.

Carrimycin inhibits coronavirus replication by decreasing the efficiency of programmed -1 ribosomal frameshifting through directly binding to the RNA pseudoknot of viral frameshift-stimulatory element.

The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity. Here, we show that carrimycin, a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials, decreases the efficiency of programmed -1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion. Carrimycin binds directly to the coronaviral frameshift-stimulatory element (FSE) RNA pseudoknot, interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes. Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses. Because the FSE mechanism is essential in all coronaviruses, carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA. This finding may open a new direction in antiviral drug discovery for coronavirus variants.

Limited impact of bacterial virulence on early mortality risk factors in Acinetobacter baumannii bacteremia observed in a Galleria mellonella model.

Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients' blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients' clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia.

Simulation of the dynamic processes of microplastic suspension and deposition in a lake sediment-water system.

The occurrence of microplastics in aquatic environments has attracted increasing interest from both the public and scientists, especially their migration behaviors. Although several environmental behaviors of microplastics have been studied, the issue of microplastic suspension and deposition in lake sediment-water systems remains to be elucidated. In this study, we built an indoor sediment-water system with input and output rivers that simulated the actual situations in lakes, and aimed to explore the suspension and deposition behavior of microplastics using eight group experiments. The abundance of microplastics in overlying water and sediments in different periods was analyzed, and the characteristics of hydrodynamic disturbance on microplastic suspension and deposition were identified. Importantly, the exchange of microplastics in sediments and water under dynamic flow conditions was assessed. The results showed that the middle-scale experiment designed in this study effectively simulated the dynamic transport process of microplastics in lakes, and the hydrodynamic force had a significant impact on the suspension and deposition behaviors of microplastics. The average abundance of polystyrene, polyethylene terephthalate and polyamide microplastics was 1.07, 0.60 and 0.83 particles/L in overlying water during the suspension experiments, respectively. This showed a pattern of first rising and then falling with the extension of suspension time. Even in the environment with the maximum input water volume (8000 ml/min) in this study, only microplastics at a depth of 0 to 2 cm from the sediment were suspended. The average abundance of microplastics was 313.02 particles/kg during the deposition experiments, which gradually increased with the extension of deposition time in sediments. Finally, microplastic sizes in water of the suspension experiments and in sediments of the deposition experiments were concentrated in the range of 500 to 1500 µm and 300 to 1000 µm, respectively.

Lipid-lowering therapies and long-term stroke prevention in East Asians: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Stroke prevention is a pressing global health priority, with reducing elevated lipids recognized as a key strategy. East Asians, constituting more than 1.6 billion individuals and the largest racial group worldwide, are a key demographic in this effort. Yet, the effectiveness of lipid-lowering therapies for stroke prevention in this population remains uncertain. AIMS AND METHODS: We conducted a systematic review and meta-analysis of large-scale randomized controlled trials (RCTs) with at least 3 years of follow-up to evaluate the long-term impact of lipid-lowering therapies on stroke incidence in East Asians. We systematically searched four electronic databases up to 11 January 2024. The association was quantified using relative risk (RR) with a 95% confidence interval (CI), and between-study heterogeneity was evaluated using the I2 statistic. In addition, we utilized the Cochrane Risk of Bias Tool to assess the risk of bias in each included RCT and applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to evaluate the certainty of the evidence. RESULTS: This study incorporated data from nine large-scale RCTs involving 54,354 participants. Our findings of overall analyses revealed that lipid-lowering therapies did not significantly affect the long-term incidence of all strokes (9 RCTs; 54,354 participants; RR = 0.98 (95% CI = 0.87-1.10); P = 0.75), ischemic stroke (7 RCTs; 52,059 participants; RR = 0.91 (95% CI, = 0.79-1.04); P = 0.16), or hemorrhage stroke (7 RCTs; 52,059 participants; RR = 1.24 (95% CI = 0.97-1.59); P = 0.09) in East Asians. Notably, there was no evidence of heterogeneity or publication bias, and the quality of evidence assessed using GRADE methodologies was rated as high. Sensitivity analyses confirmed the robustness of our results, with no single study significantly affecting the overall findings. Furthermore, subgroup analyses consistently supported the conclusions, further bolstering the reliability of our study. CONCLUSIONS: Lipid-lowering therapies did not demonstrate any beneficial effects on long-term stroke prevention among East Asians.

Modification strategies of lead halide perovskite nanocrystals for efficient and stable LEDs.

Lead halide perovskite nanocrystals (PNCs) hold immense promise in high-performance light-emitting diodes (LEDs) for future high-definition displays. Their adjustable bandgaps, vivid colors, and good carrier mobility are key factors that make them a potential game-changer. However, to fully harness their potential, the efficiency and long-term stability of PNCs-based light-emitting diodes (PNC-LEDs) must be enhanced. Recent material research results have shed light on the leading cause of performance decline in PNC-LEDs, which is ionic migration linked to surface defects and grain boundary imperfections. This review aims to present recent advancements in the modification strategies of PNCs, focusing on obtaining high-quality PNCs for LEDs. The PNC modification strategies are first summarized, including crystal structure regulation, nanocrystal size tuning, ligand exchange, and surface passivation. Then, the effects of these material design aspects on LED device performances, such as efficiency, brightness, and stability, are presented. Based on the efficient modification strategies, we propose promising material design insights for efficient and stable PNC-LEDs.

Purpurin ameliorated neuropathic allodynia and hyperalgesia by modulating neuronal mitochondrial bioenergetics and redox status in type 1 diabetic mice.

A substantial proportion of diabetic patients suffer a debilitating and persistent pain state, known as peripheral painful neuropathy that necessitates improved therapy or antidote. Purpurin, a natural anthraquinone compound from Rubia tinctorum L., has been reported to possess antidepressant activity in preclinical studies. As antidepressants have been typically used as standard agents against persistent neuropathic pain, this study aimed to probe the effect of purpurin on neuropathic pain associated with streptozotocin-induced type 1 diabetes in male C57BL6J mice. The Hargreaves test and the von Frey test were used to assess the pain-like behaviors, shown as heat hyperalgesia and mechanical allodynia respectively. Chronic treatment of diabetic mice with purpurin not only ameliorated the established symptoms of heat hyperalgesia and mechanical allodynia, but also arrested the development of these pain states given preemptively at low doses. Although purpurin treatment hardly impacted on metabolic disturbance in diabetic mice, it ameliorated exacerbated oxidative stress in pain-associated tissues, improved mitochondrial bioenergetics in dorsal root ganglion neurons and restored nerve conduction velocity in sciatic nerves. Notably, the analgesic actions of purpurin were modified by pharmacologically manipulating redox status and mitochondrial bioenergetics. These findings unveil the analgesic activity of purpurin, an effect that is causally associated with its bioenergetics-enhancing and antioxidant effects, in mice with type 1 diabetes.

Trends of antibiotic use at the end-of-life of cancer and non-cancer decedents: a nationwide population-based longitudinal study (2006-2018).

Objective: This study aimed to assess the actual burden of antibiotic use among end-of-life (EOL) patients in South Korea and to compare trends between cancer and non-cancer decedents. Design: Population-based mortality follow-back study. Setting: Data from the Korean National Health Insurance Database, covering the period from January1, 2006, to December 31, 2018, provided for research by the National Health Insurance Service (NHIS), were used. Participants: All decedents from 2006 to 2018 were included and categorized as cancer decedents or non-cancer decedents. Methods: Annual antibiotic consumption rates and prescription rates were calculated, and Poisson regression was used to estimate their trends. Results: Overall antibiotic consumption rates decreased slightly among decedents in their final month with a less pronounced annual decrease rate among cancer decedents compared to non-cancer decedents (0.4% vs 2.3% per year, P <.001). Over the study period, although narrow spectrum antibiotics were used less, utilization and prescription of broad-spectrum antibiotics steadily increased, and prescription rates were higher in cancer decedents compared to non-cancer controls. Specifically, carbapenem prescription rates increased from 5.6% to 18.5%, (RR 1.087, 95% CI 1.085-1.088, P <.001) in cancer decedents and from 2.9% to 13.2% (RR 1.115, 95% CI 1.113-1.116, P <.001) in non-cancer decedents. Conclusions: Our findings show that patients at the EOL, especially those with cancer, are increasingly and highly exposed to broad-spectrum antibiotics. Measures of antibiotic stewardship are required among this population.

Construction and Mechanism Exploration of Highly Efficient System for Bacterial Ghosts Preparation Based on Engineered Phage ID52 Lysis Protein E.

Bacterial ghosts (BGs) are hollow bacterial cell envelopes with intact cellular structures, presenting as promising candidates for various biotechnological and biomedical applications. However, the yield and productivity of BGs have encountered limitations, hindering their large-scale preparation and multi-faceted applications of BGs. Further optimization of BGs is needed for the commercial application of BG technology. In this study, we screened out the most effective lysis protein ID52-E-W4A among 13 mutants based on phage ID52 lysis protein E and optimized the liquid culture medium for preparing Escherichia coli Nissle 1917 (EcN). The results revealed a significantly higher lysis rate of ID52-E-W4A compared to that of ID52-E in the 2xYT medium. Furthermore, EcN BGs were cultivated in a fermenter, achieving an initial OD600 as high as 6.0 after optimization, indicating enhanced BG production. Moreover, the yield of ID52-E-W4A-induced BGs reached 67.0%, contrasting with only a 3.1% yield from φX174-E-induced BGs. The extended applicability of the lysis protein ID52-E-W4A was demonstrated through the preparation of Salmonella pullorum ghosts and Salmonella choleraesuis ghosts. Knocking out the molecular chaperone gene slyD and dnaJ revealed that ID52-mediated BGs could still undergo lysis. Conversely, overexpression of integral membrane enzyme gene mraY resulted in the loss of lysis activity for ID52-E, suggesting that the lysis protein ID52-E may no longer rely on SlyD or DnaJ to function, with MraY potentially being the target of ID52-E. This study introduces a novel approach utilizing ID52-E-W4A for recombinant expression, accelerating the BG formation and thereby enhancing BG yield and productivity.