Since its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 deaths as of ...April 16, 2020. SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.
We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) persons using two-sided Student's t test. We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test.
ACE2 expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle. ACE2 showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland. ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue. In the skin, digestive system, brain, and blood vessels, ACE2 expression levels were positively associated with immune signatures in both males and females. In the thyroid and lungs, ACE2 expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively.
Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally. The different host immune responses to SARS-CoV-2 infection may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity. This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.
Retinal pigment epithelium (RPE) cell damage is implicated in the pathogenesis of age‐related macular degeneration (AMD). An increase of interferon‐γ (IFN‐γ) levels was observed in patients with AMD, ...but whether inflammatory factors are causally related to AMD progression is unclear. Here, we demonstrate a direct causal relationship between IFN‐γ and RPE cell death. IFN‐γ induced human retinal pigment epithelial cell (ARPE‐19) death accompanied by increases in Fe2+, reactive oxygen species, lipid peroxidation, and glutathione (GSH) depletion, which are main characteristics of ferroptosis. Mechanistically, IFN‐γ upregulates the level of intracellular Fe2+ through inhibiting Fe2+ efflux protein SLC40A1 and induces GSH depletion by blocking cystine/glutamate antiporter, System xc‐. At the same time, treatment with IFN‐γ decreases the level of glutathione peroxidase 4 (GPx4), rendering the cells more sensitive to ferroptosis. JAK1/2 and STAT1 inhibitors could reverse the reduction of SLC7A11, GPx4 and GSH expression induced by IFN‐γ, indicating IFN‐γ induces ARPE‐19 cell ferroptosis via activation of the JAK1‐2/STAT1/SLC7A11 signaling pathway. The above results were largely confirmed in IFN‐γ‐treated mice in vivo. Finally, we used sodium iodate (NaIO3)‐induced retinal degeneration to further explore the role of ferroptosis in AMD in vivo. Consistent with the role of IFN‐γ, treatment with NaIO3 decreased SLC7A11, GPx4 and SLC40A1 expressions. NaIO3‐induced RPE damage was accompanied by increased iron, lipid peroxidation products (4‐hydroxynonenal, malondialdehyde), and GSH depletion, and ferroptosis inhibitors could reverse the above phenomenon. Taken together, our findings suggest that inhibiting ferroptosis or reducing IFN‐γ may serve as a promising target for AMD.
IFN‐γ downregulates the expression of SLC7A11 via JAK1‐2/STAT1 signaling pathway, which results in decreases in cysteine transport and, subsequently, decreased GSH synthesis. Simultaneously, IFN‐γ increases intracellular Fe2+ levels through the inhibition of SLC40A1. GSH depletion and Fe2+ accumulation cause retinal pigment epithelial cells ferroptosis and accelerate the progression of AMD.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
To evaluate the effectiveness of the Shengxuexiaoban Capsules combined with glucocorticoid therapy for immune thrombocytopenia (ITP). We collected randomized controlled trials (RCTs) using ...shengxuexiaoban capsules in combination with glucocorticoid to treat ITP by searching major Chinese and English electronic databases. The outcome indicators were the effective rate, recurrence rate, the number of platelets in the blood, recovery time of platelets, and adverse reactions. We used STATA 16.0 and RevMan 5.3 for meta-analysis and GRADE pro. for evidence quality evaluation. A total of 27 RCTs were included in the meta-analysis, and the results showed a significant difference (all p<0.05) in the effective rate, recurrence rate, the number of platelets, and the recovery time of platelets (greater than or equal to 100x10.sup.9) between ITP patients in the control group (who received glucocorticoid therapy alone) and test group (who received glucocorticoid therapy combined with the Shengxuexiaoban Capsules). And that Shengxuexiaoban capsules combined with glucocorticoid therapy were safe. The funnel plot and Egger's test results indicated no obvious publication bias. The GRADE evidence rating showed an intermediate quality of evidence rating for recurrence rate and overall effectiveness. Glucocorticoid therapy combined with the Shengxuexiaoban Capsules showed more effectiveness in the treatment of ITP. It can improve the effective rate, reduce the recurrence rate, increase the number of platelets and shorten the recovery time of platelets, and has a good safety profile.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Biomass components were classified into starch, cellulose, hemicellulose, lignin, protein and oil.•The devolatilization sensitivity was the order of ...hemicellulose > starch > oil > cellulose ≈ protein > lignin.•The Ea was in the order of starch > oil > lignin > Hem > protein > cellulose.•Oil-rich biomass was a potential material for alkene.
Pyrolysis of more biomass group components should be studied in order to obtain a more comprehensive understanding of various biomass pyrolysis. In this study, chemical properties of six biomass group components, namely, starch, cellulose, Hemicellulose (Hem), lignin, protein and oil, were evaluated and their pyrolysis behavior, gaseous product evolution, kinetics and product distributions were investigated using TG-FTIR and Py-GC/MS. The results indicated that their devolatilization sensitivity to heating rate followed the order of Hem > starch > oil > cellulose ≈ protein > lignin. Kinetic results revealed that it was difficult to pyrolyze for biomass rich in oil and lignin but easy to pyrolyze for biomass rich in cellulose, starch, Hem and protein. During their pyrolysis, polysaccharides (starch, cellulose and Hem) mainly generated oxygen-containing components such as CO and O-heterocycles; lignin mainly contributed to the formation of phenols (up to 81.4%); protein produced nitrogen-containing components (up to 52.71%), including N-heterocycles, pyrroles, pyridines, nitriles, and amines/amides; oil generated large quantities of alkenes (46.48%). Finally, this research would serve to gain further insight into biomass pyrolysis containing different group components.
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GEOZS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•A reliable multivariate integrated drought index (MIDI) was constructed.•A drought event was redefined with the MIDI using run theory.•The drought risk with multi-dimensional and multivariate ...characteristics was fully assessed.•The subzones thatwhere had high-risk occurrence of heavy-droughts were found.
It is critical to assess drought risk based on a reliably integrated drought index incorporating comprehensive information of meteorology, hydrology and agriculture drought indices, which is of great value for further understanding the future drought tendency, prevention and mitigation. Thus, the primary objective of this study was to focus on constructing a multivariate integrated drought index (MIDI) by coupling four drought indices (i.e., Precipitation Anomaly Percentage (PAP), Runoff Anomaly Percentage (RAP), Standardized Precipitation Index with 6-month aggregation time step (SPI6) and Modified Palmer Drought Severity Index (MPDSI)) to objectively and comprehensively investigate drought risk. The variable fuzzy set theory and entropy weight method are used during the MIDI construction process. Based on the MIDI, a drought event including drought duration and severity is redefined using run theory. Then copula-based drought risk is fully assessed through the joint probability distribution of drought duration and severity. Results indicate the following: (1) the constructed MIDI is consistent with the Standardized Precipitation Index (SPI) and Runoff Anomaly Percentage (RAP) series, and it is more sensitive and effective to capture historical drought events; (2) the drought characteristics present noticeable spatial variability among five subzones, and the entire basin has 49 droughts with the longest drought duration spanning 8.55months; and (3) the mainstream, especially the middle and lower reaches, has higher occurrences of severe droughts for approximately every 10years.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Quantum dots (QDs) offer new and versatile ways to harvest light energy. However, there are few examples involving the utilization of QDs in organic synthesis. Visible‐light irradiation of CdSe QDs ...was found to result in virtually quantitative coupling of a variety of thiols to give disulfides and H2 without the need for sacrificial reagents or external oxidants. The addition of small amounts of nickel(II) salts dramatically improved the efficiency and conversion through facilitating the formation of hydrogen atoms, thereby leading to faster regeneration of the ground‐state QDs. Mechanistic studies reveal that the coupling reaction occurs on the QD surfaces rather than in solution and offer a blueprint for how these QDs may be used in other photocatalytic applications. Because no sacrificial agent or oxidant is necessary and the catalyst is reusable, this method may be useful for the formation of disulfide bonds in proteins as well as in other systems sensitive to the presence of oxidants.
On the dot: A clean and efficient catalytic method for the preparation of disulfides from a variety of thiols in the absence of sacrificial reagents or external oxidants is described. Irradiation of CdSe quantum dots (QDs) with visible light results in good to excellent yields of the disulfides and equivalent amounts of H2. Mechanistic studies provide evidence for the formation of QD‐bound RS. and H. radicals as reaction intermediates.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Ferroptosis is a newly characterized form of regulated cell death mediated by iron-dependent accumulation of lipid reactive oxygen species and holds great potential for cancer therapy. However, the ...molecular mechanisms underlying ferroptosis remain largely elusive. In this study, we define an integrative role of DJ-1 in ferroptosis. Inhibition of DJ-1 potently enhances the sensitivity of tumor cells to ferroptosis inducers both in vitro and in vivo. Metabolic analysis and metabolite rescue assay reveal that DJ-1 depletion inhibits the transsulfuration pathway by disrupting the formation of the S-adenosyl homocysteine hydrolase tetramer and impairing its activity. Consequently, more ferroptosis is induced when homocysteine generation is decreased, which might be the only source of glutathione biosynthesis when cystine uptake is blocked. Thus, our findings show that DJ-1 determines the response of cancer cells to ferroptosis, and highlight a candidate therapeutic target to potentially improve the effect of ferroptosis-based antitumor therapy.
The economical consideration of using an electrocatalyst in energy‐related field, composed of non‐precious/sustainable elements is quite noteworthy. In this work, the phosphorus(V) complex of ...tris‐(pentafluorophenyl)corrole (TPFC)PV(OH)2 was reported as electrocatalyst for the hydrogen evolution reaction (HER). The electrochemical studies revealed that the HER experienced a ECEC pathway (E: electron transfer step, C: chemical step), and the possible intermediate PV−H species was suggested. (TPFC)PV(OH)2 displayed excellent HER activity in dimethylformamide (DMF) with trifluoroacetic acid (TFA) as the proton source, and the turnover frequency (TOF) reached 31.75 s−1 at an overpotential of 900 mV. Interestingly, the HER electrocatalytic performance remained extraordinary even applying water as a proton source in acetonitrile/water (v/v=2 : 3), with a TOF of 18.40 mol
H2
${{_{{\rm H}{_{2}}}$
molcat−1 h−1 at an overpotential of 900 mV.
Electrocatalytic HER: A non‐metallic phosphorus(V) corrole complex is sed for homogeneous electrocatalytic hydrogen evolution eaction (HER) in DMF and neutral aqueous systems and exhibits good catalytic activity. The turnover frequency reaches 31.75 s−1 at an overpotential of 900 mV in DMF solution.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The receiver operating characteristic (ROC) curve is a powerful statistical tool and has been widely applied in medical research. In the ROC curve estimation, a commonly used assumption is that ...larger the biomarker value, greater severity the disease. In this article, we mathematically interpret “greater severity of the disease” as “larger probability of being diseased.” This in turn is equivalent to assume the likelihood ratio ordering of the biomarker between the diseased and healthy individuals. With this assumption, we first propose a Bernstein polynomial method to model the distributions of both samples; we then estimate the distributions by the maximum empirical likelihood principle. The ROC curve estimate and the associated summary statistics are obtained subsequently. Theoretically, we establish the asymptotic consistency of our estimators. Via extensive numerical studies, we compare the performance of our method with competitive methods. The application of our method is illustrated by a real‐data example.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The incidence of infertility has recently risen. Semen quality is an important male fertility indicator, and dietary factors can affect semen quality. We conducted this systematic review and ...meta-analysis to determine the effects of healthy dietary patterns on semen quality. A literature search was conducted in 3 databases (Embase, Web of Science and PubMed) on August 21, 2021. The included cross-sectional studies examined the influence of the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and prudent diet patterns on semen quality parameters; six studies (1244 subjects) were included. By comparing high consumption with low consumption of healthy dietary patterns, the results of the meta-analysis showed significantly higher sperm concentrations (mean difference MD = 6.88 × 106 ml−1, 95% confidence interval CI: 1.26 × 106 ml−1-12.49 × 106 ml−1; P < 0.05), a significant increase in total sperm count (MD = 16.70 × 106, 95% CI: 2.37 × 106-31.03 × 106; P < 0.05), and a significant increase in progressive sperm motility (MD = 5.85%, 95% CI: 2.59%-9.12%; P < 0.01). The sperm concentration, progressive sperm motility, and total sperm count were significantly higher in men with higher versus lower consumption of healthy dietary patterns. However, the results must be interpreted with caution.
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