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The Middle Jurassic Walloon Subgroup of Daandine gas field contains numerous coal seams with abundant coalbed methane (CBM) resources. However, the vertical gas content distribution of these coal seams is unclear currently, as well as its influencing factors, affecting the formulation of CBM exploration and exploitation strategy. For this purpose, using diverse geologic, experimental, and engineering data from recent exploration and development, this article ascertains the vertical coalbed gas content distribution in the Daandine gas field and discusses how the geological factors affect it. The results show that the coalbed gas contents have two basic trends as the depth increases: (1) increase, and then decrease; (2) increase. The former trend is dominant, and the inflection point occurs in the coal groups within or close to the Tangalooma Sandstone Formation. The correlation analysis shows that the macerals have little influence on the vertical coalbed gas content distribution. The moisture contents affect the adsorption capacity of coalbeds and show a negative correlation with the gas contents, and coal groups with higher moisture contents generally have lower gas contents. Three sets of independent gas-bearing systems exist in the Walloon Subgroup, and the coalbed gas content-depth relationship is relatively independent among different gas-bearing systems. The better the caprock condition, the higher the gas content, which is particularly evident in the coals of Condamine group. The permeabilities show a significant effect on the coalbed gas contents of Daandine coals. The coal groups within or close to the Tangalooma Sandstone Formation have higher permeabilities, as well as higher gas contents, and they are positively correlated. The reason is that the CBM in the study area is dominantly microbial in origin, and the higher permeability coals are conducive to the introduction of more microbial consortia into the coal seams, enhancing the generation of secondary biogenesis methane.

Abstract Background Acute-on-chronic liver failure (ACLF) is a refractory disease with high mortality, which is characterized by a pathophysiological process of inflammation-related dysfunction of energy metabolism. Jieduan-Niwan formula (JDNWF) is a eutherapeutic Chinese medicine formula for ACLF. However, the intrinsic mechanism of its anti-ACLF effect still need to be studied systematically. Purpose This study aimed to investigate the mechanism of JDNWF against ACLF based on altered substance metabolic profile in ACLF the expression levels of related molecules. Materials and methods The chemical characteristics of JDNWF were characterized using ultra performance liquid chromatography (UPLC) coupled with triple quadrupole mass spectrometry. Wistar rats subjected to a long-term CCL4 stimulation followed by a combination of an acute attack with LPS/D-GalN were used to establish the ACLF model. Liver metabolites were analyzed by LC–MS/MS and multivariate analysis. Liver function, coagulation function, histopathology, mitochondrial metabolic enzyme activity and mitochondrial damage markers were evaluated. The protein expression of mitochondrial quality control (MQC) was investigated by western blot. Results Liver function, coagulation function, inflammation, oxidative stress and mitochondrial enzyme activity were significantly improved by JDNWF. 108 metabolites are considered as biomarkers of JDNWF in treating ACLF, which were closely related to TCA cycle. It was further suggested that JDNWF alleviated mitochondrial damage and MQC may be potential mechanism of JDNWF improving mitochondrial function. Conclusions Metabolomics revealed that TCA cycle was impaired in ACLF rats, and JDNWF had a regulatory effect on it. The potential mechanism may be improving the mitochondrial function through MQC pathway, thus restoring energy metabolism.

The present study utilized molecular docking and density functional theory (DFT) approaches, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties to investigate the binding interactions, reactivity, stability, and drug-likeness of curcumin (1), tetrahydrocurcumin (2), and tetrahydrocurcumin derivatives (3–6) as potential anti-cancer agents. MGL (Molecular Graphic Laboratory) and Discovery Studio Visualizer (DSV) software employed for docking studies. Pharmacokinetic and pharmacodynamic (ADME-Tox) analyses were conducted using SwissADME and pKCSM web servers. Total Electron Density (TED) measurements identified molecular adsorption sites, considering various factors, including quantum chemical characteristics, to assess compound effectiveness using DFT method implanted in the Gaussian software. The binding energy (Eb) from docking simulations was used to evaluate inhibitory potential. ADMET analysis suggested favorable oral bioavailability and pharmacokinetics for all studied substances, excluding compound 4. DFT and docking investigations highlighted compounds 1, 2, and 6 as optimal scaffolds for drug design based on in silico screening tests.

Gestational diabetes mellitus (GDM) is one of the common complications during pregnancy. Numerous studies have shown that GDM is associated with a series of adverse effects on both mothers and offspring. Due to the particularity of pregnancy, medical nutrition treatment is considered to be the first choice for the treatment of GDM. This contribution reviews the research progress of medical nutrition treatment in GDM, summarizes the international recommendations on the intake of various nutrients and the influence of nutrients on the prevalence of GDM, and the improvement effect of nutritional intervention on it, in order to provide references for research in related fields of GDM and the targeted development of enteral nutrition.

Natural pyrethrins (NPs), one kind of bio-pesticide, have been widely used in organic agriculture and ecological environment studies. Studies have shown that NPs may affect the metabolism of rat liver and human hepatocytes; nevertheless, the toxic effects of NPs on the liver and the related mechanisms are still incompletely understood. In this research, we utilized three types of human liver cells to investigate the mechanism of NPs’ induction of oxidative stress. The results showed that NPs exhibit noteworthy cytotoxic effects on human liver cells. These effects are characterized by the induction of LDH release, mitochondrial collapse, and an increased production of ROS and MDA content, subsequently activating the Kelch-like ECH-associated protein 1/Nuclear factor erythroid 2- related factor 2 (Keap1/Nrf-2) pathway. The ROS inhibitor N-acetyl-L-cysteine (NAC) can alleviate ROS/Nrf2-mediated oxidative stress. In addition, the siRNA knockdown of Nrf-2 exacerbated the injury, including ROS production, and inhibited cell viability. In summary, the ROS-mediated Keap1/Nrf-2 pathway could be an important regulator of NP-induced damage in human liver cells, which further illustrates the hepatotoxicity of NPs and thereby contributes to the scientific basis for further exploration.

Artemisia sphaerocephala Krasch gum (ASKG) can be carboxymethylated and greasy-based emulsified to improve its water solubility and emulsifying property, while the effect of modified ASKG on wheat flour processing as a gluten enhancer remains largely unknown. In this study, we investigated the gluten-increasing effect of ASKG in the formation of wheat flour dough and the production of greasy dough through its carboxymethylation and emulsification modification. The results showed that the carboxymethylation could reduce the optimum addition amount of ASKG from 1.0% to 0.4% in wheat flour. Carboxymethyl ASKG (C-ASKG) increased the wet gluten content, gluten index, water absorption, dough development time, dough stability time, and reduced the weakening degree. However, C-ASKG did not show better reinforcement in greasy dough than ASKG. In comparison, ASKG emulsified (E-ASKG) by wheat germ oil and palm stearin fat was shown to be more suitable for greasy dough modulation. The addition of 1.0% of ASKG and 5% of oil or fat in flour by emulsification manner reduced the difference between the oil and fat during the formation of gluten and improve the evaluation indexes of dough texture. This study demonstrated that carboxymethylation could reduce the dosage of ASKG used in wheat flour as a gluten enhancer, while emulsive ASKG was suitable for the gluten reinforcement of water-oiled dough.

Liver fibrosis poses a significant global health risk due to its association with hepatocellular carcinoma (HCC) and the lack of effective treatments. Thus, the need to discover additional novel therapeutic targets to attenuate liver diseases is urgent. Leucine-rich repeat containing 1 (LRRC1) reportedly promotes HCC development. Previously, we found that LRRC1 was significantly upregulated in rat fibrotic liver according to the transcriptome sequencing data. Herein, in the current work, we aimed to explore the role of LRRC1 in liver fibrosis and the underlying mechanisms involved. LRRC1 expression was positively correlated with liver fibrosis severity and significantly elevated in both human and murine fibrotic liver tissues. LRRC1 knockdown or overexpression inhibited or enhanced the proliferation, migration, and expression of fibrogenic genes in the human hepatic stellate cell line LX-2. More importantly, LRRC1 inhibition in vivo significantly alleviated CCl4-induced liver fibrosis by reducing collagen accumulation and hepatic stellate cells’ (HSCs) activation in mice. Mechanistically, LRRC1 promoted HSC activation and liver fibrogenesis by preventing the ubiquitin-mediated degradation of phosphorylated mothers against decapentaplegic homolog (Smad) 2/3 (p-Smad2/3), thereby activating the TGF-β1/Smad pathway. Collectively, these results clarify a novel role for LRRC1 as a regulator of liver fibrosis and indicate that LRRC1 is a promising target for antifibrotic therapies.

Abstract Acute-on-chronic liver failure (ACLF) is a critical and refractory disease and a hepatic disorder accompanied by immune dysfunction. Thus, it is essential to explore key immune-related genes of ACLF and investigate its mechanisms. We used two public datasets (GSE142255 and GSE168048) to perform various bioinformatics analyses, including WGCNA, CIBERSORT, and GSEA. We also constructed an ACLF immune-related protein–protein interaction (PPI) network to obtain hub differentially expressed genes (DEGs) and predict corresponding miRNAs. Finally, an ACLF rat model was established to verify the results. A total of 388 DEGs were identified in ACLF, including 162 upregulated and 226 downregulated genes. The enrichment analyses revealed that these DEGs were mainly involved in inflammatory-immune responses and biosynthetic metabolic pathways. Twenty-eight gene modules were obtained using WGCNA and the coral1 and darkseagreen4 modules were highly correlated with M1 macrophage polarization. As a result, 10 hub genes and 2 miRNAs were identified to be significantly altered in ACLF. The bioinformatics analyses of the two datasets presented valuable insights into the pathogenesis and screening of hub genes of ACLF. These results might contribute to a better understanding of the potential molecular mechanisms of ACLF. Finally, further studies are required to validate our current findings.

Selenium is recognized as an essential element for human health and enters human body mainly via diet. Selenium is a key constituent in selenoproteins, which exert essential biological functions, including antioxidant and anti-inflammatory effects. Several selenoproteins including glutathione peroxidases, selenoprotein P and selenoprotein S are known to play roles in the regulation of type 2 diabetes. Although there is a close association between certain selenoproteins with glucose metabolism or insulin resistance, the relationship between selenium and type 2 diabetes is complex and remains uncertain. Here we review recent advances in the field with an emphasis on roles of selenium on metabolism and type 2 diabetes. Understanding the association between selenium and type 2 diabetes is important for developing clinical practice guidelines, establishing and implementing effective public health policies, and ultimately combating relative health issues.

BackgroundHomocysteine and C-reactive protein (CRP) may serve as biomarkers of postoperative delirium. We set out to compare the role of blood concentration of homocysteine versus CRP in predicting postoperative delirium in patients.Materials and methodsIn this prospective observational cohort study, the plasma concentration of preoperative homocysteine and postoperative CRP was measured. Delirium incidence and severity within 3 days postoperatively were determined using the Confusion Assessment Method and Confusion Assessment Method-Severity algorithm.ResultsOf 143 participants [69% female, median (interquartile range, 25th–75th) age of 71 (67–76) years] who had knee or hip surgery under general anesthesia, 44 (31%) participants developed postoperative delirium. Postoperative plasma concentration of CRP was associated with postoperative delirium incidence [adjusted odds ratio (OR) per one standard deviation change in CRP: 1.51; 95% Confidence Interval (CI): 1.05, 2.16; P = 0.026], and severity [in which each one standard deviation increase in postoperative CRP was associated with a 0.47 point (95% CI: 0.18–0.76) increase in the severity of delirium, P = 0.002] after adjusting age, sex, preoperative Mini-Mental State Examination score and the days when postoperative CRP was measured. A statistically significant interaction (adjusted P = 0.044) was also observed, in which the association between postoperative plasma concentration of CRP and postoperative delirium incidence was stronger in the participants with lower preoperative plasma concentrations of homocysteine compared to those with higher preoperative levels.ConclusionPending validation studies, these data suggest that preoperative plasma concentration of homocysteine modifies the established association between postoperative plasma concentration of CRP and postoperative delirium incidence.

Many real-world applications can be described as large-scale games of imperfect information, which require extensive prior domain knowledge, especially in competitive or human–AI cooperation settings. Population-based training methods have become a popular solution to learn robust policies without any prior knowledge, which can generalize to policies of other players or humans. In this survey, we shed light on population-based deep reinforcement learning (PB-DRL) algorithms, their applications, and general frameworks. We introduce several independent subject areas, including naive self-play, fictitious self-play, population-play, evolution-based training methods, and the policy-space response oracle family. These methods provide a variety of approaches to solving multi-agent problems and are useful in designing robust multi-agent reinforcement learning algorithms that can handle complex real-life situations. Finally, we discuss challenges and hot topics in PB-DRL algorithms. We hope that this brief survey can provide guidance and insights for researchers interested in PB-DRL algorithms.

Daylily (Hemerocallis citrina Baroni) is an edible plant widely distributed worldwide, especially in Asia. It has traditionally been considered a potential anti-constipation vegetable. This study aimed to investigate the anti-constipation effects of daylily from the perspective of gastro-intestinal transit, defecation parameters, short-chain organic acids, gut microbiome, transcriptomes and network pharmacology. The results show that dried daylily (DHC) intake accelerated the defecation frequency of mice, while it did not significantly alter the levels of short-chain organic acids in the cecum. The 16S rRNA sequencing showed that DHC elevated the abundance of Akkermansia, Bifidobacterium and Flavonifractor, while it reduced the level of pathogens (such as Helicobacter and Vibrio). Furthermore, a transcriptomics analysis revealed 736 differentially expressed genes (DEGs) after DHC treatment, which are mainly enriched in the olfactory transduction pathway. The integration of transcriptomes and network pharmacology revealed seven overlapping targets (Alb, Drd2, Igf2, Pon1, Tshr, Mc2r and Nalcn). A qPCR analysis further showed that DHC reduced the expression of Alb, Pon1 and Cnr1 in the colon of constipated mice. Our findings provide a novel insight into the anti-constipation effects of DHC.

We extracted one new C-methyl flavonoid, farrerol 7-O-β-d-(6-O-galloyl)glucopyranoside (1), along with 11 known flavonoids, from the Cleistocalyx (C.) conspersipunctatus leaves. Elucidation of these flavonoid structures was accomplished through spectroscopic investigation and electronic circular dichroism (ECD) computation. Compared to corosolic acid (IC50: 15.5 ± 0.9 μM), an established inhibitor, the compound 1 (IC50: 6.9 ± 1.2 μM) was found more active in suppressing α-glucosidase. These findings imply the potential of compound 1 as a valid α-glucosidase inhibitor, which also offer evidence for future animal experiments and clinical trials. Besides, molecular docking was employed to explore the probable mechanism for α-glucosidase–compound 1 interaction. The biosynthetic pathway of these flavonoids in C. conspersipunctatus were proposed.

In this article, nano-sized calcium perrhenate was prepared using the microemulsion reaction method. By the aid of surfactant, the calcium perrhenate was suspended in pentaerythritol ester base oil to serve as a lubricating additive. The tribological performances of the oil containing calcium perrhenate at elevated temperatures were investigated by four-ball tests and ball-on-disk reciprocating sliding tests. The underlying lubricating mechanism of the calcium perrhenate additive was explored using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry/thermogravimetry, Raman spectroscopy, and X-ray photoelectron spectroscopy. The four-ball test results indicated that the oil containing calcium perrhenate featured lower friction coefficients, smaller wear scar diameters, and lower temperature rising performance than the base oil under an applied load of 392 N. The optimum lubricating property was obtained when the additive was at a concentration of 0.05 wt%. The tribological performance in a wide temperature range results showed that the friction coefficients of the oil containing calcium perrhenate were slightly lower than those of the base oil at a relatively low temperature range, and decreased as the temperature increased within a high range. The improved tribological performances owed to the formation of a protective layer, which consisted of the shear-susceptible calcium perrhenate additive as well as some native metal oxides that enhanced the layer carrying capacity during rubbing after chemical degradation of base oil. This protective layer acted as a barrier between the rubbing surfaces, preventing them from directly contacting each other at elevated temperatures.

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in China. Sinisan (SNS) is a traditional Chinese medicine formula that has been widely used in treating chronic liver diseases, including NAFLD. However, its underlying biological mechanisms are still unclear. In this study, we employed a network pharmacology approach consisting of overlapped terms- (genes or pathway terms-) based analysis, protein-protein interaction (PPI) network-based analysis, and PPI clusters identification. Unlike the previous network pharmacology study, we used the shortest path length-based network proximity algorithm to evaluate the efficacy of SNS against NAFLD. And we also used random walk with restart (RWR) algorithm and Community Cluster (Glay) algorithm to identify important targets and clusters. The screening results showed that the mean shortest path length between genes of SNS and NAFLD was significantly smaller than degree-matched random ones. Six PPI clusters were identified and ten hub targets were obtained, including STAT3, CTNNB1, MAPK1, MAPK3, AGT, NQO1, TOP2A, FDFT1, ALDH4A1, and KCNH2. The experimental study indicated that SNS reduced hyperlipidemia, liver steatosis, and inflammation. Most importantly, JAK2/STAT3 signal was inhibited by SNS treatment and was recognized as the most important signal considering the network pharmacology part. This study provides a systems perspective to study the relationship between Chinese medicines and diseases and helps to discover potential mechanisms by which SNS ameliorates NAFLD.

Introduction Postoperative delirium is one of the most common postoperative complications among elderly patients (65 years old or older). However, there are no effective treatments for this condition. Recent research suggests that continuous theta burst stimulation (cTBS), a non-invasive brain stimulation, can reduce pain level, improve cognitive function and affective symptoms in multiple diseases or dysfunctions, including anxiety disorders, major depressive disorder, sleep disorders and pain. But the potential benefits of cTBS in reducing postoperative delirium have not been investigated. Therefore, we propose determining whether cTBS can prevent and/or treat postoperative delirium in senior patients.Methods and analysis The study will be a double-blind, randomised controlled trial. Participants (65 years old or older) undergoing scheduled orthopaedic surgery (≥2 hours, general anaesthesia) will be randomised to receive either cTBS or sham stimulation with a focal figure-of-eight coil over the right dorsolateral prefrontal cortex at 80% of the resting motor threshold. Every patient will receive 2–3 sets of stimulations during postoperative days (40 s per session, 3 sessions per set, 1 set per day). Participants will be assessed twice daily by a research assistant blinded to allocation. The primary outcome will be the incidence of postoperative delirium measured by the Confusion Assessment Method on postoperative days 1, 2 and 3. The secondary outcomes will be the severity and duration of postoperative delirium, cognitive function, pain, sleep quality, activities of daily living, length of hospital stay, discharge-to-facility or home, and rate of complication and mortality during the hospital stay.Ethics and dissemination Ethical approval has been obtained from the ethics committee of Shanghai 10th People’s Hospital. The principal investigator will submit a research progress report to the ethics committee regularly. All participants will provide written informed consent. Study results will be published in a peer-reviewed journal.Trial registration number NCT04661904.

Objective: A sensitive and selective fluorescence-detection platform based on carbon quantum dots (CQDs) was designed and developed for the determination of methotrexate (MTX), for the purpose of minimizing the possible toxic threat of MTX in clinics. Methods: The approach was prepared for the first time by a simple, hydrothermal method, making the synthesis and modification processes realized in one step using polyethyleneimine (PEI), and the proposed PEI-CQDs were obtained with high fluorescence quantum yield (38%). Results: MTX was found highly responsive and effective in quenching the fluorescence of the PEI-CQDs, due to a suggested fluorescence resonance energy transfer mechanism or inner-filter effect. The linear range of MTX was between 1 and 600 μmol/L under optimum conditions, with a detection limit (LOD) as low as 0.33 μmol/L. Furthermore, the fluorescent method was established for the MTX assay, and satisfactory results were acquired in real-sample determination. The average labeled quantity was 98.2%, and the average added standard recovery was 100.9%. Conclusions: The proposed PEI-CQDs showed a remarkable potential for broad applications in biological molecule determination and environmental analysis.

As one of the most characteristic ingredients of glandular trichome secretions from Nicotiana tabacum L. (tobacco), natural cembrenediols, namely, (1S,2E,4S,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (α-cembrenediol/α-CBD) and its C-4 epimer (β-cembrenediol/β-CBD), have attracted considerable attention for their potent antitumor, neuroprotective, antimicrobial, and other activities. Many researchers are committed to exploring the possibility of utilizing these two cembrenediols and their derivatives both in human medicine and in agricultural fungicides. To the best of our knowledge, this review is the first to provide a comprehensive summary of the chemical modifications and bioactivities of α- and β-CBD from their discovery to the present day; the review highlights their potential medicinal value for humans. The extensive references from 1962 to 2022 provided herein were systematically gathered from the SciFinder, Web of Science, and Google Scholar databases. We expect this review to assist in providing practical ideas for future drug development based on α- and β-CBD and in further facilitating the utilization of the tobacco cembrenediols.

(1) Background: Carbon quantum dots (CQDs) are a new class of carbon nanomaterials with favorable features, such as tunable luminescence, unique optical properties, water solubility, and lack of cytotoxicity; they are readily applied in biomedicine. (2) Methods: S, N co-doped CQDs were prepared to develop a highly selective and sensitive fluorescence technique for the detection of methotrexate (MTX). For this purpose, citric acid and thiourea were used as C, N, and S sources in a single-step hydrothermal process to prepare the S, N co-doped CQDs, which displayed remarkable fluorescence properties. (3) Results: Two optimal emissions were observed at the excitation/emission wavelengths of 320/425 nm, respectively. The two emissions were significantly quenched in the presence of MTX. Under optimal conditions, MTX was detected in the linear concentration range of 1–300 μmol/L, with the detection limit of 0.33 μmol/L. The sensing mechanism was due to the fact that the effect of the inner filter on MTX and S, N-CQDs causes fluorescence quenching. The contents of MTX in real medicine samples were evaluated with acceptable recoveries of 98–101%. (4) Conclusions: This approach has great potential for detecting MTX in pharmaceutical analysis.

Nano silicon dioxide (Nano-SiO2) has been widely used in industries such as the field of biomedical engineering. Despite the existing evidence that Nano-SiO2 exposure could induce oxidative stress and inflammatory responses in multiple organ systems, the carcinogenicity of Nano-SiO2 exposure has rarely been investigated. Thus in this study, two types of human bronchial epithelial cell lines (16HBE and BEAS-2B) were selected as in vitro models to investigate the carcinogenicity of Nano-SiO2. Our results revealed that Nano-SiO2 induces a malignant cellular transformation in human bronchial epithelial cells according to the soft agar colony formation assay. The carcinogenesis induced by Nano-SiO2 was also confirmed in nude mice. By using immunofluorescence assay and high-performance capillary electrophoresis (HPCE), we observed a genome-wide DNA hypomethylation induced by Nano-SiO2. Besides the reduced enzyme activity of total DNMTs upon Nano-SiO2 treatment, altered expression of DNMTs and methyl-CpG binding proteins were observed. Besides, we found that the expression of NRF2 was activated by demethylation of CpG islands within the NRF2 promoter region and the overexpression of NRF2 could alleviate the carcinogenesis induced by Nano-SiO2. Taken together, our results suggested that Nano-SiO2 induces malignant cellular transformation with a global DNA hypomethylation, and the demethylation of NRF2 promoter activates the expression of NRF2, which plays an important role in protecting against the carcinogenesis induced by Nano-SiO2.

High mobility group box-1 (HMGB1) plays an important role in various liver injuries. In the case of acute liver injury, it leads to aseptic inflammation and other reactions, and also regulates specific cell death responses in chronic liver injury. HMGB1 has been demonstrated to be a good therapeutic target for treating liver failure. Quercetin (Que), as an antioxidant, is a potential phytochemical with hepatocyte protection and is also considered to be an inhibitor of HMGB1. However, the mechanism of its hepatoprotective effects remains to be characterized. The present study explored whether the hepatoprotective effect of Que antagonizes HMGB1, and subsequent molecular signaling events. Our results indicated that Que protects L02 cells from d-galactosamine (d-GaLN)-induced cellular damage by reducing intracellular reactive oxygen species (ROS) production and apoptotic responses in the mitochondrial pathway. Immunofluorescence and Western blot assays showed that HMGB1 was involved in d-GaLN-induced L02 cell damage. Further research showed that after transfection with HMGB1 short hairpin RNA (shRNA), cell viability was improved, and intracellular ROS production and apoptosis were suppressed. When co-treated with Que, the expression of HMGB1 was decreased significantly, the expression of proteins in the corresponding signal pathway were further reduced, and the production of ROS and apoptosis were further suppressed. Molecular docking also indicated the binding of Que and HMGB1. Taken together, these results indicate that Que significantly improves d-GaLN-induced cellular damage by inhibiting oxidative stress and mitochondrial apoptosis via inhibiting HMGB1.

Three new metabolites, including a cyclic tetrapeptide asperhiratide (1), an ecdysteroid derivative asperhiratine (2), and a sesquiterpene lactone asperhiratone (3), were isolated and identified from the soft coral-derived fungus Aspergillus hiratsukae SCSIO 5Bn1003, together with 10 known compounds. Their structures were elucidated via spectroscopic analysis, X-ray diffraction analysis, and electronic circular dichroism calculations. In addition, the absolute configuration of 1 was determined by Marfey’s technique and an analysis of the acid hydrolysates using a chiral phase HPLC column. Among all the compounds, 6 and 8 showed medium cytotoxic activities against four tumor cell lines (SF-268, HepG-2, MCF-7, and A549), with IC50 values ranging from 31.03 ± 3.04 to 50.25 ± 0.54 µM. Meanwhile, they strongly inhibited α-glucosidase activities, with IC50 values of 35.73 ± 3.94 and 22.00 ± 2.45 µM, which were close to and even stronger than the positive control acarbose (IC50 = 32.92 ± 1.03 µM). Compounds 6–8 showed significant antibacterial activities against Bacillus subtilis, with MIC values of 10.26 ± 0.76 µM, 17.00 ± 1.25 µM, and 5.30 ± 0.29 µM, respectively. Compounds 9 and 12 exhibited potent radical scavenging activities against DPPH, with IC50 values of 12.23 ± 0.78 µM and 7.38 ± 1.16 µM. In addition, asperhiratide (1) was evaluated for anti-angiogenic activities in the in vivo zebrafish model, which showed a weak inhibitory effect on intersegmental vessel (ISV) formation.

We have previously shown deep-sea-derived Streptomyces koyangensis SCSIO 5802 to produce two types of active secondary metabolites, abyssomicins and candicidins. Here, we report the complete genome sequence of S. koyangensis SCSIO 5802 employing bioinformatics to highlight its potential to produce at least 21 categories of natural products. In order to mine novel natural products, the production of two polycyclic tetramate macrolactams (PTMs), the known 10-epi-HSAF (1) and a new compound, koyanamide A (2), was stimulated via inactivation of the abyssomicin and candicidin biosynthetic machineries. Detailed bioinformatics analyses revealed a PKS/NRPS gene cluster, containing 6 open reading frames (ORFs) and spanning ~16 kb of contiguous genomic DNA, as the putative PTM biosynthetic gene cluster (BGC) (termed herein sko). We furthermore demonstrate, via gene disruption experiments, that the sko cluster encodes the biosynthesis of 10-epi-HSAF and koyanamide A. Finally, we propose a plausible biosynthetic pathway to 10-epi-HSAF and koyanamide A. In total, this study demonstrates an effective approach to cryptic BGC activation enabling the discovery of new bioactive metabolites; genome mining and metabolic profiling methods play key roles in this strategy.

Abstract Tetrahydrocurcumin (THC) is a major metabolite of curcumin and plays an important role in curcumin-induced biological effects. THC is a promising preventive and chemotherapeutic agent for cancer. A series of new pyrazole derivatives of THC have been synthesized as potent anticancer agents. Direct condensation of THC with various substituted hydrazines leads to new pyrazole derivatives of THC (1–18). The prepared compounds have been evaluated via in vitro MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay for their cell proliferation-inhibitory activity against human lung adenocarcinoma (A549), human cervical carcinoma (HeLa) and human breast carcinoma (MCF-7) cells. Most derivatives show significantly higher anticancer activity against all three tested cancer cell lines than the parent compound THC. Several compounds (7, 8, 12, 13 and 15) display promising anticancer activity against MCF-7 cell line with IC50 values ranging from 5.8 to 9.3 µM. The most active compound (8) is substituted with 4-bromophenyl group at the pyrazole ring and inhibits the growth of all three tested cancer cell lines with an IC50 values of (8.0 µM, A549), (9.8 µM, HeLa) and (5.8 µM, MCF-7). The obtained compounds can be a good starting point for the development of new lead molecules in the fight against cancer. Graphical Abstract

Three new cycloheximide congeners, 2,3-dehydro-α-epi-isocycloheximide (1), (E)- and (Z)-2,3-dehydroanhydrocycloheximides (2 and 3), together with three known compounds, anhydroisoheximide (4), cycloheximide (5), and isocycloheximide (6), were obtained from the cultures of Streptomyces sp. SC0581. Their structures were elucidated by extensive spectroscopic analysis in combination with theoretical conformational analysis and ECD computations. The photoinduced interconversion between 2 and 3 was observed and verified and the possible reaction path and mechanism were proposed by theoretical computations. The antifungal and cytotoxic activities of 1–6 were evaluated and suggested that 2,3-dehydrogenation results in the loss of the activities and supported that the OH-α is important to the activities of cycloheximide congeners.

The fruit of Averrhoa carambola L. (Oxalidaceae) is a commercially important fruit. Our study on the chemical constituents present in the fresh sweet fruit led to the isolation of eleven non-flavonoid phenolic compounds. Their structures were identified by analyses of spectroscopic data. They were two new alkyl phenol diglucosides, carambolasides K (1) and L (2), four phenylpropanoids, (+)-isolariciresinol 9-O-β-d-glucoside (3), (+)-lyoniresinol 9-O-β-d-glucoside (4), (−)-lyoniresinol 9-O-β-d-glucoside (5), and 1-O-feruloyl-β-d-glucose (6), three benzoic acids, protocatechuic acid (7), 1-O-vanilloyl-β-d-glucose (8), and tecomin (9), a simple phenol, koaburaside (10), and a naphthoquinone, (+)-cryptosporin (11). All of them were reported from A. carambola fruit for the first time. Compounds 1–8 and 10 showed 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical cation scavenging activity comparable to l-ascorbic acid, while compounds 3, 5, and 7 exhibited potent ferric reducing antioxidant power (FRAP). In addition, compounds 6 and 11 demonstrated weak porcine pancreatic lipase inhibitory activity.

Three pairs of new spirocyclic alkaloid enantiomers eurotinoids A–C (1–3), as well as a known biogenetically related racemate dihydrocryptoechinulin D (4) were isolated from a marine-derived fungus Eurotium sp. SCSIO F452. Their structures were determined by spectroscopic analyses and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 represent the first two “meta” products from a non-stereoselective [4 + 2] Diels-Alder cycloaddition presumably between an enone group of a diketopiperazine alkaloid and a diene group of a benzaldehyde derivative via a new head-to-tail coupling mode biosynthetically, while 3 and 4 were “ortho” products. Their enantiomers exhibited different antioxidative and cytotoxic activities. The modes of action were investigated by a preliminary molecular docking study.

Plant growth regulators (PGRs) are commonly used in cereal cropping systems to restrict plant height and control lodging. Ethephon has been reported to shorten internodes and increase grain yield of maize. To analyze the transcriptomic profiles of maize internode elongation following ethephon treatment, differentially expressed genes were compared between the treatment and control samples of inbred line Zong 31 using the Affymetrix Maize Genome Array. According to the microarray data, 326 probe sets showed significant change in expression. Further research revealed that the most remarkable effects of ethephon on maize internodes elongation occurred during a 48 h period, when 89 differentially expressed genes were detected. There were dramatic change in transcript levels at 24 h and six Auxin transport genes and four gibberellin biosynthesis pathway genes were differentially expressed in Zong 31 in response to ethephon treatment. In summary, we showed that gaseous ethylene release is involved in internode meristem cell elongation through the regulation of plant hormone signaling in maize. This work provides a platform for studies in which candidate genes will be functionally tested for involvement in internode elongation.

Recently, the engineering structural ceramics as friction and wear components in manufacturing technology and devices have attracted much attention due to their high strength and corrosion resistance. In this study, the tribological properties of Si3N4/Si3N4 sliding pairs were investigated by adding few-layer graphene to base lubricating oil on the lubrication and cooling under different experimental conditions. Test results showed that lubrication and cooling performance was obviously improved with the addition of graphene at high rotational speeds and low loads. For oil containing 0.1 wt% graphene at a rotational speed of 3000 r·min−1 and 40 N loads, the average friction coefficient was reduced by 76.33%. The cooling effect on Si3N4/Si3N4 sliding pairs, however, was optimal at low rotational speeds and high loads. For oil containing 0.05 wt% graphene at a lower rotational speed of 500 r·min−1 and a higher load of 140 N, the temperature rise was reduced by 19.76%. In addition, the wear mark depth would decrease when adding appropriate graphene. The mechanism behind the reduction in friction and anti-wear properties was related to the formation of a lubricating protective film.

In this study, the pineapple leaf cellulose film was prepared in ionic liquid by high shearing force and used for fresh-cut pineapple preservation. First, cellulose was dissolved in ionic liquid (1-butyl-3-methylimidazolium chloride ([Bmim]Cl)) using a high shear mixer. The regenerated cellulose was characterized by scanning electron microscope (SEM), x-ray diffraction (XRD), fourier transformed infrared spectra (FT-IR), and thermo gravimetric analysis (TGA). Results showed that the cellulose was dissolved in ionic liquid at room temperature with a high regeneration rate of more than 95% and for less than 2 min. It was suggested that the network of cellulose was destroyed by high shearing force. Then the cellulose film was obtained by casting on the glass plates. The mechanical properties of the films were evaluated by extension test with the tensile strength of 34 MPa. The proposed film was used for fresh-cut pineapple packaging. Results showed that it could significantly decrease weight loss and maintain the firmness of the pineapple, and thus, improve the quality of the fruit during storage. The findings demonstrate a facile biodegradable packaging route to improve food sustainability and reduce waste.

Star fruit (the fruit of Averrhoa carambola L., Oxalidaceae) is popular in tropical regions. Chemical study of the fruit yielded four new dihydrochalcone C-glycosides, carambolasides A (1), B (2), C (3), and D (4), in addition to hovertichoside C (5), isovitexin 2″-O-α-l-rhamnopyranoside (6), and carambolaflavone (7). Their structures were identified by spectroscopic and chemical methods, including electronic circular dichroism (ECD) calculation. Compounds 5–7 were reported from the fruit for the first time. Compounds 1–7 were evaluated for antioxidant activity using three assays. All of them exhibited 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical cation scavenging activity with IC50 values ranging from 7.6 to 3.9 µM, which were more potent than l-ascorbic acid (IC50 = 11.6 µM). However, they were inactive in scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and in ferric reducing antioxidant power (FRAP).

Two new quinone sesquiterpenes named myrothecols G and H (1 and 2), a pair of C-1′ diastereomers of 13-hydroxyl penicilliumin A, were isolated from the mycelia solid cultures of Myrothecium sp. SC0265. Their structures, including the absolute configurations, were established on the basis of the spectroscopic data combining with the theoretical conformational analysis. The cytotoxic activities of 1 and 2 were tested against a panel of human tumor cell lines.

Eight new compounds, sinulolides A–H (1–8), along with two known compounds, α-methoxy-2,3-dimethyl-butenolide (9) and sinularone D (10), were isolated from the soft coral Sinularia sp. The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis. The absolute configurations were determined on the basis of electronic circular dichroism (ECD) data analysis. Compounds 5 and 10 exhibited moderate effects for the inhibition of NF-κB activation.

The pericarp of Litchi chinensis was reported to be a rich source of antioxidants. This study aimed to identify the chemical structures present in litchi pericarp with antioxidant activity. Four lignans, (+)-isolariciresinol 9-O-α-l-arabinopyranoside (1), burselignan 9-O-α-l-arabinopyranoside (2), (−)-secoisolariciresinol 9-O-α-l-arabinopyranoside (3), and sisymbrifolin (4), a chromane, 2α-methoxychroman-3α,5,7-triol (5), a benzophenone, garcimangosone D (6), and two sesquiterpenes, β-d-glucopyranosyldihydrophaseate (7) and citroside A (8) were isolated. Their structures were elucidated by spectroscopic methods. Compounds 1–3, 5, and 7 were new metabolites and the others were reported from this species for the first time. Among them, compounds 1–5 showed moderate antioxidant activity in ferric reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assays.

Isodon lophathoides var. graciliflorus (Lamiaceae) has been used as an herb for making health beneficial beverages and an ingredient for making soup in China. This study revealed thirteen phenolic compounds isolated from the aerial parts of the herb for the first time. They were rosmarinic acid (1), methyl rosmarinate (2), clinopodic acid A (3), salvianolic acid A (4), nepetoidin B (5), caffeic acid (6), vinyl caffeate (7), danshensu (8), latifolicinin C (9), hydroxytyrosol (10), procatechuic aldehyde (11), 3,4-dihydroxybenzoic acid (12) and syringic acid (13). Their structures were determined by spectroscopic method including nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI-MS) and comparison of the data with the values reported in references. Ferric reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity of these compounds were evaluated, and compounds 1–8 and 13 were more potent or comparable to l-ascorbic acid. In addition, compounds 5 and 13 showed antibacterial activity against Staphyloccocus aureus and Shigella dysenteriae with IC50 values ranging from 44.15 to 79.13 μM, and compound 5 was also active towards Bacillus cereus.

In this study, we use an aqueous solution synthesis method to prepare silver perrhenate powders and suspend them into a poly alpha olefin (PAO) base oil with polyoxyethylene octylphenyl ether. Four ball tests and ball-on-disk reciprocating mode are performed to determine how silver perrhenate performs tribologically as a lubricating additive over a wide range of temperatures. The physical and chemical properties, as well as the lubricating mechanisms of the silver perrhenate additive, are characterized via X-ray diffraction, scanning electron microscope, Fourier transformation infrared spectroscopy, Raman spectrum, and X-ray photoelectron spectroscopy. The four-ball test results demonstrate that the oil added with silver perrhenate additive is more effective than the base oil in reducing friction and improving wear resistance, and provides the best lubricating performance when at a concentration of 0.5 wt%. The reciprocating mode findings indicate that the hybrid lubricant exhibits distinctively better tribological properties than the base oil at high temperatures, and its low shear strength and chemical inertness allow for low friction at elevated temperatures. The resulting silver perrhenate layer that incorporates native superalloy oxides on the worn surface can provide lubrication by serving as a barrier that prevents direct contact between the rubbing surfaces at elevated temperatures.

A new natural product named longanlactone was isolated from Dimocarpus longan Lour. seeds. Its structure was determined as 3-(2-acetyl-1H-pyrrol-1-yl)-5-(prop-2-yn-1-yl)dihydrofuran-2(3H)-one by spectroscopic methods and HRESIMS.

The allelopathic effects of different parts of the plant Xanthium italicum Moretti were evaluated by conducting bioassays against two dicot plants, amaranth (Amaranthus mangostanus L.) and lettuce (Lectuca sativa L.), and two monocot plants, wheat (Triticum aestivum Linn) and ryegrass (Lolium multiforum). Leaf and fruit extract possessed the strongest biological activity, killing all seeds of four test species at 0.05 g/mL concentration. Fruits were chosen for further investigation because of their high biomass. This led to the isolation and identification of a phytotoxin—Xanthinosin—a known sesquiterpene lactone. Xanthinosin significantly affected seedling growth of all test species at 160 µM concentration. Cultivating seeds in 800 μM xanthinosin solution resulted in a great decrease in seedling growth of all test species, especially for the two dicot plants, amaranth and lettuce, whose root length was inhibited by 78% and 89%, respectively. By comparison, the numbers were 69% lower for wheat, and 66% for ryegrass, two monocot plants. When treated with 4 mM xanthinosin solution, seed germination of all test plants was almost completely inhibited. The possibility of utilizing xanthinosin as an eco-friendly herbicide was discussed.

An activity-directed fractionation and purification process was used to isolate antioxidant components from cassava stems produced in Hainan. The ethyl acetate and n-butanol fractions showed greater DPPH˙and ABTS·+ scavenging activities than other fractions. The ethyl acetate fraction was subjected to column chromatography, to yield ten phenolic compounds: Coniferaldehyde (1), isovanillin (2), 6-deoxyjacareubin (3), scopoletin (4), syringaldehyde (5), pinoresinol (6), p-coumaric acid (7), ficusol (8), balanophonin (9) and ethamivan (10), which possess significant antioxidant activities. The relative order of DPPH· scavenging capacity for these compounds was ascorbic acid (reference) > 6 > 1 > 8 > 10 > 9 > 3 > 4 > 7 > 5 > 2, and that of ABTS·+ scavenging capacity was 5 > 7 > 1 > 10 > 4 > 6 > 8 > 2 > Trolox (reference compound) > 3 > 9. The results showed that these phenolic compounds contributed to the antioxidant activity of cassava.

Chinese water chestnut (CWC) is one of the most popular foods among Asian people due to its special taste and medical function. Experiments were conducted to test the antioxidant activity and then determine the major phenolic compound components present in CWC. CWC phenolic extract strongly inhibited linoleic acid oxidation and exhibited a dose-dependent free-radical scavenging activity against α,α-diphenyl-β-picrylhydrazyl (DPPH) radicals, superoxide anions and hydroxyl radicals, which was superior to ascorbic acid and butylated hydroxytoluene (BHT), two commercial used antioxidants. Furthermore, the CWC extract was found to have a relatively higher reducing power, compared with BHT. The major phenolic compounds present in CWC tissues were extracted, purified and identified by high-performance liquid chromatograph (HPLC) as (–)-gallocatechin gallate, (–)-epicatechin gallate and (+)-catechin gallate. This study suggests that CWC tissues exhibit great potential for antioxidant activity and may be useful for their nutritional and medicinal functions.

A new cerebroside, 1-O-β-D-glucopyranosyl-(2S,3R,8E)-2-[(2’R)-2-hydroxy- palmitoylamino]-8-octadecene-1,3-diol, along with aralia cerebroside and 1-O-β-D- glucopyranosyl-(2S,3S,4R,8E)-2-[(2’R)-2-hydroxybehenoylamino]-8-octadecene-1,3,4-triol were isolated from the roots of Serratula chinensis S. Moore. The structure of the new cerebroside was established by spectroscopic and chemical means. Occurrence of cerebrosides in Serratula is reported here for the first time.