Bioorthogonal chemical reactions are a thriving area of chemical research in recent years as an unprecedented technique to dissect native biological processes through chemistry-enabled strategies. ...However, current concepts of bioorthogonal chemistry have largely centered on 'bond formation' reactions between two mutually reactive bioorthogonal handles. Recently, in a reverse strategy, a collection of 'bond cleavage' reactions has emerged with excellent biocompatibility. These reactions have expanded our bioorthogonal chemistry repertoire, enabling an array of exciting new biological applications that range from the chemically controlled spatial and temporal activation of intracellular proteins and small-molecule drugs to the direct manipulation of intact cells under physiological conditions. Here we highlight the development and applications of these bioorthogonal cleavage reactions. Furthermore, we lay out challenges and propose future directions along this appealing avenue of research.
Cancer patients are regarded as a highly vulnerable group in the current Coronavirus Disease 2019 (COVID-19) pandemic. To date, the clinical characteristics of COVID-19-infected cancer patients ...remain largely unknown.
In this retrospective cohort study, we included cancer patients with laboratory-confirmed COVID-19 from three designated hospitals in Wuhan, China. Clinical data were collected from medical records from 13 January 2020 to 26 February 2020. Univariate and multivariate analyses were carried out to assess the risk factors associated with severe events defined as a condition requiring admission to an intensive care unit, the use of mechanical ventilation, or death.
A total of 28 COVID-19-infected cancer patients were included; 17 (60.7%) patients were male. Median (interquartile range) age was 65.0 (56.0–70.0) years. Lung cancer was the most frequent cancer type (n = 7; 25.0%). Eight (28.6%) patients were suspected to have hospital-associated transmission. The following clinical features were shown in our cohort: fever (n = 23, 82.1%), dry cough (n = 22, 81%), and dyspnoea (n = 14, 50.0%), along with lymphopaenia (n = 23, 82.1%), high level of high-sensitivity C-reactive protein (n = 23, 82.1%), anaemia (n = 21, 75.0%), and hypoproteinaemia (n = 25, 89.3%). The common chest computed tomography (CT) findings were ground-glass opacity (n = 21, 75.0%) and patchy consolidation (n = 13, 46.3%). A total of 15 (53.6%) patients had severe events and the mortality rate was 28.6%. If the last antitumour treatment was within 14 days, it significantly increased the risk of developing severe events hazard ratio (HR) = 4.079, 95% confidence interval (CI) 1.086–15.322, P = 0.037. Furthermore, patchy consolidation on CT on admission was associated with a higher risk of developing severe events (HR = 5.438, 95% CI 1.498–19.748, P = 0.010).
Cancer patients show deteriorating conditions and poor outcomes from the COVID-19 infection. It is recommended that cancer patients receiving antitumour treatments should have vigorous screening for COVID-19 infection and should avoid treatments causing immunosuppression or have their dosages decreased in case of COVID-19 coinfection.
•We retrospectively studied clinical features of 28 severe Coronavirus Disease 2019 (COVID-19)-infected cancer patients from three hospitals in Wuhan, China.•We analysed risk factors associated with occurrence of admission to an intensive care unit, usage of mechanical ventilation, or death.•COVID-19-infected cancer patients presented poor outcomes with high occurrence of clinically severe event and mortality.•Antitumour treatment within 14 days of COVID-19 diagnosis increased the risk of developing severe events.
Alkaline direct ethylene glycol fuel cells are one of the most promising power sources for portable, mobile and stationary power applications, primarily because this type of fuel cell runs on a ...sustainable fuel and the key materials that constitute the fuel cell are relatively inexpensive. This review article summarizes and discusses the past investigations on the development of alkaline direct ethylene glycol fuel cells, including the physical and chemical processes through the fuel cell structure, the electrocatalytic oxidation and electrocatalysts of ethylene glycol, the singe-cell performance, and innovative system designs.
This article reviews the past research on the development of alkaline direct ethylene glycol fuel cells, including the working principle, mechanisms and materials of the ethylene glycol oxidation, singe-cell performance, as well as innovative system designs. Display omitted
•This article reviews past research on alkaline direct ethylene glycol fuel cells.•Particular attention is paid to electrocatalytic oxidation of ethylene glycol.•Single-cell performance is summarized and discussed.•Innovative system designs and future perspectives are highlighted.
Type 2 diabetes is caused by insulin resistance coupled with an inability to produce enough insulin to control blood glucose, and thiazolidinediones (TZDs) are the only current antidiabetic agents ...that function primarily by increasing insulin sensitivity. However, despite clear benefits in glycemic control, this class of drugs has recently fallen into disuse due to concerns over side effects and adverse events. Here we review the clinical data and attempt to balance the benefits and risks of TZD therapy. We also examine potential mechanisms of action for the beneficial and harmful effects of TZDs, mainly via agonism of the nuclear receptor PPARγ. Based on critical appraisal of both preclinical and clinical studies, we discuss the prospect of harnessing the insulin sensitizing effects of PPARγ for more effective, safe, and potentially personalized treatments of type 2 diabetes.
Hydrostatic pressure is an important environmental variable that plays an essential role in biological adaptation for many extremophilic organisms (for example, piezophiles). Increase in hydrostatic ...pressure, much like increase in temperature, perturbs the thermodynamic equilibrium between native and unfolded states of proteins. Experimentally, it has been observed that increase in hydrostatic pressure can both increase and decrease protein stability. These observations suggest that volume changes upon protein unfolding can be both positive and negative. The molecular details of this difference in sign of volume changes have been puzzling the field for the past 50 years. Here we present a comprehensive thermodynamic model that provides in-depth analysis of the contribution of various molecular determinants to the volume changes upon protein unfolding. Comparison with experimental data shows that the model allows quantitative predictions of volume changes upon protein unfolding, thus paving the way to proteome-wide computational comparison of proteins from different extremophilic organisms.
Histones and their post-translational modifications have key roles in chromatin remodeling and gene transcription. Besides intranuclear functions, histones act as damage-associated molecular pattern ...molecules when they are released into the extracellular space. Administration of exogenous histones to animals leads to systemic inflammatory and toxic responses through activating Toll-like receptors and inflammasome pathways. Anti-histone treatment (e.g., neutralizing antibodies, activated protein C, recombinant thrombomodulin, and heparin) protect mice against lethal endotoxemia, sepsis, ischemia/reperfusion injury, trauma, pancreatitis, peritonitis, stroke, coagulation, and thrombosis. In addition, elevated serum histone and nucleosome levels have been implicated in multiple pathophysiological processes and progression of diseases including autoimmune diseases, inflammatory diseases, and cancer. Therefore, extracellular histones could serve as biomarkers and novel therapeutic targets in human diseases.
Considerable attention has been focused on improving the biocompatibility of Cu(
i
)-catalyzed azide-alkyne cycloaddition (CuAAC), a hallmark of bioorthogonal reaction, in living cells. Besides ...creating copper-free versions of click chemistry such as strain promoted azide-alkyne cycloaddition (SPAAC), a central effort has also been made to develop various Cu(
i
) ligands that can prevent the cytotoxicity of Cu(
i
) ions while accelerating the CuAAC reaction. Meanwhile, additional transition metals such as palladium have been explored as alternative sources to promote a bioorthogonal conjugation reaction on cell surface, as well as within an intracellular environment. Furthermore, transition metal mediated chemical conversions beyond conjugation have also been utilized to manipulate protein activity within living systems. We highlight these emerging examples that significantly enriched our protein chemistry toolkit, which will likely expand our view on the definition and applications of bioorthogonal chemistry.
Transition metal-mediated chemical conversions have rapidly expanded our intracellular protein chemistry toolbox, which would broaden our view on bioorthogonal chemistry.
Direct formate fuel cells (DFFC), which convert the chemical energy stored in formate directly into electricity, are recently attracting more attention, primarily because of the use of the ...carbon-neutral fuel and the low-cost electrocatalytic and membrane materials. As an emerging energy technology, the DFFC has made a rapid progress in recent years (currently, the state-of-the-art power density is 591 mW cm−2 at 60 °C). This article provides a review of past research on the development of this type of fuel cell, including the working principle, mechanisms and materials of the electrocatalytic oxidation of formate, singe-cell designs and performance, as well as innovative system designs. In addition, future perspectives with regard to the development of this fuel cell system are also highlighted.
This article provides a review of past research on the development of this type of fuel cell, including the working principle, mechanisms and materials of the electrocatalytic oxidation of formate, singe-cell designs and performance, as well as innovative system designs. Display omitted
•This article reviews past research on the development of direct formate fuel cells.•Particular attention is paid to mechanisms and materials of formate oxidation.•Singe-cell designs and their performance are summarized and discussed.•Innovative system designs and future perspectives are highlighted.
Summary
Long‐term prognosis varies widely among patients with hepatitis B virus (HBV)‐related liver cirrhosis. Our study aimed to investigate the applicability of albumin‐bilirubin (ALBI), Child‐Pugh ...and model for end‐stage liver disease (MELD) scores to the long‐term prognosis prediction of HBV‐related cirrhosis. Patients diagnosed with HBV‐associated cirrhosis from the First Affiliated Hospital of Wenzhou Medical University between January 2010 and December 2015 were enrolled in this study. The patients were followed up every 3 months. The prognostic performance of ALBI in long‐term outcome prediction for HBV‐related cirrhosis was compared with Child‐Pugh and MELD scores using time‐dependent receiver operating characteristic curve (tdROC) and decision curve analysis. A total of 806 patients were included in our study with 275 (34.1%) deceased during the follow‐up. Multivariate Cox regression analysis showed that ALBI grade was an independent predictor associated with mortality. The tdROC analysis showed that ALBI score (0.787, 0.830 and 0.833) was superior to MELD (0.693, P=.003; 0.717, P<.001; 0.744, P<.001) and Child‐Pugh score (0.641, P<.001; 0.649, P<.001; 0.657, P<.001) for predicting 1‐year, 2‐year and 3‐year mortality. Additionally, decision curves also got the similar results. In addition, patients with lower ALBI score had a longer life expectancy, even among patients within the same Child‐Pugh class. Thus, ALBI score was effective in predicting the long‐term prognosis for patients with HBV‐related cirrhosis and more accurate than Child‐Pugh and MELD scores.
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