Cu-Pd bimetal-decorated siloxene nanosheets for semi-hydrogenation of acetylene.

Metallic Pd has been proved highly promising when paired with Cu for industrially important acetylene semi-hydrogenation. Herein, we demonstrate that high-surface-area siloxene can feasibly enable alloying between Pd and Cu via room-temperature reduction with Si-H bonds. Unprecedentedly small Cu nanoparticles with isolated Pd were in situ loaded on siloxene, addressing the core problem of low selectivity of Pd and low activity of Cu. This devised structure outclassed the traditional impregnated SiO2 in every aspect of the catalytic performance for the semi-hydrogenation of acetylene under industry conditions, with a 91% acetylene conversion and an impressive 93% selectivity to ethylene at 200 °C, and showed long-term stability with negligible activity decay at this harsh temperature. This work provides new insights for the design of economic bimetallic loaded catalysts for balancing the activity-selectivity dilemma, demonstrating the viability of siloxene as both a synthetic reagent and a carrier material for efficient catalysis.

Picornavirus security proteins promote the release of extracellular vesicle enclosed viruses via the modulation of host kinases.

The discovery that extracellular vesicles (EVs) serve as carriers of virus particles calls for a reevaluation of the release strategies of non-enveloped viruses. Little is currently known about the molecular mechanisms that determine the release and composition of EVs produced by virus-infected cells, as well as conservation of these mechanisms among viruses. We previously described an important role for the Leader protein of the picornavirus encephalomyocarditis virus (EMCV) in the induction of virus-carrying EV subsets with distinct molecular and physical properties. EMCV L acts as a 'viral security protein' by suppressing host antiviral stress and type-I interferon (IFN) responses. Here, we tested the ability of functionally related picornavirus proteins of Theilers murine encephalitis virus (TMEV L), Saffold virus (SAFV L), and coxsackievirus B3 (CVB3 2Apro), to rescue EV and EV-enclosed virus release when introduced in Leader-deficient EMCV. We show that all viral security proteins tested were able to promote virus packaging in EVs, but that only the expression of EMCV L and CVB3 2Apro increased overall EV production. We provide evidence that one of the main antiviral pathways counteracted by this class of picornaviral proteins, i.e. the inhibition of PKR-mediated stress responses, affected EV and EV-enclosed virus release during infection. Moreover, we show that the enhanced capacity of the viral proteins EMCV L and CVB3 2Apro to promote EV-enclosed virus release is linked to their ability to simultaneously promote the activation of the stress kinase P38 MAPK. Taken together, we demonstrate that cellular stress pathways involving the kinases PKR and P38 are modulated by the activity of non-structural viral proteins to increase the release EV-enclosed viruses during picornavirus infections. These data shed new light on the molecular regulation of EV production in response to virus infection.

Lignan contents of Schisandra chinensis (Turcz.) Baill. from different origins-A new model for evaluating the content of prominent components of Chinese herbs.

BACKGROUND: As a traditional Chinese herbal medicine, Schisandra chinensis exhibits various effects such as liver protection, blood sugar regulation, blood lipid regulation, immune function regulation, antidepressant activity, etc. However, because of its intricate composition, diverse origins, and medicinal effects depending on complex compound groups, there are differences in the lignan composition of S. chinensis from different origins. Therefore, it is currently difficult to evaluate the quality of medicinal materials from plants of different origins using a single qualitative quality control index. PURPOSE: This paper aims to investigate the potential relationship between the lignan components of S. chinensis from different origins and to establish stable assessment indices for determining the lignan content of S. chinensis from multiple perspectives. METHODS: In this study, we collected S. chinensis samples of seven major origins in China, and randomly sampled 6-9 batches of each origin for a total of 60 batches. The lignan content was determined by HPLC, and its distribution law of the ratio of each lignan component of S. chinensis to Schisandrol A content was analyzed. Combining network pharmacology and differential analysis between samples, the stable and effective substances used as quality markers were determined. RESULTS: There were some correlations among the lignan contents of S. chinensis, some correlations between schisandrin A and other lignans of S. chinensis could be determined. The ratio of each component to the indicator component schisandrol A was evenly distributed and reflected the lignan content of S. chinensis to some extent. Four substances (schisandrol A, schisandrol B, schisantherin A, and schisandrin C) were determined by network pharmacology combined with the analysis results of HCA, PCA and PLS-DA to further optimize the model. They displayed a strong connection with the core target, a large contribution rate to the principal components, and a stable content in each batch of samples, suggesting that these components may be the main active substances of S. chinensis lignans. Therefore, they could be used as main indicators evaluating the advantages and disadvantages of S. chinensis by examining the consistency of component proportions. CONCLUSION: This method can intuitively evaluate the content of main lignans in S. chinensis. This quality assessment model is an exploration of the multi-component comprehensive evaluation system of S. chinensis, providing a new concept for the quality evaluation system of Chinese herbal medicines.

Heterologous expression of the Leymus chinensis metallothionein gene LcMT3 confers enhanced tolerance to salt stress in Escherichia coli, yeast, and Arabidopsis thaliana.

Salinity is poisonous to various plant physiological processes and poses an increasingly severe threat to agricultural productivity worldwide. As a tactic to mitigate this issue, the hunt for salt-tolerance genes and pathways is intensifying. The low-molecular-weight proteins known as metallothioneins (MTs) can effectively reduce salt toxicity in plants. In seeking concrete evidence of its function under salt stress conditions, a unique salt-responsive metallothionein gene, LcMT3, was isolated from the extremely salt-enduring Leymus chinensis and heterologously characterized in Escherichia coli (E. coli), yeast (Saccharomyces cerevisiae), as well as Arabidopsis thaliana. Overexpression of LcMT3 imparted resistance to salt in E. coli cells and yeast, while the development of control cells was completely inhibited. Besides, transgenic plants expressing LcMT3 exhibited significantly enhanced salinity tolerance. They had higher germination rates and longer roots than their nontransgenic counterparts during NaCl tolerance. For several physiological indices of salt tolerance, transgenic lines reduced the accumulation of malondialdehyde (MDA), relative conductivity, and reactive oxygen species (ROS) in comparison to nontransgenic Arabidopsis. They also possessed increased concentrations of proline (Pro), relative water content, chlorophyll content, coupled with three more active antioxidant enzymes (superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)). Transgenic plants also accumulated less Na+ and maintained a lower Na+/K+ ratio than control, which can be attributable to the transgene's regulatory effect on transporter proteins such as salt overly sensitive (SOS) and Na+/H+ antiporter (NHX1), as demonstrated by qPCR experiments. Collectively, LcMT3 could have a vital function in salinity resistance and be an essential candidate protein for abiotic stress.

An efficient photocatalyst based on H5PMo10V2O40/UiO-66-NH2 for direct hydroxylation of benzene to phenol by H2O2.

To realize the direct hydroxylation of benzene to phenol by hydrogen peroxide, an efficient photoactive catalyst system was prepared by the recombination of H5PMo10V2O40 and UiO-66-NH2. The heterpolyacid was uniformly distributed on the UiO-66-NH2, and the combination was stable. The composite could effectively photocatalyze the direct hydroxylation of benzene to phenol by H2O2 in the mixture solution of acetonitrile and acetic acid. The yield and selectivity were 14.08% and 98.8% under the optimum condition, respectively. The performance of the catalyst still maintained well after 5 catalytic cycles. Hence, the investigated catalyst system might be applied in the field of hydroxylation of benzene to phenol.

The association of diet carbohydrates consumption with cognitive function among US older adults modification by daily fasting duration.

Dietary carbohydrate consumption was related to cognitive function. Whereas, there was no study investigate the association of dietary carbohydrate consumption with cognitive function modification by daily fasting duration. This study aims to examine the association between dietary carbohydrate consumption and cognitive function among participants with different daily fasting duration. In this cross-sectional study, 2485 adults aged over 60 years from the nationally representative data of the National Health and Nutrition Examination Survey (NHANES, 2011-2014) were enrolled. Percentage energy from carbohydrates was present in both quartiles and continuous forms. Daily fasting duration = 24 - (timing for dinner - breakfast). Cognitive function was assessed by the Consortium to Establish a Registry for Alzheimer's Disease Word List Learning (CERAD-WL), CERAD Word List Delayed Recall (CERAD-DR), Animal Fluency (AF), and Digit Symbol Substitution (DSST) Test. Multiple logistic regression and linear regression models were developed to examine the association of dietary carbohydrates with cognitive function among participants with different daily fasting duration. Restricted cubic spline models were also applied. Compared with the lowest quartile of percentage energy from carbohydrates, the highest quartile had higher ORs of poor cognitive performance among total participants [(ORCERAD-WL 1.84 95% CI 1.25-2.71); (ORCERAD-DR 1.45 95% CI 1.10-1.91)] and participants with daily fasting duration fewer than 16 h [(ORCERAD-WL 2.14 95% CI 1.29-3.55); (ORCERAD-DR 1.51 95% CI 1.05-2.17)] but not in participants with daily fasting duration of more than 16 h. Further, the negative associations between percentage energy from carbohydrates and CERAD-WL score were still significant in addition to participants whose daily fasting duration was more than 16 h. Additionally, dose-response associations were detected between dietary carbohydrates and cognitive decline, while "U" curves were observed among participants whose daily fasting duration was more than 16 h. This study indicated that dietary carbohydrates consumption was associated with poor cognitive performance, but not in participants whose daily fasting duration was more than 16 h among US older adults. The current analysis provides evidence that a longer daily fasting duration may improve the harmful effect of dietary carbohydrates on cognitive function.

A Bifunctional Fully Integrated Wearable Tracker for Epidermal Sweat and Wound Exudate Multiple Biomarkers Monitoring.

Fully integrated wearable electronics that combine the extraordinary feature of incessant and on-body operation with the distinctive external equipment-free trait are the ultimate goal of modern wearables. Epidermal sweat and wound exudate, as two noninvasively accessible biofluids on/surrounding the skin, reflect underlying health conditions. However, the design of universal wearable sensors with the bifunctional capability to monitor both epidermal secretions is still a challenge. Here, a single bifunctional fully integrated wearable tracker for wirelessly, simultaneously, and dynamically in situ measuring multiple epidermal sweat or wound exudate biomarkers is propos. Considering the electrolytes (e.g., Na+ , K+ , and H+ ) and metabolites (e.g., uric acid (UA)) levels in sweat or wound exudate may correlate with health or wound conditions, the dynamic and skin-on tracking of the biomarkers of Na+ , K+ , pH, and UA levels in sweat under subjects' exercise and in wound exudate during subjects' wound healing are performed through the seamless integration of microfluidic, sensing, and electronic modules. Its applicability is evaluated for noninvasive hyperuricemia management in hyperuricemia/healthy subjects through a purine-rich intake test and for wound management in subjects' infected wounds through a control medical treatment.

A Flexible Microfluidic Chip-Based Universal Fully Integrated Nanoelectronic System with Point-of-Care Raw Sweat, Tears, or Saliva Glucose Monitoring for Potential Noninvasive Glucose Management.

By combining the distinctive noninvasive feature with the peculiar complete functional implementation trait, fully integrated raw noninvasive biofluid glucose biosensors offer active and remote glucose monitoring while posing minimal harm or infection risks compared to the traditional invasive manner. However, each previously reported fully integrated raw noninvasive biofluid glucose biosensor is solely focused on single-type raw noninvasive biofluid analysis. Given the diversity and complexity of subjects' physical conditions, single-type raw noninvasive biofluids are inappropriate to all crowds (e.g., sweat collection/analysis could be inapplicable for dermatopathic subjects). Here, we demonstrate the first example of a universal fully integrated nanoelectronic system with the unique capability to point-of-care and universally monitor diverse raw noninvasive biofluid (i.e., sweat, tears, and saliva) glucose by combining a flexible and disposable microfluidic enzymatic biosensor (named iezSlice) for raw biofluid pump-free sampling and measurement with a customized, handheld, and reusable wireless electronic device (named iezBar) for electrical signal transduction, conditioning, processing, and wireless transmission. We employed the specially designed high-concentration-buffer powder-loaded Kimwipes (HBP-KWs) as the microfluidic channel (microchannel) of iezSlice, guaranteeing a high-accuracy glucose analysis in various raw noninvasive biofluids. We also evaluated the potential utility of the universal fully integrated nanoelectronic system for noninvasive glucose management in healthy and diabetic subjects with the assistance of the proposed volatility-derived blood glucose concentration-free protocol. Although we focus on raw noninvasive biofluid glucose analysis in this work, the universal fully integrated nanoelectronic system may readily realize accurate monitoring of various biomolecules in raw noninvasive biofluids by introducing corresponding bioreceptors.

Folic acid oversupplementation during pregnancy disorders lipid metabolism in male offspring via regulating arginase 1-associated NOS3-AMPKα pathway.

BACKGROUND & AIMS: Folic acid supplementation is widely accepted during pregnancy, as it exerts a protective effect on neural tube defects. However, the long-term underlying effects of folic acid supplementation during pregnancy (FASDP) on offspring remain unclear. METHODS: Thirty pregnant female rats were randomly divided into normal control group, folic acid appropriate supplementation group (2.5 × FA group) and folic acid oversupplementation group (5 × FA group) and fed with corresponding folic acid concentration AIN93G diet. UPLC-Q-TOF-MS, UPLC-TQ-MS and GC-MS were performed to detect the serum metabolites profiles in adult male offspring and explore the effects of FASDP. Moreover, molecular biology technologies were used to clarify the underlying mechanism. RESULTS: We demonstrate that 2.5-folds folic acid leads to dyslipidemic-diabetic slightly in male offspring, while 5-folds folic acid aggravates the disorder and prominent hepatic lipid accumulations. Using untargeted and targeted metabolomics, total 63 differential metabolites and 12 significantly differential KEGG pathways are identified. Of note, arginine biosynthesis, arginine and proline metabolism are the two most significant pathways. Mechanistic investigations reveal that the increased levels of arginase-1 (Arg1) causes the lipid metabolism disorder by regulating nitric oxide synthase-3 (NOS3)-adenosine monophosphate activated protein kinase-α (AMPKα) pathway, resulting in lipid accumulation in hepatocytes. CONCLUSIONS: Our data suggest that maternal folic acid oversupplementation during pregnancy contributes to lipid metabolism disorder in male offspring by regulating Arg1-NOS3-AMPKα pathway.

A Bendable Biofuel Cell-Based Fully Integrated Biomedical Nanodevice for Point-of-Care Diagnosis of Scurvy.

Fully integrated nanodevices that allow the complete functional implementation without an external accessory or equipment are deemed to be one of the most ideal and ultimate goals for modern nanodevice design and construction. In this work, we demonstrate the first example of a bendable biofuel cell (BFC)-based fully integrated biomedical nanodevice with simple, palm-sized, easy-to-carry, pump-free, cost-saving, and easy-to-use features for the point-of-care (POC) diagnosis of scurvy from a single drop of untreated human serum (down to 0.2 µL) by integrating a bendable and disposable vitamin C/air microfluidic BFC (micro-BFC) (named iezCard) for self-powered vitamin C biosensing with a custom mini digital LED voltmeter (named iezBox) for signal processing and transmission, along with a ″built-in″ biocomputing BUFFER gate for intelligent diagnosis. Under the simplicity- and practicability-oriented idea, a cost-effective strategy (e.g., biomass-derived hierarchical micro-mesoporous carbon aerogels, screen-printed technique, a single piece of Kimwipes paper, LED display, and universal components) was implemented for nanodevice design rather than any top-end or pricey method (e.g., photolithography/electron-beam evaporation, peristaltic pump, wireless system, and 3D printing technique), which enormously reduces the cost of feedstock down to ∼USD 2.55 per integrated kit including a disposal iezCard (∼USD 0.08 per test) and a reusable iezBox (∼USD 2.47 for large-scale tests). These distinctive and attractive features allow such a fully integrated biomedical nanodevice to fully satisfy the basic requirements for POC diagnosis of scurvy from a single drop of raw human serum and make it particularly appropriate for resource-poor settings, where there is a lack of medical facilities, funds, and qualified personnel.

Prenatal famine exposure and estimated glomerular filtration rate across consecutive generations: association and epigenetic mediation in a population-based cohort study in Suihua China.

Prenatal malnutrition could promote renal dysfunction in adulthood, but it is unclear whether the detrimental effect could be transmitted to the next generation. We investigated whether famine exposure was associated with variation of estimated glomerular filtration rate(eGFR) in two generations and explored the mediation role of methylation alterations. The longitudinal analysis included 2909 participants from Suihua rural area. F1 and F2 generations were divided into non-famine and famine group based on their birth year and exposure status of their parents, respectively. The eGFR was calculated by using the chronic kidney disease epidemiology collaboration equation. We applied mixed-effect models to investigate the association between famine and ΔeGFR and tested blood DNA methylomes in 46 families across two generations. The mediation-analysis models were utilized to examine the mediation effect of methylation alterations on the famine-ΔeGFR association.In mixed-effect models, famine exposure was associated with declined ΔeGFR level in F1(ß:-8.32;95%CI:-11.51,-5.12) and in F2(ß:-6.11;95%CI:-11.88, -0.43). Methylation850K BeadChip data showed only 19 of 961 F1 differentially methylated sites showed concordant alterations in F2. The mediation-analysis results showed methylation alterations on AGTR1 and PRKCA might mediate the famine-ΔeGFR association. Overall, prenatal famine exposure may have long-term effects on eGFR decline across consecutive generations which might be partly mediated by methylation alterations on AGTR1 and PRKCA.

Cellular Caspase-3 Contributes to EV-A71 2Apro-Mediated Down-Regulation of IFNAR1 at the Translation Level.

Enterovirus A71 (EV-A71) is the major pathogen responsible for the severe hand, foot and mouth disease worldwide, for which few effective antiviral drugs are presently available. Interferon-α (IFN-α) has been used in antiviral therapy for decades; it has been reported that EV-A71 antagonizes the antiviral activity of IFN-α based on viral 2Apro-mediated reduction of the interferon-alpha receptor 1 (IFNAR1); however, the mechanism remains unknown. Here, we showed a significant increase in IFNAR1 protein induced by IFN-α in RD cells, whereas EV-A71 infection caused obvious down-regulation of the IFNAR1 protein and blockage of IFN-α signaling. Subsequently, we observed that EV-A71 2Apro inhibited IFNAR1 translation by cleavage of the eukaryotic initiation factor 4GI (eIF4GI), without affecting IFNAR1 mRNA levels induced by IFN-α. The inhibition of IFNAR1 translation also occurred in puromycin-induced apoptotic cells when caspase-3 cleaved eIF4GI. Importantly, we verified that 2Apro could activate cellular caspase-3, which was subsequently involved in eIF4GI cleavage mediated by 2Apro. Furthermore, inhibition of caspase-3 activation resulted in the partial restoration of IFNAR1 in cells transfected with 2A or infected with EV-A71, suggesting the pivotal role of both viral 2Apro and caspase-3 activation in the disturbance of IFN-α signaling. Collectively, we elucidate a novel mechanism by which cellular caspase-3 contributes to viral 2Apro-mediated down-regulation of IFNAR1 at the translation level during EV-A71 infection, indicating that caspase-3 inhibition could be a potential complementary strategy to improve clinical anti-EV-A71 therapy with IFN-α.

Substituted 3-benzylcoumarins 13 and 14 suppress enterovirus A71 replication by impairing viral 2Apro dependent IRES-driven translation.

Activation of the ERK signaling cascade in host cells has been demonstrated to be essential for enterovirus A71 (EV-A71) replication. Our previous study showed that MEK kinase, which specially activated downstream ERK kinase, is an important and potential target against EV-A71. Furthermore, we reported that a series of substituted 3-benzylcoumarins designed and synthesized as well as verified for inhibiting the MEK-ERK cascade were found to be effective on anti-EV-A71. In this study, we further demonstrated that two substituted 3-benzylcoumarins designated as 13 and 14 were more effective anti-MEK/ERK activity, less cytotoxicity and stronger antiviral effect represented by inhibition of viral-induced CPE, the expression of viral proteins and the replication of the viral genome, as well as the production of progeny virions, compared to those of U0126, an available MEK inhibitor, and sorafenib, a multiple-targeted kinase inhibitor in clinical use. Moreover, we explored that the likely mechanism of action of these two test compounds were to block EV-A71 2A dependent IRES-driven activity essential for successful viral replication. Hence, our results suggest that two substituted 3-benzylcoumarins 13 and 14 could be candidates as potential anti-EV-A71 agents.

Single-step construction of a picornavirus replicon RNA with precise ends.

A versatile single-step method is described for constructing a picornavirus replicon RNA with precise ends to facilitate improved understanding of viral genome function and mimic native virus replication in host cells as far as possible. The key innovation in this new approach is the use of a bridge primer to both introduce a ribozyme sequence for cis-cleavage of RNA to generate precise 5' ends of EV71 RNA and also mediate overlapping assembly of two fragments. Using an EV71 replicon as a test case, precise ends for the viral replicon were shown to be important for efficient virus replication. Thus, our work provides a novel efficient way to generating higher efficient viral replicon with precise ends and this novel method can be applied to other picornaviruses' research.