The Regulatory Mechanism of Smilax China L. Saponins against Nonalcoholic Fatty Liver Is Revealed by Metabolomics and Transcriptomics.

This study was to investigate the effects of Smilax China L. saponins (SCS) on non-alcoholic fatty liver disease (NAFLD). Rats were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, followed by SCS treatment for 8 weeks. The effect of SCS on liver injury was observed by H&E staining and the regulative mechanism of SCS on lipid formation was exposed by detecting Oil red O, insulin resistance (IR), and fatty acids synthesis (FAS). Furthermore, transcriptomics and metabolomics were performed to analyze the potential targets. The experimental results indicated that SCS exerted a positive curative effect in alleviating HFD-induced overweight, hepatic injury, steatosis, and lipid formation and accumulation in rats, and the preliminary mechanism studies showed that SCS could alleviate IR, inhibit FAS expression, and reduce Acetyl-CoA levels. Besides, the integrative analysis of transcriptomics and metabolomics exposed the targets of SCS to regulate lipid production likely being the sphingolipid metabolism and glycerophospholipid metabolism pathways. This study demonstrates that SCS significantly ameliorates lipid metabolic disturbance in rats with NAFLD by relieving insulin resistance, inhibiting the FAS enzymes, and regulating the sphingolipid and glycerophospholipid metabolism pathways.

Effects of an early intensive blood pressure-lowering strategy using remifentanil and dexmedetomidine in patients with spontaneous intracerebral hemorrhage: a multicenter, prospective, superiority, randomized controlled trial.

BACKGROUND: Although it has been established that elevated blood pressure and its variability worsen outcomes in spontaneous intracerebral hemorrhage, antihypertensives use during the acute phase still lacks robust evidence. A blood pressure-lowering regimen using remifentanil and dexmedetomidine might be a reasonable therapeutic option given their analgesic and anti-sympathetic effects. The objective of this superiority trial was to validate the efficacy and safety of this blood pressure-lowering strategy that uses remifentanil and dexmedetomidine in patients with acute intracerebral hemorrhage. METHODS: In this multicenter, prospective, single-blinded, superiority randomized controlled trial, patients with intracerebral hemorrhage and systolic blood pressure (SBP) ≥150 mmHg were randomly allocated to the intervention group (a preset protocol with a standard guideline management using remifentanil and dexmedetomidine) or the control group (standard guideline-based management) to receive blood pressure-lowering treatment. The primary outcome was the SBP control rate (<140 mmHg) at 1 h posttreatment initiation. Secondary outcomes included blood pressure variability, neurologic function and clinical outcomes. RESULTS: A total of 338 patients were allocated to the intervention (n = 167) or control group (n = 171). The SBP control rate at 1 h posttreatment initiation in the intervention group was higher than that in controls (101/161, 62.7% vs. 66/166, 39.8%, difference 23.2%, 95% CI, 12.4 to 34.1%, P < 0.001). Analysis of secondary outcomes indicated that patients in the intervention group could effectively reduce agitation while achieving lighter sedation, but no improvement in clinical outcomes was observed. Regarding safety, the incidence of bradycardia and respiratory depression was higher in the intervention group. CONCLUSIONS: Among intracerebral hemorrhage patients with a SBP ≥ 150 mmHg, a preset protocol using a remifentanil and dexmedetomidine-based standard guideline management significantly increased the SBP control rate at 1 h posttreatment compared with the standard guideline-based management. (ClinicalTrials.gov number: NCT03207100, Registration date: June 30, 2017).

Synthesis of nitrogen mustard-based fluorophores for cell imaging and cytotoxicity studies.

Nitrogen mustards are important alkylating anticancer drugs used for neoplasms treatment. However, little research about the integration of luminophore into nitrogen mustard-based compounds for both imaging and therapeutic application was reported. In this study, we report a series of novel nitrogen mustard-containing 1-furyl-2-en-1-one and 1-thienyl-2-en-1-one derivatives as intramolecular charge transfer-based luminophore for research in both imaging subcellular localization and antiproliferation toward lung cancer cells. The target products were prepared by Knoevenagel condensation and characterized by nuclear magnetic resonance and high-resolution mass spectrometer. The absorption and fluorescence studies were carried out by ultraviolet-visible and fluorescence spectrophotometers, respectively. Cell morphology was observed under an inverted microscope. Cytotoxicity test was detected by MTT assay. Cellular localization was observed by a confocal laser scanning microscope. Colony formation ability was carried out by colony formation assay. Cell migration ability was detected by transwell migration assay. Differences between the two groups were analyzed by two-tailed Student's t-test. The difference with P < 0.05 (*) was considered statistically significant. The compounds were synthesized in high yield. The λmax and Stokes shift of these compounds reach up to 567 and 150 nm, respectively. These compounds exhibited good antiproliferative activity against lung cancer cells, with compound 3h exhibiting the best IC50 of 13.1 ± 2.7 µM. Furthermore, the selected compound 3h is located preferentially in lysosomes and a small amount in nuclei, effectively inhibiting cell colony formation and migration abilities toward A549 cells. These findings suggested that nitrogen mustard-based fluorophores might be a potential effective chemotherapeutic agent in lung cancer therapy.

Curdione ameliorates sepsis-induced lung injury by inhibiting platelet-mediated neutrophil extracellular trap formation.

Sepsis-associated acute lung injury remains to be a major cause of morbidity and mortality worldwide, and there is a lack of effective therapeutic drugs. Curdione, an activeingredient of Curcuma zedoary, a traditional Chinese medicine (TCM), possesses a variety of pharmacological actions, such as anti-inflammatory, antioxidant and inhibition of platelet aggregation. However, whether curdione protects against sepsis-induced lung injury is still undetermined. In this study, we investigated the effects of curdione on sepsis-induced lung injury. Cecal ligation and puncture (CLP) surgery was performed in mice to establish a model of sepsis. Twenty-four hours after CLP, bronchoalveolar lavage fluid (BALF) and lung tissue samples were harvested for investigation. The protective effects of curdione on acute lung injury and potential mechanisms were explored by detecting pathological sections, exudative proteins, oxidative responses, inflammatory factors, platelet activation, neutrophil infiltration, and neutrophil extracellular trap (NET) formation in the lung and were further verified in vitro. We showed that treatment with curdione clearly relieved histopathological changes, reduced inflammatory cytokine elevation and total protein concentrations in BALF, and decreased oxidative stress responses in lung tissues. In addition, curdione inhibited platelet activation, further blocking the interaction between platelets and neutrophils. Finally, neutrophil infiltration and NET formation was also reduced in mice treated with curdione. In conclusion, curdione alleviates sepsis-induced lung injury by inhibiting platelet-mediated neutrophil recruitment, infiltration, and NET formation as well as its anti-inflammatory and antioxidant properties. Curdione has great therapeutic potential in sepsis.

Integrative Analysis of Transcriptome and Metabolome to Illuminate the Protective Effects of Didymin against Acute Hepatic Injury.

Based on the multiomics analysis, this study is aimed at investigating the underlying mechanism of didymin against acute liver injury (ALI). The mice were administrated with didymin for 2 weeks, followed by injection with lipopolysaccharide (LPS) plus D-galactosamine (D-Gal) to induce ALI. The pathological examination revealed that didymin significantly ameliorated LPS/D-Gal-induced hepatic damage. Also, it markedly reduced proinflammatory cytokines release by inhibiting the TLR4/NF-κB pathway activation, alleviating inflammatory injury. A transcriptome analysis proved 2680 differently expressed genes (DEGs) between the model and didymin groups and suggested that the PI3K/Akt and metabolic pathways might be the most relevant targets. Meanwhile, the metabolome analysis revealed 67 differently expressed metabolites (DEMs) between the didymin and model groups that were mainly clustered into the glycerophospholipid metabolism, which was consistent with the transcriptome study. Importantly, a comprehensive analysis of both the omics indicated a strong correlation between the DEGs and DEMs, and an in-depth study demonstrated that didymin alleviated metabolic disorder and hepatocyte injury likely by inhibiting the glycerophospholipid metabolism pathway through the regulation of PLA2G4B, LPCAT3, and CEPT1 expression. In conclusion, this study demonstrates that didymin can ameliorate LPS/D-Gal-induced ALI by inhibiting the glycerophospholipid metabolism and PI3K/Akt and TLR4/NF-κB pathways.

Effects of rumen-protected methionine supplementation on production performance, apparent digestibility, blood parameters, and ruminal fermentation of lactating Holstein dairy cows.

This study aimed to evaluate the effects of reducing dietary CP and supplementing rumen protected-methionine (RPM) on production performance, blood parameters, digestibility of nutrients or ruminal fermentation in lactating Holstein dairy cows. A total of 96 lactating cows were randomly assigned to 1 of 2 treatments: a diet containing 17.3% CP without RPM (control group; CON; n = 49) or a diet containing 16.4% CP and supplemented with 15.0 g/d of RPM (treatment group; RPM; n = 47). No effect was observed in the RPM group on milk yield, milk composition and digestibility of nutrients. The results of blood parameters showed that cows in the RPM group exhibited lower blood urea nitrogen concentration than in CON group. Rumen microbial crude protein (MCP) was higher in the RPM group compared to the CON group. Ruminal volatile fatty acid (VFA) concentrations were not different between treatments except for butyrate and isovalerate, which were higher in the RPM group than the CON group 2 h after feeding. In conclusion, reducing dietary CP with RPM supplementation did not limit milk yield, milk composition or digestibility of nutrients, but could improve nitrogen utilization, synthesis of MCP and partially increase VFA production 2 h after feeding cows.

Temporal Coherence-Based Distributed Ray Tracing of Massive Scenes.

Distributed ray tracing algorithms are widely used when rendering massive scenes, where data utilization and load balancing are the keys to improving performance. One essential observation is that rays are temporally coherent, which indicates that temporal information can be used to improve computational efficiency. In this paper, we use temporal coherence to optimize the performance of distributed ray tracing. First, we propose a temporal coherence-based scheduling algorithm to guide the task/data assignment and scheduling. Then, we propose a virtual portal structure to predict the radiance of rays based on the previous frame, and send the rays with low radiance to a precomputed simplified model for further tracing, which can dramatically reduce the traversal complexity and the overhead of network data transmission. The approach was validated on scenes of sizes up to 355 GB. Our algorithm can achieve a speedup of up to 81% compared to previous algorithms, with a very small mean squared error.

Didymin Ameliorates Liver Fibrosis by Alleviating Endoplasmic Reticulum Stress and Glycerophospholipid Metabolism: Based on Transcriptomics and Metabolomics.

Introduction: Origanum vulgare L. is a traditional Chinese herb, having a strong hepatoprotective effect. In our previous experiments, we have isolated an ingredient from this herb and identified it as didymin. This study aimed to investigate the effects and underlying mechanisms of didymin on liver injury and fibrosis, elucidating whether it was the pharmacodynamic material basis of Origanum vulgare L. Methods: Mice were injected with CCl4 for 10 weeks to induce liver fibrosis, followed by didymin treatment for 6 weeks. Then, biochemical analysis and histopathological examinations were conducted to evaluate the therapeutic effects of didymin in alleviating fibrosis. Next, the possible mechanisms of didymin were predicted by transcriptomics and then verified by the multiple relevant examinations. Results: The pharmacodynamic experiments indicated that didymin significantly attenuated CCl4-induced hepatic injury and fibrogenesis, as evidenced by the ameliorative pathological tissue, low transaminase activity, and decreased collagen accumulation. Interestingly, the transcriptome analysis predicted that the potential targets were likely to be endoplasmic reticulum stress (ERS), inflammation, apoptosis, and metabolic pathways. And the predictions were then verified by the following examinations: (1) didymin significantly inhibited ERS by regulating the ATF6, IRE1α, and PERK pathways; (2) didymin markedly alleviated hepatocyte apoptosis by restoring the expression of Bcl-2 and caspase families, as well as the mitochondrial dysfunction; (3) didymin significantly decreased the production of the pro-inflammatory cytokines (IL-1ß and IL-6); (4) didymin inhibited the glycerophospholipid metabolism pathway by decreasing the synthesis of phosphatidylethanolamines and phosphatidylcholines. Conclusion: Our findings demonstrate that didymin can ameliorate liver fibrosis, which is mainly attributed to the inhibition of ERS, inflammation, and glycerophospholipid metabolism.

Engineering controllable oxygen vacancy defects in iron hydroxide oxide immobilized on reduced graphene oxide for boosting visible light-driven photo-Fenton-like oxidation.

Visible light-driven photo-Fenton-like technology is a promising advanced oxidation process for water remediation, while the construction of effective synergetic system remains a great challenge. Herein, iron hydroxide oxide (α-FeOOH) with controllable oxygen vacancy defects were engineered on reduced graphene oxide (rGO) nanosheets (named as OVs-FeOOH/rGO) through an in-situ redox method for boosting visible light-driven photo-Fenton-like oxidation. By adjusting the pH environment to modulate the redox reaction kinetics between graphene oxide (GO) and ferrous salt precursors, the oxygen vacancy concentration in α-FeOOH could be precisely controlled. With optimized oxygen vacancy defects obtained at pH 5, the OVs-FeOOH/rGO displayed superior photo-Fenton-like performance for Rhodamine B degradation (99% within 40 mins, rate constant of 0.2278 mg-1 L min-1) with low H2O2 dosage (5 mM), standing out among the reported photo-Fenton-like catalysts. The catalyst also showed excellent reusability, general applicability, and tolerance ability of realistic environmental conditions, which demonstrates great potential for practical applications. The results reveal that moderate oxygen vacancy defects can not only strengthen absorption of visible light and organic pollutants, but also promote the charge transfer to simultaneously accelerate the photogenerated electron-hole separation and Fe(III)/Fe(II) Fenton cycle, leading to the remarkable photo-Fenton-like oxidation performance. This work sheds light on the controllable synthesis and mechanism of oxygen vacancy defects to develop efficient photo-Fenton-like catalysts for wastewater treatment.

Tormentic Acid Ameliorates Hepatic Fibrosis in vivo by Inhibiting Glycerophospholipids Metabolism and PI3K/Akt/mTOR and NF-κB Pathways: Based on Transcriptomics and Metabolomics.

This study aimed to investigate the effects and underlying mechanisms of tormentic acid (TA) on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. The rats were intragastrically administered with 50% CCl4 for 9 weeks to induce hepatic fibrosis, followed by various agents for 6 weeks. Transcriptomic analysis was carried out to predict the potential targets, and then multiple examinations were performed to verify the prediction. The results showed that TA significantly alleviated liver injury and fibrosis, as evidenced by the ameliorative pathological tissue, low transaminase activity, and decreased collagen accumulation. Besides, TA markedly reduced hepatocyte apoptosis by regulating the expression of caspase-3 and Bcl-2 families. The transcriptomic analysis revealed 2,173 differentially expressed genes (DEGs) between the TA and model groups, which could be enriched in the metabolic pathways and the PI3K/Akt and NF-κB signaling pathways. The metabolomics analysis showed that TA could regulate the glycerophospholipid metabolism pathway by regulating the synthesis of phosphatidylserines, phosphatidylethanolamines and phosphatidylcholines. Moreover, the integrative analysis of the transcriptomics and metabolomics data indicated that TA inhibited the glycerophospholipid metabolism pathway by inhibiting the expression of LPCAT4, PTDSS2, PLA2G2A and CEPT1. In addition, the relevant signaling pathways analysis confirmed that TA inhibited HSCs activation by blocking the PI3K/Akt/mTOR pathway and ameliorated inflammatory injury by inhibiting the NF-κB pathway. In conclusion, TA significantly alleviates liver fibrosis in vivo by inhibiting the glycerophospholipid metabolism pathway and the PI3K/Akt/mTOR and NF-κB signaling pathways.

AA-Score: a New Scoring Function Based on Amino Acid-Specific Interaction for Molecular Docking.

The protein-ligand scoring function plays an important role in computer-aided drug discovery and is heavily used in virtual screening and lead optimization. In this study, we developed a new empirical protein-ligand scoring function with amino acid-specific interaction components for hydrogen bond, van der Waals, and electrostatic interactions. In addition, hydrophobic, π-stacking, π-cation, and metal-ligand interactions are also included in the new scoring function. To better evaluate the performance of the AA-Score, we generated several new test sets for evaluation of scoring, ranking, and docking performances, respectively. Extensive tests show that AA-Score performs well on scoring, docking, and ranking as compared to other widely used traditional scoring functions. The performance improvement of AA-Score benefits from the decomposition of individual interaction into amino acid-specific types. To facilitate applications, we developed an easy-to-use tool to analyze protein-ligand interaction fingerprint and predict binding affinity using the AA-Score. The source code and associated running examples can be found at https://github.com/xundrug/AA-Score-Tool.

Interconversion between guanine quartets and triads on the Au(111) surface.

Based on STM imaging and DFT calculations, we show the real-space experimental evidence of the interconversion between G-quartets and G-triads on the Au(111) surface, and further reveal the relative stabilities of these two elementary motifs, which helps to increase the fundamental understanding of the relationship between G-triplex and G-quadruplex DNA structures.

Comprehensive analysis of transcriptomics and metabolomics to illustrate the underlying mechanism of helenalin against hepatic fibrosis.

This study aimed to investigate the protective mechanisms of helenalin on hepatic fibrosis. In brief, rats were intragastrically administrated with 50% CCl4 for 9 weeks to induce liver fibrosis, followed by treatment with various agents for 6 weeks. The effects of helenalin on hepatic injury were assessed by pathological examinations. The potential targets were predicted by the "Drug-Disease" bioinformatic analysis and then verified by multiple experiments. Moreover, the underlying mechanism was investigated by transcriptomics and metabolomics as a whole. The results showed that helenalin significantly alleviated hepatocyte necrosis and hepatic injury, as proved by the pathological examinations. Also, helenalin markedly attenuated hepatocyte apoptosis by regulating the expression of caspase-3 and Bcl-2 families. Besides, helenalin could significantly reduce collagen accumulation, as evidenced by the decreased contents of collagen, hyaluronic acid and laminin. Moreover, helenalin significantly down-regulated the phosphorylation of PI3K, Akt, FAK, mTOR and P70S6K, and PTEN protein expression, suggesting that helenalin inhibited the PI3K/Akt signaling cascade. Meanwhile, helenalin inhibited the NF-κB signaling pathway by reducing the phosphorylation of IκBα, NF-κB p65 and IKKα/ß, alleviating inflammation response. Interestingly, the analysis of transcriptomics and metabolomics indicated that helenalin inhibited the glycerophospholipid metabolism pathway by down-regulating the target genes (CHKA, ETNPPL, LYPLA1, PCYT2, PLD4 and PNPLA6), ultimately ameliorating hepatocyte damage. In conclusion, helenalin ameliorates hepatic fibrosis by regulating the PI3K/Akt and NF-κB signaling pathways and the glycerophospholipid metabolism pathway.

Large Gap Two-Dimensional Topological Insulators with the Significant Rashba Effect in Ethynyl and Methyl Functionalized PbSn Monolayers.

Two-dimensional (2D) topological insulators (TIs) have recently attracted a great deal of attention due to their nondissipation electron transmission, stable performance, and easy device integration. However, a primary obstacle to influencing 2D TIs is the small bandgap, which limits their room-temperature applications. Here, we adopted first-principles to predict inversion-asymmetric group IV monolayers, PbSn(C2H)2 and PbSn(CH3)2, to be quantum spin Hall (QSH) insulators with large topological gaps of 0.586 and 0.481 eV, respectively. The nontrivial band topologies, which can survive in a wide range of strain, are characterized by topological invariants Z2, gapless edge states, and the Berry curvature. Another intriguing characteristic is the significant Rashba SOC effect which can also be tuned by feasible compressive and tensile strains. Meanwhile, the hexagonal boron nitride (h-BN) provides a suitable substrate for growth of these films without influencing their topological phases. These novel materials are expected to accelerate the development of advanced quantum devices.

Understanding charge storage in Nb2CTx MXene as an anode material for lithium ion batteries.

MXenes represent an emerging family of two-dimensional materials of transition metal carbides/carbonitrides terminated with functional groups like -O, -OH, and -F on the chemically active surface of MX slabs. As a member of the family, Nb2CTx exhibits superior lithium storage capacity over most of the other MXenes as anode materials in lithium-ion batteries (LIBs). However, an in-depth understanding of the charge storage mechanism is still lacking so far. Here, through combining complementary experiments and density functional theory calculations, we provide insights into the (de)lithiation process. Specifically, Nb2CTx with dominant -O functional groups stores charge as a result of changes in the oxidation states of both transition metals Nb and O, which is supported by Bader charge analysis showing a significant change in the oxidation states of Nb and O upon lithiation. As monitored by ex situ X-ray diffraction, the interlayer spacing of Nb2CTx changes slightly upon lithium ion (de)intercalation, corresponding to a volume change of only 2.3% with a near zero-strain feature. By coupling with a LiFePO4/C cathode, the full cell presents superior rate capability and cycling stability as well. The insights into the charge storage mechanism of Nb2CTx in this work provide useful guidance for the rational design of MXene-based anode materials for high-performance LIBs.

MolGpka: A Web Server for Small Molecule pKa Prediction Using a Graph-Convolutional Neural Network.

pKa is an important property in the lead optimization process since the charge state of a molecule in physiologic pH plays a critical role in its biological activity, solubility, membrane permeability, metabolism, and toxicity. Accurate and fast estimation of small molecule pKa is vital during the drug discovery process. We present MolGpKa, a web server for pKa prediction using a graph-convolutional neural network model. The model works by learning pKa related chemical patterns automatically and building reliable predictors with learned features. ACD/pKa data for 1.6 million compounds from the ChEMBL database was used for model training. We found that the performance of the model is better than machine learning models built with human-engineered fingerprints. Detailed analysis shows that the substitution effect on pKa is well learned by the model. MolGpKa is a handy tool for the rapid estimation of pKa during the ligand design process. The MolGpKa server is freely available to researchers and can be accessed at https://xundrug.cn/molgpka.

An Approach to Computing Solvent Reorganization Energy.

A method for accurate calculation of reorganization free energy of an explicit solvent solvating a solute molecule is presented. The method relies on the knowledge of solvation free energy known either from experimental measurement or from accurate calculation. An important part of this approach lies in the calculation of entropy in solute-solvent interaction free energy using the interaction entropy method, combined with the calculation of enthalpy of solvent reorganization based on a finite number of solvent molecules near the solute molecule. This interaction entropy-solvent reorganization or IESR method enables one to compute both enthalpy and entropy components of the solvent reorganization energy from MD simulation of the solvated system. The calculated results are determined by the molecular force field only without any empirical parameter. The current method is applied to computing the reorganization energies of water solvent solvating a wide range of solute molecules including both hydrophilic and hydrophobic ones. The accuracy of the approach is indirectly verified by the excellent agreement of individual enthalpies and entropies of the solvation energies between theory and experiment.

Nanoporous Ni3P Evolutionarily Structured onto a Ni Foam for Highly Selective Hydrogenation of Dimethyl Oxalate to Methyl Glycolate.

Methyl glycolate (MG) is a versatile platform molecule to produce numerous important chemicals and materials, especially new-generation biocompatible and biodegradable poly(glycolic acid). In principle, it can be massively produced from syngas (CO + H2) via gas-phase hydrogenation of CO-derived dimethyl oxalate (DMO), but the groundbreaking catalyst represents a grand challenge. Here, we report the discovery of a Ni-foam-structured nanoporous Ni3P catalyst, evolutionarily transformed from a Ni2P/Ni-foam engineered from nano- to macro-scale, being capable of nearly fully converting DMO into MG at >95% selectivity and stable for at least 1000 h without any sign of deactivation. As revealed by kinetic experiments and theoretical calculations, in comparison with Ni2P, Ni3P achieves a higher surface electron density that is favorable for MG adsorption in a molecular manner rather than in a dissociative manner and has much higher activation energy for MG hydrogenation to ethylene glycol (EG), thereby markedly suppressing its overhydrogenation to EG.

Amount Rather than Animal vs Plant Protein Intake Is Associated with Skeletal Muscle Mass in Community-Dwelling Middle-Aged and Older Chinese Adults: Results from the Guangzhou Nutrition and Health Study.

BACKGROUND: Current literature does not indicate if the amount and animal vs plant protein are equally important in the prevention of muscle loss in middle-aged and older Chinese adults. OBJECTIVE: The aim of the study was to examine the associations between amount or animal vs plant protein and skeletal muscle mass in Chinese adults aged 40 to 80 years. DESIGN: A cross-sectional analysis of a prospective, community-based cohort was performed. PARTICIPANTS/SETTING: Participants included 1,044 men and 2,169 women aged 40 to 80 years from the Guangzhou Nutrition and Health Study 2011-2013 with body composition measurements by dual-energy x-ray absorptiometry. MAIN OUTCOME MEASURE: The skeletal muscle index (SMI) was defined as appendicular skeletal muscle mass divided by body weight. Participants in the lowest quartile of the sex-specific SMI were considered to have low muscle mass (LMM). STATISTICAL ANALYSIS: Analyses of covariance were performed to estimate the SMI across quintiles of relative dietary intake of total, animal, and plant protein and the ratio of animal-to-plant protein. Logistic regression models were applied to assess the associations between quintiles of protein intake and LMM. RESULTS: The SMI increased significantly across quintiles of relative dietary intake of total, animal, and plant protein (all P trends<0.001). Odds ratios (95% CIs) for LMM among participants in the highest (vs lowest) quintile were 0.3 (0.2, 0.4) for total protein, 0.3 (0.2, 0.5) for animal protein, and 0.4 (0.3, 0.7) for plant protein, respectively (all P trends<0.001). However, the ratio of animal-to-plant protein was not associated with either the SMI or the presence of LMM. CONCLUSION: Higher dietary intakes of total, animal, and plant protein, regardless of the ratio of animal-to-plant protein, are associated with greater skeletal muscle mass in community-dwelling middle-aged and older Chinese adults with a mean protein intake above the current recommendation for protein of 0.8 g/kg per day.

Studies on the Chemical Diversities of Secondary Metabolites Produced by Neosartorya fischeri via the OSMAC Method.

The One Strain Many Compounds (OSMAC) method was applied to explore the chemical diversities of secondary metabolites produced by Neosartorya fischeri NRRL 181. Four pyripyropenes 1⁻4, eight steroids 5⁻11, and four prenylated indole alkaloids 12⁻15, were obtained from the fungus cultured in petri dishes containing potato dextrose agar (PDA). 1,7,11-trideacetylpyripyropene A (1) and 1,11-dideacetyl pyripyropene A (2) were obtained and spectroscopically characterized (1D, 2D NMR, and HR-ESI-MS) from a natural source for the first time. It offered a sustainable source of these two compounds, which were usually used as starting materials in preparing pyripyropene derivatives. In addition, as compared with all the other naturally occurring pyripyropenes, 1 and 2 possessed unique acetylation patterns that did not follow the established late-step biosynthetic rules of pyripyropenes. The natural occurrence of 1 and 2 in the fungus implied that the timing and order of hydroxylation and acetylation in the late-step biosynthetic pathway of pyripyropenes remained to be revealed. The isolation and identification of 1⁻15 indicated that the OSMAC method could remarkably alter the metabolic profile and enrich the chemical diversities of fungal metabolites. Compounds 1⁻4 exhibited no obvious cytotoxicity against the triple-negative breast cancer cell line MDA-MB-231 as compared with taxol.