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1.
Sci Immunol ; 9(95): eadj9730, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728414

RESUMO

Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti-B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8+ CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.


Assuntos
Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Análise de Célula Única , Humanos , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/imunologia , Autoimunidade/imunologia , Neuromielite Óptica/imunologia , Neuromielite Óptica/terapia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Sistema Nervoso Central/imunologia
2.
Curr Microbiol ; 81(7): 168, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733376

RESUMO

In 2018, Nouioui et al. proposed that Bifidobacterium coryneforme was a later synonym of Bifidobacterium indicum on the basis of the digital DNA-DNA hybridization (dDDH) value (85.0%) between B. coryneforme LMG 18911T and B. indicum LMG 11587T. However, in the study of Scardovi et al. (1970), the type strains of B. indicum and B. coryneforme only exhibited 60% DNA-DNA hybridization value. In the present study, the genomes of B. coryneforme CGMCC 1.2279T, B. coryneforme JCM 5819T, B. indicum JCM 1302T, B. indicum CGMCC 1.2275T, B. indicum DSM 20214T, B. indicum LMG 27437T, B. indicum ATCC 25912T, B. indicum KCTC 3230T, B. indicum CCUG 34985T, were sequenced, and the taxonomic relationship between B. coryneforme and B. indicum was re-evaluated. On the basis of the results presented here, (i) ATCC 25912 and DSM 20214 deposited by Vittorio Scardovi are two different strains; (ii) the type strain of B. indicum is ATCC 25912T (= JCM 1302T = LMG 27437T = CGMCC 1.2275T = KCTC 3230T), and not DSM 20214 (= BCRC 14674 = CCUG 34985 = LMG 11587); (iii) B. coryneforme and B. indicum represent two different species of the genus Bifidobacterium; (iv) strain DSM 20214 (= BCRC 14674 = CCUG 34985 = LMG 11587) belongs to B. coryneforme.


Assuntos
Bifidobacterium , DNA Bacteriano , Genoma Bacteriano , Filogenia , Bifidobacterium/genética , Bifidobacterium/classificação , Bifidobacterium/isolamento & purificação , DNA Bacteriano/genética , Hibridização de Ácido Nucleico , Técnicas de Tipagem Bacteriana , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
3.
Acta Trop ; 255: 107246, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729328

RESUMO

Japanese encephalitis (JE) is a mosquito-borne disease with a spatial distribution that is linked to geo-environmental factors. The spatial distribution of JE cases and correlated geo-environmental factors were investigated in two critical counties in southern and northern China. Based on maps, enhanced thematic mapper (ETM) remote sensing datasets from Landsat and spatial datasets of JE cases, spatial distribution and spatial cluster analyses of JE cases at the village scale were performed by using the standard deviational ellipse and Ripleys K-function. Global and regional spatial cluster analyses of JE cases were also performed by using Moran's index. Regression analysis was used to analyze the relationships between geo-environmental characteristics and the risk of JE cases. At the study sites, the JE cases were not spatially clustered at the village or district (global) level, whereas there was a spatial cluster at the district (local) level. Diversity-related features for JE patients at the district and village levels were detected at two sites. In the southern counties, the distance of a village from a road was related to the village-level JE risk (OR: 0.530, 95 CI: 0.297-0.947, P = 0.032), and the number of township-level JE cases was linked to the distance of the district center from the road (R =-0.467, P = 0.025) and road length (R = 0.516, P = 0.012) in the administrative area. In northern China, the modified normalized difference water index (MNDWI) in the 5 km buffer around the village was related to village-level JE risk (OR: 0.702, 95% CI: 0.524-0.940, P = 0.018), and the number of township-level JE cases was related to the MNDWI in the administrative region (R =-0.522, P = 0.038). This study elucidates the spatial distribution patterns of JE cases and risk, as well as correlated geo-environmental features, at various spatial scales. This study will significantly assist the JE control efforts of the local Centers for Disease Control and Prevention (CDC), which is the base-level CDC, particularly concerning the allocation of medicine and medical staff, the development of immunological plans, and the allocation of pesticides and other control measures for the mosquito vectors of JE.

4.
BMC Geriatr ; 24(1): 413, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730354

RESUMO

BACKGROUND: There is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling. METHODS: A total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI < 5), and high (aCCI ≥5). The Kaplan Meier method was used to assess the cumulative incidence of osteoporosis by different levels of aCCI. The Cox proportional hazards regression model was used to estimate the association of aCCI with the risk of osteoporosis. Receiver operating characteristic (ROC) curve was adapted to assess the performance for aCCI in osteoporosis screening. RESULTS: At baseline, the mean age of all patients was 75.7 years, the mean BMI was 24.8 kg/m2, and 531 (56.1%) patients had high aCCI while 416 (43.9%) were having low aCCI. During a median follow-up of 6.6 years, 296 participants developed osteoporosis. Kaplan-Meier survival curves showed that participants with high aCCI had significantly higher cumulative incidence of osteoporosis compared with those had low aCCI (log-rank test: P < 0.001). When aCCI was examined as a continuous variable, the multivariable-adjusted model showed that the osteoporosis risk increased by 12.1% (HR = 1.121, 95% CI 1.041-1.206, P = 0.002) as aCCI increased by one unit. When aCCI was changed to a categorical variable, the multivariable-adjusted hazard ratios associated with different levels of aCCI [low (reference group) and high] were 1.00 and 1.557 (95% CI 1.223-1.983) for osteoporosis (P <  0.001), respectively. The aCCI (cutoff ≥5) revealed an area under ROC curve (AUC) of 0.566 (95%CI 0.527-0.605, P = 0.001) in identifying osteoporosis in older fall-prone men, with sensitivity of 64.9% and specificity of 47.9%. CONCLUSIONS: The current study indicated an association of higher aCCI with an increased risk of osteoporosis among older fall-prone men, supporting the possibility of aCCI as a marker of long-term skeletal-related adverse clinical outcomes.


Assuntos
Acidentes por Quedas , Osteoporose , Humanos , Masculino , Idoso , Osteoporose/epidemiologia , Osteoporose/diagnóstico , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Incidência , Medição de Risco/métodos , Fatores de Risco , Comorbidade , China/epidemiologia , Fatores Etários
6.
Talanta ; 276: 126227, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38733935

RESUMO

Fatty liver disease affects at least 25 percent of the population worldwide and is a severe metabolic syndrome. Viscosity is closely related to fatty liver disease, so it is urgent to develop an effective tool for monitoring viscosity. Herein, a NIR fluorescent probe called MBC-V is developed for imaging viscosity, consisting of dimethylaniline and malonitrile-benzopyran. MBC-V is non-fluorescent in low viscosity solutions due to intramolecular rotation. In high viscosity solution, the intramolecular rotation of MBC-V is suppressed and the fluorescence is triggered. MBC-V has long emission wavelength at 720 nm and large Stokes shift about 160 nm. Moreover, MBC-V can detect changes in cell viscosity in fatty liver cells, and can image the therapeutic effects of drug in fatty liver cells. By taking advantage of NIR emission, MBC-V can be used as an imaging tool for fatty liver disease and a way to evaluate the therapeutic effect of drug for fatty liver disease.

7.
Natl Sci Rev ; 11(6): nwad258, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38707200

RESUMO

Our understanding of pre-Cretaceous dinosaur reproduction is hindered by a scarcity of evidence within fossil records. Here we report three adult skeletons and five clutches of embryo-containing eggs of a new sauropodomorph from the Lower Jurassic of southwestern China, displaying several significant reproductive features that are either unknown or unlike other early-diverging sauropodomorphs, such as relatively large eggs with a relatively thick calcareous shell formed by prominent mammillary cones, synchronous hatching and a transitional prehatching posture between the crocodilians and living birds. Most significantly, these Early Jurassic fossils provide strong evidence for the earliest known leathery eggs. Our comprehensive quantitative analyses demonstrate that the first dinosaur eggs were probably leathery, elliptical and relatively small, but with relatively long eggshell units, and that along the line to living birds, the most significant change in reptilian egg morphology occurred early in theropod evolution rather than near the origin of Aves.

8.
Lancet Reg Health West Pac ; 46: 101083, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38745972

RESUMO

Background: Despite emerging studies suggesting that occupational physical activity (OPA) might be harmful to health, the available evidence is not definitive. Most of these research studies were conducted in high-income Western countries or in urbanized setting. In China, where over one-third of the population resides in rural area, the impact of OPA on health is not well understood. The goal of this study is to investigate how the association between OPA and mortality vary by urban-rural settings. Methods: Baseline data on OPA was gathered using the Global Physical Activity Questionnaire from 30,650 urban and 49,674 rural working adults as part of the 2013-2014 China Chronic Disease and Risk Factor Surveillance. Participants were followed for a median of 6.2 years, and death records were retrieved from the National Mortality Surveillance System until December 31, 2019. The multivariable Cox proportional hazard model was used to examine urban-rural differences in the association between OPA and all-cause and cardiovascular disease (CVD) mortality. Subgroup analyses were performed by sex, socioeconomic status, leisure time, transportation, and non-occupational physical activity. Findings: During the study period, 1342 deaths were recorded, of which 426 were caused by CVD. In rural area, working adults engaging in occupational moderate-to-vigorous physical activity (MVPA) for ≥40 h per week, compared to those without any, had an adjusted hazard ratio of 0.60 (95% CI: 0.49-0.73) for all-cause mortality and 0.55 (95% CI: 0.37-0.83) for CVD mortality. However, no significant association was found in urban area (0.84 [0.61-1.15] for all-cause mortality, Pinteraction = 0.036; and 0.94 [0.53-1.66] for CVD mortality, Pinteraction = 0.098). The negative associations of occupational MVPA with mortality were more pronounced in women, non-smokers, and those with less non-occupational physical activities. Hypertension, heart rate, and diabetes were important contributors to the relationship between occupational MVPA and mortality. Interpretation: The findings from the current study did not support the notion that high levels of OPA would induce harm. On the contrary, in rural setting, higher levels of OPA were associated with lower mortality risks. Furthermore, the observed urban-rural differences in the association between OPA and mortality underscored the need for context-specific public health guidelines on physical activities. Funding: R&D Program of Beijing Municipal Education Commission (KM202210025026),National Key Research and Development Program of China (2021YFC2500201), and Young Elite Scientist Sponsorship Program by BAST (BYESS2023385).

9.
Microbiol Spectr ; : e0379123, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747583

RESUMO

The upper and lower respiratory tract may share microbiome because they are directly continuous, and the nasal microbiome contributes partially to the composition of the lung microbiome. But little is known about the upper and lower airway microbiome of early postoperative lung transplant recipients (LTRs). Using 16S rRNA gene sequencing, we compared paired nasal swab (NS) and bronchoalveolar lavage fluid (BALF) microbiome from 17 early postoperative LTRs. The microbiome between the two compartments were significantly different in Shannon diversity and beta diversity. Four and eight core NS-associated and BALF-associated microbiome were identified, respectively. NS samples harbored more Corynebacterium, Acinetobacter, and Pseudomonas, while BALF contained more Ralstonia, Stenotrophomonas, Enterococcus, and Pedobacter. The within-subject dissimilarity was higher than the between-subject dissimilarity, indicating a greater impact of sampling sites than sampling individuals on microbial difference. There were both difference and homogeneity between NS and BALF microbiome in early postoperative LTRs. High levels of pathogens were detected in both samples, suggesting that both of them can reflect the diseases characteristics of transplanted lung. The differences between upper and lower airway microbiome mainly come from sampling sites instead of sampling individuals. IMPORTANCE: Lung transplantation is the only therapeutic option for patients with end-stage lung disease, but its outcome is much worse than other solid organ transplants. Little is known about the NS and BALF microbiome of early postoperative LTRs. Here, we compared paired samples of the nasal and lung microbiome from 17 early postoperative LTRs and showed both difference and homogeneity between the two samples. Most of the "core" microbiome in both NS and BALF samples were recognized respiratory pathogens, suggesting that both samples can reflect the diseases characteristics of transplanted lung. We also found that the differences between upper and lower airway microbiome in early postoperative LTRs mainly come from sampling sites instead of sampling individuals.

10.
Genome Res ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744529

RESUMO

While DNA N6-adenine methylation (6mA) is best known in prokaryotes, its presence in eukaryotes has generated great interest recently. Biochemical and genetic evidence supports that AMT1, a MT-A70 family methyltransferase (MTase), is crucial for 6mA deposition in unicellular eukaryotes. Nonetheless, 6mA transmission mechanism remains to be elucidated. Taking advantage of Single Molecule Real-Time Circular Consensus Sequencing (SMRT CCS), here we provide definitive evidence for semiconservative transmission of 6mA in Tetrahymena thermophila In wild-type (WT) cells, 6mA occurs at the self-complementary ApT dinucleotide, mostly in full methylation (full-6mApT); after DNA replication, hemi-methylation (hemi-6mApT) is transiently present on the parental strand, opposite to the daughter strand readily labeled by 5-bromo-2'-deoxyuridine (BrdU). In ΔAMT1 cells, 6mA predominantly occurs as hemi-6mApT. Hemi-to-full conversion in WT cells is fast, robust, and processive, while de novo methylation in ΔAMT1 cells is slow and sporadic. In Tetrahymena, regularly spaced 6mA clusters coincide with linker DNA of nucleosomes arrayed in the gene body. Importantly, in vitro methylation of human chromatin by reconstituted AMT1 complex recapitulates preferential targeting of hemi-6mApT sites in linker DNA, supporting AMT1's intrinsic and autonomous role in maintenance methylation. We conclude that 6mA is transmitted by a semiconservative mechanism: full-6mApT is split by DNA replication into hemi-6mApT, which is restored to full-6mApT by AMT1-dependent maintenance methylation. Our study dissects AMT1-dependent maintenance methylation and AMT1-independent de novo methylation, reveals a 6mA transmission pathway with striking similarity to 5-methyl cytosine (5mC) transmission at the CpG dinucleotide, and establishes 6mA as a bona fide eukaryotic epigenetic mark.

11.
Eur Radiol Exp ; 8(1): 59, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38744784

RESUMO

BACKGROUND: This study investigates the potential of diffusion tensor imaging (DTI) in identifying penumbral volume (PV) compared to the standard gadolinium-required perfusion-diffusion mismatch (PDM), utilizing a stack-based ensemble machine learning (ML) approach with enhanced explainability. METHODS: Sixteen male rats were subjected to middle cerebral artery occlusion. The penumbra was identified using PDM at 30 and 90 min after occlusion. We used 11 DTI-derived metrics and 14 distance-based features to train five voxel-wise ML models. The model predictions were integrated using stack-based ensemble techniques. ML-estimated and PDM-defined PVs were compared to evaluate model performance through volume similarity assessment, the Pearson correlation analysis, and Bland-Altman analysis. Feature importance was determined for explainability. RESULTS: In the test rats, the ML-estimated median PV was 106.4 mL (interquartile range 44.6-157.3 mL), whereas the PDM-defined median PV was 102.0 mL (52.1-144.9 mL). These PVs had a volume similarity of 0.88 (0.79-0.96), a Pearson correlation coefficient of 0.93 (p < 0.001), and a Bland-Altman bias of 2.5 mL (2.4% of the mean PDM-defined PV), with 95% limits of agreement ranging from -44.9 to 49.9 mL. Among the features used for PV prediction, the mean diffusivity was the most important feature. CONCLUSIONS: Our study confirmed that PV can be estimated using DTI metrics with a stack-based ensemble ML approach, yielding results comparable to the volume defined by the standard PDM. The model explainability enhanced its clinical relevance. Human studies are warranted to validate our findings. RELEVANCE STATEMENT: The proposed DTI-based ML model can estimate PV without the need for contrast agent administration, offering a valuable option for patients with kidney dysfunction. It also can serve as an alternative if perfusion map interpretation fails in the clinical setting. KEY POINTS: • Penumbral volume can be estimated by DTI combined with stack-based ensemble ML. • Mean diffusivity was the most important feature used for predicting penumbral volume. • The proposed approach can be beneficial for patients with kidney dysfunction.


Assuntos
Imagem de Tensor de Difusão , Aprendizado de Máquina , Animais , Masculino , Ratos , Imagem de Tensor de Difusão/métodos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Ratos Sprague-Dawley
12.
Comput Biol Chem ; 110: 108071, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38718497

RESUMO

Incomplete data presents significant challenges in drug sensitivity analysis, especially in critical areas like oncology, where precision is paramount. Our study introduces an innovative imputation method designed specifically for low-rank matrices, addressing the crucial challenge of data completion in anticancer drug sensitivity testing. Our method unfolds in two main stages: Initially, the singular value thresholding algorithm is employed for preliminary matrix completion, establishing a solid foundation for subsequent steps. Then, the matrix rows are segmented into distinct blocks based on hierarchical clustering of correlation coefficients, applying singular value thresholding to the largest block, which has been proved to possess the largest entropy. This is followed by a refined data restoration process, where the reconstructed largest block is integrated into the initial matrix completion to achieve the final matrix completion. Compared to other methods, our approach not only improves the accuracy of data restoration but also ensures the integrity and reliability of the imputed values, establishing it as a robust tool for future drug sensitivity analysis.

13.
Exp Biol Med (Maywood) ; 249: 10104, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38708425

RESUMO

Seawater-drowning-induced acute lung injury (SD-ALI) is a life-threatening disorder characterized by increased alveolar-capillary permeability, an excessive inflammatory response, and refractory hypoxemia. Perfluorocarbons (PFCs) are biocompatible compounds that are chemically and biologically inert and lack toxicity as oxygen carriers, which could reduce lung injury in vitro and in vivo. The aim of our study was to explore whether the vaporization of PFCs could reduce the severity of SD-ALI in canines and investigate the underlying mechanisms. Eighteen beagle dogs were randomly divided into three groups: the seawater drowning (SW), perfluorocarbon (PFC), and control groups. The dogs in the SW group were intratracheally administered seawater to establish the animal model. The dogs in the PFC group were treated with vaporized PFCs. Probe-based confocal laser endomicroscopy (pCLE) was performed at 3 h. The blood gas, volume air index (VAI), pathological changes, and wet-to-dry (W/D) lung tissue ratios were assessed. The expression of heme oxygenase-1 (HO-1), nuclear respiratory factor-1 (NRF1), and NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasomes was determined by means of quantitative real-time polymerase chain reaction (qRT-PCR) and immunological histological chemistry. The SW group showed higher lung injury scores and W/D ratios, and lower VAI compared to the control group, and treatment with PFCs could reverse the change of lung injury score, W/D ratio and VAI. PFCs deactivated NLRP3 inflammasomes and reduced the release of caspase-1, interleukin-1ß (IL-1ß), and interleukin-18 (IL-18) by enhancing the expression of HO-1 and NRF1. Our results suggest that the vaporization of PFCs could attenuate SD-ALI by deactivating NLRP3 inflammasomes via the HO-1/NRF1 pathway.


Assuntos
Lesão Pulmonar Aguda , Fluorocarbonos , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Fluorocarbonos/farmacologia , Cães , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Água do Mar , Masculino , Afogamento/metabolismo , Modelos Animais de Doenças , Pulmão/patologia , Pulmão/metabolismo , Pulmão/efeitos dos fármacos
14.
Int J Inj Contr Saf Promot ; : 1-12, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712966

RESUMO

As the popularity of electric bicycles (e-bikes) continues to surge, the number of accidents involving them has commensurately increased. A significant factor contributing to the high fatality rate in these accidents is the low usage of helmets among e-bike riders. Helmets have been proven to reduce the severity of injuries, yet their usage remains unexpectedly low. This issue is particularly pronounced among college students, the primary buyer group for e-bikes. Regrettably, there is a lack of research exploring their intentions to wear helmets. Understanding determinants of their intentions to wear helmets is crucial in promoting safe e-bike travel. Therefore, the present study aims to develop an integrated theoretical model that combines the Theory of Planned Behavior (TPB) and the Health Belief Model (HBM) to examine the factors influencing e-bike riders' helmet-wearing intentions among college students. Additionally, two variables-descriptive norms and law enforcement-are incorporated. The results indicate that the integrated model accounts for 76% of the variance in helmet-wearing intention, surpassing single-theory models. Specifically, the TPB accounts for 65%, while the HBM explains 53%. Notably, law enforcement emerges as the most influential factor, highlighting the crucial role of enforcing regulations and promoting awareness. Other significant factors include subjective and descriptive norms, attitudes, perceived benefits, perceived susceptibility, perceived barriers, and perceived severity. These findings provide valuable insights for policy development and targeted interventions aimed at improving helmet wear rates among e-bike riders, especially among the college student population.

15.
Thromb Res ; 238: 161-171, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38723521

RESUMO

The immune system is an emerging regulator of hemostasis and thrombosis. The concept of immunothrombosis redefines the relationship between coagulation and immunomodulation, and the Gas6/Tyro3-Axl-MerTK (TAM) signaling pathway builds the bridge across them. During coagulation, Gas6/TAM signaling pathway not only activates platelets, but also promotes thrombosis through endothelial cells and vascular smooth muscle cells involved in inflammatory responses. Thrombosis appears to be a common result of a Gas6/TAM signaling pathway-mediated immune dysregulation. TAM TK and its ligands have been found to be involved in coagulation through the PI3K/AKT or JAK/STAT pathway in various systemic diseases, providing new perspectives in the understanding of immunothrombosis. Gas6/TAM signaling pathway serves as a breakthrough target for novel therapeutic strategies to improve disease management. Many preclinical and clinical studies of TAM receptor inhibitors are in process, confirming the pivotal role of Gas6/TAM signaling pathway in immunothrombosis. Therapeutics targeting the TAM receptor show potential both in anticoagulation management and immunotherapy. Here, we review the immunological functions of the Gas6/TAM signaling pathway in coagulation and its multiple mechanisms in diseases identified to date, and discuss the new clinical strategies that may generated by these roles.

16.
Childs Nerv Syst ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709258

RESUMO

Sporadic vestibular schwannomas (VSs) are rare in children. When occurred in the pediatric population, they usually appear bilaterally and are related to neurofibromatosis type 2 (NF2). The current study reports a 4-year-old boy without family history of VS or NF2 who presented with a large (5.7-cm) VS involving the right cerebellopontine angle and internal auditory canal. Through seven-staged surgical interventions and two stereotactic γ­knife radiosurgery, the disease was stabilized. At 2-year follow-up, the child had right ear hearing loss, grade IV facial palsy, and normal motor function and gait. No definite evidence of gene mutation regarding NF2 can be identified after sequence analysis and deletion/duplication testing. This case highlights the significance of considering the possibility of sporadic VSs, even in very young children. It emphasizes the importance of not overlooking initial symptoms, as they may indicate the presence of a large tumor and could potentially result in delayed diagnosis.

17.
Planta ; 259(6): 147, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714547

RESUMO

MAIN CONCLUSION: CsNAC086 was found to promote the expression of CsFLS, thus promoting the accumulation of flavonols in Camellia sinensis. Flavonols, the main flavonoids in tea plants, play an important role in the taste and quality of tea. In this study, a NAC TF gene CsNAC086 was isolated from tea plants and confirmed its regulatory role in the expression of flavonol synthase which is a key gene involved in the biosynthesis of flavonols in tea plant. Yeast transcription-activity assays showed that CsNAC086 has self-activation activity. The transcriptional activator domain of CsNAC086 is located in the non-conserved C-terminal region (positions 171-550), while the conserved NAC domain (positions 1-170) does not have self-activation activity. Silencing the CsNAC086 gene using antisense oligonucleotides significantly decreased the expression of CsFLS. As a result, the concentration of flavonols decreased significantly. In overexpressing CsNAC086 tobacco leaves, the expression of NtFLS was significantly increased. Compared with wild-type tobacco, the flavonols concentration increased. Yeast one-hybrid assays showed CsNAC086 did not directly regulate the gene expression of CsFLS. These findings indicate that CsNAC086 plays a role in regulating flavonols biosynthesis in tea plants, which has important implications for selecting and breeding of high-flavonols-concentration containing tea-plant cultivars.


Assuntos
Camellia sinensis , Flavonóis , Regulação da Expressão Gênica de Plantas , Nicotiana , Proteínas de Plantas , Camellia sinensis/genética , Camellia sinensis/metabolismo , Flavonóis/biossíntese , Flavonóis/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Oxirredutases/genética , Oxirredutases/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/genética , Plantas Geneticamente Modificadas
18.
China CDC Wkly ; 6(18): 401-407, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38737479

RESUMO

Introduction: This research investigates trends pertaining to the prevalence of low fruit and vegetable consumption among the labor force population in China. The study considered data derived from four nationally representative cross-sectional surveys. Methods: The data under review for this study was derived from the China Chronic Disease and Risk Factor Surveillance (CCDRFS) carried out in 2010, 2013, 2015, and 2018, correspondingly. We utilized a food frequency questionnaire to evaluate the quantity and frequency of fruit and vegetable consumption. The estimated prevalence of low fruit and vegetable consumption was calculated for each survey, while considering factors such as sex, age, location, and socioeconomic status (SES). Participants' SES was ascertained via latent class analysis, serving to identify distinct classes based on criteria such as education, occupation, and household income per capita. Logistic regression was deployed to determine the statistical significance of trends. Results: From 2010 to 2018, there was a notable increase in the average daily consumption of vegetables and fruits among the working population, rising from 418.6 g/day to 491.8 g/day (P<0.01 for trend). During the same period, the prevalence of low fruit and vegetable intake declined from 51.1% to 43.5% [P<0.001 for trend; -1.6% average annual percent change (AAPC)]. This downward trend was prevalent across genders, however, certain subgroups of adults (e.g., those living in rural areas or those of low SES) saw stable consumption levels throughout this period (P>0.05 for trend). Conclusion: Over the past nine years, there has been a notable decline in the prevalence of low fruit and vegetable consumption among the labor force population in China. Moreover, the comparatively deficient intake of fruits and vegetables evident among individuals of lower SES warrants further attention.

19.
Mar Genomics ; 75: 101108, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38735675

RESUMO

Dimethylsulfoniopropionate (DMSP) is one of the most abundant sulfur-containing organic compounds on the earth, which is an important carbon and sulfur source and plays an important role in the global sulfur cycle. Marine microorganisms are an important group involved in DMSP metabolism. The strain Cobetia sp. D5 was isolated from seawater samples in the Yellow Sea area of Qingdao during an algal bloom. There is still limited knowledge on the capacity of DMSP utilization of Cobetia bacteria. The study reports the whole genome sequence of Cobetia sp. D5 to understand its DMSP metabolism pathway. The genome of Cobetia sp. D5 consists of a circular chromosome with a length of 4,233,985 bp and the GC content is 62.56%. Genomic analysis showed that Cobetia sp. D5 contains a set of genes to transport and metabolize DMSP, which can cleave DMSP to produce dimethyl sulphide (DMS) and 3-Hydroxypropionyl-Coenzyme A (3-HP-CoA). DMS diffuses into the environment to enter the global sulfur cycle, whereas 3-HP-CoA is catabolized to acetyl CoA to enter central carbon metabolism. Thus, this study provides genetic insights into the DMSP metabolic processes of Cobetia sp. D5 during a marine algal bloom, and contributes to the understanding of the important role played by marine bacteria in the global sulfur cycle.


Assuntos
Genoma Bacteriano , Compostos de Sulfônio , Enxofre , Compostos de Sulfônio/metabolismo , Enxofre/metabolismo , Água do Mar/microbiologia , Sulfetos/metabolismo , China
20.
Bioresour Technol ; 401: 130716, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38641301

RESUMO

Oleanolic acid and its derivatives are widely used in the pharmaceutical, agricultural, cosmetic and food industries. Previous studies have shown that oleanolic acid production levels in engineered cell factories are low, which is why oleanolic acid is still widely extracted from traditional medicinal plants. To construct a highly efficient oleanolic acid production strain, rate-limiting steps were regulated by inducible promoters and the expression of key genes in the oleanolic acid synthetic pathway was enhanced. Subsequently, precursor pool expansion, pathway refactoring and diploid construction were considered to harmonize cell growth and oleanolic acid production. The multi-strategy combination promoted oleanolic acid production of up to 4.07 g/L in a 100 L bioreactor, which was the highest level reported.


Assuntos
Ácido Oleanólico , Saccharomyces cerevisiae , Ácido Oleanólico/biossíntese , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Reatores Biológicos , Engenharia Metabólica/métodos , Engenharia Genética/métodos , Regiões Promotoras Genéticas
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