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Infection and Drug Resistance 2024The occurrence and dissemination of hypermucoviscous and hypervirulent (hm-hvKp) isolates in clinical settings are a critical public health problem in the world....
BACKGROUND
The occurrence and dissemination of hypermucoviscous and hypervirulent (hm-hvKp) isolates in clinical settings are a critical public health problem in the world. However, the data on these isolates in community populations are limited. This study aims to understand the prevalence and molecular characteristics of hm-hvKp isolates in community patients in Shanghai, China.
METHODS
In 2018, an active surveillance system focused on hm-hvKp in community diarrhoeal cases was implemented in Pudong New Area, Shanghai, China, involving 12 sentinel hospitals. The antimicrobial susceptibility of hm-hvKp isolates from fecal samples was tested, and whole-genome sequencing (WGS) was performed to predict the serotypes and sequence types and to identify antimicrobial resistance determinants, virulence determinants, and phylogenetic clusters.
RESULTS
The overall prevalence of hm isolates was 2.48% (31/1252), with the proportions of 1.76% (22/1252) for hm-hvKp and 0.72% (9/1252) for hm not hv . The prevalence of hm-hvKp isolates among different age groups and different months was statistically significant. All the 22 hm-hvKp isolates were susceptible to 20 antimicrobial agents and only carried gene, and KL1 and KL2 accounted for eight (36.36%) cases and seven (31.82%) cases, respectively. The eight ST23/KL1 isolates belonged to the predominant CG23-I clade, which typically possessed the virulence determinants profile of /. The five ST86/KL2 isolates were assigned to the global clusters ST86/KL2-1 (n=2), ST86/KL2-2 (n=2), ST86/KL2-3 (n=1), all lack of the gene. Shanghai ST23/KL1 and ST86/KL2 isolates were closely related to the global isolates from liver abscesses, blood, and urine.
CONCLUSION
Hm-hvKp is carried by the community population of Shanghai, with ST23/KL1 and ST86/KL2 isolates predominant. Hm-hvKp isolates of different continents, different sources, and different virulence levels were closely related. Ongoing surveillance of hm-hvKp isolates in the community population is warranted.
PubMed: 38953096
DOI: 10.2147/IDR.S468482 -
The Lancet Regional Health. Western... Jun 2024In Australia the incidence of HIV has declined steadily, yet sustained reduction of HIV transmission in this setting requires improved public health responses. As...
BACKGROUND
In Australia the incidence of HIV has declined steadily, yet sustained reduction of HIV transmission in this setting requires improved public health responses. As enhanced public health responses and prioritisation of resources may be guided by molecular epidemiological data, here we aimed to assess the applicability of these approaches in Victoria, Australia.
METHODS
A comprehensive collection of HIV-1 sequences from individuals diagnosed with HIV in Victoria, Australia, between January 1st 2000 and December 31st 2020 were deidentified and used as the basis of our assessment. These sequences were subtyped and surveillance drug resistance mutations (SDRMs) identified, before definition of transmission groups was performed using HIV-TRACE (0.4.4). Phylodynamic methods were applied using BEAST (2.6.6), assessing effective reproductive numbers for large groups, and additional demographic data were integrated to provide a high resolution view of HIV transmission in Victoria on a decadal time scale.
FINDINGS
Based on standard settings for HIV-TRACE, 70% (2438/3507) of analysed HIV-1 sequences were readily assigned to a transmission group. Individuals in transmission groups were more commonly males (aOR 1.50), those born in Australia (aOR 2.13), those with probable place of acquisition as Victoria (aOR 6.73), and/or those reporting injectable drug use (aOR 2.13). SDRMs were identified in 375 patients (10.7%), with sustained transmission of these limited to a subset of smaller groups. Informative patterns of epidemic growth, stabilisation, and decline were observed; many transmission groups showed effective reproductive numbers ( ) values reaching greater than 4.0, representing considerable epidemic growth, while others maintained low values.
INTERPRETATION
This study provides a high resolution view of HIV transmission in Victoria, Australia, and highlights the potential of molecular epidemiology to guide and enhance public health responses in this setting. This informs ongoing discussions with community groups on the acceptability and place of molecular epidemiological approaches in Australia.
FUNDING
National Health and Medical Research Council, Australian Research Council.
PubMed: 38953059
DOI: 10.1016/j.lanwpc.2024.101103 -
Frontiers in Immunology 2024Our study aimed to elucidate the role of Galectin-1 (Gal-1) role in the immunosuppressive tumor microenvironment (TME) of prostate cancer (PCa). Our previous findings...
Our study aimed to elucidate the role of Galectin-1 (Gal-1) role in the immunosuppressive tumor microenvironment (TME) of prostate cancer (PCa). Our previous findings demonstrated a correlation between elevated Gal-1 expression and advanced PCa stages. In this study, we also observed that Gal-1 is expressed around the tumor stroma and its expression level is associated with PCa progression. We identified that Gal-1 could be secreted by PCa cells, and secreted Gal-1 has the potential to induce T cell apoptosis. Gal-1 knockdown or inhibition of Gal-1 function by LLS30 suppresses T cell apoptosis resulting in increased intratumoral T cell infiltration. Importantly, LLS30 treatment significantly improved the antitumor efficacy of anti-PD-1 . Mechanistically, LLS30 binds to the carbohydrate recognition domain (CRD) of Gal-1, disrupting its binding to CD45 leading to the suppression of T cell apoptosis. In addition, RNA-seq analysis revealed a novel mechanism of action for LLS30, linking its tumor-intrinsic oncogenic effects to anti-tumor immunity. These findings suggested that tumor-derived Gal-1 contributes to the immunosuppressive TME in PCa by inducing apoptosis in effector T cells. Targeting Gal-1 with LLS30 may offer a strategy to enhance anti-tumor immunity and improve immunotherapy.
Topics: Male; Galectin 1; Prostatic Neoplasms; Humans; Animals; Tumor Microenvironment; T-Lymphocytes; Mice; Apoptosis; Immunotherapy; Cell Line, Tumor; Lymphocytes, Tumor-Infiltrating
PubMed: 38953033
DOI: 10.3389/fimmu.2024.1372956 -
PeerJ 2024Mitochondrial creatine kinase (MtCK) plays a pivotal role in cellular energy metabolism, exhibiting enhanced expression in various tumors, including colorectal cancer...
BACKGROUND
Mitochondrial creatine kinase (MtCK) plays a pivotal role in cellular energy metabolism, exhibiting enhanced expression in various tumors, including colorectal cancer (CRC). Creatine kinase mitochondrial 2 (CKMT2) is a subtype of MtCK; however, its clinical significance, biological functions, and underlying molecular mechanisms in CRC remain elusive.
METHODS
We employed immunohistochemical staining to discern the expression of CKMT2 in CRC and adjacent nontumor tissues of patients. The correlation between CKMT2 levels and clinical pathological factors was assessed. Additionally, we evaluated the association between CKMT2 and the prognosis of CRC patients using Kaplan-Meier survival curves and Cox regression analysis. Meanwhile, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of in different CRC cell lines. Finally, we explored the biological functions and potential molecular mechanisms of CKMT2 in CRC cells through various techniques, including qRT-PCR, cell culture, cell transfection, western blot, Transwell chamber assays, flow cytometry, and co-immunoprecipitation.
RESULTS
We found that CKMT2 was significantly overexpressed in CRC tissues compared with adjacent nontumor tissues. The expression of CKMT2 is correlated with pathological types, tumor size, distant metastasis, and survival in CRC patients. Importantly, CKMT2 emerged as an independent prognostic factor through Cox regression analysis. Experimental downregulation of expression in CRC cell lines inhibited the migration and promoted apoptosis of these cells. Furthermore, we identified a novel role for CKMT2 in promoting aerobic glycolysis in CRC cells through interaction with lactate dehydrogenase B (LDHB).
CONCLUSION
In this study, we found the elevated expression of CKMT2 in CRC, and it was a robust prognostic indicator in CRC patients. CKMT2 regulates glucose metabolism amplifying the Warburg effect through interaction with LDHB, which promotes the growth and progression of CRC. These insights unveil a novel regulatory mechanism by which CKMT2 influences CRC and provide promising targets for future CRC therapeutic interventions.
Topics: Humans; Colorectal Neoplasms; Warburg Effect, Oncologic; Male; Female; Cell Line, Tumor; Prognosis; Creatine Kinase, Mitochondrial Form; Disease Progression; L-Lactate Dehydrogenase; Middle Aged; Cell Proliferation; Apoptosis; Gene Expression Regulation, Neoplastic
PubMed: 38952967
DOI: 10.7717/peerj.17672 -
Biology of Sport Jul 2024Sleep and autonomic nervous system (ANS) influence each other in a bidirectional fashion. Importantly, it has been proposed that sleep has a beneficial regulatory...
Sleep and autonomic nervous system (ANS) influence each other in a bidirectional fashion. Importantly, it has been proposed that sleep has a beneficial regulatory influence over cardiovascular activity, which is mostly controlled by autonomic regulation through the activity of sympathetic and parasympathetic pathways of the ANS. A well-established method to non-invasively assess cardiac autonomic activity is heart rate variability (HRV) analysis. We aimed to investigate the effect of a 40-min nap opportunity on HRV. Twelve professional basketball players randomly accomplished two conditions: 40-min nap (NAP) and control (CON). Nocturnal sleep and naps were monitored by actigraphic recording and sleep diaries. Total sleep time (TST), time in bed (TIB), sleep efficiency (SE), sleep onset latency (SOL), and wake after sleep onset (WASO) were analyzed. HRV was analyzed in 5-min segments during quiet wake before and after each condition with controlled breathing. Were analysed high (HF) and low frequency (LF) bands, the standard deviation of NN interval (SDNN), HRV index and stress index (SI). Wellness Hooper index and Epworth Sleepiness Scale (ESS) were assessed before and after both conditions. There was no significant difference in TIB, TST, SE, WASO, and VAS between NAP and CON. A significant increase in SDNN, HRV index, and LF and a significant decrease in HF, SI, ESS, and Hooper's stress and fatigue scores were observed from pre- to post-nap. In conclusion, napping reduces sleepiness, stress and fatigue, and might provide an advantage by preparing the body for a much-required sympathetic comeback following peaceful rest.
PubMed: 38952899
DOI: 10.5114/biolsport.2024.132983 -
The Journal of Allergy and Clinical... Aug 2024Asthma is a chronic inflammatory disease of the airways that is heterogeneous and multifactorial, making its accurate characterization a complex process. Therefore,...
BACKGROUND
Asthma is a chronic inflammatory disease of the airways that is heterogeneous and multifactorial, making its accurate characterization a complex process. Therefore, identifying the genetic variations associated with asthma and discovering the molecular interactions between the omics that confer risk of developing this disease will help us to unravel the biological pathways involved in its pathogenesis.
OBJECTIVE
We sought to develop a predictive genetic panel for asthma using machine learning methods.
METHODS
We tested 3 variable selection methods: Boruta's algorithm, the top 200 genome-wide association study markers according to their respective values, and an elastic net regression. Ten different algorithms were chosen for the classification tests. A predictive panel was built on the basis of joint scores between the classification algorithms.
RESULTS
Two variable selection methods, Boruta and genome-wide association studies, were statistically similar in terms of the average accuracies generated, whereas elastic net had the worst overall performance. The predictive genetic panel was completed with 155 single-nucleotide variants, with 91.18% accuracy, 92.75% sensitivity, and 89.55% specificity using the support vector machine algorithm. The markers used range from known single-nucleotide variants to those not previously described in the literature. Our study shows potential in creating genetic prediction panels with tailored penalties per marker, aiding in the identification of optimal machine learning methods for intricate results.
CONCLUSIONS
This method is able to classify asthma and nonasthma effectively, proving its potential utility in clinical prediction and diagnosis.
PubMed: 38952894
DOI: 10.1016/j.jacig.2024.100282 -
Virus Evolution 2024Animal rotaviruses A (RVAs) are considered the source of emerging, novel RVA strains that have the potential to cause global spread in humans. A case in point was the...
Evolution of DS-1-like G8P[8] rotavirus A strains from Vietnamese children with acute gastroenteritis (2014-21): Adaptation and loss of animal rotavirus-derived during human-to-human spread.
Animal rotaviruses A (RVAs) are considered the source of emerging, novel RVA strains that have the potential to cause global spread in humans. A case in point was the emergence of G8 bovine RVA consisting of the P[8] VP4 and the DS-1-like backbone that appeared to have jumped into humans recently. However, it was not well documented what evolutionary changes occurred on the animal RVA-derived during circulation in humans. Rotavirus surveillance in Vietnam found that DS-1-like G8P[8] strains emerged in 2014, circulated in two prevalent waves, and disappeared in 2021. This surveillance provided us with a unique opportunity to investigate the whole process of evolutionary changes, which occurred in an animal RVA that had jumped the host species barrier. Of the 843 G8P[8] samples collected from children with acute diarrhoea in Vietnam between 2014 and 2021, fifty-eight strains were selected based on their distinctive electropherotypes of the genomic RNA identified using polyacrylamide gel electrophoresis. Whole-genome sequence analysis of those fifty-eight strains showed that the strains dominant during the first wave of prevalence (2014-17) carried animal RVA-derived VP1, NSP2, and NSP4 . However, the strains from the second wave of prevalence (2018-21) lost these , which were replaced with cognate human RVA-derived , thus creating strain with G8P[8] on a fully DS-1-like human RVA backbone. The G8 VP7 and P[8] VP4 s underwent some point mutations but the phylogenetic lineages to which they belonged remained unchanged. We, therefore, propose a hypothesis regarding the tendency for the animal RVA-derived to be expelled from the backbone of the progeny strains after crossing the host species barrier. This study underlines the importance of long-term surveillance of circulating wild-type strains in order to better understand the adaptation process and the fate of newly emerging, animal-derived RVA among the human population. Further studies are warranted to disclose the molecular mechanisms by which spillover animal RVAs become readily transmissible among humans, and the roles played by the expulsion of animal-derived and herd immunity formed in the local population.
PubMed: 38952820
DOI: 10.1093/ve/veae045 -
Frontiers in Public Health 2024
Topics: Humans; India; Mass Drug Administration; Filariasis; Filaricides; Disease Eradication
PubMed: 38952727
DOI: 10.3389/fpubh.2024.1384131 -
Frontiers in Genetics 2024Developmental Dysplasia of the Hip (DDH) is a skeletal disorder where late-presenting forms often escape early diagnosis, leading to limb and pain in adults. The genetic...
BACKGROUND
Developmental Dysplasia of the Hip (DDH) is a skeletal disorder where late-presenting forms often escape early diagnosis, leading to limb and pain in adults. The genetic basis of DDH is not fully understood despite known genetic predispositions.
METHODS
We employed Whole Genome Sequencing (WGS) to explore the genetic factors in late-presenting DDH in two unrelated families, supported by phenotypic analyses and validation.
RESULTS
In both cases, a novel heterozygous missense mutation in (c.193A>G [p.Lys65Glu]) was identified. This mutation impacted protein structure and function, altering downstream signaling in the Ras/ERK pathway, as demonstrated by bioinformatics, molecular dynamics simulations, and validations.
CONCLUSION
This study contributes to our understanding of the genetic factors involved in DDH by identifying a novel mutation in . The identification of the mutation suggests a possible involvement of the Ras/ERK pathway in the pathogenesis of late-presenting DDH, indicating its potential role in skeletal development.
PubMed: 38952713
DOI: 10.3389/fgene.2024.1375736 -
IScience Jun 2024The human gut microbiota comprises various microorganisms engaged in intricate interactions among themselves and with the host, affecting its health. While advancements...
The human gut microbiota comprises various microorganisms engaged in intricate interactions among themselves and with the host, affecting its health. While advancements in omics technologies have led to the inference of clear associations between microbiome composition and health conditions, we usually lack a causal and mechanistic understanding of these associations. For modeling mechanisms driving the interactions, we simulated the organism's metabolism using genome-scale metabolic models (GEMs). We used multi-objective optimization to predict and explain metabolic interactions among gut microbes and an intestinal epithelial cell. We developed a score integrating model simulation results to predict the type (competition, neutralism, mutualism) and quantify the interaction between several organisms. This framework uncovered a potential cross-feeding for choline, explaining the predicted mutualism between GG and the epithelial cell. Finally, we analyzed a five-organism ecosystem, revealing that a minimal microbiota can favor the epithelial cell's maintenance.
PubMed: 38952683
DOI: 10.1016/j.isci.2024.110092