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1.
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
2.
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
3.
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
4.
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
5.
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.

6.
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
7.
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.

8.
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.

9.
Chemosphere ; 345: 140550, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37890792

RESUMO

Both insufficient and excessive manganese exposure are associated with adverse pregnancy outcomes. However, no systematic research has established a standardized reference range for manganese levels with the consideration of the associated health risks during pregnancy. To verify the associations of prenatal manganese exposure with adverse outcomes and to identify a proper reference range for manganese based on health risks, we designed three nested case-control studies on three adverse outcomes including hypertensive disorders of pregnancy (HDP), preterm birth (PTB), and low birth weight (LBW) to investigate the associations with manganese levels. Plasma manganese concentrations in early pregnancy were measured. Conditional logistic regression analyses were used to estimate the associations of manganese levels with adverse outcomes. Restricted cubic spline (RCS) models were used to characterize the dose-response relationship of manganese and each outcome. Nonlinear associations were observed for manganese and adverse outcomes. Compared with women in the middle tertile of plasma manganese, we found that those in the highest tertile had a significantly higher risk of HDP (OR = 1.72, 95% CI: 1.02 to 2.89), that women in the lowest tertile had almost a tripled risk of delivering LBW infants (OR = 2.93, 95% CI: 1.67 to 5.17), and that women both in the lowest and the highest tertiles had significantly higher risks of PTB [OR = 1.83 (95% CI: 1.14 to 2.95); OR = 1.70 (95% CI: 1.05 to 2.76)]. U-shaped associations were found between plasma manganese and risk of PTB and infant LBW. Based on the results of RCS models, we identified a proper plasma manganese range of 1.72-3.18 µg/L, with relatively lower risks of adverse pregnancy outcomes. In conclusion, our study found U-shaped associations between manganese exposure and adverse pregnancy outcomes, and provided an optimal range of manganese concentration for pregnant women, based on health risk considerations.


Assuntos
Manganês , Resultado da Gravidez , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Coorte de Nascimento , Estudos de Casos e Controles , População do Leste Asiático , Manganês/sangue , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia
10.
Environ Sci Pollut Res Int ; 30(49): 108319-108329, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37752390

RESUMO

Air pollution exposure was known to result in body impairments by inducing inflammation and oxidation. But little is known about the associations of air pollutants with plasma fatty acid profile which may play important roles in the impairment of air pollutants based on the related mechanism, especially in pregnant women. This study aimed to explore the relationships of air pollution exposure with plasma fatty acid profile and the potential effect modification by pre-pregnancy body mass index (BMI). Based on a cohort in Wuhan, China, we measured concentrations of plasma fatty acids of 519 pregnant women enrolled from 2013 to 2016 by gas chromatography-mass spectrometry (GC-MS). Levels of exposure to air pollutants (fine particulate matter (PM2.5), inhalable particles (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO)) were estimated by using spatial-temporal land use regression models and calculated in three periods (average concentrations during 1 day, 1 week, and 1 month before the phlebotomizing day in the first trimester). Per interquartile range increment of the levels of air pollution exposure 1 day before phlebotomizing was related to 1.21-2.01% increment of omega-6 polyunsaturated fatty acids (n-6PUFA) and 0.63-1.74% decrement of omega-3 polyunsaturated fatty acids (n-3PUFA). Besides, relationships above were kept robust in the analysis during 1 week and 1 month before phlebotomizing. In women with normal BMI, plasma fatty acid profile was observed to be more sensitive to air pollutants. Our study demonstrated that increment of exposure to air pollutants was associated with higher plasma n-6PUFA known to be pro-inflammatory and lower plasma n-3PUFA known to be anti-inflammatory, which was more sensitive in pregnant women with normal BMI. Our findings suggested that changes in plasma fatty acid profile should cause concerns and may serve as biomarkers in the further studies. Future studies are needed to validate our findings and elucidate the underlying mechanisms.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Humanos , Feminino , Gravidez , Gestantes , Estudos de Coortes , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Material Particulado/análise , Ácidos Graxos/análise , Ácidos Graxos Insaturados , China , Dióxido de Nitrogênio/análise
11.
ACS Nano ; 17(19): 19323-19337, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37769163

RESUMO

Insulating thermally conductive polymer composites are in great demand in integrated-circuit packages, for efficient heat dissipation and to alleviative short-circuit risk. Herein, the continuous oriented hexagonal boron nitride (h-BN) frameworks (o-BN@SiC) were prepared via self-assembly and in situ chemical vapor infiltration (CVI) interface welding. The insulating o-BN@SiC/epoxy (o-BN@SiC/EP) composites exhibited enhanced thermal conductivity benefited from the CVI-SiC-welded BN-BN interface. Further, multiscale simulation, combining first-principles calculation, Monte Carlo simulation, and finite-element simulation, was performed to quantitatively reveal the effect of the welded BN-BN interface on the heat transfer of o-BN@SiC/EP composites. Phonon transmission in solders and phonon-phonon coupling of filler-solder interfaces enhanced the interfacial heat transfer between adjacent h-BN microplatelets, and the interfacial thermal resistance of the dominant BN-BN interface was decreased to only 3.83 nK·m2/W from 400 nK·m2/W, plunging by over 99%. This highly weakened interfacial thermal resistance greatly improved the heat transfer along thermal pathways and resulted in a 26% thermal conductivity enhancement of o-BN@SiC/EP composites, compared with physically contacted oriented h-BN/EP composites, at 15 vol % h-BN. This systematic multiscale simulation broke through the barrier of revealing the heat transfer mechanism of polymer composites from the nanoscale to the macroscale, which provided rational cognition about the effect of the interfacial thermal resistance between fillers on the thermal conductivity of polymer composites.

12.
Front Cardiovasc Med ; 10: 1153926, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37456815

RESUMO

Background: An accurate assessment of current trends in cardiovascular risks could inform public health policy. This study aims to determine 20-year trends in the prevalence of elevated cardiovascular risk and its risk factors' control among US adults. Methods: In this serial cross-sectional analysis of 23,594 adults, aged 40-79 years, without clinical atherosclerotic cardiovascular disease (ASCVD) in the National Health and Nutrition Examination Survey from 2001 to 2020, we calculated the prevalence of elevated cardiovascular risk (10-year ASCVD risk ≥ 7.5%) for all participants and subgroups with their risk factors controlled for diabetes, hypertension, or dyslipidemia. Results: The age- and sex-adjusted prevalence of elevated cardiovascular risk slightly decreased from 41.5% (95% CI, 39.7-43.3%) in 2001-2004 to 38.6% (95% CI, 36.1-41.1%) in 2017-2020 (P for trend = 0.169) while the respective sex-adjusted prevalence significantly increased from 34.4% (95% CI, 32.8-36.0%) to 39.5% (95% CI, 37.0-42.0%; P for trend <0.001). Sex and race continued to show disparities in cardiovascular risk. Furthermore, a worsening disparity in age- and sex-adjusted prevalence of elevated cardiovascular risk between young and old and a narrowing gap among different education and poverty index levels (all P trend for interaction <0.05). Differential decomposition analysis found that demographic changes (primarily population aging) led to an 8.8% increase in the prevalence of elevated cardiovascular risk from 2001 to 2004 to 2017-2020, while risk factor control led to a 3.8% decrease. The rate of individuals receiving treatment for diabetes, hypertension, or dyslipidemia increased significantly between 2001 and 2020 (all P for trend <0.05). The rate of participants with hypertension who achieved blood pressure under 130/80 mmHg and those with dyslipidemia who achieved a non-high-density lipoprotein cholesterol level under 130 mg/dl increased significantly (all P for trend <0.001). Conclusions: There is a slight reduction in the prevalence of age- and sex-adjusted elevated cardiovascular risk among US adults without clinical ASCVD between 2001 and 2020, while the sex-adjusted prevalence significantly increased. The decrease in elevated cardiovascular risk prevalence was mainly attributed to risk factor control, while demographic changes contributed to an increase.

13.
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.

14.
Arch Osteoporos ; 18(1): 67, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37169994

RESUMO

PURPOSE: Osteoporosis is a metabolic bone disease that commonly results in middle-aged and elderly people following fractures. Odanacatib (ODN), a potential osteoporosis medication, was stopped in the Long-term Odanacatib Fracture Trial (LOFT) phase III study because it increased the risk of stroke. Herein, we conducted a systematic review and meta-analysis to further assess the efficacy and safety of ODN in osteoporosis treatment. METHODS: We searched the PubMed, EMBASE, Cochrane Library, and Web of Science, using the core search terms "osteoporosis" and "odanacatib." The primary outcomes were the percentage change in markers of bone turnover and bone formation as well as that in the bone mineral density (BMD) of the lumbar spine, hip, femoral neck, and greater trochanter. The secondary outcome was the risk of adverse events (AEs), used to explore the safety of ODN. RESULTS: Ten articles-all double-blinded, randomized, placebo-controlled trials-were included. All trials were considered to be of high quality if they met the inclusion and exclusion criteria. We found that ODN increases BMD in the lumbar spine, total hip, and femoral neck, whereas it decreases the concentration of serum C-telopeptides of type I collagen (sCTx) and urinary N-telopeptide/creatinine ratio (uNTx/Cr). We found no significant differences in total, drug-related, serious, or skin AEs between the ODN and control groups. However, significant differences in fracture and stroke AEs were found between the ODN and control groups. CONCLUSION: ODN is an appealing long-term osteoporosis treatment method; however, further research should focus on the potential increased risk of fracture and stroke.


Assuntos
Conservadores da Densidade Óssea , Fraturas Ósseas , Osteoporose Pós-Menopausa , Osteoporose , Acidente Vascular Cerebral , Idoso , Feminino , Pessoa de Meia-Idade , Humanos , Conservadores da Densidade Óssea/efeitos adversos , Osteoporose Pós-Menopausa/tratamento farmacológico , Método Duplo-Cego , Osteoporose/complicações , Densidade Óssea , Fraturas Ósseas/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/complicações
15.
Front Bioeng Biotechnol ; 11: 1118468, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36777256

RESUMO

Tendon-bone insertion (TBI) injuries are common, primarily involving the rotator cuff (RC) and anterior cruciate ligament (ACL). At present, repair surgery and reconstructive surgery are the main treatments, and the main factor determining the curative effect of surgery is postoperative tendon-bone healing, which requires the stable combination of the transplanted tendon and the bone tunnel to ensure the stability of the joint. Fibrocartilage and bone formation are the main physiological processes in the bone marrow tract. Therefore, therapeutic measures conducive to these processes are likely to be applied clinically to promote tendon-bone healing. In recent years, biomaterials and compounds, stem cells, cell factors, platelet-rich plasma, exosomes, physical therapy, and other technologies have been widely used in the study of promoting tendon-bone healing. This review provides a comprehensive summary of strategies used to promote tendon-bone healing and analyses relevant preclinical and clinical studies. The potential application value of these strategies in promoting tendon-bone healing was also discussed.

16.
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
17.
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
18.
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
19.
J Colloid Interface Sci ; 629(Pt B): 12-21, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36150244

RESUMO

Photosynthesis by plants stores sunlight into chemicals and drives CO2 fixation into sugars with low biomass conversion efficiency due to the unoptimized solar spectrum utilization and various chemical conversion possibilities that follow H2O oxidation. Expanding the solar spectrum utilization and optimizing the charge transfer pathway of photosynthesis is critical to improving the conversion efficiency. Here, a group of carbon dots (CDs) with distinct content of sp2 CC domain are prepared by one-step carbonization of natural xylose, which penetrated natural chloroplasts and integrated with the grana thylakoid to promote in vitro photosynthesis. Structural characterization and electrochemical results reveal the positive impact of graphitization degree on the electron transport capacity of CDs. Classic Hill reaction and ATP production demonstrate the enhanced photosynthetic activity resulting from the CDs-mediated electron transfer of photosystem II. In-depth studies of the structure-function relationship prove the synergistic effect of intensified biotic-abiotic interaction between CDs and chloroplast, lower charge transfer resistance, and extended light absorption. This work posts a promising method to optimize electron transport and improve natural photosynthesis using artificial interventions.


Assuntos
Carbono , Xilose , Xilose/metabolismo , Carbono/metabolismo , Fotossíntese , Cloroplastos/metabolismo , Transporte de Elétrons
20.
Front Surg ; 9: 971030, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386510

RESUMO

Background: As neoadjuvant chemotherapy is widely used in breast cancer patients, the lymph node ratio has not been fully validated as a prognostic indicator of breast cancer received neoadjuvant chemotherapy. This study was conducted to investigate the prognostic value of lymph node ratio in breast cancer patients received neoadjuvant chemotherapy. Methods: Systematic searches were performed in the PubMed, Embase, and Cochrane Library databases until 15 December 2021 for studies on the association between lymph node ratio and the prognosis of breast cancer after neoadjuvant chemotherapy. Overall survival and disease-free survival were used as outcome events, and hazard ratio was chosen as the parameter to evaluate the correlation. The dose-response relationship was assessed by restricted cubic splines. In the subgroup analyses, which were used to explore potential heterogeneity among the included studies according to study region and sample size. Sensitivity analysis was performed to assess the stability of individual studies, and publication bias was determined with funnel plots, Begg's test, and Egger's test. All statistical analyses were performed using Stata 15.1. Results: A total of 12 studies with 4,864 patients were included in this meta-analysis. In this study, high lymph node ratio was significantly associated with decreased overall survival (HR: 4.74; 95%CI: 3.36-6.67; P < 0.001) and disease-free survival (HR: 4.77; 95%CI: 3.69-6.17; P < 0.001). Moreover, the dose-response meta-analysis showed a linear association between higher lymph node ratio and shorter overall survival and disease-free survival in breast cancer patients after neoadjuvant chemotherapy. Conclusions: The meta-analysis suggested that high lymph node ratio was significantly associated with short overall survival and disease-free survival in breast cancer patients after neoadjuvant chemotherapy. Therefore, lymph node ratio is an independent predictive factor for the prognosis of breast cancer patients after neoadjuvant chemotherapy, which may better refine the cancer staging system.

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