Abstract
We report a family cluster of coronavirus disease 2019 (COVID-19) caused by a presymptomatic case. There were 9 family members, including 8 laboratory-confirmed with COVID-19, and a ...6-year-old child had no evidence of infection. Among the 8 patients, 1 adult and a 13-month-old infant were asymptomatic, and 1 adult was diagnosed as having severe pneumonia.
The mixed lineage kinase domain-like （MLKL） protein is a key factor in tumor necrosis factor-induced necropto- sis. Recent studies on necroptosis execution revealed a commitment role of MLKL in ...membrane disruption. However, our knowledge of how MLKL functions on membrane remains very limited. Here we demonstrate that MLKL forms cation channels that are permeable preferentially to Mg2＋ rather than Caz＋ in the presence of Na＋ and K＋. Moreover, the N-terminal domain containing six helices （HI-H6） is sufficient to form channels. Using the substituted eysteine accessibility method, we further determine that helix HI, H2, H3, H5 and H6 are transmembrane segments, while H4 is located in the cytoplasm. Finally, MLKL-induced membrane depolarization and cell death exhibit a positive correlation to its channel activity. The 2＋ Mg -preferred permeability and five transmembrane segment topology distin- guish MLKL from previously identified Mg2＋-permeable channels and thus establish MLKL as a novel class of cation channels.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Protein corona can alter the physiochemical properties of targeting nanoparticles (NPs), as well as their physiological responses and targeting functionality. Herein, we synthesized 20 types of NPs ...with diverse surface chemistry in order to study the impacts of protein corona on targeting functionality of NPs functionalized with cyclic RGD peptides and their relationships to the polyethylene glycol (PEG) length and grafting density of targeting ligands. After protein adsorption, cyclic RGD on the surface of NP was still able to bind its receptors with increased targeted cellular uptake, even at a relatively low density. However, the cellular uptake was reduced from 26 to 76% when compared with protein nonbound NPs, which was caused by the shielding effect of the outer layer adsorbed proteins. NPs functionalized with short PEG molecules and moderate cyclic RGD density performed a better targeting efficiency. Due to PEG conjugation, the protein corona was demonstrated to be beneficial for passive targeting by decreasing macrophage cellular uptake. These relationships between surface chemistry and targeting functionality will provide guidelines for the design of targeting nanoformulations in nanomedicine.
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IJS, KILJ, NUK, PNG, UL, UM
Emerging studies show that long noncoding RNAs (lncRNAs) play important roles in carcinogenesis and cancer progression. The lncRNA ZEB1 antisense 1 (ZEB1-AS1) derives from the promoter region of ZEB1 ...and we still know little about its expressions, roles and mechanisms.
RACE was used to obtain the sequence of ZEB1-AS1. RNA interference was used to decrease ZEB1-AS1 expression. Adenovirus expression vector was used to increase ZEB1-AS1 expression. CHIP and RIP were used to detect the epigenetic mechanisms by which ZEB1-AS1 regulated ZEB1. CCK8 assay, wound healing assay and transwell assay were used to measure proliferation and migration of prostate cancer cells.
In this study, in prostate cancer cells, we found that RNAi-mediated downregulation of ZEB1-AS1 induced significant ZEB1 inhibition while artificial overexpression of ZEB1-AS1 rescued ZEB1 expression, which means that ZEB1-AS1 promotes ZEB1 expression. Also, ZEB1-AS1 indirectly inhibited miR200c, the well-known target of ZEB1, and upregulated miR200c's target BMI1. Mechanistically, ZEB1-AS1 bound and recruited histone methyltransferase MLL1 to the promoter region of ZEB1, induced H3K4me3 modification therein, and activated ZEB1 transcription. Biologically, ZEB1-AS1 promoted proliferation and migration of prostate cancer cells.
Collectively, ZEB1-AS1 functions as an oncogene in prostate cancer via epigenetically activating ZEB1 and indirectly regulating downstream molecules of ZEB1.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Inflammatory bowel disease (IBD) is defined as an immune dysregulation disease with poor prognosis. Various therapies based on gut microbe modulation have been proposed. In this study, we aim to ...explore the therapeutic effect of B. adolescentis on IBD, as well as the immune and microecology mechanism of B. adolescentis in IBD. The fecal level of B. adolescentis was decreased in the IBD patients compared with the normal people in our cohort and the GMrepo database. To further clarify the role of B. adolescentis in IBD, we induced chronic colitis with three cycles of dextran sulfate sodium (DSS). We found B. adolescentis gavage exhibited protective effects as evidenced by the significantly decreased diarrhea score, spleen weight, and increased colon length. Accordingly, the cumulative histological grading was decreased in the B. adolescentis administration group. In addition, tight junction protein and mucin family were enhanced after B. adolescentis treatment. Furthermore, distinct effects were found with decreased pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β, IL-18, IL-22, IL-9 and increased anti-inflammatory cytokines IL-10, IL-4, IL-5. Importantly, the colon lamina propria in the B. adolescentis group consisted of more Treg and Th2 cells, which inhibited extreme gut inflammation. Additionally, 16srRNA sequencing showed an evident increase in the B:F ratio in the B. adolescentis group. In particular, B. adolescentis application inhibited the excessive growth of Akkermansia and Escherichia-Shigella in genus level. In conclusion, B. adolescentis refined the DSS-induced chronic colitis by stimulating protective Treg/Th2 response and gut microbiota remodeling. B. adolescentis regularly treatment might improve the therapeutic effects for inflammatory bowel disease.
It is imperative to design a suitable material for bone regeneration that emulates the microstructure and compositional framework of natural bone while mitigating the shortcomings of current repair ...materials.
The aim of the study is to synthesize a 3D aerogel scaffold composed of PLCL/gelatin electro-spun nanofiber loaded with Simvastatin and investigate its biocompatibility as well as its performance in cell proliferation and ossification differentiation.
PLCL/gelatin nanofibers were fabricated in coaxial electrospinning with simvastatin added. Fibers were fragmented, pipetted into molds, frozen, and dried. The morphology of fibers and contact angles in 4 groups of PLCL, PLCL@S, 3D-PLCL, and 3D-PLCL@S was observed and compared. MC3T3-E1 cells were planted at the four materials to observe cell growth status, and ALP and ARS tests were conducted to compare the ossification of cells.
TEM scanning showed the coaxial fiber of the inner PLCL and outer gelatin. The mean diameter of the PLCL/gelatin fibers is 561 ± 95 nm and 631 ± 103 nm after the drug loading. SEM showed the fibers in the 3D-PLCL@S group were more curled and loose with more space interlaced. The contact angle in this group was 27.1°, the smallest one. Drug release test demonstrated that simvastatin concentration in the 3D-PLCL@S could remain at a relatively high level compared to the control group. The cell proliferation test showed that MC3T3-EI cells could embed into the scaffold deeply and exhibit higher viability in the 3D-PLCL@S group than other groups. The ossification tests of ALP and ARS also inferred that the 3D-PLCL@S scaffold could offer a better osteogenic differentiation matrix.
The PLCL/gelatin aerogel scaffold, when loaded with Simvastatin, demonstrates a more pronounced potential in enhancing osteoblast proliferation and osteogenic differentiation. We hypothesize that this scaffold could serve as a promising material for addressing bone defects.
Checkpoint inhibitor-related pneumonitis (CIP) is a complication of immunotherapy for malignant tumors that severely limits the treatment cycles as well as endangers patients' health. The chest CT ...imaging features or typing of CIP and the application of radiomics will contribute to the precise prevention, early diagnosis and instant treatment of CIP. This article reviews the advances in the CT features and the application of radiomics in CIP.
Grape quality is a key factor in determining wine quality, and it depends not only on management skills, but also on the geographic location of the producing area. In China, Shandong is the province ...with the largest wine production, and 'Cabernet Franc' is widely planted. This study evaluated the 'Cabernet Franc' fruit quality in relation to geographical conditions in five 'Cabernet Franc' producing districts of Shandong province, China, including Dezhou Aodeman Winery (DZ), Tai'an Zhongqingsongshi Winery (TA), Penglai Longhu Winery (PL), Rushan Taiyihu Winery (RS), and Rizhao Taiyangcheng Winery (RZ). At the time of veraison and maturity, fruit was harvested from five areas, and compared for cosmetic and internal fruit quality. The soluble sugar content in the Rizhao area was rich, and the weight and volume of single fruit were relatively large. The titratable acid of the berries in Tai'an area was high. RNA-seq analysis showed that the number of genes in the véraison stage was 19,571-20,750, and the number of genes in the mature stage was 19,176-20,735. The analysis found that areas with multiple high-quality characteristics tended to have more DEGs (differential expressed genes). And the DEGs in different areas were mainly distributed on chromosome 7, and at least on chromosome 15. DEGs in 5 areas were enriched on 855 GO terms and 116 KEGG pathways during berries development. Among them, it was found that the up/down-regulation of DEGs was related to the formation of berry quality, which helps to explain the impact of environment on grape quality components. In summary, this study is helpful to understand the influence of cultivation location on the quality of 'Cabernet Franc' in different production areas in Shandong province, and further provide a reference for the production of high-quality wine grapes and winemaking.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Enniatin B1 (ENN B1) is a mycotoxin that can be found in various foods. However, whether ENN B1 is hazardous to the reproductive system is still elusive. Leydig cells are testosterone-generating ...cells that reside in the interstitial compartment between seminiferous tubules. Dysfunction of Leydig cells could result in male infertility. This study aimed to examine the toxicological effects of ENN B1 against TM3 Leydig cells. ENN B1 significantly inhibited cell viability in a dose-dependent manner. ENN B1 treatment also decreased the expression of functional genes in Leydig cells. Moreover, ENN B1 induced Leydig cells apoptosis and oxidative stress. Mechanistically, ENN B1 leads to the upregulation of Bax and downregulation of Bcl-2 in Leydig cells. In addition, ENN B1 inhibited the Nrf2/HO-1 pathway, which is critical for the induction of oxidative stress. Additionally, ENN B1 treatment repressed the JAK/STAT3 signaling pathway in Leydig cells. Rescue experiments showed that activation of STAT3 resulted in alleviation of ENN B1-induced damage in Leydig cells. Collectively, our study demonstrated that ENN B1 induced Leydig cell dysfunction via multiple mechanisms.
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•ENN B1 inhibits the cellular viability and expression of functional genes in Leydig cells.•ENN B1 induces apoptosis of Leydig cells in a caspase-dependent manner.•ENN B1 induces oxidative stress via modulation of Keap1/Nrf2/HO-1 signalling pathway.•ENN B1 regulates SHP1 and the JAK/STAT3 signalling pathway in Leydig cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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