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1.
Adv Mater ; : e2402000, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738693

RESUMO

The disparity between growth substrates and application-specific substrates can be mediated by reliable graphene transfer, the lack of which currently strongly hinders the graphene applications. Conventionally, the removal of soft polymers, that support the graphene during the transfer, would contaminate graphene surface, produce cracks, and leave unprotected graphene surface sensitive to airborne contaminations. In this work, it is found that polyacrylonitrile (PAN) can function as polymer medium for transferring wafer-size graphene, and encapsulating layer to deliver high-performance graphene devices. Therefore, PAN, that is compatible with device fabrication, does not need to be removed for subsequent applications. The crack-free transfer of 4 in. graphene onto SiO2/Si wafers, and the wafer-scale fabrication of graphene-based field-effect transistor arrays with no observed clear doping, uniformly high carrier mobility (≈11 000 cm2 V-1 s-1), and long-term stability at room temperature, are achieved. This work presents new concept for designing the transfer process of 2D materials, in which multifunctional polymer can be retained, and offers a reliable method for fabricating wafer-scale devices of 2D materials with outstanding performance.

2.
Nat Genet ; 56(4): 637-651, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38565644

RESUMO

Endometrial carcinoma remains a public health concern with a growing incidence, particularly in younger women. Preserving fertility is a crucial consideration in the management of early-onset endometrioid endometrial carcinoma (EEEC), particularly in patients under 40 who maintain both reproductive desire and capacity. To illuminate the molecular characteristics of EEEC, we undertook a large-scale multi-omics study of 215 patients with endometrial carcinoma, including 81 with EEEC. We reveal an unexpected association between exposome-related mutational signature and EEEC, characterized by specific CTNNB1 and SIGLEC10 hotspot mutations and disruption of downstream pathways. Interestingly, SIGLEC10Q144K mutation in EEECs resulted in aberrant SIGLEC-10 protein expression and promoted progestin resistance by interacting with estrogen receptor alpha. We also identified potential protein biomarkers for progestin response in fertility-sparing treatment for EEEC. Collectively, our study establishes a proteogenomic resource of EEECs, uncovering the interactions between exposome and genomic susceptibilities that contribute to the development of primary prevention and early detection strategies for EEECs.


Assuntos
Carcinoma Endometrioide , Hiperplasia Endometrial , Neoplasias do Endométrio , Preservação da Fertilidade , Proteogenômica , Humanos , Feminino , Progestinas/uso terapêutico , Antineoplásicos Hormonais , Hiperplasia Endometrial/tratamento farmacológico , Preservação da Fertilidade/métodos , Estudos Retrospectivos , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia
3.
Nanoscale ; 16(16): 7862-7873, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38568087

RESUMO

Recent years have witnessed advances in chemical vapor deposition growth of graphene films on metal foils with fine scalability and thickness controllability. However, challenges for obtaining wrinkle-free, defect-free and large-area uniformity remain to be tackled. In addition, the real commercial applications of graphene films still require industrially compatible transfer techniques with reliable performance of transferred graphene, excellent production capacity, and suitable cost. Transferred graphene films, particularly with a large area, still suffer from the presence of transfer-related cracks, wrinkles and contaminants, which would strongly deteriorate the quality and uniformity of transferred graphene films. Potential applications of graphene films include moisture barrier films, transparent conductive films, electromagnetic shielding films, and optical communications; such applications call different requirements for the performance of transferred graphene, which, in turn, determine the suitable transfer techniques. Besides the reliable transfer process, automatic machines should be well developed for the future batch transfer of graphene films, ensuring the repeatability and scalability. This mini-review provides a summary of recent advances in the transfer of graphene films and offers a perspective for future directions of transfer techniques that are compatible for industrial batch transfer.

4.
Vet Microbiol ; 290: 110002, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38295489

RESUMO

African swine fever has caused substantial economic losses to China`s pig industry in recent years. Currently, the highly pathogenic African swine fever virus strain of genotype II is predominantly circulating in China, accompanied by a series of emerging isolates displaying unique genetic variations. The pathogenicity of these emerging strains is still unclear. Recently, a novel ASFV strain with a distinguishable three-large-fragment gene deletion was obtained from the field specimens, and its in vivo pathogenicity and transmission were evaluated in this study. The animal experiment involved inoculating a high dose of YNFN202103 and comparing its effects with those of the highly pathogenic strain GZ201801_2. Results showed that pigs infected by YNFN202103 exhibited significantly prolonged onset and survival time, lower viremia levels, and less severe histopathological lesions compared to GZ201801_2. These findings contributed valuable insights into the pathogenicity and transmission of ASFV and its prevention and eradication strategies in practical settings.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Doenças dos Suínos , Suínos , Animais , Vírus da Febre Suína Africana/genética , Virulência/genética , Deleção de Genes , China , Doenças dos Suínos/genética
5.
Haematologica ; 109(4): 1184-1193, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37646659

RESUMO

Therapies that demonstrate durable, long-term responses with manageable safety and tolerability are needed for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Loncastuximab tesirine (loncastuximab tesirine-lpyl [Lonca]), an anti-CD19 antibody conjugated to a potent pyrrolobenzodiazepine dimer, demonstrated single-agent antitumor activity in the pivotal phase II LOTIS-2 study in heavily pretreated patients with R/R DLBCL. Here we present updated efficacy and safety analyses from LOTIS-2, performed for all patients and in subsets of patients with a complete response (CR), including patients with CR who were event-free (no progressive disease or death) for ≥1 year and ≥2 years from cycle 1, day 1 of treatment. Lonca was administered every 3 weeks (0.15 mg/kg for 2 cycles; 0.075 mg/kg for subsequent cycles). As of the final data cutoff (September 15, 2022; median follow-up: 7.8 months [range, 0.3-42.6]), 70 of 145 (48.3%) patients achieved an overall response. Thirty-six (24.8%) patients achieved CR, of which 16 (44%) and 11 (31%) were event-free for ≥1 year and ≥2 years, respectively. In the all-treated population, the median overall survival was 9.5 months; the median progression-free survival was 4.9 months. Among patients with CR, median overall survival and progression-free survival were not reached, with 24-month overall and progression-free survival rates of 68.2% (95% CI: 50.0-81.0) and 72.5% (95% CI: 48.2-86.8), respectively. No new safety concerns were detected. With additional follow-up, Lonca continued to demonstrate durable, long-term responses with manageable safety and tolerability in patients with CR (clinicaltrials gov. Identifier: NCT03589469).


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Anticorpos Monoclonais Humanizados , Benzodiazepinas , Linfoma Difuso de Grandes Células B/patologia
7.
Front Oncol ; 13: 1282356, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023131

RESUMO

Background: The molecular classification of endometrial cancer has previously been shown to be associated with clinical outcomes. However, there are insufficient data to support the routine use of molecular classification for the treatment of patients seeking fertility preservation. Methods: Here, we retrospectively investigated 90 patients received fertility-sparing treatment. We used a next generation sequencing (NGS) panel to classify these patients into four subtypes. All patients received hormonal therapy combined with hysteroscopy. Therapeutic effects were evaluated by hysteroscopy every three months during the treatment. Results: Patients with POLE mutations had the highest disease progression rate (50.0%, P=0.013), while the microsatellite instability-high (MSI-H) group had the highest recurrence rate (50.0%, P=0.042). PIK3CA mutation (hazard ratio (HR): 0.61; 95% confidence interval (CI): 0.37-0.99; P=0.046), overweight (HR: 0.56; 95% CI: 0.32-0.96; P=0.033) and obesity (HR: 0.44; 95% CI: 0.20-0.95; P=0.036) were associated with a significantly lower cumulative complete response (CR) rate. The combination of gonadotropin-releasing hormone analogues (GnRH-a) and letrozole (HR: 3.43; 95% CI: 1.81-6.52; P< 0.001) was associated with a significantly higher cumulative CR rate. KRAS mutation was significantly associated with disease progression (P=0.002). In wild-type TP53 patients, PTEN and PIK3CA mutations significantly prolonged the duration of treatment to achieve CR (log rank P=0.034; P=0.018). Conclusion: The implementation of molecular classification for EC patients undergoing fertility-sparing treatment is promising and can facilitate the selection of appropriate medical regimes to achieve better outcomes in patients with EC who require fertility preservation treatment.

8.
Virus Evol ; 9(2): vead060, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37868933

RESUMO

Since 2018, the outbreaks of genotype II African swine fever virus (ASFV) in China and several eastern Asian countries have caused a huge impact on the local swine industry, resulting in huge economic losses. However, little is known about the origin, genomic diversity, evolutionary features, and epidemiological history of the genotype II ASFV. Here, 14 high-quality complete genomes of ASFVs were generated via sequencing of samples collected from China over the course of 3 years, followed by phylogenetic and phylodynamic analyses. The strains identified were relatively homogeneous, with a total of 52 SNPs and 11 indels compared with the prototype strain HLJ/2018, among which there were four exceptionally large deletions (620-18,023 nt). Evolutionary analyses revealed that ASFV strains distributed in eastern Asia formed a monophyly and a 'star-like' structure centered around the prototype strain, suggesting a single origin. Additionally, phylogenetic network analysis and ancestral reconstruction of geographic state indicated that genotype II ASFV strains in eastern Asia likely originated from Western Europe. Overall, these results contribute to the understanding of the history and current status of genotype II ASFV strains in eastern Asian, which could be of considerable importance in disease control and prevention.

9.
Biomater Sci ; 11(20): 6894-6905, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37650600

RESUMO

The application of hybrid nanocarriers is expected to play an active role in improving treatment of chemotherapy and phototherapy. Herein, a nanohybrid with a core of mesoporous silica nanorods and shell of folate-functionalized zeolite imidazole framework (ZIF-8/FA) was synthesized via polydopamine (PDA)-mediated integration. A chemotherapeutic drug (DOX), bubble generator (NH4HCO3, ABC), and photosensitive agent (ICG) were simultaneously loaded into the delivery system to construct smart ZIF-8/FA-coated mesoporous silica nanorods (IDa-PRMSs@ZF). We found that ICG endowed the designed delivery system with a moderate photothermal conversion efficiency of 26.06% and the capacity to release 1O2. The produced hyperthermia caused ABC to decompose and further generate carbon dioxide bubbles, thereby facilitating DOX release, sequentially. Importantly, the underlying mechanism was also investigated using mathematical kinetic modeling. The tumor inhibition rate of IDa-PRMSs@ZF under NIR irradiation reached 83.8%. This study provides a promising strategy based on rod-shaped nanohybrids for effective combination antitumor therapy.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Humanos , Oxigênio Singlete , Dióxido de Carbono , Doxorrubicina/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Dióxido de Silício/uso terapêutico , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral
10.
Gynecol Oncol ; 174: 133-141, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37182434

RESUMO

OBJECTIVE: To compare the effects of levonorgestrel-intrauterine system (LNG-IUS) with or without oral megestrol acetate (MA) versus MA alone on fertility-preserving treatment in patients with atypical endometrial hyperplasia (AEH). METHODS: This was a single-center phase II study with an open-label, randomized, controlled trial conducted between July 2017 and June 2020 at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. A total of 180 patients (18-45 years) with primary AEH were randomly assigned (1:1:1) to the MA (N = 60), LNG-IUS (N = 60), or MA + LNG-IUS (N = 60) groups, in which the patients received MA (160 mg orally daily), LNG-IUS, or MA + LNG-IUS (MA 160 mg orally daily plus LNG-IUS), respectively. The primary endpoint was complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were CR rate at 32 weeks of treatment, adverse events, and recurrence and pregnancy rates. All analyses were conducted in a modified intention to treat (ITT) population who underwent randomization and in whom treatment was initiated. RESULTS: The Kaplan-Meier estimate of 16-week CR rates (with 95% confidence interval) were 19.2% (9.0-29.4%) in the MA group, 35.0% (22.8-47.2%) in the LNG-IUS group, and 29.4% (17.2-41.6%) in the MA + LNG-IUS groups. Side effects such as weight gain, increased nocturnal urine, night sweat, insomnia and edema face seemed to occur less frequently in LNG-IUS group compared with MA group. No difference was found among groups regarding second endpoints. CONCLUSIONS: LNG-IUS or LNG-IUS plus MA did not show significant therapeutic benefit compared with MA alone. Further studies including sufficient sample-size are needed to validate these findings due to the underpowered design of this trial. FUNDING: This study was supported by the National Key Research and Development Program of China (Grant No 2019YFC1005200 and 2019YFC1005204), Shanghai Medical Centre of Key Programs for Female Reproductive Diseases (Grant No. 2017ZZ010616), Shanghai sailing program (Grant No. 19YF1404200), and Shen Kang clinical project (SHDC22021219). Trial registrationClinicalTrials.govNCT03241888. https://www. CLINICALTRIALS: gov/ct2/show/NCT03241888?term=NCT03241888&draw=2&rank=1.


Assuntos
Hiperplasia Endometrial , Dispositivos Intrauterinos Medicados , Gravidez , Humanos , Feminino , Levanogestrel , Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/complicações , Acetato de Megestrol/efeitos adversos , Estudos Prospectivos , China , Fertilidade
11.
Medicine (Baltimore) ; 102(14): e33378, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37026950

RESUMO

RATIONALE: Pegylated interferon-alpha (PEG-IFN-α) is available for the treatment of hepatitis B virus infection, which is better than interferon-alpha (IFN-α) for the inhibition of hepatitis B virus replication. Ischemic colitis has been described from non-pegylated IFN-α, which occurs mainly in patients with hepatitis C virus infection. This is the first case of ischemic colitis during pegylated IFN-α monotherapy for chronic hepatitis B. PATIENT CONCERNS: A 35-year-old Chinese man presented with complaints of acute lower abdominal pain and haematochezia, who was receiving PEG-IFN-α-2a monotherapy for chronic hepatitis B. DIAGNOSES: Colonoscopy revealed scattered ulcers and severe mucosal inflammation with edema in the left hemi colon and necrotizing changes in the descending portion. Biopsies revealed focal mucosal chronic inflammation and mucosal erosion. Therefore, the patient was diagnosed with ischemic colitis based on clinical and testing results. INTERVENTIONS: PEG-IFN-α therapy was discontinued and switched to symptomatic management. OUTCOMES: The patient was discharged from the hospital after recovery. Follow-up colonoscopy revealed normal. The temporal association between the resolution of ischemic colitis and cessation of PEG-IFN-α treatment strongly favors the diagnosis of interferon-induced ischemic colitis. LESSONS: Ischaemic colitis is a severe emergency complication of interferon therapy. Physicians should consider this complication in any patient taking PEG-IFN-α who develops abdominal discomfort and hematochezia.


Assuntos
Colite Isquêmica , Hepatite B Crônica , Masculino , Humanos , Adulto , Antivirais/efeitos adversos , Colite Isquêmica/induzido quimicamente , Colite Isquêmica/diagnóstico , Colite Isquêmica/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Interferon alfa-2/uso terapêutico , Quimioterapia Combinada , Interferon-alfa/efeitos adversos , Vírus da Hepatite B , Polietilenoglicóis/efeitos adversos , Hemorragia Gastrointestinal/tratamento farmacológico , Inflamação/tratamento farmacológico , Proteínas Recombinantes/efeitos adversos , Resultado do Tratamento
12.
J Gynecol Oncol ; 34(1): e32, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36562136

RESUMO

OBJECTIVE: To evaluate the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) plus oral megestrol acetate (MA) as fertility-preserving treatment in patients with early-stage endometrial cancer (EEC). METHODS: In this single-center, phase II study with open-label, randomized and controlled design, young patients (18-45 years) diagnosed with primary EEC were screened, who strongly required fertility-preserving treatment. Patients were randomly assigned (1:1) into MA group (160 mg oral daily) or MA (160 mg oral daily) plus LNG-IUS group. Pathologic evaluation on endometrium retrieved by hysteroscopy was performed every 3 months. The primary endpoint was complete response (CR) rate within 16 weeks of treatment. The secondary endpoints were CR rate within 32 weeks of treatment, adverse events, recurrent and pregnancy rate. RESULTS: Between July 2017 and June 2020, 63 patients were enrolled and randomly assigned. Totally 56 patients (26 in MA group; 28 in MA + LNG-IUS group) were included into primary-endpoint analyses. The median follow-up was 31.6 months (range, 3.1-94.0). No significant difference in 16-week CR rate were found between MA and MA + LNG-IUS groups (19.2% vs. 25.0%, p=0.610; odds ratio=1.40; 95% confidence interval=0.38-5.12), while the 32-week CR rates were also similar (57.1% and 61.5%, p=0.743), accordingly. More women in MA + LNG-IUS group experienced vaginal hemorrhage (46.4% vs. 16.1%; p=0.012) compared with MA group. No intergroup difference was found regarding recurrence or pregnancy rate. CONCLUSION: Compared with MA alone, the addition of LNG-IUS may not improve the early CR rate for EEC, and may produce more adverse events instead. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03241914.


Assuntos
Neoplasias do Endométrio , Levanogestrel , Humanos , Feminino , Levanogestrel/efeitos adversos , Acetato de Megestrol , Estudos Prospectivos , Endométrio , Neoplasias do Endométrio/tratamento farmacológico
13.
Front Microbiol ; 13: 980862, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246286

RESUMO

Senecavirus A (SVA) is a member of the genus Senecavirus in the family Picornaviridae that infects pigs and shows symptoms similar to foot and mouth diseases and other vesicular diseases. It is difficult to prevent, thus, causing tremendous economic loss to the pig industry. However, the global transmission routes of SVA and its natural origins remain unclear. In this study, we processed representative SVA sequences from the GenBank database along with 10 newly isolated SVA strains from the field samples collected from our lab to explore the origins, population characteristics, and transmission patterns of SVA. The SVA strains were firstly systematically divided into eight clades including Clade I-VII and Clade Ancestor based on the maximum likelihood phylogenetic inference. Phylogeographic and phylodynamics analysis within the Bayesian statistical framework revealed that SVA originated in the United States in the 1980s and afterward spread to different countries and regions. Our analysis of viral transmission routes also revealed its historical spread from the United States and the risk of the global virus prevalence. Overall, our study provided a comprehensive assessment of the phylogenetic characteristics, origins, history, and geographical evolution of SVA on a global scale, unlocking insights into developing efficient disease management strategies.

14.
Front Vet Sci ; 9: 978243, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061106

RESUMO

African swine fever (ASF) outbreak have caused tremendous economic loss to the pig industry in China since its emergence in August 2018. Previous studies revealed that many published sequences are not suitable for detailed analyses due to the lack of data regarding quality parameters and methodology, and outdated annotations. Thus, high-quality genomes of highly pathogenic strains that can be used as references for early Chinese ASF outbreaks are still lacking, and little is known about the features of intra-host variants of ASF virus (ASFV). In this study, a full genome sequencing of clinical samples from the first ASF outbreak in Guangdong in 2018 was performed using MGI (MGI Tech Co., Ltd., Shenzhen, China) and Nanopore sequencing platforms, followed by Sanger sequencing to verify the variations. With 22 sequencing corrections, we obtained a high-quality genome of one of the earliest virulent isolates, GZ201801_2. After proofreading, we improved (add or modify) the annotations of this isolate using the whole genome alignment with Georgia 2007/1. Based on the complete genome sequence, we constructed the methylation profiles of early ASFV strains in China and predicted the potential 5mC and 6mA methylation sites, which are likely involved in metabolism, transcription, and replication. Additionally, the intra-host single nucleotide variant distribution and mutant allele frequency in the clinical samples of early strain were determined for the first time and found a strong preference for A and T substitution mutation, non-synonymous mutations, and mutations that resulted in amino acid substitutions into Lysine. In conclusion, this study provides a high-quality genome sequence, updated genome annotation, methylation profile, and mutation spectrum of early ASFV strains in China, thereby providing a reference basis for further studies on the evolution, transmission, and virulence of ASFV.

15.
Microbiol Spectr ; 10(5): e0215522, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36000903

RESUMO

We reported a novel African swine fever virus (ASFV) strain that had a three-large-fragment deletion and unique variations in genome. This isolate displayed a nonhemadsorbing phenotype and had homogeneous proliferation compared with the wild-type ASFV strain. Our findings highlighted the urgent need for further investigation of ASFV variations in China. IMPORTANCE African swine fever virus (ASFV) has been circulating in China for 5 years, and low virulent strains with changes in the genome have been reported. Nevertheless, there is still a lack of knowledge about the epidemic strains at the whole-genome level. This study reported a novel strain and further analyzed its genomic and biological characteristics. In addition, our study also suggests that whole-genome sequencing plays a key role in the epidemiology investigation of ASFV variations.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Suínos , Animais , Vírus da Febre Suína Africana/genética , Febre Suína Africana/epidemiologia , Proteínas Virais/genética , Virulência , Fenótipo
17.
Front Vet Sci ; 9: 921907, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35836498

RESUMO

To date, there is no effective vaccine or antiviral therapy available to prevent or treat African swine fever virus (ASFV) infections. ASFV gene deletion strains have been proposed as promising anti-ASFV vaccine candidates. In recent years, most ASFV gene deletion strains worldwide have been recombinant strains expressing EGFP or mCherry as markers. Therefore, in this study, a new triplex real-time PCR (RT-PCR) method was established for the broad and accurate differentiation of ASFV wild-type vs. gene deletion strains. We designed three pairs of primers and probes to target B646L, EGFP, and mCherry, and RT-PCR was used to detect these three genes simultaneously. The detection method prevented non-specific amplification of porcine reproductive and respiratory syndrome virus, porcine epidemic diarrhea virus, circovirus type 2, pseudorabies virus, and classical swine fever virus genes. The minimum copy number of standard plasmid DNA detected using triplex RT-PCR was 9.49, 15.60, and 9.60 copies for B646L, EGFP, and mCherry, respectively. Importantly, of the 1646 samples analyzed in this study, 67 were positive for ASFV, all corresponding to the wild-type virus. Overall, our data show that the triplex RT-PCR method established in this study can specifically identify both ASFV wild-type and gene deletion strains.

18.
Transbound Emerg Dis ; 69(5): e2530-e2540, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35569128

RESUMO

The Porcine reproductive and respiratory syndrome virus (PRRSV), a single (+) RNA virus, is characterized by high genome variability and constant evolution. Owing to increasingly complex mutations, there is a growing difficulty in accessing the whole genome. Additionally, there is limited knowledge on PRRSV intra-host nucleotide variants, which may reflect the complex viral-host dynamics. Here, we performed next-generation sequencing on four clinical lung tissues to reveal the genomic diversity and highlight virus-host interactions. The complete genomes of the HN0713 and GDYJ1224 strains shared 90.7% and 91.3% homology with the lineage 1 strain NADC30, respectively, while the GDGZ0408 and GDHY0425 strains shared 92.0% and 91.6% homology with the JXA1 strain, respectively. Recombination analysis showed that the ORF5-7 genes of the GDGZ0408 and GDHY0425 strains, whose complete genomes belong to lineage 8.7 based on the phylogenetic tree, are both recombined with lineage 3 strains. Furthermore, nsp3, nsp10-12, ORF2 genes and a part of the 3'-UTR of the GDHY0425 strain were provided by the lineage 5.1 strain. Two lineage 1 strains (GDYJ1224 and HN0713) were produced by a recombination of lineages 8.7 and 1. Additionally, the lineage 3 strain was associated with the recombinant HN0713 strain. We determined the intra-host single nucleotide variant frequencies and found more than 200 sites at a frequency of >1% in all samples. GDGZ0408 with parts of the nsp9 and nsp10 genes of HP-PRRSV lineage 8.7 presented more genetically diverse populations than others, indicating that lineage 8.7 might drive robust intra-host single nucleotide variants (iSNVs). Moreover, in the iSNV pools, nsp2 and ORF2a presented the highest mutation dynamic. Overall, this study provided evidence for the alarmingly increasing recombination and ever-changing evolutionary dynamics of PRRSV, and revealed the potential causes of vaccine escape, providing a novel insight into the nucleotide variant population in clinical samples.


Assuntos
Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Doenças dos Suínos , Animais , China/epidemiologia , Variação Genética , Genoma Viral/genética , Genômica , Nucleotídeos , Filogenia , Síndrome Respiratória e Reprodutiva Suína/epidemiologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Recombinação Genética , Suínos , Sequenciamento Completo do Genoma/veterinária
19.
Cancer Gene Ther ; 29(10): 1452-1462, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35388173

RESUMO

Progestin is one of the main hormone treatment regimens for early-stage estrogen receptor- and progesterone receptor (PR)-positive endometrial cancer (EC). However, the response rate of EC to progestins is unsatisfactory. Investigating the mechanisms related to progestin treatment could help improve treatment efficacy. Studies have demonstrated that normal endometrial stromal cells (ESCs) increase the inhibitory effect of progestin on EC cell proliferation via paracrine signaling, but the mechanisms involved remain unclear. In this study, we found that ESCs had different morphological features between progestin-sensitive and -insensitive EC tissues. ESCs presented typical decidualization changes in progestin-sensitive cases, while they remained slim in progestin-insensitive EC lesions, indicating no response. Furthermore, ESCs enhanced the inhibitory effect of medroxyprogesterone acetate (MPA) on EC cell proliferation by secreting neuron cell adhesion molecule (NrCAM). MPA treatment enhanced NrCAM secretion by ESCs. EC xenografts in BALB/C nude mice demonstrated that MPA combined with NrCAM had an increased tumor inhibitory effect compared with MPA or NrCAM alone. Mechanistically, MPA upregulated NrCAM expression in ESCs through PR. Specifically, NrCAM increased PR expression in EC cells through TET1-induced hydroxymethylation of the PRB gene promoter region. These findings indicate that NrCAM or NrCAM combined with progestins could be a new EC treatment.


Assuntos
Neoplasias do Endométrio , Progestinas , Animais , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/farmacologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Endométrio , Epigênese Genética , Feminino , Humanos , Acetato de Medroxiprogesterona/metabolismo , Acetato de Medroxiprogesterona/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Oxigenases de Função Mista/genética , Progestinas/metabolismo , Progestinas/farmacologia , Proteínas Proto-Oncogênicas/genética , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Células Estromais/metabolismo , Células Estromais/patologia
20.
Transbound Emerg Dis ; 69(5): e2291-e2301, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35478381

RESUMO

In August 2019, lumpy skin disease occurred for the first time in Xinjiang, China, and then quickly spread to many provinces in China. Here, the virus was isolated from the skin scabs of affected cattle during June 2020 in Guangdong, China. Virus isolation, transmission electron microscopy and polymerase chain reaction identified lumpy skin disease virus (LSDV) in the skin crusts of sick cattle. For the isolation of LSDV, the most sensitive cell line is primary cattle testicular (PCT) cells, while Vero cells cannot be used for the isolation of LSDV. In addition, we evaluated the growth characteristics of LSDV in vitro. Compared with MDBK and Vero cells, LSDV produced higher virus titters in PCT cells at 72 h. Phylogenetic analysis based on second-generation sequencing of the LSDV whole genome showed that the isolated virus (LSDV/MZGD/2020) is closely related to Asian strains and formed a new branch. LSDV/MZGD/2020 is also a vaccine recombinant strain that is distinct from the recombinant strain found in Russia. Through Recombination Detection Program (RDP), Simplot and phylogenetic analyses, strong evidence for recombination events was found in Chinese field LSDV strains. The China LSDV/MZGD/2020 strain may be the result of multiple recombination events between the Neethling 2490 and Neethling vaccine LW 1959 strains. This study expands our knowledge of the genetic diversity and evolution of LSDV.


Assuntos
Doenças dos Bovinos , Doença Nodular Cutânea , Vírus da Doença Nodular Cutânea , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Chlorocebus aethiops , Surtos de Doenças/veterinária , Filogenia , Células Vero
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