Background: A growing number of cohort studies revealed an inverse association between cheese intake and cardiovascular diseases, yet the causal relationship is unclear. Objective: To assess the ...causal relationship between cheese intake, and cardiovascular diseases and cardiovascular biomarkers. Methods: A two-sample Mendelian randomization (MR) analysis based on publicly available genome-wide association studies was employed to infer the causal relationship. The effect estimates were calculated using the random-effects inverse-variance-weighted method. Results: Cheese intake per standard deviation increase causally reduced the risks of type 2 diabetes (odds ratio (OR) = 0.46; 95% confidence interval (CI), 0.34–0.63; p = 1.02 × 10−6), heart failure (OR = 0.62; 95% CI, 0.49–0.79; p = 0.0001), coronary heart disease (OR = 0.65; 95% CI, 0.53–0.79; p = 2.01 × 10−5), hypertension (OR = 0.67; 95% CI, 0.53–0.84; p = 0.001), and ischemic stroke (OR = 0.76; 95% CI, 0.63–0.91; p = 0.003). Suggestive evidence of an inverse association between cheese intake and peripheral artery disease was also observed. No associations were observed for atrial fibrillation, cardiac death, pulmonary embolism, or transient ischemic attack. The better prognosis associated with cheese intake may be explained by lower body mass index (BMI; effect estimate = −0.58; 95% CI, from −0.88 to −0.27; p = 0.0002), waist circumference (effect estimate = −0.49; 95% CI, from −0.76 to −0.23; p = 0.0003), triglycerides (effect estimate = −0.33; 95% CI, from −0.50 to −0.17; p = 4.91 × 10−5), and fasting glucose (effect estimate = −0.20; 95% CI, from −0.33 to −0.07; p = 0.0003). There was suggestive evidence of a positive association between cheese intake and high-density lipoprotein. No influences were observed for blood pressure or inflammation biomarkers. Conclusions: This two-sample MR analysis found causally inverse associations between cheese intake and type 2 diabetes, heart failure, coronary heart disease, hypertension, and ischemic stroke.
The practical application of the Zn‐metal anode for aqueous batteries is greatly restricted by catastrophic dendrite growth, intricate hydrogen evolution, and parasitic surface passivation. Herein, a ...polyanionic hydrogel film is introduced as a protective layer on the Zn anode with the assistance of a silane coupling agent (denoted as Zn–SHn). The hydrogel framework with zincophilic –SO3− functional groups uniformizes the zinc ions flux and transport. Furthermore, such a hydrogel layer chemically bonded on the Zn surface possesses an anti‐catalysis effect, which effectively suppresses both the hydrogen evolution reaction and formation of Zn dendrites. As a result, stable and reversible Zn stripping/plating at various currents and capacities is achieved. A full cell by pairing the Zn–SHn anode with a NaV3O8·1.5 H2O cathode shows a capacity of around 176 mAh g−1 with a retention around 67% over 4000 cycles at 10 A g−1. This polyanionic hydrogel film protection strategy paves a new way for future Zn‐anode design and safe aqueous batteries construction.
A unique polyanionic hydrogel is employed as an artificial protective layer for reversible Zn‐metal anodes. The polyanions in the hydrogel framework facilitate a homogeneous zinc‐ion flux, and the Zn–O bonding strengthens the interface and suppresses surface corrosion and irregular Zn dendrites growth. This strategy could apply also to other aqueous metal batteries.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L ...(CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.
The large‐scale deployment of aqueous Zn‐ion batteries is hindered by Zn anode instability including surface corrosion, hydrogen gas evolution, and irregular Zn deposition. To tackle these ...challenges, a polyhydroxylated organic molecular additive, trehalose, is incorporated to refine the solvation structure and promote planar Zn deposition. Within solvation structure regions involving trehalose, the hydroxy groups participate in the reconstruction of hydrogen bond networks, which increases the overpotential for water decomposition reaction. Moreover, at the Zn metal–molecule interface, the chemisorption of trehalose onto the surface of the zinc anode enhances corrosion resistance and facilitates the deposition of zinc in a planar manner. The optimized electrolyte significantly improves Zn striping/plating reversibility and maintains stable potentials over 1600 h at 5 mA cm−2 with a cutoff capacity of 1 mA h cm−2 in symmetric cells. When combined with the MnO2 cathode, the assembled coin cell retains ≈89% of its capacity after 1000 cycles. This organic molecule additive, emphasizing the role of polyhydroxylated organic molecules in fine‐tuning solvation structures and anode/electrolyte interfaces, holds promise for enhancing various aqueous metal batteries.
Trehalose, a widely used moisturizer, preservative, and stabilizer in the food industry, is proven to be an effective electrolyte additive to the sulfite electrolyte for aqueous zinc ion battery. It optimizes the solvation structure by decreasing free water molecules and forming hydrogen bond networks. Trehalose also stabilizes the metal‐electrolyte interface through chemisorption, benefiting planar zinc deposition and suppressing dendrite growth.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Lack of social support is a known predictor of the prognosis after acute myocardial infarction (AMI). Although as a common factor associated with social support, there are limited data on long-term ...prognostic impact of living status in young and middle-aged patients with AMI.
We analyzed data from the China Acute Myocardial Infarction (CAMI) Registry, consecutive AMI young and middle-aged patients admitted at 108 hospitals in China between January 2013 and September 2014 were included. Eligible patients were assigned to living alone and not living alone groups based on their living status. The primary endpoint was 2-year all-cause mortality. The secondary endpoints included in-hospital mortality and 2-year major adverse cardiac and cerebrovascular events (MACCEs; a composite of all-cause mortality, MI, or stroke). Multilevel logistic and multilevel Cox regression models were used to evaluate the effect of living status on short-term and long-term outcomes.
A total of 8307 consecutive AMI young and middle-aged patients were included, 192 (2.3%) patients were living alone. Of the analyzed patients, living alone was associated with 2-year all-cause mortality and MACCEs among all analyzed patients after multivariate adjustment (adjusted hazard ratio HR = 2.171 1.210-3.895, P = 0.009; adjusted HR = 2.169 1.395-3.370, P = 0.001), but not with poorer in-hospital mortality.
The analysis suggested that living alone was associated with both 2-year all-cause mortality and MACCEs in AMI young and middle-aged patients but did not show an extra effect on the in-hospital mortality after covariate adjustment.
Trial registration number: NCT01874691; Registered 31 October 2012.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
While many approaches to predict aqueous pKa values exist, the fast and accurate prediction of non‐aqueous pKa values is still challenging. Based on the iBonD experimental pKa database (39 solvents), ...a holistic pKa prediction model was established using machine learning. Structural and physical‐organic‐parameter‐based descriptors (SPOC) were introduced to represent the electronic and structural features of the molecules. The models trained with a neural network or the XGBoost algorithm showed the best prediction performance with a low MAE value of 0.87 pKa units. The approach allows a comprehensive mapping of all possible pKa correlations between different solvents and it was validated by predicting the aqueous pKa and micro‐pKa of pharmaceutical molecules and pKa values of organocatalysts in DMSO and MeCN with high accuracy. An online prediction platform was constructed based on the current model, which can provide pKa prediction for different types of X−H acidity in the most commonly used solvents.
Deep learning enables the holistic pKa prediction of various types of X−H acidities in 39 types of solvents. The accuracy of the predictions is demonstrated by a mean absolute error of 0.87 pKa units.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The progress of aqueous zinc batteries (AZBs) is limited by the poor cycling life due to Zn anode instability, including dendrite growth, surface corrosion, and passivation. Inspired by the ...anti‐corrosion strategy of steel industry, a compounding corrosion inhibitor (CCI) is employed as the electrolyte additive for Zn metal anode protection. It is shown that CCI can spontaneously generate a uniform and ≈30 nm thick solid‐electrolyte interphase (SEI) layer on Zn anode with a strong adhesion via ZnO bonding. This SEI layer efficiently prohibits water corrosion and guides homogeneous Zn deposition without obvious dendrite formation. This enables reversible Zn deposition and dissolution for over 1100 h under the condition of 1 mA cm−2 and 1 mAh cm−2 in symmetric cells. The Zn‐MnO2 full cells with CCI‐modified electrolyte deliver an ultralow capacity decay rate (0.013% per cycle) at 0.5 A g−1 over 1000 cycles. Such an innovative strategy paves a low‐cost way to achieve AZBs with long lifespan.
Inspired by the industrial steel pipeline protection, a compounding corrosion inhibitor (CCI) has been employed as the electrolyte additive for aqueous Zn metal anodes. The spontaneous deposition of CCI on Zn surface constructs a uniform organic layer which provides Zn2+ conduction and H2O repulsion. A strong adhesion between Zn and CCI leads to a dendrites‐free Zn electrodeposition and long cycling life of the aqueous Zn‐ion battery.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Fluorine-containing moieties show significant effects in improving the properties of functional molecules. Consequently, efficient methods for installing them into target compounds are in great ...demand, especially those enabled by metal-free catalysis. Here we show a diazaphospholene-catalyzed hydrodefluorination of trifluoromethylalkenes to chemoselectively construct gem-difluoroalkenes and terminal monofluoroalkenes by simple adjustment of the reactant stoichiometry. This metal-free hydrodefluorination features mild reaction conditions, good group compatibility, and almost quantitative yields for both product types. Stoichiometric experiments indicated a stepwise mechanism: hydridic addition to fluoroalkenes and subsequent β-F elimination from hydrophosphination intermediates. Density functional theory calculations disclosed the origin of chemoselectivity, regioselectivity and stereoselectivity, suggesting an electron-donating effect of the alkene-terminal fluorine atom.
Applying biodegradable chelating agents to assist in phytoremediation is a promising method to increase the remove efficiency of metal pollutants from contaminated soils. The effects of biodegradable ...chelating agents on improving the phytoremediation capacity in uranium (U) and cadmium (Cd) contaminated soil was investigated using sunflowers, which were grown in pots containing soil with U and Cd added at 15 mg/kg. After 2 months of growth, citric acid (CA), oxalic acid (OA) and ethylenediamine disuccinate (EDDS) at various concentrations (0, 2.5, 5.0 and 7.5 mmol/kg) were applied. The results showed that plant biomass decreased by 12.12% for shoot and 15.74% for root under U and Cd combined stress. Meanwhile, chelating agent treatments, especially with EDDS, enhanced U and Cd stress in plants by decreasing biomass, inhibiting photosynthesis, and increasing malondialdehyde and H2O2 levels. The U uptake of plants after CA addition was significantly greater than that after OA and EDDS addition. Nevertheless, EDDS addition has better effects on Cd uptake than CA and OA addition. U and Cd remove efficiencies reached the maximum following the application of 5.0 mmol/kg CA and 5.0 mmol/kg EDDS, which were 177.48% and 181.51% higher than that of the control, respectively. Furthermore, the bioavailable U content in soils treated with CA were higher than that in soils treated with EDDS, whereas bioavailable Cd content significantly increased due to EDDS addition. These results suggest that biodegradable chelating agents have significant effects on improving the U and Cd phytoremediation potential of sunflowers.
•EDDS enhanced the adverse effects of U and Cd in sunflower.•CA and EDDS effectively increased the uptake and translocation of U and Cd.•CA significantly promoted U bioavailability in soil-plant system. EDDS has better effects on mobilizing Cd in the soil.•CA and EDDS improved the phytoremediation efficiency of sunflower.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Although clinical studies have shown promise for targeting programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small cell lung cancer (NSCLC), the factors that predict which ...subtype patients will be responsive to checkpoint blockade are not fully understood.
We performed an integrated analysis on the multiple-dimensional data types including genomic, transcriptomic, proteomic, and clinical data from cohorts of lung adenocarcinoma public (discovery set) and internal (validation set) database and immunotherapeutic patients. Gene set enrichment analysis (GSEA) was used to determine potentially relevant gene expression signatures between specific subgroups.
We observed that
mutation significantly increased expression of immune checkpoints and activated T-effector and interferon-γ signature. More importantly, the
comutated subgroup manifested exclusive increased expression of PD-L1 and a highest proportion of
Meanwhile,
or
-mutated tumors showed prominently increased mutation burden and specifically enriched in the transversion-high (TH) cohort. Further analysis focused on the potential molecular mechanism revealed that
or
mutation altered a group of genes involved in cell-cycle regulating, DNA replication and damage repair. Finally, immunotherapeutic analysis from public clinical trial and prospective observation in our center were further confirmed that
or
mutation patients, especially those with co-occurring
mutations, showed remarkable clinical benefit to PD-1 inhibitors.
This work provides evidence that
and
mutation in lung adenocarcinoma may be served as a pair of potential predictive factors in guiding anti-PD-1/PD-L1 immunotherapy.
.
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