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1.
Gland Surg ; 13(6): 871-884, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39015720

RESUMO

Background: Although the research reports on locally advanced breast cancer (LABC) are increasing year by year, there are few reports on T1 LABC axillary lymph node metastasis (ALNM). By establishing a prediction model for T1 LABC ALNM, this study provides a reference value for the probability of ALNM of related patients, which helps clinicians to develop a more effective and individualized treatment plan for LABC. Methods: Cases with pathologically confirmed T1 breast cancer (BC) between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were identified. Logistic regression was used to analyze the correlation between LABC lymph node metastasis and every factor, and the odds ratio (OR) and 95% confidence interval (CI) were used to identify any influencing factors. A nomogram was drawn after incorporating meaningful factors identified in multivariate logistic regression into the model. The receiver operating characteristic (ROC) curve of the model was drawn, and the area under the curve (AUC) and its 95% CI were calculated. Hosmer-Lemeshow goodness-of-fit test and clinical decision curve analysis (DCA) were performed. The results were validated in the validation group. Results: A total of 200,933 female T1 BC patients were included in this study. Univariate and multivariate logistic regression analysis of T1 BC showed that progesterone receptor (PR)-negative, race, age, lobular carcinoma, micropapillary ductal carcinoma, axillary tail tumor, poor differentiation, and larger tumor diameter increased the probability of ALNM in T1 LABC. A predictive nomogram was established using the above predictors, the AUC of the modeling group was 0.739 (95% CI: 0.732-0.747), and when the AUC cut-off value was 0.026, the specificity and sensitivity of the model were 65.78% and 69.99%, respectively. Validation of the model showed that the AUC of the validation group (n=60,280) was 0.741. When all the risk factors were met, the predicted probability of N2-N3 was 50.40%. Conclusions: In this study, it was found that PR-negative, Black race, age, lobular carcinoma, micropapillary ductal carcinoma, axillary tail tumor, poor differentiation, and tumor diameter increased the probability of large lymph node metastasis in T1 LABC small tumors.

2.
Dev Cell ; 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38843837

RESUMO

The anterior visceral endoderm (AVE) differs from the surrounding visceral endoderm (VE) in its migratory behavior and ability to restrict primitive streak formation to the opposite side of the mouse embryo. To characterize the molecular bases for the unique properties of the AVE, we combined single-cell RNA sequencing of the VE prior to and during AVE migration with phosphoproteomics, high-resolution live-imaging, and short-term lineage labeling and intervention. This identified the transient nature of the AVE with attenuation of "anteriorizing" gene expression as cells migrate and the emergence of heterogeneities in transcriptional states relative to the AVE's position. Using cell communication analysis, we identified the requirement of semaphorin signaling for normal AVE migration. Lattice light-sheet microscopy showed that Sema6D mutants have abnormalities in basal projections and migration speed. These findings point to a tight coupling between transcriptional state and position of the AVE and identify molecular controllers of AVE migration.

3.
Appl Microbiol Biotechnol ; 108(1): 376, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884656

RESUMO

Mushroom poisoning contributes significantly to global foodborne diseases and related fatalities. Amanita mushrooms frequently cause such poisonings; however, identifying these toxic species is challenging due to the unavailability of fresh and intact samples. It is often necessary to analyze residues, vomitus, or stomach extracts to obtain DNA sequences for the identification of species responsible for causing food poisoning. This usually proves challenging to obtain usable DNA sequences that can be analyzed using conventional molecular biology techniques. Therefore, this study aimed to develop a DNA mini-barcoding method for the identification of Amanita species. Following the evaluation and optimization of universal primers for DNA mini-barcoding in Amanita mushrooms, we found that the internal transcribed spacer (ITS) gene sequence primer ITS-a was the most suitable DNA barcode primer for identifying Amanita species. Forty-three Amanita samples were subsequently amplified and sequenced. The sequences obtained were analyzed for intra- and inter-species genetic distances, and a phylogenetic tree was constructed. The findings indicated that the designed primers had strong universality among the Amanita samples and could accurately identify the target gene fragment with a length of 290 bp. Notably, the DNA mini-barcode accurately identified the 43 Amanita samples, demonstrating high consistency with the conventional DNA barcode. Furthermore, it effectively identified DNA from digested samples. In summary, this DNA mini-barcode is a promising tool for detecting accidental ingestion of toxic Amanita mushrooms. It may be used as an optimal barcode for species identification and traceability in events of Amanita-induced mushroom poisoning. KEY POINTS: • Development of a DNA mini-barcoding method for Amanita species identification without fresh samples. • The ITS-a primer set was optimized for robust universality in Amanita samples. • The mini-barcode is suitable for screening toxic mushroom species in mushroom poisoning cases.


Assuntos
Amanita , Código de Barras de DNA Taxonômico , DNA Fúngico , Intoxicação Alimentar por Cogumelos , Filogenia , Intoxicação Alimentar por Cogumelos/diagnóstico , Amanita/genética , DNA Fúngico/genética , Primers do DNA/genética , DNA Espaçador Ribossômico/genética , Análise de Sequência de DNA , Humanos
4.
Mol Pharm ; 21(7): 3407-3415, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822792

RESUMO

Transarterial radioembolization (TARE) is a highly effective localized radionuclide therapy that has been successfully used to treat hepatocellular carcinoma (HCC). Extensive research has been conducted on the use of radioactive microspheres (MSs) in TARE, and the development of ideal radioactive MSs is crucial for clinical trials and patient treatment. This study presents the development of a radioactive MS for TARE of HCC. These MSs, referred to as 177Lu-MS@PLGA, consist of poly(lactic-co-glycolic acid) (PLGA) copolymer and radioactive silica MSs, labeled with 177Lu and then coated with PLGA. It has an extremely high level of radiostability. Cellular experiments have shown that it can cause DNA double-strand breaks, leading to cell death. In vivo radiostability of 177Lu-MS@PLGA is demonstrated by microSPECT/CT imaging. In addition, the antitumor study has shown that TARE of 177Lu-MS@PLGA can effectively restrain tumor growth without harmful side effects. Thus, 177Lu-MS@PLGA exhibits significant potential as a radioactive MS for the treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Lutécio , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Radioisótopos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/radioterapia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Humanos , Camundongos , Lutécio/química , Radioisótopos/química , Radioisótopos/administração & dosagem , Embolização Terapêutica/métodos , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Camundongos Nus , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Neurosci Bull ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850386

RESUMO

Nicotine addiction is a concern worldwide. Most mechanistic investigations are on nicotine substance dependence properties based on its pharmacological effects. However, no effective therapeutic treatment has been established. Nicotine addiction is reinforced by environments or habits. We demonstrate the neurobiological basis of the behavioural aspect of nicotine addiction. We utilized the conditioned place preference to establish nicotine-associated behavioural preferences (NABP) in rats. Brain-wide neuroimaging analysis revealed that the medial prefrontal cortex (mPFC) was activated and contributed to NABP. Chemogenetic manipulation of µ-opioid receptor positive (MOR+) neurons in the mPFC or the excitatory outflow to the nucleus accumbens shell (NAcShell) modulated the NABP. Electrophysiological recording confirmed that the MOR+ neurons directly regulate the mPFC-NAcShell circuit via GABAA receptors. Thus, the MOR+ neurons in the mPFC modulate the formation of behavioural aspects of nicotine addiction via direct excitatory innervation to the NAcShell, which may provide new insight for the development of effective therapeutic strategies.

6.
J Med Chem ; 67(11): 9431-9446, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38818879

RESUMO

Synthetic lethality has recently emerged as a new approach for the treatment of mutated genes that were previously considered undruggable. Targeting methionine adenosyltransferase 2A (MAT2A) in cancers with deletion of the methylthioadenosine phosphorylase (MTAP) gene leads to synthetic lethality and thus has attracted significant interest in the field of precise anticancer drug development. Herein, we report the discovery of a series of novel MAT2A inhibitors featuring a pyrazolo[3,4-c]quinolin-4-one skeleton based on structure-based drug design. Further optimization led to compound 39, which has a high potency for inhibiting MAT2A and a remarkable selectivity for MTAP-deleted cancer cell lines. Compound 39 has a favorable pharmacokinetic profile with high plasma exposure and oral bioavailability, and it exhibits significant efficacy in xenograft MTAP-depleted models. Moreover, 39 demonstrates excellent brain exposure with a Kpuu of 0.64 in rats.


Assuntos
Encéfalo , Desenho de Fármacos , Inibidores Enzimáticos , Metionina Adenosiltransferase , Metionina Adenosiltransferase/antagonistas & inibidores , Metionina Adenosiltransferase/metabolismo , Humanos , Animais , Relação Estrutura-Atividade , Ratos , Encéfalo/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacocinética , Inibidores Enzimáticos/síntese química , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Antineoplásicos/química , Antineoplásicos/síntese química , Camundongos , Masculino , Ratos Sprague-Dawley , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Environ Sci Technol ; 58(20): 8846-8856, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38728579

RESUMO

Advanced oxidation process (AOP) wet scrubber is a powerful and clean technology for organic pollutant treatment but still presents great challenges in removing the highly toxic and hydrophobic volatile organic compounds (VOCs). Herein, we elaborately designed a bifunctional cobalt sulfide (CoS2)/activated carbon (AC) catalyst to activate peroxymonosulfate (PMS) for efficient toxic VOC removal in an AOP wet scrubber. By combining the excellent VOC adsorption capacity of AC with the highly efficient PMS activation activity of CoS2, CoS2/AC can rapidly capture VOCs from the gas phase to proceed with the SO4•- and HO• radical-induced oxidation reaction. More than 90% of aromatic VOCs were removed over a wide pH range (3-11) with low Co ion leaching (0.19 mg/L). The electron-rich sulfur vacancies and low-valence Co species were the main active sites for PMS activation. SO4•- was mainly responsible for the initial oxidation of VOCs, while HO• and O2 acted in the subsequent ring-opening and mineralization processes of intermediates. No gaseous intermediates from VOC oxidation were detected, and the highly toxic liquid intermediates like benzene were also greatly decreased, thus effectively reducing the health toxicity associated with byproduct emissions. This work provided a comprehensive understanding of the deep oxidation of VOCs via AOP wet scrubber, significantly accelerating its application in environmental remediation.


Assuntos
Oxirredução , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/química , Catálise , Carvão Vegetal/química , Cobalto/química , Adsorção , Carbono/química
8.
Ann Surg Treat Res ; 106(4): 225-230, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38586557

RESUMO

Purpose: Whether a dilated intrahepatic bile duct (IHBD) has any effect on the prognosis of choledochal cyst (CC) remains controversial. We aimed to summarize the clinical characteristics and prognosis of CC with IHBD dilatation. Methods: One hundred ninety-two children diagnosed with CC were identified, including 127 without IHBD dilatation (group A) and 65 with IHBD dilatation (group B). A retrospective analysis was performed to explore the clinical characteristics and prognosis of CC with IHBD dilatation based on clinical indices, symptoms, and complications. Results: Compared with group A, incidences of jaundice and fever were higher in group B (P = 0.010 and P = 0.033). Preoperative total bilirubin, direct bilirubin, and indirect bilirubin were increased in group B compared to group A (P = 0.005, P < 0.001, and P = 0.014), as were preoperative ALT, AST, γ-GT, and total bile acid (P = 0.006, P = 0.025, P < 0.001, and P = 0.024). The risk of liver fibrosis or cirrhosis was significantly increased for group B compared with group A (P = 0.012) and also occurred earlier in group B (P = 0.006). In the dilated IHBDs, 95.4% (62 of 65) recovered to normal, and more than half of dilated IHBDs (37 of 65) recovered to normal in 1 week. Conclusion: Most IHBDs can recover to normal postoperatively in a short time, and proactive treatment is recommended for CC patients with IHBD dilatation for significant abnormal liver functions.

9.
ACS Appl Mater Interfaces ; 16(15): 19691-19698, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38563689

RESUMO

A switching-type power converter providing an accurate and stable switching output voltage against line/load variations and power supply ripple is mostly complicated in system-on-chip power management integrated circuits (PMICs) within a limited occupation area. Here we fabricated domain wall (DW) nanodevices using an X-cut LiNbO3 thin film on silicon. The domain switching event occurs after a delay time predicted by Merz's law under the applied voltage. But the output current is irrespective of the applied voltage and can be adjusted by conducting wall width as well as input resistance in the circuit. The regulating currents appear repetitively across the volatile interfacial domains between the nanodevice and electrode under intermittently applied voltages. A wall-current-limited domain switching model is developed to explain the phenomenon. The multifunctional DW nanodevices with smaller occupation areas can serve as compact low-dropout regulators in PMICs, time-domain delayers in energy-efficient neural network systems, and on-chip electrostatic discharge protection besides nonvolatile memories and selectors.

10.
J Proteome Res ; 23(5): 1559-1570, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38603467

RESUMO

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of different variants of concerns with immune evasion that have been prevalent over the past three years. Nanobodies, the functional variable regions of camelid heavy-chain-only antibodies, have garnered interest in developing neutralizing antibodies due to their smaller size, structural stability, ease of production, high affinity, and low immunogenicity, among other characteristics. In this work, we describe an integrated proteomics platform for the high-throughput screening of nanobodies against different SARS-CoV-2 spike variants. To demonstrate this platform, we immunized a camel with subunit 1 (S1) of the wild-type spike protein and constructed a nanobody phage library. The binding and neutralizing activities of the nanobodies against 72 spike variants were then measured, resulting in the identification of two nanobodies (C-282 and C-39) with broad neutralizing activity against six non-Omicron variants (D614G, Alpha, Beta, Gamma, Delta, Kappa) and five Omicron variants (BA.1-5). Their neutralizing capability was validated using in vitro pseudovirus-based neutralization assays. All these results demonstrate the utility of our proteomics platform to identify new nanobodies with broad neutralizing capability and to develop a treatment for patients with SARS-CoV-2 variant infection in the future.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Camelus , Proteômica , SARS-CoV-2 , Anticorpos de Domínio Único , Glicoproteína da Espícula de Coronavírus , SARS-CoV-2/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/química , Proteômica/métodos , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Animais , Humanos , COVID-19/imunologia , COVID-19/virologia , Anticorpos Antivirais/imunologia , Testes de Neutralização
11.
J Cell Mol Med ; 28(9): e18357, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38683127

RESUMO

In our previous study, intranuclear cardiac troponin I (cTnI) may function as a co-factor of Yin Yang 1(YY1). Here, we aimed to explore the role of intranuclear cTnI in ageing hearts. Nuclear translocation of cTnI was demonstrated using Western blot and immunofluorescence. The potential nuclear localization sequences (NLSs) of cTnI were predicted by a web server and then verified in 293T cells by putative NLS-eGFP-GST and NLS-mutant transfection. The ratio of Nuclear cTnI/ Total cTnI (Nu/T) decreased significantly in ageing hearts, accompanied with ATG5-decline-related impaired cardiac autophagy. RNA sequencing was performed in cTnI knockout hearts. The differential expressed genes (DEGs) were analysed by overlapping with YY1 ChIP-sequencing data. cTnI gain and loss experiments in vitro determined those filtered DEGs' expression levels. A strong correlation was found between expression patterns cTnI and FOS. Using ChIP-q-PCR, we demonstrated that specific binding DNA sequences of cTnI were enriched in the FOS promoter -299 to -157 region. It was further verified that pcDNA3.1 (-)-cTnI could increase the promoter activity of FOS by using luciferase report assay. At last, we found that FOS can regulate the ATG5 (autophagy-related gene 5) gene by using a luciferase report assay. Taken together, our results indicate that decreased intranuclear cTnI in ageing hearts may cause impaired cardiac autophagy through the FOS/ATG5 pathway.


Assuntos
Envelhecimento , Proteína 5 Relacionada à Autofagia , Autofagia , Núcleo Celular , Miocárdio , Troponina I , Troponina I/metabolismo , Troponina I/genética , Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína 5 Relacionada à Autofagia/genética , Envelhecimento/metabolismo , Envelhecimento/genética , Animais , Miocárdio/metabolismo , Humanos , Núcleo Celular/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Camundongos , Células HEK293 , Masculino , Regiões Promotoras Genéticas , Regulação da Expressão Gênica , Miócitos Cardíacos/metabolismo , Camundongos Knockout
13.
Antioxidants (Basel) ; 13(3)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38539846

RESUMO

Molecular hydrogen, the smallest and lightest molecule, serves as an intense reducing agent. Its distinct characteristics, including minimal size and neutral charge, enhance bioavailability and facilitate significant biological effects. Previously considered physiologically inert, hydrogen has gained recognition as a powerful therapeutic agent, known for its antioxidative and anti-inflammatory properties. Electrolyzed hydrogen water (EHW), enriched with molecular hydrogen, demonstrates remarkable antioxidative capabilities, indicating potential benefits for various diseases. Inflammation-induced reactive oxygen species (ROS) amplify inflammation, leading to secondary oxidative stress and creating a crosstalk between ROS and inflammatory responses. This crosstalk contributes to the pathogenesis and progression of chronic diseases. EHW interrupts this crosstalk, reducing inflammatory cytokines and oxidative stress across various disease models, suggesting therapeutic potential. EHW is also known for its anti-inflammatory effects, extending to pain management, as evidenced in models like sciatic nerve ligation and inflammatory pain. In an inflammatory bowel disease (IBD) model, EHW effectively alleviates abdominal pain, mitigating 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced inflammation and oxidative stress, offering insights for clinical applications. Additionally, hydrogen selectively targets harmful radicals, and EHW intake helps balance stress-induced hormonal dysregulation, potentially easing disorders associated with chronic stress.

14.
Anim Reprod Sci ; 263: 107448, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428346

RESUMO

The egg production of captive African penguins differs considerably between individuals. An understanding of the physiological differences in African penguins with relatively greater and lesser egg production is meaningful for the captive breeding program of this endangered species. The objective of this study was to investigate differential microbial composition and metabolites in captive African penguins with different egg production. Fecal samples were collected from captive female African penguins during the breeding season. The results of 16 S rRNA gene sequencing showed that African penguins with different egg production had similar microbial diversities, whereas a significant difference was observed between their microbial community structure. African penguins with relatively greater egg production exhibited a higher relative abundance of Alphaproteobacteria, Rhizobiales, Bradyrhizobiaceae, Bradyrhizobium and Bosea. Meanwhile, penguins with relatively lesser egg production had an increased proportion of Klebsiella and Plesiomonas. We further identified a total of 1858 metabolites in female African penguins by liquid chromatography-mass spectrometry analysis. Among these metabolites, 13 kinds of metabolites were found to be significantly differential between African penguins with different egg production. In addition, the correlation analysis revealed that the egg production had significant correlations with most of the differential microbial bacteria and metabolites. Our findings might aid in understanding the potential mechanism underlying the phenomenon of abnormal egg production in captive African penguins, and provide novel insights into the relationship between gut microbiota and reproduction in penguins.


Assuntos
Microbioma Gastrointestinal , Spheniscidae , Humanos , Feminino , Animais , Spheniscidae/fisiologia , Microbioma Gastrointestinal/genética , Estações do Ano
15.
J Hand Surg Am ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38506783

RESUMO

PURPOSE: Resection of the radial or ulnar slip of the flexor digitorum superficialis (FDS) tendon is a known treatment option for persistent trigger finger. Risk factors for undergoing FDS slip excision are unclear. We hypothesized that patients who underwent A1 pulley release with FDS slip excision secondary to persistent triggering would have a higher comorbidity burden compared to those receiving A1 pulley release alone. METHODS: We identified all adult patients who underwent A1 pulley release with FDS slip excision because of persistent triggering either intraoperatively or postoperatively from 2018 to 2023. We selected a 3:1 age- and sex-matched control group who underwent isolated A1 pulley release. Charts were retrospectively reviewed for demographics, selected comorbidities, trigger finger history, and postoperative course. We performed multivariable logistic regression to assess the probability of FDS slip excision after adjusting for several variables that were significant in bivariate comparisons. RESULTS: We identified 48 patients who underwent A1 pulley release with FDS slip excision and 144 controls. Our multivariable model showed that patients with additional trigger fingers and a preoperative proximal interphalangeal (PIP) joint contracture were significantly more likely to undergo FDS slip excision. CONCLUSIONS: Patients who underwent A1 pulley release with FDS slip excision were significantly more likely to have multiple trigger fingers or a preoperative PIP joint contracture. Clinicians should counsel patients with these risk factors regarding the potential for FDS slip excision in addition to A1 pulley release to alleviate triggering of the affected digit. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

16.
J Med Virol ; 96(3): e29542, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38506170

RESUMO

The emerging new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs booster vaccination. We evaluated the long-term safety and immunogenicity of heterologous boosting with a SARS-CoV-2 messenger RNA vaccine SYS6006. A total of 1000 participants aged 18 years or more who had received two (Group A) or three (Group B) doses of SARS-CoV-2 inactivated vaccine were enrolled and vaccinated with one dose of SYS6006 which was designed based on the prototype spike protein and introduced mutation sites. Adverse events (AEs) through 30 days and serious AEs during the study were collected. Live-virus and pseudovirus neutralizing antibody (Nab), binding antibody (immunoglobulin G [IgG]) and cellular immunity were tested through 180 days. Solicited all, injection-site and systemic AEs were reported by 618 (61.8%), 498 (49.8%), and 386 (38.6%) participants, respectively. Most AEs were grade 1. The two groups had similar safety profile. No vaccination-related SAEs were reported. Robust wild-type (WT) live-virus Nab response was elicited with peak geometric mean titers (GMTs) of 3769.5 (Group A) and 5994.7 (Group B) on day 14, corresponding to 1602.5- and 290.8-fold increase versus baseline, respectively. The BA.5 live-virus Nab GMTs were 87.7 (Group A) and 93.2 (Group B) on day 14. All participants seroconverted for WT live-virus Nab. Robust pseudovirus Nab and IgG responses to wild type and BA.5 were also elicited. ELISpot assay showed robust cellular immune response, which was not obviously affected by virus variation. In conclusion, SYS6006 heterologous boosting demonstrated long-term good safety and immunogenicity in participants who had received two or three doses of SARS-CoV-2 inactivated vaccine.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Imunogenicidade da Vacina , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , China , COVID-19/prevenção & controle , Imunoglobulina G , Vacinas de mRNA , Vacinas de Produtos Inativados
17.
J Inflamm Res ; 17: 1397-1411, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476473

RESUMO

Purpose: To investigate the correlation between M1/M2 macrophages (M1/M2 Mφ) and cell death mode under Mycobacterium tuberculosis (Mtb) infection. Methods: Raw gene expression profiles were collected from the Gene Expression Omnibus (GEO) database. Genes related to different cell death modes were collected from the KEGG, FerrDb and GSEA databases. The differentially expressed genes (DEGs) of the gene expression profiles were identified using the limma package in R. The intersection genes of M1/M2 Mφ with different cell death modes were obtained by the VennDiagram package. Hub genes were obtained by constructing the protein-protein interactions (PPI) network and Receiver Operating Characteristic (ROC) curve analysis. The expression of cell death modes marker genes and Hub genes were verified by Western Blot and Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Results: Bioinformatics analysis was performed to screen Hub genes of Mtb-infected M1 Mφ and different cell death modes, naming NFKB1, TNF, CFLAR, TBK1, IL6, RELA, SOCS1, AIM2; Hub genes of Mtb-infected M2 Mφ and different cell death modes, naming TNF, BIRC3, MAP1LC3C, DEPTOR, UVRAG, SOCS1. Combined with experimental validation, M1 Mφ under Mtb infection showed higher expression of death (including apoptosis, autophagy, ferroptosis, and pyroptosis) genes compared to M2 Mφ and genes such as NFKB1, TNF, CFLAR, TBK1, IL6, RELA, AIM2, BIRC3, DEPTOR show differential expression. Conclusion: NFKB1, TNF, CFLAR, TBK1, IL6, RELA, AIM2 in Mtb-infected M1 Mφ, and TNF, BIRC3, DEPTOR in Mtb-infected M2 Mφ might be used as potential diagnostic targets for TB. At early stage of Mtb infection, apoptosis, autophagy, ferroptosis, and pyroptosis occurred more significantly in M1 Mφ than that in M2 Mφ, which may contribute to the transition of Mtb-infected Mφ from M1-dominant to M2-dominant and contribute to the immune escape mechanisms of Mtb.

18.
Heliyon ; 10(5): e26884, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449643

RESUMO

The Multidimensional Forced Choice (MFC) test is frequently utilized in non-cognitive evaluations because of its effectiveness in reducing response bias commonly associated with the conventional Likert scale. Nonetheless, it is critical to recognize that the MFC test generates ipsative data, a type of measurement that has been criticized due to its limited applicability for comparing individuals. Multidimensional item response theory (MIRT) models have recently sparked renewed interest among academics and professionals. This is largely due to the development of several models that make it easier to collect normative data from forced-choice tests. The paper introduces a modeling framework made up of three key components: response format, measurement model, and decision theory. Under this paradigm, four IRT models were chosen as examples. Following that, a comprehensive study is carried out to compare and characterize the parameter estimation techniques used in MFC-IRT models. This work then examines empirical research on the concept by analyzing three distinct domains: parameter invariance testing, computerized adaptive testing (CAT), and validity investigation. Finally, it is recommended that future research initiatives follow four distinct paths: modeling, parameter invariance testing, forced-choice CAT, and validity studies.

19.
Front Genet ; 15: 1372644, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510275

RESUMO

"Heteromorphic self-incompatibility" (HetSI) in plants is a mechanism of defense to avoid self-pollination and promote outcrossing. However, the molecular mechanism underlying HetSI remains largely unknown. In this study, RNA-seq was conducted to explore the molecular mechanisms underlying self-compatible (SC, "T × P" and "P × T") and self-incompatible (SI, "T × T" and "P × P") pollination in the two types of flowers of Plumbago auriculata Lam. which is a representative HetSI plant. By comparing "T × P" vs. "T × T", 3773 (1407 upregulated and 2366 downregulated) differentially expressed genes (DEGs) were identified, 1261 DEGs between "P × T" and "P × P" (502 upregulated and 759 downregulated). The processes in which these DEGs were significantly enriched were "MAPK (Mitogen-Activated Protein Kinases-plant) signaling pathway", "plant-pathogen interaction","plant hormone signal transduction", and "pentose and glucuronate interconversion" pathways. Surprisingly, we discovered that under various pollination conditions, multiple notable genes that may be involved in HetSI exhibited distinct regulation. We can infer that the HetSI strategy might be unique in P. auriculata. It was similar to "sporophytic self-incompatibility" (SSI) but the HetSI mechanisms in pin and thrum flowers are diverse. In this study, new hypotheses and inferences were proposed, which can provide a reference for crop production and breeding.

20.
Environ Res ; 251(Pt 2): 118639, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38508359

RESUMO

Frontier studies have neglected the impact of digital transformation (DT) on the synergy for pollution and carbon reduction (SPCR) from the perspective of micro enterprises. This paper explores the SPCR effect of DT, as well as its mechanism at micro-firm level. The study found that: (1) DT significantly facilitates corporate SPCR. For every 10% increase in the level of DT, the ranking of SPCR will rise by about 2.3 places. This effect is more obvious in high-tech firms and non-heavy polluters, firms in the eastern region in China, and non-SOE. (2) DT creates innovation-driven and structure-optimizing effects, which enhance the corporate green innovation ability, optimize the business structure and capital allocation structure of enterprises, and then drive the SPCR. (3) External public environmental concerns (PEC) and internal corporate ESG governance act as "accelerators" promoting the SPCR effect of DT. Based on these, policy implications are made to accelerate the pace of corporate DT, give full play to the first-mover advantage, and break the "pollution (carbon) lock-in" with a view to providing theoretical references for the listed enterprises' digitalized governance of SPCR, as well as the governmental departments' formulation of relevant guiding policies, and striving to achieve the high-quality development goal.


Assuntos
Poluição Ambiental , China , Poluição Ambiental/prevenção & controle , Carbono/química , Política Ambiental
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