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1.
Brief Bioinform ; 24(1)2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36567622

RESUMO

Genomic recombination is an important driving force for viral evolution, and recombination events have been reported for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the Coronavirus Disease 2019 pandemic, which significantly alter viral infectivity and transmissibility. However, it is difficult to identify viral recombination, especially for low-divergence viruses such as SARS-CoV-2, since it is hard to distinguish recombination from in situ mutation. Herein, we applied information theory to viral recombination analysis and developed VirusRecom, a program for efficiently screening recombination events on viral genome. In principle, we considered a recombination event as a transmission process of ``information'' and introduced weighted information content (WIC) to quantify the contribution of recombination to a certain region on viral genome; then, we identified the recombination regions by comparing WICs of different regions. In the benchmark using simulated data, VirusRecom showed a good balance between precision and recall compared to two competing tools, RDP5 and 3SEQ. In the detection of SARS-CoV-2 XE, XD and XF recombinants, VirusRecom providing more accurate positions of recombination regions than RDP5 and 3SEQ. In addition, we encapsulated the VirusRecom program into a command-line-interface software for convenient operation by users. In summary, we developed a novel approach based on information theory to identify viral recombination within highly similar sequences, providing a useful tool for monitoring viral evolution and epidemic control.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Teoria da Informação , Filogenia , Recombinação Genética
2.
BMC Bioinformatics ; 25(1): 29, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233783

RESUMO

The impairment of sperm maturation is one of the major pathogenic factors in male subfertility, a serious medical and social problem affecting millions of global couples. Regrettably, the existing research on sperm maturation is slow, limited, and fragmented, largely attributable to the lack of a global molecular view. To fill the data gap, we newly established a database, namely the Sperm Maturation Database (SperMD, http://bio-add.org/SperMD ). SperMD integrates heterogeneous multi-omics data (170 transcriptomes, 91 proteomes, and five human metabolomes) to illustrate the transcriptional, translational, and metabolic manifestations during the entire lifespan of sperm maturation. These data involve almost all crucial scenarios related to sperm maturation, including the tissue components of the epididymal microenvironment, cell constituents of tissues, different pathological states, and so on. To the best of our knowledge, SperMD could be one of the limited repositories that provide focused and comprehensive information on sperm maturation. Easy-to-use web services are also implemented to enhance the experience of data retrieval and molecular comparison between humans and mice. Furthermore, the manuscript illustrates an example application demonstrated to systematically characterize novel gene functions in sperm maturation. Nevertheless, SperMD undertakes the endeavor to integrate the islanding omics data, offering a panoramic molecular view of how the spermatozoa gain full reproductive abilities. It will serve as a valuable resource for the systematic exploration of sperm maturation and for prioritizing the biomarkers and targets for precise diagnosis and therapy of male subfertility.


Assuntos
Infertilidade Masculina , Maturação do Esperma , Masculino , Humanos , Animais , Camundongos , Maturação do Esperma/genética , Sêmen , Espermatozoides/metabolismo , Epididimo/metabolismo , Infertilidade Masculina/metabolismo
3.
Small ; 20(12): e2307408, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37940624

RESUMO

Nitrogen-doped titanium carbides (MXene) films exhibit extraordinary volumetric capacitance when high-concentration sulfuric acid electrolyte is utilized owing to the enhancement of pseudocapacitance. However, the energy storage mechanism of nitrogen-doped MXene is unclear due to the complex electrode structure and electrolyte ions' behavior. Here, based on pristine MXene (Ti3C2O2), three different MXene structures are constructed by introducing metal vacancy sites and doped nitrogen atoms, namely, defective MXene (Ti2.9C2O2), nitrogen-doped MXene (Ti3C2O1.9N0.1), and nitrogen-doped MXene with metal vacancy sites (Ti2.9C2O1.9N0.1). Then, the density functional theory (DFT)-based calculations coupled with the effective screening medium reference interaction site method (ESM-RISM) are applied to reveal the electrochemical behavior at the electrode/electrolyte interfacial area. Through analyzing the electronic structure, electrical double-layer capacitance (EDLC), and equilibrium potential of the pseudocapacitance reaction, the specific effect of structural changes on their performance can be clarified: metal vacancy sites can reduce the potential difference of gap layer (Outer Helmholtz plane) at charged state and increase the electronic capacity of Ti, which can be used to explain the high pseudocapacitance, low charge transfer resistance and high-rate capacity properties of nitrogen-doped MXene observed in experiments.

4.
Genomics ; 115(1): 110542, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36535337

RESUMO

N6-methyladenosine (m6A) modification is essential for plant growth and development. Exploring m6A methylation patterns in rice tissues is fundamental to understanding the regulatory effects of this modification. Here, we profiled the transcriptome-wide m6A landscapes of rice panicles at the booting stage (PB) and flowering stage (PF), and of flag leaves at the flowering stage (LF). The global m6A level differed significantly among the three tissues and was closely associated with the expression of writer and eraser genes. The methylated gene ratio was higher in the flag leaves than in the panicles. Compared with commonly methylated genes, tissue-specific methylated genes showed lower levels of both m6A modification and expression, and a preference for m6A deposition in the coding sequence region. The m6A profiles of the two organs had more distinct differences than the profiles of the same organ at different stages. A negative correlation between m6A levels and gene expression was observed in PF vs. PB but not in PF vs. LF, indicting the complicated regulatory effect of m6A on gene expression. The distinct expression patterns of m6A reader genes in different tissues indicate that readers may affect gene stability through binding. Overall, our findings demonstrated that m6A modification influences tissue function by regulating gene expression. Our findings provide valuable insights on the regulation and biological functions of m6A modifications in rice.


Assuntos
Oryza , Transcriptoma , Oryza/genética , RNA Mensageiro , Perfilação da Expressão Gênica , Folhas de Planta/genética , Regulação da Expressão Gênica de Plantas
5.
Angew Chem Int Ed Engl ; 63(18): e202316431, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38012084

RESUMO

Carbon nanomaterials, specifically carbon dots and carbon nitrides, play a crucial role as heterogeneous photoinitiators in both radical and cationic polymerization processes. These recently introduced materials offer promising solutions to the limitations of current homogeneous systems, presenting a novel approach to photopolymerization. This review highlights the preparation and photocatalytic performance of these nanomaterials, emphasizing their application in various polymerization techniques, including photoinduced i) free radical, ii) RAFT, iii) ATRP, and iv) cationic photopolymerization. Additionally, it discusses their potential in addressing contemporary challenges and explores prospects in this field. Moreover, carbon nitrides, in particular, exhibit exceptional oxygen tolerance, underscoring their significance in radical polymerization processes and allowing their applications such as 3D printing, surface modification of coatings, and hydrogel engineering.

6.
Small ; 19(42): e2303642, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37323120

RESUMO

Nickel sulfides with high theoretical capacity are considered as promising anode materials for sodium-ion batteries (SIBs); however, their intrinsic poor electric conductivity, large volume change during charging/discharging, and easy sulfur dissolution result in inferior electrochemical performance for sodium storage. Herein, a hierarchical hollow microsphere is assembled from heterostructured NiS/NiS2 nanoparticles confined by in situ carbon layer (H-NiS/NiS2 @C) via regulating the sulfidation temperature of the precursor Ni-MOFs. The morphology of ultrathin hollow spherical shells and confinement of in situ carbon layer to active materials provide rich channels for ion/electron transfer and alleviate the effects of volume change and agglomeration of the material. Consequently, the as-prepared H-NiS/NiS2 @C exhibit superb electrochemical properties, satisfactory initial specific capacity of 953.0 mA h g-1 at 0.1 A g-1 , excellent rate capability of 509.9 mA h g-1 at 2 A g-1 , and superior longtime cycling life with 433.4 mA h g-1 after 4500 cycles at 10 A g-1 . Density functional theory calculation shows that heterogenous interfaces with electron redistribution lead to charge transfer from NiS to NiS2 , and thus favor interfacial electron transport and reduce ion-diffusion barrier. This work provides an innovative idea for the synthesis of homologous heterostructures for high-efficiency SIB electrode materials.

7.
J Med Virol ; 95(1): e28407, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36519597

RESUMO

To control the ongoing COVID-19 pandemic, a variety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been developed. However, the rapid mutations of SARS-CoV-2 spike (S) protein may reduce the protective efficacy of the existing vaccines which is mainly determined by the level of neutralizing antibodies targeting S. In this study, we screened prevalent S mutations and constructed 124 pseudotyped lentiviral particles carrying these mutants. We challenged these pseudoviruses with sera vaccinated by Sinovac CoronaVac and ZF2001 vaccines, two popular vaccines designed for the initial strain of SARS-CoV-2, and then systematically assessed the susceptivity of these SARS-CoV-2 variants to the immune sera of vaccines. As a result, 14 S mutants (H146Y, V320I + S477N, V382L, K444R, L455F + S477N, L452M + F486L, F486L, Y508H, P521R, A626S, S477N + S698L, A701V, S477N + T778I, E1144Q) were found to be significantly resistant to neutralization, indicating reduced protective efficacy of the vaccines against these SARS-CoV-2 variants. In addition, F486L and Y508H significantly enhanced the utilization of human angiotensin-converting enzyme 2, suggesting a potentially elevated infectivity of these two mutants. In conclusion, our results show that some prevalent S mutations of SARS-CoV-2 reduced the protective efficacy of current vaccines and enhance the infectivity of the virus, indicating the necessity of vaccine renewal and providing direction for the development of new vaccines.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , Anticorpos Antivirais , Testes de Neutralização , Glicoproteína da Espícula de Coronavírus , Internalização do Vírus , Pandemias , Anticorpos Neutralizantes , Mutação
8.
Nanotechnology ; 33(15)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-34952529

RESUMO

Developing efficient and stable multifunctional electrocatalyst is very important for zinc-air batteries in practical. Herein, semiconductive spinel CuFe2O4supported Co-N co-doped carbon (Co-NC) and CoFe alloy nanoparticles were proposed. In this strategy, the three-dimensional ordered macroporous CuFe2O4support provides rich channels for mass transmission, revealling good corrosion-resistance and durability at the same time. ZIF-67 derived Co-NC decoration improves the conductivity of the catalyst. Further, the uniformly distributed Co-NC and CoFe nanoparticles (C/CF) dramatically promote the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) performance. Accordingly, C/CF@CuFe2O4catalyst shows remarkable bifunctional electrocatalytic activity, with an ORR half-wave potential of 0.86 V, and an OER over-potential of 0.46 V at 10 mA cm-2. The zinc-air battery using this catalyst exhibits a power density of 95.5 mW cm-2and a durable cyclability for over 170 h at a current density of 10 mA cm-2, which implies a great potential in practical application.

9.
BMC Genomics ; 22(Suppl 3): 793, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34736408

RESUMO

BACKGROUND: Winter wheat requires prolonged exposure to low temperature to initiate flowering (vernalization). Shoot apical meristem of the crown is the site of cold perception, which produces leaf primordia during vegetative growth before developing into floral primordia at the initiation of the reproductive phase. Although many essential genes for winter wheat cold acclimation and floral initiation have been revealed, the importance of microRNA (miRNA) meditated post-transcriptional regulation in crowns is not well understood. To understand the potential roles of miRNAs in crown tissues, we performed a temporal expression study of miRNAs in crown tissues at the three-leaf stage, winter dormancy stage, spring green-up stage, and jointing stage of winter wheat grown under natural growth conditions. RESULTS: In total, 348 miRNAs belonging to 298 miRNA families, were identified in wheat crown tissues. Among them, 92 differentially expressed miRNAs (DEMs) were found to be significantly regulated from the three-leaf stage to the jointing stage. Most of these DEMs were highly expressed at the three-leaf stage and winter dormancy stage, and then declined in later stages. Six DEMs, including miR156a-5p were markedly induced during the winter dormancy stage. Eleven DEMs, including miR159a.1, miR390a-5p, miR393-5p, miR160a-5p, and miR1436, were highly expressed at the green-up stage. Twelve DEMs, such as miR172a-5p, miR394a, miR319b-3p, and miR9676-5p were highly induced at the jointing stage. Moreover, 14 novel target genes of nine wheat or Pooideae-specific miRNAs were verified using RLM-5' RACE assay. Notably, six mTERFs and two Rf1 genes, which are associated with mitochondrial gene expression, were confirmed as targets of three wheat-specific miRNAs. CONCLUSIONS: The present study not only confirmed the known miRNAs associated with phase transition and floral development, but also identified a number of wheat or Pooideae-specific miRNAs critical for winter wheat cold acclimation and floral development. Most importantly, this study provided experimental evidence that miRNA could regulate mitochondrial gene expression by targeting mTERF and Rf1 genes. Our study provides valuable information for further exploration of the mechanism of miRNA mediated post-transcriptional regulation during winter wheat vernalization and inflorescent initiation.


Assuntos
MicroRNAs , Triticum , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Humanos , Meristema , MicroRNAs/genética , Triticum/genética
10.
Bioorg Med Chem Lett ; 30(8): 127051, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32111436

RESUMO

A series of 3-nitro-naphthalimides 1(1a-1h) were designed and synthesized as antitumor agents. MTT assay results showed that all these compounds exhibited obvious antiproliferative activity against SKOV3, HepG2, A549, T-24 and SMMC-7721 cancer cell lines, while compound 1a displayed the best antiproliferative activity against HepG2 and T-24 cell lines in comparison with mitonafide, with IC50 of 9.2 ± 1.8 and 4.133 ± 0.9 µM, respectively. In vivo antiproliferative activity assay results showed that compound 1a exhibited good antiproliferative activity in the HepG2 and T-24 models, compared with mitonafide. Action mechanism results showed that compound 1a could induced the damage of DNA and the inhibition topo I, accompanying by inducing the G2-stage arresting and the apoptosis of T-24 cancer cells through up-regulating expression levels of cyclin B1, cdc 2-pTy, Wee1, γH2AX, p21, Bax and cytochrome c and down-regulating expression of Bcl-2.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Naftalimidas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Estrutura Molecular , Naftalimidas/química , Relação Estrutura-Atividade
11.
J Theor Biol ; 395: 23-30, 2016 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-26829314

RESUMO

This study presents an alternative alignment-free relative feature analysis method based on the minimal absent word, which has potential advantages over the local alignment method in local analysis. Smooth-local-analysis-curve and similarity-distribution are constructed for a fast, efficient, and visual comparison. Moreover, when the multi-sequence-comparison is needed, the local-analysis-curves can illustrate some interesting zones.


Assuntos
Genoma Humano , Modelos Genéticos , Análise de Sequência de DNA , Animais , Humanos
12.
Small ; 11(29): 3583-90, 2015 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-25865217

RESUMO

Two-dimensional (2D) nanomaterials and heterostructured nanocrystals (NCs) are two hot topics in current nanoresearch. However, reports on heterostructured NCs with 2D features are still rare. In this work, we demonstrate a one-pot colloidal chemistry route for synthesizing Au-CuZnSe2 heterostructures with spherical Au domains attached to the edge of a sheet of CuZnSe2 . This protocol involves the preferential formation of Au clusters and the seeded growth of CuZnSe2 sheets because of the lattice matching of CuSe with Au. As an example to demonstrate the importance of such heterostructures, the electrochemical performance of Au-CuZnSe2 heterostructured nanosheets is compared with that of heterostructured nanorods, Au NCs, and CuZnSe2 NCs. The heterostructured nanosheets exhibit the best electrochemical activity.

13.
Clin Orthop Relat Res ; 473(8): 2672-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25981713

RESUMO

BACKGROUND: Arthroplasty has been shown to be superior regarding low risk of reoperation and better function score to internal fixation for treatment of displaced femoral neck fractures at short-term followup. However, there are unanswered questions regarding the efficacy of arthroplasty in the longer term compared with internal fixation. QUESTIONS/PURPOSES: We performed a meta-analysis comparing arthroplasty (hemiarthroplasty or THA) with internal fixation in patients with displaced femoral neck fractures with respect to (1) mortality, (2) reoperation, (3) functional recovery, and (4) complications, including only randomized trials with a minimum of 4 years followup. METHODS: Computerized databases, including PubMed (MEDLINE), EMBASE, Cochrane Register of Controlled Trials databases, and Web of Science™ were searched for studies published from the inception date for each database to March 2014. Eleven randomized controlled trials that compared arthroplasty (either hemiarthroplasty or THA) with internal fixation for treatment of patients with a femoral neck fracture were included in our analysis. The quality of the trials was assessed according to the Cochrane Handbook and meta-analyses were conducted using RevMan 5.2 software from the Cochrane Collaboration. The heterogeneity among studies was evaluated by the I-squared index (I2) and publication bias was assessed using forest plots. RESULTS: There were no differences between the internal fixation and arthroplasty groups for patient mortality at mid-term (48.4% vs 46.8%) or long-term followup (83.2% vs 81.5%). Arthroplasty was associated with a lower risk of reoperation at mid-term (7.2% vs 39.8%; relative risk [RR]=0.10; 95% CI, 0.06-0.07) and at long-term followup (14.3% vs 43.8%; RR=0.10; 95% CI, 0.06-0.07). Arthroplasty was associated with better functional recovery at mid-term followup (standard mean difference [SMD]=0.55; 95% CI, 0.02-1.09), whereas function at long-term followup (SMD=0.14; 95% CI, -0.35 to 0.62) was not different between the arthroplasty and internal fixation groups. There were no significant differences in subsequent ipsilateral fractures (1.5% vs 1.2%; RR=2.18; 95% CI, 0.32-14.67; p=0.42) and deep infections (2.7% vs 2.9%; RR=0.89; 95% CI, 0.40-2.01; p=0.78) between patients treated with arthroplasty and internal fixation. CONCLUSIONS: Based on our results, we found that compared with internal fixation, arthroplasty may result in a lower rate of subsequent reoperation at mid- and long-term followup, and better mid-term functional recovery. Future studies should investigate the mid- and long-term results of THAs compared with hemiarthroplasty.


Assuntos
Artroplastia de Quadril , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas , Hemiartroplastia , Articulação do Quadril/cirurgia , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/mortalidade , Fraturas do Colo Femoral/diagnóstico , Fraturas do Colo Femoral/mortalidade , Fraturas do Colo Femoral/fisiopatologia , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/mortalidade , Hemiartroplastia/efeitos adversos , Hemiartroplastia/mortalidade , Articulação do Quadril/fisiopatologia , Humanos , Razão de Chances , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/cirurgia , Recuperação de Função Fisiológica , Reoperação , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
14.
Virol Sin ; 39(2): 177-193, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38272237

RESUMO

The persistent epidemic of human mpox, caused by mpox virus (MPXV), raises concerns about the future spread of MPXV and other poxviruses. MPXV is a typical zoonotic virus which can infect human and cause smallpox-like symptoms. MPXV belongs to the Poxviridae family, which has a relatively broad host range from arthropods to vertebrates. Cross-species transmission of poxviruses among different hosts has been frequently reported and resulted in numerous epidemics. Poxviruses have a complex linear double-strand DNA genome that encodes hundreds of proteins. Genes related to the host range of poxvirus are called host range genes (HRGs). This review briefly introduces the taxonomy, phylogeny and hosts of poxviruses, and then comprehensively summarizes the current knowledge about the cross-species transmission of poxviruses. In particular, the HRGs of poxvirus are described and their impacts on viral host range are discussed in depth. We hope that this review will provide a comprehensive perspective about the current progress of researches on cross-species transmission and HRG variation of poxviruses, serving as a valuable reference for academic studies and disease control in the future.


Assuntos
Especificidade de Hospedeiro , Filogenia , Infecções por Poxviridae , Poxviridae , Animais , Humanos , Infecções por Poxviridae/virologia , Infecções por Poxviridae/transmissão , Poxviridae/genética , Poxviridae/classificação , Poxviridae/fisiologia , Genoma Viral
15.
Front Endocrinol (Lausanne) ; 15: 1419566, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38883609

RESUMO

Background: Postmenopausal osteoporosis is a prevalent disease that affects the bone health of middle-aged and elderly women. The link between gut microbiota and bone health, known as the gut-bone axis, has garnered widespread attention. Methods: We employed a two-sample Mendelian randomization approach to assess the associations between gut microbiota with osteoclasts and postmenopausal osteoporosis, respectively. Single nucleotide polymorphisms associated with the composition of gut microbiota were used as instrumental variables. By analyzing large-scale multi-ethnic GWAS data from the international MiBioGen consortium, and combining data from the eQTLGen consortium and the GEFOS consortium, we identified microbiota related to osteoclasts and postmenopausal osteoporosis. Key genes were further identified through MAGMA analysis, and validation was performed using single-cell data GSE147287. Results: The outcomes of this study have uncovered significant associations within the gut microbiome community, particularly with the Burkholderiales order, which correlates with both an increase in osteoclasts and a reduced risk of postmenopausal osteoporosis. with an odds ratio (OR) of 0.400, and a P-value of 0.011. Further analysis using single-cell data allowed us to identify two key genes, FMNL2 and SRBD1, that are closely linked to both osteoclasts and osteoporosis. Conclusion: This study utilizing Mendelian randomization and single-cell data analysis, provides new evidence of a causal relationship between gut microbiota and osteoclasts, as well as postmenopausal osteoporosis. It was discovered that the specific microbial group, the Burkholderiales order, significantly impacts both osteoporosis and osteoclasts. Additionally, key genes FMNL2 and SRBD1 were identified, offering new therapeutic strategies for the treatment of postmenopausal osteoporosis.


Assuntos
Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Osteoclastos , Osteoporose Pós-Menopausa , Polimorfismo de Nucleotídeo Único , Humanos , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Pessoa de Meia-Idade , Osso e Ossos/microbiologia , Idoso
16.
J Clin Transl Hepatol ; 12(1): 91-99, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38250469

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with limited treatment options. Inflammation caused by metabolic disturbances plays a significant role in NAFLD development. Stimulator of interferon gene (STING), a critical regulator of innate immunity, induces the production of interferons and other pro-inflammatory factors by recognizing cytoplasmic DNA to defend against pathogen infection. The STING-mediated signaling pathway appears to play a vital role in hepatic inflammation, metabolic disorders, and even carcinogenesis. Promisingly, pharmacological interventions targeting STING have shown improvements in the pathological state of NAFLD. Macrophages, dendritic cells, natural killer cells, and T cell pathways regulated by STING present potential novel druggable targets for NAFLD treatment. Further research and development in this area may offer new therapeutic options for managing NAFLD effectively.

17.
Biomolecules ; 14(3)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38540712

RESUMO

Osteoarthritis (OA) is a debilitating joint disorder that affects millions of people worldwide. Despite its prevalence, our understanding of the underlying mechanisms remains incomplete. In recent years, transient receptor potential vanilloid (TRPV) channels have emerged as key players in OA pathogenesis. This review provides an in-depth exploration of the role of the TRPV pathway in OA, encompassing its involvement in pain perception, inflammation, and mechanotransduction. Furthermore, we discuss the latest research findings, potential therapeutic strategies, and future directions in the field, shedding light on the multifaceted nature of TRPV channels in OA.


Assuntos
Osteoartrite , Canais de Potencial de Receptor Transitório , Humanos , Canais de Potencial de Receptor Transitório/metabolismo , Mecanotransdução Celular , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Osteoartrite/patologia , Inflamação
18.
Sci Total Environ ; 946: 174350, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960203

RESUMO

There is limited evidence on the effects of intrauterine chromium (Cr) exposure on children's cognitive developmental delay (CDD). Further, little is known about the genetic factors in modifying the association between intrauterine Cr exposure and CDD. The present study involved 2361 mother-child pairs, in which maternal plasma Cr concentrations were assessed, a polygenic risk score for the child was constructed, and the child's cognitive development was evaluated using the Bayley Scales of Infant Development. The risks of CDD conferred by intrauterine Cr exposure in children with different genetic backgrounds were evaluated by logistic regression. The additive interaction between intrauterine Cr exposure and genetic factors was evaluated by calculating the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). According to present study, higher intrauterine Cr exposure was significantly associated with increased CDD risk [each unit increase in ln-transformed maternal plasma Cr concentration (ln-Cr): adjusted OR (95 % CI), 1.18 (1.04-1.35); highest vs lowest quartile: adjusted OR (95 % CI), 1.57 (1.10-2.23)]. The dose-response relationship of intrauterine Cr exposure and CDD for children with high genetic risk was more prominent [each unit increased ln-Cr: adjusted OR (95 % CI), 1.36 (1.09-1.70)]. Joint effects between intrauterine Cr exposure and genetic factors were found. Specifically, for high genetic risk carriers, the association between intrauterine Cr exposure and CDD was more evident [highest vs lowest quartile: adjusted OR (95 % CI), 2.33 (1.43-3.80)]. For those children with high intrauterine Cr exposure and high genetic risk, the adjusted AP was 0.39 (95 % CI, 0.07-0.72). Conclusively, intrauterine Cr exposure was a high-risk factor for CDD in children, particularly for those with high genetic risk. Intrauterine Cr exposure and one's adverse genetic background jointly contribute to an increased risk of CDD in children.

19.
Nat Commun ; 15(1): 4194, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760364

RESUMO

The role of tumor-resident intracellular microbiota (TRIM) in carcinogenesis has sparked enormous interest. Nevertheless, the impact of TRIM-targeted antibacteria on tumor inhibition and immune regulation in the tumor microenvironment (TME) remains unexplored. Herein, we report long-term relapse-free survival by coordinating antibacteria with antitumor treatment, addressing the aggravated immunosuppression and tumor overgrowth induced by TRIM using breast and prostate cancer models. Combining Ag+ release with a Fenton-like reaction and photothermal conversion, simultaneous bacteria killing and multimodal antitumor therapy are enabled by a single agent. Free of immune-stimulating drugs, the agent restores antitumor immune surveillance and activates immunological responses. Secondary inoculation and distal tumor analysis confirm lasting immunological memory and systemic immune responses. A relapse-free survival of >700 days is achieved. This work unravels the crucial role of TRIM-targeted antibacteria in tumor inhibition and unlocks an unconventional route for immune regulation in TME and a complete cure for cancer.


Assuntos
Microambiente Tumoral , Feminino , Masculino , Humanos , Animais , Camundongos , Microambiente Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacos , Neoplasias da Mama/imunologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/terapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Microbiota/efeitos dos fármacos , Prata/química , Intervalo Livre de Doença , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Recidiva Local de Neoplasia/imunologia
20.
BMJ Open ; 14(3): e078782, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490656

RESUMO

OBJECTIVES: This study aimed to investigate the impact of adjuvant chemotherapy (ACT) on survival outcomes in older women with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC). DESIGN: A retrospective cohort study using data from the Surveillance, Epidemiology, and End Results database, which contains publicly available information from US cancer registries. SETTING AND PARTICIPANTS: The study included 45 762 older patients with BC aged over 65 years diagnosed between 2010 and 2015. METHODS: Patients were divided into two groups based on age: 65-79 years and ≥80 years. Propensity score matching (PSM) was employed to balance clinicopathological characteristics between patients who received ACT and those who did not. Data analysis used the χ2 test and Kaplan-Meier method, with a subgroup analysis conducted to identify potential beneficiaries of ACT. OUTCOME MEASURES: Overall survival (OS) and cancer-specific survival (CSS). RESULTS: Due to clinicopathological characteristic imbalances between patients with BC aged 65-79 years and those aged ≥80 years, PSM was used to categorise the population into two groups for analysis: the 65-79 years age group (n=38 128) and the ≥80 years age group (n=7634). Among patients aged 65-79 years, Kaplan-Meier analysis post-PSM indicated that ACT was effective in improving OS (p<0.05, HR=0.80, 95% CI 0.73 to 0.88), particularly in those with advanced disease stages, but did not show a significant benefit in CSS (p=0.09, HR=1.13, 95% CI 0.98 to 1.31). Conversely, for patients aged ≥80 years, ACT did not demonstrate any improvement in OS (p=0.79, HR=1.04, 95% CI 0.79 to 1.36) or CSS (p=0.09, HR=1.46, 95% CI 0.69 to 2.26) after matching. Subgroup analysis also revealed no positive impact on OS and CSS. CONCLUSIONS: Patients with HR+/HER2- BC ≥80 years of age may be considered exempt from ACT because no benefits were found in terms of OS and CSS.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Pontuação de Propensão , Programa de SEER , Quimioterapia Adjuvante/métodos
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