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1.
Bioorg Med Chem ; 93: 117455, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37643500

RESUMO

Human sirtuin 5 (SIRT5) participates in a variety of metabolic disorder-associated diseases, including cancer. Inhibition of SIRT5 has been confirmed to provide a new strategy for treatment of related diseases. Previously, we discovered a pyrimidine skeleton inhibitor XIV, which showed low micromolar inhibitory activity against SIRT5. Herein, we utilized the scaffold-hopping strategy to design and synthesize a series of 2,4,6- trisubstituted triazine derivatives. The SAR analysis led to the discovery of several new SIRT5 inhibitors with low micromolar inhibition levels. The most potent compounds 10 (IC50 = 5.38 µM), and 14 (IC50 = 4.07 µM) were further confirmed to be the substrate-competitive SIRT5 inhibitors through enzyme kinetic assays, which is consistent with the molecular docking analyses. Fluorescence-based thermal shift assays proved that these compounds may stabilize SIRT5 by binding withprotein.. In addition, compounds 10 and 14 were also revealed to have moderate selectivity to SIRT5 over SIRT1-3. This study will aid further efforts to develop highly potent and selective SIRT5 inhibitors for the treatment of cancer and other related diseases.


Assuntos
Compostos Radiofarmacêuticos , Sirtuínas , Humanos , Simulação de Acoplamento Molecular , Bioensaio , Ensaios Enzimáticos , Triazinas/farmacologia
2.
Respir Res ; 21(1): 69, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164675

RESUMO

BACKGROUND: Glycopyrrolate (GP)/formoterol fumarate (FF; GFF) metered dose inhaler is a fixed-dose combination dual bronchodilator for patients with chronic obstructive pulmonary disease (COPD); however, whether the efficacy in patients without current maintenance treatment is consistent with currently maintenance-treated patients is unclear. METHODS: Data from patients who were not maintenance-treated at screening (NMT) (n = 1943) and patients who were maintenance-treated at screening (MT) patients (n = 3040) receiving GFF, FF, GP, or placebo were pooled from the Phase III PINNACLE studies (NCT01854645, NCT01854658, NCT02343458) for post-hoc analysis. MT patients had received long-acting bronchodilators and/or inhaled corticosteroids in the 30 days prior to screening, and/or prior to randomization. NMT patients had received short-acting bronchodilators or no treatment. Outcomes included forced expiratory volume over 1 s (FEV1), clinically important deterioration (CID), rescue medication use, and safety. RESULTS: GFF provided significant lung function improvements at Week 24 versus placebo, GP, and FF for NMT patients, with pre-dose trough FEV1 treatment differences of 152 (117-188) mL, 73 (45-100) mL, and 56 (29-84) mL, respectively (least squares mean change from baseline versus comparators [95% CI]; all P < 0.0001). GFF reduced the risk of CID by 17-43% in NMT (P ≤ 0.0157) and 18-52% (P ≤ 0.0012) in MT patients compared with monotherapy and placebo, and reduced rescue medication use by 1.5 puffs/day over 24 weeks for both cohorts. Safety profiles for all cohorts were consistent with each other and the parent studies. CONCLUSIONS: NMT patients achieved better lung function with GFF versus monotherapy and placebo, without increased safety risk. Dual bronchodilator therapy may offer better outcomes than monotherapy for COPD patients when administered as first-line treatment.


Assuntos
Broncodilatadores/administração & dosagem , Fumarato de Formoterol/administração & dosagem , Glicopirrolato/administração & dosagem , Inaladores Dosimetrados , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem
3.
Chemistry ; 26(14): 3113-3118, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-31845420

RESUMO

A series of twistacene-functionalized donor (D)-π-acceptor (A) derivatives (2-5) have been designed and synthesized, in which twistacene can be regarded as a promising platform for electron-rich systems for fluorescence emitters. The connecting modes and various acceptors are also examined to investigate the effect of structural changes on the photophysical, electrochemical, and thermal properties. The strong electron-withdrawing capability of the arylboron-modified benzonitrile unit can effectively separate the HOMO and LUMO energy levels of 4/5, which is beneficial for the formation of thermally activated delayed fluorescence (TADF) molecules. Cyan and orange organic light-emitting diodes based on 4 and 5 exhibit promising electroluminescence with a maximum brightness of 7643 cd m-2 for device-4 and 14871 cd m-2 for device-5.

4.
Org Biomol Chem ; 17(34): 7964-7972, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31407769

RESUMO

We describe the design and modular synthesis of a library of substituted hexabenzoovalene derivatives (SHBO), along with the key precursor dinaphthopyrenes (3), highlighting the influence of a wide array of substituent variation on the photophysical properties via UV-vis absorption, fluorescence spectra and electrochemical methods. The results show that the cyclized hexabenzoovalenes present a stronger spectroscopic red-shift than the corresponding dinaphthopyrenes. X-ray diffraction analysis suggests that intermediate 3hx containing two nitro groups forms a trans-configuration with twisted structures. Our systematic investigation might provide a realistic design strategy to construct large one-dimensional and two-dimensional materials via bottom-up approaches.

5.
Molecules ; 24(15)2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31357491

RESUMO

Human sirtuin 2 (SIRT2), a member of the sirtuin family, has been considered as a promising drug target in cancer, neurodegenerative diseases, type II diabetes, and bacterial infections. Thus, SIRT2 inhibitors have been involved in effective treatment strategies for related diseases. Using previously established fluorescence-based assays for SIRT2 activity tests, the authors screened their in-house database and identified a compound, 4-(5-((3-(quinolin-5-yl)ureido)methyl)furan-2-yl)benzoic acid (20), which displayed 63 ± 5% and 35 ± 3% inhibition against SIRT2 at 100 µM and 10 µM, respectively. The structure-activity relationship (SAR) analyses of a series of synthesized (5-phenylfuran-2-yl)methanamine derivatives led to the identification of a potent compound 25 with an IC50 value of 2.47 µM, which is more potent than AGK2 (IC50 = 17.75 µM). Meanwhile, 25 likely possesses better water solubility (cLogP = 1.63 and cLogS = -3.63). Finally, the molecular docking analyses indicated that 25 fitted well with the induced hydrophobic pocket of SIRT2.


Assuntos
Descoberta de Drogas , Inibidores de Histona Desacetilases/química , Metilaminas/química , Sirtuína 2/química , Inibidores de Histona Desacetilases/farmacologia , Humanos , Metilaminas/farmacologia , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Sirtuína 2/antagonistas & inibidores , Relação Estrutura-Atividade
6.
Molecules ; 25(1)2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31877988

RESUMO

The emergence and spread of metallo-ß-lactamase (MBL)-mediated resistance to ß-lactam antibacterials has already threatened the global public health. A clinically useful MBL inhibitor that can reverse ß-lactam resistance has not been established yet. We here report a series of [1,2,4]triazole derivatives and analogs, which displayed inhibition to the clinically relevant subclass B1 (Verona integron-encoded MBL-2) VIM-2. 3-(4-Bromophenyl)-6,7-dihydro-5H-[1,2,4]triazolo [3,4-b][1,3]thiazine (5l) manifested the most potent inhibition with an IC50 (half-maximal inhibitory concentration) value of 38.36 µM. Investigations of 5l against other B1 MBLs and the serine ß-lactamases (SBLs) revealed the selectivity to VIM-2. Molecular docking analyses suggested that 5l bound to the VIM-2 active site via the triazole involving zinc coordination and made hydrophobic interactions with the residues Phe61 and Tyr67 on the flexible L1 loop. This work provided new triazole-based MBL inhibitors and may aid efforts to develop new types of inhibitors combating MBL-mediated resistance.


Assuntos
Bactérias/efeitos dos fármacos , Proteínas de Bactérias/antagonistas & inibidores , Proteínas do Citoesqueleto/antagonistas & inibidores , Triazóis/química , beta-Lactamases/química , Bactérias/patogenicidade , Proteínas de Bactérias/química , Proteínas do Citoesqueleto/química , Triazóis/síntese química , Triazóis/farmacologia , Resistência beta-Lactâmica/efeitos dos fármacos , Inibidores de beta-Lactamases/química , Inibidores de beta-Lactamases/farmacologia
7.
Zhonghua Xin Xue Guan Bing Za Zhi ; 42(7): 598-602, 2014 Jul.
Artigo em Zh | MEDLINE | ID: mdl-25327604

RESUMO

OBJECTIVE: To investigate the impact of premature birth on long term cardio-cerebral vascular events of puerpera. METHODS: Ambispective cohort study method was used and 3 659 pregnant women giving birth during October 1976 to December 2008 at Kailuan medical group were included and divided into premature birth (PTB) group (n = 226) and non-PTB (NPTB) group (n = 3 433) by the history of PTB. Incidence of cardio-cerebral vascular events (myocardial infarction, cerebral infarction and cerebral hemorrhage) was obtained during follow-up. Multivariable Cox proportional hazards regression models was used to assess the relative risk of cardio-cerebral vascular events. RESULTS: (1) The childbearing age, proportion of pregnancy-induced hypertension, systolic blood pressure and diastolic blood pressure before delivery were significantly higher while weight and height of newborn were significantly less in PTB group than in NPTB group (P < 0.05 or 0.01). (2) There were 71 cardio-cerebral vascular events during the follow-up of (15.19 ± 7.75) years. In PTB group, the incidence of cardio-cerebral vascular events and myocardial infarction was 3.23/1 000 person-years and 2.05/1 000 person-years, respectively, while the corresponding incidence was 1.15/1 000 person-years and 0.42/1 000 person-years, respectively in NPTB group (all P < 0.05). After adjustment for other traditional cardiovascular risk factors, the risk of total cardio-cerebral vascular events, myocardial infarction in PTB group was 2.03 fold (95% CI: 1.02-4.04, P = 0.002) and 3.11 fold (95% CI: 1.18-8.18, P < 0.001) higher than in NPTB group. CONCLUSION: PTB is an independent risk factor for total cardio-cerebral vascular events, especially myocardial infarction of puerpera.


Assuntos
Doenças Cardiovasculares/epidemiologia , Infarto do Miocárdio/epidemiologia , Nascimento Prematuro , Pressão Sanguínea , Estudos de Coortes , Feminino , Humanos , Hipertensão Induzida pela Gravidez , Incidência , Gravidez , Modelos de Riscos Proporcionais , Fatores de Risco , Acidente Vascular Cerebral
8.
Plant Physiol Biochem ; 207: 108402, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38310726

RESUMO

Tartary buckwheat (Fagopyrum tataricum) is frequently employed as a resource to develop health foods, owing to its abundant flavonoids such as rutin. However, the consumption of Tartary buckwheat (TB) is limited in food products due to the strong bitterness induced by the hydrolysis of rutin into quercetin. This transformation is facilitated by the degrading enzyme (RDE). While multiple RDE isoenzymes exist in TB, the superior coding gene of FtRDEs has not been fully explored, which hinders the breeding of TB varieties with minimal bitterness. Here, we found that FtRDE2 is the most abundant enzyme in RDE crude extracts, and its corresponding gene is specifically expressed in TB seeds. Results showed that FtRDE2 has strong rutin hydrolysis activity. Overexpression of FtRDE2 not only significantly promoted rutin hydrolysis and quercetin accumulation but also dramatically upregulated genes involved in the early phase of flavonoid synthesis (FtPAL1、FtC4H1、Ft4CL1, FtCHI1) and anthocyanin metabolism (FtDFR1). These findings elucidate the role of FtRDE2, emphasizing it as an endogenous factor contributing to the bitterness in TB and its involvement in the metabolic regulatory network. Moreover, correlation analysis revealed a positive relationship between the catalytic activity of RDE extracts and the expression level of FtRDE2 during seed germination. In summary, our results suggest that FtRDE2 can serve as a promising candidate for the molecular breeding of a TB variety with minimal bitterness.


Assuntos
Fagopyrum , Quercetina , Quercetina/metabolismo , Fagopyrum/genética , Fagopyrum/metabolismo , Melhoramento Vegetal , Rutina/metabolismo , Sementes/metabolismo
9.
Sci Rep ; 14(1): 21210, 2024 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261539

RESUMO

Primary dysmenorrhea (PD) is a common global health concern. However, limited studies explored the association between soft drinks intake and PD among female undergraduates in China. To determine the association between soft drinks (carbonated soft drinks, etc.) as well coffee intake and the incidence/severity of PD among female undergraduates in China. We performed a cross-sectional study among 1809 female undergraduates in China from September 29, 2020 to October 22, 2020. The demographic information and menstrual information of the participants were collected by a self-administrated questionnaire. Chi-square test, ANOVA test, and logistic regression test were used to investigate the association between soft drinks intake and the incidence/severity of PD. We also conducted stratification analysis among different locations (rural or urban). The prevalence of PD was 47.1% (n = 852). There were 221 (25.9%) participants suffered from severe pain. In the participants with PD, the OR of carbonated soft drinks intake was 1.244 (95% CI 1.010-1.533). Among the participants with PD from rural areas, the OR of carbonated soft drinks intake was 1.402 (95% CI 1.045-1.881), compared with the non-carbonated soft drink group. In the participants with moderate and severe PD, the OR of coffee intake was 0.451 (95% CI 0.228-0.892), compared with the non-coffee-drinking group. There was a significant association between carbonated soft drinks intake frequency and the severity of PD (P < 0.05). Our study showed that carbonated soft drinks intake is a risk factor for PD, especially in participants from rural areas. Coffee intake is a protective factor for the severity of PD. Periodical awareness programs about adverse effects of excessive soft drink consumption should be introduced to reduce the prevalence and exacerbation of PD. Coffee intake might be helpful to relieve the severity of PD.


Assuntos
Bebidas Gaseificadas , Dismenorreia , Estudantes , Humanos , Feminino , Dismenorreia/epidemiologia , Dismenorreia/etiologia , China/epidemiologia , Estudantes/estatística & dados numéricos , Bebidas Gaseificadas/efeitos adversos , Adulto Jovem , Estudos Transversais , Café/efeitos adversos , Prevalência , Adulto , Adolescente , Inquéritos e Questionários , Universidades , Fatores de Risco , População do Leste Asiático
10.
Sci Total Environ ; 904: 166765, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37660816

RESUMO

Silver nanoparticles (AgNPs) are widely present in aquatic and soil environment, raising significant concerns about their impacts on creatures in ecosystem. While the toxicity of AgNPs on microorganisms has been reported, their effects on biogeochemical processes and specific functional microorganisms remain relatively unexplored. In this study, a 28-day microcosmic experiment was conducted to investigate the dose-dependent effects of AgNPs (10 mg and 100 mg Ag kg-1 soil) on nitrogen transformation and functional microorganisms in agricultural soils. The molecular mechanisms were uncovered by examining change in functional microorganisms and metabolic pathways. To enable comparison, the toxicity of positive control with an equivalent Ag+ dose from CH3COOAg was also included. The results indicated that both AgNPs and CH3COOAg enhanced nitrogen fixation and nitrification, corresponding to increased relative abundances of associated functional genes. However, they inhibited denitrification via downregulating nirS, nirK, and nosZ genes as well as reducing nitrate and nitrite reductase activities. In contrast to high dose of AgNPs, low levels increased bacterial diversity. AgNPs and CH3COOAg altered the activities of associated metabolic pathways, resulting in the enrichment of specific taxa that demonstrated tolerance to Ag. At genus level, AgNPs increased the relative abundances of nitrogen-fixing Microvirga and Bacillus by 0.02 %-629.39 % and 14.44 %-30.10 %, respectively, compared with control group (CK). The abundances of denitrifying bacteria, such as Rhodoplanes, Pseudomonas, and Micromonospora, decreased by 19.03 % to 32.55 %, 24.73 % to 50.05 %, and 15.66 % to 76.06 %, respectively, compared to CK. CH3COOAg reduced bacterial network complexity, diminished the symbiosis mode compared to AgNPs. The prediction of genes involved in metabolic pathways related to membrane transporter and cell motility showed sensitive to AgNPs exposure in the soil. Further studies involving metabolomics are necessary to reveal the essential effects of AgNPs and CH3COOAg on biogeochemical cycle of elements in agricultural soil.


Assuntos
Nanopartículas Metálicas , Solo , Solo/química , Prata/toxicidade , Prata/análise , Ecossistema , Nitrogênio/análise , Nanopartículas Metálicas/toxicidade , Bactérias/metabolismo , Microbiologia do Solo , Desnitrificação
11.
J Med Chem ; 66(16): 11517-11535, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37556731

RESUMO

Sepsis-associated acute kidney injury (AKI) is a serious clinical problem without effective drugs. Inhibition of sirtuin 5 (SIRT5) has been confirmed to protect against AKI, suggesting that SIRT5 inhibitors might be a promising therapeutic approach for AKI. Herein, structural optimization was performed on our previous compound 1 (IC50 = 3.0 µM), and a series of 2,4,5-trisubstituted pyrimidine derivatives have been synthesized. The structure-activity relationship (SAR) analysis led to the discovery of three nanomolar level SIRT5 inhibitors, of which the most potent compound 58 (IC50 = 310 nM) was demonstrated to be a substrate-competitive and selective inhibitor. Importantly, 58 significantly alleviated kidney dysfunction and pathological injury in both lipopolysaccharide (LPS)- and cecal ligation/perforation (CLP)-induced septic AKI mice. Further studies revealed that 58 regulated protein succinylation and the release of proinflammatory cytokines in the kidneys of septic AKI mice. Collectively, these results highlighted that targeting SIRT5 has a therapeutic potential against septic AKI.


Assuntos
Injúria Renal Aguda , Sepse , Sirtuínas , Animais , Camundongos , Injúria Renal Aguda/tratamento farmacológico , Rim , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Pirimidinas/metabolismo , Sepse/complicações , Sepse/tratamento farmacológico , Sirtuínas/antagonistas & inibidores , Relação Estrutura-Atividade
12.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 4): o1235, 2012 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-22606168

RESUMO

Aromatic π-π stacking inter-actions stabilize the crystal structure of the title compound, C(10)H(12)N(2)O(3), the perpendic-ular distance between parallel planes being 3.7721 (8) Å. The morpholine ring adopts a chair comformation.

13.
Neurol Res ; 44(10): 879-887, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36117461

RESUMO

OBJECTIVE: This study plans to investigate whether miR-214-3p could bind CPLX2 to regulate temozolomide (TMZ) resistance in glioma. METHODS: The differential expression of miR-214-3p and CPLX2 was determined by qRT-PCR and Western blotting in TMZ-resistant glioma tissues. Then, TMZ-resistant glioma cells (U87/TMZ and U251/TMZ) were established and transfected with miR-214-3p mimic, miR-214-3p inhibitor, pcDNA3.1-CPLX2 or pcDNA3.1-CPLX2 plus miR-214-3p mimic to evaluate the impact of miR-214-3p and CPLX2 on the proliferation, apoptosis and TMZ resistance in U87/TMZ and U251/TMZ cells. The binding relationship between miR-214-3p and CPLX2 was reported by dual-luciferase reporter assay. RESULTS: Higher miR-214-3p and lower CPLX2 expression levels were revealed in TMZ-sensitive glioma tissues. The alterations in miR-214-3p and CPLX2 expression were more significant in TMZ-resistant tissues compared with TMZ-sensitive tissues. In cellular experiments, TMZ-resistant cells expressed higher miR-214-3p expression and lower CPLX2 expression than TMZ-sensitive cells. Transfection of miR-214-3p mimic elevated the proliferation and half maximal inhibitory concentration (IC50) and decreased the apoptosis in U87/TMZ and U251/TMZ cells. Introduction of miR-214-3p inhibitor or pcDNA3.1-CPLX2 reduced the proliferation and IC50 value and prompted the apoptosis in TMZ-resistant glioma cells. The effects of pcDNA3.1-CPLX2 on inhibiting the proliferation and IC50 value and enhancing the apoptosis in TMZ-resistant glioma cells were hindered by the transfection of miR-214-3p mimic. In addition, CPLX2 was a target gene of miR-214-3p. CONCLUSION: Downregulation of miR-214-3p inhibits TMZ resistance in glioma by promoting CPLX2.


Assuntos
Neoplasias Encefálicas , Glioma , MicroRNAs , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Glioma/tratamento farmacológico , Glioma/metabolismo , Humanos , MicroRNAs/metabolismo , Temozolomida/farmacologia , Temozolomida/uso terapêutico
14.
Front Plant Sci ; 13: 1060406, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36605964

RESUMO

Ecological stoichiometry is an important index that reflects the element cycle and ecosystem stability. In this study, two sites (sunny and shady slopes) and five forest ages (young stage, half-mature stage, near-mature stage, mature stage, and over-mature stage) in a Pinus tabuliformis plantation were chosen to illustrate the effects of forest ages and site conditions on the biomass and stoichiometric characteristics of leaves and soils in the temperate mountainous area of China. Except for young stage, the biomass of the leaves of P. tabuliformis on sunny slopes were higher than those on shady slopes in other forest ages, the average carbon content of the leaves in sunny slopes was higher than that in shady slope, while the average total nitrogen contents and average total phosphorus contents of the leaves showed the opposite of this. The biomass of leaves increased on sunny slopes, and increased first and then decreased in shady slopes with increasing forest ages. The contents of soil total carbon (STC) and soil total nitrogen (STN) decreased with increasing soil depth, while the soil total phosphorus (STP) and soil available phosphorus (SAP) contents displayed the opposite. In addition to SAP, the average content of STC, STN, and STP in shady slopes was higher than that in sunny slopes, and the ratio was the opposite. Except for STC: STN on shady slopes, the other ratios showed a downward trend with an increase in soil depth. Excluding the topsoil, the change trend of STC : STP and STN : STP in shady slopes and sunny slopes was consistent with forest ages. The results showed that forest ages and site conditions had significant effects on leaf biomass. The biomass of the leaves is mainly limited by nitrogen. These results have important significance in improving the refinement of local forestry management of Pinus tabuliformis plantations in the temperate mountainous area of China.

15.
Pharmaceutics ; 14(11)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36365238

RESUMO

A novel class of quinoxaline-arylfuran derivatives were designed, synthesized, and preliminarily evaluated for their antiproliferative activities in vitro against several cancer cell lines and normal cells. The representative derivative QW12 exerts a potent antiproliferative effect against HeLa cells (IC50 value of 10.58 µM), through inducing apoptosis and triggering ROS generation and the accumulation of HeLa cells in vitro. Western blot analysis showed that QW12 inhibits STAT3 phosphorylation (Y705) in a dose-dependent manner. The BLI experiment directly demonstrated that QW12 binds to the STAT3 recombination protein with a KD value of 67.3 µM. Furthermore, molecular docking investigation showed that QW12 specifically occupies the pY+1 and pY-X subpocket of the SH2 domain, thus blocking the whole transmission signaling process. In general, these findings indicated that the study of new quinoxaline-aryfuran derivatives as inhibitors of STAT3 may lead to new therapeutic medical applications for cancer in the future.

16.
PeerJ ; 10: e12853, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35174017

RESUMO

Autumn fertilization is an important cultivation and management measure used to provide nutrients at the hardening stage during the end of the growing season-bolstering nutrient reserves and promoting additional growth in the following spring. Previous studies mainly focused on short-term or one-time fertilization treatment of container seedlings, and few studies have observed the effects of autumn fertilization of large-area forests over multiple continuous years. The growth dynamics and nutrient changes during autumn in 324 Pinus tabuliformis saplings in the temperate zone of China (in the eastern Liaoning mountains) were studied under field conditions with different fertilizer treatments for three consecutive years. The second year of autumn fertilization promoted the growth of tree height and annual leaf length more significantly than that in the first year, the change in diameter at breast height (DBH) was significant. Tree height (TH) in spring increased at a faster rate than in autumn, while DBH stably increased throughout the year. The increase in TH, DBH, and annual leaf length (ALL) under all fertilization treatments was higher than that of the control group, and the decrease in annual branch length (ABL) was higher than that of the control group. High N significantly increased the concentration of new coniferous N (NLN), soil total N (STN), and soil alkali-hydrolyzable N (SAHN) in P. tabuliformis saplings. High P significantly increased the concentration of P in annual needles and soil total P (STP), and decreased the concentration of N in new needles. In addition, there is a certain correlation between the N and P concentration in the needles and soil, representing the competition and interactions between plant nutrient demand and soil nutrient supply. The most favorable fertilizer treatment consisted of high N and low P (urea 204 g, calcium superphosphate 104 g), which provide support for the formulation of a reasonable fertilization technology for P. tabuliformis in the mountains of Eastern Liaoning Province, China.


Assuntos
Pinus , Estações do Ano , Fertilizantes , Árvores , China , Solo , Fertilização
17.
Ann Ital Chir ; 92: 671-675, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34807005

RESUMO

OBJECTIVE: predict the relationship between EPAS-1 in the occurrence and development of renal cell carcinoma and its effect on prognosis. METHODS: The immunohistochemical EnVision two-step method was used to detect the expression of EPAS-1 protein in 145 cases of renal cell carcinoma and adjacent tissues to verify the correlation between EPAS-1 expression and clinicopathological characteristics and its effect on survival. RESULTS: The expression of EPAS-1 protein in renal cell carcinoma and adjacent tissues was 75.9% and 15.9%, respectively. Univariate analysis showed that positive expression of EPAS-1, PT staging, lymphatic metastasis, distant metastasis, and ISUP grade were associated with poor prognosis of renal cell carcinoma (P <0.05); Multivariate analysis results showed that EPAS-1 protein and ISUP classification are independent prognostic factors for renal cell carcinoma. Kaplan-Mier survival analysis showed that the survival rate of renal cell carcinoma patients increased with the expression of EPAS-1 protein decreased significantly (P <0.05). CONCLUSION: The expression of EPAS-1 protein is related to the PT stage, lymphatic metastasis, distant metastasis, and ISUP classification of renal cell carcinoma. EPAS-1 can be used as a potential prognostic marker or Treatment target. KEY WORDS: EPAS-1 prognosis, Immunohistochemistry, Molecular markers, Renal neoplasms, Renal clear cell carcinoma.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Biomarcadores Tumorais , Humanos , Imuno-Histoquímica , Neoplasias Renais/patologia , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico
18.
PeerJ ; 9: e11873, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395097

RESUMO

Carbon distribution in plants and ecological stoichiometry in soils are important indicators of element cycling and ecosystem stability. In this study, five forest ages, young forest (YF), middle-aged forest (MAF), near-mature forest (NMF), mature forest (MF), and over-mature forest (OMF) in a Pinus tabuliformis plantation were chosen to illustrate interactions among the C: N: P stoichiometry in soils and carbon distribution in plants, in the mountainous area of eastern Liaoning, China. Carbon content was highest in the leaves of MAF (505.90 g⋅kg-1) and NMF (509.00 g⋅kg-1) and the trunks of YF (503.72 g⋅kg-1), MF (509.73 g⋅kg-1), and OMF (504.90 g⋅kg-1), and was lowest in the branches over the entire life cycle of the aboveground components (335.00 g⋅kg-1). The carbon content of the fine roots decreased with soil layer depth. In YF, MAF, and NMF carbon content of fine roots at 0.5 m was always higher than that of fine roots at 1 m; however, it was the opposite in MF and OMF. The carbon content of the leaves changed with forest age; however, carbon content of branches, trunks and fine roots did not change significantly. Soil total carbon (TC), total nitrogen (TN), total phosphorus (TP), and available phosphorus (AP) content was highest in the OMF. Soil TC, TN and AP content, and TC: TN, TC: TP and TN: TP ratio decreased with increasing soil depth. Soil TC, TN, and TP content had a significant effect on the carbon content of fine roots (p < 0.05). The leaf carbon content and soil element content changed obviously with forest age, and the soil TN, TP and AP increased, which might reduce the carbon content allocation of fine roots.

19.
Zhongguo Zhen Jiu ; 41(10): 1089-94, 2021 Oct 12.
Artigo em Zh | MEDLINE | ID: mdl-34628740

RESUMO

OBJECTIVE: To compare the clinical therapeutic effect between deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle and conventional acupuncture in patients with trigeminal neuralgia (TN) of wind and heat, and explore its mechanism. METHODS: A total of 60 patients with TN of wind and heat were randomized into an observation group (30 cases) and a control group (30 cases). In the observation group, deep needling with round sharp needle was applied at Xiaguan (ST 7), and tapping with plum-blossom needle was applied at Yangbai (GB 14), Quanliao (SI 18), Dicang (ST 4), Sibai (ST 2), etc. of affected side. In the control group, conventional acupuncture was applied at the same acupoints selected in the observation group. The treatment was given once a day, 5 times a week for 4 weeks in the both groups. Before and after treatment, the scores of short-form McGill pain questionnaire (SF-MPQ), TCM syndrome, patient global impression of change (PGIC) and comprehensive symptom were observed, the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vasoactive intestinal peptide (VIP) and ß-endorphin (ß-EP) were detected, and the adverse reaction was observed in the both groups. RESULTS: After treatment, the scores of PRI, PPI, VAS, TCM syndrome, PGIC and comprehensive symptom and the serum levels of IL-6, TNF-α and VIP were decreased compared before treatment in the both groups (P<0.05), and the variations of above indexes in the observation group were larger than those in the control group (P<0.05). After treatment, the serum levels of ß-EP were increased compared before treatment in the both groups (P<0.05), and the variation of that in the observation group was larger than the control group (P<0.05). No severe adverse reaction was observed in the both groups. CONCLUSION: Deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle can effectively treat the trigeminal neuralgia of wind and heat and relieve pain, its therapeutic effect is superior to conventional acupuncture. The mechanism may be related to the regulation of serum IL-6, TNF-α, VIP and ß-EP.


Assuntos
Prunus domestica , Neuralgia do Trigêmeo , Flores , Temperatura Alta , Humanos , Neuralgia do Trigêmeo/terapia , Vento
20.
NPJ Prim Care Respir Med ; 31(1): 28, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016999

RESUMO

We built a decision-analytic model to compare the cost-effectiveness of using portable spirometer and questionnaire to screen chronic obstructive pulmonary diseases (COPD) with no screening (i.e. usual care) among chronic bronchitis patient in China. A lifetime horizon and a payer perspective were adopted. Cost data of health services including spirometry screening and treatment costs covered both maintenance and exacerbation. The result indicated that portable spirometer screening was cost-saving compared with questionnaire screening and no screening, with an incremental cost-effectiveness ratio (ICER) of -5026 and -1766 per QALY, respectively. Sensitivity analyses confirmed the robustness of the results. In summary, portable spirometer screening is likely the optimal option for COPD screening among chronic bronchitis patients China.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Análise Custo-Benefício , Custos de Cuidados de Saúde , Humanos , Programas de Rastreamento , Atenção Primária à Saúde , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia
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