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2.
Zhonghua Er Ke Za Zhi ; 58(4): 301-307, 2020 Apr 02.
Artigo em Chinês | MEDLINE | ID: mdl-32234137

RESUMO

Objective: To investigate the availability, prices and affordability of essential medicines in pediatric population across China, in the hope of improving rational use of medicines. Methods: A multicenter cross-sectional survey of medicine prices, availability and affordability was conducted in 17 provinces, municipalities and autonomous region across east, south-central part, west and north of China. Data on 42 medicines used in pediatric population, both original and generic, were collected in 55 public hospitals from May 26 to June 2, 2017. Availability was expressed as the percentage of hospitals with stock of the target medicine on the day of data collection,and median price ratio (MPR) was the ratio of price upon investigation to international reference. Based on national minimum daily wage, affordability represents the number of working days needed to earn the expense which covers a standard course using the target medicine. Statistical software SPSS 13.0 was applied for descriptive analysis of availability, MPR and affordability. Results: Mean Availability of original and generic medicine was 33% and 32%, with median MPR being 5.43 and 1.55. Among the 19 medicines with price information for both original and generic product, the median MPR was 7.73 and 2.04 respectively. Regarding the five medicines used to treat four common pediatric diseases (pneumonia,peptic ulcer, congenital hypothyroidism, refractory nephrotic syndrome), the affordability was 0.63 (0.16-6.17) d for generic medicine, and 1.03 (0.16-11.53) d for its original counterpart. Conclusions: The availability to both original and generic products of the 42 medicines used in pediatric population was low in China. The prices of generic medicines seem to be lower and affordability higher than those of original medicines. There is an urgent need to improve the availability and affordability of pediatric medicines.

3.
J Acoust Soc Am ; 147(3): EL283, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32237829

RESUMO

This work aims to investigate the acoustic characteristics of a piezoelectric micro-perforated panel (MPP) absorber, which is made of a perforated polyvinylidene fluoride (PVDF) film with a backed airgap of 2 cm, as a combination of an active component and passive absorber. In addition to its inherent passive dissipation, as the PVDF-MPP was driven with proper voltages and oscillation frequencies, sound absorption coefficients of the absorber adjacent to the driving frequencies were significantly increased. Compared with mostly previous reported hybrid passive-active absorbers, this one is more compact, and its acoustic property is adjustable, it may provide an approach to achieve intelligent noise control.

4.
Nanoscale ; 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32239037

RESUMO

We report on a transport measurement study of top-gated field effect transistors made out of InSb nanowires grown by chemical vapor deposition. The transistors exhibit ambipolar transport characteristics revealed by three distinguished gate-voltage regions: In the middle region where the Fermi level resides within the bandgap, the electrical resistance shows an exponential dependence on temperature and gate voltage. With either more positive or negative gate voltages, the devices enter the electron and hole transport regimes, revealed by the resistance decreasing linearly with decreasing temperature. From the transport measurement data of a 1 µm-long device made from a nanowire of 50 nm in diameter, we extracted a bandgap energy of 190-220 meV. The off-state current of this device is found to be suppressed within the measurement noise at a temperature of T = 4 K. A shorter, 260 nm-long device is found to exhibit a finite off-state current and a circumference-normalized on-state hole current of 11 µA µm-1 at VD = 50 mV which is the highest for such a device to our knowledge. The ambipolar transport characteristics make the InSb nanowires attractive for CMOS electronics, hybrid electron-hole quantum systems and hole based spin qubits.

5.
Ann Oncol ; 31(4): 517-524, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32151507

RESUMO

BACKGROUND: Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, genetic origin, and clinical management remain controversial. PATIENTS AND METHODS: Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by next-generation sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes. RESULTS: The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0-11.2). CONCLUSIONS: The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.

6.
Eur Rev Med Pharmacol Sci ; 24(5): 2452-2461, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32196596

RESUMO

OBJECTIVE: Gastric cancer (GC) is a common malignancy of the digestive tract. Accumulated studies proved that long non-coding RNA MCM3AP-AS1 (MCM3AP-AS1) modified the mechanism of the progression of GC. However, the molecular mechanism is still greater elusive. Hence, we aimed to explore the molecular mechanism of MCM3AP-AS1 targeting the regulation of microRNA-708-5p on cell proliferation and apoptosis in GC cells. MATERIALS AND METHODS: The expression levels of MCM3AP-AS1 (MCM3AP antisense RNA 1) in gastric mucosal cells GES-1 and gastric cancer cell lines of MGc-803 and SGC-7901 cells were detected by qRT-PCR. Moreover, the protein levels of Cyclin D1, P21, Bax and Bcl-2 in MGc-803 and SGC-7901 cells after transfection were detected by Western blot. MTT assay was performed to detect cell proliferation and flow cytometry was carried out to determine GC cell apoptosis in vitro. In the endpoint, the targeting relationship between MCM3AP-AS1 and microRNA-708-5p was detected by Dual-Luciferase reporter assay. RESULTS: The level of MCM3AP-AS1 was significantly promoted in GC cell lines. Knockdown of MCM3AP-AS1 curbed cell proliferation and enhanced apoptosis in MGc-803 and SGC-7901 cells. Furthermore, the effect of the downregulation of MCM3AP-AS1 on cell proliferation and apoptosis was reversed by knockdown of miR-708-5p, which was targeted by MCM3AP-AS1 in vitro. CONCLUSIONS: MCM3AP-AS1 regulates the proliferation and apoptosis of gastric cancer cells by targeting the expression of microRNA-708-5p. The study may be useful to the therapy target of human GC.

7.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(5): E027, 2020 Mar 26.
Artigo em Chinês | MEDLINE | ID: mdl-32213270

RESUMO

Objective: To understand the epidemiological characteristics of the cases of COVID-19 epidemic clusters, and explore the influence of family factors and social factors such as group activities on the spread of the disease. Methods: The data of cases of COVID-19 epidemic clusters from 19 January, 2020 to 25 February, 2020 were collected from the official platforms of 36 cities in 6 provinces in China. Descriptive statistical methods, χ(2) test and curve fitting were used to analyze the epidemiological characteristics of the clustered cases. Results: By 25 February, 2020, the data of 1 052 cases in 366 epidemic clusters were collected. In these clustered cases, 86.9%(914/1 050) occurred in families. Among the 1 046 cases with gender information, 513 were males (49.0%) and 533 were females (51.0%). The cases were mainly young adults between 18 and 59 years old, accounting for 68.5% (711/1 038). In the 366 epidemic clusters , the clusters in which the first confirmed cases with the history of sojourn in Wuhan or Hubei accounted for 47.0%(172/366). From 19 January to 3 February, 2020, the first confirmed cases with Wuhan or Hubei sojourn history accounted for 66.5%. From 4 to 25 February, the first confirmed cases who had Wuhan or Hubei sojourn history accounted for only 18.2%. The median of interval between the first generation case onset and the second generation case onset was 5 (2-8) days. The median of onset- diagnosis interval of the initial cases was 6 (3-9) days, and the median of onset-diagnosis interval of the secondary cases was 5 (3-8) days. Conclusions: Epidemic clusters of COVID-19 were common in many cities outside Wuhan and Hubei. Close contact in family was one of the main causes for the spread of household transmission of the virus. After 4 February, the epidemic clusters were mainly caused by the first generation or second generation cases in local areas, and the time for diagnosis became shorter.

8.
Phys Rev Lett ; 124(10): 105303, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32216438

RESUMO

Weyl points are often believed to appear in pairs with opposite chirality. In this work, we show by first-principles calculations and symmetry analysis that single Weyl phonons with linear dispersion and double Weyl phonons with quadratic dispersion are simultaneously present between two specific phonon branches in realistic materials with trigonal or hexagonal lattices. These phonon Weyl points are guaranteed to locate at high-symmetry points due to the screw rotational symmetry, forming a unique triangular Weyl complex. In sharp contrast to conventional Weyl systems with surface arcs terminated at the projections of a pair of Weyl points with opposite chirality, the phonon surface arcs of the unconventional triangular Weyl complex connect the projections of one double Weyl point and two single Weyl points. Importantly, the phonon surface arcs originating from the triangular Weyl complex are extremely long and span the entire surface Brillouin zone. Furthermore, there are only nontrivial phonon surface states across the isofrequency surface, which facilitates their detection in experiments and further applications. Our work not only offers the promising triangular phonon Weyl complex but also provides guidance for exploring triangular Weyl bosons in both phononic and photonic systems.

9.
Zhonghua Zhong Liu Za Zhi ; 42(2): 105-113, 2020 Feb 23.
Artigo em Chinês | MEDLINE | ID: mdl-32135643

RESUMO

Objective: To explore the expression of microRNA-17-5p (miR-17-5p) in esophageal squamous cell carcinoma (ESCC) and its effects on cell proliferation and invasion ability. Methods: Real-time quantitative PCR (RT-qPCR) was used to detect the miR-17-5p level in ESCC tissues and cells. MiR-17-5p inhibitor and negative control (NC) were transfected into EC9706 and TE1 cells, and miR-17-5p expression was examined by using RT-qPCR. Cell counting kit-8 (CCK-8) and EdU were conducted to detect cell proliferation and Transwell chamber was used to investigate cell invasion ability. Dual-luciferase reporter assay was used to detect the direct interaction of miR-17-5p and retinoblastoma-like protein-2 (RBL2). Western blot and RT-qPCR were used to detect the expression of RBL2 in ESCC tissues, respectively. Finally, the correlation between RBL2 and miR-17-5p was analyzed. Results: The miR-17-5p level in ESCC tissues was 4.222±0.392, significantly higher than 1.081±0.046 in normal esophageal epithelial tissues (P<0.001). The expressions of miR-17-5p in ESCC cells, including EC9706, Eca109, TE1, KYSE450, KYSE70 and KYSE520, were 13.84±1.266, 6.453±0.293, 11.41±0.520, 2.613±0.548, 5.251±0.239 and 4.251±0.195, respectively, all obviously higher than (1.007±0.079) in normal esophageal epithelial cell Het-1A (P<0.05). The miR-17-5p level in patients with ESCC Ⅲ~Ⅳ was 5.094±0.562, markedly higher than 2.934±0.364 in patients with ESCCⅠ~Ⅱ(P<0.01). Moreover, the miR-17-5p level in ESCC patients with lymph node metastasis was 5.523±0.634, markedly higher than 3.533±0.461 in ESCC patients without lymph node metastasis (P<0.05). The survival ratio of ESCC patients with higher miR-17-5p level was evidently lower than that of ESCC patients with lower miR-17-5p level (P<0.05). MiR-17-5p inhibitor significantly downregulated the miR-17-5p expression in EC9706 and TE1, which suppressed cell proliferation and invasion ability. Dual-luciferase reporter assay revealed that co-transfection of 3' untranslated region-wild type (3'UTR-WT) of RBL2 and miR-17-5p mimic significantly reduced luciferase activity in EC9706 and TE1 cells (P<0.01), which implicated that RBL2 was the direct target of miR-17-5p. The result of western blot revealed that RBL2 protein expressions in miR-17-5p group of EC9706 and TE1 cells were 0.936±0.055 and 0.923±0.048, obviously higher than 0.087±0.019 and 0.102±0.010 in control group (P<0.001). The expression of RBL2 in ESCC tissues was 0.219±0.510, markedly lower than 0.983±0.324 in normal esophageal epithelial tissues (P<0.001). The miR-17-5p level exhibited a negative correlation with RBL2 level in ESCC tissues (r=-0.462, P<0.001). Downregulation of RBL2 reversed the miR-17-5p inhibitor induced suppression of cell proliferation and invasion ability. Conclusion: MiR-17-5p participates in the carcinogenesis and development of ESCC, thus may be a potential therapeutic target for ESCC patients.


Assuntos
Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , MicroRNAs/biossíntese , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Invasividade Neoplásica
10.
Zhonghua Zhong Liu Za Zhi ; 42(0): E006, 2020 Mar 02.
Artigo em Chinês | MEDLINE | ID: mdl-32118394

RESUMO

With the increasing number of cases and widening geographical spread, the 2019 novel coronavirus disease (COVID-19) has been classified as one of the class B infectious diseases but prevented and controlled as class A infectious disease by the National Health Commission of China. The diagnosis and treatment of lung cancer patients have been challenged greatly because of extraordinary public health measures since the lung cancer patients are a high-risk population during the COVID-19 outbreak period. Strict protection for lung cancer patients is needed to avoid infection. Lung cancer patients are difficult to differentiate from patients with COVID-19 in terms of clinical symptoms, which will bring great trouble to the clinical work and physical and mental health of lung cancer patients. This review will demonstrate how to applicate appropriate and individual management for lung cancer patients to protect them from COVID-19.

11.
J Endocrinol Invest ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32147762

RESUMO

PURPOSE: To investigate the relationships between hematuria, clinicopathological features and renal outcomes in patients with biopsy-proven diabetic nephropathy (DN). METHODS: This cohort study included 261 patients with DN. Participants were divided into two groups according to number of red blood cells per high-power field (RBC/hpf) in urine sediment: the hematuria (-) group (≤ 3 RBC/hpf) and the hematuria (+) group (> 3 RBC/hpf). Basic clinical parameters were measured at the time of renal biopsy; relationships between hematuria and clinicopathological features and renal outcomes were analyzed. RESULTS: Patients in the hematuria (+) group often had overt proteinuria. Interstitial inflammation was more severe in the hematuria (+) group than in the hematuria (-) group. Glomerular arteriolar hyalinosis, interstitial fibrosis and tubular atrophy were comparable between groups. For patients with early DN (eGFR ≥ 60 ml/min/1.73 m2), urinary RBC/hpf at baseline was positively correlated with glomerular classification, interstitial fibrosis/tubular atrophy scores and interstitial inflammation scores. In prognostic analysis, hematuria was associated with a higher risk of progression to end-stage renal disease. Hematuria remained an independent predictor after adjustment for confounding factors such as sex, age, duration of diabetes, serum glucose level, hypertension, cholesterol, eGFR and urine protein excretion, especially in patients with early DN and in male patients. CONCLUSION: In this study, hematuria was associated with more severe renal pathologic lesions in patients with DN. The presence of hematuria could be an independent predictor of renal outcome in patients with early DN.

12.
PLoS Pathog ; 16(3): e1008323, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32163521

RESUMO

Fusarium is a genus of filamentous fungi that includes species that cause devastating diseases in major staple crops, such as wheat, maize, rice, and barley, resulting in severe yield losses and mycotoxin contamination of infected grains. Phenamacril is a novel fungicide that is considered environmentally benign due to its exceptional specificity; it inhibits the ATPase activity of the sole class I myosin of only a subset of Fusarium species including the major plant pathogens F. graminearum, F. asiaticum and F. fujikuroi. To understand the underlying mechanisms of inhibition, species specificity, and resistance mutations, we have determined the crystal structure of phenamacril-bound F. graminearum myosin I. Phenamacril binds in the actin-binding cleft in a new allosteric pocket that contains the central residue of the regulatory Switch 2 loop and that is collapsed in the structure of a myosin with closed actin-binding cleft, suggesting that pocket occupancy blocks cleft closure. We have further identified a single, transferable phenamacril-binding residue found exclusively in phenamacril-sensitive myosins to confer phenamacril selectivity.

13.
Nat Commun ; 11(1): 1598, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32221310

RESUMO

We propose the concept of universal fiducials based on a set of pre-made semi-synthetic antibodies (sABs) generated by customized phage display selections against the fusion protein BRIL, an engineered variant of apocytochrome b562a. These sABs can bind to BRIL fused either into the loops or termini of different GPCRs, ion channels, receptors and transporters without disrupting their structure. A crystal structure of BRIL in complex with an affinity-matured sAB (BAG2) that bound to all systems tested delineates the footprint of interaction. Negative stain and cryoEM data of several examples of BRIL-membrane protein chimera highlight the effectiveness of the sABs as universal fiducial marks. Taken together with a cryoEM structure of sAB bound human nicotinic acetylcholine receptor, this work demonstrates that these anti-BRIL sABs can greatly enhance the particle properties leading to improved cryoEM outcomes, especially for challenging membrane proteins.

14.
Mol Cell ; 77(3): 656-668.e5, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32004469

RESUMO

Class B G protein-coupled receptors (GPCRs) are important therapeutic targets for major diseases. Here, we present structures of peptide and Gs-bound pituitary adenylate cyclase-activating peptide, PAC1 receptor, and corticotropin-releasing factor (CRF), (CRF1) receptor. Together with recently solved structures, these provide coverage of the major class B GPCR subfamilies. Diverse orientations of the extracellular domain to the receptor core in different receptors are at least partially dependent on evolutionary conservation in the structure and nature of peptide interactions. Differences in peptide interactions to the receptor core also influence the interlinked TM2-TM1-TM6/ECL3/TM7 domain, and this is likely important in their diverse signaling. However, common conformational reorganization of ECL2, linked to reorganization of ICL2, modulates G protein contacts. Comparison between receptors reveals ICL2 as a key domain forming dynamic G protein interactions in a receptor- and ligand-specific manner. This work advances our understanding of class B GPCR activation and Gs coupling.

15.
Mol Cell ; 77(3): 669-680.e4, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32004470

RESUMO

Corticotropin-releasing factor (CRF) and the three related peptides urocortins 1-3 (UCN1-UCN3) are endocrine hormones that control the stress responses by activating CRF1R and CRF2R, two members of class B G-protein-coupled receptors (GPCRs). Here, we present two cryoelectron microscopy (cryo-EM) structures of UCN1-bound CRF1R and CRF2R with the stimulatory G protein. In both structures, UCN1 adopts a single straight helix with its N terminus dipped into the receptor transmembrane bundle. Although the peptide-binding residues in CRF1R and CRF2R are different from other members of class B GPCRs, the residues involved in receptor activation and G protein coupling are conserved. In addition, both structures reveal bound cholesterol molecules to the receptor transmembrane helices. Our structures define the basis of ligand-binding specificity in the CRF receptor-hormone system, establish a common mechanism of class B GPCR activation and G protein coupling, and provide a paradigm for studying membrane protein-lipid interactions for class B GPCRs.

16.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(2): 144-148, 2020 Feb 06.
Artigo em Chinês | MEDLINE | ID: mdl-32074700

RESUMO

Objective: To explore the interaction of health literacy and second-hand smoke exposure on psychopathological symptoms of middle school students. Methods: From November 2015 to January 2016, 22 628 middle school students from Shenyang of Liaoning Province, Bengbu of Anhui Province, Xinxiang of Henan Province, Ulanqab of Inner Mongolia Autonomous Region, Chongqing Municipality, and Yangjiang of Guangdong Province were enrolled by using the multi-stage cluster convenience sampling method. A questionnaire was used to collect the data including demographic information, health literacy, second-hand smoke exposure, and psychopathological symptoms. A multivariate logistic regression model was used to analyze the interaction of health literacy and second-hand smoke exposure on psychopathological symptoms of middle school students. Results: The age of students was (15.36±1.79) years old, of which 10 990 were boys, accounting for 48.6% of total students. The detection rate of psychopathological symptoms was 29.1% (6 581/22 628). The detection rate of psychopathological symptoms in those who were exposed to second-hand smoke was 38.1% (2 401/6 304), which was higher than that in the non-second-hand smoke exposure group [25.6% (4 180/16 324)] (P<0.001). The OR (95%CI) of the interaction between medium and low levels of overall health literacy, low level of interpersonal dimension of health literacy and second-hand smoke exposure was 1.19 (1.15-1.24), 2.00 (1.92-2.10) and 1.59 (1.52-1.66), respectively. Conclusion: There was a positive interaction between middle and low levels of overall health literacy, low level of interpersonal dimension of health literacy and second-hand smoke exposure on psychopathological symptoms of middle school students.


Assuntos
Exposição Ambiental/efeitos adversos , Alfabetização em Saúde/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Estudantes/psicologia , Poluição por Fumaça de Tabaco/efeitos adversos , Adolescente , China/epidemiologia , Exposição Ambiental/estatística & dados numéricos , Feminino , Humanos , Masculino , Instituições Acadêmicas , Estudantes/estatística & dados numéricos , Inquéritos e Questionários , Poluição por Fumaça de Tabaco/estatística & dados numéricos
17.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(0): E019, 2020 Feb 27.
Artigo em Chinês | MEDLINE | ID: mdl-32107910

RESUMO

We used the epidemic data of COVID-19 published on the official website of the municipal health commission in Anhui province. We mapped the spatiotemporal changes of confirmed cases, fitted the epidemic situation by the population growth curve at different stages and took statistical description and analysis of the epidemic situation in Anhui province. It was found that the cumulative incidence of COVID-19 was 156/100 000 by February 18, 2020 and the trend of COVID-19 epidemic declined after February 7, changing from J curve to S curve. The actual number of new cases began to decrease from February 2 to February 4 due to the time of case report and actual onset delayed by 3 to 5 days.

18.
Nat Commun ; 11(1): 885, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060286

RESUMO

Formylpeptide receptors (FPRs) as G protein-coupled receptors (GPCRs) can recognize formylpeptides derived from pathogens or host cells to function in host defense and cell clearance. In addition, FPRs, especially FPR2, can also recognize other ligands with a large chemical diversity generated at different stages of inflammation to either promote or resolve inflammation in order to maintain a balanced inflammatory response. The mechanism underlying promiscuous ligand recognition and activation of FPRs is not clear. Here we report a cryo-EM structure of FPR2-Gi signaling complex with a peptide agonist. The structure reveals a widely open extracellular region with an amphiphilic environment for ligand binding. Together with computational docking and simulation, the structure suggests a molecular basis for the recognition of formylpeptides and a potential mechanism of receptor activation, and reveals conserved and divergent features in Gi coupling. Our results provide a basis for understanding the molecular mechanism of the functional promiscuity of FPRs.

19.
Zhonghua Shao Shang Za Zhi ; 36(0): E003, 2020 Feb 23.
Artigo em Chinês | MEDLINE | ID: mdl-32087622

RESUMO

Statistics show that 76.74% (4 688) of 6 109 patients with chronic wounds are those over 50 years of age; the proportion of patients with underlying diseases in all age groups above 50 years ranges from 78.25% to 100.00%; among the underlying diseases of chronic wound patients, the top four diseases are diabetes mellitus , cardiovascular and cerebrovascular diseases, hypertension, and respiratory diseases. The above underlying diseases and ages of patients are the susceptibility factors of corona virus disease 2019 released by National Health Commission of China. It is an unavoidable fact that patients with chronic wounds have to go to the hospital for treatment prescribed by the physician. At the same time, we found that there were not a few patients who go far afield because of various reasons when go to the hospital for treatment. During the period of epidemic prevention and control, this kind of "go far afield" style of seeking medical treatment may increase the exposure risk during transportation. Accordingly, we convened 36 wound care clinics in different regions in Shanghai to implement the "Five Measures" to encourage patients with chronic wounds to seek medical treatment proximately. The principle of this operation is that when seeking medical treatment, trying our best to reduce as much as possible the transportation distance for patients with chronic wounds to minimize the exposure risk during the epidemic period and eventually support the epidemic prevention and control campaign.

20.
Cell ; 180(4): 645-654.e13, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32004460

RESUMO

Drugs selectively targeting CB2 hold promise for treating neurodegenerative disorders, inflammation, and pain while avoiding psychotropic side effects mediated by CB1. The mechanisms underlying CB2 activation and signaling are poorly understood but critical for drug design. Here we report the cryo-EM structure of the human CB2-Gi signaling complex bound to the agonist WIN 55,212-2. The 3D structure reveals the binding mode of WIN 55,212-2 and structural determinants for distinguishing CB2 agonists from antagonists, which are supported by a pair of rationally designed agonist and antagonist. Further structural analyses with computational docking results uncover the differences between CB2 and CB1 in receptor activation, ligand recognition, and Gi coupling. These findings are expected to facilitate rational structure-based discovery of drugs targeting the cannabinoid system.

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