Transcriptome analysis suggested that lncRNAs regulate rapeseed seedlings in responding to drought stress by coordinating the phytohormone signal transduction pathways.

The growth, yield, and seed quality of rapeseed are negatively affected by drought stress. Therefore, it is of great value to understand the molecular mechanism behind this phenomenon. In a previous study, long non-coding RNAs (lncRNAs) were found to play a key role in the response of rapeseed seedlings to drought stress. However, many questions remained unanswered. This study was the first to investigate the expression profile of lncRNAs not only under control and drought treatment, but also under the rehydration treatment. A total of 381 differentially expressed lncRNA and 10,253 differentially expressed mRNAs were identified in the comparison between drought stress and control condition. In the transition from drought stress to rehydration, 477 differentially expressed lncRNAs and 12,543 differentially expressed mRNAs were detected. After identifying the differentially expressed (DE) lncRNAs, the comprehensive lncRNAs-engaged network with the co-expressed mRNAs in leaves under control, drought and rehydration was investigated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of co-expressed mRNAs identified the most significant pathways related with plant hormones (expecially abscisic acid, auxin, cytokinins, and gibberellins) in the signal transduction. The genes, co-expressed with the most-enriched DE-lncRNAs, were considered as the most effective candidates in the water-loss and water-recovery processes, including protein phosphatase 2 C (PP2C), ABRE-binding factors (ABFs), and SMALL AUXIN UP-REGULATED RNAs (SAURs). In summary, these analyses clearly demonstrated that DE-lncRNAs can act as a regulatory hub in plant-water interaction by controlling phytohormone signaling pathways and provided an alternative way to explore the complex mechanisms of drought tolerance in rapeseed.

Twenty-four-hour urinary protein excretion in uncomplicated singleton pregnancy.

BACKGROUND: Twenty-four-hour urinary total protein excretion is an essential parameter used for evaluation of renal function and early detection of gestational complications. However, data on reference ranges of 24-hour urinary total protein excretion in normal pregnancy are scarce. OBJECTIVE: This study aimed to determine reference ranges for 24-hour urinary total protein excretion in a population with uncomplicated singleton pregnancies using a standard method for urinary total protein. In addition, the values of 24-hour urinary total protein were stratified by maternal age and prepregnancy body mass index. STUDY DESIGN: This study was based on a prospective cohort study in Shenzhen, China. The pregnant women were enrolled at their first prenatal clinical visit. All the participants were instructed to collect 24-hour urine samples during the following successive gestational periods: 6+0 to 13+6, 14+0 to 27+6, and 28+0 to 41+6 weeks. Total urinary protein excretion was analyzed by a colorimetric method. Ultimately, the study encompassed a total of 4844 pregnant women with uncomplicated pregnancies. The nonparametric percentile method was used to determine reference ranges for 24-hour urinary total protein excretion during different trimesters in women with uncomplicated pregnancies (excluding those with previous kidney disorders, gestational or chronic hypertension, preeclampsia, and pregestational diabetes mellitus, among others). RESULTS: The 24-hour urinary total protein levels expressed as medians and percentiles (5th, 95th) for each trimester were as follows: 72.0 (28.4, 165.0), 88.0 (34.0, 185.0), and 108.0 (37.5, 258.0) mg in the first, second, and third trimesters, respectively. A significant increase in 24-hour urinary total protein excretion was observed throughout pregnancy (all P values <.001). Moreover, 24-hour urinary total protein levels were higher in the older (≥35 years) than in the younger (<35 years) group from mid-gestation. Specifically, the median (interquartile range) 24-hour urinary total protein levels by age were 72.2 (50.6-100.0) vs 70.5 (50.5-100.0) mg, 85.8 (62.0-117.0) vs 96.0 (68.0-127.8) mg, and 106.6 (76.0-146.2) vs 114.7 (81.5-153.6) mg in the first, second, and third trimesters, respectively. In addition, 24-hour proteinuria was significantly increased in higher-weight (overweight or obese) subgroups compared with lower-weight (underweight or normal-weight) subgroups (all P values <.05). CONCLUSION: Our study provides reference values for 24-hour urinary total protein excretion with apparently uncomplicated pregnancies. Understanding these changes in low-risk pregnancies is essential for optimizing maternal management.

A Critical Review of Conventional and Modern Approaches to Develop Herbicide-Resistance in Rice.

Together with rice, weeds strive for nutrients and space in farmland, resulting in reduced rice yield and quality. Planting herbicide-resistant rice varieties is one of the effective ways to control weeds. In recent years, a series of breakthroughs have been made to generate herbicide-resistant germplasm, especially the emergence of biotechnological tools such as gene editing, which provides an inherent advantage for the knock-out or knock-in of the desired genes. In order to develop herbicide-resistant rice germplasm resources, gene manipulation has been conducted to enhance the herbicide tolerance of rice varieties through the utilization of techniques such as physical and chemical mutagenesis, as well as genome editing. Based on the current research and persisting problems in rice paddy fields, research on the generation of herbicide-resistant rice still needs to explore genetic mechanisms, stacking multiple resistant genes in a single genotype, and transgene-free genome editing using the CRISPR system. Current rapidly developing gene editing technologies can be used to mutate herbicide target genes, enabling targeted genes to maintain their biological functions, and reducing the binding ability of target gene encoded proteins to corresponding herbicides, ultimately resulting in herbicide-resistant crops. In this review article, we have summarized the utilization of conventional and modern approaches to develop herbicide-resistant cultivars in rice as an effective strategy for weed control in paddy fields, and discussed the technology and research directions for creating herbicide-resistant rice in the future.

Cathodic Deposition-Assisted Synthesis of Thin Glass MOF Films for High-Performance Gas Separations.

Glass metal-organic framework (MOF) films can be fabricated from their crystalline counterparts through a melt-quenching process and are prospective candidates for gas separation because of the elimination of the grain boundaries in crystalline MOF films. However, current techniques are limited to producing glass MOF films with a thickness of tens of micrometers, which leads to ultralow gas permeances. Here, we report a novel cathodic deposition-assisted synthesis of glass ZIF-62 films with a thickness as low as ~1 µm. Electrochemical analyses and deposition experiments suggest that the cathodic deposition can lead to pure crystalline ZIF-62 films with a controllable thickness of ~2 µm to ~15 µm. Accordingly, glass ZIF-62 films with a thickness of ~1 µm to ~10 µm can be obtained after a thermal treatment. The fabricated defect-free glass ZIF-62 film measuring 2 µm in thickness shows a remarkable CO2/N2 and CO2/CH4 selectivity of 31.4 and 33.4, respectively, with a CO2 permeance which is over 30 times higher than the best-performing glass ZIF-62 films in literature.

Thermal transport across copper-water interfaces according to deep potential molecular dynamics.

Nanoscale thermal transport at solid-liquid interfaces plays an essential role in many engineering fields. This work performs deep potential molecular dynamics (DPMD) simulations to investigate thermal transport across copper-water interfaces. Unlike traditional classical molecular dynamics (CMD) simulations, we independently train a deep learning potential (DLP) based on density functional theory (DFT) calculations and demonstrated its high computational efficiency and accuracy. The trained DLP predicts radial distribution functions (RDFs), vibrational densities of states (VDOS), density curves, and thermal conductivity of water confined in the nanochannel at a DFT accuracy. The thermal conductivity decreases slightly with an increase in the channel height, while the influence of the cross-sectional area is negligible. Moreover, the predicted interfacial thermal conductance (ITC) across the copper-water interface by DPMD is 2.505 × 108 W m-2 K-1, the same order of magnitude as the CMD and experimental results but with a high computational accuracy. This work seeks to simulate the thermal transport properties of solid-liquid interfaces with DFT accuracy at large-system and long-time scales.

MTM-HCC at Previous Liver Resection as a Predictor of Overall Survival in Salvage Liver Transplantation.

OBJECTIVES: Salvage liver transplantation (sLT) is considered an effective method to treat hepatocellular carcinoma (HCC) recurrence. This multicenter research aimed to identify the prognostic factors associated with recurrence-free survival (RFS) and overall survival (OS) after sLT. MATERIAL AND METHODS: A retrospective analysis of 114 patients who had undergone sLT for recurrent HCC between February 2012 and September 2020 was performed. The baseline and clinicopathological data of the patients were collected. RESULTS: The 1-, 3-, and 5-year RFS rates after sLT were 88.9%, 75.2%, and 69.2%, respectively, and the OS rates were 96.4%, 78.3%, and 70.8%. A time from liver resection (LR) to recurrence < 1 year, disease beyond the Milan criteria at sLT and macrotrabecular massive (MTM)-HCC were identified as risk factors for RFS and were further identified as independent risk factors. A time from LR to recurrence < 1 year, disease beyond the Milan criteria at sLT and MTM-HCC were also risk factors for OS and were further identified as independent risk factors. CONCLUSIONS: Compared with primary liver transplantation (pLT), more prognostic factors are available from patients who had undergone LR. We suggest that in cases of HCC recurrence within 1 year after LR, disease beyond the Milan criteria at sLT and MTM-HCC patients, sLT should be used with caution.

Trimester-specific reference intervals for hemoglobin A1c in non-diabetic pregnancy in a Chinese population.

BACKGROUND: Physiological glycated hemoglobin (HbA1c) values in each trimester are not well defined. This study aimed to determine trimester-specific reference intervals for HbA1c levels in non-diabetic pregnant women in China. METHODS: In this cross-sectional study, 5,042 Chinese pregnant women from 6 to 41 weeks of gestation were screened. An inclusion of 4,134 non-diabetic women was made to determine the reference intervals, they were divided into three trimesters: trimester 1 (T1), 6 weeks to 13 weeks + 6 days, trimester 2 (T2), 14 weeks to 27 weeks + 6 days, and trimester 3 (T3), 28 weeks to 41 weeks + 6 days. A total of 4,134 women (T1 n = 760, T2 n = 1,953, and T3 n = 1,421) provided blood samples which were analyzed for HbA1c concentrations. HbA1c was measured using high-performance liquid chromatography. The median and percentile (2.5th to 97.5th) for the HbA1c reference intervals were calculated for each trimester. RESULTS: In total, 8,732 HbA1c measurements were taken. Reference intervals for HbA1c expressed as median and percentile (2.5th to 97.5th) for each trimester were: T1: 4.7 (4.0-5.5%), T2: 4.5 (3.9-5.3%), and T3: 4.8 (4.1-5.7%) respectively. The HbA1c levels were significantly lower in the second trimester compared to those in the first trimester (p < 0.0001), and higher in the third trimester compared to the second trimester (p < 0.0001). CONCLUSIONS: The reference intervals for HbA1c levels were 3.9-5.7% with upper limits of 5.5% in the first trimester, 5.3% in the second trimester, and 5.7% in the third trimester. These findings highlight the importance of considering trimester-specific reference intervals for HbA1c in non-diabetic pregnant women to promote maternal and fetal health.

A modified Blumgart anastomosis with a simple and practicable procedure after laparoscopic pancreaticoduodenectomy: our center's experience.

BACKGROUND: Laparoscopic pancreaticoduodenectomy(LPD) has become the goal of lots of minimally invasive surgical centers in recent years. Postoperative pancreatic fistula(POPF) is still the barrier to attaining the above goal. Thus, improving anastomosis techniques to reduce the rate of POPF has been a hotspot of surgery. Blumgart pancreaticojejunostomy is considered one of the best anastomosis procedures, with low rates of POPF. However, the original Blumgart pancreaticojejunostomy method is not easy for laparoscopic operation. In consequence, we modified a Blumgart pancreaticojejunostomy technique with a simple and practicable procedure and applied to LPD. METHODS: We collected and retrospectively analyzed the perioperative clinical data of patients who underwent modified Blumgart anastomosis from February 2017 to September 2022. The above patients included 53 cases in open pancreaticojejunostomy(OPD) and 58 cases in LPD. After propensity score matching, 44 cases were included for comparison in each group. RESULTS: After propensity score matching, the average time for pancreaticojejunostomy was about 30 min in the LPD group. The Clinically relevant POPF(CR-POPF) rate was 9.1%. The length of postoperative hospitalization was 13.1 days. Compared with the OPD group, The CR-POPF rate in the LPD group are not significant differences. But the postoperative length of hospital stay was significantly shorter in the LPD group. Besides, there were no other severely postoperative complications between two groups. CONCLUSION: The modified Blumgart anastomosis technique applied to LPD in our Center not only has simple and convenient properties but also low rate of CR-POPF. And this method may be a good choice for surgeons to begin to carry out LPD.

Association between frailty and postoperative delirium: a meta-analysis of cohort study.

BACKGROUND: Frailty has been suggested as a possible risk factor for postoperative delirium (POD). However, results of previous studies were not consistent. We performed a meta-analysis of cohort study to evaluate the above association. METHODS: Relevant studies were obtained via systematic search of PubMed, Embase, SCOPUS, and Web of Science databases. Only studies with multivariate analysis were included. A random-effect model incorporating the potential heterogeneity was used to combine the results. RESULTS: Fifteen cohort studies including 3250 adult patients who underwent surgery were included, and the prevalence of frailty was 27.1% (880/3250) before surgeries. Overall, POD occurred in 513 patients (15.8%). Pooled results showed that frailty was associated with a higher risk of POD (adjusted odds ratio [OR]: 3.23, 95% confidence interval [CI]: 2.56-4.07, P < 0.001) without significant heterogeneity (P for Cochrane's Q test = 0.25, I2 = 18%). Subgroup analyses showed a more remarkable association between frailty and POD in prospective cohort studies (OR: 3.64, 95% CI: 2.95-4.49, P < 0.001) than that in retrospective cohort studies (OR: 2.32, 95% CI: 1.60-3.35, P < 0.001; P for subgroup difference = 0.04). Moreover, the association was not affected by country of the study, age group of the patient, elective or emergency surgeries, cardiac and non-cardiac surgeries, evaluation instruments for frailty, diagnostic methods for POD, or quality score of the study (P for subgroup difference all > 0.05). CONCLUSIONS: Frailty may be associated with a higher risk of POD in adult population.

A novel anastomosis technique facilitates pancreaticojejunostomy in total laparoscopic pancreaticoduodenectomy (with video).

BACKGROUND: While the best technique for pancreatic anastomosis during Whipple's procedure remains controversial, laparoscopic pancreaticoduodenectomy (LPD) has been rapidly increasing in popularity. Because of their feasibility and reliability, new pancreatic anastomosis techniques may have vital roles when adapted for LPD. Here, we describe a new pancreaticojejunostomy (PJ) technique using three sutures (termed the "three sutures" PJ technique), which facilitates pancreatic anastomosis during total LPD. METHODS: A total of 149 patients who underwent LPD using the "three sutures" PJ technique at three hospitals were included in this study (81 patients at Guangdong Provincial People's Hospital [GDPH], 60 patients at Sun Yat-Sen Memorial Hospital [SMH], and 8 patients at Affiliated Hospital of Guangdong Medical University [AHGMU]). Data on the demographic characteristics, operative outcomes, and postoperative results (pancreatic fistula rate, mortality rate, and length of hospital stay) of these patients were collected and analyzed. RESULTS: A surgical video showing the details of the "three sutures" PJ method was included. The mean operation times at GDPH, SMH, and AHGMU were 4.08 ± 0.99 h, 4.65 ± 1.53 h, and 4.67 ± 0.64 h, respectively, and the average PJ times were 17.96 ± 3.49 min, 18.19 ± 2.63 min, and 22.5 ± 3.96 min, respectively. The numbers of grade B pancreatic fistulas were 9 (11.11%), 2 (3.33%), and 1 (12.50%), respectively, and two patients had grade C fistulas, one each at GDPH and SMH. The numbers of clinically relevant postoperative pancreatic fistula (CR-POPF) were 10 (12.35%), 3 (5.00%), and 1 (12.50%) in each center, respectively. The overall rate of CR-POPF was 9.40% (14/149) among patients of all three centers. The perioperative mortality rate was 0%. CONCLUSIONS: The "three sutures" PJ technique for total LPD is a safe and reliable method, with a low risk of pancreatic fistula, short anastomosis time, and steep learning curve.

Laparoscopic nerve­sparing radical hysterectomy for the treatment of cervical cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: The effects and safety of laparoscopic nerve­sparing radical hysterectomy (LNSRH) and laparoscopic radical hysterectomy (LRH) in cervical cancer treatment remain unclear. This article aims to evaluate the role of LNSRH versus LRH in the treatment of cervical cancer. This is because the updated meta-analysis with synthesized data may provide more reliable evidence on the role of LNSRH and LRH. METHODS: We searched Pubmed et al. databases for randomized controlled trials (RCTs) involving laparoscopic nerve­sparing radical hysterectomy (LNSRH) and laparoscopic radical hysterectomy (LRH) for cervical cancer treatment from the inception of databases to June 15, 2021. The RevMan 5.3 software was used for data analyses. This meta-analysis protocol had been registered online (available at: https://inplasy.com/inplasy-2021-9-0047/ ). RESULTS: Thirteen RCTs involving a total of 1002 cervical cancer patients were included. Synthesized results indicated that the duration of surgery of the LNSRH group was significantly longer than that of the LRH group [SMD 1.11, 95% CI (0.15 ~ 2.07), P = 0.02]. The time to intestinal function recovery [SMD -1.27, 95% CI (-1.84 ~ -0.69), P < 0.001] and the time to postoperative urinary catheter removal of the LNSRH group [SMD -1.24, 95% CI (-1.62 ~ -0.86), P < 0.001] were significantly less than that of the LRH group. There were no significant differences in the estimated blood loss [SMD 0.10, 95% CI (-0.14 ~ 0.34), P = 0.41], the length of parauterine tissue resection [SMD -0.10, 95% CI (-0.25 ~ 0.05), P = 0.19], length of vaginal excision [SMD 0.04, 95% CI (-0.26 ~ 0.34), P = 0.78], and incidence of intraoperative adverse events [RR 0.97, 95% CI (0.44 ~ 2.13), P = 0.94] between the LNSRH group and the LRH group. CONCLUSIONS: LNSRH significantly results in earlier bladder and bowel function after surgery. Limited by sample size, LNSRH should be considered with caution in the future.

Genome-wide analysis of long non-coding RNAs (lncRNAs) in two contrasting rapeseed (Brassica napus L.) genotypes subjected to drought stress and re-watering.

BACKGROUND: Drought stress is a major abiotic factor that affects rapeseed (Brassica napus L.) productivity. Though previous studies indicated that long non-coding RNAs (lncRNAs) play a key role in response to drought stress, a scheme for genome-wide identification and characterization of lncRNAs' response to drought stress is still lacking, especially in the case of B. napus. In order to further understand the molecular mechanism of the response of B. napus to drought stress, we compared changes in the transcriptome between Q2 (a drought-tolerant genotype) and Qinyou8 (a drought-sensitive genotype) responding drought stress and rehydration treatment at the seedling stage. RESULTS: A total of 5546 down-regulated and 6997 up-regulated mRNAs were detected in Q2 compared with 7824 and 10,251 in Qinyou8, respectively; 369 down-regulated and 108 up- regulated lncRNAs were detected in Q2 compared with 449 and 257 in Qinyou8, respectively. LncRNA-mRNA interaction network analysis indicated that the co-expression network of Q2 was composed of 145 network nodes and 5175 connections, while the co-expression network of Qinyou8 was composed of 305 network nodes and 22,327 connections. We further identified 34 transcription factors (TFs) corresponding to 126 differentially expressed lncRNAs in Q2, and 45 TFs corresponding to 359 differentially expressed lncRNAs in Qinyou8. Differential expression analysis of lncRNAs indicated that up- and down-regulated mRNAs co-expressed with lncRNAs participated in different metabolic pathways and were involved in different regulatory mechanisms in the two genotypes. Notably, some lncRNAs were co-expressed with BnaC07g44670D, which are associated with plant hormone signal transduction. Additionally, some mRNAs co-located with XLOC_052298, XLOC_094954 and XLOC_012868 were mainly categorized as signal transport and defense/stress response. CONCLUSIONS: The results of this study increased our understanding of expression characterization of rapeseed lncRNAs in response to drought stress and re-watering, which would be useful to provide a reference for the further study of the function and action mechanisms of lncRNAs under drought stress and re-watering.

Synthesis and biological evaluation of a new series of 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives as new anticancer agents.

The diaryl ureas are very important fragments in medicinal chemistry. By means of computer-aided design, 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives were designed and synthesized, and evaluated for their antiproliferative activity against A549, HCT-116, PC-3 cancer cell lines, and HL7702 human normal liver cell lines in vitro by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Most of the target compounds demonstrate significant antiproliferative effects on all the selective cancer cell lines. The calculated IC50 values were reported. The target compound 1-(4-chlorophenyl)-3-{4-{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methoxy}phenyl}urea (7u) demonstrated the most potent inhibitory activity (IC50 = 2.39 ± 0.10 µM for A549 and IC50 = 3.90 ± 0.33 µM for HCT-116), comparable to the positive-control sorafenib (IC50 = 2.12 ± 0.18 µM for A549 and IC50 = 2.25 ± 0.71 µM for HCT-116). Conclusively, 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives as the new anticancer agents were discovered, and could be used as the potential BRAF inhibitors for further research.

Melatonin-Induced Transcriptome Variation of Rapeseed Seedlings under Salt Stress.

Salt stress inhibits the production of all crop species, including rapeseed (Brassica napus L.), the second most widely planted oil crop species. Although melatonin was confirmed to alleviate salt stress in rapeseed seedlings recently, the mechanism governing the expression levels remains unknown. Therefore, the melatonin-induced transcriptome variation of salt-stressed seedlings was explored. In this study, the transcriptomes of leaves and roots under control (CK), salt (125 mM NaCl, ST) and melatonin (125 mM NaCl plus 50 µM melatonin, MS) treatments were evaluated by using next-generation sequencing techniques. After conducting comparisons of gene expression in the roots and leaves between MS and ST, the differentially expressed gene (DEG) pools were screened. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted the significant pathways, which were mainly related to plant hormone synthesis and signal transduction, lignin and fatty acid metabolism. The functional genes in the objective KEGG pathways were identified. Furthermore, members of several transcription factor (TF) families participated in the response process. Combined with the hormone (campesterol (CS), jasmonic acid (JA), and gibberellic acid 3 (GA3)) contents measured in the seedlings, it could be concluded that melatonin induced changes in the intrinsic hormone metabolic network, which promoted seedling growth. Thus, this study identified new candidate genes and pathways active during the interactions between melatonin and salt stress, which provide clues for disclosing melatonin's function in resistance to salt injury. Our results contribute to developing a practical method for sustainable agriculture on saline lands.

Synthesis, Characterization, and Biological Activity of a Novel Series of Benzo[4,5]imidazo[2,1-b]thiazole Derivatives as Potential Epidermal Growth Factor Receptor Inhibitors.

Based on the analysis of epidermal growth factor receptor (EGFR) complexes with gefitinib with molecular docking, the scaffold-hopping strategy, combination of the active substructures, and structural optimization of EGFR inhibitors, a novel series of benzo[4,5]imidazo[2,1-b]thiazole derivatives was designed, synthesized, and evaluated for antitumor activity in human cancer cell lines and cellular toxicity against human normal cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay and EGFR inhibitory activities in vitro. Some target compounds such as 2-(benzo[4,5]imidazo[2,1-b]thiazol-3-yl)-N-(2-hydroxyphenyl)acetamide (D04) and 2-(benzo[4,5]imidazo[2,1-b]thiazol-3-yl)-N-(naphthalen-1-yl)acetamide (D08) have shown significant antitumor activity against the EGFR high-expressed human cell line HeLa. All the target compounds showed hardly any antitumor activity against the EGFR low-expressed human cell line HepG2, and nearly no cellular toxicity against the human normal cell lines HL7702 and human umbilical vein endothelial cell lines (HUVEC). The inhibitory activities against EGFR kinase in vitro of the three target compounds were greatly consistent with the anti-proliferative activities. The preliminary structure⁻activity relationships of the target compounds were summarized. Conclusively, the novel benzo[4,5]imidazo[2,1-b]thiazole derivatives as novel potential EGFR inhibitors may be used as the potential lead compounds for the development of antitumor agents.

Design, Synthesis and Biological Evaluation of a New Series of 1-Aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea Derivatives as Antiproliferative Agents.

To discover new antiproliferative agents with high efficacy and selectivity, a new series of 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea derivatives (7a-7t) were designed, synthesized and evaluated for their antiproliferative activity against A549, HCT-116 and PC-3 cancer cell lines in vitro. Most of the target compounds demonstrated significant antiproliferative effects on all the selective cancer cell lines. Among them, the target compound, 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-{4-{{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}thio}phenyl}urea (7i) was identified to be the most active one against three cell lines, which was more potent than the positive control with an IC50 value of 1.53 ± 0.46, 1.11 ± 0.34 and 1.98 ± 1.27 µM, respectively. Further cellular mechanism studies confirmed that compound 7i could induce the apoptosis of A549 cells in a concentration-dependent manner and elucidated compound 7i arrests cell cycle at G1 phase by flow cytometry analysis. Herein, the studies suggested that the 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea skeleton might be regarded as new chemotypes for designing effective antiproliferative agents.

[Critical quality evaluation and application value of network Meta-analyses in traditional Chinese medicine].

To introduce the application status of network Meta-analysis( NMA) in the field of traditional Chinese medicine,and to discuss the application value of NMA in the field of traditional Chinese medicine,this study comprehensively reviewed the systematic reviews with application of NMA in the field of traditional Chinese medicine. CNKI,Wan Fang,Sino Med,VIP,Embase,PubMed and Cochrane Library and the reference list of previous studies were searched. The AMSTAR scale was used to evaluate the quality of literature methodology,and PRISMA-NMA checklist was used to measure the degree of report specification. Overall,122 articles were included,including 80 in Chinese and 42 in English. The included studies centered on cancer,bone and joint disease,cardiovascular disease,respiratory disease,mental disease and digestive disease. Additionally,the intervention can be categorized into three groups,traditional Chinese medicine injection,oral Chinese medicine or prescription,and traditional physical therapy including acupuncture.Nearly one-third of the researches' intervention program is aimed at comparing the effect of Chinese and Western combined therapy and monotherapy. The overall methodology quality grade is medium and the report quality is average,with methodology reporting and result reporting especially need to be improved. The subgroup analysis shows that the methodology quality of the English literatures is evidently higher than Chinese literatures,and the quality of the literatures published after 2015 is higher than those published in or before 2015.This study indicates that the NMA can compare multiple treatments simultaneously,which accords with characteristics of the clinical practice in traditional Chinese medicine that is complex and individual. NMA in the field of traditional Chinese medicine is still in the process of development. With higher level of quality control and reporting as well as the improvement of the statistical methodology and the accumulation of original researches,NMA application in the field of traditional Chinese medicine will be promising.

A Metal Chelating Porous Polymeric Support: The Missing Link for a Defect-Free Metal-Organic Framework Composite Membrane.

Since the discovery of size-selective metal-organic frameworks (MOFs), researchers have tried to incorporate these materials into gas separation membranes. Impressive gas selectivities were found, but these MOF membranes were mostly made on inorganic supports, which are generally too bulky and expensive for industrial gas separation. Forming MOF layers on porous polymer supports is industrially attractive but technically challenging. Two features to overcome these problems are described: 1) a metal chelating support polymer to bind the MOF layer, and 2) control of MOF crystal growth by contra-diffusion, aiming at a very thin nanocrystalline MOF layer. Using a metal chelating poly-thiosemicarbazide (PTSC) support and adjusting the metal and organic ligand concentrations carefully, a very compact ZIF-8 (ZIF=zeolitic imidazolate framework) layer was produced that displayed interference colors because of its smooth surface and extreme thinness-within the range of visible light. High performances were measured in terms of hydrogen/propane (8350) and propylene/propane (150) selectivity.

3-Bromopyruvate inhibits cell proliferation and induces apoptosis in CD133+ population in human glioma.

The study was aimed to investigate the role of 3-bromopyruvate in inhibition of CD133+ U87 human glioma cell population growth. The results demonstrated that 3-bromopyruvate inhibited the viability of both CD133+ and parental cells derived from U87 human glioma cell line. However, the 3-bromopyruvate-induced inhibition in viability was more prominent in CD133+ cells at 10 µM concentration after 48 h. Treatment of CD133+ cells with 3-bromopyruvate caused reduction in cell population and cell size, membrane bubbling, and degradation of cell membranes. Hoechst 33258 staining showed condensation of chromatin material and fragmentation of DNA in treated CD133+ cells after 48 h. 3-Bromopyruvate inhibited the migration rate of CD133+ cells significantly compared to the parental cells. Flow cytometry revealed that exposure of CD133+ cells to 3-bromopyruvate increased the cell population in S phase from 24.5 to 37.9 % with increase in time from 12 to 48 h. In addition, 3-bromopyruvate significantly enhanced the expression of Bax and cleaved caspase 3 in CD133+ cells compared to the parental cells. Therefore, 3-bromopyruvate is a potent chemotherapeutic agent for the treatment of glioma by targeting stem cells selectively.

MicroRNA-146a and Ets-1 gene polymorphisms in ocular Behcet's disease and Vogt-Koyanagi-Harada syndrome.

AIM: MicroRNA-146a (miR-146a) is involved in certain immune-mediated diseases. Transcription factor Ets-1 strongly affects miR-146a promoter activity and directly regulates miR-146a expression. This study was performed to investigate the association of miR-146a and Ets-1 gene polymorphisms with Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) disease in a Chinese Han population. METHODS: A total of 809 patients with BD, 613 patients with VKH and 1132 normal controls were genotyped for miR-146a/rs2910164, rs57095329 and rs6864584, Ets-1/rs1128334 and rs10893872 using a PCR restriction fragment length polymorphism assay. miR-146a expression was examined in peripheral blood mononuclear cells (PBMCs) by real-time PCR. Cytokine production by PBMCs was measured by ELISA. RESULTS: A significantly decreased frequency of the homozygous rs2910164 CC genotype and C allele was observed in patients with BD compared with controls (pc(a)=1.24×10(-5), OR 0.61; pc(a)=1.33×10(-4), OR 0.75, respectively). MiR-146a expression in GG cases was 2.45-fold and 1.99-fold higher, respectively, than that in CC cases and GC cases. There was no association of the other four single nucleotide polymorphisms (SNPs) with BD. There was also no association of these five SNPs with its main clinical features. No associations were found with the five SNPs tested or with its clinical manifestations in VKH disease. Interleukin (IL)-17, tumour necrosis factor (TNF)α and IL-1ß production from rs2910164 CC cases was markedly lower than that in GG cases. No effect of genotype was observed on IL-6 and monocyte chemoattractant protein (MCP)-1 production and IL-8 expression was slightly higher in CC cases. CONCLUSIONS: Our study identified a strong association of rs2910164 of miR-146a with BD in a Chinese population and decreased expression of miR-146a and certain proinflammatory cytokines in individuals carrying the CC genotype.