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The locus at 17q12 erb-b2 receptor tyrosine kinase 2 (ERBB2) has been heavily amplificated and overexpressed in gastric cancer (GC), but it remains to be elucidated about the clinical significance of the co-amplification and co-overexpression of PGAP3 gene located around ERBB2 in GC. The profile of PGAP3 and ERBB2 in four GC cell lines and tissue microarrays containing 418 primary GC tissues was assessed to investigate the co-overexpression and clinical significance of the co-amplified genes, and to evaluate the impact of the co-amplified genes on the malignancy of GC. Co-amplification of PGAP3 and ERBB2 accompanied with co-overexpression was observed in a haploid chromosome 17 of NCI-N87 cells with double minutes (DMs). PGAP3 and ERBB2 were overexpressed and positively correlated in 418 GC patients. Co-overexpression of the PGAP3 and ERBB2 was correlated with T stage, TNM stage, tumour size, intestinal histological type and poor survival proportion in 141 GC patients. In vitro, knockdown of the endogenous PGAP3 or ERBB2 decreased cell proliferation and invasion, increased G1 phase accumulation and induced apoptosis in NCI-N87 cells. Furthermore, combined silencing of PGAP3 and ERBB2 showed an additive effect on resisting proliferation of NCI-N87 cells compared with targeting ERBB2 or PGAP3 alone. Taken together, the co-overexpression of PGAP3 and ERBB2 may be crucial due to its significant correlation with clinicopathological factors of GC. Haploid gain of PGAP3 co-amplified with ERBB2 is sufficient to facilitate the malignancy and progression of GC cells in a synergistic way.
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Receptor ErbB-2 , Neoplasias Gástricas , Humanos , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Hidrolasas de Éster Carboxílico , Receptores de Superficie CelularRESUMEN
A novel chiral P,Se-heterodonor ligand has been designed and prepared through an efficient and simple operation. This ligand can be successfully applied to Pd-catalyzed asymmetric allylic substitution with C- and N-nucleophiles, producing a diverse range of chiral allylic products in high yields and enantioselectivities (up to 99% yield and 95% ee).
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Paladio , Catálisis , Ligandos , Compuestos Organofosforados , EstereoisomerismoRESUMEN
Objective:To investigate the epidemiology, evolution and transmission characteristics of HIV-1 CRF07_BC in Nanjing between 2015 and 2019 to provide scientific basis for precise prevention and control of HIV-1 transmission.Methods:Pol gene sequences of 319 patients with HIV-1 CRF07_BC infection in Nanjing were amplified and sequenced and a maximum likelihood phylogenetic tree was then constructed. Markov Chain Monte Carlo sampling method was used to generate Maximum Clade Credibility Tree. Bayesian Skyline Plot was used to reconstruct the changing trend of the effective population size. Pairwise gene distance method was used to construct molecular network to investigate the transmission features. Results:Among the 319 patients, 303 (95.0%) were male; 264 (82.8%) had multiple sexual partners; only 14 (4.4%) had been using condoms. Most of the infections were occurred in men who have sex with men (MSM), accounting for 77.4%. The maximum likelihood phylogenetic analysis of HIV-1 CRF07_BC revealed two clusters: Cluster1 and Cluster2. Cluster1 mainly contained the strains isolated from MSM and Cluster2 mainly consisted of the strains isolated from heterosexual patients. The most recent common ancestor was 2002.47(1999.91, 2005.43) year for Cluster1 and 1996.38(1992.55, 1999.76) year for Cluster2. The evolutionary rates (95% highest posterior density, 95%HPD) of Cluster1 and Cluster2 were 1.73×10 -3 (1.36×10 -3-2.16×10 -3) substitutions·site -1·year -1 and 2.09×10 -3 (1.50×10 -3 -2.79×10 -3 ) substitutions·site -1·year -1, respectively. The effective population sizes of Cluster1 and Cluster2 tended to be stable after 2002 and 2003, respectively. In addition, Cluster1 and Cluster2 formed eleven and eight unique branches, respectively, suggesting the possibility of divergent epidemics of this genotype. A total of 35 propagation clusters were formed in the molecular propagation network, including 92 Nanjing sequences with an average degree of 4.3. Males, MSM and people with multiple sexual partners were more likely to be connected to the network. Students and young patients were more likely to be connected to the network. Conclusions:HIV-1 CRF07_BC infection was characterized by low age, multiple sexual partners, unprotected behaviors and transmission among MSM in Nanjing from 2015 to 2019. It was recommended to pay more attention to students and young people, to formulate more effective prevention and control measures for high-risk sexual behaviors, and to carry out continuous molecular monitoring of CRF07_BC strain, so as to provide scientific basis for the prevention and control of HIV CRF07_BC.
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A Brønsted acid enabled nickel-catalyzed hydroalkenylation of aldehydes and styrene derivatives has been developed. The Brønsted acid acts as a proton shuttle to transfer a proton from the alkene to the aldehyde, thereby leading to an economical and byproduct-free coupling. A series of synthetically useful allylic alcohols were obtained through one-step reactions from readily available styrene derivatives and aliphatic aldehydes in up to 88 % yield and with high linear selectivity.
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A Ni-Al bimetallic catalyzed enantioselective cycloaddition reaction of cyclopropyl carboxamides with alkynes has been developed. A series of cyclopentenyl carboxamides were obtained in up to 99% yield and 94% ee. The bifunctional-ligand-enabled bimetallic catalysis proved to be an efficient strategy for the C-C bond cleavage of unreactive cyclopropanes.
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Objective To understand the correlations between HIV-1 subtypes and changes in CD4+T cell count over time in patients with different subtypes of HIV-1 infection.Methods A total of 94 patients who were diagnosed with HIV-1 infection in Nanjing and received at least twice CD4+T cell counting test before antiretroviral therapy (ART) were recruited in this study.Descriptive analysis was used to present the rates of CD4+T cell decline for different HIV-1 subtypes.Logistic regression analysis and nonparametric test were conducted to investigate the factors responsible for CD4+T cell decline and to analyze the correlations between the rates of CD4+T cell decline and HIV-1 subtypes.Results The median monthly rate of CD4+T cell decline was-2.20 [interquartile range (IQR):-11.36-2.13] cell/μl.Of all patients,25.5% (24/94) had a significant decline (≥30%) in CD4+T cell count.Compared with the patients infected with CRF01_AE,those infected with CRF07_BC (OR=0.28,95%CI: 1.7-6.5) or other subtypes (OR=0.16,95%CI: 1.0-2.9) had a lower risk of significant decline in CD4+T cell count.In addition,results of the nonparametric test showed that the patients infected with CRF01_AE (M=-21.54,IQR:-30.97——11.92 cell/μl) had a faster CD4+T cell loss than those infected with CRF07_BC (M=-11.26,IQR:-14.06——5.63 cell/μl) (P=0.033).Conclusion HIV-1 subtype is associated with the rate of CD4+T cell decline.It is important to monitor the changes in CD4+T cell count in patients infected with CRF01_AE and to carry out timely ART.
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Objective@#To analyze the influence of growing experience on non-heterosexual orientation among male college students.@*Methods@#From October to November in 2015, a total of 2 535 male students from 96 classes in 14 colleges/departments were recruited from two colleges that participated in the experimental work of AIDS prevention by cluster random sampling method. A structured questionnaire was administered in this study, including general demographic information, growing experience and Kinsey scale (to evaluate sexual orientation). Out of 2 500 questionnaires distributed in this study, 2 332 effective copies were withdrew, with the effective rate at 93.3%. Chi square test was used to analyze the differences of non-heterosexual orientation among the individuals with different social demographic characteristics. Multivariate logistic regression model was used to analyze the influencing factors of non-heterosexual orientation.@*Results@#Among the 2 332 individuals, the proportion of self-reported non-heterosexual was 6.2% (144).The proportions of male students who identify as non-heterosexual from freshman to junior year were 5.2%(63/1216),6.9%(65/941),11.7%(13/111) and 4.7%(3/64), respectively (χ2=9.06,P=0.029). Compared with the individuals of very good relationship with parents, those with bad relationship (OR=3.3, 95%CI: 1.7-6.5) and general relationship (OR=1.7, 95%CI: 1.0-2.9) with parents had a higher risk of non-heterosexual orientation, respectively. Those encountered sexual assault had a higher risk of non-heterosexual orientation than those without encountered sexual assault (OR=5.9, 95%CI: 3.2-10.9).@*Conclusions@#This study reported a high proportion of self-reported non-heterosexual among college male students in Nanjing, and highlighted the importance of targeting students with poor parental relationships and who subjected to sexually abused.
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To identify new antifungal lead compound based on inhibitors of pyruvate dehydrogenase complex E1, a series of 5-iodo-1,4-disubstituted-1,2,3-triazole derivatives 3 were prepared and evaluated for their Escherichia coli PDHc-E1 inhibitory activity and antifungal activity. The in vitro bioassay for the PDHc-E1 inhibition indicated all the compounds exhibited significant inhibition against E. coli PDHc-E1 (IC50<21µM), special compound 3g showed the most potent inhibitory activity (IC50=4.21±0.11µM) and was demonstrated to act as a competitive inhibitor of PDHc-E1. Meanwhile, inhibitor 3g exhibited very good enzyme-selective inhibition of PDHc-E1 between pig heart and E. coli. The assay of antifungal activity showed compounds 3e, 3g, and 3n exhibited fair to good activity against Rhizoctonia solani and Botrytis cinerea even at 12.5µg/mL. Especially compound 3n (EC50=5.4µg/mL; EC90=21.1µg/mL) exhibited almost 5.50 times inhibitory potency against B. cinerea than that of pyrimethanil (EC50=29.6µg/mL; EC90=113.4µg/mL). Therefore, in this study, compound 3n was found to be a novel lead compound for further optimization to find more potent antifungal compounds as microbial PDHc-E1 inhibitors.
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Antifúngicos/síntesis química , Antifúngicos/farmacología , Piruvato Deshidrogenasa (Lipoamida)/antagonistas & inhibidores , Triazoles/síntesis química , Triazoles/farmacología , Animales , Piruvato Deshidrogenasa (Lipoamida)/metabolismo , Complejo Piruvato Deshidrogenasa/antagonistas & inhibidores , Complejo Piruvato Deshidrogenasa/metabolismo , Rhizoctonia/efectos de los fármacos , PorcinosRESUMEN
By targeting the ThDP binding site of Escherichia coli PDHc-E1, two new 'open-chain' classes of E. coli PDHc-E1 inhibitors, amide and urea derivatives, were designed, synthesized, and evaluated. The amide derivatives of compound 6d, with 4-NO2 in the benzene ring, showed the most potent inhibition of E. coli PDHc-E1. The urea derivatives displayed more potent inhibitory activity than the corresponding amide derivatives with the same substituent. Molecular docking studies confirmed that the urea derivatives have more potency due to the two hydrogen bonds formed by two NH of urea with Glu522. The docking results also indicate it might help us to design more efficient PDHc-E1 inhibitors that could interact with Glu522.
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Amidas/química , Diseño de Fármacos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Escherichia coli/efectos de los fármacos , Simulación del Acoplamiento Molecular , Piruvato Deshidrogenasa (Lipoamida)/antagonistas & inhibidores , Urea/química , Sitios de Unión , Dominio Catalítico , Escherichia coli/enzimología , Enlace de Hidrógeno , Modelos Moleculares , Estructura MolecularRESUMEN
Graphene and hexagonal boron nitride are typical conductor and insulator, respectively, while their hybrids hexagonal boron carbonitride are promising as a semiconductor. Here we demonstrate a direct chemical conversion reaction, which systematically converts the hexagonal carbon lattice of graphene to boron nitride, making it possible to produce uniform boron nitride and boron carbonitride structures without disrupting the structural integrity of the original graphene templates. We synthesize high-quality atomic layer films with boron-, nitrogen- and carbon-containing atomic layers with full range of compositions. Using this approach, the electrical resistance, carrier mobilities and bandgaps of these atomic layers can be tuned from conductor to semiconductor to insulator. Combining this technique with lithography, local conversion could be realized at the nanometre scale, enabling the fabrication of in-plane atomic layer structures consisting of graphene, boron nitride and boron carbonitride. This is a step towards scalable synthesis of atomically thin two-dimensional integrated circuits.
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Ternary two-dimensional dichalcogenide alloys exhibit compositionally modulated electronic structure, and hence, control of dopant concentration within each individual layer of these compounds provides a powerful tool to efficiently modify their physical and chemical properties. The main challenge arises when quantifying and locating the dopant atoms within each layer in order to better understand and fine-tune the desired properties. Here we report the synthesis of molybdenum disulfide substitutionally doped with a broad range of selenium concentrations, resulting in over 10% optical band gap modulations in atomic layers. Chemical analysis using Z-contrast imaging provides direct maps of the dopant atom distribution in individual MoS2 layers and hence a measure of the local optical band gaps. Furthermore, in a bilayer structure, the dopant distribution is imaged layer-by-layer. This work demonstrates that each layer in the bilayer system contains similar local Se concentrations, randomly distributed, providing new insights into the growth mechanism and alloying behavior in two-dimensional dichalcogenide atomic layers. The results show that growth of uniform, ternary, two-dimensional dichalcogenide alloy films with tunable electronic properties is feasible.
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We present a quantitative analysis of the electron transfer between single gold nanorods and monolayer graphene under no electrical bias. Using single-particle dark-field scattering and photoluminescence spectroscopy to access the homogeneous linewidth, we observe broadening of the surface plasmon resonance for gold nanorods on graphene compared to nanorods on a quartz substrate. Because of the absence of spectral plasmon shifts, dielectric interactions between the gold nanorods and graphene are not important and we instead assign the plasmon damping to charge transfer between plasmon-generated hot electrons and the graphene that acts as an efficient acceptor. Analysis of the plasmon linewidth yields an average electron transfer time of 160 ± 30 fs, which is otherwise difficult to measure directly in the time domain with single-particle sensitivity. In comparison to intrinsic hot electron decay and radiative relaxation, we furthermore calculate from the plasmon linewidth that charge transfer between the gold nanorods and the graphene support occurs with an efficiency of â¼10%. Our results are important for future applications of light harvesting with metal nanoparticle plasmons and efficient hot electron acceptors as well as for understanding hot electron transfer in plasmon-assisted chemical reactions.
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We report the direct growth of large, atomically thin GaSe single crystals on insulating substrates by vapor phase mass transport. A correlation is identified between the number of layers and a Raman shift and intensity change. We found obvious contrast of the resistance of the material in the dark and when illuminated with visible light. In the photoconductivity measurement we observed a low dark current. The on-off ratio measured with a 405 nm at 0.5 mW/mm(2) light source is in the order of 10(3); the photoresponsivity is 17 mA/W, and the quantum efficiency is 5.2%, suggesting possibility for photodetector and sensor applications. The photocurrent spectrum of few-layer GaSe shows an intense blue shift of the excitation edge and expanded band gap compared with bulk material.
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<p><b>OBJECTIVE</b>Effects of red palm oil on major plasma carotenoids, tocopherol, retinol and serum lipids were evaluated when used in Chinese diet.</p><p><b>METHODS</b>Red palm oil group (RPO) composed of 20 male subjects(aged 18-32) and soybean oil group (SBO) composed of 22 male subjects (aged 18-32). Dietary fat provided about 28% of total calories, and the test oil accounted for about 60% of total dietary fat. In the 3 weeks of pretest period, diets were prepared with soybean oil, and then in the next 6 weeks subjects in each group consumed the diet prepared by test oil.</p><p><b>RESULTS</b>Plasma alpha-carotene, beta-carotene and lycopene concentration of RPO group significantly increased at the time of interim (21 days) and of the end (42 days) (P < 0.05), and alpha-tocopherol concentration significantly increased at the time of the end (42 days) in this study. Though Chinese plasma retinol level was relatively low when compared with that of Westerners, red palm oil diet showed no significant effect on adult Chinese plasma retinol level. Serum concentration of total cholesterol, triglyceride, high density lipoprotein cholesterol, apolipoprotein AI and apolipoprotein B of all subjects showed no significant changes in RPO group during the study.</p><p><b>CONCLUSIONS</b>The data in our study suggest that red palm oil is a good source of carotenoids and vitamin E when used in Chinese diet preparation, and it can significantly increase plasma concentration of alpha-carotene, beta-carotene, lycopene and alpha-tocopherol.</p>
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Adolescente , Adulto , Humanos , Masculino , Administración Oral , Carotenoides , Sangre , China , Dieta , Lípidos , Sangre , Aceite de Palma , Aceites de Plantas , Farmacología , Tocoferoles , Sangre , Vitamina A , SangreRESUMEN
<p><b>OBJECTIVES</b>To investigate the effects of calcium and vitamin D supplementation in fortified milk on physical development in Chinese school girls aged 10 - 12 years.</p><p><b>METHODS</b>A non-randomized, double-blind intervention trial was carried out at nine primary schools of Beijing for two years. Seven hundred and fifty-seven girls (with an average age of 10.1 years) were recruited from nine primary schools in Beijing, China. They were divided into three trial groups, a control group (n = 259) having regular diet without milk supplementation, Group 1 (n = 238) having regular diet supplemented with 144 ml/d of calcium-fortified milk, and Group 2 (n = 260) having regular diet supplemented with 144 ml/d of calcium and vitamin D-fortified milk. Data of dietary intake and physical activities were collected by questionnaire, and height, weight, sitting height and knee height were measured before, during and after intervention.</p><p><b>RESULTS</b>Two years after intervention, the percentage increases in height and weight were significantly greater in Groups 1 and 2 than those in control group (9.52%, 9.26% and 8.59% in height, and 34.53%, 35.38% and 30.91% in weight, respectively). The percentage increase of sitting height was greater in Group 1 than those in Group 2, and then than that in control group (9.21%, 8.58% and 7.87%, respectively). The percentage increase of knee height was significantly greater in Group 1 than that in Group 2 and control group (9.00%, 8.37% and 8.44%, respectively).</p><p><b>CONCLUSION</b>Calcium and vitamin D-fortified milk supplementation could promote their physical development in girls aged 10 - 12 years.</p>