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1.
Bone ; 183: 117076, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38521235

RESUMO

The skeleton serves as a supportive and protective organ for the body. As individuals age, their bone tissue undergoes structural, cellular, and molecular changes, including the accumulation of senescent cells. Extracellular vesicles (EVs) play a crucial role in aging through the cellular secretome and have been found to induce or accelerate age-related dysfunction in bones and to contribute further via the circulatory system to the aging of phenotypes of other bodily systems. However, the extent of these effects and their underlying mechanisms remain unclear. Therefore, this paper attempts to give an overview of the current understanding of age-related alteration in EVs derived from bones. The role of EVs in mediating communications among bone-related cells and other body parts is discussed, and the significance of bones in the whole-body aging process is highlighted. Ultimately, it is hoped that gaining a clearer understanding of the relationship between EVs and aging mechanisms may serve as a basis for new treatment strategies for age-related degenerative diseases in the skeleton and other systems.


Assuntos
Senescência Celular , Vesículas Extracelulares , Humanos , Corpo Humano , Envelhecimento , Osso e Ossos
2.
Cancer Lett ; 588: 216809, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38471646

RESUMO

Human papillomavirus (HPV) is predominantly associated with HPV-related cancers, however, the precise mechanisms underlying the HPV-host epigenetic architectures in HPV carcinogenesis remain elusive. Here, we employed high-throughput chromosome conformation capture (Hi-C) to comprehensively map HPV16/18-host chromatin interactions. Our study identified the transcription factor Sp1 as a pivotal mediator in programming HPV-host interactions. By targeting Sp1, the active histone modifications (H3K27ac, H3K4me1, and H3K4me3) and the HPV-host chromatin interactions are reprogrammed, which leads to the downregulation of oncogenes located near the integration sites in both HPV (E6/E7) and the host genome (KLF5/MYC). Additionally, Sp1 inhibition led to the upregulation of immune checkpoint genes by reprogramming histone modifications in host cells. Notably, humanized patient-derived xenograft (PDX-HuHSC-NSG) models demonstrated that Sp1 inhibition promoted anti-PD-1 immunotherapy via remodeling the tumor immune microenvironment in cervical cancer. Moreover, single-cell transcriptomic analysis validated the enrichment of transcription factor Sp1 in epithelial cells of cervical cancer. In summary, our findings elucidate Sp1 as a key mediator involved in the programming and reprogramming of HPV-host epigenetic architecture. Inhibiting Sp1 with plicamycin may represent a promising therapeutic option for HPV-related carcinoma.


Assuntos
Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Cromatina/genética , Epigênese Genética , Papillomavirus Humano 16/metabolismo , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/metabolismo , Papillomavirus Humano , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/terapia , Fatores de Transcrição/genética , Microambiente Tumoral , Neoplasias do Colo do Útero/patologia
3.
Mol Ther ; 32(4): 1158-1177, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38332583

RESUMO

Osteoclast precursors (OCPs) are thought to commit to osteoclast differentiation, which is accelerated by aging-related chronic inflammation, thereby leading to osteoporosis. However, whether the fate of OCPs can be reshaped to transition into other cell lineages is unknown. Here, we showed that M2 macrophage-derived extracellular vesicles (M2-EVs) could reprogram OCPs to downregulate osteoclast-specific gene expression and convert OCPs to M2 macrophage-like lineage cells, which reshaped the fate of OCPs by delivering the molecular metabolite glutamate. Upon delivery of glutamate, glutamine metabolism in OCPs was markedly enhanced, resulting in the increased production of α-ketoglutarate (αKG), which participates in Jmjd3-dependent epigenetic reprogramming, causing M2-like macrophage differentiation. Thus, we revealed a novel transformation of OCPs into M2-like macrophages via M2-EVs-initiated metabolic reprogramming and epigenetic modification. Our findings suggest that M2-EVs can reestablish the balance between osteoclasts and M2 macrophages, alleviate the symptoms of bone loss, and constitute a new approach for bone-targeted therapy to treat osteoporosis.


Assuntos
Vesículas Extracelulares , Osteoporose , Humanos , Osteoclastos/metabolismo , Ácido Glutâmico/metabolismo , Macrófagos/metabolismo , Osteoporose/genética , Osteoporose/terapia , Osteoporose/metabolismo
4.
BMC Genomics ; 25(1): 198, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378450

RESUMO

BACKGROUND: Cervical cancer (CC) causes more than 311,000 deaths annually worldwide. The integration of human papillomavirus (HPV) is a crucial genetic event that contributes to cervical carcinogenesis. Despite HPV DNA integration is known to disrupt the genomic architecture of both the host and viral genomes in CC, the complexity of this process remains largely unexplored. RESULTS: In this study, we conducted whole-genome sequencing (WGS) at 55-65X coverage utilizing the PacBio long-read sequencing platform in SiHa and HeLa cells, followed by comprehensive analyses of the sequence data to elucidate the complexity of HPV integration. Firstly, our results demonstrated that PacBio long-read sequencing effectively identifies HPV integration breakpoints with comparable accuracy to targeted-capture Next-generation sequencing (NGS) methods. Secondly, we constructed detailed models of complex integrated genome structures that included both the HPV genome and nearby regions of the human genome by utilizing PacBio long-read WGS. Thirdly, our sequencing results revealed the occurrence of a wide variety of genome-wide structural variations (SVs) in SiHa and HeLa cells. Additionally, our analysis further revealed a potential correlation between changes in gene expression levels and SVs on chromosome 13 in the genome of SiHa cells. CONCLUSIONS: Using PacBio long-read sequencing, we have successfully constructed complex models illustrating HPV integrated genome structures in SiHa and HeLa cells. This accomplishment serves as a compelling demonstration of the valuable capabilities of long-read sequencing in detecting and characterizing HPV genomic integration structures within human cells. Furthermore, these findings offer critical insights into the complex process of HPV16 and HPV18 integration and their potential contribution to the development of cervical cancer.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/genética , Células HeLa , Infecções por Papillomavirus/genética , DNA , Genômica , Integração Viral/genética
5.
BJOG ; 131(3): 309-318, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37408516

RESUMO

OBJECTIVE: Human papillomavirus (HPV) integration is a crucial genetic step in cervical carcinogenesis. This study aimed to evaluate the performance of an HPV integration test for the triage of HPV-positive women. DESIGN: An observational cohort study. SETTING: A cervical cancer screening programme in China. POPULATION: 1393 HPV-positive women aged 25-65 years undergoing routine cervical cancer screening and HPV integration testing with 1-year follow-up. METHODS: The sensitivity, specificity, positive predictive value and negative predictive value between HPV integration and cytology were compared. MAIN OUTCOME MEASURES: Cervical intraepithelial neoplasia grade 3 or more severe (CIN3+). RESULTS: Among 1393 HPV-positive patients, 138 (9.9% [8.3-11.5%]) were HPV integration test positive compared with 537 who had abnormal cervical cytology (38.5% [36.0-41.1%]). Compared with cytology, HPV integration exhibited higher specificity (94.5% [93.3-95.8%] versus 63.8% [61.2-66.4%]) and equivalent sensitivity (70.5% [61.4-79.7%] versus 70.5% [61.4-79.7%]) for detection of CIN3+. HPV integration-negative women accounted for 90.1% (1255/1393) of the total population and had a low immediate CIN3+ risk (2.2%). At 1-year follow-up, the progression rate in the HPV integration-positive women was higher than in the HPV integration-negative women (12.0% versus 2.1%, odds ratio 5.6, 95% CI, 2.6-11.9). In 10 conservatively managed integration-negative CIN2 patients, all showed spontaneous regression and seven showed HPV clearance after 1-year follow-up. CONCLUSION: The HPV integration test may be a precise risk stratification tool for HPV-positive women and could avoid excessive use of invasive biopsies.


Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Gravidez , Neoplasias do Colo do Útero/patologia , DNA Viral , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Detecção Precoce de Câncer , Displasia do Colo do Útero/diagnóstico , Estudos de Coortes , Papillomaviridae/genética , Esfregaço Vaginal , Colposcopia
6.
Food Chem X ; 20: 100898, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-38144730

RESUMO

This study aimed to explore effects of indica rice addition, rice soaking time and rice soup addition on total sugar and alcohol content of semi-dry Hakka rice wine (HRW) and compare its difference in physicochemical properties and volatiles with traditional sweet rice wine (TSRW) via HPLC, GC-MS and E-tongue. The optimal fermentation conditions of semi-dry HRW were 50 % indica rice addition, 12 h rice soaking time and 85 % rice soup addition. The total sugar (16.13 mg/mL) of semi-dry HRW was significantly lower than that of TSRW (135.79 mg/mL), especially the trehalose, glucose, sucrose and maltose. Its alcohol content was significantly higher than that of TSRW. There were significant differences in volatile components between semi-dry HRW and TSRW, especially esters, alcohols and ketones, but no significant differences in organic acids and amino acids. Results obtained could provide reference data for improving the fermentation process and quality of semi-dry HRW.

7.
Mater Today Bio ; 23: 100845, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37942423

RESUMO

Combination immunotherapy of cancer vaccines with immune checkpoint inhibitors (ICIs) represents a promising therapeutic strategy for immunosuppressed and cold tumors. However, this strategy still faces challenges, including the limited therapeutic efficacy of cancer vaccines and immune-related adverse events associated with systematic delivery of ICIs. Herein, we demonstrate the antitumor immune response induced by outer membrane vesicle from Akkermansia muciniphila (Akk-OMV), which exhibites a favorable safety profile, highlighting the potential application as a natural and biocompatible self-adjuvanting vesicle. Utilizing tumor cell-derived exosome as an antigen source and Akk-OMV as a natural adjuvant, we construct a cancer vaccine formulation of extracellular vesicles hybrid lipid nanovesicles (Lipo@HEV) for enhanced prophylactic and therapeutic vaccination by promoting dendritic cell (DC) maturation in lymph node and activating cytotoxic T cell (CTL) response. The Lipo@HEV is further loaded with plasmid to enable gene therapy-mediated PD-L1 blockade upon peritumoral injection. Meanwhile, it penetrates into lymph node to initiate DC maturation and CTL activation, synergistically inhibiting the established tumor. The fabrication of extracellular vesicles hybrid plasmid-loaded lipid nanovesicles reveals a promising gene therapy-guided and vesicle-based hybrid system for therapeutic cancer vaccination and synergistic immunotherapy strategy.

8.
PLoS One ; 18(11): e0292875, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37939128

RESUMO

In recent years, the landscape ecological security of Xishuangbanna in southwest China has become an essential factor affecting the cross-border ecological security in South Asia and Southeast Asia. Based on the change of land use in Xishuangbanna, with the help of "3S" technology, landscape ecology theory, and gray prediction model, the spatial and developmental trends of landscape ecological security in Xishuangbanna from 1996-2030 could be determined. In more than 20 years, the woodland landscape area in Xishuangbanna decreased, and the fragmentation of construction land has increased overall. In 1996, the overall landscape ecological safety was good, with 63.5% of the total area of grade I and II. In 2003, the proportion of the grade I and grade II areas decreased, with landscape ecological security problems appearing. In 2010, the overall landscape ecological security area reached 74.5%, the largest proportion in more than 20 years. The grade V area accounted for only 9% and was mainly distributed on the border of Menghai County and central Jinghong City. In 2017, The grade IV and V areas was further increased, and the ecological security problem intensified. The prediction results showed that from 2023 to 2030, the regions of grades I and II increased, but the proportion of level V regions increased. Furthermore, the grade IV transformed to grade V rapidly, reaching its highest value in more than 20 years. From 1996 to 2030, the landscape ecological security space significantly evolved, showing an evident "east-south" trend in movement and eventually shifting to the southeast.


Assuntos
Conservação dos Recursos Naturais , Urbanização , Conservação dos Recursos Naturais/métodos , Florestas , China , Tecnologia , Ecossistema , Ecologia/métodos
9.
Gene ; 885: 147704, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37572797

RESUMO

The role of histone deacetylases (HDACs) in the tumor immune microenvironment of gynecologic tumors remains unexplored. We integrated data from The Cancer Genome Atlas and Human Protein Atlas to examine HDAC expression in breast, cervical, ovarian, and endometrial cancers. Elevated HDAC expression correlated with poor prognosis and highly malignant cancer subtypes. Gene Set Enrichment Analysis revealed positive associations between HDAC expression and tumor proliferation signature, while negative associations were found with tumor inflammation signature. Increased HDAC expression was linked to reduced infiltration of natural killer (NK), NKT, and CD8+ T cells, along with negative associations with the expression of PSMB10, NKG7, CCL5, CD27, HLA-DQA1, and HLA-DQB1. In a murine 4T1 breast cancer model, treatment with suberoylanilide hydroxamic acid (SAHA; HDAC inhibitor) and PD-1 antibody significantly inhibited tumor growth and infiltration of CD3+ and CD8+ T cells. Real-time polymerase chain reaction revealed upregulated expressions of Psmb10, Nkg7, Ccl5, Cd8a, Cxcr6, and Cxcl9 genes, while Ctnnb1 and Myc genes were inhibited, indicating tumor suppression and immune microenvironment activation. Our study revealed that HDACs play tumor-promoting and immunosuppressive roles in gynecologic cancers, suggesting HDAC inhibitors as potential therapeutic agents for these cancers.


Assuntos
Neoplasias dos Genitais Femininos , Histona Desacetilases , Feminino , Humanos , Animais , Camundongos , Histona Desacetilases/genética , Neoplasias dos Genitais Femininos/genética , Ácidos Hidroxâmicos/farmacologia , Linfócitos T CD8-Positivos/metabolismo , Vorinostat , Inibidores de Histona Desacetilases/farmacologia , Microambiente Tumoral/genética , Proteínas de Membrana , Complexo de Endopeptidases do Proteassoma
10.
Shock ; 60(2): 181-189, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37295017

RESUMO

ABSTRACT: Background: Circular RNAs (circRNAs) have been shown to mediate atherosclerosis (AS) process by regulating vascular smooth muscle cells (VSMCs) function. However, whether circ_0091822 mediates VSMCs function to regulate AS process is unclear. Methods: Oxidized low-density lipoprotein (ox-LDL) was used to treat VSMCs for constructing AS cell models. Vascular smooth muscle cells proliferation, invasion, and migration were examined by cell counting kit 8 assay, EdU assay, transwell assay, and wound healing assay. Protein expression was tested by western blot analysis. The expression of circ_0091822, microRNA (miR)-339-5p, and blocking of proliferation 1 (BOP1) was determined using quantitative real-time PCR. RNA interaction was examined using dual-luciferase reporter assay and RIP assay. Results: Ox-LDL treatment enhanced VSMCs proliferation, invasion, and migration. Circ_0091822 was overexpressed in the serum of AS patients and ox-LDL-induced VSMCs. Circ_0091822 knockdown inhibited ox-LDL-induced VSMCs proliferation, invasion, and migration. Circ_0091822 sponged miR-339-5p, and miR-339-5p inhibitor reversed the function of circ_0091822 knockdown. MiR-339-5p targeted BOP1, and BOP1 also reversed the repressing effect of miR-339-5p on ox-LDL-induced VSMCs functions. Circ_0091822/miR-339-5p/BOP1 axis promoted the activity of Wnt/ß-catenin pathway. Conclusions: Circ_0091822 might be a therapeutic target for AS, which facilitated ox-LDL-induced VSMCs proliferation, invasion, and migration through modulating miR-339-5p/BOP1/Wnt/ß-catenin pathway.


Assuntos
MicroRNAs , Músculo Liso Vascular , Humanos , beta Catenina , Lipoproteínas LDL/farmacologia , Miócitos de Músculo Liso , Proliferação de Células/genética , MicroRNAs/genética , Movimento Celular/genética , Apoptose , Células Cultivadas , Proteínas de Ligação a RNA
11.
Hum Vaccin Immunother ; 19(1): 2211896, 2023 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-37249318

RESUMO

This phase III clinical trial aimed to assess the safety and demonstrate the immunogenicity of a candidate freeze-dried purified Vero cell-based rabies vaccine (PVRV-WIBP) developed for human use. A cohort of 40 participants in stage 1 and 1956 subjects in stage 2 with an age range of 10-50 years were recruited for the phase III clinical trial. For safety analysis in stage 1, 20 participants received either 4-dose or 5-dose regimen of PVRV-WIBP. In stage 2, 1956 subjects were randomly divided into the 5-dose PVRV-WIBP, 5-dose PVRV-LNCD, and 4-dose PVRV-WIBP groups. The serum neutralizing antibody titer against rabies was determined on day 7 or 14 and day 35 or 42. Adverse reactions were recorded for more than 6 months. Most adverse reactions, which were mild and moderate in severity, occurred and resolved within 1 week after each injection in the PVRV-WIBP (4 and 5 doses) and PVRV-LNCD (5 doses) groups. All three groups achieved complete seroconversion 14 days after the initial dose and 14 days after completing the full vaccination schedule, the susceptible subjects in the PVRV-WIBP group (4-dose or 5-dose regimen) displayed higher neutralizing antibody titers against the rabies virus compared to those in the PVRV-LNCD group (5-dose regimen). PVRV-WIBP induced non-inferior immune responses versus PVRV-LNCD as assessed by seroconversion rate. PVRV-WIBP was well tolerated and non-inferior to PVRV-LNCD in healthy individuals aged 10-50 years. The results indicated that PVRV-WIBP (both 4- and 5-dose schedules) could be an alternative to rabies post-exposure prophylaxis.


Assuntos
Soropositividade para HIV , Vacina Antirrábica , Vírus da Raiva , Raiva , Animais , Chlorocebus aethiops , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Raiva/prevenção & controle , População do Leste Asiático , Anticorpos Antivirais , Anticorpos Neutralizantes , Células Vero , Imunogenicidade da Vacina
12.
Phys Rev Lett ; 130(18): 181001, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37204893

RESUMO

Dark photons can be the ultralight dark matter candidate, interacting with Standard Model particles via kinetic mixing. We propose to search for ultralight dark photon dark matter (DPDM) through the local absorption at different radio telescopes. The local DPDM can induce harmonic oscillations of electrons inside the antenna of radio telescopes. It leads to a monochromatic radio signal and can be recorded by telescope receivers. Using the observation data from the FAST telescope, the upper limit on the kinetic mixing can already reach 10^{-12} for DPDM oscillation frequencies at 1-1.5 GHz, which is stronger than the cosmic microwave background constraint by about one order of magnitude. Furthermore, large-scale interferometric arrays like LOFAR and SKA1 telescopes can achieve extraordinary sensitivities for direct DPDM search from 10 MHz to 10 GHz.

13.
EBioMedicine ; 92: 104612, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37224771

RESUMO

BACKGROUND: Cervical cancer is the fourth leading cause of mortality among gynecological malignancies. However, the identification of cervical cancer stem cells remains unclear. METHODS: We performed single-cell mRNA sequencing on ∼122,400 cells from 20 cervical biopsies, including 5 healthy controls, 4 high-grade intraepithelial neoplasias, 5 microinvasive carcinomas of the cervix, and 6 invasive cervical squamous carcinomas. Bioinformatic results were validated by multiplex immunohistochemistry (mIHC) in cervical cancer tissue microarrays (TMA) (n = 85). FINDINGS: We identified cervical cancer stem cells and highlighted the functional changes in cervical stem cells during malignant transformation. The original non-malignant stem cell properties (characterized by high proliferation) gradually diminished, whereas the tumor stem cell properties (characterized by epithelial-mesenchymal transformation and invasion) were enhanced. The mIHC results of our TMA cohort confirmed the existence of stem-like cells and indicated that cluster correlated with neoplastic recurrence. Subsequently, we investigated malignant and immune cell heterogeneity in the cervical multicellular ecosystem across different disease stages. We observed global upregulation of interferon responses in the cervical microenvironment during lesion progression. INTERPRETATION: Our results provide more insights into cervical premalignant and malignant lesion microenvironments. FUNDING: This research was supported by the Guangdong Provincial Natural Science Foundation of China (2023A1515010382), Grant 2021YFC2700603 from the National Key Research & Development Program of China and the Hubei Provincial Natural Science Foundation of China (2022CFB174 and 2022CFB893).


Assuntos
Carcinoma de Células Escamosas , Lesões Pré-Cancerosas , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Colo do Útero , Ecossistema , Transcriptoma , Recidiva Local de Neoplasia/patologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Carcinoma de Células Escamosas/genética , Células-Tronco Neoplásicas/patologia , Microambiente Tumoral/genética
14.
Food Chem ; 416: 135844, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36893639

RESUMO

The dynamics of physicochemical properties, microbial community and flavor metabolites during fermentation of two typical Hakka rice wine were investigated. Results showed that total sugar content was 136.83 g/L in sweet rice wine, which almost 8 times higher than that in semi-dry rice wine. Its amino acid contents especially bitterness amino acids were also higher than those in semi-dry rice wine. Most organic acids in Hakka rice wine had the tendency of increase in initial stage of fermentation, following a decrease and finally being almost stable. A total of 131 volatiles including esters, alcohols, aldehydes, acids, ketones were detected. Pediococcus, Bacillus, Acinetobacter, Pantoea, Enterobacter and Lactobacillus were the dominant bacterial genera and Monascus, Saccharomyces, Rhizopus were the dominant fungal genera, which are strongly associated with the significant changes in flavor metabolites during Hakka rice wine fermentation. The obtained findings provided reference data for the optimization of Hakka rice wine fermentation.


Assuntos
Microbiota , Oryza , Vinho , Vinho/análise , Fermentação , Oryza/química , Fungos/metabolismo , Aminoácidos/metabolismo
15.
Anal Chem ; 95(6): 3379-3389, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36735954

RESUMO

Timely identification of human papillomavirus (HPV) infection is crucial for the prevention of cervical cancer. Current HPV detection methods mainly rely on polymerase chain reaction (PCR), which often requires bulky equipment and a long assay time. In this work, we report a heating-membrane-assisted multiplexed microfluidics platform that couples recombinase polymerase amplification (RPA) and CRISPR technology (termed M3-CRISPR) for fast and low-cost detection of multiple HPV subtypes. The heating membrane can provide convenient temperature control for the on-chip RPA and CRISPR assays. This stand-alone system allows simultaneous detection of HPV16 and HPV18 with high specificity and detection sensitivity (0.5 nM and 1 × 10-18 M for unamplified and amplified plasmids, respectively) in 30 min with a fluorescence-based readout. Furthermore, we introduced an optimized lateral flow dipstick (LFD) into the portable system to allow visualized detection of HPV DNA. The LFD-based readout also reached a detection sensitivity of 1 × 10-18 M for amplified plasmids and realized successful detection of HPV subtypes in the clinical samples. Finally, we established an automatic microfluidic system that enables the sample-in-answer-out detection of HPV subtypes. We believe that this fast, convenient, and affordable molecular diagnostic platform can serve as a useful tool in point-of-care testing of HPV or other pathogens.


Assuntos
Infecções por Papillomavirus , Recombinases , Humanos , Recombinases/metabolismo , Técnicas de Amplificação de Ácido Nucleico/métodos , Microfluídica , Sensibilidade e Especificidade , Infecções por Papillomavirus/diagnóstico , Sistemas CRISPR-Cas/genética , Nucleotidiltransferases/genética , DNA Viral/genética
16.
Expert Rev Mol Med ; 25: e6, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36691778

RESUMO

Ovarian cancer is the most lethal female reproductive system tumour. Despite the great advances in surgery and systemic chemotherapy over the past two decades, almost all patients in stages III and IV relapse and develop resistance to chemotherapy after first-line treatment. Ovarian cancer has an extraordinarily complex immunosuppressive tumour microenvironment in which immune checkpoints negatively regulate T cells activation and weaken antitumour immune responses by delivering immunosuppressive signals. Therefore, inhibition of immune checkpoints can break down the state of immunosuppression. Indeed, Immune checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape of many solid tumours. However, ICIs have yielded modest benefits in ovarian cancer. Therefore, a more comprehensive understanding of the mechanistic basis of the immune checkpoints is needed to improve the efficacy of ICIs in ovarian cancer. In this review, we systematically introduce the mechanisms and expression of immune checkpoints in ovarian cancer. Moreover, this review summarises recent updates regarding ICI monotherapy or combined with other small-molecule-targeted agents in ovarian cancer.


Assuntos
Antineoplásicos , Neoplasias Ovarianas , Humanos , Feminino , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia , Recidiva Local de Neoplasia , Antineoplásicos/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Microambiente Tumoral
17.
J Pers Med ; 13(1)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36675811

RESUMO

N6-methyladenosine (m6A) modulates RNA metabolism and functions in cell differentiation, tissue development, and immune response. After acute burns, skin wounds are highly susceptible to infection and poor healing. However, our understanding of the effect of burn injuries on m6A methylation and their potential mechanism is still limited. Human m6A-mRNA&lncRNA Epitranscriptomic microarray was used to obtain comprehensive mRNA and lncRNA transcriptome m6A profiling and gene expression patterns after burn injuries in human skin tissue. Bioinformatic and functional analyses were conducted to find molecular functions. Microarray profiling showed that 65 mRNAs and 39 lncRNAs were significantly hypermethylated; 5492 mRNAs and 754 lncRNAs were significantly hypomethylated. Notably, 3989 hypomethylated mRNAs were down-expressed and inhibited many wound healing biological processes and pathways including in the protein catabolic process and supramolecular fiber organization pathway; 39 hypermethylated mRNAs were up-expressed and influenced the cell surface receptor signaling pathway and inflammatory response. Moreover, we validated that m6A regulators (METTL14, METTL16, ALKBH5, FMR1, and HNRNPC) were significantly downregulated after burn injury which may be responsible for the alteration of m6A modification and gene expression. In summary, we found that homeostasis in the skin was disrupted and m6A modification may be a potential mechanism affecting trauma infection and wound healing.

18.
Sci Total Environ ; 869: 161782, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36702273

RESUMO

Wildfires directly affect global ecosystem stability and severely threaten human life. The mountainous areas of Southwest China experience frequent wildfires. Mapping the susceptibility patterns and analyzing the drivers of wildfires are crucial for effective wildfire management, especially considering that the inclusion of seasonal dimensions will produce more dynamic results. Using Yunnan Province of China as a case study area, a method was attempted to distinguish dependable wildfires by season, while possible wildfire drivers were obtained and refined within seasons. The patterns of wildfire susceptibility in different seasons were modeled based on the Maxent and random forest models. Then, the spatial relationships between wildfire and potential drivers were analyzed integrating with GeoDetector to evaluate the variable importance of drivers and the marginal effect of drivers. The results showed that the two models effectively depicted each season's wildfire susceptibility. The susceptible wildfire areas in spring and winter are located throughout Yunnan Province, with anthropogenic factors being the most significant drivers. During the summer and autumn, wildfire risk areas are relatively concentrated, showing a trend of dominant drought-driven and humid conditions. The differences in wildfire drivers across seasons reflect the lagged effect of climate factors on wildfires, leading to significant discrepancies in the marginal effects of how seasonal drivers affect wildfires. The findings improve our understanding of the effects of the interseasonal variability of environmental variables on wildfires and promote the development of specific seasonal wildfire management strategies.

20.
Phys Rev Lett ; 129(23): 231101, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36563204

RESUMO

For the newly discovered W-boson mass anomaly, one of the simplest dark matter (DM) models that can account for the anomaly without violating other astrophysical and experimental constraints is the inert two Higgs doublet model, in which the DM mass (m_{S}) is found to be within ∼54-74 GeV. In this model, the annihilation of DM via SS→bb[over ¯] and SS→WW^{*} would produce antiprotons and gamma rays, and may account for the excesses identified previously in both particles. Motivated by this, we reanalyze the AMS-02 antiproton and Fermi-LAT Galactic center γ-ray data. For the antiproton analysis, the novel treatment is the inclusion of the charge-sign-dependent three-dimensional solar modulation model as constrained by the time-dependent proton data. We find that the excess of antiprotons is more distinct than previous results based on the force-field solar modulation model. The interpretation of this excess as the annihilation of SS→WW^{*} (SS→bb[over ¯]) requires a DM mass of ∼40-80 (40-60) GeV and a velocity-averaged cross section of O(10^{-26}) cm^{3} s^{-1}. As for the γ-ray data analysis, besides adopting the widely used spatial template fitting, we employ an orthogonal approach with a data-driven spectral template analysis. The fitting to the GeV γ-ray excess yields DM model parameters overlapped with those to fit the antiproton excess via the WW^{*} channel. The consistency of the DM particle properties required to account for the W-boson mass anomaly, the GeV antiproton excess, and the GeV γ-ray excess suggests a common origin of them.

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