Trace Dual-Salt Electrolyte Additive Enabling a LiF-Rich Solid Electrolyte Interphase for High-Performance Lithium Metal Batteries.

The composition and physiochemical properties of the solid electrolyte interphase (SEI) significantly impact the electrochemical cyclability of the Li metal. Here, we introduce a trace dual-salt electrolyte additive (TDEA) that accelerates LiF production from FEC decomposition and improves the LiF distribution, resulting in earlier LiF precipitation and the formation of a LiF-rich SEI on the Li anode. TDEA at a millimolar-level concentration was found to alter the morphology of deposited Li, suppress Li dendrite formation, and increase the cycling time and operating current density for Li anodes. Li∥NCM811 full cells using TDEA-based electrolytes exhibited approximately two times longer lifespan than those without additives. Additionally, the TDEA-based electrolytes enabled a high energy density of 347 Wh kg-1 for 500-mAh pouch cells, maintaining stable cycling over 180 cycles under stringent conditions (N/P = 1.26 and E/C = 2.2 g A h-1). Our findings suggest that the proposed TDEA strategy offers a promising path to achieving high-performance Li metal batteries.

The metabolic slowdown caused by the deletion of pspA accelerates protein aggregation during stationary phase facilitating antibiotic persistence.

Entering a dormant state is a prevailing mechanism used by bacterial cells to transiently evade antibiotic attacks and become persisters. The dynamic progression of bacterial dormancy depths driven by protein aggregation has been found to be critical for antibiotic persistence in recent years. However, our current understanding of the endogenous genes that affects dormancy depth remains limited. Here, we discovered a novel role of phage shock protein A (pspA) gene in modulating bacterial dormancy depth. Deletion of pspA of Escherichia coli resulted in increased bacterial dormancy depths and prolonged lag times for resuscitation during the stationary phase. ∆pspA exhibited a higher persister ratio compared to the wild type when challenged with various antibiotics. Microscopic images revealed that ∆pspA showed accelerated formation of protein aggresomes, which were collections of endogenous protein aggregates. Time-lapse imaging established the positive correlation between protein aggregation and antibiotic persistence of ∆pspA at the single-cell level. To investigate the molecular mechanism underlying accelerated protein aggregation, we performed transcriptome profiling and found the increased abundance of chaperons and a general metabolic slowdown in the absence of pspA. Consistent with the transcriptomic results, the ∆pspA strain showed a decreased cellular ATP level, which could be rescued by glucose supplementation. Then, we verified that replenishment of cellular ATP levels by adding glucose could inhibit protein aggregation and reduce persister formation in ∆pspA. This study highlights the novel role of pspA in maintaining proteostasis, regulating dormancy depth, and affecting antibiotic persistence during stationary phase.

Trial of Intensive Blood-Pressure Control in Older Patients with Hypertension.

BACKGROUND: The appropriate target for systolic blood pressure to reduce cardiovascular risk in older patients with hypertension remains unclear. METHODS: In this multicenter, randomized, controlled trial, we assigned Chinese patients 60 to 80 years of age with hypertension to a systolic blood-pressure target of 110 to less than 130 mm Hg (intensive treatment) or a target of 130 to less than 150 mm Hg (standard treatment). The primary outcome was a composite of stroke, acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. RESULTS: Of the 9624 patients screened for eligibility, 8511 were enrolled in the trial; 4243 were randomly assigned to the intensive-treatment group and 4268 to the standard-treatment group. At 1 year of follow-up, the mean systolic blood pressure was 127.5 mm Hg in the intensive-treatment group and 135.3 mm Hg in the standard-treatment group. During a median follow-up period of 3.34 years, primary-outcome events occurred in 147 patients (3.5%) in the intensive-treatment group, as compared with 196 patients (4.6%) in the standard-treatment group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.92; P = 0.007). The results for most of the individual components of the primary outcome also favored intensive treatment: the hazard ratio for stroke was 0.67 (95% CI, 0.47 to 0.97), acute coronary syndrome 0.67 (95% CI, 0.47 to 0.94), acute decompensated heart failure 0.27 (95% CI, 0.08 to 0.98), coronary revascularization 0.69 (95% CI, 0.40 to 1.18), atrial fibrillation 0.96 (95% CI, 0.55 to 1.68), and death from cardiovascular causes 0.72 (95% CI, 0.39 to 1.32). The results for safety and renal outcomes did not differ significantly between the two groups, except for the incidence of hypotension, which was higher in the intensive-treatment group. CONCLUSIONS: In older patients with hypertension, intensive treatment with a systolic blood-pressure target of 110 to less than 130 mm Hg resulted in a lower incidence of cardiovascular events than standard treatment with a target of 130 to less than 150 mm Hg. (Funded by the Chinese Academy of Medical Sciences and others; STEP ClinicalTrials.gov number, NCT03015311.).

Blood-rsCDM: a new rapid and simplified carbapenemase detection method for detecting carbapenemases in Enterobacterales directly from positive blood cultures.

OBJECTIVE: We aim to validate and evaluate a new rapid and simplified method, called Blood-rsCDM, for the detection and characterization of carbapenemase using 3-aminophenylboronic acid (APBA) and ethylenediaminetetraacetic acid (EDTA) ß-lactamase inhibitors from positive blood cultures. METHOD: We utilized a panel of 172 Enterobacterales strains, including blaKPC (77), blaNDM (48), blaIMP (9), blaVIM (2), blaOXA-181 (2), blaKPC and blaNDM (6), as well as 28 carbapenem-susceptible Enterobacterales isolates, to assess the performance of Blood-rsCDM and the EDTA-carbapenem inactivation method (eCIM). Carbapenemase class was determined using specific inhibitors at 4 h and 6 h by Blood-rsCDM. RESULTS: Blood-rsCDM exhibited a sensitivity of 97.9% at both time points, with a specificity of 100%, regardless of the culture duration. The sensitivity of eCIM was 94.4%, with a specificity of 100%. Blood-rsCDM accurately characterized KPC-producing isolates as 77/77, metallo-ß-lactamases (MBLs) as 58/59, and KPC and NDM carbapenemases as 6/6 at 4 h. There was no difference in results between the 4 h and 6 h time points. However, Blood-rsCDM could not differentiate OXA-181-producing strains. For eCIM, the characterization numbers for KPC-, OXA-181-, and MBLs-producing strains were 77/77, 2/2, and 57/59, respectively, but it failed to detect the coproduction of KPC and NDM isolates. CONCLUSION: Blood-rsCDM accurately discriminates carbapenemase within 4 h and is capable of directly differentiating multi-enzyme (KPC and NDM) presence from positive blood culture broths. Therefore, Blood-rsCDM represents a rapid, simple, easy-to-read, and accurate tool that can be utilized in resource-limited settings.

Application of MALDI-TOF mass spectrometry for identification of Nocardia species.

BACKGROUND: Nocardiosis, despite its rarity and underreporting, is significant due to its severe impact, characterized by high morbidity and mortality rates. The development of a precise, reliable, rapid, and straightforward technique for identifying the pathogenic agent in clinical specimens is crucial to reduce fatality rates and facilitate timely antimicrobial treatment. In this study, we aimed to identify Nocardia spp. in clinical isolates, using MALDI-TOF MS as the primary method, with molecular methods as the gold standard. Clinical Nocardia isolates were identified using 16S rRNA/hsp65/gyrB/secA1/rpoB gene sequencing. Identification performance of the Bruker MALDI Biotyper 3.1 (V09.0.0.0_8468) and MBT Compass 4.1 (V11.0.0.0_10833) for Nocardia identification was evaluated. RESULTS: Seventy-six Nocardia isolates were classified into 12 species through gene sequencing. The MALDI Biotyper 3.1 (V09.0.0.0_8468) achieved 100% genus-level accuracy and 84.2% species accuracy (64/76). The MBT Compass 4.1 with the BDAL Database (V11.0.0.0_10833) improved species identification to 98.7% (75/76). The updated database enhanced species level identification with scores > 1.7, increasing from 77.6% (59/76) to 94.7% (72/76), a significant improvement (P = 0.001). The new and simplified extraction increased the proportion of strains identified to the species level with scores > 1.7 from 62.0% (18/29) to 86.2% (25/29) (P = 0.016). An in-house library construction ensured accurate species identification for all isolates. CONCLUSIONS: The Bruker mass spectrometer can accurately identify Nocardia species, albeit with some variations observed between different database versions. The MALDI Biotyper 3.1 (V09.0.0.0_8468) has limitations in identifying Nocardia brasiliensis, with some strains only identifiable to the genus level. MBT Compass 4.1 (V11.0.0.0_10833) effectively addresses this shortfall, improving species identification accuracy to 98.7%, and offering quick and reliable identification of Nocardia. Both database versions incorrectly identified the clinically less common Nocardia sputorum as Nocardia araoensis. For laboratories that have not upgraded their databases and are unable to achieve satisfactory identification results for Nocardia, employing the new and simplified extraction method can provide a degree of improvement in identification outcomes.

Optimal parameter selection for the THz-CCS system based on an incoherent light source.

Terahertz cross correlation spectroscopy (THz-CCS) systems using broadband incoherent light as the pumping source have received increasing attention from researchers in recent years. However, a comprehensive and in-depth understanding of THz-CCS is still needed to obtain a detailed optimization scheme. Here we systematically investigate the influences of the detection parameters, light propagation process, and pump source on the CCS signals. The impacts of the filter slopes and time constants in lock-in detection are revealed for optimizing the signal-to-noise ratio and bandwidth of the THz signal. By varying the optical fiber length and dispersion coefficient, the dispersion insensitivity of THz-CCS was experimentally demonstrated. The comparison of different pump sources (SLD and ASE) shows that the over-wide and non-flat pump spectrum may attenuate the CCS signal because of the energy waste brought by the photomixing process under the limited bandwidth of the photomixer. Our research may lead to a deeper understanding and further optimization of the THz-CCS system, which will promote the development and widespread application of what is to the best of our knowledge a new technique.

Associations between genetically predicted concentrations of plasma proteins and the risk of prostate cancer.

BACKGROUND: Prostate cancer (PCa) is a leading cause of cancer-related death in men. Understanding the proteomic landscape associated with PCa risk can provide insights into its molecular mechanisms and pave the way for potential therapeutic interventions. METHODS: A proteome-wide Mendelian randomization (MR) analysis was employed to determine associations between genetically predicted protein concentrations in plasma and PCa risk. From an initial list of 4,364 proteins, significant associations were identified and validated. Multiple sensitivity analyses were also conducted to enhance the robustness of our findings. RESULTS: Of the 4,364 genetically predicted proteins, 308 exhibited preliminary associations with PCa risk. After rigorous statistical refinement, genetically predicted concentrations of 14 proteins showed positive associations with PCa risk, with odds ratios spanning from 1.55 (95% CI 1.28-1.87) for ATG4B to 2.67 (95% CI 1.94-3.67) for HCN1. In contrast, genetically predicted concentrations of ATG7, B2M, MSMB, and TMEM108 demonstrated inverse associations with PCa. The replication analysis further substantiated positive associations for MDH1 and LSM1, and a negative one for MSMB with PCa. A meta-analysis harmonizing primary and replication data mirrored these findings. Furthermore, the MVMR analysis pinpointed B2M and MSMB as having significant associations with PCa risk. CONCLUSION: The genetic evidence unveils a refined set of proteins associated with PCa risk. The findings underscore the potential of these proteins as molecular markers or therapeutic targets for PCa, calling for deeper mechanistic studies and exploration into their translational relevance.

A log odds of positive lymph nodes-based predictive model effectively forecasts prognosis and guides postoperative adjuvant chemotherapy duration in stage III colon cancer: a multi-center retrospective cohort study.

BACKGROUND: The log odds of positive lymph nodes (LODDS) was considered a superior staging system to N stage in colon cancer, yet its value in determining the optimal duration of adjuvant chemotherapy for stage III colon cancer patients has not been evaluated. This study aims to assess the prognostic value of a model that combines LODDS with clinicopathological information for stage III colon cancer patients and aims to stratify these patients using the model, identifying individuals who could benefit from varying durations of adjuvant chemotherapy. METHOD: A total of 663 consecutive patients diagnosed with stage III colon cancer, who underwent colon tumor resection between November 2007 and June 2020 at Sun Yat-sen University Cancer Center and Longyan First Affiliated Hospital of Fujian Medical University, were enrolled in this study. Survival outcomes were analyzed using Kaplan-Meier, Cox regression. Nomograms were developed to forecast patient DFS, with the Area Under the Curve (AUC) values of time-dependent Receiver Operating Characteristic (timeROC) and calibration plots utilized to assess the accuracy and reliability of the nomograms. RESULTS: Multivariate analysis revealed that perineural invasion (HR = 1.776, 95% CI: 1.052-3.003, P = 0.032), poor tumor differentiation (HR = 1.638, 95% CI: 1.084-2.475, P = 0.019), and LODDS groupings of 2 and 1 (HR = 1.920, 95% CI: 1.297-2.842, P = 0.001) were independent predictors of disease-free survival (DFS) in the training cohort. Nomograms constructed from LODDS, perineural invasion, and poor tumor differentiation demonstrated robust predictive performance for 3-year and 5-year DFS in both training (3-year AUC = 0.706, 5-year AUC = 0.678) and validation cohorts (3-year AUC = 0.744, 5-year AUC = 0.762). Stratification according to this model showed that patients in the high-risk group derived significant benefit from completing 8 cycles of chemotherapy (training cohort, 82.97% vs 67.17%, P = 0.013; validation cohort, 89.49% vs 63.97%, P = 0.030). CONCLUSION: The prognostic model, integrating LODDS, pathological differentiation, and neural invasion, demonstrates strong predictive accuracy for stage III colon cancer prognosis. Moreover, stratification via this model offers valuable insights into optimal durations of postoperative adjuvant chemotherapy.

Clinical manifestations, antimicrobial resistance and genomic feature analysis of multidrug-resistant Elizabethkingia strains.

BACKGROUND: Elizabethkingia is emerging as an opportunistic pathogen in humans. The aim of this study was to investigate the clinical epidemiology, antimicrobial susceptibility, virulence factors, and genome features of Elizabethkingia spp. METHODS: Clinical data from 71 patients who were diagnosed with Elizabethkingia-induced pneumonia and bacteremia between August 2019 and September 2021 were analyzed. Whole-genome sequencing was performed on seven isolates, and the results were compared with a dataset of 83 available Elizabethkingia genomes. Genomic features, Kyoto Encyclopedia of Genes and Genomes (KEGG) results and clusters of orthologous groups (COGs) were analyzed. RESULTS: The mean age of the patients was 56.9 ± 20.7 years, and the in-hospital mortality rate was 29.6% (21/71). Elizabethkingia strains were obtained mainly from intensive care units (36.6%, 26/71) and emergency departments (32.4%, 23/71). The majority of the strains were isolated from respiratory tract specimens (85.9%, 61/71). All patients had a history of broad-spectrum antimicrobial exposure. Hospitalization for invasive mechanical ventilation or catheter insertion was found to be a risk factor for infection. The isolates displayed a high rate of resistance to cephalosporins and carbapenems, but all were susceptible to minocycline and colistin. Genomic analysis identified five ß-lactamase genes (blaGOB, blaBlaB, blaCME, blaOXA, and blaTEM) responsible for ß-lactam resistance and virulence genes involved in stress adaptation (ureB/G, katA/B, and clpP), adherence (groEL, tufA, and htpB) and immune modulation (gmd, tviB, cps4J, wbtIL, cap8E/D/G, and rfbC). Functional analysis of the COGs revealed that "metabolism" constituted the largest category within the core genome, while "information storage and processing" was predominant in both the accessory and unique genomes. The unique genes in our 7 strains were mostly enriched in KEGG pathways related to microRNAs in cancer, drug resistance (ß-lactam and vancomycin), ABC transporters, biological metabolism and biosynthesis, and nucleotide excision repair mechanisms. CONCLUSION: The Elizabethkingia genus exhibits multidrug resistance and carries carbapenemase genes. This study presents a comparative genomic analysis of Elizabethkingia, providing knowledge that facilitates a better understanding of this microorganism.

Vitamin C, vitamin E, ß-carotene and risk of Parkinson's disease: a systematic review and dose-response meta-analysis of observational studies.

OBJECTIVE: This study aimed to explore the relationship between the intake of vitamin C, vitamin E and ß-carotene, and the risk of Parkinson's disease (PD). METHODS: Web of Science, Embase, PubMed, Cochrane library, CNKI, and WanFang databases were searched from inception to 29 August 2022 for observational studies reporting the odds ratios (ORs) or relative risks (RRs) or hazard ratios (HRs) and 95% confidence intervals (CIs) of PD by Vitamin C/Vitamin E/ß-carotene intake. Random-effects models, publication bias assessment, subgroup, sensitivity and dose-response analyses were performed, using.Stata version 12.0. RESULTS: A total of 13 studies were included. There was no significant association between high-dose vitamin C intake and the risk of PD compared with low-dose vitamin C intake (RR = 0.98, 95%CI:0.89,1.08). Compared with low-dose intake, high-dose intake of vitamin E can prevent the risk of PD (RR = 0.87, 95%CI:0.77,0.99). Compared with lower ß-carotene intake, there was a borderline non-significant correlation between higher intake and PD risk (RR = 0.91, 95%CI:0.82,1.01), and high dose ß-carotene intake was found to be associated with a lower risk of PD in women (RR = 0.78, 95%CI:0.64,0.96). CONCLUSION: This study shows that vitamin E intake can reduce the risk of PD and play a preventive role.

A novel circumferential continuous reinforcing suture for anastomosis after laparoscopic resection for rectal cancer and sigmoid cancer: a retrospective case-controlled study.

INTRODUCTION: This study aimed to investigate the effectiveness of a novel method for anastomosis reinforcement to minimize the occurrence of anastomotic complications after surgical resection of rectal and sigmoid cancer. METHODS: We recruited 378 patients who underwent laparoscopic rectal anterior resection of rectal cancer and sigmoid cancer in SYSUCC. The occurrence rates of intraoperative bleeding, operation time, and postoperative anastomotic complications were compared between the treatment group receiving anastomotic reinforcement and the control group without anastomotic reinforcement. RESULTS: The incidence of anastomotic leakage in the treatment group was significantly lower than that in the control group (1.59% vs. 11.64%, p < 0.001). Following the application of inverse probability of treatment weighting (IPTW) to adjust for factors influencing the occurrence of anastomotic leakage, the incidence of anastomotic leakage remained significantly lower in the treatment group compared to the control group (2.54% vs. 12.08%, p < 0.001). CONCLUSION: The circumferential continuous anastomosis reinforcing suture method, recommended for laparoscopic surgery for rectal and sigmoid cancer, has the potential to effectively minimize the occurrence of anastomotic complications.

An evaluation model of hepatic steatosis based on CT value and serum uric acid/HDL cholesterol ratio can predict intrahepatic recurrence of colorectal cancer liver metastasis.

BACKGROUND: Intrahepatic recurrence is one of the main causes of treatment failure in patients with colorectal cancer liver metastasis (CRLM). Hepatic steatosis was reported to provide fertile soil for metastasis. The effect of irinotecan-inducted hepatic steatosis on the progression of liver metastasis remains to be verified. Therefore, we aim to clarify the effect of hepatic steatosis on postoperative intrahepatic recurrence in CRLM and whether it is relevant to irinotecan-based chemotherapy. METHODS: Data for a total of 284 patients undergoing curative surgical treatment for CRLMs were retrospectively reviewed between March 2007 and June 2018. Hepatic steatosis score (HSS) was established by combining Liver to Spleen CT ratio (LSR) and Uric acid to HDL-cholesterol ratio (UHR) to detect the presence of hepatic steatosis. RESULTS: The evaluation model is consistent with pathological results and has high prediction ability and clinical application value. Patients with HSS high risk (HSS-HR) had significantly worse prognosis than those with HSS low risk (HSS-LR) (3-year intrahepatic RFS: 42.7% vs. 29.4%, P = 0.003; 5-year OS: 45.7% vs. 26.5%, P = 0.002). Univariate and multivariate analysis confirmed its essential role in the prediction of intrahepatic RFS. Besides, patients treated with preoperative irinotecan chemotherapy were more likely to end up with HSS-HR than those with non-irinotecan chemotherapy (63.3% vs. 21.8%, P < 0.001). Furthermore, irinotecan chemotherapy is relevant to worse prognosis in baseline HSS-HR patients. CONCLUSION: In summary, patients with HSS-HR had significantly worse 5-year OS and 3-year intrahepatic RFS. Irinotecan chemotherapy is more likely to lead to HSS-HR and pre-existing hepatic steatosis may be a worse prognostic factor limiting patients underwent IRI-based chemotherapy.

Tetrahedral DNA-linked aptamer-antibody-based sandwich-type electrochemical sensor with Ag@Au core-shell nanoparticles as a signal amplifier for highly sensitive detection of α-fetoprotein.

The conventional electrochemical detection strategy for alpha-fetoprotein (AFP) is limited by the antigen-antibody (Ag-Ab) reactions and suffers from low sensitivity and poor reproducibility due to the inconsistency of Ab-modified electrodes. Herein, we designed and explored a sandwich-type electrochemical sensor for highly sensitive detection of AFP based on aptamer (Apt)-AFP-Ab interaction mode with silver@gold (Ag@Au) core-shell nanoparticles (NPs) as a signal amplifier. AuNPs were electrodeposited onto MXene (Ti3C2TX)-modified glassy carbon electrode (GCE) to get AuNPs/MXene/GCE and further used as the signal amplification substrate. The tetrahedral DNA-linked AFP aptamers were immobilized onto AuNPs/MXene/GCE surface via Au-S bonds and used as the sensing and recognition platform for AFP capturing. Ag@AuNPs with core-shell structures were synthesized, characterized, and bound with Ab as detection elements by catalyzing H2O2 reduction. In the presence of AFP, a stable Apt-AFP-Ab sandwich structure was formed owing to the high affinities of aptamer and Ab toward the target AFP. The catalytic current produced by H2O2 reduction increased linearly with the logarithm of AFP concentration from 5 × 10-4 ng/mL to 1 × 105 ng/mL, accompanied by a low detection limit (1.6 × 10-4 ng/mL). Moreover, the novel sandwich-type electrochemical sensor shows high sensitivity, outstanding selectivity, and promising performance in the analysis of actual samples, displaying a broad application prospect in bioanalysis.

Relationship between virulence and carbapenem resistance phenotype of Klebsiella pneumoniae from blood infection: identification of a carbapenem-resistant and hypervirulent strain. / è¡€æ¶²æ„ŸæŸ“æ¥æºè‚ºç‚Žå ‹é›·ä¼¯èŒæ¯’åŠ›ä¸Žç¢³é’éœ‰çƒ¯ç±»è€è¯è¡¨åž‹çš„å ³ç³»åŠç¢³é’éœ‰çƒ¯ç±»è€è¯é«˜æ¯’åŠ›èŒæ ªçš„é‰´å®š.

OBJECTIVES: To investigate the relationship between the virulence and the carbapenem resistance phenotype of Klebsiella pneumoniae from blood infection, and to identify carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-HVKP)strains. METHODS: A total of 192 Klebsiella pneumoniae strains were isolated from blood culture of patients with bloodstream infections from 2016 to 2019, of which 96 isolates were carbapenem-resistant Klebsiella pneumoniae (CRKP) and 96 were carbapenem-sensitive Klebsiella pneumoniae (CSKP). The drug susceptibility was detected by VITEK-2 automatic microbial analyzer; carbapenemase genes, virulence genes and capsule typing were detected by polymerase chain reaction; the high viscosity phenotype of strains was detected by string test, and the genome characteristics of CR-HVKP were detected by whole genome sequencing. Serum killing and biofilm formation test were used to further verify the virulence of CR-HVKP. RESULTS: There were significant differences in drug resistance to common antibiotics, except for minocycline between CSKP and CRKP isolates (all P<0.05). 92 out of 96 CRKP isolates carried carbapenemase genes, mainly blaKPC-2. The string tests were positive in 4 isolates of CRKP and 36 isolates of CSKP (P<0.05). The detection rates of virulence genes Kfu, aerobictin, iutA, ybtS, rmpA, magA, allS, and capsule antigen K1 and K2 in CSKP group were significantly higher than those in CRKP group (all P<0.05). One HVKP strain was detected in the CRKP group (CR-HVKP) and 36 HVKP was detected in the CSKP group (P<0.05). The CR-HVKP strain belonged to the MLST412, serotype K57, expressed iutA, entB, mrkD, fimH, and rmpA virulence genes, and showed strong biofilm formation and significantly increased serum resistance. Whole genome sequencing results showed that this CR-HVKP isolate carried blaSHV-145, blaTEM-1, blaCTX-M-3, fosA6, oqxA5, oqxB26, and aac(3)-IId resistance genes, accompanied by abnormalities in outer membrane protein K (OmpK) 35 and OmpK36. CONCLUSIONS: The drug resistance of CRKP is significantly higher than that of CSKP, while CRKP carrying fewer virulence genes in both number and types compared to CSKP. A new MLST type of carbapenem-resistant and hypervirulent Klebsiella pneumoniae strain has been detected, which requires clinical awareness and epidemiological monitoring.

[Carbapenemase Genes, Virulence Genes, and Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Derived From Bloodstream Infections]. / è¡€æµæ„ŸæŸ“ç¢³é’éœ‰çƒ¯è€è¯è‚ºç‚Žå ‹é›·ä¼¯èŒçš„è€è¯åŸºå› å’Œæ¯’åŠ›åŸºå› åŠåˆ†å­æµè¡Œç— å­¦ç ”ç©¶.

Objective: To investigate the clinical characteristics and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolated from patients with bloodstream infections in a large tertiary-care general hospital in Southwest China. Methods: A total of 131 strains of non-repeating CRKP were collected from the blood cultures of patients who had bloodstream infections in 2015-2019. The strains were identified by VITEK-2, a fully automated microbial analyzer, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The minimum inhibitory concentration (MIC) was determined by microbroth dilution method. The common carbapenemase resistant genes and virulence factors were identified by PCR. Homology analysis was performed by multilocus sequencing typing. Whole genome sequencing was performed to analyze the genomic characteristics of CRKP without carbapenemase. Results: The 131 strains of CRKP showed resistance to common antibiotics, except for polymyxin B (1.6% resistance rate) and tigacycline (8.0% resistance rate). A total of 105 (80.2%) CRKP strains carried the Klebsiella pneumoniae carbapenemase (KPC) resistance gene, 15 (11.4%) strains carried the New Delhi Metallo-ß-lactamase (NDM) gene, and 4 (3.1%) isolates carried both KPC and NDM genes. Sequence typing (ST) 11 (74.0%) was the dominant sequence type. High detection rates for mrkD (96.2%), fimH (98.5%), entB (100%), and other virulence genes were reported. One hypervirulent CRKP strain was detected. The seven strains of CRKP that did not produce carbapenemase were shown to carry ESBL or AmpC genes and had anomalies in membrane porins OMPK35 and OMPK36, according to whole genome sequencing. Conclusion: In a large-scale tertiary-care general hospital, CRKP mainly carries the KPC gene, has a high drug resistance rate to a variety of antibiotics, and possesses multiple virulence genes. Attention should be paid to CRKP strains with high virulence.

Rational Lithium Salt Molecule Tuning for Fast Charging/Discharging Lithium Metal Battery.

The electrolytes for lithium metal batteries (LMBs) are plagued by a low Li+ transference number (T+) of conventional lithium salts and inability to form a stable solid electrolyte interphase (SEI). Here, we synthesized a self-folded lithium salt, lithium 2-[2-(2-methoxy ethoxy)ethoxy]ethanesulfonyl(trifluoromethanesulfonyl) imide (LiETFSI), and comparatively studied with its structure analogue, lithium 1,1,1-trifluoro-N-[2-[2-(2-methoxyethoxy)ethoxy)]ethyl]methanesulfonamide (LiFEA). The special anion chemistry imparts the following new characteristics: i) In both LiFEA and LiETFSI, the ethylene oxide moiety efficiently captures Li+, resulting in a self-folded structure and high T+ around 0.8. ii) For LiFEA, a Li-N bond (2.069 Å) is revealed by single crystal X-ray diffraction, indicating that the FEA anion possesses a high donor number (DN) and thus an intensive interphase "self-cleaning" function for an ultra-thin and compact SEI. iii) Starting from LiFEA, an electron-withdrawing sulfone group is introduced near the N atom. The distance of Li-N is tuned from 2.069 Šin LiFEA to 4.367 Šin LiETFSI. This alteration enhances ionic separation, achieves a more balanced DN, and tunes the self-cleaning intensity for a reinforced SEI. Consequently, the fast charging/discharging capability of LMBs is progressively improved. This rationally tuned anion chemistry reshapes the interactions among Li+, anions, and solvents, presenting new prospects for advanced LMBs.

A positive feedback circuit driven by m6A-modified circular RNA facilitates colorectal cancer liver metastasis.

BACKGROUND: Liver metastasis is the leading cause of death in patients with colorectal cancer (CRC). Emerge evidence suggests that circular RNA (circRNA) is a pivotal player in cancer progression. However, its role in CRC liver metastasis remains largely unknown. METHODS: Circ-YAP expression was detected by qRT-PCR and in situ hybridization. The function of circ-YAP was tested by wound healing, transwell and CCK-8 assays. RNA immunoprecipitation, pull-down, luciferase reporter, chromatin immunoprecipitation assays were used to investigate the mechanism underlying circ-YAP promoting CRC liver metastasis. CRC liver metastasis animal model was established to assess the effect of circ-YAP in vivo. RESULTS: Circ-YAP was notably upregulated in CRC with liver metastasis, which was associated with dismal prognosis. Circ-YAP promoted CRC cell migration and invasion in vitro, and facilitated liver metastasis in patient-derived xenografts (PDX) models in vivo. Mechanistically, circ-YAP encoded a novel truncated protein containing 220 amino acids, termed as YAP-220aa, which competitively bound to LATS1, resulting in YAP dephosphorylation and nuclear translocation, thereby activating a cohort of metastasis-promoting genes. Importantly, N6-methyladenosine (m6A) modification orchestrated efficient initiation of circ-YAP translation, requiring m6A reader YTHDF3 and eIF4G2 translation initiation complex. Intriguingly, circ-YAP was transcriptionally enhanced by YAP/TEAD complex, thus forming a positive regulatory feed-forward loop. CONCLUSIONS: Our findings reveal a previously uncharacterized oncoprotein encoded by circ-YAP, implying a promising biomarker and therapeutic target for CRC patients with liver metastasis.

Evaluation of the Autof ms1000 mass spectrometry for rapid clinical identification of filamentous fungi.

BACKGROUND: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has revolutionized microbial identification. However, there is a lack of data on its performance in identifying filamentous fungi. The objective of our study was to evaluate the accuracy of the Autof ms1000 mass spectrometry for identifying filamentous fungi in the clinical microbiology laboratory. RESULTS: Among 106 samples tested using the Autof ms1000 system, 101 (95.28%) were identified at the genus or species level, and 81 (76.41%) were accurately identified at the species level. Additionally, we developed a new rapid formic acid extraction method with simple pretreatment for filamentous fungi that saved time and provided accurate results. CONCLUSIONS: The Autof ms1000 mass spectrometer proved to be a valuable tool for identifying filamentous fungi. However, upgrading the database is recommended for correctly identifying rare strains.

Association of MPPED2 gene variant rs10767873 with kidney function and risk of cardiovascular disease in patients with hypertension.

Changes in kidney function and the progression of chronic kidney disease (CKD) are associated with the risk of cardiovascular disease (CVD) and influenced by genetic factors. However, the association between genetic variants and kidney function in patients treated with antihypertensive drugs remains uncertain. This study aimed to examine the association between 30 variants locating at the 22 genes and the risk of kidney function evaluated by the estimated glomerular filtration rate (eGFR) in 1911 patients with hypertension from a Chinese community-based longitudinal cohort (including 1220 participants with CKD and 691 without CKD at baseline). By using multivariate linear regression analysis after adjustment for age, sex, traditional cardiovascular risk factors, and the use of antihypertensive drugs, as well as after correction for multiple comparison, patients with rs10767873T allele of the metallophosphoesterase domain containing 2 (MPPED2) gene were associated with higher level of eGFR (ß = 0.041, p = 0.01) and lower levels of serum creatinine (ß = -0.068, p = 0.001) and serum uric acid (ß = -0.047, p = 0.02). But variant rs10767873 was not found to be associated with the risk of CKD, regardless of the types of antihypertensive drugs used. During a median 2.25-year follow-up, 152 CVD events were documented. Interestingly, patients with the rs10767873TT genotype had an increased risk of CVD events (hazard ratio, 1.74, 95% confidence interval, 1.11 to 2.73; p = 0.02) compared with patients carrying the wild-type genotype of rs10767873CC. In conclusion, our findings suggest variant rs10767873 of the MPPED2 gene is associated with kidney function and risk of CVD in Chinese hypertensive patients.

Thickness-dependent loss-induced failure of an ideal ENZ-enhanced optical response in planar ultrathin transparent conducting oxide films.

Ultrathin planar transparent conducting oxide (TCO) films are commonly used to enhance the optical response of epsilon-near-zero (ENZ) devices; however, our results suggest that thickness-dependent loss renders them ineffective. Here, we investigated the thickness-dependent loss of indium tin oxide (ITO) films and their effect on the ENZ-enhanced optical responses of ITO and ITO/SiO2 multilayer stacks. The experimental and computational results show that the optical loss of ITO films increases from 0.47 to 0.70 as the thickness decreases from 235 to 52 nm, which results in a reduction of 60% and 45% in the maximum field enhancement factor of a 52-nm monolayer ITO and 4-layer ITO/SiO2 multilayer stack, respectively. The experimental results show that the ENZ-enhanced nonlinear absorption coefficient of the 52-nm single-layer ITO film is -1.6 × 103 cm GW-1, which is 81% lower than that of the 235-nm ITO film (-8.6 × 103 cm GW-1), indicating that the thickness-dependent loss makes the ultrathin TCO films unable to obtain greater nonlinear responses. In addition, the increased loss reduces the cascading Berreman transmission valley intensity of the 4-layer ITO/SiO2 multilayer stack, resulting in a 42% reduction in the ENZ-enhanced nonlinear absorption coefficient compared to the 235-nm ITO film and a faster hot electron relaxation time. Our results suggest that the thickness and loss trade-off is an intrinsic property of TCO films and that the low-loss ultrathin TCO films are the key to the robust design and fabrication of novel ENZ devices based on flat ultrathin TCO films.