Interleukin-33: Expression, regulation and function in adipose tissues.

Interleukin-33 (IL-33) is a pleiotropic cytokine of the IL-1 family that plays a key role in innate and adaptive immune responses and contributes to tissue homeostasis. Its role in adipose tissue function has been extensively studied, as adipose tissue serves as an important mediator of metabolic dysfunction. In adipose tissue, IL-33 is primarily produced by stromal cells. Its production is regulated by factors, such as androgens, aging, sympathetic innervation, and various inflammatory stimuli that affect the proliferation and differentiation of IL-33-producing stromal cells. Many studies have elucidated the mechanisms by which IL-33 interacts with the immune system components, local nerve fibers, and adipocytes to influence energy balance, with important consequences in obesity, cold-induced thermogenesis, and aging-related metabolic dysfunction. Here, we detail our current understanding of the molecular events that regulate the production of IL-33 within adipose tissue and discuss its role in regulating adipose function.

Influence of electrohydrodynamics on the drying characteristics, microstructure and volatile composition of apricot abalone mushroom (Pleurotus eryngii).

The study explored the use of current fluid dynamics drying technology for apricot abalone mushroom, examining how different output voltages (15, 25, and 35 kV) affected drying characteristics, microstructure, and volatile components. Comparisons were made with samples dried using hot air drying (HAD) and natural air drying (AD). Results revealed that HAD had the fastest drying rate at 0.29664(g·h-1). However, apricot abalone mushroom treated with electrohydrodynamic drying (EHD) maintained a color closer to fresh samples, exhibited a 21% increase in the ordered structure of protein secondary structure, a 12.5-fold increase in bound water content, and the most stable cell structure compared to HAD and AD treatments. A total of 83 volatile organic compounds were identified in the apricot abalone mushroom, with alcohols and aldehydes being the most prominent in terms of threshold and relative content, peaking in the 35 kV treatment group. These findings provide both experimental and theoretical insights into applying current fluid dynamics for drying apricot abalone mushroom.

Giant viruses as reservoirs of antibiotic resistance genes.

Nucleocytoplasmic large DNA viruses (NCLDVs; also called giant viruses), constituting the phylum Nucleocytoviricota, can infect a wide range of eukaryotes and exchange genetic material with not only their hosts but also prokaryotes and phages. A few NCLDVs were reported to encode genes conferring resistance to beta­lactam, trimethoprim, or pyrimethamine, suggesting that they are potential vehicles for the transmission of antibiotic resistance genes (ARGs) in the biome. However, the incidence of ARGs across the phylum Nucleocytoviricota, their evolutionary characteristics, their dissemination potential, and their association with virulence factors remain unexplored. Here, we systematically investigated ARGs of 1416 NCLDV genomes including those of almost all currently available cultured isolates and high-quality metagenome-assembled genomes from diverse habitats across the globe. We reveal that 39.5% of them carry ARGs, which is approximately 37 times higher than that for phage genomes. A total of 12 ARG types are encoded by NCLDVs. Phylogenies of the three most abundant NCLDV-encoded ARGs hint that NCLDVs acquire ARGs from not only eukaryotes but also prokaryotes and phages. Two NCLDV-encoded trimethoprim resistance genes are demonstrated to confer trimethoprim resistance in Escherichia coli. The presence of ARGs in NCLDV genomes is significantly correlated with mobile genetic elements and virulence factors.

Soil keystone viruses are regulators of ecosystem multifunctionality.

Ecosystem multifunctionality reflects the capacity of ecosystems to simultaneously maintain multiple functions which are essential bases for human sustainable development. Whereas viruses are a major component of the soil microbiome that drive ecosystem functions across biomes, the relationships between soil viral diversity and ecosystem multifunctionality remain under-studied. To address this critical knowledge gap, we employed a combination of amplicon and metagenomic sequencing to assess prokaryotic, fungal and viral diversity, and to link viruses to putative hosts. We described the features of viruses and their potential hosts in 154 soil samples from 29 farmlands and 25 forests distributed across China. Although 4,460 and 5,207 viral populations (vOTUs) were found in the farmlands and forests respectively, the diversity of specific vOTUs rather than overall soil viral diversity was positively correlated with ecosystem multifunctionality in both ecosystem types. Furthermore, the diversity of these keystone vOTUs, despite being 10-100 times lower than prokaryotic or fungal diversity, was a better predictor of ecosystem multifunctionality and more strongly associated with the relative abundances of prokaryotic genes related to soil nutrient cycling. Gemmatimonadota and Actinobacteria dominated the host community of soil keystone viruses in the farmlands and forests respectively, but were either absent or showed a significantly lower relative abundance in that of soil non-keystone viruses. These findings provide novel insights into the regulators of ecosystem multifunctionality and have important implications for the management of ecosystem functioning.

Effect of electrohydrodynamic (EHD) drying on active ingredients, textural properties and moisture distribution of yam (Dioscorea opposita).

This paper systematically investigates the changes in material properties during electrohydrodynamic (EHD) drying, the discharge characteristics of the EHD system as well as the active ingredients, textural properties (hardness, adhesiveness, etc.) and moisture distribution of yam under EHD, air drying and hot air drying were investigated. The results showed that the active particles and the ionized wind generated during the discharge process of the electrohydrodynamic drying device had a significant effect on the drying. Compared to thermal drying, 21 kV drying resulted in the most complete cellular structure, the best internal bound water content as well as textural properties of yam. It played a positive role in the retention of internal nutrients in yam, and the total phenol and allantoin contents were increased by 25.74% and 81.99%, respectively. These results elucidate the advantages of electrohydrodynamic drying in yam drying and provide a reference for the application of EHD in drying.

Unraveling the habitat preferences, ecological drivers, potential hosts, and auxiliary metabolism of soil giant viruses across China.

BACKGROUND: Soil giant viruses are increasingly believed to have profound effects on ecological functioning by infecting diverse eukaryotes. However, their biogeography and ecology remain poorly understood. RESULTS: In this study, we analyzed 333 soil metagenomes from 5 habitat types (farmland, forest, grassland, Gobi desert, and mine wasteland) across China and identified 533 distinct giant virus phylotypes affiliated with nine families, thereby greatly expanding the diversity of soil giant viruses. Among the nine families, Pithoviridae were the most diverse. The majority of phylotypes exhibited a heterogeneous distribution among habitat types, with a remarkably high proportion of unique phylotypes in mine wasteland. The abundances of phylotypes were negatively correlated with their environmental ranges. A total of 76 phylotypes recovered in this study were detectable in a published global topsoil metagenome dataset. Among climatic, geographical, edaphic, and biotic characteristics, soil eukaryotes were identified as the most important driver of beta-diversity of giant viral communities across habitat types. Moreover, co-occurrence network analysis revealed some pairings between giant viral phylotypes and eukaryotes (protozoa, fungi, and algae). Analysis of 44 medium- to high-quality giant virus genomes recovered from our metagenomes uncovered not only their highly shared functions but also their novel auxiliary metabolic genes related to carbon, sulfur, and phosphorus cycling. CONCLUSIONS: These findings extend our knowledge of diversity, habitat preferences, ecological drivers, potential hosts, and auxiliary metabolism of soil giant viruses. Video Abstract.

Hidden diversity and potential ecological function of phosphorus acquisition genes in widespread terrestrial bacteriophages.

Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.

Study on the thawing characteristics of beef in ultrasound combined with plasma-activated water.

The effects of deionized water thawing (DT), plasma-activated water thawing (PT), ultrasound (150 W, 40 kHz) combined with deionized water thawing (UDT), and ultrasound combined with plasma-activated water thawing (UPT) on the thawing characteristics and the physicochemical properties of the beef were investigated. The results showed that the UPT group had a faster thawing rate (38 % higher compared to the PT group) and good bactericidal ability (75 % higher compared to the UDT group), and had no adverse effect on the color and pH value of the beef. Plasma-activated water (PAW) can maintain the stability of the beef fiber, improve the water holding capacity (WHC), inhibit lipid oxidation, and reduce the loss of soluble substances such as protein. Therefore, UPT thawing is a promising meat thawing technology, which provides practical guidance and methods for the wide application of UPT in the field of meat thawing.

Influence of electrohydrodynamics on the drying characteristics and volatile components of iron stick yam.

The drying characteristics, rehydration capacity, color, infrared spectra and volatile components of iron stick yam slices were investigated under different alternating current (AC) voltages (13, 17, 21 kV), hot air drying (HAD) (60 °C) and natural drying (AD) by electrohydrodynamic (EHD) drying and HAD experimental devices. The results showed that slices of iron stick yam dried the quickest with HAD, which also had the fastest drying rate; while drying the slices of iron stick yam with EHD led to a better rehydration capacity, higher brightness L* and whiteness, a more stable protein secondary structure, and a greater variety and content of volatile components compared with AD and HAD. These finding indicated that EHD is a more promising method for drying iron stick yam.

Influence of electrohydrodynamics on the drying characteristics and physicochemical properties of garlic.

Electrohydrodynamic (EHD) drying, natural air drying (AD) and hot air drying (HAD) were used to comprehensively study the drying characteristics and physicochemical properties of garlic, and low-field nuclear magnetic resonance (NMR), infrared spectroscopy, scanning electron microscopy and other technologies were used as detection methods. In terms of drying characteristics, HAD has the largest effective diffusion coefficient of moisture and the shortest average drying time. EHD-treated garlic slices had the most attractive color, the highest rehydration rate, the most stable cell structure, the highest content of active ingredients, and the most stable protein secondary structure. Therefore, electrohydrodynamic drying is a promising garlic slice drying technology and provides an effective method for the large-scale production of high-quality garlic.

IL-33 promotes pancreatic ß-cell survival and insulin secretion under diabetogenic conditions through PPARγ.

Pancreatic ß-cell dysfunction plays a vital role in the development of diabetes. IL-33 exerts anti-diabetic effects via its anti-inflammatory properties and has been demonstrated to increase insulin secretion in animal models. However, IL-33, as a pleiotropic cytokine, may also exert a deleterious effect on ß-cells, which has not been rigorously studied. In the present study, we found that IL-33 promoted cell survival and insulin secretion in MIN6 (a mouse pancreatic ß-cell line) cells under diabetogenic conditions. IL-33 increased the expression of its receptor ST2 and the transcription factor PPARγ, whereas PPARγ inhibition impaired IL-33-mediated ß-cell survival and insulin release. IL-33 did not repress the expression of pro-inflammatory mediators, including Tf, Icam1, Cxcl10, and Il1b, whereas it significantly reduced the expression of Ccl2. IL-33 decreased TNF-α secretion and increased IL-10 secretion; these effects were completely reversed by PPARγ inhibition. IL-33 increased glucose uptake and expression of Glut2. It upregulated the expression of glycolytic enzyme genes, namely, Pkm2, Hk2, Gpi1, and Tpi, and downregulated the expression of Gck, Ldha, and Mct4. However, it did not alter hexokinase activity. Moreover, IL-33 increased the number and activity of mitochondria, accompanied by increased ATP production and reduced accumulation of ROS. IL-33 upregulated the expression of PGC-1α and cytochrome c, and mitochondrial fission- and fusion-associated genes, including Mfn1, Mfn2, and Dnm1l. IL-33-mediated mitochondrial homeostasis was partially reversed by PPARγ inhibition. Altogether, IL-33 protects ß-cell survival and insulin secretion that could be partially driven via PPARγ, which regulates glucose uptake and promotes mitochondrial function and anti-inflammatory responses.

Use of Ceftazidime-Avibactam for Suspected or Confirmed Carbapenem-Resistant Organisms in Children: A Retrospective Study.

Background: The incidence of carbapenem-resistant organism (CRO) infections is increasing in children. However, pediatric-specific treatment strategies present unique challenges. Ceftazidime/avibactam is a ß-lactam/ß-lactamase inhibitor combination, showing adequate efficiency against CRO isolates. However, clinical data on the efficacy of ceftazidime/avibactam in children are still lacking. Methods: This was a retrospective study of children (aged <18 years) infected with confirmed or suspected carbapenem-resistant pathogens and treated with ceftazidime-avibactam at the First Affiliated Hospital of Zhengzhou University between 2020 and 2022. Results: We identified 38 children aged 14 (5.0-16.3) years; 20 (52.6%) had hematologic malignancies. 25 children with confirmed CRO infections were administered ceftazidime-avibactam as targeted therapy. The median treatment was 10 (6.0-16.5) days. Among them, 24 had infections caused by carbapenem-resistant Enterobacterales (CRE) (18 carbapenem-resistant Klebsiella pneumoniae and six carbapenem-resistant Escherichia coli species) and one with carbapenem-resistant Pseudomonas aeruginosa strains. The source of infection was the bloodstream in 60.0% of the cases (15/25). The clinical response rate was 84.0% (21/25), and 30-day mortality rate was 20% (5/25). 13 children were administered ceftazidime-avibactam as empiric therapy for suspected infections. The median treatment was 8 (6.0-13.0) days. No deaths occurred and clinical response was achieved in 12 of the 13 patients (92.3%) who empirically treated with ceftazidime-avibactam. Conclusion: Ceftazidime-avibactam is important for improving survival, and clinical response in children with infections caused by CRO.

Obesity alters immunopathology in cancers and inflammatory diseases.

Obesity is characterized by chronic low-grade inflammation and is strongly associated with multiple immunological diseases, including cancer and inflammatory diseases. Recent animal studies revealed that obesity-induced immunological changes worsen immune-driven diseases and cause resistance to immunotherapy. Here, we discuss the role of obesity in the immunopathology and treatment responses of cancers, respiratory and allergic diseases, and IL-17-mediated inflammatory diseases. We summarize the unique features of the inflammatory state of these diseases, which are orchestrated by obesity. In particular, obesity alters the immune landscape in cancers with a reprogrammed metabolic profile of tumor-infiltrating immune cells. Obesity exacerbates airway inflammation by dysregulating multiple immune-cell subsets. Obesity also dysregulates Th17, IL-17-producing mucosal-associated invariant T (MAIT), and γδ T cells, which contribute to IL-17-mediated inflammatory response in multiple sclerosis, inflammatory bowel disease, psoriasis, atopic dermatitis, and rheumatoid arthritis. By identifying the effects of obesity on immunological diseases, new strategies could be devised to target immune dysregulation caused by obesity.

IL-33 Downregulates Hepatic Carboxylesterase 1 in Acute Liver Injury via Macrophage-derived Exosomal miR-27b-3p.

Background and Aims: We previously reported that carboxylesterase 1 (CES1) expression was suppressed following liver injury. The study aimed to explore the role of interleukin (IL)-33 in liver injury and examine the mechanism by which IL-33 regulates CES1. Methods: IL-33 and CES1 levels were determined in the livers of patients and lipopolysaccharide (LPS)-, acetaminophen (APAP)-treated mice. We constructed IL-33 and ST2 knockout (KO) mice. ST2-enriched immune cells in livers were screened to identify the responsible cells. Macrophage-derived exosome (MDE) activity was tested by adding exosome inhibitors. Micro-RNAs (miRs) were extracted from control and IL-33-stimulated MDEs (IL-33-MDEs) and subjected miR sequencing (miR-Seq). Candidate miR was tested in vitro and in vivo and its binding of a target gene was assessed by luciferase reporter assays. Lentivirus-vector cellular transfection and transcript silencing were used to examine pathways mediating IL-33 suppression of miR-27b-3p. Results: Patient liver IL-33 and CES1 expression levels were inversely correlated. CES1 downregulation in liver injury was rescued in both IL-33-deficient and ST2 KO mice. Macrophages were shown to be responsible for IL-33 effects. IL-33-MDEs reduced CES1 levels in hepatocytes. Exosomal miR-Seq and qRT-PCR demonstrated increased miR-27b-3p levels in IL-33-MDEs; miR-27b-3p was implicated in Nrf2 targeting. IL-33 inhibition of miR-27b-3p was found to be GATA3-dependent. Conclusions: IL-33-ST2-GATA3 pathway signaling increases miR-27b-3p content in MDEs, which upon being internalized by hepatocytes reduce CES1 expression by inhibiting Nrf2. The elucidation of this mechanism in this study contributes to a better understanding of CES1 dysregulation in liver injury.

Risk factors and clinical outcomes of carbapenem-resistant Klebsiella pneumoniae bacteraemia in children: a retrospective study.

OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is increasingly being identified in children, but data on the clinical outcomes in this population are limited. This study aimed to characterise the risk factors for 30-day mortality with CRKP bloodstream infection (BSI) in children. METHODS: A retrospective study was performed from January 2018 to December 2021 at the First Affiliated Hospital of Zhengzhou University. Patients aged < 18 years and with CRKP BSI were included. Multivariable Cox and logistic regression were performed to determine risk factors for death and the development of septic shock following CRKP infection, respectively. RESULTS: This study identified 33 neonates aged 0-4 weeks and 37 older children. The 30-day mortality rate was 39.4% in neonates and 43.2% in older children. In the neonatal population, a higher Pitt bacteremia score (HR 1.694; 95% CI 1.313-2.186; P < 0.001) was an independent risk factor for 30-day mortality. In the non-neonatal population, higher platelet count (HR 0.990; 95% CI 0.982-0.998; P = 0.010), the use of carbapenems (HR 0.212; 95% CI 0.064-0.702; P = 0.011) and appropriately targeted antimicrobial treatment (HR 0.327; 95% CI 0.111-0.969; P = 0.044) were associated with decreased 30-day mortality. Monocyte count < 0.1 × 109 cells/L (OR 3.615; 95% CI 1.165-11.444; P = 0.026) and a higher Pitt bacteremia score (OR 1.330; 95% CI 1.048-1.688; P = 0.019) were identified as risk factors for the development of septic shock. CONCLUSIONS: Carbapenem-resistant Klebsiella pneumoniae BSI was associated with high mortality in children. Appropriate antimicrobial treatment is important to improve survival, but more work is needed to assess the efficacy of specific treatment regimens in children.

Mechanism of cognitive impairment induced by d-galactose and l-glutamate through gut-brain interaction in tree shrews.

d-Galactose (d-gal) and l-glutamate (l-glu) impair learning and memory. The mechanism of interaction between the gut microbiome and brain remains unclear. In this study, a model of cognitive impairment was induced in tree shrews by intraperitoneal (ip) injection of d-gal (600 mg/kg/day), intragastric (ig) administration with l-glu (2000 mg/kg/day), and the combination of d-gal (ip, 600 mg/kg/day) and l-glu (ig, 2000 mg/kg/day). The cognitive function of tree shrews was tested by the Morris water maze method. The expression of Aß1-42 proteins, the intestinal barrier function proteins occludin and P-glycoprotein (P-gp), and the inflammatory factors NF-κB, TLR2, and IL-18 was determined by immunohistochemistry. The gut microbiome was analyzed by 16SrRNA high-throughput sequencing. After administering d-gal and l-glu, the escape latency increased (p < .01), and the times of crossing the platform decreased (p < .01). These changes were greater in the combined administration of d-gal and l-glu (p < .01). The expression of Aß1-42 was higher in the perinuclear region of the cerebral cortex (p < .01) and intestinal cell (p < .05). There was a positive correlation between the cerebral cortex and intestinal tissue. Moreover, the expression of NF-κB, TLR2, IL-18, and P-gp was higher in the intestine (p < .05), while the expression of occludin and the diversity of gut microbes were lower, which altered the biological barrier of intestinal mucosal cells. This study indicated that d-gal and l-glu could induce cognitive impairment, increase the expression of Aß1-42 in the cerebral cortex and intestinal tissue, decrease the gut microbial diversity, and alter the expression of inflammatory factors in the mucosal intestines. The dysbacteriosis may produce inflammatory cytokines to modulate neurotransmission, causing the pathogenesis of cognitive impairment. This study provides a theoretical basis to explore the mechanism of learning and memory impairment through the interaction of microbes in the gut and the brain.

Functional Guilds, Community Assembly, and Co-occurrence Patterns of Fungi in Metalliferous Mine Tailings Ponds in Mainland China.

Metalliferous mine tailings ponds are generally characterized by low levels of nutrient elements, sustained acidic conditions, and high contents of toxic metals. They represent one kind of extreme environments that are believed to resemble the Earth's early environmental conditions. There is increasing evidence that the diversity of fungi inhabiting mine tailings ponds is much higher than previously thought. However, little is known about functional guilds, community assembly, and co-occurrence patterns of fungi in such habitats. As a first attempt to address this critical knowledge gap, we employed high-throughput sequencing to characterize fungal communities in 33 mine tailings ponds distributed across 18 provinces of mainland China. A total of 5842 fungal phylotypes were identified, with saprotrophic fungi being the major functional guild. The predictors of fungal diversity in whole community and sub-communities differed considerably. Community assembly of the whole fungal community and individual functional guilds were primarily governed by stochastic processes. Total soil nitrogen and total phosphorus mediated the balance between stochastic and deterministic processes of the fungal community assembly. Co-occurrence network analysis uncovered a high modularity of the whole fungal community. The observed main modules largely consisted of saprotrophic fungi as well as various phylotypes that could not be assigned to known functional guilds. The richness of core fungal phylotypes, occupying vital positions in co-occurrence network, was positively correlated with edaphic properties such as soil enzyme activity. This indicates the important roles of core fungal phylotypes in soil organic matter decomposition and nutrient cycling. These findings improve our understanding of fungal ecology of extreme environments.

Diverse Methylmercury (MeHg) Producers and Degraders Inhabit Acid Mine Drainage Sediments, but Few Taxa Correlate with MeHg Accumulation.

Methylmercury (MeHg) is a notorious neurotoxin, and its production and degradation in the environment are mainly driven by microorganisms. A variety of microbial MeHg producers carrying the gene pair hgcAB and degraders carrying the merB gene have been separately reported in recent studies. However, surprisingly little attention has been paid to the simultaneous investigation of the diversities of microbial MeHg producers and degraders in a given habitat, and no studies have been performed to explore to what extent these two contrasting microbial groups correlate with MeHg accumulation in the habitat of interest. Here, we collected 86 acid mine drainage (AMD) sediments from an area spanning approximately 500,000 km2 in southern China and profiled the sediment-borne putative MeHg producers and degraders using genome-resolved metagenomics. 46 metagenome-assembled genomes (MAGs) containing hgcAB and 93 MAGs containing merB were obtained, including those from various taxa without previously known MeHg-metabolizing microorganisms. These diverse MeHg-metabolizing MAGs were formed largely via multiple independent horizontal gene transfer (HGT) events. The putative MeHg producers from Deltaproteobacteria and Firmicutes as well as MeHg degraders from Acidithiobacillia were closely correlated with MeHg accumulation in the sediments. Furthermore, these three taxa, in combination with two abiotic factors, explained over 60% of the variance in MeHg accumulation. Most of the members of these taxa were characterized by their metabolic potential for nitrogen fixation and copper tolerance. Overall, these findings improve our understanding of the ecology of MeHg-metabolizing microorganisms and likely have implications for the development of management strategies for the reduction of MeHg accumulation in the AMD sediments. IMPORTANCE Microorganisms are the main drivers of MeHg production and degradation in the environment. However, little attention has been paid to the simultaneous investigation of the diversities of microbial MeHg producers and degraders in a given habitat. We used genome-resolved metagenomics to reveal the vast phylogenetic and metabolic diversities of putative MeHg producers and degraders in AMD sediments. Our results show that the diversity of MeHg-metabolizing microorganisms (particularly MeHg degraders) in AMD sediments is much higher than was previously recognized. Via multiple linear regression analysis, we identified both microbial and abiotic factors affecting MeHg accumulation in AMD sediments. Despite their great diversity, only a few taxa of MeHg-metabolizing microorganisms were closely correlated with MeHg accumulation. This work underscores the importance of using genome-resolved metagenomics to survey MeHg-metabolizing microorganisms and provides a framework for the illumination of the microbial basis of MeHg accumulation via the characterization of physicochemical properties, MeHg-metabolizing microorganisms, and the correlations between them.

Clinical Outcomes and Risk Factors for Death following Carbapenem-Resistant Klebsiella pneumoniae Infection in Solid Organ Transplant Recipients.

Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are associated with significant morbidity and mortality. Among solid organ transplant recipients (SOTRs), clinical outcomes and risk factors for death following such infections remain not well documented. A single-center retrospective study was performed. All SOTRs with a CRKP infection at the First Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2021 were included. Multivariable Cox regression was performed to determine risk factors for death following CRKP infection. We identified 94 SOTRs with CRKP infection, with a median age of 50 years old. CRKP infections resulted in 38.3% of overall 30-day mortality. On multivariable analysis, independent risk factors for death following CRKP infection included older age (hazard ratio [HR], 1.044; 95% confidence interval [CI], 1.007 to 1.083; P = 0.02), allograft failure (HR, 3.962; 95% CI, 1.628 to 9.644; P = 0.002), and septic shock (HR, 8.512; 95% CI, 3.294 to 21.998; P < 0.001). Receiving appropriate targeted therapy was associated with a reduced hazard of death (HR, 0.245; 95% CI, 0.111 to 0.543; P = 0.001). Our study characterized the clinical features and mortality in SOTRs with CRKP infection. The protective effects of appropriate targeted therapy highlight the importance of assessing how antibiotic choices affect the clinical outcomes among SOTRs. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are increasingly identified in solid organ transplant recipients (SOTRs), but data on the clinical outcomes and risk factors for death following such infections remain limited. Here, we reported CRKP infection was associated with 38.3% of overall 30-day mortality in SOTRs. Independent risk factors for death after CRKP infection included older age, allograft failure, and septic shock. Appropriate targeted therapy was important for alleviating the impact of CRKP infections on these SOTRs.

An area under the concentration-time curve threshold as a predictor of efficacy and nephrotoxicity for individualizing polymyxin B dosing in patients with carbapenem-resistant gram-negative bacteria.

BACKGROUND: Evidence supports therapeutic drug monitoring of polymyxin B, but clinical data for establishing an area under the concentration-time curve across 24 h at steady state (AUCss,24 h) threshold are still limited. This study aimed to examine exposure-response/toxicity relationship for polymyxin B to establish an AUCss,24 h threshold in a real-world cohort of patients. METHODS: Using a validated Bayesian approach to estimate AUCss,24 h from two samples, AUCss,24 h threshold that impacted the risk of polymyxin B-related nephrotoxicity and clinical response were derived by classification and regression tree (CART) analysis and validated by Cox regression analysis and logical regression analysis. RESULTS: A total of 393 patients were included; acute kidney injury (AKI) was 29.0%, clinical response was 63.4%, and 30-day all-cause mortality was 35.4%. AUCss,24 h thresholds for AKI of > 99.4 mg h/L and clinical response of > 45.7 mg h/L were derived by CART analysis. Cox and logical regression analyses showed that AUCss,24 h of > 100 mg h/L was a significant predictor of AKI (HR 16.29, 95% CI 8.16-30.25, P < 0.001) and AUCss,24 h of ≥ 50 mg h/L (OR 4.39, 95% CI 2.56-7.47, P < 0.001) was independently associated with clinical response. However, these exposures were not associated with mortality. In addition, the correlation between trough concentration (1.2-2.8 mg/L) with outcomes was similar to AUCss,24 h. CONCLUSIONS: For critically ill patients, AUCss,24 h threshold of 50-100 mg h/L was associated with decreased nephrotoxicity while assuring clinical efficacy. Therapeutic drug monitoring is recommended for individualizing polymyxin B dosing.