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AbstractTwo new cucurbitane-type triterpenoid saponins, 2,20β,22β-trihydroxy-16α,23(R)-epoxycucurbita-1,5,24-triene-3,11-dione 2-O-β-D-glucopyranoside (1), 2,20β,22α-trihydroxy-16α,23(S)-epoxycucurbita-1,5,11,24-tetraene-3-one 2-O-β-D-glucopyranoside (2) were isolated from the fruit of Citrullus colocynthis (L.) Schrad. Their structures were elucidated by mass spectrometry, IR, 1D, and 2D NMR spectroscopy, etc. Besides, both of the compounds showed significant hepatoprotective activities at 10 μM against paracetamol-induced HepG2 cell damage. [ABSTRACT FROM AUTHOR]

The authors review the literature on last mile delivery logistics within commercial and humanitarian supply chains from 2010 to the end of 2021. The scope of the last mile, including last mile logistics, last mile distribution, and last-mile mile delivery, is covered. A unifying terminology of the major concepts in this field and a bibliometric analysis are provided. Based on the analysis, the authors further classify and discuss the literature into three clusters: humanitarian relief, commercial logistics, and emerging technologies. Within each generated cluster, research gaps and current trends are identified. Future research directions are suggested based on this literature review. [ABSTRACT FROM AUTHOR]

The cervical spine injury is a complicated procedure in the combination of different injury loads and postures. The aim of this study is to investigate the injury mechanism considering different types of cervical curvatures subjected to contusion loads. A finite element model of a cervical spinal cord was constructed. Gray matter, white matter and pia matter were modeled and hyperelastic material properties were assigned. Convergence analysis and validation analysis were carried out. The model was simulated in 3 different spinal curvatures and loaded by 2 directions with 4 compression degrees. The maximum von Mises stress in the whole model was concentrated in the pia matter in all loading cases. When investigating spinal cord injury, the pia matter must be considered. For all three curvatures, the stress in the gray matter and white matter was higher in front-to-back loading condition than that in back-to-front loading condition. The front-to-back impact may cause a larger damage. A back-to-front load damaged the structure around the central canal and a front-to-back contusion load damaged the anterior horn of the spinal cord at most time. From the view of the maximum stress, the lordotic curvature did not show significant buffering effect. However, the pathological curvature had large areas affected and the lordotic curvature showed some benefits to some degree from the view of stress distribution. [ABSTRACT FROM AUTHOR]

Spermatogenesis process plays a major role in male fertility. Quercetin, a flavonoid, is found in daily food or traditional Chinese medicine, which has a significant effect on treating inflammatory diseases. Several studies have shown that quercetin can improve male spermatogenesis. However, the intrinsic mechanism has not been systematically investigated. The network pharmacology approaches were utilized to investigate the mechanisms of quercetin against spermatogenesis impairment (SI). 78 potential therapeutic targets of quercetin against SI were identified. The enrichment analysis showed that the mechanism of quercetin on SI is closely related to its anti-inflammatory pharmacological effects. It is indicated that quercetin could be used for treating SI through inflammation-related targets or pathways including NF-κB, MAPK, JAK-STAT and Toll-like receptor signaling pathways. [ABSTRACT FROM AUTHOR]

Tubulin polymerisation inhibitors that target colchicine binding site were powerful anticancer agents. Although along the years many colchicine binding site inhibitors (CBSIs) have been reported, few piperidine derivatives were identified as CBSIs. In this regard, we focussed efforts on the piperidine as a promising chemotype to develop potent CBSIs. Herein, novel piperidine derivatives were synthesised and evaluated for their antiproliferative activities. Among them, compound 17a displayed powerful anticancer activity with the IC50 value of 0.81 µM against PC3 cells, which was significantly better than 5-fluorouracil. It could inhibit tubulin polymerisation binding at the colchicine site and inhibit the tumour growth in vitro and in vivo. Further biological studies depicted that 17a suppressed the colony formation, induced apoptosis, and inhibited epithelial-mesenchymal transition against PC3 cells. These results revealed that compound 17a is a promising colchicine binding site inhibitor for the treatment of cancer and it is worthy of further exploitation. [ABSTRACT FROM AUTHOR]

Tubulin polymerisation inhibitors exhibited an important role in the treatment of patients with prostate cancer. Herein, we reported the medicinal chemistry efforts leading to a new series of benzothiazoles by a bioisosterism approach. Biological testing revealed that compound 12a could significantly inhibit in vitro tubulin polymerisation of a concentration dependent manner, with an IC50 value of 2.87 μM. Immunofluorescence and EBI competition assay investigated that compound 12a effectively inhibited tubulin polymerisation and directly bound to the colchicine-binding site of β-tubulin in PC3 cells. Docking analysis showed that 12a formed hydrogen bonds with residues Tyr357, Ala247 and Val353 of tubulin. Importantly, it displayed the promising antiproliferative ability against C42B, LNCAP, 22RV1 and PC3 cells with IC50 values of 2.81 μM, 4.31 μM, 2.13 μM and 2.04 μM, respectively. In summary, compound 12a was a novel colchicine site tubulin polymerisation inhibitor with potential to treat prostate cancer. [ABSTRACT FROM AUTHOR]

With increasing international trade, food safety is becoming a global health concern, the requirement for food quality increases constantly. There is an urgent need for a new method to identify the potential problems and support policies for regulations. Metabonomics is an advanced tool suitable for the analysis of food safety. This paper shows that metabonomics has favorable prospects for applications in veterinary drugs, banned substances, safety evaluation of genetically modified food, food adulteration, and foodborne illnesses. Although metabonomics has been proven as a useful tool for food safety risk monitoring and assessment, there are still some significant challenges existing in its application. [ABSTRACT FROM AUTHOR]

In this study, phytoremediation of polycyclic aromatic hydrocarbon (PAH)-contaminated sediments with different contents of sediment organic matter (SOM) by Potamogeton crispus L. was investigated to find out the key factor controlling PAH dissipation enhancements. After a 36-day experiment, dissipation ratios of phenanthrene and pyrene in sediments were improved by P. crispus but decreased with increasing SOM content, no matter with or without P. crispus. Furthermore, the results of polyphenol oxidase activity and PAH bioavailability showed that they were both higher in planted treatments than in unplanted treatments. Finally, the enhancements of rapidly desorbing fraction (i.e., the main portion to be readily biodegradable) in sediments with SOM contents of 1.20%, 3.14%, and 5.08% by plants were 20.0%, 40.7%, and 66.7% for phenanthrene, 22.2%, 36.8%, and 58.8% for pyrene, respectively, which is consistent with the change trends of dissipation enhancements of the contaminants in sediments. However, there was no significant correlation between the enhancement of polyphenol oxidase activity and the dissipation enhancement. These results suggested that the improved bioavailability by P. crispus should be the key factor leading to the dissipation enhancements of the contaminants in sediments with different SOM contents, which provides essential information for phytoremediation of PAH-contaminated sediments. [ABSTRACT FROM AUTHOR]

Six palladium(II) complexes, [Pd(bipy)(Bzphe-N,O)] (I-a), [Pd(bipy)(p-Mbzphe-N,O)]·2H2O (I-b), [Pd(bipy)(p-Nbzphe-N,O)]·2H2O (I-c), [Pd(phen)(Bmined by X-ray diffraction. The cytotoxicity test indicates that the complexes exert cytotoxic effects against KB, BGC-823, Bel-7402, and HL-60, but none of them shows higher cytotoxicity than cisplatin. The structure-activity relationship suggests that bomined by X-ray diffraction. The cytotoxicity test indicates that the complexes exert cytotoxic effects against KB, BGC-823, Bel-7402, and HL-60, but none of them shows higher cytotoxicity than cisplatin. The structure-activity relationship suggests that bothN-containing ligands andN-carbonyl reagent have important effect on cytotoxicity, however, the IC50values do not show definite correlation with their variation. [ABSTRACT FROM PUBLISHER]

Two new ruthenium(II) complexes, [Ru(dmp)2(BHIP)]2+ (1) and [Ru(dmb)2(BHIP)]2+ (2), were synthesized and characterized by elemental analysis, ESI-MS, and 1H NMR. DNA-binding constants of these complexes with calf-thymus DNA (ct-DNA) were determined to be 2.09 (±0.18) × 104 (mol L−1)−1 (s = 2.58) and 1.48 (±0.17) × 105 (mol L−1)−1 (s = 1.57), respectively. Viscosity measurements show that 1 and 2 interact with ct-DNA by intercalation. Upon irradiation at 365 nm, 1 and 2 induce cleavage of pBR322 DNA. The cytotoxicity of these complexes was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis induced by the complexes was studied by flow cytometry. The results of the cell cycle arrest show that 2 can inhibit the proliferation of BEL-7402 cells in the G0/G1 phase. [ABSTRACT FROM PUBLISHER]

A 2D cadmium(II) coordination polymer with oxalate and 2,2'-bipyridine, [Cd2(bpy)(ox)2(H2O)2]n · nH2O, was synthesized and the single crystal structure was determined by X-ray crystallography. Thermal properties and the decomposition kinetics of the title complex were studied showing that the decomposition of this complex in N2 is a two-step process, A [image omitted]. Kinetic parameters were obtained. [ABSTRACT FROM AUTHOR]

Platelets are major sources of microparticles (MPs) in peripheral bloodstream, and platelet-secreted MPs (P-MPs) transfer biological information to neighboring cells. In the present study, we found that the platelet- and P-MPs-derived microRNA-4306 (miR-4306) expression were downregulated in coronary artery disease (CAD) and platelet-derived miR-4306 was an independent poor prognostic factor in CAD. Plasma miRNA-4306 mainly cofractionated with MPs instead of Argonaute2 complexes or HDL. P-MPs could effectively deliver miR-4306 into human monocyte-derived macrophages (HMDMs). MiR-4306 noticeably inhibited the HMDMs migration in vitro and reduced the number of macrophage cells in cardiac tissue in myocardial infarction mice. This functional impact of miR-4306 was mediated directly through VEGFA to inhibit ERK/NF-κB signaling. In conclusion, our study suggested that intercellular transfer of miR-4306 by platelet microparticles inhibited the HMDMs migration through VEGFA/ERK1/2/NF-κB signaling pathways. [ABSTRACT FROM AUTHOR]

The current study applied a 2 × 2 experimental design to investigate the effects of ongoing task absorption on event-based prospective memory performance of children aged 3 and 5 years. Children were required to label pictures as ongoing task but to remember to refrain from picture naming and to respond to the target cues in a different way as the prospective memory task. Two differently absorbing ongoing tasks (high absorbing scenario game task vs. low absorbing computer-based task) were administered. Results indicated that prospective memory performance of 5-year-old children was significantly better than that of 3-year-old children. Ongoing task absorption affected the ongoing task performance of preschoolers, but not overall prospective memory performance. Only the 3-year-olds were negatively affected by high ongoing task absorption, which was not the case for the 5-year-olds. The findings are discussed within the light of the multiprocess theory. [ABSTRACT FROM AUTHOR]

This article analyzes the obstacles in the application of the Internet of Things in the supply chain by means of evolutionary game theory. Through modeling, the game payoff matrix of core enterprises and suppliers as well as their replicator dynamic equations are obtained. Subsequently, an analysis of two populations that adopt the key technology of the Internet of Things, radio frequency identification (RFID), is conducted through replicator dynamics. The two populations achieve an evolutionarily stable strategy through continuous imitation and adjustment to the strategy. Furthermore, through the analysis of relevant parameters, the influence on the RFID application strategy selected by core enterprises and suppliers of factors such as implementation risk, tag cost, system cost, maintenance cost, compelling force of core enterprises, and expected return, among others, is verified. [ABSTRACT FROM PUBLISHER]

Extra long span rail transit bridges are generally slender and sensitive to excitations, and alignment control of the bridges should be conducted during construction. In this paper, the self-adaptive Kalman Filter (SKF) method was applied to the alignment control of the second longest rail transit bridge in the world. Each influential factor of the bridge alignment was firstly introduced. Then, the finite-element analysis and field tests of the bridge were carried out to obtain the influential factors that induced bridge cambers quantitatively. Combining with the cambers, the SKF method was applied to the alignment control of the bridge. Comparisons of the SFK-predicted alignment with the target alignment or the field measured alignment were carried out. Results show the SKF for alignment control of bridges is feasible and reliable. [ABSTRACT FROM PUBLISHER]

The present study applied a 2 × 2 experimental design to assess prospective memory (PM) development across preschool age and to examine the effect of task instructor status (researcher vs. significant other) on PM performance in 80 preschool children. Participants were required to name pictures (ongoing task [OT]), and to remember to refrain from naming but instead give a different response to certain target cues (PM task). Although the OT was of comparable difficulty for both age groups (as indicated by no performance differences), results still indicated significantly higher PM performance in 5-year-olds than in 3-year-olds, confirming the age-related increase of PM capacities between 3 and 5 years. Furthermore, results showed a performance-enhancing effect of significant others as task instructors on both age-groups. Post-hoc analysis revealed that 3-year-olds instructed by a significant other still performed marginally worse than 5-year-olds instructed by a researcher, underlining the finding that substantial changes of PM capacities take place during early childhood. [ABSTRACT FROM AUTHOR]

ContextThe roots ofIlex asprella(Hook. et Arn.) Champ. ex Benth. (Aquifoliaceae) are widely used in Chinese medicine to treat influenza, amygdalitis, pertussis, etc. Their mechanism of action is still unknown, which raises the need to identify new bioactive compounds in this plant. ObjectiveIn this study, we isolated a novel saponin containing sulphonic groups, namely, asprellcoside A (1) and a known phenolic glycoside compound (2) from the roots ofIlex asprellaand evaluated their bioactivities. Materials and methodsMolecular structures were elucidated by analysing their spectral and chemical properties. The viability of A549 cells was tested using a MTT assay. Ability of the compounds to inhibit viruses was determined using the neuraminidase activity assay. Their anti-inflammatory effects were tested using the IP-10 activity assay using various concentrations (compound1: 0.6, 0.2, 0.6, 1.70, 5.00 and 15.00 μM; compound2: 0.4, 1.2, 3.6, 11.0, 33.0 and 100 μM). Their inhibitory effect on platelet aggregation induced by adenosine diphosphate (ADP) in rabbit plasma was determined at 60 and 80 μM. ResultsBoth compounds inhibit influenza virus strain A/PuertoRico/8/1934 (H1N1) strongly with EC50values of 4.1 and 1.7 μM, respectively. Both compounds inhibit the secretion of IP-10 with EC50values of 6.6 and 2.5 μM, respectively. Compound1alone inhibited platelet aggregation significantly, with the rate of suppression being 47 ± 8 and 38 ± 3%, at 60 and 80 μM, respectively. ConclusionsThe results suggest that both compounds may be valid therapeutics against influenza virus infection and that compound1may be a novel agent for treating thrombosis. [ABSTRACT FROM PUBLISHER]

Aristolochic acid (AA) are persistent soil pollutants in the agricultural fields of the Balkan Peninsula. Preparations containing aristolochic acid are widely used for anti-inflammatory, diuretic, etc. To study the hepatotoxicity of aristolochic acid, 80 healthy SD rats were selected and divided into 20 mg/kg- AA group, 4 mg/kg-AA group, and 2 mg/kg-AA group and blank group, 20 rats per group. Mainly tested the body weight, liver function, liver tissue oxidative stress and pathological changes of liver tissue in rats. The ALT and AST activities in the serum of the rats in the administration groups were increased compared with the blank group. The activity of MDA in the administration groups was higher than that in the blank group; the activities of SOD, T-AOC and GSH-PX were significantly lower than those in the blank group. HE tissue sections also found that the administration groups showed varying degrees of hepatocyte boundary blur, nuclear fragmentation, and fibrosis tendency. Transmission electron microscopy showed that the mitochondria of the rat liver became more and more severely damaged with the increase of dose. Compared with the blank group, the mRNA expression of Bax, Caspase-9 and Caspase-3 in the administration groups were determined, while the mRNA expression of the Bcl-2 was increased. And compared with the blank control group, the expression levels of apoptotic proteins caspase-9 and caspase-3 increased significantly in the 20 mg/kg-AA group. Aristolochic acid can induce liver injury in rats through oxidative stress pathway and mitochondrial apoptosis pathway. [ABSTRACT FROM AUTHOR]

By using a mixed-ligand approach, a Co(II) coordination polymer (CP) with the chemical formula of [Co(L)(ip)·H2O]n (1, L = 1,3-bis(benzimidazol-1-yl)-2-propanol, H2ip = isophthalic acid) was synthesized under solvothermal conditions. Furthermore, to develop new candidates for cancer treatment, the treatment effect of the compound on the human cervical carcinoma cell line Hela was evaluated. First, the autophagy level of the Hela cell line after compound treatment was measured by flow cytometry. Then, the autophagic genes expression was detected by the reverse transcription-polymerase chain reaction (RT-PCR) determination. [ABSTRACT FROM AUTHOR]

Recently, gestational diabetes mellitus (GDM) exhibits an obvious trend of increase in pregnant mothers and usually causes several abnormities or diseases for the offspring. Although several studies have been reported for potential molecular mechanisms, relevant genes or mutated sites have not been intensively investigated in China. In the present study, 218 pregnant mothers (GDM group: 103 individuals and control group: 115 individuals) in China were enrolled to conduct genome-wide association study (GWAS) and pathway analyses for the purpose of related genes associated with GDM in China. Our results identified 23 SNPs exhibiting closely association with GDM using multiple tests. Annotation of these 23 SNPs identified four genes (SYNPR, CDH18, CTIF, and PTGIS), which suggests that the four genes may associate with GDM. GO enrichment and KEGG pathway analysis showed that gene SYNPR, CDH18, and PTGIS were enriched or located into the pathways or process associated with glycometabolism (e.g. insulin resistance and glucose tolerance), which further indicates that the three genes may associate with the GDM. The identification of these potential genes associating with GDM enriched the potential molecular mechanisms of GDM in Asia and will provide abundant stocks for subsequent clinical verifications for better understanding the molecular mechanisms, diagnosis, drug development and clinical treatment of GDM. [ABSTRACT FROM AUTHOR]

Two Cu(II)-based coordination polymers with the chemical formula of [Cu(bibb)(1,4-NDC)](DMF) (1, bibb = 1,4-bis(benzimidazol-1-yl)−2-butylene, 1,4-H2NDC = 1,4-naphthalenedicarboxylic acid, DMF = N,N-dimethylformamide) and [Cu(bibb)(1,4-NDC)](DMA) (2, N,N-dimethylacetamide) have been prepared. The structural solution and refinement results based on the crystal data show that complex 1 exhibits a rarely 2-fold interpenetrating 3D (4,5)-connected xah framework, and complex 2 possesses an unusual 3D (3,4)-connected dmc topology. Furthermore, the protective activity of compounds 1 and 2 on Viral myocarditis (VMC) was detected on CVB3-induced mouse viral myocarditis model. The relative expression of the inflammatory factors nf-κb and p38 in myocardial cells after compounds 1 and 2 treatment was measured with reverse transcription-polymerase chain reaction (RT-PCR). The release level of the inflammatory cytokines IL-1 and MCP-1 by myocardial cells was determined with enzyme linked immunosorbent assay (ELISA) detection kit. [ABSTRACT FROM AUTHOR]

Aim: To investigate the clinical features of five glial fibrillary acidic protein (GFAP) antibody positive patients with suspected benign tumors and explore its underlying pathogenesis. Materials and methods: Overall, 1018 serum and cerebrospinal fluid (CSF) samples were tested by indirect immunofluorescence assay and data from five patients with suspected tumors and positive for GFAP autoantibody in the CSF were analyzed retrospectively. Results: The positive rate of GFAP antibody in the serum and CSF was 3.93% by indirect immunofluorescence assay. Tumors were diagnosed before or after neurologic onset in 5 of 40 patients (12.5%) and no deterioration of the tumors was found during the long-term follow-up. Of the five patients, one patient suffered a thyroid nodule, one patient had a small nodule in the left lung, two patients suffered meningiomas, and one patient had a suspicious eosinophilic granuloma. Conclusion: GFAP autoimmunity may be a paraneoplastic immune response with a low frequency of tumor in Chinese patients with GFAP astrocytopathy. [ABSTRACT FROM AUTHOR]

Background: Recently, gestational diabetes mellitus (GDM) exhibits an obvious trend of increase in pregnant mothers and usually causes several abnormities or diseases for the offspring. Although several studies have been reported for potential molecular mechanisms, relevant genes or mutated sites have not been intensively investigated in China.Materials and Methods: In the present study, 218 pregnant mothers (GDM group: 103 individuals and control group: 115 individuals) in China were enrolled to conduct genome-wide association study (GWAS) and pathway analyses for the purpose of related genes associated with GDM in China.Results: Our results identified 23 SNPs exhibiting closely association with GDM using multiple tests. Annotation of these 23 SNPs identified four genes (SYNPR, CDH18, CTIF, and PTGIS), which suggests that the four genes may associate with GDM. GO enrichment and KEGG pathway analysis showed that gene SYNPR, CDH18, and PTGIS were enriched or located into the pathways or process associated with glycometabolism (e.g. insulin resistance and glucose tolerance), which further indicates that the three genes may associate with the GDM.Conclusion: The identification of these potential genes associating with GDM enriched the potential molecular mechanisms of GDM in Asia and will provide abundant stocks for subsequent clinical verifications for better understanding the molecular mechanisms, diagnosis, drug development and clinical treatment of GDM. [ABSTRACT FROM AUTHOR]

In contrast to reinforced concrete (RC) structures on land, RC shield tunnels in coastal regions deteriorate rapidly after their construction because of the combined effects of multiple mechanical and environmental stressors. In this paper, by considering the coastal hazards associated with chloride and the impacts of hydrostatic pressure, a novel approach is presented to estimate the life-cycle structural performance of a shield tunnel that has undergone deterioration due to chloride-induced steel corrosion. Deterioration processes in segmental linings are investigated via corrosion-accelerated experiments on individual segments, and the combined effects of corrosive agents and loads are emphasized. Monte Carlo simulation is used to estimate the time-variant failure probability of shield tunnels in a marine environment. In an illustrative example, the effects of structural location, hydrostatic pressure and material properties on the life-cycle reliability of shield tunnels are investigated. [ABSTRACT FROM AUTHOR]

Morpholine is a common chemical used as emulsifier in the preparation of wax coatings for some fruit to help them remain fresh and protect against insects and fungal contamination. It has been reported that morpholine has acute toxic effects on rodents. In the present study, morpholine concentrations were analysed in fruits (citrus fruits, apples, strawberries and grapes) and juices (apple juice and orange juice) in order to determine dietary exposure among the Chinese population. A total of 732 fruit and juice samples were collected during 2015-2016, which covered major foods in China. Fruit and juice consumption data were taken from China National Nutrient and Health Survey (2002) and include data from 16,407 fruit or juice consumers. It was found that mean dietary exposure to morpholine residues from fruits and/or juices for general Chinese consumers and children 2-6 years old were 0.42 and 1.24 µg/kg bw/day, respectively. The 97.5% intake in general Chinese consumers and children 2-6 years old were 2.25 and 6.90 µg/kg bw/day, respectively. The primary food sources of the morpholine dietary intake of general Chinese consumers were citrus fruits (57.4%) and apples (40.8%). These findings suggested that dietary exposure to morpholine in the Chinese population was lower than the acceptable daily intake of morpholine, and there are no health concerns. [ABSTRACT FROM AUTHOR]

Objectives: Flat colorectal adenomas have a high risk of malignancy; however, their detection is often difficult due to their flat morphology. In this retrospective, large-scale study, we investigated the prevalence and characteristics of flat adenomas in a population in China. Methods: We analyzed the data collected for 16951 consecutive patients who underwent colonoscopy at four participating hospitals between September 2013 and September 2015. All colonoscopies were performed without magnification. Results: Among the 1,6951 patients, 2938 (17.3%) had adenoma and 796 (4.7%) had flat adenomas. The detection of flat adenoma showed a weak correlation with the detection of adenoma (r=0.666). Multivariable logistic regression analysis revealed the following independent factors influencing the detection of flat adenomas: patient-related factors of age, presence of warning symptoms, history of adenomas and bowel preparation as well as endoscopist-related factors of endoscopist's level of proficiency, number of colonoscopy operators and withdrawal time. Conclusions: The prevalence of flat adenomas in our study on Chinese patients was consistent with that reported from other countries. Factors conducive to the detection of flat adenomas were patient age of >60 years, warning symptoms, history of adenoma, good bowel preparation, experienced endoscopist, single-operator colonoscopy and colonoscopy withdrawal time of >6 min. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the effectiveness and safety of endoscopic resection for gastric gastrointestinal stromal tumors (GISTs). Material and methods: The effectiveness and safety of endoscopic resection were mainly assessed by complete resection rate, postoperative adverse event rate, and recurrence rate. Moreover, a comparison of endoscopic with laparoscopic resection for gastric GISTs was made through weighted mean difference by STATA 12.0 with regard to operation time, blood loss, and length of stay after including patients who underwent endoscopic or laparoscopic resection for gastric GISTs in the comparative studies. Results: Eleven studies investigating endoscopic resection for GISTs were included. For stromal tumors <2 cm in average diameters the pooled rates of complete resection, postoperative adverse events and recurrence were 0.97, 0.08, and 0.03, respectively. Only five retrospective studies directly compared endoscopic with laparoscopic resection for gastric GISTs with average diameters from 1.1 cm to 3.8 cm, and endoscopic resection had a shorter operation time than laparoscopic resection, but there were no significant differences in intraoperative blood loss, length of stay, postoperative complications, and postoperative recurrence rates between the two approaches. Conclusions: Endoscopic resection is predominantly tried for gastric GISTs of relatively small size. It seems effective and safe for gastric GISTs <2 cm in average diameter, with relatively short operation times. [ABSTRACT FROM AUTHOR]

A series of novel pyrimidine derivatives with (pyridin-3-ylmethyl)thio and phenylamino moieties were synthesized from ethyl acetoacetate, thiourea, 3-pyridinylmethyl chloride hydrochloride, and substituted anilines by multi-step reactions. The structures of the target compounds were characterized by IR, 1H NMR, 13C NMR and elemental analysis. The in vitro antifungal activities against Botrytis cinerea and Sclerotinia sclerotiorum were evaluated. The result showed that N-phenyl-6-methyl-2- ((pyridin-3-ylmethyl)thio) pyrimidin-4-amine (4a) displayed high inhibition activity against Botrytis cinerea with 87.5%inhibition at 100 µg/mL; 4a, and N-(4-isopropylphenyl)-6-methyl-2-((pyridin-3-ylmethyl)thio)pyrimidin-4-amine (4c), N-(4-methoxyphenyl)-6-methyl-2-((pyridin-3-ylmethyl)thio)pyrimidin-4-amine (4d) and N-(2-hydroxy-5-chloro)-6-methyl-2-((pyridin-3-ylmethyl)thio)pyrimidin- 4-amine (4h) exhibited sufficient activities against Sclerotinia sclerotiorum with 86.6% -93.7% inhibitions at the same concentration. [ABSTRACT FROM AUTHOR]

Patients withEGFRmutations showed unfavorable response to programmed cell death-1 (PD-1) blockade immunotherapy in non-small cell lung cancer (NSCLC). Yet the underlying association betweenEGFRmutation and immune resistance remains largely unclear. We performed an integrated analysis of PD-ligand 1(PD-L1)/CD8 expression and mutation profile based on the repository database and resected early-stage NSCLC in Guangdong Lung Cancer Institute (GLCI). Meanwhile, 2 pool-analyses were set to clarify the correlation betweenEGFRmutation and PD-L1 expression, and the association ofEGFRstatus with response to anti-PD-1/L1 therapy. Pool-analysis of 15 public studies suggested that patients withEGFRmutations had decreased PD-L1 expression (odds ratio: 1.79, 95% CI: 1.10–2.93; P = 0.02). Analysis of The Cancer Genome Atlas (TCGA) and the GCLI cohort confirmed the inverse correlation betweenEGFRmutation and PD-L1 expression. Furthermore, patients withEGFRmutation showed a lack of T-cell infiltration and shrinking proportion of PD-L1+/CD8+TIL (P = 0.034). Importantly, patients withEGFRmutations, especially the sensitive subtype, showed a significantly decreased mutation burden, based on analysis of the discovery and validation sets. Finally, a pool-analysis of 4 randomized control trials confirmed that patients withEGFRmutation did not benefit from PD-1/L1 inhibitors (Hazard ratio [HR] = 1.09, P = 0.51) while patients withEGFRwild-type did (HR = 0.73, P < 0.00001). This study provided evidence of a correlation betweenEGFRmutations and an uninflamed tumor microenvironment with immunological tolerance and weak immunogenicity, which caused an inferior response to PD-1 blockade in NSCLCs. [ABSTRACT FROM AUTHOR]

The Chibaisong magmatic Cu–Ni sulphide deposit is located in Tonghua City, Jilin Province, in the eastern part of the northern margin of the North China Craton. The geological characteristics of the deposit have been investigated, and pyrrhotite Re–Os isotope dating has been utilized to constrain the age. Five pyrrhotite samples separated from the Chibaisong Cu–Ni sulphide deposit yielded a Re–Os isotopic isochron age of 2237 ± 62 Ma (mean squared weighted deviation = 1.13,n = 5), indicating that the only Palaeoproterozoic magmatic Cu–Ni sulphide deposit in China is the Chibaisong Cu–Ni sulphide deposit. The geodynamic setting during ore formation was related to the Liaoning–Jilin Palaeoproterozoic rift split. The Re–Os isotope analyses showed an initial187Os/188Os ratio of 0.778 ± 0.033, and (187Os/188Os)iand γOs(t) values ranged from 0.7531 to 0.8013 (average 0.7734) and from 574 to 617 (average 592), respectively, indicating that abundant crustal material (5–10%) was mixed with the Cu–Ni sulphide ore system during magma ascent and ore formation. [ABSTRACT FROM AUTHOR]