The COVID-19 pandemic has emerged as a global health emergency due to its association with severe pneumonia and relative high mortality. However, the molecular characteristics and pathological features underlying COVID-19 pneumonia remain largely unknown. To characterize molecular mechanisms underlying COVID-19 pathogenesis in the lung tissue using a proteomic approach, fresh lung tissues were obtained from newly deceased patients with COVID-19 pneumonia. After virus inactivation, a quantitative proteomic approach combined with bioinformatics analysis was used to detect proteomic changes in the SARS-CoV-2-infected lung tissues. We identified significant differentially expressed proteins involved in a variety of fundamental biological processes including cellular metabolism, blood coagulation, immune response, angiogenesis, and cell microenvironment regulation. Several inflammatory factors were upregulated, which was possibly caused by the activation of NF-κB signaling. Extensive dysregulation of the lung proteome in response to SARS-CoV-2 infection was discovered. Our results systematically outlined the molecular pathological features in terms of the lung response to SARS-CoV-2 infection, and provided the scientific basis for the therapeutic target that is urgently needed to control the COVID-19 pandemic.

TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model

Complex environmental conditions can significantly affect bacterial genome size by unknown mechanisms. The So0157-2 strain of Sorangium cellulosum is an alkaline-adaptive epothilone producer that grows across a wide pH range. Here, we show that the genome of this strain is 14,782,125 base pairs, 1.75-megabases larger than the largest bacterial genome from S. cellulosum reported previously. The total 11,599 coding sequences (CDSs) include massive duplications and horizontally transferred genes, regulated by lots of protein kinases, sigma factors and related transcriptional regulation co-factors, providing the So0157-2 strain abundant resources and flexibility for ecological adaptation. The comparative transcriptomics approach, which detected 90.7% of the total CDSs, not only demonstrates complex expression patterns under varying environmental conditions but also suggests an alkaline-improved pathway of the insertion and duplication, which has been genetically testified, in this strain. These results provide insights into and a paradigm for how environmental conditions can affect bacterial genome expansion.

Background The therapeutic potential of exosomes derived from stem cells has attracted increasing interest recently, because they can exert similar paracrine functions of stem cells and overcome the limitations of stem cells transplantation. Exosomes derived from bone mesenchymal stem cells (BMSC-Exos) have been confirmed to promote osteogenesis and angiogenesis. The magnetic nanoparticles (eg. Fe3O4, γ-Fe2O3) combined with a static magnetic field (SMF) has been commonly used to increase wound healing and bone regeneration. Hence, this study aims to evaluate whether exosomes derived from BMSCs preconditioned with a low dose of Fe3O4 nanoparticles with or without the SMF, exert superior pro-osteogenic and pro-angiogenic activities in bone regeneration and the underlying mechanisms involved. Methods Two novel types of exosomes derived from preconditioned BMSCs that fabricated by regulating the contents with the stimulation of magnetic nanoparticles and/or a SMF. Then, the new exosomes were isolated by ultracentrifugation and characterized. Afterwards, we conducted in vitro experiments in which we measured osteogenic differentiation, cell proliferation, cell migration, and tube formation, then established an in vivo critical-sized calvarial defect rat model. The miRNA expression profiles were compared among the exosomes to detect the potential mechanism of improving osteogenesis and angiogenesis. At last, the function of exosomal miRNA during bone regeneration was confirmed by utilizing a series of gain- and loss-of-function experiments in vitro. Results 50 µg/mL Fe3O4 nanoparticles and a 100 mT SMF were chosen as the optimum magnetic conditions to fabricate two new exosomes, named BMSC-Fe3O4-Exos and BMSC-Fe3O4-SMF-Exos. They were both confirmed to enhance osteogenesis and angiogenesis in vitro and in vivo compared with BMSC-Exos, and BMSC-Fe3O4-SMF-Exos had the most marked effect. The promotion effect was found to be related to the highly riched miR-1260a in BMSC-Fe3O4-SMF-Exos. Furthermore, miR-1260a was verified to enhance osteogenesis and angiogenesis through inhibition of HDAC7 and COL4A2, respectively. Conclusion These results suggest that low doses of Fe3O4 nanoparticles combined with a SMF trigger exosomes to exert enhanced osteogenesis and angiogenesis and that targeting of HDAC7 and COL4A2 by exosomal miR-1260a plays a crucial role in this process. This work could provide a new protocol to promote bone regeneration for tissue engineering in the future. Graphical abstract

BackgroundType 2 diabetes is associated with acute and chronic complications and poses a large economic, social, and medical burden on patients and their families as well as society.ObjectiveThis study aims to evaluate the direct economic burden of type 2 diabetes in China. Data source: systematic review on cost of illness, health care costs, direct service costs, drug costs, and health expenditures in relation to type 2 diabetes was conducted up to 2014 using databases such as Pubmed; EBSCO; Elsevier ScienceDirect, Web of Science; and a series of Chinese databases, including Wanfang Data, China National Knowledge Infrastructure (CNKI), and the China Science and Technology Journal Database. Factors influencing hospitalization and drug fees were also identified. Study eligibility criteria: (1) estimation of the direct economic burden including hospitalization and outpatient cost of type 2 diabetes patients in China; (2) evaluation of the factors influencing the direct economic burden. Articles only focusing on the cost-effectiveness analysis of diabetes drugs were excluded.ResultsThe direct economic burden of type 2 diabetes has increased over time in China, and in 2008, the direct medical cost reached $9.1 billion, Both outpatient and inpatient costs have increased. Income level, type of medical insurance, the level of hospital care, and type and number of complications are primary factors influencing diabetes related hospitalization costs. Compared to urban areas, the direct non-medical cost of type 2 diabetes in rural areas is significantly greater.ConclusionsThe direct economic burden of type 2 diabetes poses a significant challenge to China. To address the economic burden associated with type 2 diabetes, measures need to be taken to reduce prevalence rate and severity of diabetes and hospitalization cost.

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SAPHO syndrome is predominant in middle-age women, characterized by dermatological and osteoarticular manifestations with unknown aetiology. CT scan and bone scintigraphy are useful for diagnosis. There is still no standard treatment to control the disease.

In this study, we sequenced 18S rRNA genes (rDNA) from 49 fungal strains representing 31 species from 15 genera. Most of these species are common airborne fungi and pathogens that may cause various public health concerns. Sequence analysis revealed distinct divergence between Zygomycota and Ascomycota. Within Ascomycota, several strongly supported clades were identified that facilitate the taxonomic placement of several little-studied fungi. Wallemia appeared as the group most diverged from all the other Ascomycota species. Based on the 18S rDNA sequence variation, 108 oligonucleotide probes were designed for each genus and species included in this study. After homology searches and DNA hybridization evaluations, 33 probes were verified as genus or species specific. The optimal hybridization temperatures to achieve the best specificity for these 33 probes were determined. These new probes can contribute to the molecular diagnostic research for environmental monitoring.