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1.
Langmuir ; 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39352068

RESUMO

This study aims to understand the bulk and interfacial performance of potato protein microgels. Potato protein (PoP) was used to produce microgels of submicrometer diameter via a top-down approach of thermal cross-linking followed by high-shear homogenization of the bulk gel. Bulk "parent" gels were formed at protein concentrations [PoP] = 5-18 wt %, which subsequently varied in their bulk shear elastic modulus (G') by several orders of magnitude (1-100 kPa), G' increasing with increasing [PoP]. The PoP microgels (PoPM) formed from these parent gels had diameters varying between 100 and 300 nm (size increasing with increasing G' and [PoP]), as observed via dynamic light scattering and atomic force microscopy (AFM) of PoPM adsorbed onto silicon. Interfacial rheology (interfacial shear storage and loss moduli, Gi' and Gi″) and interfacial tension (γ) of adsorbed films of PoP (i.e., nonheated PoP) and PoPM (both at tetradecane-water interfaces) were also studied, as well as the bulk rheology of the PoPM dispersions. The results showed that PoPM dispersions (at 50 vol %) had significantly higher bulk viscosity and shear thinning properties compared to the nonmicrogelled PoP at the same overall [PoP], but the bulk rheological behavior was in sharp contrast to the interfacial rheological performance, where Gi' and Gi″ of PoP were higher than for any of the PoPM. This suggests that the deformability and size of the microgels were key in determining the interfacial rheology of the PoPM. These findings may be attributed to the limited capacity for "unfolding" and lateral interactions of the larger PoPM at the interface, which are presumed to be stiffer due to their production from the strongest PoP gels. Our study further confirmed that heating and cooling the adsorbed films of PoPM after their adsorption showed little change, highlighting that hydrogen bonding was limited between the microgel particles.

2.
Curr Med Imaging ; 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39360543

RESUMO

OBJECTIVE: This study aims to optimize the downgrading of BI-RADS class 4a nodules by combining various sectional elastography techniques with age. MATERIALS AND METHODS: We performed conventional ultrasonography, strain elastography (SE), and shear wave elastography (SWE) on patients. Quantitative parameters recorded included age, cross-sectional and longitudinal area ratios (C-EI/B, L-EI/B), strain rate ratios (C-SR, L-SR), overall average elastic modulus values (C-Emean1, L-Emean1), five-point average elastic modulus values (C-Emean2, L-Emean2), and maximum elastic modulus values (C-Emax, L-Emax). RESULTS: Histopathological evaluations showed that out of 230 lesions, 45 were malignant, and 185 were benign. The sensitivity and specificity of conventional ultrasonography were 100% and 0%, respectively. In contrast, SE and SWE exhibited higher specificity but lower sensitivity. Crosssectional parameters (C-EI/B, C-SR, C-Emean1, C-Emean2, and C-Emax) outperformed their longitudinal counterparts, with C-SR and C-Emax showing the highest specificity (72.43% and 73.51%) and satisfactory sensitivity (80.00% and 88.89%). Combining age with C-SR and C-Emax significantly improved diagnostic efficiency, achieving a sensitivity of 97.78% and a specificity of 77.30%. CONCLUSION: Integrating age with C-SR and C-Emax effectively reduces unnecessary biopsies for most BI-RADS 4a benign lesions while maintaining a very low misdiagnosis rate.

3.
J Health Commun ; : 1-10, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39376089

RESUMO

Media coverage of depression on social media with specific framings could shape people's perception and attitude, which is significant in reducing the stigma and promoting support for depression sufferers. Adopting the lens of moral foundation theory (MFT), this study aims to explore the effect of inherent moral framings within depression coverage on social media on the stigma and approval attitudes toward depression in audiences' responses. A large language model and a dictionary-based approach were respectively adopted to score depression-related media coverages (n = 919) and corresponding comments (n = 92,505) collected from the Weibo platform against MFT's five dimensions and (de)stigma attitudes. The results indicated that care, purity, and fairness framings are prevalent in depression coverage, surpassing moral framings such as betrayal, harm, and cheating. Most responses expressed approval rather than stigma. Moreover, the use of care and loyalty framings can elicit approval responses but decrease audience engagement.

4.
J Immunother Cancer ; 12(10)2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39384195

RESUMO

BACKGROUND: Histone deacetylase (HDAC), a kind of protease that regulates gene expression by modifying protein acetylation levels, is usually aberrantly activated in tumors. The approved pan-HDAC inhibitors (HDACi) have exhibited clinical benefits for hematopoietic malignancies. Recently, HDACis have emerged as enhancers of antitumor immunity. However, the effect of HDACs on the tumor immune microenvironment of lung adenocarcinoma (LUAD) and the underlying mechanism is largely unknown. METHODS: C57BL/6J and BALB/c nude mice with subcutaneous tumors were used for in vivo therapeutic effects and mechanistic investigations. Flow cytometry was used to measure the toxicity and exhaustion of human CD8+T cells after co-culturing with tumor cells and to determine the immunophenotype of tumor-infiltrating CD8+T cells. A series of experimental techniques, including RNA sequencing, quantitative PCR, western blot, ELISA, mass spectrometry, co-immunoprecipitation, chromatin immunoprecipitation and immunohistochemistry, were used to explore the underlying molecular mechanism. RESULTS: The pan-HDACi vorinostat (SAHA) promoted CD8+T cell infiltration and effector function in LUAD through suppressing FGL1, a newly identified major ligand of LAG-3. Mechanistically, SAHA inhibited the activity of HDAC1, an essential deacetylase of JAK1. This increased the acetylation level of JAK1 at lysine 1109, thus promoting its proteasomal degradation and subsequently reducing STAT3-driven FGL1 transcription. The combination regimen of SAHA and anti-LAG-3 therapy was further explored in an immunocompetent LUAD mouse model. Compared with those receiving control or single agent treatments, mice receiving combination therapy exhibited a lower tumor burden and superior CD8+T-cell-killing activity. CONCLUSIONS: Our results revealed a novel mechanism by which the HDACi SAHA potentiates CD8+T-cell-mediated antitumor activity through the HDAC1/JAK1/FGL1 axis, providing a rationale for the combined use of HDACis and immunotherapy.


Assuntos
Adenocarcinoma de Pulmão , Histona Desacetilase 1 , Inibidores de Histona Desacetilases , Janus Quinase 1 , Neoplasias Pulmonares , Animais , Camundongos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Histona Desacetilase 1/metabolismo , Histona Desacetilase 1/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/imunologia , Janus Quinase 1/metabolismo , Vorinostat/farmacologia , Vorinostat/uso terapêutico , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Camundongos Nus , Camundongos Endogâmicos C57BL , Feminino
5.
Front Psychiatry ; 15: 1417355, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39364381

RESUMO

Background: Adolescence is a period characterized by rapid biological and psychological change, and adolescents have a heightened risk of depression. Parental rearing is an important influencing factor for depression in adolescence. However, the mechanism of influence needs further exploration. Methods: A total of 1839 adolescents were recruited from a junior and a senior high school in Zhongshan City, Guangdong Province, China. They were requested to completed the Parental Bonding Instrument (PBI), Self-Compassion Scale (SCS), and Depression Anxiety and Stress Scale-21(DASS-21). Results: Adolescents recalled their mothers as being more caring and controlling than their fathers. Parental care (maternal care, paternal care) and parental encouragement of autonomy (maternal encouragement of autonomy, paternal encouragement of autonomy) were both negative predictors of depression, while parental control (maternal control, paternal control) was positive predictor of depression. Self-compassion mediated all relationships between parental rearing styles (parental care, parental encouragement of autonomy, and parental control) and depression but played different mediating roles (complete or incomplete mediating role) in different relationships. Conclusion: Self-compassion plays a mediator role in all relationships between perceived parental rearing styles (parental care, parental encouragement of autonomy, and parental control) and depression. Adolescents who grown up with less parental care, less parental encouragement of autonomy, and high parental control deserve special attention. Educators and clinicians could help those adolescents reduce the occurrence of depression by increasing their level of self-compassion.

6.
Plant Physiol ; 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39365781

RESUMO

NONPHOTOTROPIC HYPOCOTYL3 (NPH3) is a key regulator of hypocotyl phototropism under both low- and high-intensity blue light (LBL/HBL), mediating phototropin1 (phot1) and phot2 signaling. NPH3 undergoes dephosphorylation and is released from the plasma membrane (PM) upon blue light irradiation. However, how its phosphorylation status and PM localization mediate phot1 and phot2 signaling in Arabidopsis (Arabidopsis thaliana) remains elusive. In this study, we found that fusing NPH3 with GFP at its C terminus (N3G) impaired its release from the PM, a defect exacerbated by a phosphorylation-deficient mutation, resulting in a dephosphorylated NPH3-GFP (N3AG). Unlike N3G, transgenic lines expressing N3AG exhibited defective hypocotyl phototropism under HBL, which could be rescued by myristoylation at the N-terminus of N3AG (mN3AG), indicating that NPH3 phosphorylation is not essential for HBL-induced phototropic responses when it is artificially anchored at the PM via its N terminus. Furthermore, genetic analysis revealed that N3AG anchored to the PM by its N terminus (as in mN3AG) only rescues phot1-mediated HBL responses, which require RPT2. However, N3AG failed to regulate phot2-mediated HBL signaling, regardless of its PM orientation. Taken together, our results revealed that NPH3 phosphorylation is essential for phot2-mediated hypocotyl phototropism under HBL, but is not required for phot1-mediated HBL signaling when the NPH3 N terminus is PM-anchored.

7.
Psychol Rep ; : 332941241288537, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39364575

RESUMO

Hiding effort has become prevalent among adolescents; however, whether this behavior benefits or harms their social impression remains unclear. The study explored whether hiding effort is an effective impression management strategy to obtain high popularity, likeability, interpersonal trust, and cooperation intention from peers. Using hypothetical scenarios, Study 1 (N = 243) found that hiding effort led to lower popularity, likeability, interpersonal trust, and cooperation intention among adolescents. Study 2 (N = 176) replicated the findings of Study 1 and found that the hiding-effort adolescents did not realize these negative consequences. Furthermore, Study 2 revealed that authenticity mediated the effect of hiding effort on popularity, likeability, interpersonal trust, and cooperation intention. The findings provided theoretical and practical implications for educators and adolescents. Educators should foster environments where effort and authenticity are rewarded. Adolescents should understand the cost of hiding efforts from peers.

8.
Cell Death Dis ; 15(10): 714, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39353892

RESUMO

MAT2B works together with MAT2A to synthesize S-Adenosyl methionine (SAM) as the primary methyl donor. MAT2B, despite lacking catalytic activity, exerts regulatory control over the enzymatic activity of MAT2A. In addition to the enzymatic activity regulation, we find that, in an NADP+-dependent manner, MAT2B binds and stabilizes MAT2A. Disruption of the cellular NADP+ remodels the protein level of MAT2A. The pentose phosphatase pathway regulates the level of MAT2A protein through the interaction of NADP+ with MAT2B. Additionally, MAT2B-MAT2A interaction regulates the mRNA m6A modification and stability. In liver tumors, the Mat2a mRNA level is elevated but the protein level is decreased by the restricted NADP+. Blocking the interaction between MAT2B and MAT2A by the keto diet can suppress liver tumor growth. These findings reveal that MAT2B is essential for regulating the protein levels of MAT2A and connecting SAM synthesis to mRNA m6A.


Assuntos
Adenosina , Neoplasias Hepáticas , Metionina Adenosiltransferase , Metionina Adenosiltransferase/metabolismo , Metionina Adenosiltransferase/genética , Humanos , Adenosina/metabolismo , Adenosina/análogos & derivados , Animais , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , NADP/metabolismo , Camundongos , S-Adenosilmetionina/metabolismo , Linhagem Celular Tumoral , Ligação Proteica
9.
Nanotechnology ; 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39389093

RESUMO

Accurate and point-of-care cholesterol detection is of paramount significance for the prevention of cardiovascular diseases. The colorimetric assay based on peroxidase is a commonly used approach for cholesterol detection, without requiring any complicated biomolecular labeling or sophisticated instrumentation. Copper nanoclusters (CuNCs), exhibiting luminescent properties and peroxidase activity, have garnered significant attention in biomedical application recently. Herein, the glutathione-stabilized copper nanoclusters (GSH-CuNCs) were prepared with an easy one-pot method, employing glutathione as both a reducing agent and stabilizer. An optimization of the GSH-CuNCs preparation was carried out to obtain the highest peroxidase-like activity. UV-Vis absorption was measured to explore the steady-state kinetics of the GSH-CuNCs-catalyzed oxidation of 3,3',5,5' - tetramethylbenzidine (TMB) by H2O2. A colorimetric method for cholesterol detection was developed by combining the catalytic reaction of CuNCs and the enzymatic oxidation of cholesterol with cholesterol oxidase (ChOx). Under the optimized conditions, the UV-Vis absorbance of oxidized TMB (oxTMB) is proportional to the concentration of cholesterol within the range of 6.2-187.5 µM, and the limit of detection (LOD) is determined to be 3.0 µM. More importantly, cholesterol levels can be directly distinguished with the naked eye. Furthermore, the practicality of the method for detecting cholesterol in human serum has been verified with promising results. As expected, this simple, cost-effective, and easy-to-operate colorimetric method for cholesterol detection has potential applications in clinical diagnosis and provides valuable insights into the colorimetric sensing based on CuNCs.

10.
Vaccines (Basel) ; 12(9)2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39340020

RESUMO

Children's susceptibility to influenza increased after COVID-19 control measures were lifted. This study investigated parental hesitancy toward seasonal influenza vaccination (SIV) for children and its determinants in the post-pandemic era. An online survey of full-time adult factory workers was conducted in Shenzhen, China in December 2023. This analysis was based on 1175 parents who had at least one child under the age of 18 years. Among all parents, 37.1% were hesitant to have their index child receive SIV. Mothers exhibited lower parental hesitancy toward SIV compared to fathers (31.9% versus 41.3%, p < 0.001). After adjusting for significant background characteristics, mothers and fathers who were more satisfied with the SIV health promotion materials, perceived more severe consequences of seasonal influenza for their children, and perceived more benefits, cues to action, and self-efficacy related to their children's SIV were less likely to exhibit hesitancy toward SIV. Higher frequency of exposure to information about the increasing number of patients or severe cases due to seasonal influenza and other upper respiratory infections on social media was associated with lower parental hesitancy toward SIV among fathers but not mothers. There is a strong need to address parental hesitancy toward SIV for children in the post-pandemic era.

11.
Chem Biodivers ; : e202400655, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39327547

RESUMO

Rubi fructus (Fupenzi) is the Chinese medicine for both food and medicine, which can be used to tonify kidney yang, strengthen essence and shrink urine, but its effective components and mechanism are not clear. In this paper, the active components of Fupenzi in vivo and in vitro were detected. Adenine was used to replicate the model of kidney yang deficiency, and organ index, biochemical index and histopathology were used to evaluate the effect of different doses of Fupenzi on tonifying kidney yang. Metabonomics technique was used to analyze the metabolic regulation mechanism of Fupenzi in improving kidney yang deficiency syndrome. The results showed that 61 chemical constituents of Fupenzi were identified in vitro. A total of 51 chemical components were identified, including 30 prototype components and 21 metabolic components, which may be theeffective components of Fupenzi. The results of pharmacodynamics showed that Fupenzi can effectively improve the symptom of kidney-yang deficiency, which may be mainly through primary bile acid biosynthesis, linoleic acid metabolism, steroid hormone biosynthesis, ß-alanine metabolism, glutathione metabolism, porphyrin and chlorophyll metabolism, unsaturated fatty acid biosynthesis, arachidonic acid metabolism, arginine and proline metabolism and other metabolic pathways to improve adenine-induced metabolic disorders in rats with kidney-yang deficiency syndrome.

12.
Struct Equ Modeling ; 31(5): 891-908, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39308934

RESUMO

Dynamic structural equation modeling (DSEM) is a useful technique for analyzing intensive longitudinal data. A challenge of applying DSEM is the missing data problem. The impact of missing data on DSEM, especially on widely applied DSEM such as the two-level vector autoregressive (VAR) cross-lagged models, however, is understudied. To fill the research gap, we evaluated how well the fixed effects and variance parameters in two-level bivariate VAR models are recovered under different missingness percentages, sample sizes, the number of time points, and heterogeneity in missingness distributions through two simulation studies. To facilitate the use of DSEM under customized data and model scenarios (different from those in our simulations), we provided illustrative examples of how to conduct Monte Carlo simulations in Mplus to determine whether a data configuration is sufficient to obtain accurate and precise results from a specific DSEM.

13.
Microorganisms ; 12(9)2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39338573

RESUMO

The aim of this review was to delve into the extent of mosquito virome coverage (proportion of viral reads) via meta-viromic sequencing and uncover potential factors of heterogeneity that could impact this coverage. Data sources were PubMed, Web of Science, Embase, Scopus, Science-Direct, Google Scholar, and the China National Knowledge Infrastructure. Pooled coverage was estimated using random-effects modeling, and subgroup analyses further reveal potential heterogeneous factors. Within the three mosquito genera studied, Culex exhibited the highest pooled viral coverage of mosquito viromes at 7.09% (95% CI: 3.44-11.91%), followed by Anopheles at 5.28% (95% CI: 0.45-14.93%), and Aedes at 2.11% (95% CI: 0.58-7.66%). Subgroup analyses showed that multiple processing methods significantly affected the viral coverage of mosquito viromes, especially pre-treatment of mosquito samples with saline buffer/medium and antibiotics prior to DNase/RNase treatment and removal of the host genome prior to RNA library construction. In conclusion, the results of this study demonstrate that the viral coverage of mosquito viromes varies between mosquito genera and that pre-treatment of mosquito samples with saline buffer/medium and antibiotics before DNase/RNase treatment and removing host genomes prior to RNA library construction are critical for the detection of RNA viruses in mosquito vectors using meta-viromic sequencing.

14.
Phys Rev Lett ; 133(10): 106701, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39303256

RESUMO

Quantum geometry plays a pivotal role in the second-order response of PT-symmetric antiferromagnets. Here we study the nonlinear response of 2D altermagnets protected by C_{n}T symmetry and show that their leading nonlinear response is third order. Furthermore, we show that the contributions from the quantum metric and Berry curvature enter separately: the longitudinal response for all planar altermagnets only has a contribution from the quantum metric quadrupole (QMQ), while transverse responses in general have contributions from both the Berry curvature quadrupole (BCQ) and QMQ. We show that for the well-known example of d-wave altermagnets the Hall response is dominated by the BCQ. Both longitudinal and transverse responses are strongly dependent on the crystalline anisotropy. While altermagnets are strictly defined in the limit of vanishing spin orbit coupling (SOC), real altermagnets exhibit weak SOC, which is essential to observe this response. Specifically, SOC gaps the spin-group protected nodal line, generating a response peak that is sharpest when SOC is weak. Two Dirac nodes also contribute a divergence to the nonlinear response, whose scaling changes as a function of SOC. Finally, we apply our results to thin films of the 3D altermagnet RuO_{2}. Our work uncovers distinct features of altermagnets in nonlinear transport, providing experimental signatures as well as a guide to disentangling the different components of their quantum geometry.

15.
J Exerc Sci Fit ; 22(4): 408-416, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39309731

RESUMO

Background: Children with ADHD demand for effective intervention with minimum side effect to improve executive function (EF) and health well-being. Method: This study used a three-arm partially-blinded randomized controlled trial to test the effects of two different kinds of 8-week game-based training programs (game-based HIIT program, GameHIIT; and game-based structured aerobic exercise program, GameSAE) on EF and other health indicators of children with ADHD, which was compared with a non-treatment control group. Results: A total of 49 children with ADHD completed the program. Analyses of EF tests and parental survey indicated that (i) there is no significant intragroup difference among all measures between pre-/post-intervention tests for two game-based intervention groups. The only significant intergroup difference was observed in self-monitor score of parent-reported child's EF between GameSAE group and the control (large effect). Similarly, cerebral hemodynamic responses also found no significant group effect for all EF tests. However, the time effects were observed in several channels in the GameHIIT group in two EF tests (Color Words Stroop Test and Tower of London Test). No significant change of participants' overall ADHD symptoms was found in the pre-/post-tests for three groups. Nonetheless, further analyses revealed that both of two game-based training programs exhibited the significant positive effects on child's PA levels and the large effects on levels of physical fitness, when they were compared to the control. Conclusion: By this study, a significant enhancement in physical fitness and PA levels were found in both game-based PA interventions when they were compared with control group. However, the effectiveness of game-based PA interventions on improving EF or reducing ADHD symptoms remains unclear. This implies that a larger intervention dosage or a tailored intervention design may be warranted to improve the EF of children with ADHD.

16.
Fetal Pediatr Pathol ; 43(5): 387-398, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39219028

RESUMO

BACKGROUND: Neuroblastoma, a pediatric malignancy, is significantly influenced by genetic factors. Prior research indicates that the OGG1 rs1052133 G > C polymorphism correlates with a decreased risk of neuroblastoma. METHODS: We analyzed 57 neuroblastoma and 21 adrenal samples, using immunohistochemistry to measure OGG1 and STUB1 expression levels. We conducted a survival analysis to explore relationship between the expressions and neuroblastoma prognosis. RESULTS: Notably higher OGG1 expression and significantly lower STUB1 expression in neuroblastoma. OGG1 levels were significantly correlated with patient age, tumor location, histological grade, Shimada classification, INSS stage, and risk category. A negative association was observed between OGG1 and STUB1 expressions. Higher OGG1 expression was linked to reduced PFS and OS. Lower STUB1 expression was associated with unfavorable PFS. Additionally, OGG1 expression and risk category emerged as independent predictors of prognosis. CONCLUSION: OGG1 potentially functions as an oncogene in NB, with its activity possibly modulated by STUB1 through the ubiquitination pathway.


Assuntos
DNA Glicosilases , Neuroblastoma , Ubiquitina-Proteína Ligases , Humanos , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Feminino , Masculino , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Pré-Escolar , Lactente , DNA Glicosilases/genética , DNA Glicosilases/metabolismo , Criança , Prognóstico , Ubiquitinação , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Reparo do DNA
17.
Cell Mol Biol Lett ; 29(1): 123, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277732

RESUMO

BACKGROUND: Loss-of-function mutations of ZBTB24 cause immunodeficiency, centromeric instability, and facial anomalies syndrome 2 (ICF2). ICF2 is a rare autosomal recessive disorder with immunological defects in serum antibodies and circulating memory B cells, resulting in recurrent and sometimes fatal respiratory and gastrointestinal infections. The genotype-phenotype correlation in patients with ICF2 indicates an essential role of ZBTB24 in the terminal differentiation of B cells. METHODS: We used the clustered regularly interspaced short palindromic repeats (CRISPER)/Cas9 technology to generate B cell specific Zbtb24-deficient mice and verified the deletion specificity and efficiency by quantitative polymerase chain reaction (Q-PCR) and western blotting analyses in fluorescence-activated cell sorting (FACS)-sorted cells. The development, phenotype of B cells and in vivo responses to T cell dependent or independent antigens post immunization were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Adoptive transfer experiment in combination with in vitro cultures of FACS-purified B cells and RNA-Seq analysis were utilized to specifically determine the impact of Zbtb24 on B cell biology as well as the underlying mechanisms. RESULTS: Zbtb24 is dispensable for B cell development and maintenance in naive mice. Surprisingly, B cell specific deletion of Zbtb24 does not evidently compromise germinal center reactions and the resulting primary and secondary antibody responses induced by T cell dependent antigens (TD-Ags), but significantly inhibits T cell independent antigen-elicited antibody productions in vivo. At the cellular level, Zbtb24-deficiency specifically impedes the plasma cell differentiation of B1 cells without impairing their survival, activation and proliferation in vitro. Mechanistically, Zbtb24-ablation attenuates heme biosynthesis partially through mTORC1 in B1 cells, and addition of exogenous hemin abrogates the differentiation defects of Zbtb24-null B1 cells. CONCLUSIONS: Zbtb24 seems to regulate antibody responses against TD-Ags B cell extrinsically, but it specifically promotes the plasma cell differentiation of B1 cells via heme synthesis in mice. Our study also suggests that defected B1 functions contribute to recurrent infections in patients with ICF2.


Assuntos
Diferenciação Celular , Doenças da Imunodeficiência Primária , Fatores de Transcrição , Animais , Camundongos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Face/anormalidades , Síndromes de Imunodeficiência/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Doenças da Imunodeficiência Primária/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo
18.
Reprod Biol ; 24(4): 100954, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39306921

RESUMO

The integrated stress response (ISR) is implicated in age-related diseases, while the molecular chaperone heat shock protein 70 (HSP70) can facilitate proper protein folding. However, the regulatory mechanism of ISR in insufficient testosterone synthesis of aging Leydig cells (LCs) remains unclear. This study aims to elucidate the regulatory role of ISR in inadequate testosterone synthesis of aging LCs. We observed a positive correlation between testosterone and HSP70 levels, which were found to be decreased in elderly men. ISR was detected in testicular tissue from old mice. The expression of testosterone synthesis related protein and the content of testosterone decreased in testicular tissue of old mice. Conversely, inhibition of the integrated stress response in testicular tissue led to an increase in steroid synthase expression among old mice. Furthermore, inhibiting ISR specifically within aging LCs resulted in enhanced protein translation efficiency and increased expression levels of new HSP70 and steroidogenic acute regulatory protein (StAR). These findings suggest that ISR occurrence within aging LCs affects StAR protein expression through regulation of HSP70-mediated translation, consequently impairing testosterone synthesis.

19.
Fetal Pediatr Pathol ; : 1-11, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39269732

RESUMO

Introduction: Angiosarcoma is an exceedingly rare entity in pediatric population. Herein, we report two pediatric angiosarcoma with novel phenotypic and genotypic profile. Methods: The two patients' information was summarized by clinical data, histopathology, immunohistochemistry, genetic, treatment, and prognosis. Results: Two Chinese children presented with abdominal mass or consumptive hypothyroidism at 2 and 6 years. A patient presented with a unique histopathology of epithelioid AS with smooth muscle hyperplasia, and carried a novel somatic mutation in FAT1 (c.3929C > T/p. Ser1310Leu) along with germ-line variants in CDK8 (c.895A > C/p. Lys299Gln), FANCI (c.3906-07inv/p. Glu1303Lys), and MST1R (c.3581-83delinsACG/p. Arg1194-Ser1195delinsHisGly). The other patient presented with a novel -clinical phenotype of consumptive hypothyroidism. They received postoperative treatment and were monitored for 20 and 26 months, showing good recovery. Conclusion: The phenotypic and genotypic spectrum of AS in pediatric population was expanded by these two patients, which requires the accumulating more cases to gain a deeper understanding.

20.
Phytother Res ; 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39243217

RESUMO

Quercetin has shown potential antihypertensive-like activities in several studies. The present study aimed to test the effect of quercetin supplementation on kidney damage and long-term prognosis in hypertensive patients. The data of enrolled hypertensive patients were acquired from the NHANES dataset. The flavanol intake data was extracted from the FNDDS flavonoid database. Information regarding mortality was extracted from the NCHS. A total of 5801 hypertensive patients were included in this study. Preliminary analysis found that the total flavanols intake dosage was the independent influence factor of the kidney damage prevalence in hypertension, and it was found that only the quercetin supplementation was the protective factor for kidney damage after stratification analysis. For every 10 mg/d increase in quercetin intake, the kidney damage prevalence decreased by 8% [OR = 0.92, 95% CI: 0.85-0.99, p = 0.032]. The comprehensive analysis results suggested that hypertensive patients in the quercetin-high group had a lower kidney damage prevalence and a higher survival probability than those in the quercetin-low group. The urine microalbumin of hypertensive patients in the quercetin-high group was significantly lower than that of hypertensive patients in the quercetin-low group. In addition, at a median follow-up time of 122 months, the mortality decreased by 9% [HR = 0.91, 95% CI: 0.84-0.99, p = 0.031] for every 10 mg/d increase in quercetin intake. The findings suggested that high quercetin intake was associated with low kidney damage prevalence and high survival probability. Based on the existing evidence, promoting quercetin supplementation as a supplementary treatment for hypertensive patients was warranted.

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