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1.
Cell ; 185(13): 2265-2278.e14, 2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35568034

RESUMO

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.


Assuntos
COVID-19 , Vacinas , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Camundongos , SARS-CoV-2/genética
2.
Immunity ; 55(8): 1501-1514.e3, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35777362

RESUMO

SARS-CoV-2 Omicron variant has presented significant challenges to current antibodies and vaccines. Herein, we systematically compared the efficacy of 50 human monoclonal antibodies (mAbs), covering the seven identified epitope classes of the SARS-CoV-2 RBD, against Omicron sub-variants BA.1, BA.1.1, BA.2, and BA.3. Binding and pseudovirus-based neutralizing assays revealed that 37 of the 50 mAbs lost neutralizing activities, whereas the others displayed variably decreased activities against the four Omicron sub-variants. BA.2 was found to be more sensitive to RBD-5 antibodies than the other sub-variants. Furthermore, a quaternary complex structure of BA.1 RBD with three mAbs showing different neutralizing potencies against Omicron provided a basis for understanding the immune evasion of Omicron sub-variants and revealed the lack of G446S mutation accounting for the sensitivity of BA.2 to RBD-5 mAbs. Our results may guide the application of the available mAbs and facilitate the development of universal therapeutic antibodies and vaccines against COVID-19.


Assuntos
Anticorpos Neutralizantes , COVID-19 , Anticorpos Monoclonais , Anticorpos Antivirais , Vacinas contra COVID-19 , Humanos , Glicoproteínas de Membrana , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Proteínas do Envelope Viral
3.
Mol Cell ; 83(9): 1502-1518.e10, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37086726

RESUMO

2',3'-cGAMP, produced by the DNA sensor cGAS, activates stimulator of interferon genes (STING) and triggers immune response during infection. Tremendous effort has been placed on unraveling the mechanism of STING activation. However, little is known about STING inhibition. Here, we found that apo-STING exhibits a bilayer with head-to-head as well as side-by-side packing, mediated by its ligand-binding domain (LBD). This type of assembly holds two endoplasmic reticulum (ER) membranes together not only to prevent STING ER exit but also to eliminate the recruitment of TBK1, representing the autoinhibited state of STING. Additionally, we obtained the filament structure of the STING/2',3'-cGAMP complex, which adopts a bent monolayer assembly mediated by LBD and transmembrane domain (TMD). The active, curved STING polymer could deform ER membrane to support its ER exit and anterograde transportation. Our data together provide a panoramic vision regarding STING autoinhibition and activation, which adds substantially to current understanding of the cGAS-STING pathway.


Assuntos
Proteínas Serina-Treonina Quinases , Transdução de Sinais , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Membrana/metabolismo , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , DNA , Imunidade Inata
4.
EMBO J ; 43(8): 1484-1498, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38467833

RESUMO

Since SARS-CoV-2 Omicron variant emerged, it is constantly evolving into multiple sub-variants, including BF.7, BQ.1, BQ.1.1, XBB, XBB.1.5 and the recently emerged BA.2.86 and JN.1. Receptor binding and immune evasion are recognized as two major drivers for evolution of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, the underlying mechanism of interplay between two factors remains incompletely understood. Herein, we determined the structures of human ACE2 complexed with BF.7, BQ.1, BQ.1.1, XBB and XBB.1.5 RBDs. Based on the ACE2/RBD structures of these sub-variants and a comparison with the known complex structures, we found that R346T substitution in the RBD enhanced ACE2 binding upon an interaction with the residue R493, but not Q493, via a mechanism involving long-range conformation changes. Furthermore, we found that R493Q and F486V exert a balanced impact, through which immune evasion capability was somewhat compromised to achieve an optimal receptor binding. We propose a "two-steps-forward and one-step-backward" model to describe such a compromise between receptor binding affinity and immune evasion during RBD evolution of Omicron sub-variants.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Enzima de Conversão de Angiotensina 2 , Glicoproteína da Espícula de Coronavírus/genética , Anticorpos
5.
Brief Bioinform ; 24(3)2023 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-37020333

RESUMO

Molecular clustering analysis has been developed to facilitate visual inspection in the process of structure-based virtual screening. However, traditional methods based on molecular fingerprints or molecular descriptors limit the accuracy of selecting active hit compounds, which may be attributed to the lack of representations of receptor structural and protein-ligand interaction during the clustering. Here, a novel deep clustering framework named ClusterX is proposed to learn molecular representations of protein-ligand complexes and cluster the ligands. In ClusterX, the graph was used to represent the protein-ligand complex, and the joint optimisation can be used efficiently for learning the cluster-friendly features. Experiments on the KLIFs database show that the model can distinguish well between the binding modes of different kinase inhibitors. To validate the effectiveness of the model, the clustering results on the virtual screening dataset further demonstrated that ClusterX achieved better or more competitive performance against traditional methods, such as SIFt and extended connectivity fingerprints. This framework may provide a unique tool for clustering analysis and prove to assist computational medicinal chemists in visual decision-making.


Assuntos
Ligantes , Análise por Conglomerados
6.
Brief Bioinform ; 24(5)2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37605947

RESUMO

Predicting the biological properties of molecules is crucial in computer-aided drug development, yet it's often impeded by data scarcity and imbalance in many practical applications. Existing approaches are based on self-supervised learning or 3D data and using an increasing number of parameters to improve performance. These approaches may not take full advantage of established chemical knowledge and could inadvertently introduce noise into the respective model. In this study, we introduce a more elegant transformer-based framework with focused attention for molecular representation (TransFoxMol) to improve the understanding of artificial intelligence (AI) of molecular structure property relationships. TransFoxMol incorporates a multi-scale 2D molecular environment into a graph neural network + Transformer module and uses prior chemical maps to obtain a more focused attention landscape compared to that obtained using existing approaches. Experimental results show that TransFoxMol achieves state-of-the-art performance on MoleculeNet benchmarks and surpasses the performance of baselines that use self-supervised learning or geometry-enhanced strategies on small-scale datasets. Subsequent analyses indicate that TransFoxMol's predictions are highly interpretable and the clever use of chemical knowledge enables AI to perceive molecules in a simple but rational way, enhancing performance.


Assuntos
Inteligência Artificial , Benchmarking , Redes Neurais de Computação
7.
Nano Lett ; 24(1): 156-164, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38147652

RESUMO

Graphene nanoribbons (GNRs), quasi one-dimensional (1D) narrow strips of graphene, have shown promise for high-performance nanoelectronics due to their exceptionally high carrier mobility and structurally tunable bandgaps. However, producing chirality-uniform GNRs on insulating substrates remains a big challenge. Here, we report the successful growth of bilayer GNRs with predominantly armchair chirality and ultranarrow widths (<5 nm) on insulating hexagonal boron nitride (h-BN) substrates using chemical vapor deposition (CVD). The growth of GNRs is catalyzed by transition metal nanoparticles, including Fe, Co, and Ni, through a unique tip-growth mechanism. Notably, GNRs catalyzed by Ni exhibit a high purity (97.3%) of armchair chirality. Electron transport measurements indicate that the ultrathin bilayer armchair GNRs exhibit quasi-metallic behavior. This quasi-metallicity is further supported by density functional theory (DFT) calculations, which reveal a significantly reduced bandgap in bilayer armchair GNRs. The chirality-specific GNRs reported here offer promising advancements for the application of graphene in nanoelectronics.

8.
Eur J Clin Invest ; 54(3): e14129, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37988199

RESUMO

BACKGROUND: The occurrence of gout is closely related to metabolism, but there is still a lack of evidence on the causal role of metabolites in promoting or preventing gout. METHODS: We applied a two-sample Mendelian randomization (MR) analysis to assess the association between 486 serum metabolites and gout using genome-wide association study statistics. The inverse variance weighting method was used to generate the main results, while sensitivity analyses using MR-Egger, weighted median, Cochran's Q test, Egger intercept test, and leave-one-out analysis, were performed to assess the stability and reliability of the results. We also performed a metabolic pathway analysis to identify potential metabolic pathways. RESULTS: After screening, 486 metabolites were retained for MR analysis. After screening by IVW and sensitivity analysis, 14 metabolites were identified with causal effect on gout (P < 0.05), among which hexadecanedioate was the most significant candidate metabolite associated with a lower risk of gout (IVW OR = 0.50; 95% CI = 0.38-0.67; P = 1.65 × 10-6 ). Metabolic pathway analysis identified one pathway that may be associated with the disease. CONCLUSION: This MR study combining genomics with metabolomics provides a novel insight into the causal role of blood metabolites in the risk of gout, which implies that examination of certain blood metabolites would be a feasible strategy for screening populations with a higher risk of gout.


Assuntos
Estudo de Associação Genômica Ampla , Gota , Humanos , Reprodutibilidade dos Testes , Gota/genética , Causalidade , Ácidos Graxos
9.
Mol Psychiatry ; 28(10): 4374-4389, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37280283

RESUMO

Activation of innate immunity in the brain is a prominent feature of Alzheimer's disease (AD). The present study investigated the regulation of innate immunity by wild-type serum injection in a transgenic AD mouse model. We found that treatment with wild-type mouse serum significantly reduced the number of neutrophils and microglial reactivity in the brains of APP/PS1 mice. Mimicking this effect, neutrophil depletion via Ly6G neutralizing antibodies resulted in improvements in AD brain functions. Serum proteomic analysis identified vascular endothelial growth factor-A (VEGF-A) and chemokine (C-X-C motif) ligand 1 (CXCL1) as factors enriched in serum samples, which are crucial for neutrophil migration and chemotaxis, leukocyte migration, and cell chemotaxis. Exogenous VEGF-A reversed amyloid ß (Aß)-induced decreases in cyclin-dependent kinase 5 (Cdk5) and increases in CXCL1 in vitro and blocked neutrophil infiltration into the AD brain. Endothelial Cdk5 overexpression conferred an inhibitory effect on CXCL1 and neutrophil infiltration, thereby restoring memory abilities in APP/PS1 mice. Our findings uncover a previously unknown link between blood-derived VEGF signaling and neutrophil infiltration and support targeting endothelial Cdk5 signaling as a potential therapeutic strategy for AD.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Camundongos , Animais , Camundongos Transgênicos , Fator A de Crescimento do Endotélio Vascular , Infiltração de Neutrófilos , Proteômica , Doença de Alzheimer/terapia , Transtornos da Memória , Modelos Animais de Doenças , Precursor de Proteína beta-Amiloide/genética , Presenilina-1/genética
10.
J Periodontal Res ; 59(3): 589-598, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38481308

RESUMO

OBJECTIVES: In order to evaluate the effect of methacrylated hyaluronic acid (HAMA) hydrogels containing the recombinant human amelogenin (rhAm) in vitro and in vivo. BACKGROUND: The ultimate goal in treating periodontal disease is to control inflammation and achieve regeneration of periodontal tissues. In recent years, methacrylated hyaluronic acid (HAMA) containing recombinant human amyloid protein (rhAm) has been widely used as a new type of biomaterial in tissue engineering and regenerative medicine. However, there is a lack of comprehensive research on the periodontal regeneration effects of this hydrogel. This experiment aims to explore the application of photoresponsive recombinant human amelogenin-loaded hyaluronic acid hydrogel for periodontal tissue regeneration and provide valuable insights into its potential use in this field. MATERIALS AND METHODS: The effects of rhAm-HAMA hydrogel on the proliferation of human periodontal ligament cells (hPDLCs) were assessed using the CCK-8 kit. The osteogenic differentiation of hPDLCs was evaluated through ALP staining and real-time PCR. Calvarial parietal defects were created in 4-week-old Sprague Dawley rats and implanted with deproteinized bovine bone matrix in different treatment groups. The animals were euthanized after 4 and 8 weeks of healing. The bone volume of the defect was observed by micro-CT and histological analysis. RESULTS: Stimulating hPDLCs with rhAm-HAMA hydrogel did not significantly affect their proliferation (p > .05). ALP staining and real-time PCR results demonstrated that the rhAm-HAMA group exhibited a significant upregulation of osteoclastic gene expression (p < .05). Micro-CT results revealed a significant increase in mineralized tissue volume fraction (MTV/TV%), trabecular bone number (Tb.N), and mineralized tissue density (MTD) of the bone defect area in the rhAm-HAMA group compared to the other groups (p < .05). The results of hematoxylin and eosin staining and Masson staining at 8 weeks post-surgery further supported the results of the micro-CT. CONCLUSIONS: The results of this study indicate that rhAm-HAMA hydrogel could effectively promote the osteogenic differentiation of hPDLCs and stabilize bone substitutes in the defects that enhance the bone regeneration in vivo.


Assuntos
Amelogenina , Regeneração Óssea , Diferenciação Celular , Proliferação de Células , Ácido Hialurônico , Hidrogéis , Ligamento Periodontal , Ratos Sprague-Dawley , Ácido Hialurônico/farmacologia , Animais , Regeneração Óssea/efeitos dos fármacos , Amelogenina/farmacologia , Amelogenina/uso terapêutico , Humanos , Ligamento Periodontal/efeitos dos fármacos , Ratos , Proliferação de Células/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Osteogênese/efeitos dos fármacos , Masculino , Microtomografia por Raio-X , Células Cultivadas , Metacrilatos , Materiais Biocompatíveis/farmacologia
11.
J Periodontal Res ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38962931

RESUMO

AIM: To evaluate whether the ribosome-crosslinked collagen membrane (RCCM) is non-inferior to the natural collagen membrane (NCM) used in regeneration surgery in terms of clinical attachment level (CAL) gain at 6 months. METHODS: Eighty patients diagnosed as generalized periodontitis presenting with isolated infrabony defect (≥4 mm deep) were enrolled and randomized to receive regenerative surgery, either with NCM or RCCM, both combined with deproteinized bovine bone mineral (DBBM). CAL, pocket probing depth (PPD), and gingival recession (GR) were recorded at baseline, 3, and 6 months postoperatively. Periapical radiographs were taken at baseline, immediately, and 6 months after surgery. Early wound healing index (EHI) and patients' responses were recorded at 2 weeks postoperatively. RESULTS: At 6 months post-surgery, the mean CAL gain was 3.1 ± 1.5 mm in the NCM group and 2.9 ± 1.5 mm in the RCCM group, while the mean PPD was 4.3 ± 1.1 mm in the NCM group and 4.2 ± 1.0 mm in the RCCM group. Both groups demonstrated a statistically significant improvement from the baseline (p < .01). RCCM was non-inferior to NCM concerning the primary outcome (CAL gain at 6 months). The GR at 6 months postoperatively was 1.3 ± 1.2 and 1.2 ± 1.1 mm, which showed no difference compared with baseline. At 6 months follow-up, the radiographic linear bone fill (RLBF) was 6.5 ± 2.8 and 5.5 ± 2.6 mm (p > .05), while the bone fill percentage (BF%) was 102.3 ± 53.5% and 92.3 ± 40.1% (p > .05), in the NCM and RCCM groups, respectively. There was no significant difference in EHI and postoperative responses between two groups. CONCLUSION: RCCM + DBBM resulted in no-inferior clinical and radiographic outcomes to NCM + DBBM for the treatment of isolated infrabony defect in 6 months.

12.
Drug Resist Updat ; 67: 100915, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36641841

RESUMO

AIMS: This study aims at investigating the role of a neighbor long non-coding RNA (lncRNA) of HDAC4 (LOC85009) in docetaxel (DTX) resistance of lung adenocarcinoma (LUAD). METHODS: RT-qPCR was used to analyze LOC85009 expression in DTX-resistant LUAD cells. In vitro and in vivo experiments were applied to detect the influence of LOC85009 on LUAD cell growth and xenograft tumor growth. DNA pull down assay, RNA pull down assay, ChIP assay, CoIP assay and RIP assay were performed to identify the direct interactions between factors. RESULTS: LOC85009 was lowly-expressed in DTX-resistant LUAD cells. Functionally, LOC85009 overexpression inhibited DTX resistance and cell proliferation but triggered cell apoptosis. Moreover, we identified that LOC85009 was transferred from LUAD cells to DTX-resistant LUAD cells via exosomes. Exosomal LOC85009 inhibited DTX resistance, proliferation and autophagy while induced apoptosis in DTX-resistant cells. Additionally, we found that LOC85009 sequestered ubiquitin-specific proteinase 5 (USP5) to destabilize upstream transcription factor 1 (USF1) protein, thereby inactivating ATG5 transcription. CONCLUSIONS: Exosomal LOC85009 inhibits DTX resistance through regulation of ATG5-induced autophagy via USP5/USF1 axis, suggesting that LOC85009 might be a potential target to reverse DTX resistance in the treatment of LUAD.


Assuntos
Adenocarcinoma , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares , MicroRNAs , Humanos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Autofagia/genética , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína 5 Relacionada à Autofagia/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , MicroRNAs/genética
13.
Drug Resist Updat ; 68: 100933, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36821972

RESUMO

Alternative polyadenylation (APA) is a widespread mechanism generating RNA molecules with alternative 3' ends. Herein, we discovered that TargetScan includes a novel XBP1 transcript with a longer 3' untranslated region (UTR) (XBP1-UL) than that included in NCBI. XBP1-UL exhibited a lowered level in blood samples from lung adenocarcinoma (LUAD) patients and in those after DDP treatment. Consistently, XBP1-UL was reduced in A549 cells compared to normal BEAS-2B cells, as well as in DDP-treated/resistant A549 cells relative to controls. Moreover, due to decreased usage of the distal polyadenylation site (PAS) in 3'UTR, XBP1-UL level was lowered in A549 cells and decreased further in DDP-resistant A549 (A549/DDP) cells. Importantly, use of the distal PAS (dPAS) and XBP1-UL level were gradually reduced in A549 cells under increasing concentrations of DDP, which was attributed to DDP-induced endoplasmic reticulum (ER) stress. Furthermore, XBP1 transcripts with shorter 3'UTR (XBP1-US) were more stable and presented stronger potentiation on DDP resistance. The choice of proximal PAS (pPAS) was attributed to CPSF6 elevation, which was caused by BRCA1-distrupted R-loop accumulation in CPSF6 5'end. DDP-induced nuclear LINC00221 also facilitated CPSF6-induced pPAS choice in the pre-XBP1 3'end. Finally, we found that unlike the unspliced XBP1 protein (XBP1-u), the spliced form XBP1-s retarded p53 degradation to facilitate DNA damage repair of LUAD cells. The current study provides new insights into tumor progression and DDP resistance in LUAD, which may contribute to improved LUAD treatment.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Regiões 3' não Traduzidas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Resistencia a Medicamentos Antineoplásicos/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Apoptose , Proteína 1 de Ligação a X-Box/genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-38401063

RESUMO

Objective: The effectiveness of manual acupuncture for treating bronchial asthma is still debatable and broad, and the effects of different acupuncture points, treatment durations, or illness trajectories have never been rigorously assessed. The objective of this revised systematic review and subgroup meta-analysis of randomized controlled trials (RCTs) is to ascertain the clinical efficacy of manual acupuncture on bronchial asthma and whether these effects varied depending on the acupuncture points, length of treatment, or course of the disease. Materials and methods: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria were followed for creating a systematic review and meta-analysis. From the beginning through March 25, 2022, six electronic databases were checked. For the treatment of asthma, all RCTs contrasting acupuncture therapy along with conventional treatment against conventional treatment alone were chosen. The information was examined using Review Manager version 5.3 and Comprehensive Meta-Analysis version 3. Clinical efficacy (including the effective rate and the recurrence rate) was the primary outcome, and pulmonary function (including FEV1%, PEF) and The secondary results were T-lymphocyte immunity (containing CD3+, CD4+, and CD8+). Based on the acupuncture points, length of therapy, and nature of the condition, subgroup analyses were carried out. Results: There were a total of 21 RCTs that enrolled 2510 individuals. According to the meta-findings, analysis's manual acupuncture in addition to conventional treatment significantly increased the effective rate when compared to conventional treatment alone [OR = 5.14 95% CI 3.58-7.38, P < .00001], lung functions [FEV1% (MD = 6.18, 95% CI 2.40-9.96, P = .001) and PEF (MD = 0.45 95% CI 0.18-0.73, P = .001)], immune functions [CD3+ T lymphocytes (MD = 7.55 95% CI 6.55-8.56, P < .00001), CD4+ T-lymphocytes (MD = 5.11 95% CI 4.09-6.13, P < .00001), T-lymphocyte CD8+ (MD = -0.37.11 95% CI -3.62--2.51, P < .00001)] and noteworthy reduction in the recurrence rate (OR = 0.19 95% CI 0.10-0.38, P < .00001). Results from the subgroup analysis were consistent. Conclusion: Manual acupuncture combined with Western Medicine is more effective than conventional treatment alone for bronchial asthma. Combination therapy can significantly improve clinical efficacy, lung function, and immune function while reducing the relapse rate. But to further support the results of this investigation, high-quality RCTs with long-term outcomes are still required, taking into account the inherent limitations of the included studies. Registration number: PROSPERO (no. CRD42022357805) (https://www.crd.york.ac.uk/prospero/).

15.
Br J Cancer ; 129(8): 1261-1273, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37644092

RESUMO

BACKGROUND: Recent studies suggested that NDUFS1 has an important role in human cancers; however, the effects of NDUFS1 on gastric cancer (GC) are still not fully understood. METHODS: We confirmed that NDUFS1 is downregulated in GC cells through western blot immunohistochemistry and bioinformation analysis. The effect of NDUFS1 on GC was studied by CCK-8, colony formation, transwell assay in vitro and Mouse xenograft assay in vivo. Expression and subcellular localization of NDUFS1 and the content of mitochondrial reactive oxygen species (mROS) was observed by confocal reflectance microscopy. RESULTS: Reduced expression of NDUFS1 was found in GC tissues and cell lines. Also, NDUFS1 overexpression inhibited GC cell proliferation, migration, and invasion in vitro as well as growth and metastasis in vivo. Mechanistically, NDUFS1 reduction led to the activation of the mROS-hypoxia-inducible factor 1α (HIF1α) signaling pathway. We further clarified that NDUFS1 reduction upregulated the expression of fibulin 5 (FBLN5), a transcriptional target of HIF1α, through activation of mROS-HIF1α signaling in GC cells. CONCLUSIONS: The results of this study indicate that NDUFS1 downregulation promotes GC progression by activating an mROS-HIF1α-FBLN5 signaling pathway.

16.
Angew Chem Int Ed Engl ; 62(25): e202302505, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-36992624

RESUMO

Although solid-state batteries (SSBs) are high potential in achieving better safety and higher energy density, current solid-state electrolytes (SSEs) cannot fully satisfy the complicated requirements of SSBs. Herein, a covalent organic framework (COF) with multi-cationic molecular chains (COF-MCMC) was developed as an efficient SSE. The MCMCs chemically anchored on COF channels were generated by nano-confined copolymerization of cationic ionic liquid monomers, which can function as Li+ selective gates. The coulombic interaction between MCMCs and anions leads to easier dissociation of Li+ from coordinated states, and thus Li+ transport is accelerated. While the movement of anions is restrained due to the charge interaction, resulting in a high Li+ conductivity of 4.9×10-4  S cm-1 and Li+ transference number of 0.71 at 30 °C. The SSBs with COF-MCMC demonstrate an excellent specific energy density of 403.4 Wh kg-1 with high cathode loading and limited Li metal source.


Assuntos
Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Condutividade Elétrica , Cátions , Lítio , Fontes de Energia Elétrica
17.
Inorg Chem ; 60(17): 13718-13726, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34436870

RESUMO

The assembly of heterometallic cluster substituted polyoxometalates (POMs) remains a great challenge for inorganic synthetic chemistry up to now. Herein, a series of 5p-4f heterometallic cluster substituted POMs were successfully isolated by a facile one-step hydrothermal reaction method, namely H17(H2en)3[SbIII9SbVLn3O14(H2O)3][(SbW9O33)3(PW9O34)]·28H2O(1-Ln, Ln = Ce, Sm, Eu, Gd, Tb, Dy) (en = ethylenediamine). Interestingly, by replacing en with imidazole, another series of 5p-4f heterometallic cluster substituted POMs H13(HIm)4K2Na4(H2O)9[SbIII9SbVLn3O14(H2O)3][(SbW9O33)3(PW9O34)]·26H2O (2-Ln, Ln = Sm, Eu, Gd, Tb, Dy, Im = imidazole) were obtained. Structural analyses indicate that both 1-Ln and 2-Ln are made up of an unprecedented 5p-4f heterometallic {Sb10Ln3O14(H2O)3} cluster stabilized simultaneously by mixed trilacunary heteropolyanions including {A-α-PW9O34} and {B-α-SbW9O33}. Impedance measurements indicate that both compounds exhibit different proton conduction properties, and the conductivity of 2 can reach up to 1.64 × 10-2 S cm-1 at 85 °C under 98% relative humidity. Moreover, the fluorescence emission behaviors of both compounds have been studied.

18.
J Periodontal Res ; 56(3): 547-557, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33522612

RESUMO

BACKGROUND: An increasing number of patients with chronic periodontitis (CP) have received implant restoration. However, very few studies have evaluated the probable risk indicators of implant loss in patients with CP. OBJECTIVE: The aim of this study is to evaluate implant long-term survival rates in patients with CP. The results are analyzed to discern potential risk indicators of implant loss. METHODS: A total of 1549 implants were inserted in 827 non-smokers and systemically healthy CP patients between March 2011 and March 2019. Clinical variables (age; sex; implant location; implant diameter; implant length; implant type; bone quality; bone graft, periodontal disease status, and insertion torque) were recorded. Kaplan-Meier survival curves illustrated the cumulative survival rate. The relationship between variables and implant loss was discerned by univariate analysis. Further multivariate Cox proportional hazard regression analysis was carried out for the variables with P < 0.2. RESULTS: The cumulative survival rates were 98.8% after 3 months, 97.9% after 6 months, 97.7% after 1 year, and 97.4% after 2 to 9 years. After adjusting possible confounders, the multivariable Cox regression model revealed statistically significant influences of implant location, history of bone graft, and insertion torque on implant loss. Implants with history of bone graft were more likely to loss. Implants inserted in the anterior area had a higher implant loss risk; insertion torque of <15 Newton-centimeter (Ncm) showed a relatively high risk of being lost. CONCLUSIONS: The study represented public hospital insight into long-term implant results of patients with CP. Under the premise of strict periodontal control, patients with the history of CP exhibited relatively high implant survival rate. Anterior implant location, history of bone graft, and insertion torque <15 Ncm are associated with a lower implant survival rate and could be considered at a higher risk of implant failure in patients with CP.


Assuntos
Perda do Osso Alveolar , Implantes Dentários , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/epidemiologia , Implantes Dentários/efeitos adversos , Falha de Restauração Dentária , Seguimentos , Humanos , não Fumantes , Estudos Retrospectivos , Taxa de Sobrevida
19.
Phys Chem Chem Phys ; 23(20): 11961-11967, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34002190

RESUMO

Monolayer phosphorene has outstanding spintronic properties including a nanosecond spin lifetime, and micrometer spin relaxation length, combined with excellent mechanical flexibility, making it rather attractive in low-dimensional flexible spintronic devices. However, knowledge on the spin-transport properties of phosphorene under mechanical strain is currently very limited. Here, we study the transport properties of the spin-polarized photocurrent in the flexible Ni-phosphorene-Ni photodetector, which is driven by the photogalvanic effect (PGE) under mechanical tension stress and bending. Broadband PGE photocurrent is generated at zero bias under the illumination of linearly polarized light due to the broken inversion symmetry of the photodetector. Remarkable spin-transport performances including the fully spin-polarized photocurrent, perfect spin-valve effect, and enhanced pure spin current are generated in a broad visible range by applying appropriate mechanical tension stress or bending. Our results indicate that the PGE-driven phosphorene-based photodetector has promising applications in flexible and low-power spintronic devices.

20.
Chemistry ; 26(72): 17376-17380, 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33090590

RESUMO

Dual/multi-component organic doped systems with room-temperature phosphorescence (RTP) properties have been developed. However, the unknown luminescence mechanism still greatly limits the development of the doped materials. Herein, a new doped system exhibiting phosphorescence/fluorescence dual emission (Φphos =4-24 % and τphos =101-343 ms) is successfully constructed through prediction and design. A series of isoquinoline derivatives with different alkoxy chains were selected as the guests. Benzophenone was chosen as the host owing to the characteristics of low melting point and good crystallinity. The alkoxy chain lengths of the guests are first reported to be used to control the fluorescence and phosphorescence intensities of the doped materials, which results in different prompt emission colors. Additionally, the doped ratio of the guest and host can also control the luminous intensities of the materials. In particular, the doped materials still exhibit phosphorescent properties even if the ratio of the guest/host is as low as 1:100 000.

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