Gram matrix: an efficient representation of molecular conformation and learning objective for molecular pretraining.

Accurate prediction of molecular properties is fundamental in drug discovery and development, providing crucial guidance for effective drug design. A critical factor in achieving accurate molecular property prediction lies in the appropriate representation of molecular structures. Presently, prevalent deep learning-based molecular representations rely on 2D structure information as the primary molecular representation, often overlooking essential three-dimensional (3D) conformational information due to the inherent limitations of 2D structures in conveying atomic spatial relationships. In this study, we propose employing the Gram matrix as a condensed representation of 3D molecular structures and for efficient pretraining objectives. Subsequently, we leverage this matrix to construct a novel molecular representation model, Pre-GTM, which inherently encapsulates 3D information. The model accurately predicts the 3D structure of a molecule by estimating the Gram matrix. Our findings demonstrate that Pre-GTM model outperforms the baseline Graphormer model and other pretrained models in the QM9 and MoleculeNet quantitative property prediction task. The integration of the Gram matrix as a condensed representation of 3D molecular structure, incorporated into the Pre-GTM model, opens up promising avenues for its potential application across various domains of molecular research, including drug design, materials science, and chemical engineering.

KinomeMETA: meta-learning enhanced kinome-wide polypharmacology profiling.

Kinase inhibitors are crucial in cancer treatment, but drug resistance and side effects hinder the development of effective drugs. To address these challenges, it is essential to analyze the polypharmacology of kinase inhibitor and identify compound with high selectivity profile. This study presents KinomeMETA, a framework for profiling the activity of small molecule kinase inhibitors across a panel of 661 kinases. By training a meta-learner based on a graph neural network and fine-tuning it to create kinase-specific learners, KinomeMETA outperforms benchmark multi-task models and other kinase profiling models. It provides higher accuracy for understudied kinases with limited known data and broader coverage of kinase types, including important mutant kinases. Case studies on the discovery of new scaffold inhibitors for membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase and selective inhibitors for fibroblast growth factor receptors demonstrate the role of KinomeMETA in virtual screening and kinome-wide activity profiling. Overall, KinomeMETA has the potential to accelerate kinase drug discovery by more effectively exploring the kinase polypharmacology landscape.

Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: ClinicalTrail.gov NCT05782192.

A Model of Basement Membrane-Associated Gene Signature Predicts Liver Hepatocellular Carcinoma Response to Immune Checkpoint Inhibitors.

Liver hepatocellular carcinoma (LIHC) is a highly lethal malignant tumor originating from the digestive system, which is a serious threat to human health. In recent years, immunotherapy has shown significant therapeutic effects in the treatment of LIHC, but only for a minority of patients. The basement membrane (BM) plays an important role in the occurrence and development of tumors, including LIHC. Therefore, this study is aimed at establishing a risk score model based on basement membrane-related genes (BMRGs) to predict patient prognosis and response to immunotherapy. First, we defined three patterns of BMRG modification (C1, C2, and C3) by consensus clustering of BMRG sets and LIHC transcriptome data obtained from public databases. Survival analysis showed that patients in the C2 group had a better prognosis, and Gene Set Variation Analysis (GSVA) revealed that the statistically significant pathways were mainly enriched in the C2 group. Moreover, we performed Weighted Correlation Network Analysis (WGCNA) on the above three subgroups and obtained 179 intersecting genes. We further applied function enrichment analyses, and the results demonstrated that they were mainly enriched in metabolism-related pathways. Furthermore, we conducted the LASSO regression analysis and obtained 4 BMRGs (MPV17, GNB1, DHX34, and MAFG) that were significantly related to the prognosis of LIHC patients. We further constructed a prognostic risk score model based on the above genes, which was verified to have good predictive performance for LIHC prognosis. In addition, we analyzed the correlation between the risk score and the tumor immune microenvironment (TIM), and the results showed that the high-risk scoring group tended to be in an immunosuppressed status. Finally, we investigated the relationship between the risk score and LIHC immune function. The results demonstrated that the risk score was closely related to the expression levels of multiple immune checkpoints. Patients in the low-risk group had significantly higher IPS scores, and patients in the high-risk group had lower immune escape and TIDE score. In conclusion, we established a novel risk model based on BMRGs, which may serve as a biomarker for prognosis and immunotherapy in LIHC.

GPR176 Is a Biomarker for Predicting Prognosis and Immune Infiltration in Stomach Adenocarcinoma.

Immunotherapy based on immune checkpoint inhibitors (ICIs) is considered to be a promising treatment for stomach adenocarcinoma (STAD), but only a minority of patients benefit from it. It is believed that the poor therapeutic efficacy is attributed to the complex tumor immune microenvironment (TIM) of STAD. Therefore, elucidating the specific regulatory mechanism of TIM in STAD is critical. Previous study suggests that GRP176 may be involved in regulating the pace of circadian behavior, and its role in tumors has not been reported. In this study, we first found that GPR176 was highly expressed in STAD and negatively correlated with patient prognosis. Next, we investigated the relationship between GPR176 and clinical characteristics, and the results showed that the stage is closely related to the level of GPR176. In addition, our further analysis found that GRP176 expression level was significantly correlated with chemotherapeutic drug sensitivity and ICI response. KEGG and GO analyses showed that GPR176 might be involved in stromal remodeling of STAD. Furthermore, we analyzed the association between GPR176 expression and immune implication, and the results revealed that GPR176 was negatively related to the infiltration of various immune cells. Interestingly, GPR176 induced the conversion of TIM while reducing the tumor immune burden (TMB). The expression of GRP176 is closely related to the level of various immunomodulators. Moreover, we performed univariate and multivariate regression analyses on the immunomodulators and finally obtained 4 genes (CRCR4, TNSF18, PDCD1, and TGFB1). Then, we constructed a GRP176-related immunomodulator prognostic model (GRIM) based on the above 4 genes, which was validated to have good predictive power. Finally, we developed a nomogram based on the risk score of GRIM and verified its accuracy. These results suggested that GPR176 is closely related to the prognosis and TIM of STAD. GPR176 may be a new potential target for immunotherapy in STAD.

Use of Consumer Wearables in Health Research: Issues and Considerations.

As wearable devices, which allow individuals to track and self-manage their health, become more ubiquitous, the opportunities are growing for researchers to use these sensors within interventions and for data collection. They offer access to data that are captured continuously, passively, and pragmatically with minimal user burden, providing huge advantages for health research. However, the growth in their use must be coupled with consideration of their potential limitations, in particular, digital inclusion, data availability, privacy, ethics of third-party involvement, data quality, and potential for adverse consequences. In this paper, we discuss these issues and strategies used to prevent or mitigate them and recommendations for researchers using wearables as part of interventions or for data collection.

A Liquid-Liquid-Solid System to Manipulate the Cascade Reaction for Highly Selective Electrosynthesis of Aldehyde.

Electrocatalytic synthesis of aldehydes from alcohols exhibits unique superiorities as a promising technology, in which cascade reactions are involved. However, the cascade reactions are severely limited by the low selectivity resulting from the peroxidation of aldehydes in a traditional liquid-solid system. Herein, we report a novel liquid-liquid-solid system to regulate the selectivity of benzyl alcohol electrooxidation. The selectivity of benzaldehyde increases 200-fold from 0.4 % to 80.4 % compared with the liquid-solid system at a high current density of 136 mA cm-2 , which is the highest one up to date. In the tri-phase system, the benzaldehyde peroxidation is suppressed efficiently, with the conversion of benzaldehyde being decreased from 87.6 % to 3.8 %. The as-produced benzaldehyde can be in situ extracted to toluene phase and separated from the electrolyte to get purified benzaldehyde. This strategy provides an efficient way to efficiently enhance the selectivity of electrocatalytic cascade reactions.

The Euscaphis japonica genome and the evolution of malvids.

Malvids is one of the largest clades of rosids, includes 58 families and exhibits remarkable morphological and ecological diversity. Here, we report a high-quality chromosome-level genome assembly for Euscaphis japonica, an early-diverging species within malvids. Genome-based phylogenetic analysis suggests that the unstable phylogenetic position of E. japonica may result from incomplete lineage sorting and hybridization event during the diversification of the ancestral population of malvids. Euscaphis japonica experienced two polyploidization events: the ancient whole genome triplication event shared with most eudicots (commonly known as the γ event) and a more recent whole genome duplication event, unique to E. japonica. By resequencing 101 samples from 11 populations, we speculate that the temperature has led to the differentiation of the evergreen and deciduous of E. japonica and the completely different population histories of these two groups. In total, 1012 candidate positively selected genes in the evergreen were detected, some of which are involved in flower and fruit development. We found that reddening and dehiscence of the E. japonica pericarp and long fruit-hanging time promoted the reproduction of E. japonica populations, and revealed the expression patterns of genes related to fruit reddening, dehiscence and abscission. The key genes involved in pentacyclic triterpene synthesis in E. japonica were identified, and different expression patterns of these genes may contribute to pentacyclic triterpene diversification. Our work sheds light on the evolution of E. japonica and malvids, particularly on the diversification of E. japonica and the genetic basis for their fruit dehiscence and abscission.

Pickering Emulsion Catalysis: Interfacial Chemistry, Catalyst Design, Challenges, and Perspectives.

Pickering emulsions are particle-stabilized surfactant-free dispersions composed of two immiscible liquid phases, and emerge as attractive catalysis platform to surpass traditional technique barrier in some cases. In this review, we have comprehensively summarized the development and the catalysis applications of Pickering emulsions since the pioneering work in 2010. The explicit mechanism for Pickering emulsions will be initially discussed and clarified. Then, summarization is given to the design strategy of amphiphilic emulsion catalysts in two categories of intrinsic and extrinsic amphiphilicity. The progress of the unconventional catalytic reactions in Pickering emulsion is further described, especially for the polarity/solubility difference-driven phase segregation, "smart" emulsion reaction system, continuous flow catalysis, and Pickering interfacial biocatalysis. Challenges and future trends for the development of Pickering emulsion catalysis are finally outlined.

Recognition of Water-Induced Effects toward Enhanced Interaction between Catalyst and Reactant in Alcohol Oxidation.

Pickering emulsion stabilized by solid nanoparticles provides a diverse solvent microenvironment and enables to promote the phase transfer of reaction substrates/products in catalytic reactions, but the intrinsic role of solvent is still not clear. Herein, using benzyl alcohol (BA) as a model reactant, we demonstrate the nature of the water-promoted activity for alcohol oxidation over the Pd/MgAl-LDO catalyst. Depending on the water in the solvent, we observe different reactivities regarding the proportion of the water in the system. Kinetic isotope effects confirm the participation and positive effects of water for oxidation of BA. The water promotion effects are recognized and identified by the water vapor pulse adsorption coupled with temperature program desorption. Moreover, the adsorption behavior of BA or benzaldehyde at the interface of water and Pd/MgAl-LDO is also investigated by quasi-in-situ Raman spectroscopy. In addition, the mechanism of water-promoted alcohol oxidation is rationally proposed based on the Langmuir-Hinshelwood mechanism. The general applicability of the water promotion effects is further demonstrated over different supports and substrates, which well achieves excellent catalytic activity and selectivity in Pickering emulsion compared to that in the pure toluene system.

Retracted: The Effects of Ludartin on Cell Proliferation, Cell Migration, Cell Cycle Arrest and Apoptosis Are Associated with Upregulation of p21WAF1 in Saos-2 Osteosarcoma Cells In Vitro.

The authors repeated experiments and found that the results shown in figure 2 were not reproducible. Reference: Shuang-li Zhang, Bao-lin Li, Wei Li, Ming Lu, Lin-ying Ni, Hui-li Ma, Qing-gang Meng. The Effects of Ludartin on Cell Proliferation, Cell Migration, Cell Cycle Arrest and Apoptosis Are Associated with Upregulation of p21WAF1 in Saos-2 Osteosarcoma Cells In Vitro. Med Sci Monit 2018; 24: LBR4926-4933. 10.12659/MSM.909193.

[Evolution of Sichuan Dao-di herbs recorded in ancient works of materia medica of different historical periods].

Sichuan province is very famous for its abundant resources of traditional Chinese medicine(TCM).However, within the scope of administrative division of Sichuan province, the origin records of Dao-di herbs in different historical periods show a dynamic distribution process. On the basis of carefully sorting out the geographical scope of Sichuan province in different historical periods, this article focuses on the textual research of the Dao-di herbs in Sichuan province recorded in the seven mainstream ancient works of materia medica.The results showed that, according to the records of Mingyi bielu and Bencaojing Jizhu, the main distribution areas of Dao-di herbs were mainly in the central and eastern regions of Sichuan province, mainly including Moschus, Coptidis Rhizoma, Zingiberis Rhizoma, Aconiti Lateralis Radix Praeparata and most of the rest materia medica had become unused in the historical process. Qianjin Yifang records that the distribution areas of Dao-di herbs were mainly in the middle and eastern part of Sichuan province.Aconiti Radix, Lateralis Radix Praeparata, Zingiberis Rhizoma, Notopterygii Rhizoma et Radix are still the Dao-di herbs of Sichuan province. According to the book of Bencao Tujing,the main distribution areas of Dao-di herbs are Chengdu Plain, Yibin and Santai, While Toosendan Fructus, Chuanxiong Rhizoma, Zanthoxyli Pericarpium, Aconiti Radix are still the Dao-di herbs of Sichuan province. Ben Cao Gang Mu records the place of origin as Sichuan.Coptidis Rhizoma, Toosendan Fructus, Cyathulae Radix are still the Dao-di herbs of Sichuan pro-vince. Yaowu Chuchanbian and Zengding Weiyao Tiaobian records the place of origin as Sichuan, as well as Kangding, Songpan, Dujiang-yan, Jiangyou, Nanchong, Ya'an, etc. Moschus, Coptidis Rhizoma, Eucommiae Cortex, Phellodendri Chinensis Cortex are still the Dao-di herbs of Sichuan province. The results of this article provide a new understanding of the history and distribution changes of Dao-di herbs in Sichuan province, and can help to further understand the formation connotation of Sichuan Dao-di herbs.

[A new lignan from Euscaphis konishii].

The chemical constituents from the extract of the twigs of Euscaphis konishii with anti-hepatoma activity were investigated, twelve compounds by repeated chromatography with silica gel, Sephadex LH-20 and preparative-HPLC. The structures of the chemical components were elucidated by spectroscopy methods, as konilignan(1),(7R, 8S)-dihydrodehydrodico-niferylalcohol-9-O-ß-D-glucopyranoside(2),illiciumlignan B(3),threo-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-panediol(4),erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-panediol(5), matairesinol(6), wikstromol(7), isolariciresinol(8),(+)-lyoniresinol(9), 4-ketopinoresinol(10), syringaresin(11), and vladinol D(12). Among them, compound 1 is a new lignan. Compounds 10 and 12 had moderate inhibitory activity on HepG2 cells, with IC_(50) values of 107.12 µmol·L~(-1) and 183.56 µmol·L~(-1), respectively.

[Chemical constituents from the leaves of Cinnamomum camphora var. linaloolifera and their anti-inflammatory activities].

Thirteen compounds were isolated and purified from the leaves of Cinnamomum camphora by the macroporous resin,silica gel,and Sephadex LH-20 column chromatographies. Those compounds were further identified by IR,UV,MS,and NMR techniques:( 2 S)-1-( 3″,4″-methylenedioxy phenyl)-3-( 2',6'-dimethoxy-4'-hydroxyphenyl)-propan-2-ol( 1),( 2 R,3 R)-5,7-dimethoxy-3',4'-methylenedioxy flavanol( 2),9-hydroxysesamin( 3),sesamin( 4),piperitol( 5),kobusin( 6),(-)-aptosimon( 7),acuminatolide( 8),1ß,11-dihydroxy-5-eudesmene( 9),lasiodiplodin( 10),vanillin( 11),p-hydroxybenzaldehyde( 12),and p-hydroxybenzoic acid ethyl ester( 13). Compound 1 was a novel compound,and compounds 2,6,7,9 and 10 were isolated from Cinnamomum plants for the first time. Compounds 4,7 and 10 were found to possess good inhibitory effect on IL-6 production in LPS-induced BV2 cells at a concentration of 20 µmol·L-1 in the in vitro bioassay,with inhibition rates of 51. 26% ± 4. 13%,67. 82% ± 3. 77% and85. 81%±1. 19%,respectively.

Evaluation of a risk index for predicting short-term and long-term outcomes in patients with ST-elevation myocardial infarction.

OBJECTIVE: This study aimed to evaluate the usefulness of the admission risk index (RI) to predict short-term and long-term outcomes in a broad population with ST-elevation myocardial infarction (STEMI) using data from the Chinese Acute Myocardial Infarction Registry. BACKGROUND: The RI was developed as a simple tool to predict risk of death in STEMI patients. The performance in predicting short-term and long-term risk of death in Chinese patients receiving percutaneous coronary intervention and conservative treatment for STEMI remains unclear. METHODS: Age, heart rate (HR), and systolic blood pressure (SBP) were used to calculate RI using (HR×[age/10]2 )/SBP. We used the prediction tool to predict mortality over 12 months. RESULTS: The C-index of the admission RI for predicting in-hospital, 1-, 6-, and 12-months mortality were 0.78, 0.78, 0.78, and 0.77, respectively, compared with 0.75 of the Global Registry in Acute Coronary Events score. Based on the receiver operating characteristic curve analysis, the RI was categorized into quintiles for convenient clinical use, and it revealed a nearly 15-fold gradient of increasing mortality from 2.29 to 32.5% (p < .0001) while RI >34 had the highest mortality. By categorizing into five different risk groups, the short-term and long-term mortality of patients receiving different treatments could be distinguished. CONCLUSIONS: RI based on three routine variables and easily calculated by any medical practitioner is useful for predicting in-hospital and long-term mortality in patients with STEMI at the initial consultation with clinicians.

[Research progress on production districts of Sichuan Dao-di herbs].

Dao-di herbs are the Chinese herbs which have high quality and best clinic effects. Sichuan is one of the proviences most rich in Chinese herb resources,which has 7 290 species of Chinese herbs, such as Curcumae Longae Rhizoma, Chuanxiong Rhizoma, Aconiti Lateralis Radix Praeparata, Ophiopogonis Radix, Coptidis Rhizoma, Gentianae Radix, Rhei Radix et Rhizoma, Curcumae Rhizoma, Gardeniae Fructus, ect. After textual research on materia medica of the 7 290 Chinese herbs, we find there are 86 Dao-di herbs in Sichuan, such as Chuanxiong Rhizoma from Dujiangyan, Aconiti Lateralis Radix Praeparata from Jiangyou, Fritillariae Radix, Notoptergii Rhizoma et Radix, Angelicae Dahuricae Radix from Suining, Ophiopogonis Radix from Santai, Salviae Miltiorrhizae Radix et Rhizoma from Zhongjiang, Magnoliae Officinalis Cortex from Pingwu. In China more attention is paid to the production of Dao-di herbs. In 2018, the State Administration of Traditional Chinese Medicine launched the "Construction Plan of national production base of genuine medicinal materials". Developing genuine medicinal materials in genuine production areas is one of the effective ways to ensure the quality of medicinal materials. Based on the study of geographical environment and ecological factors(altitude, climate, soil) in Sichuan province. The Dao-di herbs of Sichuan province are divided into 4 districts, including, Sichuan basin medicinal materials production area, mountain and the basin edge medicinal materials production area, Panxi medicinal materials production area, Plateau Mountain Canyon medicinal materials production area. The suitable regions and best suitable regions of the 86 Dao-di herbs in Sichuan are determined by remote sensing and GIS spatial analysis of the suitable environmental indicators of these Dao-di herbs. Our study is beneficial to the rational distribution of the production and to improvement of the quality of traditional Chinese medicine in Sichuan province.

Comparative transcriptome among Euscaphis konishii Hayata tissues and analysis of genes involved in flavonoid biosynthesis and accumulation.

BACHGROUND: Euscaphis konishii Hayata, a member of the Staphyleaceae Family, is a plant that has been widely used in Traditional Chinese Medicine and it has been the source for several types of flavonoids. To identify candidate genes involved in flavonoid biosynthesis and accumulation, we analyzed transcriptome data from three E. konishii tissues (leaf, branch and capsule) using Illumina Hiseq 2000 platform. RESULTS: A total of 91.7, 100.3 and 100.1million clean reads were acquired for the leaf, branch and capsule, respectively; and 85,342 unigenes with a mean length of 893.60 bp and N50 length of 1307 nt were assembled using Trinity program. BLASTx analysis allowed to annotate 40,218 unigenes using public protein databases, including NR, KOG/COG/eggNOG, Swiss-Prot, KEGG and GO. A total of 14,291 (16.75%) unigenes were assigned to 128 KEGG pathways, and 900 unigenes were annotated into 22 KEGG secondary metabolites, including flavonoid biosynthesis. The structure enzymes involved in flavonoid biosynthesis, such as phenylalanine ammonia lyase, cinnamate 4-hydroxylase, 4-coumarate CoA ligase, shikimate O-hydroxycinnamoyltransferase, coumaroylquinate 3'-monooxygenase, caffeoyl-CoA O-methyltransferase, chalcone synthase, chalcone isomerase, flavanone 3-hydroxylase, flavonoid 3'-hydroxylase, flavonoid 3',5'-hydroxylase, flavonolsynthese, dihydroflavonol 4-reductase, anthocyanidinreductase, leucoanthocyanidin dioxygenase, leucoanthocyanidin reductase, were identified in the transcriptome data, 40 UDP-glycosyltransferase (UGT), 122 Cytochrome P450 (CYP) and 25 O-methyltransferase (OMT) unigenes were also found. A total of 295 unigenes involved in flavonoid transport and 220 transcription factors (97 MYB, 84 bHLH and 39 WD40) were identified. Furthermore, their expression patterns among different tissues were analyzed by DESeq, the differentially expressed genes may play important roles in tissues-specific synthesis, accumulation and modification of flavonoids. CONCLUSION: We present here the de novo transcriptome analysis of E. konishii and the identification of candidate genes involved in biosynthesis and accumulation of flavonoid. In general, these results are an important resource for further research on gene expression, genomic and functional genomics in E. konishii and other related species.

Low-Temperature Fast Production of Carbon and Acetic Acid Dual-Promoted Pd/C Catalysts.

The Pd/C catalysts are widely used in synthesis of fine chemicals in industry, but their production suffers from a complicated two-step process involving impregnation and reduction, and requires large amounts of solvents and reductant, which would lead to a series of issues such as time consumption, resource waste and environmental pollution. Herein, ultra-small Pd nanoparticles uniformly anchored on carbon nanotubes (Pd/CNTs) were synthesized by using a one-pot and low-temperature reduction strategy. The present process/technology is very sensitive to and controlled by the supports and solvents, and the carbon support and acetic acid synergistically play crucial and decisive roles in the fast production of Pd/C catalysts. Also, the used solvents can be recycled and reutilized, which meets the requirements of sustainable chemistry and green economy. When the as-obtained Pd/CNTs catalyst was used to catalyze the oxidation of benzyl alcohol to benzaldehyde, it achieved a conversion efficiency as high as 99.3 % and a high selectivity up to >99.9 %. The simple, scalable and environmentally friendly strategy can be extended to anchor Pd nanoparticles on various carbon substrates, which sheds a new light on the synthesis of Pd/C catalysts.

The isolation, absolute configuration and activities of 18(4 → 3)-abeo-abietane lactones from Tripterygium wilfordii.

Phytochemical studies on the leaves of Tripterygium wilfordii led to the isolation of seven new 18(4 → 3)-abeo-abietane lactones, triptergulides E - K (1 - 7). The structure of the new compounds was elucidated on the basis of their spectroscopic analysis, and the absolute configurations of compounds were confirmed by ECD, calculated ECD, and X-ray crystallographic analysis using anomalous scattering of Cu Kα radiation. Some compounds showed moderate inhibitory activities against NO, IL-6, and TNF-α production in LPS RAW 264.7 macrophage in vitro.

Hypoxia-activated cytotoxic agent tirapazamine enhances hepatic artery ligation-induced killing of liver tumor in HBx transgenic mice.

Transarterial chemoembolization (TACE) is the main treatment for intermediate stage hepatocellular carcinoma (HCC) with Barcelona Clinic Liver Cancer classification because of its exclusive arterial blood supply. Although TACE achieves substantial necrosis of the tumor, complete tumor necrosis is uncommon, and the residual tumor generally rapidly recurs. We combined tirapazamine (TPZ), a hypoxia-activated cytotoxic agent, with hepatic artery ligation (HAL), which recapitulates transarterial embolization in mouse models, to enhance the efficacy of TACE. The effectiveness of this combination treatment was examined in HCC that spontaneously developed in hepatitis B virus X protein (HBx) transgenic mice. We proved that the tumor blood flow in this model was exclusively supplied by the hepatic artery, in contrast to conventional orthotopic HCC xenografts that receive both arterial and venous blood supplies. At levels below the threshold oxygen levels created by HAL, TPZ was activated and killed the hypoxic cells, but spared the normoxic cells. This combination treatment clearly limited the toxicity of TPZ to HCC, which caused the rapid and near-complete necrosis of HCC. In conclusion, the combination of TPZ and HAL showed a synergistic tumor killing activity that was specific for HCC in HBx transgenic mice. This preclinical study forms the basis for the ongoing clinical program for the TPZ-TACE regimen in HCC treatment.