The rapid outbreak of coronavirus disease 2019 (COVID-19) has been a matter of international concern as the disease is spreading fast 1, 2. Considering that the contagious disease has led to an ...enormous impact globally, there is an urgent need to identify the risk populations with poor prognosis. Ageing is associated with certain changes in pulmonary physiology, pathology and function, during the period of lung infection. Therefore, age-related differences in responsiveness and tolerance become obvious and lead to worse clinical outcomes in elderly individuals 3. Previous studies have mentioned that older COVID-19 patients are at an increased risk of death 4–7. However, the age-related clinical characteristics, disease courses and outcomes other than death in COVID-19 patients remain unclear.
Age significantly determined the clinical features and prognosis of COVID-19. The prognosis was worse in patients older than 60 years, calling for clinicians to pay more attention to patients of this age.
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Standard and proper antituberculosis (anti-TB) treatment is essential for patients with TB, and rifamycin antibiotics are key components of anti-TB therapy. Therapeutic drug monitoring (TDM) of ...rifamycin antibiotics can shorten the time to response and complete treatment of TB. Notably, antimicrobial activities of the major active metabolites of rifamycin are similar to those of their parent compounds. Thus, a rapid and simple assay was developed for simultaneous determination of rifamycin antibiotics and their major active metabolites in plasma to evaluate their impact on target peak concentrations. Here, the authors have developed and validated a method for simultaneous determination of rifamycin antibiotics and their active metabolites in human plasma using ultrahigh-performance liquid chromatography tandem mass spectrometry.
Analytical validation of the assay was performed in accordance with the bioanalytical method validation guidance for industry described by the US Food and Drug Administration and the guidelines for bioanalytical method validation described by the European Medicines Agency.
The drug concentration quantification method for rifamycin antibiotics, including rifampicin, rifabutin, and rifapentine, and their major active metabolites was validated. Significant differences in the proportions of active metabolites in rifamycin antibiotics may affect the redefinition of their effective concentration ranges in the plasma. The method developed herein is expected to redefine the ranges of "true" effective concentrations of rifamycin antibiotics (including parent compounds and their active metabolites).
The validated method can be successfully applied for high-throughput analysis of rifamycin antibiotics and their active metabolites for TDM in patients receiving anti-TB treatment regimens containing these antibiotics. Proportions of active metabolites in rifamycin antibiotics markedly varied among individuals. Depending on the clinical indications of patients, the therapeutic ranges for rifamycin antibiotics may be redefined.
The homojunction of oxygen/metal vacancies and its interfacial n–p effect on the physiochemical properties are rarely reported. Interfacial n–p homojunctions of TiO2 are fabricated by directly ...decorating interfacial p‐type titanium‐defected TiO2 around n‐type oxygen‐defected TiO2 nanocrystals in amorphous–anatase homogeneous nanostructures. Experimental measurements and theoretical calculations on the cell lattice parameters show that the homojunction of oxygen and titanium vacancies changes the charge density of TiO2; a strong EPR signal caused by oxygen vacancies and an unreported strong titanium vacancies signal of 2D 1H TQ‐SQ MAS NMR are present. Amorphous–anatase TiO2 shows significant performance regarding the photogeneration current, photocatalysis, and energy storage, owing to interfacial n‐type to p‐type conductivity with high charge mobility and less structural confinement of amorphous clusters. A new “homojunction of oxygen and titanium vacancies” concept, characteristics, and mechanism are proposed at an atomic‐/nanoscale to clarify the generation of oxygen vacancies and titanium vacancies as well as the interface electron transfer.
The homojunction of oxygen and titanium vacancies developed in the amorphous–anatase interface of nanostructured TiO2 results in a unique n–p electronic transmission, which is mostly preferred to the mobility of electronic charge carriers. It also contributes to significant performance regarding photogeneration current, photocatalysis, and energy storage.
Hydroxide exchange membrane fuel cells offer possibility of adopting platinum-group-metal-free catalysts to negotiate sluggish oxygen reduction reaction. Unfortunately, the ultrafast hydrogen ...oxidation reaction (HOR) on platinum decreases at least two orders of magnitude by switching the electrolytes from acid to base, causing high platinum-group-metal loadings. Here we show that a nickel-molybdenum nanoalloy with tetragonal MoNi
phase can catalyze the HOR efficiently in alkaline electrolytes. The catalyst exhibits a high apparent exchange current density of 3.41 milliamperes per square centimeter and operates very stable, which is 1.4 times higher than that of state-of-the-art Pt/C catalyst. With this catalyst, we further demonstrate the capability to tolerate carbon monoxide poisoning. Marked HOR activity was also observed on similarly designed WNi
catalyst. We attribute this remarkable HOR reactivity to an alloy effect that enables optimum adsorption of hydrogen on nickel and hydroxyl on molybdenum (tungsten), which synergistically promotes the Volmer reaction.
miRNAs contribute to plant resistance against pathogens. Previously, we found that the function of miR398b in immunity in rice differs from that in Arabidopsis. However, the underlying mechanisms are ...unclear. In this study, we characterized the mutants of miR398b target genes and demonstrated that multiple superoxide dismutase genes contribute to miR398b-regulated rice immunity against the blast fungus Magnaporthe oryzae. Out of the four target genes of miR398b, mutations in Cu/Zn-Superoxidase Dismutase1 (CSD1), CSD2 and Os11g09780 (Superoxide DismutaseX, SODX) led to enhanced resistance to M. oryzae and increased hydrogen peroxide (H
O
) accumulation. By contrast, mutations in Copper Chaperone for Superoxide Dismutase (CCSD) resulted in enhanced susceptibility. Biochemical studies revealed that csd1, csd2 and sodx displayed altered expression of CSDs and other superoxide dismutase (SOD) family members, leading to increased total SOD enzyme activity that positively contributed to higher H
O
production. By contrast, the ccsd mutant showed CSD protein deletion, resulting in decreased CSD and total SOD enzyme activity. Our results demonstrate the roles of different SODs in miR398b-regulated resistance to rice blast disease, and uncover an integrative regulatory network in which miR398b boosts total SOD activity to upregulate H
O
concentration and thereby improve disease resistance.
Low‐dimensional Ruddlesden–Popper (LDRP) perovskites are a current theme in solar energy research as researchers attempt to fabricate stable photovoltaic devices from them. However, poor exciton ...dissociation and insufficiently fast charge transfer slows the charge extraction in these devices, resulting in inferior performance. 1,4‐Butanediamine (BEA)‐based low‐dimensional perovskites are designed to improve the carrier extraction efficiency in such devices. Structural characterization using single‐crystal X‐ray diffraction reveals that these layered perovskites are formed by the alternating ordering of diammonium (BEA2+) and monoammonium (MA+) cations in the interlayer space (B‐ACI) with the formula (BEA)0.5MAn
PbnI3n+1. Compared to the typical LDRP counterparts, these B‐ACI perovskites deliver a wider light absorption window and lower exciton binding energies with a more stable layered perovskite structure. Additionally, ultrafast transient absorption indicates that B‐ACI perovskites exhibit a narrow distribution of quantum well widths, leading to a barrier‐free and balanced carrier transport pathway with enhanced carrier diffusion (electron and hole) length over 350 nm. A perovskite solar cell incorporating BEA ligands achieves record efficiencies of 14.86% for (BEA)0.5MA3Pb3I10 and 17.39% for (BEA)0.5Cs0.15(FA0.83MA0.17)2.85Pb3(I0.83Br0.17)10 without hysteresis. Furthermore, the triple cations B‐ACI devices can retain over 90% of their initial power conversion efficiency when stored under ambient atmospheric conditions for 2400 h and show no significant degradation under constant illumination for over 500 h.
A new type of ACI perovskite is prepared through the alternating ordering of BEA2+ and MA+ cations in the interlayer space (B‐ACI). The high exciton extraction efficiency and a narrow distribution of quantum well widths of B‐ACI perovskite enable a device with a record efficiency of 17.39%. Furthermore, the devices show stronger resistance to humidity, heating, and light soaks than previous equivalents.
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•Hierarchical NiMn-LDH nanosheets with well-aligned and highly oriented are successfully grown on Ni foam.•Rapid, ease of operation and tunable strategy: urea hydrolysis method.•High ...specific capacitance: 1511.1Fg−1 at 2.5Ag−1, 0.67Fcm−2 at 3mAcm−2.•Excellent rate capability: 80.1% retention at 48Ag−1; good cyclic stability: capacitance retention 92.8% after 3000 cycling.
Well-aligned hierarchical NiMn-layered double hydroxide (NiMn-LDH) nanosheets are successfully grown on Ni foam by a facile one-step wet-method, wherein urea hydrolysis supplies alkali and carbonate ion. As-obtained NiMn-LDH@Ni foam presents highly oriented layered structure with ultrathin nanosheets. By fine tuning Ni/Mn mole ratio, the optimized Ni3Mn1-LDH@Ni foam displays maximum specific capacitance (1511Fg−1 at 2.5Ag−1), excellent rate capability (80.1% retention at 48Ag−1), high coulombic efficiency and long-term cycling life. In principle, this work provides a rapid and tunable strategy approach for synthesis of NiMn-LDH with largely enhanced supercapacitor behavior.
miRNAs contribute to plant resistance against pathogens. Previously, we found that the function of miR398b in immunity in rice differs from that in Arabidopsis. However, the underlying mechanisms are ...unclear.
In this study, we characterized the mutants of miR398b target genes and demonstrated that multiple superoxide dismutase genes contribute to miR398b-regulated rice immunity against the blast fungus Magnaporthe oryzae.
Out of the four target genes of miR398b, mutations in Cu/Zn-Superoxidase Dismutase1 (CSD1), CSD2 and Os11g09780 (Superoxide DismutaseX, SODX) led to enhanced resistance to M. oryzae and increased hydrogen peroxide (H₂O₂) accumulation. By contrast, mutations in Copper Chaperone for Superoxide Dismutase (CCSD) resulted in enhanced susceptibility. Biochemical studies revealed that csd1, csd2 and sodx displayed altered expression of CSDs and other superoxide dismutase (SOD) family members, leading to increased total SOD enzyme activity that positively contributed to higher H₂O₂ production. By contrast, the ccsd mutant showed CSD protein deletion, resulting in decreased CSD and total SOD enzyme activity.
Our results demonstrate the roles of different SODs in miR398b-regulated resistance to rice blast disease, and uncover an integrative regulatory network in which miR398b boosts total SOD activity to upregulate H₂O₂ concentration and thereby improve disease resistance.
Resistance to chemotherapy continues to be a critical issue in the clinical therapy of triple‐negative breast cancer (TNBC). Epithelial–mesenchymal transition (EMT) is thought to contribute to ...chemoresistance in several cancer types, including breast cancer. Identification of the key signaling pathway that regulates the EMT program and contributes to chemoresistance in TNBC will provide a novel strategy to overcome chemoresistance in this subtype of cancer. Herein, we demonstrate that Notch1 positively associates with melanoma cell adhesion molecule (MCAM), a unique EMT activator, in TNBC tissue samples both at mRNA and protein levels. High expression of Notch1 and MCAM both predicts a poor survival in basal‐like/TNBC patients, particularly in those treated with chemotherapy. The expression of Notch1 and MCAM in MDA‐MB‐231 cells gradually increases in a time‐dependent manner when exposing to low dose cisplatin. Moreover, the expressions of Notch1 and MCAM in cisplatin‐resistant MDA‐MB‐231 cells are significantly higher than wild‐type counterparts. Notch1 promotes EMT and chemoresistance, as well as invasion and proliferation of TNBC cells via direct activating MCAM promoter. Inhibition of Notch1 significantly downregulates MCAM expression, resulting in the reversion of EMT and chemoresistance to cisplatin in TNBC cells. Our study reveals the regulatory mechanism of the Notch1 pathway and MCAM in TNBC and suggesting that targeting the Notch1/MCAM axis, in conjunction with conventional chemotherapies, might be a potential avenue to enhance the therapeutic efficacy for patients with TNBC.
What's new?
Epithelial‐mesenchymal transition (EMT) likely contributes to chemoresistance in triple‐negative breast cancers (TNBC), but the underlying mechanisms remain unclear. Here, the expression of Notch1 positively associated with melanoma cell adhesion molecule (MCAM), a unique EMT activator, in TNBC tissue samples. High expression of Notch1 and MCAM predicted poor survival, particularly in patients treated with chemotherapy. Notch1 and MCAM levels were significantly higher in cisplatin‐resistant than wild‐type TNBC cells. The findings suggest that Notch1 regulates MCAM in EMT and contributes to cisplatin resistance in TNBC. Targeting the Notch1/MCAM axis might be a potential avenue to enhance therapeutic efficacy in patients with TNBC.
A considerable challenge in the conversion of carbon dioxide into useful fuels comes from the activation of CO2 to CO2.− or other intermediates, which often requires precious‐metal catalysts, high ...overpotentials, and/or electrolyte additives (e.g., ionic liquids). We report a microwave heating strategy for synthesizing a transition‐metal chalcogenide nanostructure that efficiently catalyzes CO2 electroreduction to carbon monoxide (CO). We found that the cadmium sulfide (CdS) nanoneedle arrays exhibit an unprecedented current density of 212 mA cm−2 with 95.5±4.0 % CO Faraday efficiency at −1.2 V versus a reversible hydrogen electrode (RHE; without iR correction). Experimental and computational studies show that the high‐curvature CdS nanostructured catalyst has a pronounced proximity effect which gives rise to large electric field enhancement, which can concentrate alkali‐metal cations resulting in the enhanced CO2 electroreduction efficiency.
The needle has landed: CdS nanostructures with sharp tips can generate large electric fields that lead to increased CO2 concentrations for CO2‐to‐CO conversion. The localized electric fields are significantly enhanced when two nanoneedles are in close proximity. These advantages result in CO2 electrocatalytic reduction with a 95.5±4.0 % CO Faraday efficiency.
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