Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for ...systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.
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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
Efficient electrocatalysts capable of operating continuously at industrial ampere‐level current densities are crucial for large‐scale applications of electrocatalytic water decomposition for hydrogen ...production. However, long‐term industrial overall water splitting using a single electrocatalyst remains a major challenge. Here, bimetallic polyphthalocyanine (FeCoPPc)‐anchored Ru nanoclusters, an innovative electrocatalyst comprising the hydrogen evolution reaction (HER) active Ru and the oxygen evolution reaction (OER) active FeCoPPc, engineered for efficient overall water splitting are demonstrated. By density functional theory calculations and systematic experiments, the electrocatalytic coenhancement effect resulting from unique charge redistribution, which synergistically boosts the HER activity of Ru and the OER activity of FeCoPPc by optimizing the adsorption energy of intermediates, is unveiled. As a result, even at a large current density of 2.0 A cm−2, the catalyst exhibits low overpotentials of 220 and 308 mV, respectively, for HER and OER. It exhibits excellent stability, requiring only 1.88 V of cell voltage to achieve a current density of 2.0 A cm−2 in a 6.0 m KOH electrolyte at 70 °C, with a remarkable operational stability of over 100 h. This work provides a new electrocatalytic coenhancement strategy for the design and synthesis of electrocatalyst, paving the way for industrial‐scale overall water splitting applications.
Here, an innovative electrocatalyst, bimetallic polyphthalocyanine (FeCoPPc)‐anchored Ru nanoclusters, designed for efficient overall water splitting under industrial conditions is demonstrated. This electrocatalyst uses the unique electrocatalytic coenhancement effect, resulting from unique charge redistribution, optimizes the desorption of hydrogen by Ru in hydrogen evolution reaction process and reduces the energy barrier of OOH* formation, achieving outstanding industrial overall water splitting performance.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Ultrathin 2D porous carbon-based materials offer numerous fascinating electrical, catalytic, and mechanical properties, which hold great promise in various applications. However, it remains a ...formidable challenge to fabricate these materials with tunable morphology and composition by a simple synthesis strategy. Here, a facile one-step self-flowering method without purification and harsh conditions is reported for large-scale fabrication of high-quality ultrathin (≈1.5 nm) N-doped porous carbon nanosheets (NPC) and their composites. It is demonstrated that the layered tannic/oxamide (TA/oxamide) hybrid is spontaneously blown, exfoliated, bloomed, in situ pore-formed, and aromatized during pyrolysis to form flower-like aggregated NPC. This universal one-step self-flowering system is compatible with various precursors to construct multiscale NPC-based composites (Ru@NPC, ZnO@NPC, MoS
@NPC, Co@NPC, rGO@NPC, etc.). Notably, the programmable architecture enables NPC-based materials with excellent multifunctional performances, such as microwave absorption and hydrogen evolution. This work provides a facile, universal, scalable, and eco-friendly avenue to fabricate functional ultrathin porous carbon-based materials with programmability.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In this paper, a fluorescent biosensor has been developed for protein detection based on poly(thymine) (poly T)-templated copper nanoparticles (Cu NPs) and terminal protection of small molecule ...linked-DNA. This strategy was demonstrated by using small molecule biotin and its binding protein streptavidin (SA) as a model case. In this assay, biotin-linked poly T (biotin-T30) probe was specifically bound to the target protein SA with strong affinity in the presence of SA. The selective binding events confirmed that biotin-T30 probe was protected against the hydrolysis by exonuclease I (Exo I), which could effectively template the formation of fluorescent Cu NPs. The results revealed that the developed strategy was highly sensitive for detecting SA in the concentration range from 0.5 to 1000nM with a detection limit of 0.1nM. In addition, the relative standard deviation was 3.6% in 5 repetitive assays of 50nM SA, which indicated that the reproducibility of the method was acceptable. Besides desirable sensitivity, the developed biosensor also showed high selectivity, low cost, and simplified operations. Thus, it could hold considerable potential to construct a simple, selective and sensitive fluorescent platform for detection of small molecule–protein interactions in molecular diagnostics and genomic research.
•A novel fluorescent biosensor has been developed for protein detection based on poly T-templated Cu NPs and terminal protection assay.•This strategy was free of any fluorescence dye label, and without any other complex design.•The proposed method was simple, rapid and cost-effective, all the process was performed within several minutes at room temperature.•This sensor exhibited highly sensitive and selective detection of streptavidin with a detection limit of 0.1nM.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To explore a new supramolecular interaction as the main driving force to induce hierarchical self-assembly (HSA) is of great importance in supramolecular chemistry. Herein, we present a ...radical-induced HSA process through the construction of well-defined rhomboidal metallacycles containing triphenylamine (TPA) moieties. The light-induced radical generation of the TPA-based metallacycle has been demonstrated, which was found to subsequently drive hierarchical self-assembly of metallacycles in both solution and solid states. The morphologies of nanovesicle structures and nanospheres resulting from hierarchical self-assembly have been well-illustrated by using TEM and high-angle annular dark-field STEM (HAADF-STEM) micrographs. The mechanism of HSA is supposed to be associated with the TPA radical interaction and metallacycle stacking interaction, which has been supported by the coarse-grained molecular dynamics simulations. This study provides important information to understand the fundamental TPA radical interaction, which thus injects new energy into the hierarchical self-assembly of supramolecular coordination complexes (SCCs). More interestingly, the stability of TPA radical cations was significantly increased in these metallacycles during the hierarchical self-assembly process, thereby opening a new way to develop stable organic radical cations in the future.
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IJS, KILJ, NUK, PNG, UL, UM
In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating ...HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.
Introduction
This study explores the preference for daily versus on‐demand pre‐exposure prophylaxis (PrEP) among men who have sex with men (MSM) in developing countries when both regimens are ...available.
Methods
From 11 December 2018 to 19 October 2019, we recruited MSM for an open‐label real‐world PrEP demonstration study in four major cities in China. Subjects selected their preferred PrEP (oral tenofovir/emtricitabine) regimen (daily vs. on‐demand) at recruitment and underwent on‐site screening before initiation of PrEP. We used logistic regression to assess preference for daily PrEP and correlates.
Results
Of 1933 recruited MSM, the median age was 29 years, 7.6% was currently married to or living with a female; the median number of male sexual partners was four and 6.1% had used post‐exposure prophylaxis (PEP) in the previous six months. HIV infection risk was subjectively determined as very high (>75%) in 7.0% of subjects, high (50% to 75%) in 13.3%, moderate (25% to 49%) in 31.5% and low or none (0% to 24%) in 48.1%. On average, participants preferred on‐demand PrEP over daily PrEP (1104 (57.1%) versus 829 (42.9%)) at recruitment. In multivariable analysis, currently being married to or living with a female was associated with 14.6 percentage points lower preference for daily PrEP (marginal effect = −0.146 95% CI: −0.230, −0.062, p = 0.001); whereas the number of male sexual partners (marginal effect = 0.003 95% CI: 0.000, 0.005, p = 0.034) and a subjective assessment of being very high risk of HIV infection (vs. low and no risk, marginal effect size = 0.105 95% CI: 0.012, 0.198, p = 0.027) were associated with increased preference for daily versus on‐demand PrEP. Among the 1933 potential participants, 721 (37.3%) did not attend the subsequent on‐site screening. Lower‐income, lower education level, lower subjective expected risk of HIV infection risk and younger age positively correlated with the absence of on‐site screening.
Conclusions
MSM in China prefer both daily and on‐demand PrEP when both regimens are provided free. Social structural factors and subjective risk of HIV infection have significant impacts on PrEP preference and use. The upcoming national PrEP guideline should consider incorporating both regimens and the correlates to help implement PrEP in China.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
A highly sensitive and selective fluorescent biosensor has been exploited for the determination of p-NP and ALP activity based on the GSH-CuNCs mediated-inner filter effect.
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•The ...IFE-based strategy can eliminate environmental interference and background noises efficiently.•The GSH-CuNCs were facilely prepared and without any other complicated separation process.•This strategy was free of any fluorescence dye label and other complex design.•The IFE-based method had a much higher sensitivity and selectivity compared with the traditional fluorescent assay.
A simple and highly selective fluorescence biosensor has been exploited for p-nitrophenol (p-NP) and alkaline phosphatase (ALP) activity detection based on the glutathione-stabilized copper nanoclusters (GSH-CuNCs) mediated-inner filter effect (IFE). The GSH-CuNCs were prepared by employing GSH as stabilizer and ascorbic acid (AA) as reductant. The obtained GSH-CuNCs exhibited a strong blue fluorescence emission at 420 nm with an excitation wavelength of 365 nm, which overlapped largely with the absorption spectra of p-nitrophenol (p-NP). Therefore, the luminescence of GSH-CuNCs could be quenched by p-NP through inner filter effect. In addition, ALP catalyzed the substrate p-nitrophenyl phosphate (p-NPP) to form p-nitrophenol (p-NP), which also leading to the fluorescence quenching of GSH-CuNCs. The fluorescent strategy was realized for the sensitive determination of p-NP and ALP activity with the promising limit of detection of 20 nM (for p-NP) and 0.003 mU⋅mL−1 (for ALP). Furthermore, the method could be applied to detect the p-NP content in river water samples and ALP activity in human serum samples.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
In oligotrophic oceans, low bioavailability of Fe is a key factor limiting primary productivity. However, excessive Fe in cells leads to the Fenton reaction, which is toxic to cells. ...Cyanobacteria must strictly maintain intracellular Fe homeostasis. Here, we knocked out a series of genes encoding efflux systems in Synechocystis sp. PCC 6803, and found eight genes that are required for high Fe detoxification. Unexpectedly, the HlyBD‐TolC efflux system plays an important role in the adaptation of Synechocystis under Fe‐deficient conditions. Mutants of HlyD and TolC grew worse than the wild‐type strain under low‐Fe conditions and showed significantly lower intracellular Fe contents than the wild‐type strain. We excluded the possibility that the low Fe sensitivity of the HlyBD‐TolC mutants was caused by a loss of the S‐layer, the main extracellular protein secreted via this efflux system. Inactivation of the HlyD protein influenced type IV pili formation and direct inactivation of type IV pili related genes affected the adaptation to low‐Fe conditions. HlyBD‐TolC system is likely involved in the formation of type IV pili and indirectly influenced Fe acquisition. Our findings suggest that efflux system in non‐siderophore‐producing cyanobacteria can facilitate Fe uptake and help cells adapt to Fe‐deficient conditions via novel pathways.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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