Characterization and Implications of IncP-2A Plasmid pMAS152 Harboring Multidrug Resistance Genes in Extensively Drug-Resistant Pseudomonas aeruginosa.

Bacterial antimicrobial resistance (AMR) poses a significant global public health challenge. The escalation of AMR is primarily attributed to the horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs), often facilitated by plasmids. This underscores the critical need for a comprehensive understanding of the resistance mechanisms and transmission dynamics of these plasmids. In this study, we utilized in vitro drug sensitivity testing, conjugation transfer assays, and whole-genome sequencing to investigate the resistance mechanism of an extensively drug-resistant (XDR) Pseudomonas aeruginosa clinical isolate, MAS152. We specifically focused on analyzing the drug-resistant plasmid pMAS152 it harbors and its potential for widespread dissemination. Bioinformatics analysis revealed that MAS152 carries a distinct IncpP-2A plasmid, pMAS152, characterized by a 44.8 kb multidrug resistance (MDR) region. This region houses a 16S rRNA methyltransferase (16S-RMTase) gene, rmtB, conferring high-level resistance to aminoglycoside antibiotics. Notably, this region also contains an extended-spectrum ß-Lactamase (ESBL) gene, blaPER-1, and an efflux pump operon, tmexCD-oprJ, which mediate resistance to ß-Lactams and quinolone antibiotics, respectively. Such a combination of ARGs, unprecedented in reported plasmids, could significantly undermine the effectiveness of first-line antibiotics in treating P. aeruginosa infections. Investigation into the genetic environment of the MDR region suggests that Tn2 and IS91 elements may be instrumental in the horizontal transfer of rmtB. Additionally, a complex Class I integron with an ISCR1 structure, along with TnAs1, seems to facilitate the horizontal transfer of blaPER-1. The conjugation transfer assay, coupled with the annotation of conjugation-related genes and phylogenetic analysis, indicates that the plasmid pMAS152 functions as a conjugative plasmid, with other genus Pseudomonas species as potential hosts. Our findings provide vital insights into the resistance mechanisms and transmission potential of the XDR P. aeruginosa isolate MAS152, underlining the urgent need for novel strategies to combat the spread of AMR. This study highlights the complex interplay of genetic elements contributing to antibiotic resistance and underscores the importance of continuous surveillance of emerging ARGs in clinical isolates.

Toward Professionalism of Biobanking in China: A Survey on Working Status, Career Development, Challenges, and Prospects of Biobankers.

Biobanking has become an increasingly important activity to provide resources for medical research support. In China, establishing and maintaining a biobank have been the latest trend in a research hospital. However, biobanking is still an emerging young field in terms of professionalization and professionalism. The development of professionalization in biobanking faces many challenges involving the development of skills, identities, norms, and values associated with becoming part of a professional group. Biobanking professionals (i.e., biobankers) are the most important factor and driving force toward professionalization in biobanking. To better understand biobankers' performance, needs, concerns, and career development, we conducted two comprehensive surveys among biobankers in China in 2019 and 2021, respectively. The questionnaires covered four major areas: (1) basic information and the status of biobankers; (2) job performance evaluation, salary, recognitions, rewards, and so on; (3) occupational training and career development; and (4) challenges and prospects and so on. The surveys revealed that most biobankers in China have positive working attitudes and a high desire for their future career development, but due to the uncertain evaluation mechanisms and promotion routes, etc., the participants were more optimistic about biobanking development compared to the biobanker's career development (77.0% and 57.4% respectively in 2021, p < 0.05). The biobankers expected more training opportunities and salary packages. Because biobankers are an integral factor and driving force to ensure the successful biobanking operation and advancement, the survey data analysis revealed interesting findings and references for the development of professionalism in biobanking. This survey will provide first-hand information to governments, biobank management teams, and the general public to further support, promote, or optimize (1) biobanking operation and sustainability, (2) biobankers' career development, (3) biobank management and quality control, and (4) strategic plans and approaches to establish a higher quality professional team of biobankers.

Patient-derived rectal cancer organoids-applications in basic and translational cancer research.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and among the leading causes of death in both men and women. Rectal cancer (RC) is particularly challenging compared with colon cancer as the treatment after diagnosis of RC is more complex on account of its narrow anatomical location in the pelvis adjacent to the urogenital organs. More and more existing studies have begun to refine the research on RC and colon cancer separately. Early diagnosis and multiple treatment strategies optimize outcomes for individual patients. However, the need for more accurate and precise models to facilitate RC research is underscored due to the heterogeneity of clinical response and morbidity interrelated with radical surgery. Organoids generated from biopsies of patients have developed as powerful models to recapitulate many aspects of their primary tissue, consisting of 3-D self-organizing structures, which shed great light on the applications in both biomedical and clinical research. As the preclinical research models for RC are usually confused with colon cancer, research on patient-derived RC organoid models enable personalized analysis of cancer pathobiology, organizational function, and tumor initiation and progression. In this review, we discuss the various applications of patient-derived RC organoids over the past two years in basic cancer biology and clinical translation, including sequencing analysis, drug screening, precision therapy practice, tumor microenvironment studies, and genetic engineering opportunities.

Which Matters More in Fighting COVID-19-Government Policy or Community Participation?

Objective: As a heavily populated megacity, Shanghai faces major epidemic risks. However, Shanghai's control of COVID-19 has been successful owing to both the strict government policy and wide community participation. Here, we investigated the impact of these stakeholders and examined who played a major role across different epidemic stages. Design: We extended the classic susceptible-exposed-infectious-recovered (SEIR) model considering the heterogeneous contact structure in four social sceneries, i.e., school, workplace, public entertainment venues, and neighborhood community, which could reflect the impact of lockdown policy and wide participation of residents happened at the community level. Result: The simulation results showed that without lockdown policy and only with community participation, the daily new confirmed cases would gradually increase to more than 7,000 [292/1,000,000] at the end of Sep. However, without community participation and only with a lockdown policy, the daily new confirmed cases sharply decreased to 30 [1.2/1,000,000] at the end of the 1st month and remained low for several months. However, when a lockdown policy was gradually lifted, the new confirmed cases increased exponentially, eventually reaching more than 17,000 [708/1,000,000]. Therefore, a government lockdown policy was necessary for the rapid control of COVID-19 during the outbreak stage while community participation is more important in keeping the number of new confirmed cases low during the reopening stage. Conclusion: Government lockdown policy and community participation play different roles in the control of COVID-19 at different stages of the epidemic: although the government played a leading role in setting up policies, the broader participation of community fever clinics (CFCs) and the general public were especially crucial in winning the battle against COVID-19 in the long run.

A Systematic Review of Oral Biopsies, Sample Types, and Detection Techniques Applied in Relation to Oral Cancer Detection.

Background: Early identification of the stage of oral cancer development can lead to better treatment outcomes and avoid malignant transformation. Therefore, this review aims to provide a comprehensive overview that describes the development of standardized procedures for oral sample collection, characterization, and molecular risk assessment. This can help investigators to choose the appropriate sampling method and downstream analyses for different purposes. Methods: This systematic review was conducted according to the PRISMA guidelines. Using both PubMed and Web of Science databases, four independent authors conducted a literature search between 15 and 21 June 2021. We used key search terms to broaden the search for studies. Non-conforming articles were removed using an EndNote-based and manual approach. Reviewers used a designed form to extract data. Results: This review included a total of 3574 records, after eliminating duplicate articles and excluding papers that did not meet the inclusion criteria. Finally, 202 articles were included in this review. We summarized the sampling methods, biopsy samples, and downstream analysis. The biopsy techniques were classified into tissue and liquid biopsy. The common sequential analysis of tissue biopsy includes histopathological examination such as H&E or IHC to identify various pathogenic features. Meanwhile, liquid samples such as saliva, blood, and urine are analyzed for the purpose of screening to detect mutations in cancer. Commonly used technologies are PCR, RT-PCR, high-throughput sequencing, and metabolomic analysis. Conclusions: Currently, tissue biopsies provide increased diagnostic value compared to liquid biopsy. However, the minimal invasiveness and convenience of liquid biopsy make it a suitable method for mass screening and eventual clinical adoption. The analysis of samples includes histological and molecular analysis. Metabolite analysis is rising but remains scarce.

Multi-kingdom microbiota analyses identify bacterial-fungal interactions and biomarkers of colorectal cancer across cohorts.

Despite recent progress in our understanding of the association between the gut microbiome and colorectal cancer (CRC), multi-kingdom gut microbiome dysbiosis in CRC across cohorts is unexplored. We investigated four-kingdom microbiota alterations using CRC metagenomic datasets of 1,368 samples from 8 distinct geographical cohorts. Integrated analysis identified 20 archaeal, 27 bacterial, 20 fungal and 21 viral species for each single-kingdom diagnostic model. However, our data revealed superior diagnostic accuracy for models constructed with multi-kingdom markers, in particular the addition of fungal species. Specifically, 16 multi-kingdom markers including 11 bacterial, 4 fungal and 1 archaeal feature, achieved good performance in diagnosing patients with CRC (area under the receiver operating characteristic curve (AUROC) = 0.83) and maintained accuracy across 3 independent cohorts. Coabundance analysis of the ecological network revealed associations between bacterial and fungal species, such as Talaromyces islandicus and Clostridium saccharobutylicum. Using metagenome shotgun sequencing data, the predictive power of the microbial functional potential was explored and elevated D-amino acid metabolism and butanoate metabolism were observed in CRC. Interestingly, the diagnostic model based on functional EggNOG genes achieved high accuracy (AUROC = 0.86). Collectively, our findings uncovered CRC-associated microbiota common across cohorts and demonstrate the applicability of multi-kingdom and functional markers as CRC diagnostic tools and, potentially, as therapeutic targets for the treatment of CRC.

Depressive symptoms and chronic lung disease in middle-aged and older Chinese adults: Prospective bidirectional association and mediation analysis.

BACKGROUND: We investigated the prospective bidirectional association between depressive symptoms and chronic lung disease (CLD) and explored biologically and behaviorally relevant mediators in this bidirectional association among Chinese middle-aged and older population in the China Health and Retirement Longitudinal Study. METHODS: Multivariable-adjusted Cox proportional hazard models were used to examine baseline depressive symptoms in relation to incident CLD risk among 12,546 adults and examine CLD condition in association with incidence of elevated depressive symptoms among 6,929 participants from 2011 to 2018. Elevated depressive symptoms were assessed with the 10-item Center for Epidemiologic Studies Depression scale and CLD was determined by self-reported physician diagnosis. Causal mediation analysis was performed to examine the direct and indirect effects of a priori selected nine blood biomarkers and four lifestyle factors in the bidirectional association. RESULTS: Elevated depressive symptoms significantly increased CLD risk by 68% (HR=1.68, 95%CI=1.46-1.93) after a mean follow-up of 5.9 years and the strong positive association was consistently shown in almost all the subgroups. Having positive CLD status at baseline was associated with 17% increased risk of developing elevated depressive symptoms (HR=1.17, 95%CI=1.01-1.35) during an average of 4.6 years follow-up period. Significant inflammatory, metabolic or pulmonary function related mediators were not identified. LIMITATIONS: Inadequate follow-up time and limited mediator variable information may reduce chance of identifying significant mediators. CONCLUSIONS: Elevated depressive symptoms and CLD were mutual risk factors in middle-aged and older Chinese adults. Early screening and treatment of depression is needed to reduce CLD risk and related comorbidities including new-onset depression so as to relieve substantial disease burdens of CLD and depression in China.

The Application of High-Throughput Technologies for the Study of Microbiome and Cancer.

Human gut microbiome research, especially gut microbiome, has been developing at a considerable pace over the last decades, driven by a rapid technological advancement. The emergence of high-throughput technologies, such as genomics, transcriptomics, and others, has afforded the generation of large volumes of data, and in relation to specific pathologies such as different cancer types. The current review identifies high-throughput technologies as they have been implemented in the study of microbiome and cancer. Four main thematic areas have emerged: the characterization of microbial diversity and composition, microbial functional analyses, biomarker prediction, and, lastly, potential therapeutic applications. The majority of studies identified focus on the microbiome diversity characterization, which is reaching technological maturity, while the remaining three thematic areas could be described as emerging.

An Overview of Epidemiology of COVID-19 in Macau S.A.R.

The Greater Bay Area of southern China has a population of over 71 million people. The area is well-connected with Hubei province, the epicenter of the COVID-19 outbreak. Macau, as the most densely populated city in the world, is very vulnerable to infectious disease outbreaks. Since its return to the sovereignty of China 20 years ago, the city has experienced outbreaks such as severe acute respiratory syndrome (SARS), Swine flu, and COVID-19. At the time of writing, 10 confirmed imported/local transmission cases were recorded. The government undertook measures to attain and then maintain 40 days without new cases. In this article, we report on the 10 confirmed cases and discuss the measures that the Macau Special Administrative Region (S.A.R.) government undertook during the COVID-19 pandemic.