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1.
Chem Biodivers ; 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33811740

RESUMO

Five new decalins, monalbidins A-E (1, 2 and 7-9), together with 16 known compounds (3-6 and 10-21), were isolated from the AcOEt extract of marine derived fungus Monascus albidus BB3 cultured in GPY medium. Among the known compounds, 1-hydroxymonacolin L (11), dehydromonacolin J (15), 8-O-acetylmonacolin J (19) and O-acetylmonacolin K (21) were separated from natural sources for the first time. Their structures were determined by comprehensive analysis on the 1D and 2D NMR, HR-ESI-MS, UV and IR data, and their absolute configurations were assigned by experimental and calculated ECD data, and X-ray single-crystal diffraction analysis. Monalbidins C and D (7 and 8), monacolin K methyl ester (13), dehydromonacolin L (14), dehydromonacolin K (16), monacolin K (20) and O-acetylmonacolin K (21) showed moderate cytotoxicity against human cancer cell lines SUNE1, HepG2, QGY7701, HCT116 and MDA-MB-231.

2.
Mol Cell ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33857403

RESUMO

From biosynthesis to assembly into nucleosomes, histones are handed through a cascade of histone chaperones, which shield histones from non-specific interactions. Whether mechanisms exist to safeguard the histone fold during histone chaperone handover events or to release trapped intermediates is unclear. Using structure-guided and functional proteomics, we identify and characterize a histone chaperone function of DNAJC9, a heat shock co-chaperone that promotes HSP70-mediated catalysis. We elucidate the structure of DNAJC9, in a histone H3-H4 co-chaperone complex with MCM2, revealing how this dual histone and heat shock co-chaperone binds histone substrates. We show that DNAJC9 recruits HSP70-type enzymes via its J domain to fold histone H3-H4 substrates: upstream in the histone supply chain, during replication- and transcription-coupled nucleosome assembly, and to clean up spurious interactions. With its dual functionality, DNAJC9 integrates ATP-resourced protein folding into the histone supply pathway to resolve aberrant intermediates throughout the dynamic lives of histones.

3.
Virus Res ; 297: 198393, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33727092

RESUMO

Duck enteritis virus (DEV) can cause an acute, contagious and lethal disease of many species of waterfowl. An infectious bacterial artificial chromosome clone of DEV vaccine strain pE1 (pDEV-EF1) has been constructed in our previous study. Based on pE1, a recombinant mutated clone pDL (pVP26CFP-gCRFP), which carries a red fluorescent protein (mRFP) gene fused to the viral envelope protein gC in combination with a cyan fluorescent protein (CFP) gene fused to the viral capsid VP26, was constructed by two-step Red/ET recombination and the recombinant virus rDL (rVP26CFP-gCRFP) was rescued from chicken embryo fibroblasts (CEFs) by calcium phosphate transfection. Western blot analysis revealed that VP26-CFP and gC-mRFP were both expressed in fusion forms in rDL-infected CEFs, and subcellular localization study showed that gC-mRFP was mainly localized in whole cell at 36, 48 h post infection (p.i.); and then mostly migrated to the cytoplasm after 60 h.p.i., ; whereas VP26-CFP was localized in the nucleus in all stages of virus infection. Additionally, viral particles at different stages of morphogenesis (A capsids, B capsids, C capsids) were observed in virus-infected cells by transmission electron microscopy, indicating that exogenous gene insertion has no effect on virus assembly. This study has laid a foundation for visually studying localization, transportation of DEV capsid proteins and envelope glycoproteins as well as virus assembly, virion movement and virus-cell interaction.

4.
Preprint | medRxiv | ID: ppmedrxiv-21251540

RESUMO

The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2500 COVID-19 cases associated with this variant have been detected in the US since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight the primary ports of entry for B.1.1.7 in the US and locations of possible underreporting of B.1.1.7 cases. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.

5.
Preprint | medRxiv | ID: ppmedrxiv-21250486

RESUMO

With the emergence of SARS-CoV-2 variants that may increase transmissibility and/or cause escape from immune responses1-3, there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant first detected in the UK4,5 could be serendipitously detected by the ThermoFisher TaqPath COVID-19 PCR assay because a key deletion in these viruses, spike {Delta}69-70, would cause a "spike gene target failure" (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern that lack spike {Delta}69-70, such as B.1.351 (also 501Y.V2) detected in South Africa6 and P.1 (also 501Y.V3) recently detected in Brazil7. We identified a deletion in the ORF1a gene (ORF1a {Delta}3675-3677) in all three variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a {Delta}3675-3677 as the primary target and spike {Delta}69-70 to differentiate, we designed and validated an open source PCR assay to detect SARS-CoV-2 variants of concern8. Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence spread of B.1.1.7, B.1.351, and P.1.

6.
Endocrine ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33548014

RESUMO

PURPOSE: To investigate the relationship between parathyroid hormone (PTH) levels and body weight, body mass index (BMI), lipid profiles, and fat distribution in subjects with primary hyperparathyroidism (PHPT) and controls. METHODS: This was a cross-sectional study in 192 patients with PHPT and 202 controls. Serum concentrations of calcium, 25-hydroxyvitamin D (25(OH)D), PTH, lipids profiles, and other hormones were quantified. Bone mineral density was assessed by dual-energy X-ray absorptiometry. Fat distribution evaluation utilizing quantitative computed tomography was conducted in another 66 patients with PHPT and 155 controls. RESULTS: PHPT patients were older (P < 0.001) and had less body weight (P < 0.001), lower BMI (P = 0.019), lower serum concentrations of 25(OH)D (P < 0.001), total cholesterol (P = 0.036), low-density lipoprotein-cholesterol (P = 0.036), and higher circulating concentration of free fatty acid (FFA) (P = 0.047) as compared with controls. After adjusting multiple confounders, PTH was positively correlated with weight (r = 0.311, P < 0.001), BMI (r = 0.268, P < 0.01), and visceral adipose tissue area (VAA) (r = 0.191, P < 0.05) in the first tertile of PTH. However, these associations were not observed in the second tertile. While in the third tertile, PTH was negatively correlated with weight (r = -0.200, P < 0.05), BMI (r = -0.223, P < 0.05) and marginally with VAA (r = -0.306, P = 0.065), it showed positive association with FFA (r = 0.230, P < 0.05). CONCLUSIONS: The inverted U-shape relationship between PTH and body weight, BMI, VAA found in this study is helpful to explain the conflicting results among these parameters, and extend our understanding of the metabolic effects of PTH.

7.
Eur J Med Chem ; 213: 113174, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33515864

RESUMO

In order to discover and develop drug-like anti-inflammatory agents against arthritis, based on "Hit" we found earlier and to overcome drawbacks of toxicity, twelve series of total 89 novel pyrimidine, pyrazolo[4,3-d]pyrimidine and thieno[3,2-d]pyrimidine derivatives were designed, synthesized and screened for their anti-inflammatory activity against NO and toxicity for normal liver cells (LO2). Relationships of balance toxicity and activity have been summarized through multi-steps, and title compounds 22o, 22l were found to show lower toxicity (against LO2: IC50 = 2934, 2301 µM, respectively) and potent effect against NO release (IR = 98.3, 97.67%, at 10 µM, respectively). Furthermore, compound 22o showed potent iNOS inhibitory activity with value of IC50 is 0.96 µM and could interfere stability and formation of the active dimeric iNOS. It's anti-inflammatory activity in vivo was assessed by AIA rat model. Furthermore, the results of metabolic stability, CYP, PK study in vivo, acute toxicity study and subacute toxicity assessment indicated this compound had good drug-like properties for treatment.

8.
BMC Surg ; 21(1): 21, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407324

RESUMO

BACKGROUND: The purpose of this study was to investigate the clinical effect of minimally invasive surgery for inguinal cryptorchidism. METHODS: The patients were divided into the minimally invasive surgery group (n = 100) and the traditional surgery group (n = 58). In the minimally invasive surgery group, patients with low inguinal cryptorchidism (n = 54) underwent surgery with a transscrotal incision, and patients with high inguinal cryptorchidism (n = 46) underwent laparoscopic surgery. RESULTS: There was no difference in the hospital stay duration or cost between the minimally invasive surgery group and the traditional surgery group (P > 0.05). As for the operative time, minimally invasive surgery of low inguinal cryptorchidism was shorter than traditional surgery (P = 0.033), while minimally invasive surgery of high inguinal cryptorchidism was comparable to traditional surgery (P = 0.658). Additionally, there were no cases of testicular atrophy, testicular retraction, inguinal hernia or hydrocele in either group. There was no significant difference in the incidence of poor wound healing between the two groups (P > 0.05). Although there was no significant difference in the incidence of scrotal hematoma between the two groups (P > 0.05), the incidence in the minimally invasive surgery group was higher than that in the traditional surgery group. CONCLUSIONS: Minimally invasive surgery including a transscrotal incision for low inguinal cryptorchidism and laparoscopic surgery for high inguinal cryptorchidism is as safe and effective as traditional surgery, and could also provide a good cosmetic effect for children.


Assuntos
Criptorquidismo , Hérnia Inguinal , Laparoscopia , Hidrocele Testicular , Criptorquidismo/cirurgia , Hérnia Inguinal/cirurgia , Humanos , Lactente , Masculino , Orquidopexia , Estudos Retrospectivos , Escroto/cirurgia , Hidrocele Testicular/cirurgia , Resultado do Tratamento
9.
Preprint | medRxiv | ID: ppmedrxiv-21249183

RESUMO

BackgroundValue of radiomics features from the adrenal gland and periadrenal fat CT images for predicting disease progression in patients with COVID-19 has not been studied. MethodsA total of 1,245 patients (685 moderate and 560 severe patients) were enrolled in a retrospective study. We proposed 3D V-Net to segment adrenal glands in onset CT images automatically, and periadrenal fat was obtained using inflation operation around the adrenal gland. Next, we built a clinical model (CM), three radiomics models (adrenal gland model [AM], periadrenal fat model [PM], and fusion of adrenal gland and periadrenal fat model [FM]), and radiomics nomogram (RN) after radiomics features extracted to predict disease progression in patients with COVID-19. ResultsThe auto-segmentation framework yielded a dice value of 0.79 in the training set. CM, AM, PM, FM, and RN obtained AUCs of 0.712, 0.692, 0.763, 0.791, and 0.806, respectively in the training set. FM and RN had better predictive efficacy than CM (P < 0.0001) in the training set. RN showed that there was no significant difference in the validation set (mean absolute error [MAE] = 0.04) and test set (MAE = 0.075) between predictive and actual results. Decision curve analysis showed that if the threshold probability was more than 0.3 in the validation set or between 0.4 and 0.8 in the test set, it could gain more net benefits using RN than FM and CM. ConclusionRadiomics features extracted from the adrenal gland and periadrenal fat CT images may predict progression in patients with COVID-19. FundingThis study was funded by Science and Technology Foundation of Guizhou Province (QKHZC [2020]4Y002, QKHPTRC [2019]5803), the Guiyang Science and Technology Project (ZKXM [2020]4), Guizhou Science and Technology Department Key Lab. Project (QKF [2017]25), Beijing Medical and Health Foundation (YWJKJJHKYJJ-B20261CS) and the special fund for basic Research Operating Expenses of public welfare research institutes at the central level from Chinese Academy of Medical Sciences (2019PT320003).

10.
Anal Chem ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33284015

RESUMO

Accurate and sensitive detection of single-base mutations in RNAs is of great value in basic studies of life science and medical diagnostics. However, the current available RNA detection methods are challenged by heterogeneous clinical samples in which trace RNA mutants usually existed in a large pool of normal wild sequences. Thus, there is still great need for developing the highly sensitive and highly specific methods in detecting single-base mutations of RNAs in heterogeneous clinical samples. In the present study, a new chimeric DNA probe-aided ligase chain reaction-based electrochemical method (cmDNA-eLCR) was developed for RNA mutation detection through the BSA-based carrier platform and the horseradish peroxidase-hydrogen peroxide-tetramethylbenzidine (HRP-H2O2-TMB) system. The denaturing polyacrylamide gel electrophoresis and a fluorophore-labeled probe was ingeniously designed to demonstrate the advantage of cmDNA in ligation to normal DNA templated by RNA with the catalysis of T4 RNA ligase 2 as well as its higher selectivity than DNA ligase system. Finally, the proposed cmDNA-eLCR, compared with the traditional eLCR, showed excellent performance in discriminating single base-mismatched sequences, where the signal response for mismatched targets at a high concentration could overlap completely with that for the blank control. Besides, this cmDNA-eLCR assay had a wide linear range crossing six orders of magnitude from 1.0 × 10-15 to1.0 × 10-10 M with a limit of detection as low as 0.6 fM. Furthermore, this assay was applied to detect RNA in real sample with a satisfactory result, thereby demonstrating its great potential in diagnosis of RNA-related diseases.

11.
J Agric Food Chem ; 68(52): 15418-15427, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33332120

RESUMO

Inspired by sanguinarine and chelerythrine, a novel antifungal 2-phenylphthalazin-2-ium scaffold as a simple analogue was designed. Most of the 30 compounds showed excellent inhibition activity against almost all eight phytopathogenic fungi, far superior to sanguinarine and chelerythrine. A third of the compounds were more active than azoxystrobin in most cases. Compounds 26 and 27 showed the highest total activity against all the fungi with EC50 means of ca. 4.6 µg/mL. Fusarium solani showed the highest susceptibility with an EC50 mean of 3.62 µg/mL to 19 compounds. A concentration of 25.0 µg/mL 27 can fully control the Colletotrichum gloeosporioides infection in apples over 9 days. Electron microscopic observations showed that 27 was able to damage the structures of the hypha and cell membrane. The structure-activity relationship showed that the presence of electron-withdrawing groups on the C-ring increases the activity against most of the fungi. Thus, 2-phenylphthalazin-2-ium compounds represent promising leads for the development of novel fungicides.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Fenantridinas/química , Fenantridinas/farmacologia , Fungos/efeitos dos fármacos , Fungos/crescimento & desenvolvimento , Estrutura Molecular , Doenças das Plantas/microbiologia , Relação Estrutura-Atividade
12.
J Biol Chem ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033071

RESUMO

Reactive oxygen species (ROS) are an unavoidable host environmental cue for intracellular pathogens such as Mycobacterium tuberculosis and Mycobacterium bovis; however, the signaling pathway in mycobacteria for sensing and responding to environmental stress remains largely unclear. Here, we characterize a novel CmtR-Zur-ESX3-Zn2+ regulatory pathway in M. bovis that aids mycobacterial survival under oxidative stress. We demonstrate that CmtR functions as a novel redox sensor, and that its expression can be significantly induced under H2O2 stress. CmtR can physically interact with the negative regulator Zur and de-represses the expression of the esx-3 operon, which leads to Zn2+ accumulation and promotion of ROS detoxication in mycobacterial cells. Zn2+ can also act as an effector molecule of the CmtR regulator, using which the latter can de-repress its own expression for further inducing bacterial antioxidant adaptation. Consistently, CmtR can induce the expression of EsxH, a component of esx-3 operon involved in Zn2+ transportation that has been reported earlier, and inhibit phagosome maturation in macrophages. Lastly, CmtR significantly contributes to bacterial survival in macrophages and in the lungs of infected mice. Our findings reveal the existence of an antioxidant regulatory pathway in mycobacteria and provide novel information on stress-triggered gene regulation and its association with host-pathogen interaction.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33034423

RESUMO

An estimate of one third of preventable medication errors occurred annually due to patients' misunderstanding of use instructions. To safeguard consumers' over-the-counter (OTC) medicine use and to develop future initiatives, this study evaluated the use, comprehensibility and clarity of the information labels on OTC packages from consumers' perspectives in Taiwan. This cross-sectional study was conducted at 29 community pharmacies; 50 pharmacy clerkship students helped participant enrolment from June to September 2017. Participants (n = 470) were 20 years old or above, Mandarin speaking, and with specific OTC purchases. A face-to-face survey was administered to investigate the degree to which participants read the package labels and their comprehension of correct medicine use. An 11-item survey was used to measure participants' specific OTC purchases (3 items), the use (2 items), comprehensibility (1 item) and clarity (2 items) of OTC package labels, in addition to the sociodemographic information (3 items). Participants were also solicited to provide opinions regarding package label redesign. Descriptive statistics and logistic regressions were applied for analyses. Findings show that most (84.0%) participants read instruction labels before use, with indications (79.4%), drug names (64.5%) and dosage and administration (59.8%) being the top reads. Only 30.0% of the participants fully understood how to take the medicines correctly. Younger (OR = 1.033, p < .001) and female participants (OR = 1.965, p = .014) with a higher level of education (OR = 1.940, p = .034) tended to read package label information prior to purchase or use. Younger participants (OR = 1.030, p < .001) and those who read OTC medicine labels before use (OR = 2.317, p = .004) were more likely to correctly understand medicine use. The findings indicate that older, male adults with a lower level of education should be targeted to ensure their correct understanding of OTC labels. Pharmacists should recite pertinent label information and, concomitantly, ensure consumers' understanding when providing medicine counselling.

14.
Liver Int ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33025657

RESUMO

Liver plays a critical role in metabolism, nutrient storage and detoxification. Emergency signals or appropriate immune response leads to pathological inflammation and breaks the steady state when liver dysfunction appears, which makes body more susceptible to chronic liver infection, autoimmune diseases and tumour. Compelling proof has illustrated the non-redundant importance of C-C chemokine receptor type 2 (CCR2), one of G-protein-coupled receptors, in different diseases. Selectively expressed on the surface of cells, CCR2 is involved in various signalling pathways and regulates the migration of cells. Especially, a peculiar role of CCR2 has been identified within decades in the onset and progression of hepatic diseases, which led to particular focusing on CCR2 as a new therapeutic and diagnostic target for non-alcoholic fatty liver disease and hepatocellular carcinoma. In this review, we discuss the effect of CCR2 in monocytes/macrophages on liver diseases. The application and translation of the decades of discoveries into therapies promise novel approaches in the treatment of liver disease.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33016819

RESUMO

PURPOSE: The aim of this study was to investigate the safety and clinical efficacy of mini-laparoscopic pyeloplasty in treating ureteropelvic junction obstruction (UPJO) in infants. MATERIAL AND METHODS: We retrospectively analysed the clinical data of 66 infants with UPJO from January 2013 to August 2018 at our hospital. They were divided into the laparoscopic surgery group (group A) and the open surgery group (group B), depending on the surgical method. RESULTS: The bleeding volume, analgesia duration, postoperative hospitalization duration, and incision length in group A were significantly less than those in group B (p < .05). The incidence of incision dehiscence was 0% in group A and 11.7% in group B (p = .045). At the postoperative follow-up, the incidence of anastomotic stenosis was 6.2% in group A and 5.9% in group B (p = .719). The anteroposterior diameter and glomerular filtration rate were significantly improved at the one-year follow-up, but there was no significant difference between the groups (p > .05). CONCLUSIONS: Mini-laparoscopic pyeloplasty to treat UPJO in infants has the same early clinical efficacy and safety as open surgery, and this procedure has the advantages of fewer incisions, less pain, quicker recovery, and better cosmetic outcomes.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33092086

RESUMO

The issue of trans-boundary water conflict has become an important factor affecting the relations between basin countries. The key to solve the current conflict problem is to realize the fair and reasonable allocation of trans-boundary water resources. Based on the satisfaction perspective, we developed an asymmetric Nash negotiation model to obtain an optimal and feasible allocation scheme for the trans-boundary water resources. Firstly, based on the two international water laws, we analyzed the influencing factors including water demand differences, resource endowment differences, and water efficiency differences, and by combing with the flexible weight constraint, we built the fair and reasonable allocation pattern for trans-boundary water resources. Secondly, under the constraint of the allocation pattern, we determined the ideal negotiation scheme of each basin country by considering their selection preference. Thirdly, we built a satisfaction degree function and established an asymmetric Nash negotiation model. This is used to build a fair negotiation mechanism among basin countries, and the allocation scheme after negotiation is regarded as the optimal allocation scheme. Lastly, we took the Lancang-Mekong river basin as an example. For this example, the results indicate the following: (1) after considering multiple factors comprehensively, China and Thailand obtained a higher proportion of trans-boundary water resource quota under different preference scenarios, while Myanmar obtained a lower proportion of trans-boundary water resource quota; (2) taking each basin country as the negotiation agent, the optimal allocation scheme with the introduction of fair negotiation mechanism has a higher degree of satisfaction, with an average of over 87.19%, which is more stable and easy to be accepted by all basin countries; (3) from the perspective of the change rate and the average satisfaction of the basin countries, the optimal allocation scheme under the resource endowment preference scenario obtained the highest satisfaction among basin countries. This study aims to improve the practicability and acceptability of trans-boundary water resources allocation, thus providing technical support for reducing trans-boundary water resources conflicts.

17.
J Dig Dis ; 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33128287

RESUMO

OBJECTIVE: This study aimed to determine the risk factors and establish a risk score for post-transjugular intrahepatic portosystemic shunt (TIPS) overt hepatic encephalopathy (OHE). METHODS: Altogether 299 and 62 cirrhotic patients receiving TIPS from January 2015 to March 2018 were divided into the derivation and validation cohorts, respectively. The data of the derivation cohort were analyzed for risk factors of post-TIPS OHE. A risk score was established from the derivation cohort and verified by the validation cohort. RESULTS: During a median follow-up of 112.6 weeks, 52 (17.4%) patients in the derivation cohort experienced post-TIPS OHE. Logistic regression showed that alcoholic cirrhosis (odds ratio [OR] 3.068, 95% confidence interval [CI] 1.423-6.613, P = 0.004), stent diameter of 10 mm (OR 12.046 [95% CI 2.308-62.862], P = 0.003), portal pressure gradient (PPG) decrement ≥60% (OR 3.548 [95% CI 1.741-7.230], P < 0.001), model for end-stage liver disease (MELD) score ≥10 (OR 2.695 [95% CI 1.203-6.035], P = 0.016), blood ammonia (OR 1.009 [95% CI 1.000-1.018], P = 0.043) and notable hydrothorax (OR 4.393 [95% CI 1.554-12.415], P = 0.005) were associated with an increased risk of post-TIPS OHE. The risk score reached a promising risk evaluation of post-TIPS OHE when verified by the validation cohort (sensitivity 71.4%, specificity 70.7%, accuracy 71.0%). CONCLUSIONS: Alcoholic cirrhosis and notable hydrothorax are independent risk factors for post-TIPS OHE in liver cirrhosis, together with the stent diameter of 10 mm, PPG decrement ≥60%, MELD score ≥10 and blood ammonia. The established risk score is reliable to identify high-risk individuals of developing post-TIPS OHE.

18.
Acta Neurol Scand ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32975833

RESUMO

OBJECTIVE: The fractional amplitude of low-frequency fluctuation (fALFF) method was used to identify the regional brain activity deficits of self-limited focal epilepsy with centrotemporal spikes (SLFECS) relative to normal controls (NCs). METHODS: A total of 21 SLFECS (10 females, 11 males; mean age, 8.57 ± 1.5 years) and 21 status-matched (age, sex, and education) NCs (10 females, 11 males; mean age, 8.76 ± 2.19 years) were recruited. The fALFF method was applied to identify SLFECS-related regional brain alterations. Receiver operating characteristic (ROC) curve was applied to identify the ability of these regional brain areas in distinguishing the SLFECS group from the NCs group. The relationships between the regional brain activity deficits and clinical features were evaluated by Pearson's correlation analysis. RESULTS: Self-limited focal epilepsy with centrotemporal spikes was associated with widespread regional brain activity alterations, including left cuneus with higher fALFF values, and bilateral striatum, bilateral precentral gyrus, ventral and dorsal pathway of sensory area, left dorsolateral prefrontal cortex, and left Rolandic area with lower fALFF values. ROC curve revealed excellent AUC value (0.964) of these areas in distinguishing the SLFECS group from the NCs group with high degree of sensitivity (90.5%) and specificity (95.2%). Intelligence quotient score positively correlated with the fALFF value in the left striatum (r = 0.453, p = 0.039). CONCLUSIONS: The fALFF parameter could be served as a potential biomarker to identify the SLFECS-related regional brain deficits in the sensorimotor cortex and their pathways, which may be the etiology of paresthesia in SLFECS.

19.
Sci Rep ; 10(1): 15315, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943705

RESUMO

Duck reovirus (DRV) is a fatal member of the genus Orthoreovirus in the family Reoviridae. The disease caused by DRV leads to huge economic losses to the duck industry. Post-translational modification is an efficient strategy to enhance the immune responses to virus infection. However, the roles of protein phosphorylation in the responses of ducklings to Classic/Novel DRV (C/NDRV) infections are largely unknown. Using a high-resolution LC-MS/MS integrated to highly sensitive immune-affinity antibody method, phosphoproteomes of Cairna moschata spleen tissues under the C/NDRV infections were analyzed, producing a total of 8,504 phosphorylation sites on 2,853 proteins. After normalization with proteomic data, 392 sites on 288 proteins and 484 sites on 342 proteins were significantly changed under the C/NDRV infections, respectively. To characterize the differentially phosphorylated proteins (DPPs), a systematic bioinformatics analyses including Gene Ontology annotation, domain annotation, subcellular localization, and Kyoto Encyclopedia of Genes and Genomes pathway annotation were performed. Two important serine protease system-related proteins, coagulation factor X and fibrinogen α-chain, were identified as phosphorylated proteins, suggesting an involvement of blood coagulation under the C/NDRV infections. Furthermore, 16 proteins involving the intracellular signaling pathways of pattern-recognition receptors were identified as phosphorylated proteins. Changes in the phosphorylation levels of MyD88, NF-κB, RIP1, MDA5 and IRF7 suggested a crucial role of protein phosphorylation in host immune responses of C. moschata. Our study provides new insights into the responses of ducklings to the C/NDRV infections at PTM level.

20.
Adv Ther ; 37(11): 4660-4674, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32970315

RESUMO

INTRODUCTION: Simultaneous administration of acetylsalicylic acid (ASA) and clopidogrel has demonstrated efficacy in the treatment of acute coronary syndrome. Clopidogrel + ASA in a fixed-dose combination (FDC) provides a pharmaceutical option to enhance adherence to the coadministration of dual antiplatelet therapy (DAPT). Herein, we evaluate the bioequivalence of enteric ASA and clopidogrel in an FDC compared with simultaneous administration of the individual formulations. METHODS: This study is a randomized, single-center, open-label, three-sequence, three-period, two-treatment, crossover study conducted in healthy Chinese male and female subjects under fed conditions. Subjects were randomized to receive, in each period, a single dose of (1) a combination tablet containing 75-mg clopidogrel and 100-mg enteric ASA (test formulation) or (2) coadministration of one 75-mg clopidogrel tablet and one 100-mg enteric-coated ASA tablet (reference formulations) under fed conditions. Plasma samples were analyzed for ASA, salicylic acid, clopidogrel, and the clopidogrel metabolite SR26334. For ASA, the reference-scaled average bioequivalence (RSABE) analysis was conducted for Cmax of ASA because within-subject standard deviation (SDW) was ≥ 0.294 for log-transformed Cmax. RESULTS: The point estimate (test/reference geometric mean ratio) was between 0.80 and 1.25, and the upper one-sided 95% confidence interval (CI) for the scaled average bioequivalence metric was ≤ 0 (-0.08). AUC of ASA as SDW was < 0.294 for log-transformed AUClast and AUC. Estimates of 90% CIs for log-transformed AUClast and AUC ratios were within the bioequivalence range of 0.80 to 1.25 (0.98-1.08 and 1.00-1.10, respectively). For clopidogrel, the 90% CIs for the ratios comparing log-transformed Cmax, AUClast, and AUC ratios of clopidogrel following administration of test versus reference formulation were calculated using the ABE method and were well within the acceptable range of 0.80 to 1.25 (1.02-1.12, 0.92-0.99, and 0.92-0.98, respectively). CONCLUSION: FDC of ASA and clopidogrel was bioequivalent to the simultaneous administration of the individual formulations in healthy Chinese subjects under fed conditions. TRIAL REGISTRATION: CTR20190376.

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