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1.
Transl Cancer Res ; 13(4): 1606-1622, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38737697

RESUMO

Background: RNA-binding motif protein 39 (RBM39) is a well-known RNA-binding protein involved in tumorigenesis; however, its role in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the role of RBM39 in HCC. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the differential expression of RBM39 in HCC and normal tissues. The prognostic and diagnostic value of RBM39 in HCC was accessed by Kaplan-Meier analysis, Cox regression, and receiver operating characteristic (ROC) curve analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to validate the mRNA and protein expression of RBM39 in HCC. Moreover, gene set enrichment analysis (GSEA) was performed to identify key pathways related to RBM39. The correlation between RBM39 expression and immune cell infiltration was evaluated using a single-sample gene set enrichment analysis (ssGSEA). CCK8 and wound healing assays were performed to investigate the proliferation and migration abilities of HCC cells with RBM39 knockdown. Results: RBM39 expression was upregulated in the HCC tissues. High RBM39 expression was significantly associated with advanced T stage, histological grade, and pathological stage and predicted poor overall survival (OS), disease-specific survival (DSS), and progress-free interval (PFI) in HCC patients. The upregulation of RBM39 expression was an independent prognostic factor for OS. Moreover, GSEA enrichment analysis indicated that RBM39 was functionally involved in pathways associated with the cell cycle, DNA replication, the p53 signaling pathway, and primary immunodeficiency. RBM39 expression was associated with infiltration of Th2 cells and dendritic cells (DC). RBM39 knockdown significantly inhibited the proliferation and migration of HCC cells. Conclusions: These findings suggest that high RBM39 expression is associated with poor prognosis and promotes HCC cell proliferation and migration. Based on these results, RBM39 is a promising prognostic biomarker with functional significance for HCC.

2.
ACS Nano ; 18(20): 12905-12916, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38721835

RESUMO

For most frequent respiratory viruses, there is an urgent need for a universal influenza vaccine to provide cross-protection against intra- and heterosubtypes. We previously developed an Escherichia coli fusion protein expressed extracellular domain of matrix 2 (M2e) and nucleoprotein, named NM2e, and then combined it with an aluminum adjuvant, forming a universal vaccine. Although NM2e has demonstrated a protective effect against the influenza virus in mice to some extent, further improvement is still needed for the induction of immune responses ensuring adequate cross-protection against influenza. Herein, we fabricated a cationic solid lipid nanoadjuvant using poly(lactic acid) (PLA) and dimethyl-dioctadecyl-ammonium bromide (DDAB) and loaded NM2e to generate an NM2e@DDAB/PLA nanovaccine (Nv). In vitro experiments suggested that bone marrow-derived dendritic cells incubated with Nv exhibited ∼4-fold higher antigen (Ag) uptake than NM2e at 16 h along with efficient activation by NM2e@DDAB/PLA Nv. In vivo experiments revealed that Ag of the Nv group stayed in lymph nodes (LNs) for more than 14 days after initial immunization and DCs in LNs were evidently activated and matured. Furthermore, the Nv primed T and B cells for robust humoral and cellular immune responses after immunization. It also induced a ratio of IgG2a/IgG1 higher than that of NM2e to a considerable extent. Moreover, NM2e@DDAB/PLA Nv quickly restored body weight and improved survival of homo- and heterosubtype influenza challenged mice, and the cross-protection efficiency was over 90%. Collectively, our study demonstrated that NM2e@DDAB/PLA Nv could offer notable protection against homo- and heterosubtype influenza virus challenges, offering the potential for the development of a universal influenza vaccine.


Assuntos
Adjuvantes Imunológicos , Vacinas contra Influenza , Poliésteres , Compostos de Amônio Quaternário , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/química , Vacinas contra Influenza/administração & dosagem , Animais , Camundongos , Poliésteres/química , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Compostos de Amônio Quaternário/química , Feminino , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/imunologia , Nanopartículas/química , Proteção Cruzada/imunologia , Adjuvantes de Vacinas/química , Proteínas da Matriz Viral/imunologia
3.
Heliyon ; 10(9): e29738, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38699043

RESUMO

Alginate is the most abundant polysaccharide compound in brown algae, which is widely used in various fields. At present, the determination of the content of alginate is mostly carried out using sulfuric acid and trifluoroacetic acid hydrolysis followed by the determination of the content, but the results are not satisfactory, and there are problems such as low hydrolysis degree and low recovery rate. Therefore, in this study, based on the optimization of high performance liquid chromatographic conditions for pre-column derivatization of 1-phenyl-3-methyl-5-pyrazolone (PMP), the hydrolysis effects of sulfuric acid, trifluoroacetic acid (TFA), oxalic acid, and formic acid were compared and the hydrolysis conditions were optimized. The results showed that formic acid was the best hydrolyzing acid. The optimal hydrolysis conditions were 95 % formic acid at 110 °C for 10 h. The hydrolysis effect was stable, with high recovery and low destruction of monosaccharides, which made it possible to introduce formic acid into the subsequent polysaccharide hydrolysis. The pre-column derivatization high performance liquid chromatography method established in this study was accurate and reliable, and the hydrolysis acid with better effect was screened, which provided a theoretical basis for the subsequent determination of alginate content.

4.
Nat Commun ; 15(1): 3310, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632249

RESUMO

Asian soybean rust (ASR), caused by Phakopsora pachyrhizi, is a devastating disease that is present in all major soybean-producing regions. The limited availability of resistant germplasm has resulted in a scarcity of commercial soybean cultivars that are resistant to the disease. To date, only the Chinese soybean landrace SX6907 has demonstrated an immune response to ASR. In this study, we present the isolation and characterization of Rpp6907-7 and Rpp6907-4, a gene pair that confer broad-spectrum resistance to ASR. Rpp6907-7 and Rpp6907-4 encode atypic nucleotide-binding leucine-rich repeat (NLR) proteins that are found to be required for NLR-mediated immunity. Genetic analysis shows that only Rpp6907-7 confers resistance, while Rpp6907-4 regulates Rpp6907-7 signaling activity by acting as a repressor in the absence of recognized effectors. Our work highlights the potential value of using Rpp6907 in developing resistant soybean cultivars.


Assuntos
Phakopsora pachyrhizi , Glycine max , Genes de Plantas , Doenças das Plantas/genética
5.
Aging (Albany NY) ; 16(5): 4832-4840, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461437

RESUMO

Osteoporosis is a usual bone disease in aging populations, principally in postmenopausal women. Anti-resorptive and anabolic drugs have been applied to prevent and cure osteoporosis and are associated to a different of adverse effects. Du-Zhong is usually applied in Traditional Chinese Medicine to strengthen bone, regulate bone metabolism, and treat osteoporosis. Chlorogenic acid is a major polyphenol in Du-Zhong. In the current study, chlorogenic acid was found to enhance osteoblast proliferation and differentiation. Chlorogenic acid also inhibits the RANKL-induced osteoclastogenesis. Notably, ovariectomy significantly decreased bone volume and mechanical properties in the ovariectomized (OVX) rats. Administration of chlorogenic acid antagonized OVX-induced bone loss. Taken together, chlorogenic acid seems to be a hopeful molecule for the development of novel anti-osteoporosis treatment.


Assuntos
Osteoclastos , Osteoporose , Humanos , Ratos , Feminino , Animais , Ácido Clorogênico/farmacologia , Ácido Clorogênico/uso terapêutico , Ácido Clorogênico/metabolismo , Osteogênese , Osteoporose/metabolismo , Osteoblastos/metabolismo , Diferenciação Celular
7.
Int J Biol Sci ; 20(1): 265-279, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164180

RESUMO

Endometrial carcinoma (EC) is a common type of uterine cancer in developed countries, originating from the uterine epithelium. The incidence rate of EC in Taiwan has doubled from 2005. Cancer stem cells (CSCs) are a subpopulation of cancer cells that have high tumorigenicity and play a crucial role in the malignant processes of cancer. Targeting molecules associated with CSCs is essential for effective cancer treatments. This study delves into the role of Exosome component 5 (EXOSC5) in EC. Data from The Cancer Genome Atlas suggests a correlation between high EXOSC5 mRNA expression and unfavorable EC prognosis. EXOSC5 knockdown diminished EC-CSC self-renewal and reduced expression of key cancer stemness proteins, including c-MYC and SOX2. Intriguingly, this knockdown significantly curtailed tumorigenicity and CSC frequency in EC tumor spheres. A mechanistic examination revealed a reduction in netrin4 (NTN4) levels in EXOSC5-depleted EC cells. Moreover, NTN4 treatment amplified EC cell CSC activity and, when secreted, NTN4 partnered with integrin ß1, subsequently triggering the FAK/SRC axis to elevate c-MYC activity. A clear positive relation between EXOSC5 and NTN4 was evident in 93 EC tissues. In conclusion, EXOSC5 augments NTN4 expression, activating c-MYC via the integrin ß1/FAK/SRC pathway, offering potential avenues for EC diagnosis and treatment.


Assuntos
Neoplasias do Endométrio , Integrina beta1 , Humanos , Feminino , Integrina beta1/metabolismo , Transdução de Sinais/genética , Neoplasias do Endométrio/metabolismo , Células-Tronco Neoplásicas/metabolismo , Linhagem Celular Tumoral , Antígenos de Neoplasias/metabolismo , Proteínas de Ligação a RNA/metabolismo , Complexo Multienzimático de Ribonucleases do Exossomo/metabolismo , Netrinas/metabolismo
8.
Sensors (Basel) ; 24(2)2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38276357

RESUMO

Sonar imaging technology is widely used in the field of marine and underwater monitoring because sound waves can be transmitted in elastic media, such as the atmosphere and seawater, without much interference. In underwater object detection, due to the unique characteristics of the monitored sonar image, and since the target in an image is often accompanied by its own shadow, we can use the relative relationship between the shadow and the target for detection. To make use of shadow-information-aided detection and realize accurate real-time detection in sonar images, we put forward a network based on a lightweight module. By using the attention mechanism with a global receptive field, the network can make the target pay attention to the shadow information in the global environment, and because of its exquisite design, the computational time of the network is greatly reduced. Specifically, we design a ShuffleBlock model adapted to Hourglass to make the backbone network lighter. The concept of CNN dimension reduction is applied to MHSA to make it more efficient while paying attention to global features. Finally, CenterNet's unreasonable distribution method of positive and negative samples is improved. Simulation experiments were carried out using the proposed sonar object detection dataset. The experimental results further verify that our improved model has obvious advantages over many existing conventional deep learning models. Moreover, the real-time monitoring performance of our proposed model is more conducive to the implementation in the field of ocean monitoring.

9.
Virol Sin ; 39(1): 134-143, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38070873

RESUMO

The monkeypox virus (MPXV) has triggered a current outbreak globally. Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control. It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads, as it is one of the DNA viruses with the largest genome and the most AT-biased, and has a significant number of tandem repeats. Here we evaluated the performance of metagenomic and amplicon sequencing techniques, and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland. We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens. Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes. Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences. Besides, several intra-host single nucleotide variations were identified in the first imported mpox case. This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens. The findings of this study will significantly enhance the surveillance of MPXV.


Assuntos
Monkeypox virus , Mpox , Humanos , Monkeypox virus/genética , Mpox/diagnóstico
10.
Int Urol Nephrol ; 56(2): 625-633, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37450242

RESUMO

PURPOSE: We undertook a multicenter epidemiological survey among hospitalized patients with chronic kidney disease (CKD), aiming to reveal the characteristics of elderly CKD by comparing it with non-elderly CKD. METHODS: Medical records were obtained from 18 military hospitals across China from 1 January 2009 to 31 December 2011. The characteristics of chronic kidney disease in the elderly were analyzed through comparing with those in younger patients with chronic kidney disease. RESULTS: A total of 380,461 hospitalized patients were included in the database, with 25,826 (6.8%) diagnosed with CKD. Unlike non-elderly, the top-three causes of chronic kidney disease among elderly patients were diabetic nephropathy (24.1%), hypertension-related renal impairment (20.9%), and primary glomerular disease (11.1%). 71.6% of the elderly patients with CKD had more than one comorbidities and the number of morbidities increased with age. In-hospital mortality of the elderly was significantly higher than those of younger patients (3.3% vs. 1.0%). Multiple logistic regression analysis showed that age, CKD 5 stage, acidosis, cardiovascular and cerebrovascular diseases, infection disease, neoplasm, and dementia were independent risk factors for death from CKD in the elderly. The median length of stay (LOS) was similar between elderly and younger CKD patients. The median cost was higher for elderly CKD patients than for younger CKD patients. Among elderly individuals with CKD, LOS, and hospitalization costs also increased with an increase in the number of coexisting diseases. CONCLUSIONS: Diabetic nephropathy,  and hypertension-related kidney injury were the leading causes of chronic kidney disease in elderly patients, which is different from the non-elderly. Elderly patients with chronic kidney disease were more likely to have a higher burden of comorbidities, which were associated with worse in-hospital outcomes.


Assuntos
Nefropatias Diabéticas , Hipertensão , Insuficiência Renal Crônica , Humanos , Idoso , Pessoa de Meia-Idade , Estudos Transversais , Nefropatias Diabéticas/complicações , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/complicações , Hipertensão/complicações , Fatores de Risco
12.
Nat Plants ; 9(12): 1986-1999, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38012346

RESUMO

Tea is one of the world's oldest crops and is cultivated to produce beverages with various flavours. Despite advances in sequencing technologies, the genetic mechanisms underlying key agronomic traits of tea remain unclear. In this study, we present a high-quality pangenome of 22 elite cultivars, representing broad genetic diversity in the species. Our analysis reveals that a recent long terminal repeat burst contributed nearly 20% of gene copies, introducing functional genetic variants that affect phenotypes such as leaf colour. Our graphical pangenome improves the efficiency of genome-wide association studies and allows the identification of key genes controlling bud flush timing. We also identified strong correlations between allelic variants and flavour-related chemistries. These findings deepen our understanding of the genetic basis of tea quality and provide valuable genomic resources to facilitate its genomics-assisted breeding.


Assuntos
Camellia sinensis , Camellia sinensis/genética , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Genômica , Chá
13.
Sci Bull (Beijing) ; 68(21): 2598-2606, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37758615

RESUMO

Cross-species transmission of viruses from wildlife animal reservoirs, such as bats, poses a threat to human and domestic animal health. Previous studies have shown that domestic animals have important roles as intermediate hosts, enabling the transmission of genetically diverse coronaviruses from natural hosts to humans. Here, we report the identification and characterization of a novel canine coronavirus (VuCCoV), which caused an epidemic of acute diarrhea in Vulpes (foxes) in Shenyang, China. The epidemic started on November 8, 2019, and caused more than 39,600 deaths by January 1, 2022. Full-length viral genomic sequences were obtained from 15 foxes with diarrhea at the early stage of this outbreak. The VuCCoV genome shared more than 90% nucleotide identity with canine coronavirus (CCoV) for three of the four structural genes, with the S gene showing a larger amount of divergence. In addition, 67% (10/15) of the VuCCoV genomes contained an open reading frame (ORF3) gene, which was previously only detected in CCoV-I genomes. Notably, VuCCoV had only two to three amino acid differences at the partial RNA-dependent RNA polymerase (RdRp) level to bat CoV, suggesting a close genetic relationship. Therefore, these novel VuCCoV genomes represent a previously unsampled lineage of CCoVs. We also show that the VuCCoV spike protein binds to canine and fox aminopeptidase N (APN), which may allow this protein to serve as an entry receptor. In addition, cell lines were identified that are sensitive to VuCCoV using a pseudovirus system. These data highlight the importance of identifying the diversity and distribution of coronaviruses in domestic animals, which could mitigate future outbreaks that could threaten livestock, public health, and economic growth.


Assuntos
Coronavirus Canino , Raposas , Animais , Cães , Humanos , Coronavirus Canino/genética , Animais Selvagens , SARS-CoV-2/genética , Animais Domésticos , Surtos de Doenças/veterinária , Diarreia/epidemiologia
14.
Vaccines (Basel) ; 11(9)2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37766130

RESUMO

Current COVID-19 vaccines can effectively reduce disease severity and hospitalisation; however, they are not considerably effective in preventing infection and transmission. In this context, mucosal vaccines are pertinent to prevent SARS-CoV-2 infection and spread. In this study, we generated a replication-competent recombinant chimeric influenza A virus (IAV) expressing the receptor-binding domain (RBD) of a SARS-CoV-2 prototype in the C-terminus of the neuraminidase (NA) of A/Puerto Rico/08/1934 H1N1 (PR8). The remaining seven segments from A/WSN/1933 H1N1 (WSN) were named PR8NARBD/WSN. We observed that the recombinant virus with the WSN backbone demonstrated improved expression of NA and RBD. A single intranasal dose of PR8NARBD/WSN(103PFU) in mice generated robust mucosal immunity, neutralising antibodies, cellular immunity, and tissue-resident memory T cells specific to SARS-CoV-2 and IAV. Importantly, immunisation with PR8NARBD/WSN viruses effectively protected mice against lethal challenges with H1N1, H3N2 IAV, and SARS-CoV-2 Beta variant and significantly reduced lung viral loads. Overall, our research demonstrates the promising potential of PR8NARBD/WSN as an attractive vaccine against emerging SARS-CoV-2 variants and influenza A virus infections.

15.
Front Public Health ; 11: 1089764, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711249

RESUMO

Aim: Breastfeeding generates short-term and long-term benefits for both mother and child. Exclusive breastfeeding (EBF) is promoted in China for years, but its practice still lags far behind the international average, even among low- and middle- income countries. This study aimed to investigate factors associated with EBF during postpartum. Methods: This study was conducted in a tertiary referral hospital in Gansu Province, Northwest China from October 2019 to April 2020. 3,738 postnatal women were finally included and each of them completed an elaborately designed questionnaire. Infant feeding patterns (EBF or not) and reasons for NEBF (non-exclusive breastfeeding) were collected. The feeding knowledge score was based on 17 questions in relation to breastfeeding. The total score ranges from 0 to 17. Higher score means better understanding about breastfeeding knowledge. Multivariate logistic regression models were used to determine associated factors of EBF during postpartum. A subgroup analysis was conducted to investigate the association between feeding knowledge score and exclusive breastfeeding. Results: Six weeks after childbirth, 1891 mothers (50.6%) maintained EBF. Among the NEBF mothers, 57.01% (n = 1,053) of them stopped exclusive breastfeeding due to self-perceived lack of breast milk production. Factors associated with NEBF were higher maternal age, ethnic minorities and cesarean section. Protective factors of EBF included multipara, positive feeding attitude and high breastfeeding knowledge score. In subgroup analysis, we found the breastfeeding knowledge score had a significant impact on the mothers of Han nationality, underwent cesarean or natural delivery, both primiparous and multiparous, and those with positive attitude towards breastfeeding (p < 0.05). Conclusion: We need a comprehensive and individualized framework of strategies to support children, mothers and their families. During puerperium, improving maternal knowledge of breastfeeding is beneficial to EBF practice. However, for ethnic minorities and those with less active breastfeeding attitudes, breastfeeding knowledge is of limited use, more researches are needed to explore the uncovered reasons, so that more personalized interventions could be developed for them.


Assuntos
Aleitamento Materno , Cesárea , Gravidez , Criança , Lactente , Humanos , Feminino , Estudos Transversais , Período Pós-Parto , China/epidemiologia , Mães
16.
Bioengineering (Basel) ; 10(8)2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37627791

RESUMO

Tricalcium phosphate (TCP) has gained attention due to its interconnected porous structures which promote fibrovascular invasion and bony replacement. Moreover, when gelatin is added and crosslinked with genipin (GGT), TCP exhibits robust biocompatibility and stability, making it an excellent bone substitute. In this study, we incorporated emodin and lumbrokinase (LK) into GGT to develop an antibacterial biomaterial. Emodin, derived from various plants, possesses antibacterial and anti-inflammatory properties. LK comprises proteolytic enzymes extracted from the earthworm Lumbricus rubellus and exhibits fibrinolytic activity, enabling it to dissolve biofilms. Additionally, LK stimulates osteoblast activity while inhibiting osteoclast differentiation. GGT was combined with emodin and lumbrokinase to produce the GGTELK composite. The biomedical effects of GGTELK were assessed through in vitro assays and an ex vivo bone defect model. The GGTELK composite demonstrated antibacterial properties, inhibiting the growth of S. aureus and reducing biofilm formation. Moreover, it exhibited anti-inflammatory effects by reducing the secretion of IL-6 in both in vivo cell experiments and the ex vivo model. Therefore, the GGTELK composite, with its stability, efficient degradation, biocompatibility, and anti-inflammatory function, is expected to serve as an ideal bone substitute.

17.
Clin Lab ; 69(8)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37560872

RESUMO

BACKGROUND: Macacine alphaherpesvirus 1 (BV) was first reported in the 1930s and only about 60 cases have been diagnosed since then. METHODS: A 53-year-old male who worked as a veterinary surgeon, developed a fever with nausea and vomiting in April 2021 in Beijing, China. Real-time polymerase chain reaction (PCR) and metagenomics Next Generation Sequencing (mNGS) were used for diagnosis. RESULTS: BV DNA was confirmed by mNGS and PCR. The case died 51 days after onset, due to the damage to the brain and spinal cord caused by a viral infection and hypoxic-ischemic encephalopathy. The typical BV inclusion bodies in the brain were found for the first time. CONCLUSIONS: Here we reported the first human infection case of BV in China. This fatal case highlights the potential threat of BV to occupational workers and the essential role of surveillance.


Assuntos
Herpesvirus Cercopitecino 1 , Masculino , Humanos , Pessoa de Meia-Idade , China/epidemiologia , Reação em Cadeia da Polimerase em Tempo Real , Pequim , Sequenciamento de Nucleotídeos em Larga Escala
18.
BMC Med ; 21(1): 233, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37400857

RESUMO

BACKGROUND: Several COVID-19 vaccines are in widespread use in China. Few data exist on comparative immunogenicity of different COVID-19 vaccines given as booster doses. We aimed to assess neutralizing antibody levels raised by injectable and inhaled aerosolized recombinant adenovirus type 5 (Ad5)-vectored COVID-19 vaccine as a heterologous booster after an inactivated COVID-19 vaccine two-dose primary series. METHODS: Using an open-label prospective cohort design, we recruited 136 individuals who had received inactivated vaccine primary series followed by either injectable or inhaled Ad5-vectored vaccine and measured neutralizing antibody titers against ancestral SARS-CoV-2 virus and Omicron BA.1 and BA.5 variants. We also measured neutralizing antibody levels in convalescent sera from 39 patients who recovered from Omicron BA.2 infection. RESULTS: Six months after primary series vaccination, neutralizing immunity against ancestral SARS-CoV-2 was low and neutralizing immunity against Omicron (B.1.1.529) was lower. Boosting with Ad5-vectored vaccines induced a high immune response against ancestral SARS-CoV-2. Neutralizing responses against Omicron BA.5 were ≥ 80% lower than against ancestral SARS-CoV-2 in sera from prime-boost subjects and in convalescent sera from survivors of Omicron BA.2 infection. Inhaled aerosolized Ad5-vectored vaccine was associated with greater neutralizing titers than injectable Ad5-vectored vaccine against ancestral and Omicron SARS-CoV-2 variants. CONCLUSIONS: These findings support the current strategy of heterologous boosting with injectable or inhaled Ad5-vectored SARS-CoV-2 vaccination of individuals primed with inactivated COVID-19 vaccine.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , Estudos Prospectivos , SARS-CoV-2
19.
China CDC Wkly ; 5(26): 584-591, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37457851

RESUMO

Introduction: Since 2019, numerous variants of concern for severe acute respiratory syndrome virus 2 (SARS-CoV-2) have emerged, leading to significant outbreaks. The development of novel, highly accurate, and rapid detection techniques for these new SARS-CoV-2 variants remains a primary focus in the ongoing efforts to control and prevent the coronavirus disease 2019 (COVID-19) pandemic. Methods: Reverse transcription-recombinase polymerase amplification combined with the clustered regularly interspaced short palindromic repeats-associated protein 12a (CRISPR/Cas12a) system was used to validate the detection of the Omicron BA.2, BA.4, and BA.5 variants of SARS-CoV-2. Results: Our results demonstrate that the CRISPR/Cas12a assay is capable of effectively detecting the SARS-CoV-2 BA.2, BA.4, and BA.5 variants with a limit of detection of 10, 1, and 10 copies/µL, respectively. Importantly, our assay successfully differentiated the three SARS-CoV-2 Omicron strains from one another. Additionally, we evaluated 46 SARS-CoV-2 positive clinical samples consisting of BA.2 (n=20), BA.4 (n=6), and BA.5 (n=20) variants, and the sensitivity of our assay ranged from 90% to 100%, while the specificity was 100%. Discussion: This research presents a swift and reliable CRISPR-based method that may be employed to track the emergence of novel SARS-CoV-2 variants.

20.
J Cachexia Sarcopenia Muscle ; 14(4): 1855-1864, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37300354

RESUMO

BACKGROUND: Frailty and sarcopenia are prevalent in chronic kidney disease (CKD) populations and could increase the risk for adverse health outcomes. Few studies assess the correlation between frailty, sarcopenia and CKD in non-dialysis patients. Therefore, this study aimed to determine frailty-associated factors in elderly CKD stage I-IV patients, expected to early identify and intervene in the frailty of elderly CKD patients. METHODS: A total of 774 elderly CKD I-IV patients (>60 years of age) recruited from 29 clinical centers in China between March 2017 and September 2019 were included in this study. We established a Frailty Index (FI) model to evaluate frailty risk and verified the distributional property of FI in the study population. Sarcopenia was defined according to the criteria of the Asian Working Group for Sarcopenia 2019. Multinomial logistic regression analysis was used to assess the associated factors for frailty. RESULTS: Seven hundred seventy-four patients (median age 67 years, 66.0% males) were included in this analysis, with a median estimated glomerular filtration rate of 52.8 mL/min/1.73 m2 . The prevalence of sarcopenia was 30.6%. The FI exhibited a right-skewed distribution. The age-related slope of FI was 1.4% per year on a logarithmic scale (r2  = 0.706, 95% CI 0.9, 1.8, P < 0.001). The upper limit of FI was around 0.43. The FI was related to mortality (HR = 1.06, 95% CI 1.00, 1.12, P = 0.041). Multivariate multinomial logistic regression analysis showed that sarcopenia, advanced age, CKD stage II-IV, low level of serum albumin and increased waist-hip ratio were significantly associated with high FI status, while advanced age and CKD stage III-IV were significantly associated with for median FI status. Moreover, the results from the subgroup were consistent with the leading results. CONCLUSIONS: Sarcopenia was independently associated with an increased risk for frailty in elderly CKD I-IV patients. Patients with sarcopenia, advanced age, high CKD stage, high waist-hip ratio and low serum albumin level should be assessed for frailty.


Assuntos
Fragilidade , Insuficiência Renal Crônica , Sarcopenia , Masculino , Humanos , Idoso , Feminino , Fragilidade/epidemiologia , Sarcopenia/etiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Taxa de Filtração Glomerular , Prevalência
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