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2.
Signal Transduct Target Ther ; 6(1): 329, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471087

RESUMO

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

3.
Adv Sci (Weinh) ; : e2102027, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473427

RESUMO

The organic passivated carbon nanotube (CNT)/silicon (Si) solar cell is a new type of low-cost, high-efficiency solar cell, with challenges concerning the stability of the organic layer used for passivation. In this work, the stability of the organic layer is studied with respect to the internal and external (humidity) water content and additionally long-term stability for low moisture environments. It is found that the organic passivated CNT/Si complex interface is not stable, despite both the organic passivation layer and CNTs being stable on their own and is due to the CNTs providing an additional path for water molecules to the interface. With the use of a simple encapsulation, a record power conversion efficiency of 22% is achieved and a stable photovoltaic performance is demonstrated. This work provides a new direction for the development of high-performance/low-cost photovoltaics in the future and will stimulate the use of nanotubes materials for solar cells applications.

4.
Oxid Med Cell Longev ; 2021: 2951697, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471463

RESUMO

Purpose: Although doxorubicin chemotherapeutic drug is commonly used to treat various solid and hematological tumors, its clinical use is restricted because of its adverse effects on the normal cells/tissues, especially cardiotoxicity. The use of resveratrol may mitigate the doxorubicin-induced cardiotoxic effects. For this aim, we systematically reviewed the potential chemoprotective effects of resveratrol against the doxorubicin-induced cardiotoxicity. Methods: In the current study, a systematic search was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline for the identification of all relevant studies on "the role of resveratrol on doxorubicin-induced cardiotoxicity" in the electronic databases of Web of Science, PubMed, and Scopus up to March 2021 using search terms in their titles and abstracts. Two hundred and eighteen articles were screened in accordance with a predefined set of inclusion and exclusion criteria. Finally, 33 eligible articles were included in this systematic review. Results: The in vitro and in vivo findings demonstrated a decreased cell survival, increased mortality, decreased heart weight, and increased ascites in the doxorubicin-treated groups compared to the control groups. The combined treatment of resveratrol and doxorubicin showed an opposite pattern than the doxorubicin-treated groups alone. Furthermore, this chemotherapeutic agent induced the biochemical and histopathological changes on the cardiac cells/tissue; however, the results (for most of the cases) revealed that these alterations induced by doxorubicin were reversed near to normal levels (control groups) by resveratrol coadministration. Conclusion: The results of this systematic review stated that coadministration of resveratrol alleviates the doxorubicin-induced cardiotoxicity. Resveratrol exerts these chemoprotective effects through several main mechanisms of antioxidant, antiapoptosis, and anti-inflammatory.

5.
Mol Med Rep ; 24(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34476506

RESUMO

The present study aimed to explore the regulatory mechanism of long intergenic non­protein coding (LINC)00238 in hepatocellular carcinoma (HCC). LINC00238 expression in HCC tissues and cell lines was measured using reverse transcription­quantitative PCR. LncTar was used to predict the binding sites between LINC00238 and transmembrane protein 106C (TMEM106C). Survival analysis of LINC00238, TMEM106C and activating transcription factor 3 (ATF3) in patients with HCC was performed based on TCGA data. The proliferation, apoptosis, migration, and invasion of HCC cells were measured by 3­(4,5­dimethylthiazol­2­yl)­5­(3­carboxymethoxyphenyl)­2­(4­sulfophenyl)­2H­tetrazolium assay, flow cytometer, wound healing and Transwell assays, respectively. LINC00238 promoted apoptosis and inhibited proliferation, migration and invasion of HCC cells. LINC00238 was downregulated in HCC. TMEM106C was a target of LINC00238 and TMEM106C expression was negatively regulated by LINC00238. TMEM106C suppressed the apoptosis pathway and decreased the expression of caspase­7, tissue inhibitor of metalloproteinase 2, programmed cell death 4 and ATF3. Notably, ATF3 was the upstream promoter of LINC00238 and positively regulated LINC00238 expression. In conclusion, LINC00238 inhibited HCC progression by inhibiting TMEM106 expression and activating the TMEM106C­mediated apoptosis pathway.

6.
BMC Cardiovasc Disord ; 21(1): 433, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34517822

RESUMO

BACKGROUND: A high level of total cholesterol is associated with several lipid metabolism disorders, including atherosclerosis and cardiovascular diseases. ATP-binding cassette (ABC) transporter A1 (ABCA1) and miR-33-5p play crucial roles in atherosclerosis by controlling cholesterol efflux. While citrate is a precursor metabolite for lipid and cholesterol synthesis, little is known about the association between citrate synthase (CS) and cholesterol efflux. This study investigated the role of the miR-33-5p/ABCA1/CS axis in regulating cholesterol efflux in vascular endothelial cells (VECs). MATERIALS AND METHODS: VECs were treated with oxidized low-density lipoprotein cholesterol (ox-LDL), or pretreated with plasmids overexpressing CS, ABCA1, siRNAs against CS and ABCA1, and an miR-33-5p inhibitor. Cell apoptosis, cellular senescence-associated ß-galactosidase activity, inflammation, and cholesterol efflux were detected. RESULTS: Treatment with ox-LDL decreased ABCA1 and CS levels and increased miR-33-5p expression and apoptosis in dose-dependent manners. In contrast, treatment with the miR-33-5p inhibitor and ABCA1 and CS overexpression plasmids inhibited the above-mentioned ox-LDL-induced changes. In addition, treatment with ox-LDL decreased cholesterol efflux, induced aging, and promoted the production of inflammatory cytokines (i.e., IL-6 and tumor necrosis factor TNF-α), as well as the expression of Bax and Caspase 3 proteins in VECs. All these changes were rescued by miR-33-5p inhibition and ABCA1 and CS overexpression. The inhibition of ABCA1 and CS by siRNAs eliminated the effects mediated by the miR-33-5p inhibitor, and knockdown of CS eliminated the effects of ABCA1 on VECs. CONCLUSIONS: This study demonstrated the crucial roles played by the miR-33-5p/ABCA1/CS axis in regulating cholesterol efflux, inflammation, apoptosis, and aging in VECs, and also suggested the axis as a target for managing lipid metabolism disorders.

7.
J Microbiol Biotechnol ; 31(1)2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34489378

RESUMO

Vibrio parahaemolyticus isrecognized as one of the most important foodborne pathogens responsible for gastroenteritis in humans. The blaCARB-17 gene is an intrinsic ß-lactamase gene and a novel species-specific genetic marker of V. parahaemolyticus. In this study, a loop-mediated isothermal amplification (LAMP) assay combined with a lateral flow dipstick (LFD) was developed targeting this blaCARB-17 gene. The specificity of LAMP-LFD was ascertained by detecting V. parahaemolyticus ATCC 17802 and other seven non-V. parahaemolyticus strains. Finally, the practicability of LAMP-LFD was confirmed by detection with V. parahaemolyticus-contaminated samples and natural food samples. The results showed that the optimized reaction parameters of LAMP are as follows: 2.4 mmol/L Mg2+, 0.96 mmol/L dNTPs, 4.8 U Bst DNA polymerase, 8:1 ratio of inner primer to outer primer, at 63 °C for 40 min. The optimized reaction time of the LFD assay is 60 min. Cross-reactivity analysis with seven non-V. parahaemolyticus strains showed that LAMP-LFD was exclusively specific for V. parahaemolyticus. The detection limit of LAMP-LFD for V. parahaemolyticus genomic DNA was 2.1×10-4 ng/µL, corresponding to 630 fg/reaction and displaying a sensitivity that is 100-fold higher than that of conventional PCR. LAMP-LFD in a spiking study revealed a detection limit of approximately 6 cfu/mL, which was similar with conventional PCR. The developed LAMP-LFD specifically identified the 10 V. parahaemolyticus isolates from 30 seafood samples. It suggested that this LAMP-LFD may be a suitable diagnostic method for detecting V. parahaemolyticus in aquatic foods.

8.
Am J Trop Med Hyg ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491217

RESUMO

Bullous scabies (BS) is a rare atypical clinical variant of scabies and is easily confused with bullous disorders. The diagnosis of BS is always a challenge, and physicians often misdiagnose BS patients. Patients with BS admitted from 2012 to 2020 were enrolled in this study. The clinical, dermoscopic, and pathological characteristics of the patients were analyzed retrospectively. Ten patients with BS were enrolled in this study. Seven of the 10 patients were male. The bullae were most commonly found on the thighs and arms (80% of patients). Only 30% of patients (3/10) tested positive for mites and/or eggs by the initial skin scraping, but 100% (5/5) of the patients who received dermoscopy tested positive. Among these 10 patients, only five received a skin biopsy. Subepidermal (4/5) and intraepidermal (1/5) bullae with eosinophil and neutrophil infiltration were observed in five patients. Direct immunofluorescence (DIF) indicated linear deposition of IgG in the basement membrane zone in three patients. Physicians should consider the possibility of BS in patients with blisters, pruritus, and poor response to corticosteroids. Dermoscopy should be prioritized for the differential diagnosis of BS to exclude other bullous disorders. Finally, a biopsy should be performed on each patient with bullae.

9.
Nanoscale ; 13(33): 14197-14206, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34477701

RESUMO

Surface modification by loading a water oxidation co-catalyst (WOC) is generally considered an efficient means to optimize the sluggish surface oxygen evolution reaction (OER) of a hematite photoanode for photoelectrochemical (PEC) water oxidation. However, the surface WOC usually exerts little impact on the bulk charge separation of hematite. Herein, an ultrathin citrate-Ni0.9Co0.1(OH)x [Cit-Ni0.9Co0.1(OH)x] is conformally coated on the fluorine-doped hematite (F-Fe2O3) photoanode for PEC water oxidation to simultaneously promote the internal hole extraction and surface hole injection of the target photoanode. Besides, the conformally coated Cit-Ni0.9Co0.1(OH)x overlayer passivates the redundant surface trap states of F-Fe2O3. These factors result in a superior photocurrent density of 2.52 mA cm-2 at 1.23 V versus a reversible hydrogen electrode (V vs. RHE) for the target photoanode. Detailed investigation manifests that the hole extraction property in Cit-Ni0.9Co0.1(OH)x is mainly derived from the Ni sites, while Co incorporation endows the overlayer with more catalytic active sites. This synergistic effect between Ni and Co contributes to a rapid and continuous hole migration pathway from the bulk to the interface of the target photoanode, and then to the electrolyte for water oxidation.

10.
J Control Release ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34481927

RESUMO

There is a great challenge in regenerating cartilage defects, which usually involve absent bearing capacity and poor adaptation to joint movement, further exacerbating subchondral bone damage. Therefore, ideal tissue-engineering cartilage scaffolds should be endowed with biomimetic and sustained-release function for promoting long-term chondrogenesis while protecting subchondral bone. Herein, in situ self-assembling gel based on glyceryl monooleate (GMO)-hyaluronic acid (HA) composite lyotropic liquid crystal (HLC) was developed as the biomimetic scaffold to deliver kartogenin for long-term cartilage regeneration. Compared to the GMO based (LLC) gel, HLC gel with modified lattice structure exhibited improved rheological properties for better joint protection by increasing mechanical strength, elasticity and lubrication. Besides, HLC gel successfully prolonged drug release and retention in the joint cavity over 4 weeks to provide combined effect of kartogenin and HA in cartilage repair. Pharmacodynamic studies demonstrated that HLC gel was the most effective to promote chondrogenesis and protect subchondral bone, making the damaged bone tissue restored to normal in divergent features as evidenced by the MRI, Micro-CT and histological results. Therefore, the HLC gel with joint protection and controlled drug release can serve as a firm scaffold for providing long-term cartilage repair.

11.
Technol Health Care ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34486995

RESUMO

BACKGROUND: Wearable lower extremity exoskeletons can provide walking assistance for the physical rehabilitation of paralyzed individuals. However, most of the existing exoskeletons require crutches to maintain balance, thus a self-balancing type is needed to improve applicability. OBJECTIVE: The purpose of this work is to study the kinematic characteristics of a novel lower extremity exoskeleton for crutch-less walking rehabilitation, and evaluate the movement performance through practical experiments. METHODS: Based on the human lower limb structure and movement characteristics, a fully actuated 10 degrees-of-freedom (DoF) lower extremity exoskeleton was proposed. The kinematic characteristics of the exoskeleton were analyzed by the D-H method and geometric method, and the model validity was verified through simulations and experiments. RESULTS: The closed-form solutions for both forward and inverse kinematics models were obtained. The consistent results of theoretical calculation and numerical simulation have shown the accuracy of the established models. The practical experiments regarding six trials have demonstrated the movement performance of the proposed exoskeleton, including sit, stance, leg extension/flexion, and left/right swing. CONCLUSIONS: The kinematic characteristics of the proposed 10-DoF lower extremity exoskeleton are similar to the human lower limb, and it could meet the motion demands of crutch-less walking rehabilitation.

12.
J Hazard Mater ; 423(Pt A): 127029, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34479086

RESUMO

Imidacloprid (IMI), as the most widely used neonicotinoid insecticide, poses a serious threat to the water ecosystem due to the inefficient elimination in the traditional water treatment. Chitosan (CTS)-stabilized biochar (BC)-supported Ag nanoparticles (CTS@AgBC) are applied to eliminate the IMI in the water treatment effectively. Batch experiments depict that the modification of BC by CTS and Ag nanoparticles remarkably improve its adsorption performance. The pseudo-second-order and Elovich models have good performance in simulating the adsorption processes of CTS@AgBC and BC. This indicates that the chemical adsorption on real surfaces plays the dominant role in the adsorption of IMI by CTS@AgBC and BC. In addition, the multihead attention (MHA)-based convolutional neural network (CNN) combined with the time-dependent Cox regression model are initially applied to predict and dissect the adsorption elimination processes of IMI by CTS@AgBC. The proposed MHA-CNN model achieves more accurate concentration prediction of IMI than traditional models. According to influence weights by MHA module, biochar category, pH, and treatment temperature are considered the three dominant environmental variables to determine the IMI elimination processes. This study provides insights into roles of environmental variables in the elimination of IMI by CTS@AgBC and the accurate prediction of IMI concentration.

13.
PLoS Negl Trop Dis ; 15(9): e0009730, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34492012

RESUMO

In recent years, the human gut microbiome has been recognised to play a pivotal role in the health of the host. Intestinal homeostasis relies on this intricate and complex relationship between the gut microbiota and the human host. While much effort and attention has been placed on the characterization of the organisms that inhabit the gut microbiome, the complex molecular cross-talk between the microbiota could also exert an effect on gastrointestinal conditions. Blastocystis is a single-cell eukaryotic parasite of emerging interest, as its beneficial or pathogenic role in the microbiota has been a subject of contention even to-date. In this study, we assessed the function of the Blastocystis tryptophanase gene (BhTnaA), which was acquired by horizontal gene transfer and likely to be of bacterial origin within Blastocystis. Bioinformatic analysis and phylogenetic reconstruction revealed distinct divergence of BhTnaA versus known bacterial homologs. Despite sharing high homology with the E. coli tryptophanase gene, we show that Blastocystis does not readily convert tryptophan into indole. Instead, BhTnaA preferentially catalyzes the conversion of indole to tryptophan. We also show a direct link between E. coli and Blastocystis tryptophan metabolism: In the presence of E. coli, Blastocystis ST7 is less able to metabolise indole to tryptophan. This study examines the potential for functional variation in horizontally-acquired genes relative to their canonical counterparts, and identifies Blastocystis as a possible producer of tryptophan within the gut.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34494423

RESUMO

In the present study, a magnetic mimic multi-enzyme system was developed by encapsulating the aryloxyphenoxypropionate (AOPP) herbicide hydrolase QpeH and alcohol oxidase (AOx) in zeolitic imidazolate framework (ZIF-8) nanocrystals with magnetic Fe3O4 nanoparticles (MNPs) to detect AOPP herbicides. The structural, protein loading capacity and loading ratio, porosity, and magnetic properties of QpeH/AOx@mZIF-8 were characterized by scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, nitrogen sorption, and vibrating sample magnetometry. An AOPP herbicide colorimetric biosensor made with QpeH/AOx@mZIF-8 had the highest sensitivity toward quizalofop-P-ethyl (QpE) with a limit of detection of 8.2 µM. This system was suitable to detect two other AOPP herbicides, including fenoxaprop-P-ethyl (FpE) and haloxyfop-P-methyl (HpE). The practical application of the biosensor was verified through quantitative analysis of QpE residues in industrial wastewater and field soils. Furthermore, QpeH/AOx@mZIF-8 exhibited excellent long-term storage stability (at least 50 days), easy separation by magnet, and reusability (at least 10 cycles), supporting its promising role in simple and low-cost detection of AOPP herbicides in real environmental samples.

15.
ACS Sens ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34494426

RESUMO

Tumor-derived exosomes play a vital role in the process of cancer development. Quantitative analysis of exosomes and exosome-shuttled proteins would be of immense value in understanding cancer progression and generating reliable predictive biomarkers for cancer diagnosis and treatment. Recent studies have indicated the critical role of exosomal programmed death ligand 1 (PD-L1) in immune checkpoint therapy and its application as a patient stratification biomarker in cancer immunotherapy. Here, we present a nanoplasmonic exosome immunoassay utilizing gold-silver (Au@Ag) core-shell nanobipyramids and gold nanorods, which form sandwich immune complexes with target exosomes. The immunoassay generates a distinct plasmonic signal pattern unique to exosomes with specific exosomal PD-L1 expression, allowing rapid, highly sensitive exosome detection and accurate identification of PD-L1 exosome subtypes in a single assay. The developed nanoplasmonic sandwich immunoassay provides a novel and viable approach for tumor cell-derived exosome detection and analysis with quantitative molecular details of key exosomal proteins, manifesting its great potential as a transformative diagnostic tool for early cancer detection, prognosis, and post-treatment monitoring.

16.
PLoS One ; 16(9): e0256628, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34492040

RESUMO

Paratuberculosis a contagious and chronic disease in domestic and wild ruminants, is caused by Mycobacterium avium subspecies paratuberculosis (MAP). Typical clinical signs include intractable diarrhea, progressive emaciation, proliferative enteropathy, and mesenteric lymphadenitis. Paratuberculosis is endemic to many parts of the world and responsible for considerable economic losses. In this study, different types of paratuberculosis and MAP in sheep and goats were investigated in Inner Mongolia, a northern province in China contiguous with two countries and eight other provinces. A total of 4434 serum samples were collected from six cities in the western, central, and eastern regions of Inner Mongolia and analyzed using the ELISA test. In addition, tissue samples were collected from seven animals that were suspected to be infected with MAP. Finally, these tissues samples were analyzed by histopathological examination followed by polymerase chain reaction (PCR), IS1311 PCR-restriction enzyme analysis (PCR-REA), and a sequence analysis of five genes. Among all 4434 ruminant serum samples collected from the six cities in the western, central, and eastern regions of Inner Mongolia, 7.60% (337/4434) measured positive for the MAP antibody. The proportions of positive MAP antibody results for serum samples collected in the western, central, and eastern regions were 5.10% (105/2058), 6.63% (85/1282), and 13.44% (147/1094), respectively. For the seven suspected infected animals selected from the herd with the highest rate of positivity, the gross pathology and histopathology of the necropsied animals were found to be consistent with the pathological features of paratuberculosis. The PCR analysis further confirmed the diagnosis of paratuberculosis. The rest of the results demonstrated that herds of sheep and goats in Inner Mongolia were infected with both MAP type II and type III. To the best of our knowledge, this is the first study of the two subtypes of MAP strains in sheep and goats in Inner Mongolia.

17.
Biomed Res Int ; 2021: 6618257, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497852

RESUMO

Background: This study is aimed at investigating whether dapagliflozin adjunct to insulin therapy further improves glycemic control compared to insulin therapy alone in patients with newly diagnosed type 2 diabetes (T2D). Methods: This single-centre, randomized, controlled, open-labeled trial recruited newly diagnosed T2D patients. Subjects were randomized 1 : 1 to the dapagliflozin add-on to continuous subcutaneous insulin infusion (CSII) group (DAPA) or the CSII therapy group for 5 weeks. Standard meal tests were performed 3 times at days -3, 7, and 35 for glucose, C-peptide, and insulin level determination. Two-time continuous glucose monitoring (CGM) was performed at baseline and at the end of the study. The primary endpoint was the difference in the mean amplitude of glycemic excursions (MAGEs) between the groups. Results: A total of 66 subjects completed the study, with 34 and 32 patients in the DAPA and CSII groups, respectively. Patients in the DAPA group exhibited significant decreases in MAGE levels at the endpoint. We also observed that patients in the DAPA group had a lower homoeostasis model assessment insulin resistance (HOMA-IR) and a higher homoeostasis model assessment B (HOMA-B) value at 1 week and 5 weeks compared to those with insulin therapy, respectively. In addition, our data showed that patients in the DAPA group showed a significantly lower insulin dose (0.07 U/kg) and weighed less than those in the CSII group. Conclusion: Our data indicate that dapagliflozin adjunct to insulin is a safe and effective therapy for improving glycemic variations, insulin sensitivity, and weight loss in newly diagnosed T2D patients.

18.
Mol Brain ; 14(1): 136, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496926

RESUMO

Innately aversive experiences produce rapid defensive responses and powerful emotional memories. The midbrain periaqueductal gray (PAG) drives defensive behaviors through projections to brainstem motor control centers, but the PAG has also been implicated in aversive learning, receives information from aversive-signaling sensory systems and sends ascending projections to the thalamus as well as other forebrain structures which could control learning and memory. Here we sought to identify PAG subregions and cell types which instruct memory formation in response to aversive events. We found that optogenetic inhibition of neurons in the dorsolateral subregion of the PAG (dlPAG), but not the ventrolateral PAG (vlPAG), during an aversive event reduced memory formation. Furthermore, inhibition of a specific population of thalamus projecting dlPAG neurons projecting to the anterior paraventricular thalamus (aPVT) reduced aversive learning, but had no effect on the expression of previously learned defensive behaviors. By contrast, inactivation of dlPAG neurons which project to the posterior PVT (pPVT) or centromedial intralaminar thalamic nucleus (CM) had no effect on learning. These results reveal specific subregions and cell types within PAG responsible for its learning related functions.

19.
Virol J ; 18(1): 181, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488793

RESUMO

BACKGROUND: Transmitted drug resistance (TDR) that affects the effectiveness of the first-line antiretroviral therapy (ART) regimen is becoming prevalent worldwide. However, its prevalence and transmission among HIV-1 treatment-naïve patients in Guangdong, China are rarely reported. We aimed to comprehensively analyze the prevalence of TDR and the transmission clusters of HIV-1 infected persons before ART in Guangdong. METHODS: The HIV-1 treatment-naïve patients were recruited between January 2018 and December 2018. The HIV-1 pol region was amplified by reverse transcriptional PCR and sequenced by sanger sequencing. Genotypes, surveillance drug resistance mutations (SDRMs) and TDR were analyzed. Genetic transmission clusters among patients were identified by pairwise Tamura-Nei 93 genetic distance, with a threshold of 0.015. RESULTS: A total of 2368 (97.17%) HIV-1 pol sequences were successfully amplified and sequenced from the enrolled 2437 patients. CRF07_BC (35.90%, 850/2368), CRF01_AE (35.56%, 842/2368) and CRF55_01B (10.30%, 244/2368) were the main HIV-1 genotypes circulating in Guangdong. Twenty-one SDRMs were identified among fifty-two drug-resistant sequences. The overall prevalence of TDR was 2.20% (52/2368). Among the 2368 patients who underwent sequencing, 8 (0.34%) had TDR to protease inhibitors (PIs), 22 (0.93%) to nucleoside reverse transcriptase inhibitors (NRTIs), and 23 (0.97%) to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Two (0.08%) sequences showed dual-class resistance to both NRTIs and NNRTIs, and no sequences showed triple-class resistance. A total of 1066 (45.02%) sequences were segregated into 194 clusters, ranging from 2 to 414 sequences. In total, 15 (28.85%) of patients with TDR were included in 9 clusters; one cluster contained two TDR sequences with the K103N mutation was observed. CONCLUSIONS: There is high HIV-1 genetic heterogeneity among patients in Guangdong. Although the overall prevalence of TDR is low, it is still necessary to remain vigilant regarding some important SDRMs.

20.
J Colloid Interface Sci ; 606(Pt 2): 1340-1351, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34500150

RESUMO

The fabrication of stable and efficient catalysts for green and economic catalytic transformation is significant. Here, highly stable covalent triazine frameworks (CTF-1) were used as the supporting material for anchoring ultrafine Pd nanoparticles (NPs) via a facile impregnation process and a one-pot calcination-reduction strategy. The widespread dispersion of ultrafine Pd NPs was a result of the abundant high nitrogen-content triazine groups of CTF-1 that endowed the catalyst Pd@CTF-1 with high catalytic activity. The catalytic performance of Pd@CTF-1 was demonstrated by the one-pot N-alkylation of benzaldehyde with aniline (or nitrobenzene) under mild reaction conditions, and Pd@CTF-1 exhibited a wide range of general applicability for N-alkylation reactions. The reaction mechanism for the N-alkylation reaction was also studied in detail. In addition, the Pd@CTF-1 catalyst exhibited high thermal and chemical stability, maintaining good catalytic efficiency after multiple reaction cycles. This study provides new insights for the fabrication of organic supporting materials with highly dispersed active catalytic sites that can lead to excellent catalytic performance for efficient, economical, and green reactions.

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