Analysis and application of volatile metabolic profiles of Escherichia coli: a preliminary GC-IMS-based study.

Nosocomial infections caused by Escherichia coli (E. coli) may pose serious risks to patients, and early identification of pathogenic bacteria and drug sensitivity results can improve patient prognosis. In this study, we clarified the composition and relative content of volatile organic compounds (VOCs) generated by E. coli in tryptic soy broth (TSB) using gas chromatography-ion mobility spectrometry (GC-IMS). We explored whether imipenem (IPM) could be utilized to differentiate between carbapenem-sensitive E. coli (CSEC) and carbapenem-resistant E. coli (CREC). The results revealed that 36 VOCs (alcohols, aldehydes, acids, esters, ketones, pyrazines, heterocyclic compounds, and unknown compounds) were detected using GC-IMS. Besides, the results indicated that changes in the relative content of VOCs as well as changes in the signal intensity of fingerprints were able to assess the growth state of bacteria during bacterial growth and help identify E. coli. Lastly, under selective pressure of IPM, volatile fingerprints of E. coli could be employed as a model to distinguish CSEC from CREC strains.

Gas Chromatography-Ion Mobility Spectrometry Reveals Acetoin as a Biomarker for Carbapenemase-Producing Klebsiella pneumoniae.

BACKGROUND This study aimed to detect the volatile organic compound (VOC), 3-hydroxy-2-butanone (acetoin) using gas chromatography-ion mobility spectrometry (GC-IMS) in antimicrobial-resistant Klebsiella pneumoniae (K. pneumoniae) carbapenemase (KPC)-producing bacteria. MATERIAL AND METHODS Using stromal fluid of blood culture bottles (BacT/ALERT® SA) as the medium, 3-hydroxy-2-butanone (acetoin) released by K. pneumoniae during growth was detected using GC-IMS. The impact of imipenem (IPM) and carbapenemase inhibitors [avibactam sodium or pyridine-2,6-dicarboxylic acid (DPA)] on the emission of 3-hydroxy-2-butanone (acetoin) from various carbapenemase-producing K. pneumoniae was further investigated. Subsequently, VOCal software was used to generate a pseudo-3D plot of 3-hydroxy-2-butanone (acetoin), and the relative peak volumes were exported for data analysis. Standard strains served as references, and the findings were validated with clinical isolates. RESULTS The pattern of temporal changes in the 3-hydroxy-2-butanone (acetoin) release from K. pneumoniae in the absence of IPM was consistent with the growth curve. After the IPM addition, carbapenemase-positive strains released significantly higher contents of 3-hydroxy-2-butanone (acetoin) than carbapenemase-negative strains at the late exponential growth phase (T2). Notably, adding avibactam sodium significantly decreased the 3-hydroxy-2-butanone (acetoin) content released from the class A carbapenemase-producing strains as compared to the absence of the carbapenemase inhibitor. Conversely, adding DPA significantly decreased the 3-hydroxy-2-butanone (acetoin) content released from the class B carbapenemase-producing strains (both standard and clinical strains, all P<0.05). CONCLUSIONS This study demonstrated the potential of 3-hydroxy-2-butanone (acetoin) as a VOC biomarker for detecting carbapenemase-producing K. pneumoniae, as revealed by GC-IMS analysis.

Novel herbicide flusulfinam: absolute configuration, enantioseparation, enantioselective bioactivity, toxicity and degradation in paddy soils.

BACKGROUND: Flusulfinam, a novel chiral herbicide, effectively controls Echinochloa crusgalli and Digitaria sanguinalis in paddy fields, indicating significant potential for practical agricultural applications. However, limited information is available on flusulfinam from a chiral perspective. A comprehensive evaluation of the enantiomeric levels of flusulfinam was performed. RESULTS: Two enantiomers, R-(+)- and S-(-)-flusulfinam, were separately eluted using a Chiralcel OX-RH column. The bioactivity of R-flusulfinam against the two was 1.4-3.1 fold that of Rac-flusulfinam against two weed species. R-flusulfinam toxicity to Danio rerio larvae and Selenastrum capricornutumwere was 0.8- and 3.0-fold higher than Rac-flusulfinam, respectively. Degradation experiments were conducted using soil samples from four Chinese provinces. The findings indicated that S-flusulfinam (half-life T1/2 = 40.8 days) exhibits preferential degradation than R-flusulfinam (T1/2 = 46.2-57.8 days) in the soils of three provinces. Under anaerobic conditions, soil from Anhui exhibited preferential degradation of R-flusulfinam (T1/2 = 46.2 days) over S-flusulfinam (T1/2 = 63 days). Furthermore, two hydrolysis products of flusulfinam (M299 and M100) are proposed for the first time. CONCLUSION: The enantioselective bioactivity, toxicity and degradation of flusulfinam were investigated. Our findings indicate that R-flusulfinam is an extremely effective and low-toxicity enantiomer for the tested species. The soil degradation test indicated that the degradation of flusulfinam was accelerated by higher organic matter content and lower soil pH. Furthermore, microbial communities may play a crucial role in driving the enantioselective degradation processes. This study lays the groundwork for the systematic evaluation of flusulfinam from an enantiomeric perspective. © 2024 Society of Chemical Industry.

Clinical Characteristics, Prognosis and Treatment of Bloodstream Infections with Enterobacter Cloacae Complex in a Chinese Tertiary Hospital: A Retrospective Study.

Objective: This research aimed to analyze the clinical characteristics, prognosis, and antimicrobial treatment of bloodstream infections (BSI) caused by Enterobacter cloacae complex (ECC). Methods: The clinical data of patients with bloodstream infections caused by Enterobacter cloacae complex from April 2017 to June 2023 were collected retrospectively. These data were then analyzed in subgroups based on the detection results of extended-spectrum ß-lactamase (ESBL), 30-day mortality, and the type of antimicrobial agent used (ß-lactam/ß-lactamase inhibitor combinations (BLICs) or carbapenems). Results: The proportion of ESBL-producing Enterobacter cloacae complex was 32.5% (37/114). Meanwhile, ICU admission, receiving surgical treatment within 3 months, and biliary tract infection were identified as risk factors for ESBL-producing ECC-BSI. Additionally, immunocompromised status and Sequential Organ Failure Assessment (SOFA) score ≥ 6.0 were identified as independent risk factors of 30-day mortality in patients with ECC-BSI (n = 108). Further analysis in BSI patients caused by non-ESBL-producing ECC revealed that patients treated with BLICs (n = 45) had lower SOFA scores and lower incidence of hypoproteinemia and sepsis compared with patients treated with carbapenems (n = 20). Moreover, in non-ESBL-producing ECC-BSI patients, the univariate Cox regression analysis indicated a significantly lower 30-day mortality rate in patients treated with BLICs compared to those treated with carbapenems (hazard ratios (HR) [95% CI] 0.190 [0.055-0.662], P = 0.009; adjusted HR [95% CI] 0.106 [0.013-0.863], P = 0.036). Conclusion: This study investigated the factors influencing the susceptibility to infection by ESBL-producing strains and risk factors for 30-day mortality in ECC-BSI patients. The results revealed that ESBL-negative ECC-BSI patients treated with BLICs exhibited significantly lower 30-day mortality compared to those treated with carbapenems. BLICs were found to be more effective in ECC-BSI patients with milder disease (ESBL-negative and SOFA ≤6.0).

A comparative analysis of distracted driving behavior among drivers of different income levels: A case study in huainan, China.

This research aims to investigate the differences and causes behind distracted driving behavior among drivers with varying income levels. A comparative survey of 1121 drivers in Huainan City, China, was conducted, including 562 drivers from high-end communities representing the high-income group, and 559 drivers from general communities representing the low-income group. Employing social norms, risk perception, and experience as independent variables, the study further examines the role of in-group bias as a mediating variable, with distracted driving behavior serving as the dependent variable, through the construction of two structural equation models for analysis. The study found that among the high-income driver group, in-group bias significantly mediates the impact of social norms, risk perception, and experience on distracted driving behavior; however, this mediating effect is less pronounced in the low-income driver group. This finding is crucial for understanding the potential distracted driving behaviors induced by in-group bias within the high-income driver group and for effectively promoting driving safety. In summary, this research provides new insights into reducing distracted driving behavior among the high-income driver group, thereby enhancing road safety.

GC-IMS facilitates identification of carbapenem-resistant Klebsiella pneumoniae in simulated blood cultures.

This study aimed to identify carbapenem-resistant Klebsiella pneumoniae (CRKP) based on changes in levels of its volatile organic compounds (VOCs) in simulated blood cultures (BCs) using the gas chromatography-ion mobility spectrometry (GC-IMS) technique. A comprehensive analysis of volatile metabolites produced by Klebsiella pneumoniae (K. pneumoniae) in BC bottles was conducted using GC-IMS. Subsequently, the released VOCs were analyzed to examine differences in VOC release between CRKP and carbapenem-susceptible Klebsiella pneumoniae (CSKP). A total of 54 VOCs were detected, of which 18 (6 VOCs found in both monomer and dimer forms) were successfully identified. The VOCs produced by K. pneumoniae in BC bottles (BacT/ALERT® SA) were primarily composed of organic acids, alcohols, esters, and ketones. The content of certain VOCs was significantly different between CRKP and CSKP after the addition of imipenem (IPM). Moreover, the inclusion of carbapenemase inhibitors facilitated the identification of carbapenemase-producing K. pneumoniae based on the variations in VOCs. This study demonstrates the utility of GC-IMS technology in identifying CRKP, and reveals that changes in VOCs are closely related to the growth and metabolism of K. pneumoniae, indicating that they can be leveraged to promote early identification of CRKP bacteremia. However, further in-depth studies and experiments are needed to validate our findings.

Comparison of bacteremic pneumonia caused by Escherichia coli and Klebsiella pneumoniae: A retrospective study.

OBJECTIVES: To compare the prognosis of bacteremic pneumonia caused by Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) pathogens. METHODS: A retrospective analysis was carried out on the clinical data of 162 patients who were diagnosed with bacterial pneumonia caused by either K. pneumoniae or E. coli between 2016-2019. The primary outcome of the analysis was the patients' 30-day mortality rate. RESULTS: There were 82 patients in the E. coli bacteremic pneumonia (E. coli-BP) group and 80 patients in the K. pneumoniae bacteremic pneumonia (KP-BP) group. The 30-day mortality rate was 43.75% (n=35/80) in the KP-BP group and 21.95% (n=18/82) in the E. coli-BP group (p<0.001). Following the adjustment for confounding variables in 4 distinct models, the hazard ratios for the primary outcome in KP-BP were determined to be 0.70 (95% confidence interval [CI]: [0.44-1.02]) in Model 1, 0.72 (95% CI: [0.46-1.14]) in Model 2, 0.99 (95% CI: [0.57-1.73]) in Model 3, and 1.22 (95% CI: [0.69-2.18]) in Model 4. CONCLUSION: Patients diagnosed with KP-BP exhibited a similar prognosis as those diagnosed with E. coli-BP. For patients with KP-BP, the risk of mortality was significantly higher for those who were in the intensive care unit, were infected with carbapenem-resistant strains, or had a high sequential organ failure assessment score. In patients with E. coli-BP, the Pitt bacteremia score was strongly associated with the 30-day mortality rate.

Developmental toxicity and metabolomics analyses of zebrafish (Danio rerio) embryos exposed to Fenoxaprop-p-ethyl.

Fenoxaprop-p-ethyl (FEN) is an aryloxy phenoxy propionate herbicide that has been widely used in paddy fields. Previous studies have indicated that FEN is highly toxic to aquatic organisms, but little is known about the developmental effects of FEN. This study investigated acute and developmental toxicity, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities, and metabolomic analyses in zebrafish embryos after 96 h of exposure. FEN exhibited high acute toxicity to zebrafish embryos and larvae. Exposure to FEN could reduce heartbeat and hatching rates and increase malformation rates in embryos. Oxidative damage was also caused in embryos. The results of metabolomics analysis showed that 102 differentially abundant metabolites were found in zebrafish embryos in the 0.05 mg/L FEN treatment group, and 60 differentially abundant metabolites were found in the 0.20 mg/L FEN treatment group. These differentially abundant metabolites mainly belonged to 9 metabolic pathways, of which folate pathways and ABC transport protein pathways had the greatest impact. These results suggested that FEN induced high acute and developmental toxicity in zebrafish embryos.

Whole-Exome Sequencing Identifies Mutation Profile and Mutation Signature-Based Clustering Associated with Prognosis in Appendiceal Pseudomyxoma Peritonei.

Pseudomyxoma peritonei (PMP) is a rare malignant clinical syndrome with little known about the global mutation profile. In this study, whole-exome sequencing (WES) was performed in 49 appendiceal PMP to investigate mutation profiles and mutation signatures. A total of 4,020 somatic mutations were detected, with a median mutation number of 56 (1-402). Tumor mutation burden (TMB) was generally low (median 1.55 mutations/Mb, 0.12-11.26 mutations/Mb). Mutations were mainly enriched in the function of cancer-related axonogenesis, extracellular matrix-related processes, calcium signaling pathway, and cAMP signaling pathway. Mutations in FCGBP, RBFOX1, SPEG, RTK-RAS, PI3K-AKT, and focal adhesion pathways were associated with high-grade mucinous carcinoma peritonei. These findings revealed distinct mutation profile in appendiceal PMP. Ten mutation signatures were identified, dividing patients into mutation signature cluster (MSC) 1 (N = 28, 57.1%) and MSC 2 (N = 21, 42.9%) groups. MSC (P = 0.007) was one of the four independent factors associated with 3-year survival. TMB (P = 0.003) and microsatellite instability (P = 0.002) were independent factors associated with MSC 2 grouping. Taken together, our findings provided a broader view in the understanding of molecular pathologic mechanism in appendiceal PMP and may be critical to developing an individualized approach to appendiceal PMP treatment. IMPLICATIONS: This work describes exhaustive mutation profile of PMP based on WES data and derives ten mutation signatures, which divides patients into two clusters and serve as an independent prognostic factor associated with 3-year survival.

Comparison of gene mutation profile in different lung adenocarcinoma subtypes by targeted next-generation sequencing.

BACKGROUND: Disease prognosis after resection of lung cancer could be affected by pathological subtypes. In this study, we investigated the difference of gene variation and significantly altered pathways between adenocarcinoma in situ (AIS)/microinvasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) subtypes to reveal the molecular mechanism of prognosis differences. METHODS: Sixty one tumor tissues were subjected to DNA extraction and customized 136 gene targeted next-generation sequencing. Comparisons between groups were performed with two-sided Fisher's exact test for categorical variables and two-tailed unpaired t test for numerical variables. RESULTS: A total of 402 somatic mutations involved in 70 genes were detected in all these samples, and 74.29% of these genes were mutated in at least two samples. PMS2, ARID1A, EGFR, and POLE were the most frequently mutated genes. ALK_EML4 fusion was observed in one IAC patient and RET_ KIF5B fusion in one AIS patient. A significant higher proportion of patients with TP53 gene mutation was observed in the IAC group (P = 0.0057). The average onset age in IAC group is 62.48 years, which is greater than other subtypes (P = 0.0166). It revealed that mutations in genes involved in the mTOR signaling pathway (56.52% vs 26.32%, P = 0.0288) and Hippo signaling pathway (34.78% vs 10.53%, P = 0.0427) were significantly enriched in IAC subtypes, suggesting the key involvement of mTOR and Hippo signaling pathways in lung tumor development and malignant progression. CONCLUSIONS: This study revealed the heterogeneity of gene mutations and significantly altered pathways between different lung cancer subtypes, suggesting the potential mechanism of different prognosis.

Prognostic risk of immune-associated signature in the microenvironment of brain gliomas.

Understanding the key factors in the tumor microenvironment (TME) that affect the prognosis of gliomas is crucial. In this study, we sought to uncover the prognostic significance of immune cells and immune-related genes in the TME of gliomas. We incorporated data of 970 glioma patient samples from the Chinese Glioma Genome Atlas (CGGA) database as the training set, and an additional set of 666 samples from The Cancer Genome Atlas (TCGA) database served as the validation set. From our analysis, we identified 21 immune-related differentially expressed genes (DEGs) in the TME, which holds implications for glioma prognosis. Based on these genes, we constructed a prognostic risk model on the 21 genes. The prognostic risk model demonstrated robust performance with an area under the curve (AUC) value of 0.848. Notably, the risk score derived from the model emerged as an independent prognostic factor of gliomas, with high risk scores indicative of an unfavorable prognosis. Furthermore, we observed that high infiltration levels of certain immune cells, namely, activated dendritic cells, M0 macrophages, M2 macrophages, and regulatory T cells (Tregs), correlated with an unfavorable glioma prognosis. In conclusion, our findings suggested that the TME of gliomas harbored a distinct immune-associated signature, comprising 21 immune-related genes and specific immune cells. These elements significantly influence the prognosis and present potential as novel indicators in the clinical assessment of glioma patient outcomes.

Clinical Characteristics and Prognosis of Hospital-Acquired Klebsiella pneumoniae Bacteremic Pneumonia versus Escherichia coli Bacteremic Pneumonia: A Retrospective Comparative Study.

Objective: This research aimed to investigate the variations in clinical features and prognosis of HABP caused by E. coli and K. pneumoniae. We also aimed to evaluate the risk variables related to 30-day death in the investigated groups. Methods: A single-center retrospective cohort research lasting four years was performed. A total of 117 patients with HABP were involved in this research. The primary prognosis was 30-day death. Results: Among 117 patients with HABP, 60 patients were infected with K. pneumoniae (KP-HABP), and 57 patients were infected with E. coli (E. coli-HABP). A higher proportion of males, ICU admission, undergoing tracheotomy and trachea cannulation, carbapenem-resistant strains, inappropriate empirical therapy (IET), immune compromise, diabetes mellitus, and sepsis were observed in the patients with KP-HABP (all P < 0.05). Meanwhile, the median SOFA score and Pitt score were significantly (P < 0.001) higher in the KP-HABP group compared to the E. coli-HABP group. The 30-day death was 48.33% in the KP-HABP group and 24.56% in the E. coli-HABP group (P = 0.008). After adjusting for the main covariates, the hazard ratios for 30-day mortality in KP-HABP were 1.58 (95% CI:0.80-3.12), 3.24 (95% CI:1.48-7.06), 5.67 (95% CI:2.00-16.07), and 5.99 (95% CI:2.10-17.06), respectively. Multivariate logistic regression models revealed that IET, hypoproteinaemia, cerebral vascular disease (CVD), and SOFA score ≥ 5.0 were the independent risk variables for 30-day death in KP-HABP. Simultaneously, SOFA score ≥ 4.0 and Pitt score ≥ 2.0 were independent risk factors for 30-day mortality in E. coli-HABP. Conclusion: The clinical features of HABP vary depending on whether it is caused by Escherichia coli or K. pneumoniae. KP-HABP patients have higher 30-day mortality than E. coli-HABP patients. To ensure greater validity, it is necessary to further verify this conclusion using a larger sample size.

Early Lactate/Albumin and Procalcitonin/Albumin Ratios as Predictors of 28-Day Mortality in ICU-Admitted Sepsis Patients: A Retrospective Cohort Study.

BACKGROUND Lactate/albumin (LA/ALB) and procalcitonin/albumin (PCT/ALB) ratios have been implicated in predicting mortality in sepsis patients. However, their prognostic value and relationship to sepsis severity require further investigation. This retrospective study aimed to assess the prognostic value of lactate/albumin (LA/ALB) and procalcitonin/albumin (PCT/ALB) ratios in septic patients admitted to the Intensive Care Unit (ICU). MATERIAL AND METHODS A total of 340 adult sepsis patients admitted to the ICU were included in the derivation cohort. LA/ALB and PCT/ALB ratios were calculated and analyzed in relation to sepsis severity and survival status. Additionally, a validation cohort of 75 sepsis patients from another medical center was selected. RESULTS In the derivation cohort, higher LA/ALB and PCT/ALB ratios and SOFA scores were significantly associated with increased mortality (P<0.001). The LA/ALB and PCT/ALB ratios positively correlated with SOFA score. Survival analysis revealed significantly higher 28-day mortality in sepsis patients with elevated PCT/ALB (≥0.256) and LA/ALB (≥0.079) ratios upon ICU admission. The constructed prediction model incorporating LA/ALB ratio, PCT/ALB ratio, and SOFA score yielded an AUC of 0.826, demonstrating good predictive ability. The associations between LA/ALB and PCT/ALB ratios and 28-day mortality in sepsis patients were validated in the validation cohort. CONCLUSIONS The LA/ALB and PCT/ALB ratios at ICU admission provide valuable prognostic information for predicting 28-day mortality in sepsis patients. Combining these ratios with SOFA score improves the assessment of prognosis in sepsis patients.

GrapevineXL reliably predicts multi-annual dynamics of vine water status, berry growth, and sugar accumulation in vineyards.

Climate and water availability greatly affect each season's grape yield and quality. Using models to accurately predict environment impacts on fruit productivity and quality is a huge challenge. We calibrated and validated the functional-structural model, GrapevineXL, with a data set including grapevine seasonal midday stem water potential (Ψxylem), berry dry weight (DW), fresh weight (FW), and sugar concentration per volume ([Sugar]) for a wine grape cultivar (Vitis vinifera cv. Cabernet Franc) in field conditions over 13 years in Bordeaux, France. Our results showed that the model could make a fair prediction of seasonal Ψxylem and good-to-excellent predictions of berry DW, FW, [Sugar] and leaf gas exchange responses to predawn and midday leaf water potentials under diverse environmental conditions with 14 key parameters. By running virtual experiments to mimic climate change, an advanced veraison (i.e. the onset of ripening) of 14 and 28 days led to significant decreases of berry FW by 2.70% and 3.22%, clear increases of berry [Sugar] by 2.90% and 4.29%, and shortened ripening duration in 8 out of 13 simulated years, respectively. Moreover, the impact of the advanced veraison varied with seasonal patterns of climate and soil water availability. Overall, the results showed that the GrapevineXL model can predict plant water use and berry growth in field conditions and could serve as a valuable tool for designing sustainable vineyard management strategies to cope with climate change.

Assessment of Effective Antimicrobial Regimens and Mortality-Related Risk Factors for Bloodstream Infections Caused by Carbapenem-Resistant Acinetobacter baumannii.

Objective: This study aimed to determine the clinical features, risk factors, and effective antimicrobial therapy for Carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infection (BSI). Methods: This was a retrospective analysis of data from patients with CRAB bacteremia in a Chinese tertiary hospital between January 2012 and October 2021. Risk factors, predictors of 30-day mortality, and effective antimicrobial therapy for CRAB BSI were identified using logistic and cox regression analyses. Results: Data from 276 patients with Acinetobacter baumannii (AB) BSI were included, of whom 157 (56.9%) had CRAB BSI. The risk factors that were significantly associated with CRAB BSI included previous intensive care unit (ICU) stay (P < 0.001), immunocompromised status (P < 0.001), cephalosporin use (P = 0.014), and fluoroquinolone use (P = 0.007). The 30-day mortality of the CRAB BSI group was 49.7% (78/157). ICU stay after BSI (P = 0.047), sequential organ failure assessment (SOFA) score ≥10 (P < 0.001), and multiple organ failure (MOF) (P = 0.037) were independent predictors of 30-day mortality. Among antibiotic strategies for the treatment of patients with CRAB BSI, we found that definitive regimens containing cefoperazone/sulbactam were superior to those without cefoperazone/sulbactam in reducing the 30-day mortality rate (25.4% vs 53.4%, P = 0.005). After propensity score matching, we observed a significant increase in the 30-day mortality (77.8%vs 33.3%, P = 0.036) in patients receiving tigecycline monotherapy compared to those receiving cefoperazone/sulbactam monotherapy. The mortality rate of patients receiving tigecycline with cefoperazone/sulbactam was also higher than that of patients receiving cefoperazone-sulbactam monotherapy; however, the difference was not significant (28.6%vs 19.0%, P = 0.375). Conclusion: The severity of patient conditions was significantly associated with mortality in patients with CRAB BSI. Those Patients treated with cefoperazone/sulbactam had better clinical prognoses, and tigecycline should be used with caution.

Ceftazidime/Avibactam, Polymyxin or Tigecycline as a Rescue Strategy for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae in Bloodstream Infection: A Retrospective Cohort Study.

Objective: To analyze the clinical characteristics, outcomes, and risk factors of patients treated with ceftazidime/avibactam, polymyxin, or tigecycline (CPT) compared with those receiving a conventional therapy (CT) (ie, imipenem, levofloxacin, or gentamicin). Methods: A single-center retrospective cohort study included patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection (CRKP-BSI) treated at one Chinese tertiary hospital between March 2012 and November 2022 was performed. Clinical characteristics, outcomes, and risk factors of patients treated with CPT or CT were compared. Predictors of 30-day mortality of patients with CRKP-BSI were also analysed in our study. Results: Among 184 recruited patients with CRKP-BSI, 39.7% (73/184) were treated with CPT, while 60.3% (111/184) were treated with CT. Compared to patients treated with CT, patients treated with CPT had worse conditions, as evidenced by a higher rate of underlying diseases and invasive procedures; however, they also had a better prognosis and lower rates of 14-day treatment failure (p = 0.024). In addition, univariate analysis and multivariate analysis showed that SOFA score [odds ratio (OR) = 1.310, 95% confidence interval (CI) 1.157-1.483; p < 0.001] and cold weather (OR = 3.658, 95% CI 1.474-9.081; p = 0.005) were independent risk factors for 30-day mortality. Conclusion: Compared to CRKP-BSI patients treated with CT, patients treated with CPT had worse conditions but better prognoses. CRKP-BSI occurred more frequently in hot weather; however, higher 30-day mortality was associated with cold weather. A randomized trial is needed to confirm these observational results.

Comprehensive evaluation of water ecological environment in watersheds: a case study of the Yangtze River Economic Belt, China.

The Yangtze River Economic Belt, an inland economic zone with global influence, has shown a trend of prosperous economic development in recent years. Economic development, water pollution, resource depletion, and other environmental problems continue to emerge. The steady state of the water ecological environment is an important aspect of ecological security. To investigate the regional water ecological security state, this study constructs a comprehensive evaluation indicator system within the framework of "driving force-carrying source-state-management" (DCSM). The entropy weight method was used to determine the weight of each indicator, and the weighted rank sum ratio model was introduced to classify the water ecological environment of the Yangtze River Economic Belt from 2010 to 2019. Finally, an adversarial interpretative structure model is used to refine the ranking of each region. The results show that the bearing state and driving force subsystems are closely related to the water ecological environment. The top three indicators are wastewater discharge of industrial added value of 10,000 yuan, water consumption per 10,000 yuan of industrial gross product, and water consumption per 10,000 yuan of tertiary gross domestic product. In addition, there are clear differences in the water ecological environment of the Yangtze River Economic Belt. The classification results show that Zhejiang and Jiangsu are rated as "excellent''; Yunnan, Guizhou, Anhui, and Jiangxi are in the "good" level; and Sichuan, Hunan, Chongqing, and Hubei are in the "medium" level. Shanghai is "poor." As a whole, the downstream is superior, the upstream is second, and the midstream is poor in an asymmetric "U"-shaped distribution. During the study period, the overall state of water ecology in the Yangtze River Economic Belt was at a medium level and has not yet reached a safe and steady state. The performance of areas with traditional industrialization as the main development path was poor. Therefore, it is necessary to pay attention to the overall water ecological security in the basin in the future, strengthen the regulatory role of the government's water ecological management, promote reform of traditional industries and resource-based regions, and achieve the sustainable development of the water ecological environment.

Identification of FLRT2 as a key prognostic gene through a comprehensive analysis of TMB and IRGPs in BLCA patients.

Introduction: The tumor immune environment and immune-related genes are instrumental in the development, progression, and prognosis of bladder cancer (BLCA). This study sought to pinpoint key immune-related genes influencing BLCA prognosis and decipher their mechanisms of action. Methods and results: We analyzed differentially expressed genes (DEGs) between high- and low- tumor mutational burden (TMB) groups. Subsequently, we constructed a reliable prognostic model based on immune-related gene pairs (IRGPs) and analyzed DEGs between high- and low-risk groups. A total of 22 shared DEGs were identified across differential TMB and IRGPs-derived risk groups in BLCA patients. Through univariate Cox and multivariate Cox analyses, we highlighted five genes - FLRT2, NTRK2, CYTL1, ZNF683, PRSS41 - significantly correlated with BLCA patient prognosis. Notably, the FLRT2 gene emerged as an independent prognostic factor for BLCA, impacting patient prognosis via modulation of macrophage infiltration in immune microenvironment. Further investigation spotlighted methylation sites - cg25120290, cg02305242, and cg01832662 - as key regulators of FLRT2 expression. Discussion: These findings identified pivotal prognostic genes in BLCA and illuminated the intricate mechanisms dictating patient prognosis. This study not only presents a novel prognostic marker but also carves out potential avenues for immunotherapy and targeted therapeutic strategies in BLCA. By demystifying the profound impact of immune-related genes and the tumor immune environment, this study augments the comprehension and prognostic management of bladder cancer.

Risk Factors for 30-Day Mortality in Patients with Bacteremic Pneumonia Caused by Escherichia coli and Klebsiella pneumoniae: A Retrospective Study.

Objective: Escherichia coli and Klebsiella pneumoniae are prevalent Gram-negative microorganisms responsible for pneumonia, as well as the primary Enterobacteriaceae pathogens causing bacteremic pneumonia. The objective of this research is to analyze the risk factors associated with bacteremic pneumonia caused by these pathogens and develop a predictive model. Patients and Methods: This retrospective investigation encompassed a cohort of 252 patients diagnosed with Escherichia coli or Klebsiella pneumoniae-induced bacteremic pneumonia between 2018 and 2022. The primary endpoint was 30-day mortality, which was analyzed using multifactorial logistic regression, nomogram construction, and Bootstrap validation. Results: Among the 252 patients diagnosed with Escherichia coli and Klebsiella pneumoniae, 65 succumbed to the disease while 187 survived. The overall 30-day mortality was found to be 25.8%. A multifactorial logistic regression analysis revealed that diastolic blood pressure, cerebrovascular diseases/transient ischemic attacks (TIA), immunosuppression, blood urea nitrogen, Pitt score, and CURB-65 score were statistically significant factors. The Nomogram model demonstrated an AUC of 0.954, which closely aligns with the Bootstrap-derived mean AUC of 0.953 (95% CI: 0.952-0.954). Conclusion: In patients with bacteremic pneumonia caused by Escherichia coli and Klebsiella pneumoniae, Low diastolic blood pressure (≤61 mmHg), pre-existing cerebrovascular disease/ transient ischemic attacks (TIA), immunosuppression status, elevated blood urea nitrogen levels (≥8.39 mmol/L), high Pitt score (≥3), and a high CURB-65 score (≥2) are all independent risk factors for Escherichia coli and Klebsiella pneumoniae bacteremic pneumonia, among which the first three warrant particular attention.

Lactate increases tumor malignancy by promoting tumor small extracellular vesicles production via the GPR81-cAMP-PKA-HIF-1α axis.

Lactate and tumor cell-derived extracellular vesicles (TEVs) both contribute to tumor progression. However, it is still unclear whether lactate can accelerate tumor development by directly promoting TEV production. Here, we show that lactate decreases intracellular cAMP levels and subsequent PKA activation via GPR81, which inhibits the PKA-induced ubiquitination of HIF-1α that causes degradation. Then, the HIF-1α-mediated transcription of Rab27a is enhanced, leading to increased TEV release. In this way, lactate promotes lung metastasis by murine melanoma. In addition, we show that serum lactate levels are positively correlated with serum EV levels and Rab27a and HIF-1α protein levels in the tumor tissues of lung cancer patients. Thus, our results reveal a novel mechanism underlying lactate-mediated tumor progression induced by TEVs and provide new strategies for tumor therapy.