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.

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.

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.

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.

Metagenomic and metatranscriptomic insights into sulfate-reducing bacteria in a revegetated acidic mine wasteland.

The widespread occurrence of sulfate-reducing microorganisms (SRMs) in temporarily oxic/hypoxic aquatic environments indicates an intriguing possibility that SRMs can prevail in constantly oxic/hypoxic terrestrial sulfate-rich environments. However, little attention has been given to this possibility, leading to an incomplete understanding of microorganisms driving the terrestrial part of the global sulfur (S) cycle. In this study, genome-centric metagenomics and metatranscriptomics were employed to explore the diversity, metabolic potential, and gene expression profile of SRMs in a revegetated acidic mine wasteland under constantly oxic/hypoxic conditions. We recovered 16 medium- to high-quality metagenome-assembled genomes (MAGs) containing reductive dsrAB. Among them, 12 and four MAGs belonged to Acidobacteria and Deltaproteobacteria, respectively, harboring three new SRM genera. Comparative genomic analysis based on seven high-quality MAGs (completeness >90% and contamination <10%; including six acidobacterial and one deltaproteobacterial) and genomes of three additional cultured model species showed that Acidobacteria-related SRMs had more genes encoding glycoside hydrolases, oxygen-tolerant hydrogenases, and cytochrome c oxidases than Deltaproteobacteria-related SRMs. The opposite pattern was observed for genes encoding superoxide reductases and thioredoxin peroxidases. Using VirSorter, viral genome sequences were found in five of the 16 MAGs and in all three cultured model species. These prophages encoded enzymes involved in glycoside hydrolysis and antioxidation in their hosts. Moreover, metatranscriptomic analysis revealed that 15 of the 16 SRMs reported here were active in situ. An acidobacterial MAG containing a prophage dominated the SRM transcripts, expressing a large number of genes involved in its response to oxidative stress and competition for organic matter.

Risk Factors for Mortality and Outcomes in Hematological Malignancy Patients with Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections.

Background: This study aimed to identify risk factors for mortality and outcomes in hematological malignancy (HM) patients with bloodstream infection (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: A retrospective study was conducted at a tertiary teaching hospital in Henan Province, China, between January 2018 and December 2021. All BSIs caused by CRKP in hospitalized HM patients were identified. Data on patient demographics, disease, laboratory tests, treatment regimens, outcomes of infection, and the antimicrobial susceptibility of each isolate were collected from medical records. Results: A total of 129 patients with CRKP BSI were included in the study, and the 28-day mortality rate was 80.6% (104/129). In Cox analysis an absolute neutrophil count < 500 at discharge (hazard ratio [HR] 6.386, 95% confidence interval [CI] 3.074-13.266, p < 0.001), intensive care unit admission (HR 1.834, 95% CI 1.065-3.157, p = 0.029), and higher Pitt bacteremia score (HR 1.185, 95% CI 1.118-1.255, p < 0.001) were independent risk factors associated with 28-day mortality. Survival curve analysis indicated that compared with ceftazidime-avibactam-based therapy, both polymyxin b (HR 8.175, 95% CI 1.099-60.804, p = 0.040) and tigecycline (HR 14.527, 95% CI 2.000-105.541, p =0.008) were associated with a higher risk of mortality. Conclusion: In HM patients CRKP BSI resulted in high mortality. Intensive care unit admission, higher Pitt bacteremia score, and absolute neutrophil count < 500 at discharge were independently associated with higher mortality. Early initiation of new agents such as ceftazidime-avibactam may improve outcomes.

Interleukin-33: Metabolic checkpoints, metabolic processes, and epigenetic regulation in immune cells.

Interleukin-33 (IL-33) is a pleiotropic cytokine linked to various immune cells in the innate and adaptive immune systems. Recent studies of the effects of IL-33 on immune cells are beginning to reveal its regulatory mechanisms at the levels of cellular metabolism and epigenetic modifications. In response to IL-33 stimulation, these programs are intertwined with transcriptional programs, ultimately determining the fate of immune cells. Understanding these specific molecular events will help to explain the complex role of IL-33 in immune cells, thereby guiding the development of new strategies for immune intervention. Here, we highlight recent findings that reveal how IL-33, acting as an intracellular nuclear factor or an extracellular cytokine, alters metabolic checkpoints and cellular metabolism, which coordinately contribute to cell growth and function. We also discuss recent studies supporting the role of IL-33 in epigenetic alterations and speculate about the mechanisms underlying this relationship.

A Prediction Model for Tacrolimus Daily Dose in Kidney Transplant Recipients With Machine Learning and Deep Learning Techniques.

Tacrolimus is a major immunosuppressor against post-transplant rejection in kidney transplant recipients. However, the narrow therapeutic index of tacrolimus and considerable variability among individuals are challenges for therapeutic outcomes. The aim of this study was to compare different machine learning and deep learning algorithms and establish individualized dose prediction models by using the best performing algorithm. Therefore, among the 10 commonly used algorithms we compared, the TabNet algorithm outperformed other algorithms with the highest R2 (0.824), the lowest prediction error [mean absolute error (MAE) 0.468, mean square error (MSE) 0.558, and root mean square error (RMSE) 0.745], and good performance of overestimated (5.29%) or underestimated dose percentage (8.52%). In the final prediction model, the last tacrolimus daily dose, the last tacrolimus therapeutic drug monitoring value, time after transplantation, hematocrit, serum creatinine, aspartate aminotransferase, weight, CYP3A5, body mass index, and uric acid were the most influential variables on tacrolimus daily dose. Our study provides a reference for the application of deep learning technique in tacrolimus dose estimation, and the TabNet model with desirable predictive performance is expected to be expanded and applied in future clinical practice.

Globally distributed mining-impacted environments are underexplored hotspots of multidrug resistance genes.

Mining is among the human activities with widest environmental impacts, and mining-impacted environments are characterized by high levels of metals that can co-select for antibiotic resistance genes (ARGs) in microorganisms. However, ARGs in mining-impacted environments are still poorly understood. Here, we conducted a comprehensive study of ARGs in such environments worldwide, taking advantage of 272 metagenomes generated from a global-scale data collection and two national sampling efforts in China. The average total abundance of the ARGs in globally distributed studied mine sites was 1572 times per gigabase, being rivaling that of urban sewage but much higher than that of freshwater sediments. Multidrug resistance genes accounted for 40% of the total ARG abundance, tended to co-occur with multimetal resistance genes, and were highly mobile (e.g. on average 16% occurring on plasmids). Among the 1848 high-quality metagenome-assembled genomes (MAGs), 85% carried at least one multidrug resistance gene plus one multimetal resistance gene. These high-quality ARG-carrying MAGs considerably expanded the phylogenetic diversity of ARG hosts, providing the first representatives of ARG-carrying MAGs for the Archaea domain and three bacterial phyla. Moreover, 54 high-quality ARG-carrying MAGs were identified as potential pathogens. Our findings suggest that mining-impacted environments worldwide are underexplored hotspots of multidrug resistance genes.

Remarkable effects of microbial factors on soil phosphorus bioavailability: A country-scale study.

Low soil phosphorus (P) bioavailability causes the widespread occurrence of P-limited terrestrial ecosystems around the globe. Exploring the factors influencing soil P bioavailability at large spatial scales is critical for managing these ecosystems. However, previous studies have mostly focused on abiotic factors. In this study, we explored the effects of microbial factors on soil P bioavailability of terrestrial ecosystems using a country-scale sampling effort. Our results showed that soil microbial biomass carbon (MBC) and acid phosphatase were important predictors of soil P bioavailability of agro- and natural ecosystems across China although they appeared less important than total soil P. The two microbial factors had a positive effect on soil P bioavailability of both ecosystem types and were able to mediate the effects of several abiotic factors (e.g., mean annual temperature). Meanwhile, we revealed that soil phytase could affect soil P bioavailability at the country scale via ways similar to those of soil MBC and acid phosphatase, a pattern being more pronounced in agroecosystems than in natural ecosystems. Moreover, we obtained evidence for the positive effects of microbial genes encoding these enzymes on soil P bioavailability at the country scale although their effect sizes varied between the two ecosystem types. Taken together, this study demonstrated the remarkable effects of microbial factors on soil P bioavailability at a large spatial scale, highlighting the importance to consider microbial factors in managing the widespread P-limited terrestrial ecosystems.