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Abstract Background Organoids are approved by the US FDA as an alternative to animal experiments to guide drug development and for sensitivity screening. Stable organoids models of gastric cancer are desirable for personalized medicine and drug screening. Methods Tumor tissues from a primary cancer of the stomach and metastatic cancer of the lymph node were collected for 3D culture. By long-term culture for over 50 generations in vitro, we obtained stably growing organoid lines. We analyzed short tandem repeats (STRs) and karyotypes of cancer cells, and tumorigenesis of the organoids in nude mice, as well as multi-omics profiles of the organoids. A CCK8 method was used to determine the drugs sensitivity to fluorouracil (5-Fu), platinum and paclitaxel. Results Paired organoid lines from primary cancer (SPDO1P) and metastatic lymph node (SPDO1LM) were established with unique STRs and karyotypes. The organoid lines resulted in tumorigenesis in vivo and had clear genetic profiles. Compared to SPDO1P from primary cancer, upregulated genes of SPDO1LM from the metastatic lymph node were enriched in pathways of epithelial-mesenchymal transition and angiogenesis with stronger abilities of cell migration, invasion, and pro-angiogenesis. Based on drug sensitivity analysis, the SOX regimen (5-Fu plus oxaliplatin) was used for chemotherapy with an optimal clinical outcome. Conclusions The organoid lines recapitulate the drug sensitivity of the parental tissues. The paired organoid lines present a step-change toward living biobanks for further translational usage.

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 β-Lactamase (ESBL) gene, blaPER-1, and an efflux pump operon, tmexCD-oprJ, which mediate resistance to β-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.

The areca nut, commonly known as betel nut, has been the subject of consistent scientific study over the past 5 decades. Betel nut is a natural compound chewed for its psychostimulating effects. Arecoline, the primary alkaloid of betel nut, is a muscarinic acetylcholine receptor agonist producing cholinergic effects on the parasympathetic nervous system and a psychoactive agent, contributing to the psycho-stimulating effects. Importantly the betel nut use is also associated with oral leucoplakia, submucous fibrosis, and squamous cell carcinoma. This narrative review explores the past, present, and future aspects of betel nut use, its historical applications, the development of biomarkers research, its health value concerns, and health economic impacts.

Biobanks are foundational infrastructures that collect and provide standardized, high-quality, and research-ready biological material and associated data. The advent of high-throughput technologies has further supported the creation of biobanks globally. However, the same rate of growth has not occurred in the field of infectious diseases, where biobanks are significantly fewer as compared to other scientific fields such as oncology. This narrative review presents the main aspects that need to be taken into consideration for the construction and application of biological sample infrastructure for infectious diseases, with a number of examples taken from the recent COVID-19 pandemic.

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.

ObjectiveAs 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.DesignWe 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.ResultThe 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.ConclusionGovernment 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.

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.

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.

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.