COVID-19 is associated with 5.1% mortality. Although the virological, epidemiological, clinical, and management outcome features of COVID-19 patients have been defined rapidly, the inflammatory and ...immune profiles require definition as they influence pathogenesis and clinical expression of COVID-19. Here we show lymphopenia, selective loss of CD4+ T cells, CD8+ T cells and NK cells, excessive T-cell activation and high expression of T-cell inhibitory molecules are more prominent in severe cases than in those with mild disease. CD8+ T cells in patients with severe disease express high levels of cytotoxic molecules. Histochemical studies of lung tissue from one fatality show sub-anatomical distributions of SARS-CoV-2 RNA and massive infiltration of T cells and macrophages. Thus, aberrant activation and dysregulation of CD8+ T cells occur in patients with severe COVID-19 disease, an effect that might be for pathogenesis of SARS-CoV-2 infection and indicate that immune-based targets for therapeutic interventions constitute a promising treatment for severe COVID-19 patients.
Berberine (BBR) has been confirmed to have multiple bioactivities in clinic, such as cholesterol-lowering, anti-diabetes, cardiovascular protection and anti- inflammation. However, BBR's plasma level ...is very low; it cannot explain its pharmacological effects in patients. We consider that the in vivo distribution of BBR as well as of its bioactive metabolites might provide part of the explanation for this question. In this study, liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS(n)-IT-TOF) as well as liquid chromatography that coupled with tandem mass spectrometry (LC-MS/MS) was used for the study of tissue distribution and pharmacokinetics of BBR in rats after oral administration (200 mg/kg). The results indicated that BBR was quickly distributed in the liver, kidneys, muscle, lungs, brain, heart, pancreas and fat in a descending order of its amount. The pharmacokinetic profile indicated that BBR's level in most of studied tissues was higher (or much higher) than that in plasma 4 h after administration. BBR remained relatively stable in the tissues like liver, heart, brain, muscle, pancreas etc. Organ distribution of BBR's metabolites was also investigated paralleled with that of BBR. Thalifendine (M1), berberrubine (M2) and jatrorrhizine (M4), which the metabolites with moderate bioactivity, were easily detected in organs like the liver and kidney. For instance, M1, M2 and M4 were the major metabolites in the liver, among which the percentage of M2 was up to 65.1%; the level of AUC (0-t) (area under the concentration-time curve) for BBR or the metabolites in the liver was 10-fold or 30-fold higher than that in plasma, respectively. In summary, the organ concentration of BBR (as well as its bioactive metabolites) was higher than its concentration in the blood after oral administration. It might explain BBR's pharmacological effects on human diseases in clinic.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Microvascular invasion (MVI) is a valuable predictor of survival in hepatocellular carcinoma (HCC) patients. This study developed predictive models using eXtreme Gradient Boosting (XGBoost) ...and deep learning based on CT images to predict MVI preoperatively.
Methods
In total, 405 patients were included. A total of 7302 radiomic features and 17 radiological features were extracted by a radiomics feature extraction package and radiologists, respectively. We developed a XGBoost model based on radiomics features, radiological features and clinical variables and a three-dimensional convolutional neural network (3D-CNN) to predict MVI status. Next, we compared the efficacy of the two models.
Results
Of the 405 patients, 220 (54.3%) were MVI positive, and 185 (45.7%) were MVI negative. The areas under the receiver operating characteristic curves (AUROCs) of the Radiomics-Radiological-Clinical (RRC) Model and 3D-CNN Model in the training set were 0.952 (95% confidence interval (CI) 0.923–0.973) and 0.980 (95% CI 0.959–0.993), respectively (
p
= 0.14). The AUROCs of the RRC Model and 3D-CNN Model in the validation set were 0.887 (95% CI 0.797–0.947) and 0.906 (95% CI 0.821–0.960), respectively (
p
= 0.83). Based on the MVI status predicted by the RRC and 3D-CNN Models, the mean recurrence-free survival (RFS) was significantly better in the predicted MVI-negative group than that in the predicted MVI-positive group (RRC Model: 69.95 vs. 24.80 months,
p
< 0.001; 3D-CNN Model: 64.06 vs. 31.05 months,
p
= 0.027).
Conclusion
The RRC Model and 3D-CNN models showed considerable efficacy in identifying MVI preoperatively. These machine learning models may facilitate decision-making in HCC treatment but requires further validation.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented threat to global public health. Herein, we utilized a combination of targeted and untargeted tandem mass spectrometry to ...analyze the plasma lipidome and metabolome in mild, moderate, and severe COVID-19 patients and healthy controls. A panel of 10 plasma metabolites effectively distinguished COVID-19 patients from healthy controls (AUC = 0.975). Plasma lipidome of COVID-19 resembled that of monosialodihexosyl ganglioside (GM3)-enriched exosomes, with enhanced levels of sphingomyelins (SMs) and GM3s, and reduced diacylglycerols (DAGs). Systems evaluation of metabolic dysregulation in COVID-19 was performed using multiscale embedded differential correlation network analyses. Using exosomes isolated from the same cohort, we demonstrated that exosomes of COVID-19 patients with elevating disease severity were increasingly enriched in GM3s. Our work suggests that GM3-enriched exosomes may partake in pathological processes related to COVID-19 pathogenesis and presents the largest repository on the plasma lipidome and metabolome distinct to COVID-19.
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•Quantitative lipidomic and metabolomic profiling of COVID-19 plasma•Plasma metabolite panel distinguished COVID-19 from healthy controls (AUC = 0.975)•Differential correlation analyses uncovered metabolic dysregulation in COVID-19•GM3-enriched exosomes are positively correlated with COVID-19 pathogenesis
Plasma metabolite panel effectively distinguished COVID-19 patients from healthy controls (AUC = 0.975). Plasma monosialodihexosyl gangliosides (GM3s) were negatively correlated with CD4+ T cell count in COVID-19 patients, and GM3-enriched exosomes were positively correlated with disease severity. These observations suggest that GM3-enriched exosomes may participate in pathological processes associated with COVID-19 progression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
The palladium‐catalyzed Heck reaction is a well‐known, Nobel Prize winning transformation for producing alkenes. Unlike the alkenyl and aryl variants of the Heck reaction, the alkyl‐Heck reaction is ...still underdeveloped owing to the competitive side reactions of alkyl–palladium species. Herein, we describe the development of a deaminative alkyl‐Heck‐type reaction that proceeds through C−N bond activation by visible‐light photoredox catalysis. A variety of aliphatic primary amines were found to be efficient starting materials for this new process, affording the corresponding alkene products in good yields under mild reaction conditions. Moreover, this strategy was successfully applied to deaminative carbonylative alkyl‐Heck‐type reactions.
Single‐electron process: A deaminative alkyl‐Heck‐type reaction and its carbonylative variant proceed through photocatalytic C−N bond activation. This process represents a significant complement to the classic palladium‐catalyzed Heck reaction, and features easily available starting materials, good reaction efficiency, and mild reaction conditions. Tppy=2,4,6‐triphenylpyridine.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The new and low-cost iron embedded carbon composites (Fe-BC-700) were prepared by a facile pyrolysis technology. The as-prepared material exhibited an extremely high removal efficiency of biphenol A ...in the presence of peroxymonosulfate (PMS). Besides the sulfate radicals (SO4−) from the PMS activation, the inherent persistent free radicals (PFR) in biochar also played an important role in the degradation of BPA.
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•Fe-BC-700 with Fe0, abundant functional groups and nanofibers was facilely prepared.•The high removal efficiency of BPA depends on activation and non-activation factors.•The contribution of the different factors was quantified for the first time.
Activation of peroxymonosulfate (PMS) to degrade recalcitrant organic pollutants has attracted much attention, however, this process usually needs expensive or toxic catalysts. Herein, we prepared a Fe functionalized biochar composite that contain Fe0, porous carbon with abundant functional groups and nanofibers (Fe-BC-700) to activate PMS and efficiently remove bisphenol A (BPA). The contribution of different participants in the complicated system involving Fe species, carbon composites, and radicals and nonradicals were quantitatively investigated. Under optimal conditions (0.2 g/L PMS and 0.15 g/L catalyst), 20 mg/L of BPA can be completely removed in 5 min by Fe-BC-700. The effects including the activation of PMS by Fe species to produce sulfate radicals (SO4−), the electron transfer by the nanofiber-mesoporous carbon structure, and the inherent persistent free radicals (PFR) in biochar, were demonstrated to contribute to the high performance. A series of contrast experiments showed that PMS activated by Fe contributed to about 36% of BPA degradation, while the carbon composites, especially carbon nanofibers contributed to 17%, and the other 47% was ascribed to the adsorption of carbon composites (may further undergoing degradation). Meanwhile, the degradation by SO4− accounted for about 23% (by quenching experiments), while the nonradical pathway contributed to 30%. This work suggests that the non-activation factors in PMS/porous catalyst/pollutant system cannot be neglected.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
•Chemical compositions in fruit of three mulberry species from the same area were analysed.•The black mulberry fruit has the highest levels of organic acids, vitamin C, Fe, flavonoids and ...anthocyanins.•The white mulberry fruit has the highest contents of two essential fatty acids (linoleic acid and α-linolenic acid).
Mulberries are a widely cultivated foodstuff both in China and worldwide. However, there are stark differences in the nutritional values of mulberry species. To better appreciate these differences, we here describe the chemical characteristics of white (Morus alba L.), Russian (M. alba var. tatarica L.), and black (Morus nigra L.) mulberry fruits cultivated in the Xinjiang province of China. The chemical composition analysis was performed by official methods procedures. The amino acids were analysed by the phenyl isothiocyanate method. The 2,6-dichloroindophenol titrimetric method, the aluminium chloride colorimetric method, and the pH differential method were also used in measuring the content of reduced ascorbic acid, total flavonoids, and total monomeric anthocyanins, respectively. The black mulberry fruits had the highest content of reduced ascorbic acid (48.4mg/100gfw), titratable acidity (47.1mg/gfw), and Fe (11.9mg/100gfw) of these 3 species. The Russian mulberry fruits had the highest EAA/TAA (essential amino acid/total amino acid) ratio at 44% followed by the white mulberry (42%) and the black mulberry (29%). The black mulberry fruits had found to be richest in terms of total flavonoids and total monomeric anthocyanins. These results are helpful for selecting mulberry species with abundant nutrients and phytochemicals for commercial cultivation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Sodium-ion batteries (SIBs) have demonstrated greater potential for application in large-scale energy storage devices than lithium-ion batteries (LIBs) owing to the natural abundance, low cost and ...environmental benignity of sodium resources. However, the low energy density and poor cycling life limit their commercial applications. The development of high-performance anode materials is one of the key issues for SIBs. Compared with carbonaceous materials, metallic Sn-, Sb- and SnSb alloy-based anodes have developed rapidly due to their high theoretical capacity, high electrical conductivity and safe reaction potential. The major challenge for them is the large volume change during the sodiation/desodiation process, resulting in rapid capacity decay. Numerous efforts have been devoted to solving this problem. This review summarizes recent progress on this cutting-edge topic. A range of Sn-, Sb- and SnSb-based anode materials have been introduced with respect to size control and nanostructure design. It is found that the use of ultra-small nanoparticles, elaborate interface design, heterogeneous element (N, S
etc.
) doping, multi-dimensional integration
etc.
are efficient strategies to enhance the electrochemical performance of these anode materials. The ingenious nanostructures and their synthesis methods reported in this review may provide new insights to the rational design of novel anode materials for practical application in advanced energy storage devices in the near future.
Sodium-ion batteries with metallic Sn- and Sb-based anodes have great potential for application in large-scale green energy storage devices.
Kharasch–Sosnovsky reaction is one of the most powerful methods for allylic oxidation of alkenes. However, the inherent radical mechanism and use of peroxides as both oxidants and oxygen nucleophiles ...render dearth of universal catalytic systems for highly enantioselective variants and limited scope. Herein, an alternative to the asymmetric Kharasch–Sosnovsky reaction that utilized a chiral copper catalyst and purple‐LED irradiation to enable the three‐component coupling of 1,3‐dienes, oxime esters, and carboxylic acids is reported. This protocol features mild conditions, remarkable scope and functional group tolerance as evidenced by >80 examples and utility in the late‐stage modification of pharmaceuticals and natural products. Detailed mechanistic studies provide evidences for the radical‐based reaction pathway.
An alternative to the asymmetric Kharasch–Sosnovsky reaction that utilized a chiral copper catalyst and purple‐LED irradiation to enable the three‐component coupling of 1,3‐dienes, oxime esters, and carboxylic acids is reported. This protocol features mild conditions, remarkable scope and functional group tolerance as evidenced by >80 examples and utility in the late‐stage modification of pharmaceuticals and natural products.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Understanding the effects of intermolecular interactions on metal‐to‐metal charge transfer (MMCT) is crucial to develop molecular devices by grafting MMCT‐based molecular arrays. Herein, we report a ...series of solvent‐free {Fe2Co2} compounds sharing the same cationic tetranuclear {Fe(PzTp)(CN)32Co(dpq)22}2+ (PzTp−=tetrakis(pyrazolyl)borate, dpq=dipyrido3,2‐d:2′,3′‐fquinoxaline) square units but having anions with different size, including BF4−, PF6−, OTf−, and Fe(PzTp)(CN)3−. Intermolecular π⋅⋅⋅π interactions between dpq ligands, which coordinate to cobalt ions in the {Fe(PzTp)(CN)32Co(dpq)22}2+ units, can be modulated by introducing different counterions, regulating the distortion of the CoN6 octahedron and ligand field around the cobalt ions. This change results in different MMCT behavior. Computational analyzes reveal the substantial role of the intermolecular interactions tuned by the presence of different counteranions on the MMCT behavior.
Transfer window: A series of solvent‐free {Fe(PzTp)(CN)32Co(dpq)22}⋅2 A− compounds were synthesized. The variation in π⋅⋅⋅π interactions between dpq ligands coordinated to Co centers can alter the distortion of the CoN6 octahedron and ligand field around the Co ions, thereby allowing control of the thermally and photo‐induced metal‐to‐metal charge transfer (MMCT).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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