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Phytosterols (PS) have been shown to regulate cholesterol metabolism and alleviate hyperlipidemia (HLP), but the mechanism is still unclear. In this study, we investigated the mechanism by which PS regulates cholesterol metabolism in high-fat diet (HFD) mice. The results showed that PS treatment reduced the accumulation of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in the serum of HFD mice, while increasing the serum levels of high-density lipoprotein cholesterol (HDL-C). Compared with HFD mice, PS not only increased the antioxidant activity of the liver but also regulated the mRNA expression levels of enzymes and receptors related to cholesterol metabolism. The hypolipidemic effect of PS was abolished by antibiotic (Abx) intervention and reproduced by fecal transplantation (FMT) intervention. The results of 16S rRNA sequencing analysis showed that PS modulated the gut microbiota of mice. PS reduced the relative abundance of Lactobacillus and other bile salt hydrolase- (BSH-) producing gut microbiota in HFD mice, which are potentially related to cholesterol metabolism. These findings partially explain the mechanisms by which PS regulates cholesterol metabolism. This implies that regulation of the gut microbiota would be a potential target for the treatment of HLP.

Twelve undescribed and 13 known eudesmane-type sesquiterpenoids were obtained from Artemisia leucophylla, and structurally elucidated based on comprehensive analyses of spectral data, including HRESIMS, IR, 1D and 2D NMR, and ECD calculation. The absolute configuration of compound 1 was determined by a single X-ray single crystal diffraction. Chemically, compounds 1-5 featured unprecedented 1,2-seco-1-nor-eudesmane-type skeleton with a cis-fused 6/5 bicyclic system. Antihepatoma evaluation against three human hepatoma cell lines (HepG2, Huh7, and SK-Hep-1) for all compounds demonstrated that compound 7 displayed the most active cytotoxicity with IC

Background To report the incidence and risk factors of suction loss during small incision lenticule extraction (SMILE). Methods This retrospective comparative case control study included 8493 eyes of 4261 patients. Patients underwent SMILE surgery between January 2014 and September 2019 were included. Videos of suction loss were reviewed, and the direct causes of suction loss were noted. An independent samples t-test was used for comparisons between the suction loss group and the control group. A binary logistic regression model was used to determine the possible significant risk factors that might increase the likelihood of suction loss during SMILE surgery. Results Suction loss occurred in 31 (0.37%) eyes of 30 patients; 23 (74.2%) cases occurred in the right eye (the first operative eye) and 8 (25.8%) cases occurred in the left eye. Among the 30 patients, 23 (76.7%) were male and 7 (23.3%) were female. The incidence in the six consecutive years were 0, 2.13, 0.34, 0.24, 0.22, and 0.25%. Head and eye movements during surgery caused suction loss in 16 (51.6%) and 15 (48.4%) eyes, respectively. Comparison between the suction loss group and the control group showed that the first operative eye and male sex are at a significantly high risk for suction loss (p Conclusions The risk factors of suction loss were first operative eye and male sex. Head and eye movements due to patient anxiety are the most common direct causes of suction loss. Surgeon’s experience may help to reduce the incidence of suction loss. Preoperative education and better communication during surgery needs to be emphasized. Trial registration Retrospectively registered. ChiCTR-ORC-17011040. Registered 1 April 2017. Name of registry: The observation of clinical results after corneal refractive surgery. Data of enrolment of the first participant to the trial: 1 January 2014.

A random bioassay revealed that the EtOH extract and EtOAc fraction of Artemisia dubia Wall. (Asteraceae) exhibited cytotoxic activity against HepG2 cells with inhibitory ratios of 57.1% and 84.2% at a concentration of 100.0 μg/mL. Bio-guided isolation combined by LC-MS-IT-TOF analyses of the active fractions led to the isolation of 20 previously undescribed guaiane-type sesquiterpenoid dimers named artemidubolides A-T (1-20). Their structures and the absolute configurations were determined by comprehensive spectral analyses, comparison of the experimental and calculated ECD spectra, and seven compounds (artemidubolides A, B, D, F, K, O and R) were confirmed unequivocally by single crystal X-ray diffraction analysis. Structurally, artemidubolides A-Q were [4 + 2] Diels-Alder adducts of two monomeric guaianolides, and artemidubolides R-T were linked though an ester bond. All the isolated compounds were evaluated for their hepatomatic cytotoxicity against HepG2, Huh7, and SK-Hep-1 cell lines to demonstrate that 18 compounds exhibited obvious cytotoxicity against three tested hepatoma cell lines with IC

The dried fruit of Amomum villosum (Amomi Fructus) is an important spices and traditional Chinese medicine. In this study, the EtOH extract of Amomi Fructus was revealed with hypoglycemic effects on db/db mice by increasing plasma insulin levels. After extracted with EtOAc, the EtOAc fraction showed increased activity in stimulating glucagon-like peptide-1 (GLP-1) secretion compared with the EtOH extract. In order to clarify the antidiabetic constituents, four undescribed norlignans, amovillosumins A‒D, were isolated from the EtOAc fraction, and the subsequent chiral resolution yielded three pairs of enantiomers. Their structures were determined by extensive spectroscopic data (1D and 2D NMR, HRESIMS, IR, UV and [α]

Autophagy plays a pivotal role in the progression and management of colorectal cancer (CRC). Recently, numerous articles focusing on the role of autophagy in CRC have emerged. The present study was conducted to provide a comprehensive analysis of the current state and changing trends in the relationship of autophagy and CRC over the past 20 years.The Web of Science Core Collection (WOSCC) was utilized to extracted all publications with respect to autophagy and CRC during 2002-2021. The contributions of various countries/regions, institutions and journals in this field were analyzed, moreover, research hotspots and promising future trends predicted through keywords were identified by the online platform of bibliometrics, CiteSpace and VOSviewer.A total of 2418 related publications from 2002 to 2021 were identified and collected. China occupied first place with respect to the number of publications, followed by the USA and South Korea. Shanghai Jiao Tong University published the most papers in this field. Most publications were published in Oncotarget. Additionally, analysis of the keywords identified 4 clusters with various research focuses: "mechanism-related research", "clinical-related research", "tumorigenesis research" and "chemotherapy-related research". The three latest hot keywords in this field were epithelial-mesenchymal transition (EMT), promote and invasion.The number of publications and research interest on autophagy and CRC are increasing annually, and the USA had prominent academic positions in the field. Shanghai Jiao Tong University represents a high level of research and the latest progress in this field can be tracked at Oncotarget. Throughout the research history of autophagy and CRC in the past 20 years, previous studies have mainly concentrated on apoptosis and drug resistance in tumor cells, while EMT in regulating tumorigenesis and development of clinical drugs that inhibit tumor invasion through autophagy may be novel hotspots in the future.

PURPOSE: The objective of our meta-analysis was to estimate the effect of VTS on obstetric outcomes of ART singletons. METHODS: PubMed, Embase, MEDLINE, and ClinicalTrials.gov were searched up to January 2019 to find studies reporting the obstetric outcomes of ART singletons with VTS. Dichotomous data were expressed as odds ratios (OR) with 95% confidence intervals (CI). Continuous data were expressed as weighted mean difference (WMD) with 95% CI. RESULTS: A total of 17 observational studies encompassing more than 60,000 ART singletons were included in this meta-analysis. The impact of VTS on singletons was highly dependent on the definition of VTS, precisely, the vanishing timing and intrauterine growth stage. When VTS happened at or before 14 weeks, regardless of intrauterine growth stage, there were no differences in terms of gestational age (GA) [WMD = − 0.08, 95% CI = − 0.27, 0.10], preterm birth (< 37 weeks) (PTB) [OR = 1.23, 95% CI = 0.89, 1.70], and low birth weight (< 2.5 kg) (LBW) [OR = 1.56, 95% CI = 1.00, 2.43] in original singletons versus singleton with VTS. On the contrary, VTS occurred after 14 weeks was associated with significantly shorter GW and lower BW, as well as higher risks of PTB and LBW. When the sac reduced in VTS was an empty gestational sac, there would be no differences in GW, PTB, and LBW between singletons versus singletons with VTS, whereas the loss of a fetus with cardiac-activity was associated with adverse obstetric outcomes. CONCLUSIONS: This meta-analysis suggests whether or not VTS is harmful to obstetric outcomes is highly dependent on the vanishing timing and intrauterine growth stage.

Depression is associated with high mortality and morbidity rates worldwide. By our random screening, it was first revealed that 23 magnolol derivatives were synthesized followed by in vitro and in vivo evaluation of their antidepressive potential. Compound 7c was found to be the most promising compound, with EC50 values of 396.5 and 383.0 μM agitating on MT1 and MT2 receptors, respectively. Additionally, we carried out in vivo experiments to confirm the efficacy and safety of compound 7c; the compound was found to be orally bioavailable and highly effective, leading to a significant reduction of immobility time in a mouse model of depression (forced swimming test and tail suspension test); the acting mechanism was explored by determining its effect on the levels of monoamine neurotransmitters and their metabolites in different mice brain regions; the acute toxicity study showed that the 50% lethal dose (LD50) of 7c was higher than 2000 mg/kg, p. o. A total of 25 metabolites of 7c were identified, including 5 metabolites in phase I and 20 metabolites in phase II. Altogether, these results indicate that magnolol derivative 7c is a promising lead compound for the development of a new chemical class of antidepressant drugs.

Four new C16-noriridals (1–4) and two reported C16-noriridals (5–6), together with two new formyl-monocycloiridals (7–8) and three known monocycloiridals (9–11) were isolated from the rhizomes of Iris pseudoacorus. Irispseudoacorins A–D (1–4) and iridojaponals A–B (5–6) were C16-noriridals which shared a 6/5/7 tricyclic ring system (1–2, 5–6) or 6/5 tricyclic ring system (3–4). The formyl-monocycloiridals (7–8) were detected in the crude extracts of I. pseudoacorus by LC-MS analysis which suggested they were originated from natural sources rather than artificial products during the isolation. Their structures were determined by UV, IR, extensive NMR spectra and X-ray diffraction analyses. The known monocycloiridals 9–10 displayed pronounced cytotoxic effects against five human tumor cell lines. The IC50 values of 9 were ranging from 12.63 to 24.69 μM.

Twenty-four gramine derivatives were synthesized and evaluated on MT1 and 5-HT1A receptors in vitro. Among them, seven derivatives (7, 8, 16, 19, 20, 21, and 24) exhibited higher agonisting activities on MT1 or 5-HT1A receptors. Compared with gramine, derivatives 7, 8, 16, 19, 20, 21, and 24 displayed 1.6–3.5-fold increase in agonistic rates on 5-HT1A receptor. Particularly, derivatives 7, 19, and 21 exhibited significant agonistic activities on MT1 and 5-HT1A receptors with EC50 values of 0.51, 0.39, 0.50 mΜ and 0.28, 0.46, 0.23 mΜ, respectively. The preliminary structure–activity relationships of gramine derivatives were summarized for further investigation on MT1 and 5-HT1A receptors as new potential agonists.

The exact cause instigating multiple myeloma (MM) has not been fully elucidated, and the disease has a median survival of 6 months without any treatment. To identify potential biomarkers of MM, serum proteins reflecting alteration in their proteomes were analyzed in 6 patients with MM compared with 6 healthy controls using two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of flight mass spectrometry. The most notable differentially expressed proteins were validated by immunoblotting and changes in mRNA expression were evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 11 differentially expressed protein spots were found. The expression levels of 7 proteins [Immunoglobulin heavy constant µ; proto-oncogene diffuse B-cell lymphoma (DBL2); 26S protease regulatory subunit 4 (P26s4); serum albumin; haptoglobin; and two unknown proteins with isoelectronic point (pI) of 6.41 and molecular weight of 35.4 kDa, and pI of 8.05 and molecular weight of 27.4 kDa, respectively] were downregulated in MM compared with healthy controls. Expression of gel actin-related protein 2/3 complex subunit 1A (ARPC1A); immunoglobulin heavy constant γ 1; fibrinogen α chain (FGA) fragment D; and zinc finger protein 70 were increased in serum of MM patients. Protein expressions of ARPC1A, FGA, P26s4 and DBL2 were measured by immunoblotting in an independent cohort of 12 MM patients and 10 healthy controls. RT-qPCR analysis demonstrated that ARPC1A expression only mimicked protein expression, whereas FGA, PSMC1 (encoding P26s4) and MCF2 (encoding DBL2) did not exhibit significant changes in mRNA expression between control and MM samples. These proteins represent putative serological biomarkers for patients with MM.

Carotid and vertebral artery dissections are estimated to account for ∼20% of strokes in patients under 45-years-old. This meta-analysis compared the efficacy and safety of treatment with anticoagulants versus antiplatelet agents to determine the optimal therapy. We searched 4 electronic databases for clinical trials published from January 1, 1980 to August 25, 2021 that included patients who received anticoagulant or antiplatelet therapy for carotid and/or vertebral artery dissections. The curative effect was judged by recanalization evaluated by imaging. The primary outcomes were all cause death and ischemic stroke; secondary outcomes included hemorrhage and transient ischemic attack (TIA). Patients who received only a single drug treatment were divided into antiplatelet or anticoagulant groups; all received conservative treatment without surgical intervention. For this investigation, we pooled the available studies to conduct a meta-analysis, which included 7 articles with 1126 patients. The curative effect of vascular recanalization was not significantly different between the 2 treatment groups (odds ratio [OR] = 0.913, 95% confidence interval [CI]: 0.611-1.365, P = .657); similarly, no significant differences were found regarding the primary outcomes all cause death (OR = 1.747, 95%CI: 0.202-15.079, P = .612) and ischemic stroke (OR = 2.289, 95%CI: 0.997-5.254, P = .051). Patients treated with anticoagulants were more likely to experience TIA (OR = 0.517, 95%CI: 0.252-1.060, P = .072) and hemorrhage (OR = 0.468, 95%CI: 0.210-1.042, P = .063), but the differences were not statistically significant. Overall, there were no statistically significant differences between anticoagulant therapy and antiplatelet therapy for the treatment of carotid and vertebral artery dissections.

Identify the prevalence of postoperative anxiety and depression as well as their correlations with clinical features and survival profiles in non-small-cell lung cancer (NSCLC) patients who underwent resection. Four hundred NSCLC patients who underwent resection were recruited, and their anxiety and depression were assessed by hospital anxiety and depression scale (HADS) at discharge after surgery. Besides, 480 healthy controls (HCs) were also enrolled and assessed by HADS. The HADS-Anxiety score of NSCLC patients (7.8 ± 3.9) was greatly higher than that of HCs (4.8 ± 2.7), and the anxiety prevalence of NSCLC patients (49.6%) were dramatically increased compared with HCs (13.8%). Furthermore, the HADS-Depression score (7.2 ± 3.6) of NSCLC patients was considerably increased compared with HCs (4.2 ± 2.6), and the depression prevalence of NSCLC patients (38.3%) was significantly raised compared with HCs (10.0%). Besides, anxiety correlated with gender, marital status, hypertension, diabetes, pathological differentiation, tumor size, lymph node metastasis, TNM stage and carcinoembryonic antigen level, meanwhile, depression correlated with marital status, employment status before surgery, diabetes, pathological differentiation, and TNM stage in NSCLC patients. Additionally, the anxiety and depression predicted shorter disease-free survival in NSCLC patients. And the anxiety predicted worse overall survival (OS), while no association of depression with OS was observed in NSCLC patients. Post-operative anxiety and depression are highly prevalent and implicated in the ongoing care and prognosis prediction in NSCLC patients who underwent resection.

Ten new (1-10) and ten known (11-20) diterpenoids involving ent-atisane, ent-seco-atisane, ent-kaurane and ent-seco-kaurane types were isolated from Sapium insigne under the guidance of LCMS-IT-TOF analyses. Their structures were characterized by extensive spectroscopic analyses (HRESIMS, UV, IR, 1D and 2D NMR). A putative biosynthetic pathway was proposed for ent-seco-atisane diterpenoids. Their inhibitory activities on α-glucosidase in vitro were tested for the first time. Compound 4 showed moderate inhibitory effect on α-glucosidase with an IC50 value of 0.34 mM via a noncompetitive inhibition mechanism (Ki = 0.27 mM). The preliminary structure-activity relationships of the ent-atisane diterpenoids inhibiting α-glucosidase were discussed.

In the situation of high-speed or heavy load, pneumatic cylinders usually generate cushion failure like collision or rebound, so that the key question to be solved for the cylinders is cushion. In order to obtain a better cushion method, the paper used the ideal cushion characteristic curve of hydraulic cylinders for reference; and throttling area equation, temperature equation, flow rate equation and motion equation were established. By building the simulation module in Matlab/Simulink, the rule of throttling area approaching to the ideal cushion curve was found, which provide theoretical basis for the design of cylinders cushion devices.

Purpose Current evidence suggests that preconditioning with erythropoietin (EPO) can protect against ischemia reperfusion injury in rodents. However, randomized controlled trials (RCTs) assessing the efficacy and safety of high-dose EPO in kidney transplantation have yielded inconclusive results. Herein, we performed a meta-analysis of RCTs to assess whether the administration of high-dose EPO can improve graft function and the potential adverse events. Methods Relevant RCT studies that investigated high-dose EPO on graft function after kidney transplantation were comprehensively searched in Pubmed, Embase, and Cochrane Library until July 10, 2014. All statistical analyses were performed using Review Manager 5.0 and STATA 12.0. Results A total of 4 RCTs involving 356 patients were identified. Comprehensively, a trend of reduction in the incidence of delayed graft function could be observed in the EPO group (EPO vs. placebo groups: RR = 0.88); however, the result did not reach the significance level (95% CI, 0.72–1.08; P = 0.21). Furthermore, no significant difference in the incidences of adverse events was observed between the two groups. Conclusions The current meta-analysis indicates that the administration of high-dose EPO is, to some extent, prone to protect kidney function without increasing the susceptibility to adverse events.

A rigid-elastic coupling multi-body dynamic model of an in-wheel motor vehicle with double pivot suspension was established. The steering effort performance is analyzed. Results showed an excessive steering force of the vehicle with double pivot suspension. By optimizing the suspension parameters using response surface surrogate model and genetic algorithm, the characteristic of steering effort was improved.

Seven new phenolic glycosides including two heterocyclic phenolic derivatives orcinosides I-J (1-2) and five chlorophenolic glycosides curculigines J-N (3-7), together with nineteen known compounds were isolated from the rhizome of Curculigo orchioides. Based on extensive spectroscopic analyses (UV, IR, HRESIMS, 1D and 2D NMR), the structures of the new compounds were identified. Orcinoside I (1) and J (2) displayed xanthine oxidase inhibitory activities with IC50 values 0.25 and 0.62mM respectively.

Background Human leukocyte antigen-G (HLA-G) is involved in the development and progression of human cancers, and numerous molecular epidemiological studies have been conducted to explore the potential relationship of HLA-G 14-bp insertion/deletion (ins/del) polymorphism with cancer risk. However, results from published studies were inconclusive. Methods Both PUBMED and EMBASE databases were searched comprehensively to identify eligible studies investigating the association of HLA-G 14-bp ins/del polymorphism with cancer risk. Statistical analysis was performed by using STATA 12.0 and Review Manager 5.0. Results Fourteen eligible studies with 2340 cancer patients and 3967 controls were included and analyzed with odds ratio (OR) and its corresponding 95% confidence interval (CI). Overall, no significant association between HLA-G 14-bp ins/del polymorphism and overall cancer risk was detected in all comparison models. Further subgroup analyses based on ethnicity and cancer types demonstrated the significant association among Asians (ins/del vs. del/del: OR = 0.80, 95% CI, 0.66–0.95; ins/ins + ins/del vs. del/del: OR = 0.80, 95% CI, 0.65–0.97) and for breast cancer (ins allele vs. del allele: OR = 0.76, 95% CI, 0.61–0.96; ins/ins vs. del/del: OR = 0.57, 95% CI, 0.37–0.87; and ins/ins vs. ins/del + del/del: OR = 0.60, 95% CI, 0.42–0.87). Conclusion This study suggested that HLA-G 14-bp ins/del polymorphism might contribute to breast cancer susceptibility and overall cancer risk among Asians. Further well-designed studies with larger sample size are warranted to validate our conclusion.

A multi-body dynamic rigid-flexible coupling model of an in-wheel motor vehicle is built. This vehicle is based on a particular class-A car. An overall investigation of the influence of unsprung mass on vehicle ride comfort is conducted. With the increment of unsprung mass, overall vehicle ride comfort is decreased. The degradation of wheel dynamic load performance is most obvious. Suspension parameters are optimized based on the multi-body dynamic model of the vehicle and Response Surface Method. The suspension deflection and wheel dynamic load of the vehicle using optimized suspension parameters are improved significantly, while the body vertical acceleration increased slightly.

A double pivot suspension used for in-wheel motor electric vehicle was designed, and the virtual prototype model of the suspension assembly was build. The suspension parameters changed greatly during steering. In order to solve this problem, this paper proposed a non-linear response surface model to fit the relationship of suspension parameters and design variables. An optimization scheme was designed based on the response surface model. The suspension performance was improved significantly using optimized variables.

A rigid-elastic coupling multi-body dynamic model of a car was established. The controllability and stability including constant cornering, steering returnability and steering effort performances are analyzed. Results show that there is still a feasibility to enhance the understeer. By optimizing the suspension parameters using DOE method, the characteristic of understeer was improved. Simulation analysis indicated that the characteristics of steering effort and steering returnability were not affected due to change of suspension parameters.

The method offers a highly enantioselective access to novel spirocyclic dihydropyranone derivatives.

Based on development of Chinese LDPE composites preparation engineering, this paper especially aims to analyze various modification methods on physical property improvements of LDPE/CaCO3 polymers. Most widely and advanced used methods of mixing technology research status and characteristics are reviewed and discussed. By studying inductive LDPE/CaCO3 composites effect, we are able to analyze composite conditions such as parameter value that are positive to reactions and briefly probe the challenges facing kinds of composite materials in the future.

Introduction This work was to analyze characteristics of breast cancer (BC) in Central China, summarize main characteristics in China and compare with USA. Methods BC main characteristics from four hospitals in Central China from 2002 to 2012 were collected and analyzed. All the single and large-scale clinical reports covering at least ten years were selected and summarized to calculate the BC characteristics of China. BC Characteristics in USA were selected based on the database from Surveillance, Epidemiology, and End Results (SEER) Program. Results Age distribution in Central China was normal with one age peak at 45–49 years, displaying differences from USA and Chinese American with two age peaks. BC characteristics in Central China displayed distinct features from USA and Chinese American, including significant younger onset age, lower proportion of patients with stage I, lymph node negative, small tumor size and ER positive. A total ten long-term and large-scale clinical reports were selected for BC characteristics of Mainland China analysis. A total of 53,571 BC patients were enrolled from 1995 to 2012. The main characteristics of BC in Mainland China were similar as that in Central China, but were significant different from developed regions of China (Hong Kong and Taiwan), USA and Chinese American. Conclusions BC characteristics in Central China displayed representative patterns of Mainland China, while showed distinct patterns from Chinese patients in other developed areas and USA.

Basic fibroblast growth factor (bFGF) plays an important role in angiogenesis. However, the underlying mechanisms are not clear. Mg(2+) is the most abundant intracellular divalent cation in the body and plays critical roles in many cell functions. We investigated the effect of bFGF on the intracellular Mg(2+) concentration ([Mg(2+)](i)) in human umbilical vein endothelial cells (HUVECs). bFGF increased [Mg(2+)](i) in a dose-dependent manner, independent of extracellular Mg(2+). This bFGF-induced [Mg(2+)](i) increase was blocked by tyrosine kinase inhibitors (tyrphostin A-23 and genistein), phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY294002) and a phospholipase Cgamma (PLCgamma) inhibitor (U73122). In contrast, mitogen-activated protein kinase inhibitors (SB202190 and PD98059) did not affect the bFGF-induced [Mg(2+)](i) increase. These results suggest that bFGF increases the [Mg(2+)](i) from the intracellular Mg(2+) stores through the tyrosine kinase/PI3K/PLCgamma-dependent signaling pathways.

Supplemental Digital Content is available in the text, Papillary renal cell carcinoma (pRCC) is the second most prevalent subtype of kidney cancers. In the current study, we analyzed the global microRNA (miRNA) expression profiles in pRCC, with the aim to evaluate the relationship of miRNA expression with the progression and prognosis of pRCC. A total of 163 treatment-naïve primary pRCC patients were identified from the Cancer Genome Atlas dataset and included in this retrospective observational study. The miRNA expression profiles were graded by tumor-node-metastasis information, and compared between histologic subtypes. Furthermore, the training-validation approach was applied to identify miRNAs of prognostic values, with the aid of Kaplan–Meier survival, and univariate and multivariate Cox regression analyses. Finally, the online DAVID (Database for Annotation, Visualization, and Integrated Discover) program was applied for the pathway enrichment analysis with the target genes of prognosis-associated miRNAs, which were predicted by 3 computational algorithms (PicTar, TargetScan, and Miranda). In the progression-related miRNA profiles, 26 miRNAs were selected for pathologic stage, 28 for pathologic T, 16 for lymph node status, 3 for metastasis status, and 32 for histologic types, respectively. In the training stage, the expression levels of 12 miRNAs (mir-134, mir-379, mir-127, mir-452, mir-199a, mir-200c, mir-141, mir-3074, mir-1468, mir-181c, mir-1180, and mir-34a) were significantly associated with patient survival, whereas mir-200c, mir-127, mir-34a, and mir-181c were identified by multivariate Cox regression analyses as potential independent prognostic factors in pRCC. Subsequently, mir-200c, mir-127, and mir-34a were confirmed to be significantly correlated with patient survival in the validation stage. Finally, target gene prediction analysis identified a total of 113 target genes for mir-200c, 37 for mir-127, and 180 for mir-34a, which further generated 15 molecular pathways. Our results identified the specific miRNAs associated with the progression and aggressiveness of pRCC, and 3 miRNAs (mir-200c, mir-127, and mir-34a) as promising prognostic factors of pRCC.

The first enantioselective aza-Morita—Baylis—Hillman reaction of acrylates with ketimines derived from isatins is developed.

The first enantioselective vinylogous aldol–cyclization cascade reaction of allyl pyrazoleamides with isatins is reported. With 1 mol% of Takemoto catalyst, optically active spirocyclic oxindole–dihydropyranones were obtained in excellent yields (93–99%) and good-to-excellent enantioselectivities (82–97% ee).

Human cancers are endowed with sustained vascularization capability, and their growth, invasion, and metastasis are vascularization dependent. Recently, accumulated body of evidence suggests that endothelial progenitor cells (EPCs) can support vasculogenesis and induce angiogenesis through paracrine mechanisms. In addition, numerous clinical studies have revealed the increase in the number of EPCs in the peripheral blood of cancer patients and demonstrated the correlation of circulating EPCs (CEPCs) with the clinical outcomes. This review highlights current enrichment procedures and methods for the detection of CEPCs and different biomarkers to identify CEPCs as well as the functions of EPCs in tumor vascularization. Furthermore, we systematically review available studies on the clinical relevance of CEPCs in cancer patients to explore the potential diagnostic and prognostic values of CEPCs. Although several contrasting results exist, CEPCs can conceivably serve as a promising biomarker for the early diagnosis, prognosis prediction, and treatment response indication in the future. Additionally, further well-designed clinical studies with larger sample size and unique, specific enumeration procedures are warranted to achieve further insight into the clinical implications of CEPCs.

The first organocatalytic Mannich coupling of pyrazoleamides with ketimines of type (I)/(VI) is reported.

A efficient procedure using a bifunctional squaramide catalyst is presented for the domino Mannich cyclization of isatin imines and 1,3-dicarbonyl compounds (II) and (IV) to produce 3-amino-2-oxindoles in high yields and excellent stereoselectivities.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancers in adults, and microRNAs (miRNAs) differentially expressed in ccRCC tumors have been identified and proposed to predict prognosis. In the present study, we comprehensively analyzed the genome-wide miRNA expression profiles in ccRCC, with the aim to generate a tumor-specific miRNA signature of prognostic values. The miRNA profiles in tumor and the adjacent normal tissue were analyzed, and the association of the differentially expressed miRNAs with patient survival was examined with univariate Cox regression analysis. Finally, a tumor-specific miRNA signature was generated and examined with Kaplan–Meier survival, univariate, and multivariate Cox regression analyses. A total of 147 miRNAs were found differentially expressed between tumor and matched non-tumor tissues from 58 ccRCC patients. The prognostic values of these differentially expressed miRNAs were subsequently analyzed in the 411 ccRCC patients, and 22 miRNAs were found significantly correlated with patient survival. Finally, a tumor-specific miRNA signature of 22 miRNAs was generated and validated as an independent prognostic parameter. A tumor-specific miRNA signature consisting of 22 miRNAs was identified and validated as an independent prognostic factor, which could serve as a novel biomarker for ccRCC prognostication and help in predicting treatment outcome.

The enantioselective addition of alcohols to isatin-derived N-Boc ketimines is investigated for the first time.

Techniques have been developed which allow HPLC (high performance liqid chromatography) to be used for the quantitative determination of [ 99m Tc]pertechnetate in radiopharmaceuticals and biological samples. An instrumental technique accounts for 99m Tc species which do not elute from the HPLC column, while a chemical technique obviates interferences caused by Sn(II). These two techniques are incorporated into an anion exchange HPLC procedure which is applied to the determination of [ 99m Tc]pertechnetate in 99m Tc-diphosphonate radiopharmaceuticals and biological samples.