Advances in the application of co-culture strategies in organoids

As a good in vitro research model, organoids are more and more widely used in the biomedical field. By developing self-assembled 3D structures using various tissue culture techniques, organoids can rebuild the high complexity of cells in the inherent structure of the organ, and are therefore unanimously used to study mechanisms regulating body development and disease, high-throughput drug screening, and personalized treatment and so on. To better recapitulate cell-to-cell interactions within the microenvironment, co-culture strategies have been extended to more cell types, and their rapid development offers broader prospects for organoids and paves the way for the treatment of human diseases and regenerative medicine. This review discussed the role of co-culture strategies in organoid generation, and focused on the application of various cellular components and microorganisms in organoid construction, thereby providing reference and help for scholars to construct and develop organoids with a higher degree of in vivo simulation

Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality

Funding: HRS and MF are supported by the Medical Research Council [MR/R008345/1]. CJ’s salary came through MRC core funding MC_UU_12023/26. SJS is funded by the Wellcome Trust [WT 209560/Z/17/Z]. CRS has received funding from the Medical Research Council [MR/R008345/1], the National Institute for Health Research [11/46/23] and the New Zealand Health Research Council [20/1018] and Ministry for Business, Innovation and Employment. EV is funded by the Medical Research Council [MR/R008345/1] through the EAVE II grant and supported by the Scottish Government. We also acknowledge the support of HDR UK. The views and opinions expressed here are those of the authors and do not necessarily reflect those of the Health Technology Assessment programme, NIHR, NHS, or the UK Department of Health.Background Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. Methods Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. Results One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. Conclusions The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected.Publisher PDFPeer reviewe

Duck Eggs and Black-Yolked Salted Duck Eggs: Bacterial Diversity on Eggshells and Gene Function Prediction Using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt)

After comparing the bacterial load of black-yolked salted duck eggs (BSE) and that of duck eggs with different cleanliness degrees, it was found that the total bacterial count on the shell of severely stained eggs (DE) was distinctly higher than that on the shell of non-visually stained eggs (CE), and the total bacterial count in the shell membrane and contents of BSE increased greatly. Furthermore, 16S rDNA gene sequencing was used to analyze the differences in the composition and abundance of bacterial communities in CE, DE and BSE. It turned out that Proteobacteria, Firmicutes and Actinobacteria were the dominant phyla, accounting for 34.35%, 27.25% and 17.28% of the total abundance, respectively, while Bacteroidetes accounted for 8.29% of the total abundance. Proteobacteria was the dominant bacteria in DE and accounted for 89.01% of the total abundance, while the relative abundance of Firmicutes and Actinobacteria were 6.16% and 3.98%. The dominant phyla in BSE were Proteobacteria (76.50%), Bacteroidetes (8.00%), Actinobacteria (6.76%) and Firmicutes (5.43%). The abundance of Proteobacteria in DE and BSE was significantly increased. The dominant bacterial genera in CE were Nesterdella (9.08%), Campylobacter (7.91%), Streptococcus (3.41%) and Oligomonas (2.92%). In DE, Psychrobacter was the dominant genus, accounting for 86.01% of the total abundance, and the relative abundance of Acinetobacter was 2.20%. The dominant bacteria in BSE were Rolstonia (22.91%), Serratia (5.05%) and Actinomycetes (3.32%). The cluster analysis of bacterial diversity showed that the dominant microorganisms of BSE were close to those of DE. The microbial phenotype analysis showed that the dominant microorganisms of BSE were Gram-negative bacteria, had high oxidative stress tolerance and pathogenicity, and could tolerate oxidizing detergents. The results of microbial gene function prediction and species composition of metabolic pathways demonstrated that bacterial carbohydrate decomposition, lipid transport and metabolic oxidation in DE were stronger than those in CE. More coenzyme transport and metabolic pathways could make the biochemical reactions of bacteria from DE faster to produce more secondary metabolites, thus resulting in changes in the quality of duck eggs. This is consistent with the highest bacterial abundance in the secondary metabolite biosynthesis, transport and catabolism pathways in BSE. The results of this study provide theoretical support for the cleaner production of duck eggs

A Study on the Radiosensitivity of Radiation-Induced Lung Injury at the Acute Phase Based on Single-Cell Transcriptomics

Background and AimsRadiation-induced lung injury (RILI) is the most common complication associated with chest tumors, such as lung and breast cancers, after radiotherapy; however, the pathogenic mechanisms are unclear. Single-cell RNA sequencing has laid the foundation for studying RILI at the cellular microenvironmental level. This study focused on changes during the acute pneumonitis stage of RILI at the cellular microenvironmental level and investigated the interactions between different cell types.MethodsAn acute RILI model in mice and a single-cell transcriptional library were established. Intercellular communication networks were constructed to study the heterogeneity and intercellular interactions among different cell types.ResultsA single-cell transcriptome map was established in a mouse model of acute lung injury. In total, 18,500 single-cell transcripts were generated, and 10 major cell types were identified. The heterogeneity and radiosensitivity of each cell type or subtype in the lung tissues during the acute stage were revealed. It was found that immune cells had higher radiosensitivity than stromal cells. Immune cells were highly heterogeneous in terms of radiosensitivity, while some immune cells had the characteristics of radiation resistance. Two groups of radiation-induced Cd8+Mki67+ T cells and Cd4+Cxcr6+ helper T cells were identified. The presence of these cells was verified using immunofluorescence. The ligand-receptor interactions were analyzed by constructing intercellular communication networks. These explained the origins of the cells and revealed that they had been recruited from endothelial cells to the inflammatory site.ConclusionsThis study revealed the heterogeneity of in vivo radiosensitivity of different cell types in the lung at the initial stage post irradiatio

The impact of ageing mechanisms on musculoskeletal system diseases in the elderly

Ageing is an inevitable process that affects various tissues and organs of the human body, leading to a series of physiological and pathological changes. Mechanisms such as telomere depletion, stem cell depletion, macrophage dysfunction, and cellular senescence gradually manifest in the body, significantly increasing the incidence of diseases in elderly individuals. These mechanisms interact with each other, profoundly impacting the quality of life of older adults. As the ageing population continues to grow, the burden on the public health system is expected to intensify. Globally, the prevalence of musculoskeletal system diseases in elderly individuals is increasing, resulting in reduced limb mobility and prolonged suffering. This review aims to elucidate the mechanisms of ageing and their interplay while exploring their impact on diseases such as osteoarthritis, osteoporosis, and sarcopenia. By delving into the mechanisms of ageing, further research can be conducted to prevent and mitigate its effects, with the ultimate goal of alleviating the suffering of elderly patients in the future

The association of long-term trajectories of BMI, its variability, and metabolic syndrome: a 30-year prospective cohort study

Background Limited data exists on how early-life weight changes relate to metabolic syndrome (MetS) risk in midlife. This study examines the association between long-term trajectories of body mass index (BMI), its variability, and MetS risk in Chinese individuals. Methods In the Hanzhong Adolescent Hypertension study (March 10, 1987–June 3, 2017), 1824 participants with at least five BMI measurements from 1987 to 2017 were included. Using group-based trajectory modeling, different BMI trajectories were identified. BMI variability was assessed through standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Logistic regression analyzed the relationship between BMI trajectory, BMI variability, and MetS occurrence in midlife (URL: https://www.clinicaltrials.gov; Unique identifier: NCT02734472). Findings BMI trajectories were categorized as low-increasing (34.4%), moderate-increasing (51.8%), and high-increasing (13.8%). Compared to the low-increasing group, the odds ratios (ORs) [95% CIs] for MetS were significantly higher in moderate (4.27 [2.63–6.91]) and high-increasing groups (13.11 [6.30–27.31]) in fully adjusted models. Additionally, higher BMI variabilities were associated with increased MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 2.30 [2.02–2.62], 1.22 [1.19–1.26], and 4.29 [3.38–5.45]). Furthermore, BMI trajectories from childhood to adolescence were predictive of midlife MetS, with ORs in moderate (1.49 [1.00–2.23]) and high-increasing groups (2.45 [1.22–4.91]). Lastly, elevated BMI variability in this period was also linked to higher MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 1.24 [1.08–1.42], 1.00 [1.00–1.01], and 1.21 [1.05–1.38]). Interpretation Our study suggests that both early-life BMI trajectories and BMI variability could be predictive of incident MetS in midlife

Ribosomal protein S3 mediates drug resistance of proteasome inhibitor: potential therapeutic application in multiple myeloma

Multiple myeloma (MM) remains incurable due to drug resistance. Ribosomal protein S3 (RPS3) has been identified as a non-Rel subunit of NF-κB. However, the detailed biological roles of RPS3 remain unclear. Here, we report for the first time that RPS3 is necessary for MM survival and drug resistance. RPS3 was highly expressed in MM, and knockout of RPS3 in MM inhibited cell growth and induced cell apoptosis both in vitro and in vivo. Overexpression of RPS3 mediated the proteasome inhibitor resistance of MM and shortened the survival of MM tumor-bearing animals. Moreover, our present study found an interaction between RPS3 and the thyroid hormone receptor interactor 13 (TRIP13), an oncogene related to MM tumorigenesis and drug resistance. We demonstrated that the phosphorylation of RPS3 was mediated by TRIP13 via PKCδ, which played an important role in activating the canonical NF-κB signaling and inducing cell survival and drug resistance in MM. Notably, the inhibition of NF-κB signaling by the small-molecule inhibitor targeting TRIP13, DCZ0415, was capable of triggering synergistic cytotoxicity when combined with bortezomib in drug-resistant MM. This study identifies RPS3 as a novel biomarker and therapeutic target in MM