Novel Insights into Alkyl Polyglucoside Biosurfactant Promoting Anaerobic Dark Fermentation for Hydrogen Production in Sludge.

Anaerobic fermentation of excess sludge (ES) for hydrogen production is a crucial strategy for resource utilization and environmentally friendly treatment. However, the low hydrolysis efficiency of ES and the depletion of produced hydrogen have become the limiting factors for low hydrogen yield. This study innovatively applied the bio-based surfactant alkyl polyglucoside (APG) to enhance the efficiency of dark fermentation for hydrogen production from ES. When the APG content was 100 mg/g (calculated based on total suspended solids), the maximum hydrogen production reached 17.8 mL/g VSS, approximately 3.7 times that in the control group. Mechanistic analysis revealed that APG promoted the release of organic matter from ES. APG also facilitated the release of soluble protein and soluble polysaccharide, increasing the organic matter reduction rate to 34.8%, significantly higher than other groups. APG enhanced the accumulation of volatile fatty acids and promoted the proportion of small molecular carboxylic acids. Enzyme activity analysis revealed that APG promoted the activity of hydrolytic enzymes but inhibited the activity of hydrogen-consuming enzymes. The research results provide a green and environmentally friendly strategy for the efficient resource utilization of ES.

Analysis of the influencing factors and clinical related characteristics of pulmonary tuberculosis in patients with type 2 diabetes mellitus.

BACKGROUND: In China, the prevalence of type 2 diabetes mellitus (T2DM) among diabetic patients is estimated to be between 90%-95%. Additionally, China is among the 22 countries burdened by a high number of tuberculosis cases, with approximately 4.5 million individuals affected by active tuberculosis. Notably, T2DM poses a significant risk factor for the development of tuberculosis, as evidenced by the increased incidence of T2DM coexisting with pulmonary tuberculosis (T2DM-PTB), which has risen from 19.3% to 24.1%. It is evident that these two diseases are intricately interconnected and mutually reinforcing in nature. AIM: To elucidate the clinical features of individuals diagnosed with both T2DM and tuberculosis (T2DM-PTB), as well as to investigate the potential risk factors associated with active tuberculosis in patients with T2DM. METHODS: T2DM-PTB patients who visited our hospital between January 2020 and January 2023 were selected as the observation group, Simple DM patients presenting to our hospital in the same period were the control group, Controls and case groups were matched 1:2 according to the principle of the same sex, age difference ( ± 3) years and disease duration difference ( ± 5) years, patients were investigated for general demographic characteristics, diabetes-related characteristics, body immune status, lifestyle and behavioral habits, univariate and multivariate analysis of the data using conditional logistic regression, calculate the odds ratio (OR) values and 95%CI of OR values. RESULTS: A total of 315 study subjects were included in this study, including 105 subjects in the observation group and 210 subjects in the control group. Comparison of the results of both anthropometric and biochemical measures showed that the constitution index, systolic blood pressure, diastolic blood pressure and lymphocyte count were significantly lower in the case group, while fasting blood glucose and high-density lipoprotein cholesterol levels were significantly higher than those in the control group. The results of univariate analysis showed that poor glucose control, hypoproteinemia, lymphopenia, TB contact history, high infection, smoking and alcohol consumption were positively associated with PTB in T2DM patients; married, history of hypertension, treatment of oral hypoglycemic drugs plus insulin, overweight, obesity and regular exercise were negatively associated with PTB in T2DM patients. Results of multivariate stepwise regression analysis found lymphopenia (OR = 17.75, 95%CI: 3.40-92.74), smoking (OR = 12.25, 95%CI: 2.53-59.37), history of TB contact (OR = 6.56, 95%CI: 1.23-35.03) and poor glycemic control (OR = 3.37, 95%CI: 1.11-10.25) was associated with an increased risk of developing PTB in patients with T2DM, While being overweight (OR = 0.23, 95%CI: 0.08-0.72) and obesity (OR = 0.11, 95%CI: 0.02-0.72) was associated with a reduced risk of developing PTB in patients with T2DM. CONCLUSION: T2DM-PTB patients are prone to worse glycemic control, higher infection frequency, and a higher proportion of people smoking, drinking alcohol, and lack of exercise. Lymphopenia, smoking, history of TB exposure, poor glycemic control were independent risk factors for T2DM-PTB, and overweight and obesity were associated with reduced risk of concurrent PTB in patients with T2DM.

Daidzein protects endothelial cells against high glucose-induced injury through the dual-activation of PPARα and PPARγ.

Endothelial damage caused by persistent glucose and lipid metabolism disorders is the main reason of diabetic vascular diseases. Daidzein exerts positive effects on vascular dysfunction. Peroxisome proliferator-activated receptors (PPARs) regulate critically glucose and lipid metabolism. However, the interaction of daidzein to PPARs is still insufficiently explored. In this study, the cell proliferation was detected by EdU. The intrinsic activity and binding affinity of daidzein for human PPARs (hPPARs) were estimated by transactivation reporter gene test and HPLC-UV method, respectively. Daidzein significantly reversed high glucose (HG, at 30 mmol/l)-induced injury in HUVECs, which was inhibited by both PPARα and PPARγ antagonist, but no PPARß antagonist. Daidzein selectively activated hPPARα and hPPARγ1, but weakly hPPARß. Additionally, daidzein also bound to both hPPARα and hPPARγ1. The findings suggested that daidzein may be a PPARα and PPARγ dual-agonist. The amelioration of daidzein on HUVECs from hyperglycemia may be mediated by the activation of PPARα and PPARγ receptors.

The combination of high uric acid and high C-reactive protein increased the risk of cardiovascular disease: A 15-year prospective cohort study.

BACKGROUND AND AIMS: Uric acid (UA) and C-reactive protein (CRP) may interact synergistically to accelerate the initiation and progression of cardiovascular disease (CVD). This study investigated the effects of a combination of high UA and high CRP on the risks of CVD. METHODS AND RESULTS: A total of 90,270 participants recruited from the Kailuan study were included, who were divided into four groups according to the presence/absence of hyperuricemia and inflammation. Cox regression was applied to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CVD. C-statistics, net classification index (NRI), and integrated discrimination improvement (IDI) were used to compare the incremental predictive of UA, CRP, and their combined effects on CVD. Mediation analysis was to explore the impact of CRP on the association between UA and CVD. Over a median follow-up of 14.95 years, we identified 11398 incident CVD cases. Compared to the low UA/low CRP group, the high UA/low CRP, low UA/high CRP and high UA/high CRP groups showed progressively higher risks of CVD, HR (95% CI): 1.18(1.10-1.27), 1.27(1.21-1.33) and 1.50 (1.33-1.69), respectively. The incorporation of UA and CRP into the traditional China-PAR model led to improvement in the C-statistic, NRI, and IDI, and was better than incorporation of either UA or CRP alone. Mediation analysis showed that CRP mediated the association between UA and CVD, accounting for 11.57% of the total effects. CONCLUSIONS: High UA/high CRP is associated with increased risks of CVD. Incorporation of both UA and CRP provided additional value for risk stratification.

Discovery of a Monoclonal Antibody That Targets Cell-Surface Pseudaminic Acid of Acinetobacter baumannii with Direct Bactericidal Effect.

The therapeutic effects of antibodies include neutralization of pathogens, activation of the host complement system, and facilitation of phagocytosis of pathogens. However, antibody alone has never been shown to exhibit bactericidal activity. In this study, we developed a monoclonal antibody that targets the bacterial cell surface component Pseudaminic acid (Pse). This monoclonal antibody, Pse-MAB1, exhibited direct bactericidal activity on Acinetobacter baumannii strains, even in the absence of the host complements or other immune factors, and was able to confer a protective effect against A. baumannii infections in mice. This study provides new insight into the potential of developing monoclonal antibody-based antimicrobial therapy of multidrug resistant bacterial infections, especially those which occurred among immunocompromised patients.

Early detection of OXA-232-producing Klebsiella pneumoniae in China predating its global emergence.

Antibiotic resistance is a global health issue, with Klebsiella pneumoniae (KP) posing a particular threat due to its ability to acquire resistance to multiple drug classes rapidly. OXA-232 is a carbapenemase that confers resistance to carbapenems, a class of antibiotics often used as a last resort for treating severe bacterial infections. The study reports the earliest known identification of six OXA-232-producing KP strains that were isolated in Zhejiang, China, in 2008 and 2009 within a hospital, two years prior to the first reported identification of OXA-232 in France. The four KP strains carry the OXA-232 gene and exhibit hypervirulent loci, suggesting a broader temporal and geographical spread and integration of this resistance and virulence than previously recognized with implications for public health. Global analysis of all OXA-232-bearing KP strains revealed that OXA-232-encoding plasmids are conservative, while the strains were very diverse suggesting the plasmid mediated transmission of this carbapenemase genes. Importantly, a large proportion of the OXA-232-bearing KP strains also carried virulence plasmids, in particular the recent emergence of ST15 type of KP that carried both OXA-232-encoding plasmids and hypervirulent (hv) plasmids in China since 2019, highlighting the importance of the emergence of this type of KP strains in clinical setting. The early detection and investigations of OXA-232 in these strains warrants the retrospective studies to uncover the true timeline of antibiotic resistance spread, which could provide valuable insights for shaping future strategies to tackle the global health crisis.

Loss of UBE2S causes meiosis I arrest with normal spindle assembly checkpoint dynamics in mouse oocytes.

The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin-ligase, is responsible for the degradation of proteins. Ubiquitin-conjugating enzyme E2 S (UBE2S), an E2 ubiquitin-conjugating enzyme, delivers ubiquitin to APC/C. APC/C has been extensively studied, but the functions of UBE2S in oocyte maturation and mouse fertility are not clear. In this study, we used Ube2s knockout mice to explore the role of UBE2S in mouse oocytes. Ube2s-deleted oocytes were characterized by meiosis I arrest with normal spindle assembly and spindle assembly checkpoint dynamics. However, the absence of UBE2S affected the activity of APC/C. Cyclin B1 and securin are two substrates of APC/C, and their levels were consistently high, resulting in the failure of homologous chromosome separation. Unexpectedly, the oocytes arrested in meiosis I could be fertilized and the embryos could become implanted normally, but died before embryonic day 10.5. In conclusion, our findings reveal an indispensable regulatory role of UBE2S in mouse oocyte meiosis and female fertility.

Molecular epidemiology and clinical impact of Klebsiella spp. causing bloodstream infections in Hong Kong.

BACKGROUND: The epidemiological features of the Klebsiella pneumoniae causing bloodstream infections in Hong Kong and their potential threats to human health remained unknown. METHODS: K. pneumoniae strains collected from four hospitals in Hong Kong during the period of 2009-2018 were subjected to molecular typing, string test, antimicrobial susceptibility testing, whole genome sequencing and analysis. Clinical data of patients from whom these strains were isolated were analyzed retrospectively using univariate and multivariate logistic regression approaches. FINDINGS: The 240 Klebsiella spp. strains belonged to 123 different STs and 63 different capsule loci (KLs), with KL1 and KL2 being the major type. 86 out of 212 BSI-KP (40.6%) carried at least one of the virulence genes iuc, iro, rmpA or rmpA2. Virulence plasmid correlated well with the string test positive result, yet 8 strains without rmp genes were also hypermucoviscous, which was due to wzc mutation. The mortality rate of bloodstream infection patients was 43.0%. Univariant analysis showed that factors including renal replacement therapy (FDR adjusted p = 0.0007), mechanical ventilation (FDR adjusted p < 0.0001) and respiratory sepsis (FDR adjusted p < 0.0001) were found to pose the highest risk of death upon infection by Klebsiella spp. INTERPRETATION: This study revealed the high mortality rate and risk factors associated with bloodstream infections caused by K. pneumoniae in Hong Kong, which warrants immediate action to develop effective solution to tackle this problem. FUNDING: Theme Based Research Scheme (T11-104/22-R), Research Impact Fund (R5011-18 F) and Postdoctoral Fellowship (PDFS2223-1S09).

Transmission of azithromycin-resistant gene, erm(T), of Gram-positive bacteria origin to Klebsiella pneumoniae.

The erm(T) gene encodes the 23 s rRNA methyltransferase and confers erythromycin resistance in Gram-positive bacteria, while has rarely been identified in Gram-negative bacteria. In this study, we identified a small IncQ1 plasmid of 6135 bp harboring the erm(T) gene in a clinical K. pneumoniae strain and confirmed the role of the erm(T) gene in mediating azithromycin resistance. This plasmid was found to be generated by incorporating the erm(T) gene from mobile elements into an IncQ1 plasmid. Our data indicated the spread of the erm(T) gene from Gram-positive bacteria to Gram-negative bacteria and the clonal spread of the ST11-KL47 type K. pneumoniae strains carrying this plasmid. Generation of this kind of multi-host plasmid will promote the dissemination of the erm(T) gene among Gram-negative bacteria and result in failures of azithromycin in treating bacterial infections.

Structurally diverse cucurbitane-type triterpenoids from the tubers of Hemsleya chinensis with cytotoxic activity.

Ten previously undescribed cucurbitane-type triterpenoids, namely hemslyencins A-F (1-6) and hemslyencosides A-D (7-10), together with twenty previously reported compounds (11-30), were isolated from the tubers of Hemsleya chinensis. Their structures were elucidated by unambiguous spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR data). Hemslyencins A and B (1 and 2) possessing unique 9, 11-seco-ring system with a six-membered lactone moiety, were the first examples among of the cucurbitane-type triterpenoids, and hemslyencins C and D (3 and 4) and hemslyencoside D (10) are the infrequent pentacyclic cucurbitane triterpenes featuring a 6/6/6/5/6 fused system. The cytotoxic activities of all isolated compounds were evaluated against MCF-7, HCT-116, HeLa, and HepG2 cancer cells, and their structure-activity relationships (SARs) was discussed as well. Compounds 17, 25, and 26 showed significant cytotoxic effects with IC50 values ranging from 1.31 to 9.89 µM, among which compound 25 induced both apoptosis and cell cycle arrest at G2/M phase in a dose dependent manner against MCF-7 cells.

Continuous-wave long-wavelength infrared difference-frequency generation in ZGP driven by near-infrared fiber lasers.

We report the continuous-wave (cw) difference-frequency generation (DFG) in a ZnGeP2 (ZGP) crystal that produces tunable long-wavelength infrared (LWIR) lasing. Particularly, we experimentally demonstrate the feasibility to drive DFG in ZGP by all-fiber near-infrared fiber lasers consisting of a 1.3 µm tunable cw random Raman fiber laser (RRFL) and a 1.5 µm erbium-doped fiber amplifier seeded by a tunable distributed feedback (DFB) laser, making the whole system compact and robust. As a result, the demonstrated LWIR DFG presents a broadband spectral tuning range spanning from 9.5 to 11.5 µm, and the output powers in the spectral range of 9.5-11 µm are larger than 40 µW pumped by watt-level fiber lasers. Meanwhile, as a typical application, a proof-of-concept demonstration of gas sensing of SF6 is executed based on the generated cw LWIR source. Our work demonstrates that the combination of ZGP crystal and fiber lasers can provide an effective and robust approach for the generation of cw LWIR radiation with useful power and broadband wavelength tunability.

Distinct uric acid trajectories are associated with incident cardiac conduction block.

BACKGROUND: The association of longitudinal uric acid (UA) changes with cardiac conduction block risk is unclear. We aimed to identify the trajectories of UA and explore its association with cardiac conduction block. METHODS: A total of 67,095 participants with a mean age of 53.12 years were included from the Kailuan cohort in Tangshan, China, who were free of cardiac conduction block and with repeated measurements of UA from 2006 to 2012. UA trajectories during 2006 to 2012 were identified by group-based trajectory modeling. Cox proportional hazard regression models were used to assess the association of UA trajectories with cardiac conduction block. RESULTS: We categorized three observed discrete trajectories of UA during 2006-2012 period: low-stable, moderate-stable, and high-stable. Over a median follow-up of 6.19 years, we identified 1405 (2.09%) incident cardiac conduction block. Compared to those in the low-stable trajectory, the adjusted hazard ratios (HRs) (95% confidence interval [CI]) of cardiac conduction block in the moderate-stable and high-stable trajectory were 1.30 (1.16-1.47) and 1.86 (1.56-2.22), and HRs of atrioventricular block were 1.39 (1.12-1.72) and 2.90 (2.19-3.83), and HRs of bundle branch blocks were 1.27 (1.10-1.47) and 1.43 (1.13-1.79). Notably, although the average UA level in the moderate-stable UA trajectory group is within the normal range, the risk of cardiac conduction block has increased. CONCLUSIONS: The moderate-stable and high-stable trajectories are associated with increased risk for new-onset cardiac conduction block. Monitoring UA trajectories may assist in identifying subpopulations at higher risk for cardiac conduction block.

Effect of 10-year cumulative blood pressure exposure on atherosclerotic cardiovascular disease of different age groups: kailuan cohort study.

Background: The level at which cumulative blood pressure (BP) can increase the risk of ASCVD in different age groups remains unclear. This study aimed to investigate the association of 10-year cumulative BP levels with the long-term risk of ASCVD of different age groups. Methods: Cumulative BP exposure was assessed using the time-weighted average (TWA) BP divided into four BP groups. The participants were also divided into four groups according to their baseline age (<50, 50-59, 60-69, or ≥70 years). The association between TWA BP and the risk of ASCVD was assessed by age group using multivariate Cox models. The China-PAR prediction model was used to assess the ability of TWA BP to predict ASCVD. Results: In the group aged <50 years, the hazard ratios and 95% confidence intervals for the risk of ASCVD were 2.66 (1.04-6.80), 3.38 (1.54-7.43), and 3.13 (1.36-7.24) for the elevated BP, stage 1 hypertension, and stage 2 hypertension groups, respectively, when compared with the normal BP group. There was a significant difference in the risk of ASCVD between the age groups, with participants aged <50 years having the highest risk, followed by those aged 50-59, 60-69, and ≥70 years. Conclusions: The risk of ASCVD with high cumulative BP exposure was age-dependent, with a gradual decrease in risk with increasing age.

Histone lactylation inhibits RARγ expression in macrophages to promote colorectal tumorigenesis through activation of TRAF6-IL-6-STAT3 signaling.

Macrophages are phenotypically and functionally diverse in the tumor microenvironment (TME). However, how to remodel macrophages with a protumor phenotype and how to manipulate them for therapeutic purposes remain to be explored. Here, we show that in the TME, RARγ is downregulated in macrophages, and its expression correlates with poor prognosis in patients with colorectal cancer (CRC). In macrophages, RARγ interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6), which prevents TRAF6 oligomerization and autoubiquitination, leading to inhibition of nuclear factor κB signaling. However, tumor-derived lactate fuels H3K18 lactylation to prohibit RARγ gene transcription in macrophages, consequently enhancing interleukin-6 (IL-6) levels in the TME and endowing macrophages with tumor-promoting functions via activation of signal transducer and activator of transcription 3 (STAT3) signaling in CRC cells. We identified that nordihydroguaiaretic acid (NDGA) exerts effective antitumor action by directly binding to RARγ to inhibit TRAF6-IL-6-STAT3 signaling. This study unravels lactate-driven macrophage function remodeling by inhibition of RARγ expression and highlights NDGA as a candidate compound for treating CRC.

Identification of NADPH Oxidase Genes Crucial for Rice Multiple Disease Resistance and Yield Traits.

Reactive oxygen species (ROS) act as a group of signaling molecules in rice functioning in regulation of development and stress responses. Respiratory burst oxidase homologues (Rbohs) are key enzymes in generation of ROS. However, the role of the nine Rboh family members was not fully understood in rice multiple disease resistance and yield traits. In this study, we constructed mutants of each Rboh genes and detected their requirement in rice multiple disease resistance and yield traits. Our results revealed that mutations of five Rboh genes (RbohA, RbohB, RbohE, RbohH, and RbohI) lead to compromised rice blast disease resistance in a disease nursery and lab conditions; mutations of five Rbohs (RbohA, RbohB, RbohC, RbohE, and RbohH) result in suppressed rice sheath blight resistance in a disease nursery and lab conditions; mutations of six Rbohs (RbohA, RbohB, RbohC, RbohE, RbohH and RbohI) lead to decreased rice leaf blight resistance in a paddy yard and ROS production induced by PAMPs and pathogen. Moreover, all Rboh genes participate in the regulation of rice yield traits, for all rboh mutants display one or more compromised yield traits, such as panicle number, grain number per panicle, seed setting rate, and grain weight, resulting in reduced yield per plant except rbohb and rbohf. Our results identified the Rboh family members involved in the regulation of rice resistance against multiple pathogens that caused the most serious diseases worldwide and provide theoretical supporting for breeding application of these Rbohs to coordinate rice disease resistance and yield traits.

Severe photochemical pollution was found in large petrochemical complexes: A typical case study in North China.

Large petrochemical complex (PC) widely exists in both developing and developed countries, and is expected to have a special photochemical pollution in local scale due to huge VOCs emissions. Here, a typical large-scale PC in North China was selected as the study case, to explore the character, formation and influence of local photochemical pollution regarding PCs based on an improved 0-D chemical model. In the study PC, VOCs-rich character was apparent with THCs level of 90.8 ± 28.0 ppb and THCs/NOx ratio of ∼26.2 mol/mol. Severe O3 pollution was found in warm months with monthly mean MDA1O3 of 67.3-96.0 ppb. Model simulations showed the heavy O3 pollution in this PC was attributed to high precursors rather than to unfavorable meteorology, and was more sensitive to NOx (with response of 1.42 g/g) than to THCs (with response of 0.12 g/g). The photochemical pollution formation potential of the emission plumes of this PC was very enormous, with production rate of 19.6 ppb h-1 for O3, 2.9 ppb h-1 for HCHO and 1.1 ppb h-1 for CH3CHO on daytime average, 1-5 greater than in normal urban areas. The higher production rates happened in morning hours, which explained the earlier peak time of observed O3 in PCs. And about 70% of photochemical pollution (represented by O3) would be transported to surroundings, leading to the significant photochemical-pollution hazard to the vicinity of PCs.

Two new 3D Supramolecular Frameworks as Photocatalysts for Degradation of Methyl Blue.

We successfully synthesized two new supramolecular frameworks, namely {[Cu2(L1)(H2O)2]·(H2O)}n (1) and {[Ag(L2)(bpp)]2n·2(H2O)}n (2) (H2L1 = 2-hydroxy-5-sulfobenzoic acid, HL2 = 8-hydroxyquinoline-2-sulfonic acid) under hydrothermal condition. These single-crystal structures were determined via X-ray single crystal diffraction analyses. Solids 1 and 2 acted as photocatalysts and performed good photocatalytic activities for MB degradation under UV light irradiation.

Broad-spectrum resistance gene RPW8.1 balances immunity and growth via feedback regulation of WRKYs.

Arabidopsis RESISTANCE TO POWDERY MILDEW 8.1 (RPW8.1) is an important tool for engineering broad-spectrum disease resistance against multiple pathogens. Ectopic expression of RPW8.1 leads to enhanced disease resistance with cell death at leaves and compromised plant growth, implying a regulatory mechanism balancing RPW8.1-mediated resistance and growth. Here, we show that RPW8.1 constitutively enhances the expression of transcription factor WRKY51 and activates salicylic acid and ethylene signalling pathways; WRKY51 in turn suppresses RPW8.1 expression, forming a feedback regulation loop. RPW8.1 and WRKY51 are both induced by pathogen infection and pathogen-/microbe-associated molecular patterns. In ectopic expression of RPW8.1 background (R1Y4), overexpression of WRKY51 not only rescues the growth suppression and cell death caused by RPW8.1, but also suppresses RPW8.1-mediated broad-spectrum disease resistance and pattern-triggered immunity. Mechanistically, WRKY51 directly binds to and represses RPW8.1 promoter, thus limiting the expression amplitude of RPW8.1. Moreover, WRKY6, WRKY28 and WRKY41 play a role redundant to WRKY51 in the suppression of RPW8.1 expression and are constitutively upregulated in R1Y4 plants with WRKY51 being knocked out (wrky51 R1Y4) plants. Notably, WRKY51 has no significant effects on disease resistance or plant growth in wild type without RPW8.1, indicating a specific role in RPW8.1-mediated disease resistance. Altogether, our results reveal a regulatory circuit controlling the accumulation of RPW8.1 to an appropriate level to precisely balance growth and disease resistance during pathogen invasion.

Global genomic profiling of Klebsiella pneumoniae: A spatio-temporal population structure analysis.

Klebsiella pneumoniae is an important clinical bacterial pathogen that has hypervirulent and multidrug-resistant variants. Uniform Manifold Approximation and Projection (UMAP) was used to cluster genomes of 16 797 K. pneumoniae strains collected, based on core genome distance, in over 100 countries during the period 1937 to 2021. A total of 60 high-density genetic clusters of strains representing the major epidemic strains were identified among these strains. Using UMAP bedding, the relationship between genetic cluster, capsular polysaccharide (KL) types and sequence type (ST) of the strains was clearly demonstrated, with some important STs, such as ST11 and ST258, found to contain multiple clusters. Strains within the same cluster often exhibited significant diverse features, such as originating from different areas and being isolated in different years, as well as carriage of different resistance and virulence genes. These data enable the routes of evolution of the globally prevalent K. pneumoniae strains to be traced. Alarmingly, carbapenem-resistant K. pneumoniae strains accounted for 51.7% of the test strains and worldwide transmission was observed. Carbapenem-resistant and hypervirulent K. pneumoniae strains are mainly reported in China; however, these strains are increasingly reported in other parts of the world. Also identified in this study were several key genetic loci that facilitate development of a new K. pneumoniae typing method to differentiate between high- and low-risk strains. In particular, the acrR, ompK35 and hha genes were predicted to play a key role in expression of the resistance and virulence phenotypes.

Association between cardiac conduction block and cardiovascular disease and all-cause mortality: The kailuan study.

BACKGROUND: Although bundle branch block and atrioventricular block are recognized to be association with cardiovascular disease (CVD) and mortality, the relationship between cardiac conduction block (CCB) and both CVD and all-cause mortality has yet to be explored. AIMS: To explore the relationship between CCB and CVD and all-cause mortality. METHODS AND RESULTS: We included 145,805 subjects (mean age 49.7 years, 81.2% males) from the kailuan study. CCB was diagnosed through a 12­lead electrocardiograph (ECG). Mortality and CVD events were ascertained through multiple sources, including a municipal social insurance institution, hospital records, death certificates, and regular active follow-ups. After a mean follow-up of 12.5 years, 18,301 cases developed all-cause mortality. After excluding 4443 subjects with CVD presence at baseline, 13,208 cases of CVD occurred among the 141,362 study subjects during follow-up. Compared with non-CCB group, the cumulative incidence of CVD and all-cause mortality for CCB group was 18.38% VS 12.14% and 33.45% VS 14.18%, respectively. The multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) with CCB group were 1.25(1.17-1.34) for CVD, and 1.31(1.25-1.38) for all-cause mortality. Additionally, there were generally stronger associations for CCB with all-cause mortality and CVD in younger participants compared with their older counterparts (Ps-interaction <0.001). CONCLUSION: CCB can increase the risk of CVD and all-cause mortality in the general population. Our findings highlight the importance of strategies for preventing CCB to reduce the risk of CVD and mortality.