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1.
Artigo em Inglês | MEDLINE | ID: mdl-34508310

RESUMO

Green building development(GBD) plays an important role in improving carbon emission reduction efficiency of the construction industry(CEEOCI), and accelerating the construction industry to achieve carbon neutrality goals. In this paper, for the first time, the topic of "green building development promotes carbon neutrality in the construction industry" is included in the crossover research category of industrial economics and space economics. A framework for the analysis of the impact mechanism of GBD and CEEOCI under the dual perspective of "industry-space" is proposed. Based on China's provincial panel data from 2008 to 2019, using the intermediary adjustment model and the spatial Dubin model to analyze and test the industrial mechanism, spatial mechanism, and spatial effect attenuation boundary of the GBD effect on CEEOCI. The results show GBD is found to promote CEEOCI, and both the GBD and CEEOCI have a clear "center-periphery" spatial pattern. Meanwhile, the impact of GBD on CEEOCI has a "industry-space" two-dimensional mechanism. From an industrial perspective, GBD can change the supply-demand relationship of the construction market by promoting the greening of supporting industries in the construction industry and stimulating green consumption in the market, and ultimately achieve the overall improvement of CEEOCI. From a spatial perspective, GBD can form a new sectoral growth pole and provide elemental support for the improvement of CEEOCI through the polarization effect, but the polarization effect is higher in the range of 1000 km, while attenuation occurs outside the range of 1000 km. This paper provides not only a scientific and effective medium and macro analysis framework for green building development emission reduction performance evaluation but also a new theoretical basis and policy direction for the construction industry to improve carbon reduction efficiency and achieve industrial carbon neutrality.

2.
Dev Cell ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34508658

RESUMO

Membrane contact between intracellular organelles is important in mediating organelle communication. However, the assembly of molecular machinery at membrane contact site and its internal organization correlating with its functional activity remain unclear. Here, we demonstrate that a gel-like condensation of Cidec, a crucial protein for obesity development by facilitating lipid droplet (LD) fusion, occurs at the LD-LD contact site (LDCS) through phase separation. The homomeric interaction between the multivalent N terminus of Cidec is sufficient to promote its phase separation both in vivo and in vitro. Interestingly, Cidec condensation at LDCSs generates highly plastic and lipid-permeable fusion plates that are geometrically constrained by donor LDs. In addition, Cidec condensates are distributed unevenly in the fusion plate generating stochastic sub-compartments that may represent unique lipid passageways during LD fusion. We have thus uncovered the organization and functional significance of geometry-constrained Cidec phase separation in mediating LD fusion and lipid homeostasis.

3.
Int J Mol Sci ; 22(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34502445

RESUMO

The dried root of Salvia miltiorrhiza is a renowned traditional Chinese medicine that was used for over 1000 years in China. Salvianolic acid B (SalB) is the main natural bioactive product of S. miltiorrhiza. Although many publications described the regulation mechanism of SalB biosynthesis, few reports simultaneously focused on S. miltiorrhiza root development. For this study, an R2R3-MYB transcription factor gene (SmMYB52) was overexpressed and silenced, respectively, in S. miltiorrhiza sterile seedlings. We found that SmMYB52 significantly inhibited root growth and indole-3-acetic acid (IAA) accumulation, whereas it activated phenolic acid biosynthesis and the jasmonate acid (JA) signaling pathway. Quantitative real-time polymerase chain reaction (qRT-PCR) analyses revealed that SmMYB52 suppressed the transcription levels of key enzyme-encoding genes involved in the IAA biosynthetic pathway and activated key enzyme-encoding genes involved in the JA and phenolic acid biosynthesis pathways. In addition, yeast one-hybrid (Y1H) and dual-luciferase assay showed that SmMYB52 directly binds to and activates the promoters of several key enzyme genes for SalB biosynthesis, including SmTAT1, Sm4CL9, SmC4H1, and SmHPPR1, to promote the accumulation of SalB. This is the first report of a regulator that simultaneously affects root growth and the production of phenolic acids in S. miltiorrhiza.

4.
Adv Mater ; : e2007778, 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510563

RESUMO

Cancer has been one of the most common life-threatening diseases for a long time. Traditional cancer therapies such as surgery, chemotherapy (CT), and radiotherapy (RT) have limited effects due to drug resistance, unsatisfactory treatment efficiency, and side effects. In recent years, photodynamic therapy (PDT), photothermal therapy (PTT), and chemodynamic therapy (CDT) have been utilized for cancer treatment owing to their high selectivity, minor resistance, and minimal toxicity. Accumulating evidence has demonstrated that selective delivery of drugs to specific subcellular organelles can significantly enhance the efficiency of cancer therapy. Mitochondria-targeting therapeutic strategies are promising for cancer therapy, which is attributed to the essential role of mitochondria in the regulation of cancer cell apoptosis, metabolism, and more vulnerable to hyperthermia and oxidative damage. Herein, the rational design, functionalization, and applications of diverse mitochondria-targeting units, involving organic phosphine/sulfur salts, quaternary ammonium (QA) salts, peptides, transition-metal complexes, guanidinium or bisguanidinium, as well as mitochondria-targeting cancer therapies including PDT, PTT, CDT, and others are summarized. This review aims to furnish researchers with deep insights and hints in the design and applications of novel mitochondria-targeting agents for cancer therapy.

5.
Endocr Connect ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34524970

RESUMO

OBJECTIVE: To investigate the relationship between serum uric acid (SUA) level and renal outcome in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy(DN). METHODS: A total of 393 Chinese patients with T2DM and biopsy-proven DN and followed at least one year were enrolled in this study. Patients were stratified by the quartiles of baseline level of SUA: Q1 group286.02± 46.66 µmol/L (n=98); Q2 group: 358.23±14.03µmol/L (n=99); Q3 group: 405.50±14.59µmol/L (n=98) and Q4 group: 499.14±56.97µmol/L (n=98).Renal outcome was defined by progression to end stage renal disease (ESRD). Kaplan-Meier survival analysis and Cox proportional hazards model were used to analyze the association between SUA quartiles and the renal outcomes. RESULTS: During the median 3-year follow-up period, there were 173 ESRD outcome events (44.02%) during follow-up. No significant difference among SUA level the risk of progression of DN (P=0.747) was shown in the Kaplan-Meier survival analysis. In multivariable-adjusted model, HRs for developing ESRD were 1.364(0.621-2.992; p=0.439), 1.518(0.768-3.002; p=0.230) and 1.411(0.706-2.821; p=0.330) for the Q2, Q3 and Q4, respectively, in comparison with the Q1 (P=0.652). CONCLUSIONS: No significant association between SUA level and renal outcome of ESRD in Chinese patients with T2DM and DN was found in our study. Besides, the role of uric acid-lowering therapy in delaying DN progression and improve ESRD outcome had not yet been proven. Further study was needed to clarify the renal benefit of the uric acid-lowering therapy in the treatment of DN.

6.
Cell Signal ; : 110148, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34530056

RESUMO

Spi-B transcription factor (SPIB) is a member of the E-twenty-six (ETS) transcription factor family. Previous studies have shown that the expression of SPIB is downregulated in human colorectal cancer tissues. The purpose of our study was to explore the biological function and related mechanism of SPIB in colorectal cancer cells. Our study found that SPIB could inhibit the proliferation, migration and invasion of CRC cells; inhibit angiogenesis; and induce CRC cells cycle arrest in G2/M phase and promote the apoptosis of CRC cells. We also found that compared with the control group, the 50% inhibitory concentration (IC50) values of oxaliplatin and 5-FU in the SPIB overexpression group were significantly reduced. Western blot results showed that the overexpression of SPIB upregulated cleaved-PARP(c-PARP), nuclear factor kB p65 (NFkB p65), phospho-NFkB p65 (p-NFkB P65), JNK1, and C-Jun protein expression levels compared with the control group. The silence of SPIB downregulated c-PARP, NFκB p65, p-NFκB p65, JNK1, and C-Jun protein expression levels. A dual-luciferase reporter assay showed that SPIB could activate the promoter of MAP4K1 and enhance the expression of MAP4K1. After silencing MAP4K1, the protein expression levels of c-PARP, NFkB P65, p-NFkB P65, JNK1, and C-Jun were downregulated. In summary, we found that SPIB is a tumor suppressor in colorectal cancer cells and that SPIB sensitizes colorectal cancer cells to oxaliplatin and 5-FU, SPIB exerts its anti-colorectal cancer effect by activating the NFkB and JNK signaling pathways through MAP4K1. The above findings may provide a reference for new molecular markers and therapeutic targets for CRC.

7.
BMC Cancer ; 21(1): 1038, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530755

RESUMO

BACKGROUND: To develop and validate multivariate models integrating endoscopic biopsy, tumor markers, and CT findings based on late arterial phase (LAP) to predict serosal invasion in gastric cancer (GC). METHODS: The preoperative differentiation degree, tumor markers, CT morphological characteristics, and CT value-related and texture parameters of 154 patients with GC were analyzed retrospectively. Multivariate models based on regression analysis and machine learning algorithms were performed to improve the diagnostic efficacy. RESULTS: The differentiation degree, carbohydrate antigen (CA) 199, CA724, CA242, and multiple CT findings based on LAP differed significantly between T1-3 and T4 GCs in the primary cohort (all P < 0.05). Multivariate models based on regression analysis and random forest achieved AUCs of 0.849 and 0.865 in the primary cohort, respectively. CONCLUSION: We developed and validated multivariate models integrating endoscopic biopsy, tumor markers, CT morphological characteristics, and CT value-related and texture parameters to predict serosal invasion in GCs and achieved favorable performance.

8.
Sci Rep ; 11(1): 18486, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531508

RESUMO

The prevalence of coronary artery disease (CAD) in Tibetan Highlanders is lower than that in plain-living individuals, but the mechanism still unclear. Gut microbiota (GM) disorder is considered one of the potential factors involved in the pathogenesis of CAD, but the GM characteristics of Tibetan Highlanders suffering from CAD are unknown. We sequenced the V3-V4 region of the 16S ribosomal RNA of gut bacteria from fecal samples from Tibetan and Han CAD patients and healthy individuals inhabiting the Qinghai-Tibet Plateau, as well as from Han CAD patients and healthy individuals living at sea level, and we analyzed the GM characteristics of these subjects by bioinformatics analysis. The results showed that Tibetan Highlanders suffering from CAD had higher GM α-diversity, with differently distributed cluster compared with healthy Tibetan Highlanders and Han CAD patients living at high and low altitudes. Genera Catenibacterium, Clostridium_sensu_stricto, Holdemanella, and Ruminococcus 2 were enriched in Tibetan Highlanders suffering from CAD compared with healthy Tibetan Highlanders and Han CAD patients living at high- and low-altitudes. Prevotella was enriched in Tibetan Highlanders suffering from CAD compared with Han CAD patients living at high- and low-altitudes. Moreover, Catenibacterium was positively correlated with Prevotella. Additionally, Catenibacterium, Holdemanella, and Prevotella were positively correlated with fermented dairy product, carbohydrate and fiber intake by the subjects, while Clostridium_sensu_stricto was negatively correlated with protein intake by the subjects. In conclusion, our study indicated that Tibetan Highlanders suffering from CAD showed distinct GM, which was linked to their unique dietary characteristics and might associated with CAD.

9.
Trials ; 22(1): 566, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34521466

RESUMO

BACKGROUND: Non-alcohol fatty liver disease (NAFLD) is the most common chronic liver disease in the world, with a high incidence and no effective treatment. At present, the targeted therapy of intestinal microbes for NAFLD is highly valued. Lycium barbarum polysaccharide (LBP), as the main active ingredient of Lycium barbarum, is considered to be a new type of prebiotic substance, which can improve NAFLD by regulating the gut microbiota. The purpose of this study is to evaluate the safety and efficacy of LBP supplementation in modulating gut microbiota for NAFLD patients. METHODS: This randomized, double-blind, placebo-control study will be conducted in the physical examination center of the Ningxia Hui Autonomous Region People's Hospital. A total of 50 patients with NAFLD confirmed by abdominal ultrasound, laboratory tests, and questionnaire surveys will be recruited and randomly assigned into the control group (maltodextrin placebo capsules) and the intervention group (LBP supplementation capsules) for 3 months. Neither patients, nor investigators, nor data collectors will know the contents in each capsule and the randomization list. The primary outcome measure is the level of ALT concentration relief after the intervention. Secondary outcomes include gut microbiota abundance and diversity, intestinal permeability, patient's characteristic demographic data and body composition, adverse effects, and compliance from patients. DISCUSSION: LBPs are potential prebiotics with the property of regulating host gut microbiota. Our previous studies have documented that LBP supplement can improve the liver damage and the gut microflora dysbiosis in NAFLD rats. This treatment would provide a more in-depth understanding of the effect of this LBP supplementation. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000034740 . Registered on 17 July 2020.


Assuntos
Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Animais , Suplementos Nutricionais , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ratos
10.
Artigo em Inglês | MEDLINE | ID: mdl-34534084

RESUMO

Raw polarimetric images are captured by a focal plane polarimeter which is covered by a micro-polarizer array (MPA). The design of the MPA plays a crucial role in polarimetric imaging. MPAs are predominantly designed according to expert engineering experience and rules of thumb. Typically, only one optimization criterion, maximizing bandwidth, is used to design the MPA. To select a design, an exhaustive search is usually performed on a very limited set of available polarizing patterns, which must be constrained in order to make the search tractable. In contrast, this paper proposes a fully automated and optimal MPA design method (AO-MPA) which generates significantly improved MPAs. Instead of the single criterion of bandwidth, we propose six design principles, and show how they can be utilized to mutually optimize the MPA design by formulating a tri-objective optimization problem with multiple constraints. A much larger set of possible MPA patterns is rapidly and automatically searched by applying advanced multi-objective optimization techniques. We have tested AO-MPA using two groups of experiments, in which AO-MPA is compared against several other leading MPA design methods, and the patterns generated by AO-MPA are compared against state-of-the-art patterns from the literature. The results, obtained using a public benchmark dataset, show that the AO-MPA method is very computationally efficient, and can find all optimal MPA patterns for all array sizes. Moreover, for each size, AO-MPA obtains all optimal layouts simultaneously. AO-MPA generates designs which require fewer polarization orientations, while also yielding better performance in estimating intensity measurements, Stokes vector and the degree of linear polarization. This results in MPAs which are easier to manufacture while also being more robust to noise.

11.
Front Immunol ; 12: 723585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489974

RESUMO

Objectives: Our objective was to determine the antibody and cytokine profiles in different COVID-19 patients. Methods: COVID-19 patients with different clinical classifications were enrolled in this study. The level of IgG antibodies, IgA, IgM, IgE, and IgG subclasses targeting N and S proteins were tested using ELISA. Neutralizing antibody titers were determined by using a toxin neutralization assay (TNA) with live SARS-CoV-2. The concentrations of 8 cytokines, including IL-2, IL-4, IL-6, IL-10, CCL2, CXCL10, IFN-γ, and TNF-α, were measured using the Protein Sample Ella-Simple ELISA system. The differences in antibodies and cytokines between severe and moderate patients were compared by t-tests or Mann-Whitney tests. Results: A total of 79 COVID-19 patients, including 49 moderate patients and 30 severe patients, were enrolled. Compared with those in moderate patients, neutralizing antibody and IgG-S antibody titers in severe patients were significantly higher. The concentration of IgG-N antibody was significantly higher than that of IgG-S antibody in COVID-19 patients. There was a significant difference in the distribution of IgG subclass antibodies between moderate patients and severe patients. The positive ratio of anti-S protein IgG3 is significantly more than anti-N protein IgG3, while the anti-S protein IgG4 positive rate is significantly less than the anti-N protein IgG4 positive rate. IL-2 was lower in COVID-19 patients than in healthy individuals, while IL-4, IL-6, CCL2, IFN-γ, and TNF-α were higher in COVID-19 patients than in healthy individuals. IL-6 was significantly higher in severe patients than in moderate patients. The antibody level of anti-S protein was positively correlated with the titer of neutralizing antibody, but there was no relationship between cytokines and neutralizing antibody. Conclusions: Our findings show the severe COVID-19 patients' antibody levels were stronger than those of moderate patients, and a cytokine storm is associated with COVID-19 severity. There was a difference in immunoglobulin type between anti-S protein antibodies and anti-N protein antibodies in COVID-19 patients. And clarified the value of the profile in critical prevention.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/imunologia , Citocinas/sangue , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , COVID-19/classificação , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-34528199

RESUMO

Green development of cities has been gaining attention worldwide, especially in urban agglomerations, where market integration is promoting. However, it is not clear whether the market integration in urban agglomerations is conducive to promote the green development of cities. Hence, this research aims to address this question. This research employed the data of 100 cities in China's Yangtze River Economic Belt from 2006 to 2019 and a comprehensive analytic framework including a panel threshold model to explore the impact of urban agglomeration market integration on urban green development and the nonlinear adjustment mechanism. The main findings are shown below: (1) urban agglomerations market integration was found to be significant to promote green development of the city, but there are two dimensions: the horizontal dimension and the efficiency dimension, (2) the optimal dimensions for urban agglomeration market integration to promote green development of the city were found has regional and urban heterogeneity. Therefore, it is necessary for the city to formulate differentiated green development strategies, (3) when human capital advancement and knowledge sharing intervene, urban agglomeration market integration will have a "jumping" threshold impact on green development of the city through the level path; and under the adjustment of environmental regulations and the green transformation mechanism of the industrial structure, the influence of the urban agglomeration market integration on the efficiency of urban green development presents a "U-shaped" threshold characteristic, (4) lastly, the conclusions enlighten urban agglomeration market integration and heterogeneous green development model for approaching a better performance in urban green development.

13.
Water Environ Res ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34528319

RESUMO

There have been multiple reports of COVID-19 virus, SARS-CoV-2 RNA presence in influent wastewater of water reclamation facilities (WRFs) across the world. In this study, the removal of SARS-CoV-2 RNA was investigated in a WRF by collecting samples from various stages relayed to hydraulic retention time (HRT) and analyzed for viral RNA (N1 and N2) gene markers and wastewater characteristics. SARS-CoV-2 RNA was detected in 28 out of 28 influent wastewater and primary effluent samples. Secondary effluent showed 4 out of 9 positive samples, and all tertiary and final effluent samples were below the detection limit for the viral markers. The reduction was significant (p-value < 0.005, one-way ANOVA test) in secondary treatment, ranging from 1.4-2.0 log10 removal. Adjusted N1 viral marker had a positive correlation with total suspended solids, total Kjeldahl nitrogen and ammonia concentrations (Spearman's ρ = 0.61, 0.67, and 0.53, respectively, p-value < 0.05), while demonstrating a strongly negative correlation with HRT (Spearman's ρ = -0.58, p-value < 0.01).

14.
J Chem Theory Comput ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34516136

RESUMO

SARS-CoV-2 that caused COVID-19 has spread since the end of 2019. Its major effects resulted in over four million deaths around the whole world by August 2021. Therefore, understanding virulence mechanisms is important to prevent future outbreaks and for COVID-19 drug development. The envelope (E) protein is an important structural protein, affecting virus assembly and budding. The E protein pentamer is a viroporin, serving as an ion transferring channel in cells. In this work, we applied molecular dynamic simulations and topological and electrostatic analyses to study the effects of palmitoylation on the E protein pentamer. The results indicate that the cation transferring direction is more from the lumen to the cytosol. The structure of the palmitoylated E protein pentamer is more stable while the loss of palmitoylation caused the pore radius to reduce and even collapse. The electrostatic forces on the two sides of the palmitoylated E protein pentamer are more beneficial to attract cations in the lumen and to release cations into the cytosol. The results indicate the importance of palmitoylation, which can help the drug design for the treatment of COVID-19.

15.
J Nutr Biochem ; : 108863, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34517094

RESUMO

Autoimmune hepatitis (AIH) is an immune-mediated type of chronic liver inflammation accompanied by intestinal flora imbalance. Probiotics have been reported to ameliorate imbalances in the intestinal flora. This study aimed to investigate the effects of compound probiotic in the AIH mouse model. AIH mice were gavaged with compound probiotic and injected intraperitoneally with dexamethasone (dex) for 42 days. The results showed that these treatments suppressed hepatic inflammatory cell infiltration, serum transaminase, and Th1 and Th17 cells. However, Treg cells were increased only in the probiotics group, which indicates an immunomodulatory role of the compound probiotic. The compound probiotic maintained intestinal barrier integrity, blocked lipopolysaccharide (LPS) translocation, and inhibited the activation of the TLR4/NF-κB pathway and the production of inflammatory factors in the liver and ileum. Moreover, the compound probiotic treatment increased the abundance of beneficial bacteria and reduced the abundance of potentially harmful bacteria in gut. Compound probiotic may improve ileal barrier function while increasing the diversity of the intestinal flora, blocking the translocation of gut-derived LPS to the liver and therefore preventing activation of the TLR4/NF-κB pathway. The resulting inhibition of pro-inflammatory factor production facilitates AIH remission.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34481088

RESUMO

Zinc (Zn) plays a role in the antioxidant capacity and immunity of aquatic animals. A twelve-week feeding experiment was performed to estimate the impact of dietary zinc on antioxidant enzyme-related gene expression, antioxidant enzyme activity and non-specific immune functions of soft-shelled turtles, Pelodiscus sinensis. Six fishmeal-based experimental diets with 32.45% protein were formulated, which contained 35.43, 46.23, 55.38, 66.74, 75.06 and 85.24 mg/kg Zn, respectively. Catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels improved with an elevation in dietary Zn from 35.43 to 55.38 mg/kg and then reduced when dietary Zn was further elevated. The expression levels of Nrf2 and antioxidant-related genes CuZnSOD, MnSOD, CAT, GPX1, GPX2, GPX3 and GPX4 escalated with elevating Zn concentration up to 55.38 mg/kg in diets and then reduced as dietary Zn elevated. The expression levels of Kelch-like ECH-associating protein 1 (keap1) showed a reverse trend with that of Nrf2. The contents of malondialdehyde (MDA) in the 55.38 and 66.74 mg/kg Zn diet-fed groups were the lowest. Alkaline phosphatase activity (AKP), superoxide anion (O2-), lysozyme activity and total antioxidant capacity (T-AOC) improved with an escalation in dietary Zn concentration up to 66.74 mg/kg. Optimal dietary Zn improved antioxidant capability, immunity, and antioxidant enzyme-related gene expression. The dietary Zn demand for soft-shelled turtles were 60.93 and 61.63 mg/kg, based on second regression analysis of SOD and T-AOC activity, respectively.

18.
Antimicrob Agents Chemother ; : AAC0047021, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491808

RESUMO

Eliminating the latent HIV reservoir remains a difficult problem for creating an HIV functional cure or achieving remission. The "block-and-lock" strategy aims to steadily suppress transcription of the viral reservoir and lock the HIV promoter in deep latency using latency-promoting agents (LPAs). However, to date, most of the investigated LPA candidates are not available for clinical trials, and some of them exhibit immune-related adverse reactions. The discovery and development of new, active, and safe LPA candidates for an HIV cure are necessary to eliminate residual HIV-1 viremia through the "block-and-lock" strategy. In this study, we demonstrated that a new small-molecule compound, Q308, silenced the HIV-1 provirus by inhibiting Tat-mediated gene transcription and selectively downregulating the expression levels of the facilitated chromatin transcription (FACT) complex. Strikingly, Q308 induced the preferential apoptosis in HIV-1 latently infected cells, indicating that Q308 may reduce the size of the viral reservoir and thus further prevent viral rebound. These findings highlight that Q308 is a novel and safe anti-HIV-1 inhibitor candidate for a functional cure.

19.
J Agric Food Chem ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493043

RESUMO

In this study, pyrralylisoleucine (Pyrr-Ile) and pyrralylalanine (Pyrr-Ala), two dipeptide-bound pyrralines with different C-termini were synthesized as the representatives of dietary advanced glycation end products (dAGEs). The structures of Pyrr-Ile and Pyrr-Ala were characterized by high-resolution mass spectrometry, nuclear magnetic resonance, and Fourier transform infrared spectroscopy. Then, the transport of Pyrr-Ile and Pyrr-Ala across intestinal epithelial cells was investigated using Caco-2 cell monolayers, and their interaction with aminopeptidase N (APN) was analyzed. The results showed that the apparent permeability coefficient (Papp) of Pyrr-Ala was (14.1 ± 2.26) × 10-7 cm·s-1 calculated by free pyrraline, while the Papp values of Pyrr-Ile were (32.4 ± 5.35) × 10-7 and (19.1 ± 1.46) × 10-7 cm·s-1 when they were, respectively, calculated according to their dipeptide-bound or free form. Both Pyrr-Ala and Pyrr-Ile were potential substrates of APN, and their hydrolysis by APN may make the intact transmembrane transport of Pyrr-Ala and Pyrr-Ile more difficult, especially for Pyrr-Ala. Besides, the occurrence of product inhibition in hydrolysis of Pyrr-Ile was possible. Pyrr-Ile and Pyrr-Ala were different in Papp values and transport forms, which suggested that the C-terminus may play an important role in their transport across the Caco-2 cell monolayers. In addition, the results highlight the intact transmembrane transport of dipeptide-bound pyrraline.

20.
Nanoscale ; 13(31): 13174-13194, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34477725

RESUMO

2D heterostructures have very recently witnessed a boom in scientific and technological activities owing to the customized spatial orientation and tailored physical properties. A large amount of 2D heterostructures have been constructed on the basis of the combination of mechanical exfoliation and located transfer method, opening wide possibilities for designing novel hybrid systems with tuned structures, properties, and applications. Among the as-developed 2D heterostructures, in-plane graphene and h-BN heterostructures have drawn the most attention in the past few decades. The controllable synthesis, the investigation of properties, and the expansion of applications have been widely explored. Herein, the fabrication of graphene and h-BN heterostructures is mainly focused on. Then, the spatial configurations for the heterostructures are systematically probed to identify the highly related unique features. Moreover, as a most promising approach for the scaled production of 2D materials, the in situ CVD fabrication of the heterostructures is summarized, demonstrating a significant potential in the controllability of size, morphology, and quality. Further, the recent applications of the 2D heterostructures are discussed. Finally, the concerns and challenges are fully elucidated and a bright future has been envisioned.

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