The pandemic of coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has caused an unprecedented global social and economic impact, and ...high numbers of deaths. Many risk factors have been identified in the progression of COVID‐19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID‐19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high‐sensitivity C‐reactive protein, proinflammatory cytokines such as interleukin (IL)‐6, IL‐1β, Krebs von den Lungen‐6 (KL‐6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID‐19.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The response of immune cells in cardiac injury is divided into three continuous phases: inflammation, proliferation and maturation. The kinetics of the inflammatory and proliferation phases directly ...influence the tissue repair. In cardiac homeostasis, cardiac tissue resident macrophages (cTMs) phagocytose bacteria and apoptotic cells. Meanwhile, NK cells prevent the maturation and transport of inflammatory cells. After cardiac injury, cTMs phagocytose the dead cardiomyocytes (CMs), regulate the proliferation and angiogenesis of cardiac progenitor cells. NK cells prevent the cardiac fibrosis, and promote vascularization and angiogenesis. Type 1 macrophages trigger the cardioprotective responses and promote tissue fibrosis in the early stage. Reversely, type 2 macrophages promote cardiac remodeling and angiogenesis in the late stage. Circulating macrophages and neutrophils firstly lead to chronic inflammation by secreting proinflammatory cytokines, and then release anti-inflammatory cytokines and growth factors, which regulate cardiac remodeling. In this process, dendritic cells (DCs) mediate the regulation of monocyte and macrophage recruitment. Recruited eosinophils and Mast cells (MCs) release some mediators which contribute to coronary vasoconstriction, leukocyte recruitment, formation of new blood vessels, scar formation. In adaptive immunity, effector T cells, especially Th17 cells, lead to the pathogenesis of cardiac fibrosis, including the distal fibrosis and scar formation. CMs protectors, Treg cells, inhibit reduce the inflammatory response, then directly trigger the regeneration of local progenitor cell via IL-10. B cells reduce myocardial injury by preserving cardiac function during the resolution of inflammation.
Irritable bowel syndrome (IBS) is a common disorder in gastrointestinal system and impairs the quality of life of the patients. Clostridium butyricum (CB) is a probiotics that has been used in ...several gastrointestinal diseases. The efficacy of CB in treating IBS is still unknown. This prospective, multi-centre, randomized, double-blind, placebo-controlled trial aimed to assess the efficacy and safety of CB in treating diarrhea-predominant IBS (IBS-D) and analyze the fecal microbiota after treatment. Two hundred patients with IBS-D were recruited and were given CB or placebo for 4 weeks. End points included change from baseline in IBS symptoms, quality of life, stool consistency and frequency. Compared with placebo, CB is effective in improving the overall IBS-D symptoms (-62.12 ± 74.00 vs. -40.74 ± 63.67, P = 0.038) as well as quality of life (7.232 ± 14.06 vs. 3.159 ± 11.73, P = 0.032) and stool frequency (-1.602 ± 1.416 vs. -1.086 ± 1.644, P = 0.035). The responder rates are found higher in CB compared with the placebo (44.76% vs. 30.53%, P = 0.042). The change in fecal microbiota was analyzed and function pathways of CB in treating IBS-D were predicted. In conclusion, CB improves overall symptoms, quality of life and stool frequency in IBS-D patients and is considered to be used as a probiotics in treating IBS-D clinically.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In cellular networks, proximity users may communicate directly without going through the base station, which is called Device-to-device (D2D) communications and it can improve spectral efficiency. ...However, D2D communications may generate interference to the existing cellular networks if not designed properly. In this paper, we study a resource allocation problem to maximize the overall network throughput while guaranteeing the quality-of-service (QoS) requirements for both D2D users and regular cellular users (CUs). A three-step scheme is proposed. It first performs admission control and then allocates powers for each admissible D2D pair and its potential CU partners. Next, a maximum weight bipartite matching based scheme is developed to select a suitable CU partner for each admissible D2D pair to maximize the overall network throughput. Numerical results show that the proposed scheme can significantly improve the performance of the hybrid system in terms of D2D access rate and the overall network throughput. The performance of D2D communications depends on D2D user locations, cell radius, the numbers of active CUs and D2D pairs, and the maximum power constraint for the D2D pairs.
The National Drug Price Negotiation (NDPN) policy has entered a normalisation stage, aiming to alleviate, to some extent, the disease-related and economic burdens experienced by cancer patients. This ...study analysed the use and subsequent burden of anticancer medicines among cancer patients in a first-tier city in northeast China.
We assessed the usage of 64 negotiated anticancer medicines using the data on the actual drug deployment situation, the frequency of medical insurance claims and actual medication costs. The affordability of these medicines was measured using the catastrophic health expenditure (CHE) incidence and intensity of occurrence. Finally, we used the defined daily doses (DDDs) and defined daily doses cost (DDDc) as indicators to evaluate the actual use of these medicines in the region.
During the study period, 63 of the 64 medicines were readily available. From the perspective of drug usage, the frequency of medical insurance claims for negotiated anticancer medicines and medication costs showed an increasing trend from 2018 to 2021. Cancer patients typically sought medical treatment at tertiary hospitals and purchased medicines at community pharmacies. The overall quantity and cost of medications for patients covered by the Urban Employee Basic Medical Insurance (UEBMI) were five times higher than those covered by the Urban and Rural Resident Medical Insurance (URRMI). The frequency of medical insurance claims and medication costs were highest for lung and breast cancer patients. Furthermore, from 2018 to 2021, CHE incidence showed a decreasing trend (2.85-1.60%) under urban patients' payment capability level, but an increasing trend (11.94%-18.42) under rural patients' payment capability level. The average occurrence intensities for urban (0.55-1.26 times) and rural (1.27-1.74 times) patients showed an increasing trend. From the perspective of drug utilisation, the overall DDD of negotiated anticancer medicines showed an increasing trend, while the DDDc exhibited a decreasing trend.
This study demonstrates that access to drugs for urban cancer patients has improved. However, patients' medical behaviours are affected by some factors such as hospital level and type of medical insurance. In the future, the Chinese Department of Health Insurance Management should further improve its work in promoting the fairness of medical resource distribution and strengthen its supervision of the nation's health insurance funds.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study explores the role of the long noncoding RNA (LncRNA) CRNDE in cisplatin (CDDP) resistance of gastric cancer (GC) cells. Here, we show that LncRNA CRNDE is upregulated in carcinoma tissues ...and tumor‐associated macrophages (TAMs) of GC patients. In vitro experiments show that CRNDE is enriched in M2‐polarized macrophage‐derived exosomes (M2‐exo) and is transferred from M2 macrophages to GC cells via exosomes. Silencing CRNDE in M2‐exo reverses the promotional effect of M2‐exo on cell proliferation in CDDP‐treated GC cells and homograft tumor growth in CDDP‐treated nude mice. Mechanistically, CRNDE facilitates neural precursor cell expressed developmentally downregulated protein 4‐1 (NEDD4‐1)‐mediated phosphatase and tensin homolog (PTEN) ubiquitination. Silencing CRNDE in M2‐exo enhances the CDDP sensitivity of GC cells treated with M2‐exo, which is reduced by PTEN knockdown. Collectively, these data reveal a vital role for CRNDE in CDDP resistance of GC cells and suggest that the upregulation of CRNDE in GC cells may be attributed to the transfer of TAM‐derived exosomes.
SYNOPSIS
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes, suppressing PTEN expression in GC cells. The latter leads to a reduced sensitivity of GC cells to cisplatin.
LncRNA CRNDE is enriched in TAMs of GC patients.
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes in vitro.
CRNDE facilitates NEDD4‐1‐mediated PTEN ubiquitination in GC cells.
Exosomal transfer of LncRNA CRNDE is linked to cisplatin resistance in GC cells caused by reduced PTEN levels.
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes, suppressing PTEN expression in GC cells. The latter leads to a reduced sensitivity of GC cells to cisplatin.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Whether amino acids act on cellular insulin signaling remains unclear, given that increased circulating amino acid levels are associated with the onset of type 2 diabetes (T2D). Here, we ...report that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake. Mice fed phenylalanine-rich chow or phenylalanine-producing aspartame or overexpressing human phenylalanyl-tRNA synthetase (hFARS) develop insulin resistance and T2D symptoms. Mechanistically, FARS phenylalanylate lysine 1057/1079 of IRβ (F-K1057/1079), inactivating IRβ and preventing insulin from promoting glucose uptake by cells. SIRT1 reverse F-K1057/1079 and counteract the insulin-inactivating effects of hFARS and phenylalanine. F-K1057/1079 and SIRT1 levels in white blood cells from T2D patients are positively and negatively correlated with T2D onset, respectively. Blocking F-K1057/1079 with phenylalaninol sensitizes insulin signaling and relieves T2D symptoms in
hFARS
-transgenic and db/db mice. These findings shed light on the activation of insulin signaling and T2D progression through inhibition of phenylalanylation.
Alterations in membrane proteins (MPs) and their regulated pathways have been established as cancer hallmarks and extensively targeted in clinical applications. However, the analysis of ...MP-interacting proteins and downstream pathways across human malignancies remains challenging. Here, we present a systematically integrated method to generate a resource of cancer membrane protein-regulated networks (CaMPNets), containing 63,746 high-confidence protein-protein interactions (PPIs) for 1962 MPs, using expression profiles from 5922 tumors with overall survival outcomes across 15 human cancers. Comprehensive analysis of CaMPNets links MP partner communities and regulated pathways to provide MP-based gene sets for identifying prognostic biomarkers and druggable targets. For example, we identify CHRNA9 with 12 PPIs (e.g., ERBB2) can be a therapeutic target and find its anti-metastasis agent, bupropion, for treatment in nicotine-induced breast cancer. This resource is a study to systematically integrate MP interactions, genomics, and clinical outcomes for helping illuminate cancer-wide atlas and prognostic landscapes in tumor homo/heterogeneity.
Fabricating solar cells with tandem structure is an efficient way to broaden the photon response range without further increasing the thermalization loss in the system. In this work, a tandem organic ...solar cell (TOSC) based on highly efficient nonfullerene acceptors (NFAs) with series connection type is demonstrated. To meet the different demands of front and rear sub‐cells, two NFAs named F‐M and NOBDT with a whole absorption range from 300 to 900 nm are designed, when blended with wide bandgap polymer poly(2,6‐(4,8‐bis(5‐(2‐ethylhexyl)thiophen‐2‐yl)‐benzo1,2‐b:4,5‐b′dithiophene))‐alt‐(5,5‐(1′,3′‐di‐2‐thienyl‐5′,7′‐bis(2‐ethylhexyl)benzo1′,2′‐c:4′,5′‐c′dithiophene‐4,8‐dione)) (PBDB‐T) and narrow bandgap polymer PTB7‐Th, respectively, the PBDB‐T: F‐M system exhibits a high Voc of 0.98 V and the PTB7‐Th: NOBDT system shows a remarkable Jsc of 19.16 mA cm−2, which demonstrate their potential in the TOSCs. With the guidance of optical simulation, by systematically optimizing the thickness of each layer in the TOSC, an outstanding power conversion efficiency of 14.11%, with a Voc of 1.71 V, a Jsc of 11.72 mA cm−2, and a satisfactory fill factor of 0.70 is achieved; this result is one of the top efficiencies reported to date in the field of organic solar cells.
A non‐fullerene tandem organic solar cell (OSC) with high efficiency is fabricated. Two non‐fullerene acceptors named F‐M and NOBDT with a whole absorption range from 300–900 nm are designed for the front and rear sub‐cell respectively; the tandem cell based on them demonstrates an outstanding PCE of 14.11%, which is among the top PCEs in the field of OSCs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Microglia have been recently shown to manifest a very interesting phenotypical heterogeneity across different regions in the mammalian central nervous system (CNS). However, the underlying mechanism ...and functional meaning of this phenomenon are currently unclear. Baseline diversities of adult microglia in their cell number, cellular and subcellular structures, molecular signature as well as relevant functions have been discovered. But recent transcriptomic studies using bulk RNAseq and single-cell RNAseq have produced conflicting results on region-specific signatures of microglia. It is highly speculative whether such spatial heterogeneity contributes to varying sensitivities of individual microglia to the same physiological and pathological signals in different CNS regions, and hence underlie their functional relevance for CNS disease development. This review aims to thoroughly summarize up-to-date knowledge on this specific topic and provide some insights on the potential underlying mechanisms, starting from microgliogenesis. Understanding regional heterogeneity of microglia in the context of their diverse neighboring neurons and other glia may provide an important clue for future development of innovative therapies for neuropsychiatric disorders.
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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
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