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1.
J Am Chem Soc ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32069054

RESUMO

We report the use metal organic frameworks for the selective inclusion of nucleic acids with different size, shape and capability of conformational transition. Three MOFs, Co-IRMOF-74-II, -III, and -IV, composed of Co2+ and organic linkers (linker-II, -III and -IV), respectively, were used for nucleic acid inclusion into their pores from solution, which is a spontaneous process from disordered free state to restricted ordered state. The pores of these MOFs were precisely controlled to provide selectivity between different structural nucleic acids. These MOFs preferentially adsorb flexible single strand nucleic acids due to spatial size matching selection and preferentially adsorb unstable rigid structural nucleic acids with larger cross-section size owing to conformations changes. In addition, the transcribed RNA enters the MOF pores in a directional manner, giving priority to the 3' end entering the MOF pores. Furthermore, under complicated mixtures of various structures, flexible single strand nucleic acids and unstable rigid structure nucleic acids were selectively adsorbed, leaving stable secondary structure nucleic acids in the solution, which can be collected to characterize the structure. It indicates that MOF materials has a great potential for application in the field of enrichment and determine all type of structural nucleic acids, especially in the field of monitoring all structural RNA due to the dynamic change of RNA conformations.

2.
Nature ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015508

RESUMO

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1-3. Despite intense research efforts, how, when and where new diseases appear are still the source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to Wuhan Central Hospital on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.

3.
Biomater Sci ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32002530

RESUMO

In this work, we developed multi-shelled hollow nanospheres [RGD@am-ZnO@CuO@Au@DOX HNSs] as multifunctional therapeutic agents to achieve effective and targeted Zn2+/Cu2+ therapy, induced drug delivery under low pH/red-light conditions, and enhanced phototherapy under single red-light. The photothermal and photodynamic performance of am-ZnO@CuO@Au HNSs was enhanced relative to that of am-ZnO nanoparticles (NPs) or am-ZnO@CuO HNSs by utilizing the resonance energy transfer process and broad red-light absorption. The pH-sensitive am-ZnO@CuO@Au HNSs were dissolved to Zn2+/Cu2+ in the acidic endosomes/lysosomes of cancer cells, resulting in a cancer cell killing effect. The release performance of doxorubicin (DOX) from RGD@am-ZnO@CuO@Au@DOX HNSs was evaluated under low pH and red-light-irradiated conditions, and targeting of HNSs was confirmed by dual-modal imaging (magnetic resonance/fluorescence) of the tumor area. Moreover, in vivo synergistic therapy using RGD@am-ZnO@CuO@Au@DOX HNSs was further evaluated in mice bearing human pulmonary adenocarcinoma (A549) cells, achieving a remarkable synergistic antitumor effect superior to that obtained by monotherapy. This study validated that RGD@am-ZnO@CuO@Au@DOX HNSs can be a promising candidate for efficient postoperative cancer therapy.

4.
J Hazard Mater ; 390: 122144, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32006845

RESUMO

Many studies have examined changes in soil microbial community structure and composition by carbon nanomaterials (CNMs). Few, however, have investigated their impact on microbial community functions. This study explored how fullerene (C60) and multi-walled carbon nanotubes (M50) altered functionality of an agricultural soil microbial community (Archaea, Bacteria and Eukarya), using microcosm experiments combined with GeoChip microarray. M50 had a stronger effect than C60 on alpha diversity of microbial functional genes; both CNMs increased beta diversity, resulting in functional profiles distinct from the control. M50 exerted a broader, severer impact on microbially mediated nutrient cycles. Together, these two CNMs affected CO2 fixation pathways, microbial degradation of diverse carbohydrates, secondary plant metabolites, lipids and phospholipids, proteins, as well as methanogenesis and methane oxidation. They also suppressed nitrogen fixation, nitrification, dissimilatory nitrogen reduction, eukaryotic assimilatory nitrogen reduction, and anaerobic ammonium oxidation (anammox). Phosphorus and sulfur cycles were less vulnerable; only phytic acid hydrolysis and sulfite reduction were inhibited by M50 but not C60. Network analysis suggested decoupling of nutrient cycles by CNMs, manifesting closer and more hierarchical gene networks. This work reinforces profound impact of CNMs on soil microbial community functions and ecosystem services, laying a path for future investigation in this direction.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 300-306, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027293

RESUMO

OBJECTIVE: To study the single nucleotide polymorphisms (SNPs) in promoter region of the Jk gene and its allele frequency as well as distribution characteristics in the Chinese Han nationality population. METHODS: 127 blood samples containing 8 Jk(a-b-) and 119 samples (as control) taken randomly from voluntary blood donors of Chinese Han nationality persons in Shenzhen Blood Center were collected. The Kidd phenotypes were identified by using the serologic test and urea hemolysis test; the Jk promoter, exon 1-11 region and respective flanking area were amplified and sequenced, then the sequence information was analyzed. RESULTS: 8 Jk(a-b-) samples all carried JkB/JkB allele which belongs to 2 kind of Jknull genotypes commonly observed in Chinese Han nationality population. 6 IVS5-1g>a and 2 896G>A were found in 8 Jk(a-b-) samples. Besides, all Jk(a-b-) samples were homozygous for JkB/JkB allele. Three SNPs-110(rs900974), -160(rs1484877) and -258(rs1484878) in promoter region of the Jk gene were found and sequenceds calculation of allele and genotype frequencies showed that the result accorded with Hardy-Weinberg equilibrium, indicating that the population in this study possesses representative characteristics of the Chinese Han nationality population. CONCLUSION: The polymorphism of the Jk gene occurs in promoter region. This study calculates the allele frequencies of three SNPs-110(rs900974), -160(rs1484877) and -258(rs1484878) in promoter region of the Jk gene, and shows their distribution characteristics in distinct Kidd phenotypes. These findings provide the basic foundation for further population genetics research.


Assuntos
Polimorfismo de Nucleotídeo Único , Alelos , Antígenos de Grupos Sanguíneos , China , Frequência do Gene , Genótipo , Humanos , Sistema do Grupo Sanguíneo Kidd , Regiões Promotoras Genéticas
6.
Sci Total Environ ; 716: 137017, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32036136

RESUMO

How to attenuate water surfactant pollution using carbon nanomaterials (CNMs) has been gaining increasing research attention in recent years. However, how the composition of cationic surfactants and physicochemical properties of CNMs may affect cationic surfactant maximum removal efficiency (Refficiency-max) with minimal cost from the aqueous phase and the associated mechanisms remain largely unclear. To address this knowledge gap, we compared removal efficiency of three cationic surfactants including dodecyl dimethyl benzyl ammonium chloride (DDBAC), tetradecyl dimethyl benzyl ammonium chloride (TDBAC) and hexadecyltrimethylammonium bromide (CTAB) by various carbon nanotubes (CNTs), including pristine and OH- or COOH-functionalized multiwalled- (MWCNTs) and single-walled (SWCNTs) CNTs. The results showed that Refficiency-max of CTAB by pristine MWCNTs with an outer diameter OD < 8 nm is 50.36 ± 0.56%, while that by OH-MWCNTs with OD < 8 nm is merely 22.72 ± 0.21%. Surface area and porosity of CNTs strongly affect Refficiency-max of cationic surfactants. The MWCNTs with a smaller OD have a higher Refficiency-max than that with a larger one especially for CTAB, due to their larger surface area and porosity. Among various CNTs, SWCNTs is an ideal choice for removing cationic surfactants, especially for non-aromatic CTAB. Interestingly, for most cases, cationic surfactant removal by CNTs decreased when the amount of CNTs added exceeded a certain level, attributable to their aggregation. This implies that it is impossible to completely remove some cationic surfactants even when excess CNTs were added. The π-π bonding dominates over hydrophobic interaction in regulating cationic surfactant removal especially for those with aromatic structure. Aromatic cationic surfactants such as DDBAC and TDBAC can be removed more readily by CNTs than those without a benzene ring due to their strong π-π interactions. TDBAC has a longer hydrophobic chain relative to DDBAC, leading to a better removal efficiency by CNTs, due to stronger hydrophobic interaction.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32043350

RESUMO

Specific chemical reactions only happen in the tumor region and produce abundant special chemicals to in situ trigger a train of biological and pathological effects that may enable tumor-specific curative effects to treat cancer without causing serious side effects on normal cells or organs. Chemodynamic therapy (CDT) is a rising tactic for cancer therapy, which induces cancer cell death via a localized Fenton reaction. However, the tumor therapeutic effect is limited by the efficiency of the chemical reaction and relies heavily on the catalyst. Here, we constructed hollow porous carbon coated FeS2 (HPFeS2@C)-based nanocatalysts for triple-enhanced CDT. Tannic acid was encapsulated in HPFeS2@C for reducing Fe3+ to Fe2+, which had a better catalytic activity to accelerate the Fenton reaction. Afterward, glucose oxidase (GOx) in nanocatalysts could consume glucose in the tumor microenvironment and in situ synchronously produce H2O2, which could improve Fenton reaction efficiency. Meanwhile, the consumption of glucose could lead to the starvation effect for cancer starvation therapy. The photothermal effects of HPFeS2@C could generate heat, which further sped up the Fenton process and implemented synergetic photothermal therapy/starvation therapy/CDT. The biodistribution of nanoparticles was investigated by multimodal magnetic resonance, ultrasound, and photoacoustic imaging. These nanocatalysts could trigger the catalytic Fenton reaction at a high degree, which might provide a good paradigm for nanocatalytic tumor therapy.

8.
J Proteomics ; 215: 103650, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31958639

RESUMO

Mycobacterium tuberculosis (Mtb) serine/threonine protein phosphatase PstP plays an important role in regulating Mtb cell division and growth by reversible phosphorylation signaling. However, the substrates of Mtb with which the PstP interacts, and the underlying molecular mechanisms are still largely unknown. In this study, we performed an Mtb proteome microarray to globally identify the PstP bindings. In this way, we discovered 78 interactors between PstP and Mtb proteins, and found a novel connections with EthR. The interaction between PstP and EthR has been validated by Bio-Layer interferometry and Yeast-two-hybrid. And functional studies showed that PstP significantly enhances the binding between EthR and related DNA domain through its interaction with EthR. Phenotypically, overexpression of PstP promoted the resistance of Mycobacterium smegmatis with the antibiotic of ethionamide. Overall, we hopefully wish that the PstP interactors identified in this study will serve as a useful resource for further systematic studies of the roles that PstP plays in the regulation of Mtb dephosphorylation. SIGNIFICANCE: Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, which is responsible of ~1.5 million death per year. Understanding the knowledge about the basic biological regulation pathways in Mtb is an effective approach to discover the novel drug targets for cure TB. PstP is a serine/threonine protein phosphatase in Mtb, and plays important roles in regulating Mtb cell division and growth by reversible phosphorylation signaling. In this study, we identified 78 PstP interacting Mtb proteins using Mtb proteome microarray, which could preliminarily explain the roles of PstP played in Mtb. Moreover, functional analysis showed that a novel transcription factor EthR had been found regulated by PstP through binding, which could enhance the resistance to the antibiotic ETH. Overall, this network constructed with PstP-Mtb proteins could serve as a valuable resource for studying Mtb growth.

9.
Plant Physiol Biochem ; 147: 289-294, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31901451

RESUMO

The broad application and unique properties of graphene oxide (GO) nanosheets make them interact with other pollutants and subsequently alter their behaviors and toxicities. However, investigation on the effects of GO nanosheets on plant uptake of co-occurring heavy metals is scarce. We evaluated the mutual effects of cadmium (Cd) at 1 mg/L and different concentrated GO nanosheets (0, 1 and 10 mg/L) on the rice seed germination, further seedling growth, Cd uptake and accumulation in rice roots and shoots in a hydroponic system. The effects of GO were concentration dependent. GO alone at 1 mg/L showed no apparent effects, while GO alone at 10 mg/L accelerated the rice seed germination and root growth due to the improved water uptake. Cd alone showed adverse effects on the rice seed germination, which was alleviated by the presence of GO at 1 or 10 mg/L. GO at 10 mg/L also increased the membrane permeability, thus enhancing Cd uptake by rice roots and shoots. These results indicate that GO can change the effects of Cd on the rice seed germination and Cd uptake as well as accumulation in the roots and shoots of rice seedlings, which is helpful for understanding the fate and ecotoxicological impacts of both GO and Cd.

10.
Chin J Integr Med ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974753

RESUMO

BACKGROUND: Knee osteoarthritis (OA) is a major cause of disability among the older adults. Few treatments are safe and effective. Moxibustion is commonly used in treating knee OA in Chinese medicine (CM). CO2 Laser moxibustion device is a substitute for traditional moxibustion, which mimics the effects of traditional moxibustion. More data are needed to support its application in knee OA. OBJECTIVE: The trial aims to assess the effect and safety of CO2 laser moxibustion in patients with knee osteoarthritis compared with a sham control. METHODS: This is a protocol for a multicenter, randomized, double-blind, placebo-controlled trial. A total of 392 participants were recruited and assigned to the CO2 laser moxibustion group and sham laser moxibustion group with a 1:1 ratio at 6 outpatient clinics in Shanghai, China. Participants in both groups received treatment at the affected knee(s) at the acupuncture point Dubi (ST 35) and an Ashi point. There were 3 sessions per week for 4 weeks, and an additional 20-week follow-up. Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores at week 4. Secondary outcomes were WOMAC function score, stiffness score and overall score, VAS pain, Short-Form heath survey (SF-36), and patients' global assessment. The serum levels of cytokines involved in progress of knee OA were explored. Safety was assessed during the whole trial. Masking effectiveness was assessed by both participants and treatment providers. DISCUSSION: CO2 laser moxibustion device, designed as a substitute for CM moxibustion, is easy to use and control with no choking smoke and smell, and is a plausible method for double-blind research. This study would provide rigorous evidence for the effect and safety of CO2 laser moxibustion in treating knee OA (Trial registration No.: ISRCTN15030019).

11.
Artigo em Inglês | MEDLINE | ID: mdl-31976816

RESUMO

Background: Central sensitization driven by glial activation-mediated neuroinflammation is recognized as a key mechanism in pain processing. Laser moxibustion using low-intensity laser irradiation of corresponding acupoints significantly relieves knee osteoarthritis (KOA) pain. However, the underlying mechanism of its effects on KOA pain is still not completely understood. Objective: In this study, we aimed to investigate whether laser moxibustion could alleviate KOA pain by inhibiting spinal glial activation and proinflammatory cytokines upregulation in monosodium iodoacetate (MIA)-induced KOA pain in rats. Materials and methods: Sprague-Dawley rats were divided randomly into three groups: Saline + Sham Laser, MIA + Laser, and MIA + Sham Laser. A 10.6 µm laser was used to irradiate ST35 (Dubi) for 10 min once every 2 days for a total of seven applications. The paw withdrawal mechanical threshold and weight-bearing distribution were performed to evaluate the nociceptive behaviors. Spinal expressions of microglial marker, ionized calcium binding adaptor molecule-1 (Iba-1); astrocyte marker, glial fibrillary acidic protein (GFAP); pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were measured 14 days after MIA injection. Results: The results showed that laser moxibustion significantly reversed the MIA-induced mechanical hyperalgesia and weight-bearing difference up to 14 days compared with MIA + Sham Laser group (p < 0.05 or p < 0.01). Moreover, both the protein level and immunofluorescence intensity of Iba-1 in the ipsilateral spinal cord dorsal horn were markedly decreased in the MIA + Laser group than those in the MIA + Sham Laser group (p < 0.01). However, there was no significant difference in the expression of GFAP between groups (p > 0.05). In addition, laser moxibustion decreased the upregulation of TNF-α, IL-1ß, and IL-6 compared with the MIA + Sham Laser group (p < 0.01). Conclusions: This study demonstrated that laser moxibustion at ST35 significantly alleviated MIA-induced KOA pain through inhibition of the microglial activation-mediated neuroinflammation, at least partially, by suppressing the production of proinflammatory cytokines, which may provide a potential analgesic target for KOA pain relief.

12.
DNA Cell Biol ; 39(2): 273-288, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31968175

RESUMO

Cleistogenes songorica is a cultivated turfgrass species that employs a mixed breeding system. To determine the morphological differences and molecular mechanisms of the chasmogamous (CH) and cleistogamous (CL) flowers of this species, we evaluated seed traits and analyzed six transcription factor (TF) families related to floral development. The seed traits from the CH and CL flowers were significantly different. In total, 12 CsAP2, 13 CsSPL, 9 CsGRF, 21 CsMYB, 15 CsMADS, and 1 CsLFY differentially expressed genes were identified from the transcriptome of the C. songorica flowers, which was further supported by evolutionary relationships and conserved motifs. All collinear gene pairs had a Ka/Ks ratio <1. Analysis of the promoters and miRNAs of the TFs revealed that the members of the six TF families may coregulate the divergence of CH and CL flowers during evolution. Two CsAP2, 8 CsSPL, 6 CsGRF, 3 CsMYB (targeted by miR172s, miR156s, miR396a/b and miR159a/b, respectively), and 15 CsMADS genes as well as 1 CsLFY gene may be involved in the development of CH and CL flowers. This study is the first to analyze the differences between CH and CL flowers at the TF-family level, which will help in the understanding of dimorphic turfgrasses.


Assuntos
Flores/genética , Poaceae/genética , Fatores de Transcrição/genética , Regulação da Expressão Gênica de Plantas/genética , MicroRNAs/genética , Fenótipo , Plantas/genética , RNA Mensageiro/genética , Sementes/genética , Fatores de Transcrição/metabolismo , Transcriptoma/genética
13.
Nat Genet ; 52(2): 198-207, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31932695

RESUMO

Mutations in ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, are the most common alterations of the SWI/SNF complex in estrogen-receptor-positive (ER+) breast cancer. We identify that ARID1A inactivating mutations are present at a high frequency in advanced endocrine-resistant ER+ breast cancer. An epigenome CRISPR-CAS9 knockout (KO) screen identifies ARID1A as the top candidate whose loss determines resistance to the ER degrader fulvestrant. ARID1A inactivation in cells and in patients leads to resistance to ER degraders by facilitating a switch from ER-dependent luminal cells to ER-independent basal-like cells. Cellular plasticity is mediated by loss of ARID1A-dependent SWI/SNF complex targeting to genomic sites of the luminal lineage-determining transcription factors including ER, forkhead box protein A1 (FOXA1) and GATA-binding factor 3 (GATA3). ARID1A also regulates genome-wide ER-FOXA1 chromatin interactions and ER-dependent transcription. Altogether, we uncover a critical role for ARID1A in maintaining luminal cell identity and endocrine therapeutic response in ER+ breast cancer.

14.
Org Lett ; 22(3): 884-890, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31927966

RESUMO

An aerobic catalytic oxidation process is described for the olefin oxyamination using acids and primary amines as the sources of O and N. Our mechanistic findings point to the formation of triiodide as a critical catalytic intermediate to account for the tolerance of electron-rich nucleophiles. This dual iodide and copper catalytic system is suitable for a formal [5+1] annulation process to access valuable lactam structures and highlighted by the synthesis of the pharmaceutical Zamifenacin.

15.
Redox Biol ; 29: 101406, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31926629

RESUMO

The formation of reactive oxygen species (ROS) is a well-documented process in noise-induced hearing loss (NIHL). We have also previously shown that activation of 5' adenosine monophosphate (AMP)-activated protein kinase (AMPKα) at its catalytic residue T172 is one of the key reactions triggering noise-induced outer hair cell (OHC) death. In this study, we are addressing the link between ROS formation and activation of AMPKα in OHCs after noise exposure. In-vivo treatment of CBA/J mice with the antioxidant N-acetyl cysteine (NAC) reduced noise-induced ROS formation (as assessed by the relative levels of 4-hydroxynonenal and 3-nitrotyrosine) and activation of AMPKα in OHCs. Forskolin, an activator of adenylyl cyclase (AC) and an antioxidant, significantly increased cyclic adenosine monophosphate (cAMP) and decreased ROS formation and noise-induced activation of AMPKα. Consequently, treatment with forskolin attenuated noise-induced losses of OHCs and NIHL. In HEI-OC1 cells, H2O2-induced activation of AMPKα and cell death were inhibited by the application of forskolin. The sum of our data indicates that noise activates AMPKα in OHCs through formation of ROS and that noise-exposure-induced OHC death is mediated by a ROS/AMPKα-dependent pathway. Forskolin may serve as a potential compound for prevention of NIHL.

16.
J Ethnopharmacol ; 252: 112580, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31972322

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Wu-Mei-Wan (WMW), a classic traditional Chinese herb medicine, is one of the most important formulations to treat digestive diseases from ancient times to the present. Previous study showed that WMW has satisfactory curative effects on experimental colitis, which motivating the application of WMW on colitis-associated complications. AIM OF THE STUDY: Intestinal fibrosis is usually considered to be a common complication of inflammatory bowel disease (IBD), particularly Crohn's disease (CD). Currently, no effective preventive measures or medical therapies are available for that. This work was designed to evaluate the effect and related mechanism of WMW on chronic colitis-associated intestinal fibrosis mice model. MATERIALS AND METHODS: The chronic colitis-associated intestinal fibrosis mice model was established by weekly intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS). The mice survival rate, disease activity index (DAI), colon length and histological score were examined to assess the therapeutic effect of WMW. Masson's trichrome staining, hydroxyproline assay, immunohistochemical staining and western blot analysis were used to evaluate fibrosis level. Colon inflammation was determined by ELISA and immunofluorescence staining. Immunofluorescence staining was used to evaluate fibroblasts proliferation and epithelial to mesenchymal transition (EMT), and the expression of key molecules in fibrosis was analyzed by western blot. RESULTS: Here we showed that WMW alleviates chronic colitis with improved survival rate, DAI, colon length and histological score. WMW inhibited the progression of intestinal fibrosis, decreased the expression of various fibrosis markers, such as α-SMA, collagen I, MMP-9 and fibronectin. In addition, WMW treatment reduced cytokines IL-6 and IFN-γ, and downregulated proinflammatory NF-κBp65 and STAT3 signaling pathways. Importantly, administration of WMW led to the inhibition of colon fibroblast proliferation and EMT, which are important mediators during fibrosis. Several key profibrotic pathways, including TGF-ß/Smad and Wnt/ß-catenin pathways, were downregulated by WMW treatment. CONCLUSION: Our work demonstrated that WMW can prevent intestinal fibrosis and the mechanisms involved may be related to the inhibition of colon fibroblasts activation.

17.
Nat Commun ; 11(1): 93, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900398

RESUMO

Lithium metal anodes have attracted extensive attention owing to their high theoretical specific capacity. However, the notorious reactivity of lithium prevents their practical applications, as evidenced by the undesired lithium dendrite growth and unstable solid electrolyte interphase formation. Here, we develop a facile, cost-effective and one-step approach to create an artificial lithium metal/electrolyte interphase by treating the lithium anode with a tin-containing electrolyte. As a result, an artificial solid electrolyte interphase composed of lithium fluoride, tin, and the tin-lithium alloy is formed, which not only ensures fast lithium-ion diffusion and suppresses lithium dendrite growth but also brings a synergistic effect of storing lithium via a reversible tin-lithium alloy formation and enabling lithium plating underneath it. With such an artificial solid electrolyte interphase, lithium symmetrical cells show outstanding plating/stripping cycles, and the full cell exhibits remarkably better cycling stability and capacity retention as well as capacity utilization at high rates compared to bare lithium.

18.
J Gerontol A Biol Sci Med Sci ; 75(2): 340-347, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-30753311

RESUMO

BACKGROUND: Air pollution has been associated with various health outcomes. Its effect on hand-grip strength, a measurement of the construct of muscle strength and health status, remains largely unknown. METHODS: We used the survey data from 31,209 adults ≥ 50 years of age within Wave 1 of the Study on Global AGEing and Adult Health in six low- and middle-income countries. The outdoor concentration of fine particulate matter pollution (PM2.5) was estimated using satellite data. Domestic fuel type and ventilation were used as indicators of indoor air pollution. We used multilevel linear regression models to examine the association between indoor and outdoor air pollution and hand-grip strength, as well as the potential effect modifiers. RESULTS: We found inverse associations between both indoor and outdoor air pollution and hand-grip strength. Each 10 µg/m3 increase in 3 years' averaged concentrations of outdoor PM2.5 corresponded to 0.70 kg (95% CI: -1.26, -0.14) lower hand-grip strength; and compared with electricity/liquid/gas fuel users, those using solid fuels had lower hand-grip strength (ß = -1.25, 95% CI: -1.74, -0.75). However, we did not observe a statistically significant association between ventilation and hand-grip strength. We further observed that urban residents and those having a higher education level had a higher association between ambient PM2.5 and hand-grip strength, and men, young participants, smokers, rural participants, and those with lower household income had higher associations between indoor air pollution and hand-grip strength. CONCLUSION: This study suggests that both indoor and outdoor air pollution might be important risk factors of poorer health and functional status as indicated by hand-grip strength.

19.
Sci Total Environ ; 708: 135234, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31812410

RESUMO

To protect ecosystems, threshold concentrations (e.g., HC5) for chemicals are often derived using the toxicity data obtained at fixed times. Since the toxicity (e.g., LC50) usually decreases with exposure time, the threshold concentrations are expected to be time-dependent, giving rise to the uncertainty in the chemical environmental criteria. Here, using the LC50 data with at least 3 different exposure durations (24, 48 and 96 h) for compounds, we explored the time evolutions of HC5 across 20 chemicals. Results showed that all chemical's HC5 decreased with time, but their decreasing rates of HC5 (k) are significantly different: for some chemicals the k are lower than 0.001 (e.g., methoxychlor and dieldrin), while for some chemicals the k are higher than 0.05 (e.g., PCP and aldicarb). Furthermore, we found that k is negatively related to the bioconcentration factors (BCF), and positively related to the damage recovery rates (kR). Our work demonstrated that time is an important source of the ecological threshold uncertainty, and this uncertainty is associated with chemical-specific toxicokinetic and toxicodynamic characteristics. We recommend that to effectively protect the ecological communities, higher assessment factor should be adopted in deriving the acute environmental criteria for these chemicals with high BCF and low kR, fluoranthene and diazinon.

20.
J Clin Invest ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31661461

RESUMO

CD8+ T cell responses are necessary for immune control of simian immunodeficiency virus (SIV). However, the key parameters that dictate antiviral potency remain elusive, conceivably because most studies to date have been restricted to analyses of circulating CD8+ T cells. We conducted a detailed clonotypic, functional, and phenotypic survey of SIV-specific CD8+ T cells across multiple anatomical sites in chronically infected rhesus macaques with high (>10,000 copies/mL plasma) or low burdens of viral RNA (<10,000 copies/mL plasma). No significant differences in response magnitude were identified across anatomical compartments. Rhesus macaques with low viral loads (VLs) harbored higher frequencies of polyfunctional CXCR5+ SIV-specific CD8+ T cells in various lymphoid tissues and higher proportions of unique Gag-specific CD8+ T cell clonotypes in the mesenteric lymph nodes relative to rhesus macaques with high VLs. In addition, public Gag-specific CD8+ T cell clonotypes were more commonly shared across distinct anatomical sites than the corresponding private clonotypes, which tended to form tissue-specific repertoires, especially in the peripheral blood and the gastrointestinal tract. Collectively, these data suggest that functionality and tissue localization are important determinants of CD8+ T cell-mediated efficacy against SIV.

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