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1.
Ecol Evol ; 14(4): e11278, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628918

RESUMO

Although several phylogeographic studies of Asian snakes have been conducted, most have focused on pitvipers, with non-venomous snakes, such as colubrids or natricids, remaining poorly studied. The Chinese keelback water snake (Trimerodytes percarinatus Boulenger) is a widespread, semiaquatic, non-venomous species occurring in China and southeastern Asia. Based on mitochondrial DNA (mtDNA) and single nucleotide polymorphism (SNP) data, we explored the population genetic structure, genetic diversity, and evolutionary history of this species. MtDNA-based phylogenetic analysis showed that T. percarinatus was composed of five highly supported and geographically structured lineages. SNP-based phylogenetic analysis, principal component analysis, and population structure analysis consistently revealed four distinct, geographically non-overlapping lineages, which was different from the mtDNA-based analysis in topology. Estimation of divergence dates and ancestral area of origin suggest that T. percarinatus originated ~12.68 million years ago (95% highest posterior density: 10.36-15.96 Mya) in a region covering southwestern China and Vietnam. Intraspecific divergence may have been triggered by the Qinghai-Xizang Plateau uplift. Population demographics and ecological niche modeling indicated that the effective population size fluctuated during 0.5 Mya and 0.002 Mya. Based on the data collected here, we also comment on the intraspecific taxonomy of T. percarinatus and question the validity of the subspecies T. p. suriki.

2.
J Hazard Mater ; 470: 134160, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38574665

RESUMO

OBJECTIVE: To investigate the effects of polycyclic aromatic hydrocarbons(PAHs) on puberty in boys. METHODS: 695 subjects were selected from four primary schools in Chongqing, China. 675 urine samples from these boys were collected four PAH metabolites: 1-hydroxypyrene, 2-hydroxynaphthoic, 2-hydroxyfluorene, and 9-hydroxyphenanthrene. Pubertal development of 695 boys was assessed at follow-up visits starting in December 2015 and occurring every six months thereafter until now, data used in this article ending in June 2021. A total of 12 follow-up visits were performed. Cox proportional hazards regression models were used to analyze the relationship between PAH metabolite concentrations and indicators of pubertal timing. RESULTS: The mean age at puberty onset of testicular volume, facial hair, pubic hair, first ejaculation, and axillary hair in boys was 11.66, 12.43, 12.51, 12.72 and 13.70 years, respectively. Cox proportional hazards regression models showed that boys with moderate level of 1-OHPyr exposure was associated with earlier testicular development (hazard ratio [HR] = 1.276, 95% confidence interval [CI]: 1.006-1.619), with moderate level of 2-OHNap were at higher risk of early testicular development (HR = 1.273, 95% CI: 1.002-1.617) and early axillary hair development (HR = 1.355, 95% CI: 1.040-1.764), with moderate level of 2-OHFlu was associated with earlier pubic hair development (HR = 1.256, 95% CI: 1.001-1.577), with high level of 9-OHPhe were at higher risk of early fisrt ejaculation (HR = 1.333, 95% CI: 1.005-1.767) and early facial hair development (HR = 1.393, 95% CI: 1.059-1.831). CONCLUSION: Prepubertal exposure to PAHs may be associated with earlier pubertal development in boys.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38573719

RESUMO

Participants in an eye-movement experiment performed a modified version of the Landolt-C paradigm (Williams & Pollatsek, 2007) to determine if there are preferred viewing locations when they searched for target squares embedded in linear arrays of spatially contiguous clusters of squares (i.e., sequences of one to four squares having missing segments of variable size and orientation). The results of this experiment indicate that, although the peaks of the single- and first-of-multiple-fixation landing-site distributions were respectively located near the centers and beginnings of the clusters, thereby replicating previous patterns that have been interpreted as evidence for the default saccadic-targeting hypothesis, the same dissociation was evident on nonclusters (i.e., arbitrarily defined regions of analysis). Furthermore, properties of the clusters (e.g., character number and gap size) influenced fixation durations and forward saccade length, suggesting that ongoing stimulus processing affects decisions about when and where (i.e., how far) to move the eyes. Finally, results of simulations using simple oculomotor-based, default-targeting, and dynamic-adjustment models indicated that the latter performed better than the other two, suggesting that the dynamic-adjustment strategy likely reflects the basic perceptual and motor constraints shared by a variety of visual tasks, rather than being specific to Chinese reading. The theoretical implications of these results for existing and future accounts of eye-movement control are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

4.
Front Public Health ; 12: 1348234, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590814

RESUMO

China is actively encouraging households to replace traditional solid fuels with clean energy. Based on the Chinese Families Panel Survey (CFPS) data, this paper uses propensity scores matching with the difference-in-differences model to examine the impact of clean energy in the household sector on residents' health status, and whether such an energy transition promotes health equity by favoring relatively disadvantaged social groups. The results show that: (1) The use of cleaner cooking fuels can significantly improve residents' health status; (2) The older adult and women have higher health returns from the clean energy transition, demonstrating that, from the perspective of age and gender, the energy transition contributes to the promotion of health equity; (3) The clean energy transition has a lower or insignificant health impact on residents who cannot easily obtain clean energy or replace non-clean energy at an affordable price. Most of these individuals live in low-income, energy-poor, or rural households. Thus, the energy transition exacerbates health inequalities. This paper suggests that to reduce the cost of using clean energy and help address key issues in health inequality, Chinese government efforts should focus on improving the affordability, accessibility, and reliability of clean energy.


Assuntos
Poluição do Ar em Ambientes Fechados , Humanos , Feminino , Idoso , Poluição do Ar em Ambientes Fechados/análise , Disparidades nos Níveis de Saúde , Reprodutibilidade dos Testes , China , Iniquidades em Saúde
5.
Womens Health Rep (New Rochelle) ; 5(1): 334-339, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596477

RESUMO

Intravascular leiomyoma (IVL) is usually defined as a histologically benign leiomyoma that originates in a uterine fibroid or the intrauterine vein wall and grows and expands intravenously. We report a case in which pelvic IVL was detected early and discuss the early diagnosis of and best treatment for this tumor.

6.
J Transl Med ; 22(1): 341, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594751

RESUMO

BACKGROUND: Chemoimmunotherapy has shown promising advantages of eliciting immunogenic cell death and activating anti-tumor immune responses. However, the systemic toxicity of chemotherapy and tumor immunosuppressive microenvironment limit the clinical application. METHODS: Here, an injectable sodium alginate hydrogel (ALG) loaded with nanoparticle albumin-bound-paclitaxel (Nab-PTX) and an immunostimulating agent R837 was developed for local administration. Two murine hepatocellular carcinoma and breast cancer models were established. The tumor-bearing mice received the peritumoral injection of R837/Nab-PTX/ALG once a week for two weeks. The antitumor efficacy, the immune response, and the tumor microenvironment were investigated. RESULTS: This chemoimmunotherapy hydrogel with sustained-release character was proven to have significant effects on killing tumor cells and inhibiting tumor growth. Peritumoral injection of our hydrogel caused little harm to normal organs and triggered a potent antitumor immune response against both hepatocellular carcinoma and breast cancer. In the tumor microenvironment, enhanced immunogenic cell death induced by the combination of Nab-PTX and R837 resulted in 3.30-fold infiltration of effector memory T cells and upregulation of 20 biological processes related to immune responses. CONCLUSIONS: Our strategy provides a novel insight into the combination of chemotherapy and immunotherapy and has the potential for clinical translation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Camundongos , Animais , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Imiquimode/farmacologia , Imiquimode/uso terapêutico , Morte Celular Imunogênica , Linhagem Celular Tumoral , Neoplasias Hepáticas/tratamento farmacológico , Imunoterapia/métodos , Imunidade , Microambiente Tumoral
7.
Nat Commun ; 15(1): 3035, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600088

RESUMO

People living with HIV (PLWH) experience increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors associated with this vulnerability remain uncertain. In the general population, alterations in the N-glycans on IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG N-glycans in cross-sectional and longitudinal samples from 1214 women and men, living with and without HIV. PLWH exhibit an accelerated accumulation of pro-aging-associated glycan alterations and heightened expression of senescence-associated glycan-degrading enzymes compared to controls. These alterations correlate with elevated markers of inflammation and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit a reduced ability to elicit anti-HIV Fc-mediated immune activities. These findings hold potential for the development of biomarkers and tools to identify and prevent premature aging and comorbidities in PLWH.


Assuntos
Senilidade Prematura , Infecções por HIV , Masculino , Humanos , Feminino , Imunoglobulina G , Estudos Transversais , Envelhecimento , Inflamação/complicações , Polissacarídeos
8.
ACS Appl Mater Interfaces ; 16(14): 18008-18018, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38556992

RESUMO

Nanostructured electrode materials become a vital component for future electrode materials because of their short electron and ion transport distances for fast charge and discharge processes and sufficient space between particles for volume expansion. So, achieving a smaller size of the nanomaterial with stable structure and high electrode performance is always the pursuit. Herein, the hybrid electrode material system hydrogen-substituted graphdiyne (HsGDY)/Cu2O-quantum dots (QDs) composed of an active carbon substrate and vibrant metal oxide QD load was established by HsGDY and cuprous oxide. The HsGDY frame with conjugated structure not only delivers impressive capacity by a self-exchange mechanism but also characterizes a matrix to forge strong connections with numerous active Cu2O-QDs for the prevention of aggregation, leading to a homogeneous storage and transport of charge in a bulk material of crisscross structural pores. QD-based electrode materials would exhibit desired capacities by their large surface area, abundant active surface atoms, and the short diffusion pathway. The hybrid system of HsGDY/Cu2O-QDs delivers an ultrahigh capacity of 1230 mA h g-1 with loading density reaching up to 1 mg cm-2. In the meantime, the electrode exhibits a long cycle stability of over 8000 cycles. The synergistic effect endows the hybrid system electrode with an approximately theoretical energy density, suggesting the great potential of such carbon/QD hybrid material system applied for high-performance batteries.

9.
Heliyon ; 10(7): e28867, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38601545

RESUMO

Thyroid storm (TS) leading to acute liver failure is rare but fatal in clinical practice and hepatic failure can remarkably limit medication options for TS. We successfully cured a patient with TS complicated with acute hepatic failure using therapeutic plasma exchange (TPE) and a double plasma molecular absorption system (DPMAS) and summarized the case characteristics of 10 similar critical patients reported worldwide. We recommend that patients with TS complicated with liver failure disuse propylthiouracil or methimazole. TPE should be utilized to rapidly decrease thyroid hormone levels, and DPMAS should be considered for supportive treatment in the presence of hepatic encephalopathy or dramatic bilirubin elevations.

10.
Materials (Basel) ; 17(7)2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38611994

RESUMO

The impacts of various aggregate particle sizes and cement contents on the internal structure of pervious concrete were investigated. Accordingly, test blocks with different aggregate particle sizes and cement contents were dissected and photographed. Subsequently, the captured images were processed using the ImageJ software (1.53i) to analyze the profiles of the test blocks and identify the internal mesoscopic parameters of the pervious concrete. This study discusses the relationship between microscopic parameters and macroscopic factors based on experimental results. It also fits functional equations linking the permeability coefficient with pore parameters, matrix parameters, and compressive strength. The results indicated that, as the aggregate size increased, the internal pore diameter of the pervious concrete increased, whereas the total area and width of the cement matrix decreased. This resulted in a low permeability coefficient and high compressive strength of the test block. Increasing the cement content in pervious concrete reduced the porosity and increased the width and area of the internal matrix. Consequently, the permeability coefficient decreased, and the compressive strength of the test block increased.

11.
Mater Today Bio ; 26: 101054, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38633865

RESUMO

The hypoxic tumor microenvironment (TME) of osteosarcoma (OS) is the Achilles' heel of oxygen-dependent photodynamic therapy (PDT), and tremendous challenges are confronted to reverse the hypoxia. Herein, we proposed a "reducing expenditure of O2 and broadening sources" dual-strategy and constructed ultrasmall IrO2@BSA-ATO nanogenerators (NGs) for decreasing the O2-consumption and elevating the O2-supply simultaneously. As O2 NGs, the intrinsic catalase (CAT) activity could precisely decompose the overexpressed H2O2 to produce O2 in situ, enabling exogenous O2 infusion. Moreover, the cell respiration inhibitor atovaquone (ATO) would be at the tumor sites, effectively inhibiting cell respiration and elevating oxygen content for endogenous O2 conservation. As a result, IrO2@BSA-ATO NGs systematically increase tumor oxygenation in dual ways and significantly enhance the antitumor efficacy of PDT. Moreover, the extraordinary photothermal conversion efficiency allows the implementation of precise photothermal therapy (PTT) under photoacoustic guidance. Upon a single laser irradiation, this synergistic PDT, PTT, and the following immunosuppression regulation performance of IrO2@BSA-ATO NGs achieved a superior tumor cooperative eradicating capability both in vitro and in vivo. Taken together, this study proposes an innovative dual-strategy to address the serious hypoxia problem, and this microenvironment-regulable IrO2@BSA-ATO NGs as a multifunctional theranostics platform shows great potential for OS therapy.

13.
Pattern Recognit ; 1522024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38645435

RESUMO

Deep learning models for medical image segmentation are usually trained with voxel-wise losses, e.g., cross-entropy loss, focusing on unary supervision without considering inter-voxel relationships. This oversight potentially leads to semantically inconsistent predictions. Here, we propose a contextual similarity loss (CSL) and a structural similarity loss (SSL) to explicitly and efficiently incorporate inter-voxel relationships for improved performance. The CSL promotes consistency in predicted object categories for each image sub-region compared to ground truth. The SSL enforces compatibility between the predictions of voxel pairs by computing pair-wise distances between them, ensuring that voxels of the same class are close together whereas those from different classes are separated by a wide margin in the distribution space. The effectiveness of the CSL and SSL is evaluated using a clinical cone-beam computed tomography (CBCT) dataset of patients with various craniomaxillofacial (CMF) deformities and a public pancreas dataset. Experimental results show that the CSL and SSL outperform state-of-the-art regional loss functions in preserving segmentation semantics.

14.
J Biol Eng ; 18(1): 21, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486263

RESUMO

BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare intermediate vascular tumor with unclear pathogenesis. Recently, three dimensional (3D) cell spheroids and organoids have played an indispensable role in the study of many diseases, such as infantile hemangioma and non-involuting congenital hemangiomas. However, few research on KHE are based on the 3D model. This study aims to evaluate the 3D superiority, the similarity with KHE and the ability of drug evaluation of EOMA spheroids as an in vitro 3D KHE model. RESULTS: After two days, relatively uniform morphology and high viability of EOMA spheroids were generated by the rotating cell culture system (RCCS). Through transcriptome analysis, compared with 2D EOMA cells, focal adhesion-related genes such as Itgb4, Flt1, VEGFC, TNXB, LAMA3, VWF, and VEGFD were upregulated in EOMA spheroids. Meanwhile, the EOMA spheroids injected into the subcutaneous showed more obvious KMP than 2D EOMA cells. Furthermore, EOMA spheroids possessed the similar characteristics to the KHE tissues and subcutaneous tumors, such as diagnostic markers (CD31 and LYVE-1), cell proliferation (Ki67), hypoxia (HIF-1α) and cell adhesion (E-cadherin and N-cadherin). Based on the EOMA spheroid model, we discovered that sirolimus, the first-line drug for treating KHE, could inhibit EOMA cell proliferation and downregulate the VEGFC expression. Through the extra addition of VEGFC, the effect of sirolimus on EOMA spheroid could be weakened. CONCLUSION: With a high degree of similarity of the KHE, 3D EOMA spheroids generated by the RCCS can be used as a in vitro model for basic researches of KHE, generating subcutaneous tumors and drug screening.

15.
Int Immunopharmacol ; 132: 111926, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38552297

RESUMO

Mortality due to malignant tumors is one of the major factors affecting the life expectancy of the global population. Therapeutic antibodies are a cutting-edge treatment method for restricting tumor growth. B7-H3 is highly expressed in tumor tissues, but rarely in normal tissues. B7-H3 is closely associated with poor prognosis in patients with tumors. B7-H3 is an important target for antitumor therapy. In this study, the fully human anti-B7H3 single-chain antibodies (scFvs) were isolated and screened from the fully human phage immune library with B7H3 as the target. The antibodies screened from a fully human phage library had low immunogenicity and high affinity, which was more beneficial for clinical application. Leveraging B7-H3 scFvs as a foundation, we constructed two distinct recombinant antibody formats, scFv-Fc and IgG1, characterized by elevated affinity and a prolonged half-life. The results demonstrated that the recombinant antibodies had high specificity and affinity for the B7-H3 antigen and inhibited tumor cell growth by enhancing the ADCC. After treatment with anti-B7H3 recombinant antibody, the number of infiltrating T cells in the tumor increased and the secretion of IFN- γ by infiltrating T cells increased in vivo. Additionally, the use of pleural fluid samples obtained from tumor-afflicted patients revealed the ability of anti-B7-H3 recombinant antibodies to reverse CD8+ T cell exhaustion. In summary, we screened the fully human anti-B7H3 recombinant antibodies with specificity and high affinity that increase immune cell infiltration and IFN-γ secretion, thereby inhibiting tumor cell growth to a certain extent. This finding provides a theoretical basis for the development of therapeutic tumor antibodies and could help promote further development of antibody-based drugs.

16.
Int J Biol Macromol ; 265(Pt 1): 130834, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38484815

RESUMO

Blending poly (butylene adipate-co-terephthalate) (PBAT) and polylactic acid (PLA) is a cost-effective strategy to obtain biodegradable plastic with complementary properties. However, the incompatibility between PBAT and PLA is a great challenge for fabricating high-performance composite films. Herein, the ethyl acetate fractionated lignin with the small glass transition temperature and low molecular weight was achieved and incorporated into the PBAT/PLA composite as a compatibilizer. The fractionated lignin can be uniformly dispersed within the PBAT/PLA matrix through a melt blending process and interact with the molecular chain of PBAT and PLA as a bonding bridge, which enhances the intermolecular interactions and reduces the interfacial tension of PBAT/PLA. By adding fractionated lignin, the tensile strength of the PBAT/PLA composite increased by 35.4 % and the yield strength increased by 37.7 %. Owing to lignin, the composite films possessed the ultraviolet shielding function and exhibited better water vapor barrier properties (1.73 ± 0.08 × 10-13 g·cm/cm2·s·Pa). This work conclusively demonstrated that fractionated lignin can be used as a green compatibilizer and a low-cost functional filler for PBAT/PLA materials, and provides guidance for the application of lignin in biodegradable plastics.


Assuntos
Alcenos , Plásticos Biodegradáveis , Lignina , Ácidos Ftálicos , Adipatos , Poli A , Poliésteres
17.
J Immunother Cancer ; 12(3)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38519053

RESUMO

BACKGROUND: The survival benefit observed in children with neuroblastoma (NB) and minimal residual disease who received treatment with anti-GD2 monoclonal antibodies prompted our investigation into the safety and potential clinical benefits of anti-CD3×anti-GD2 bispecific antibody (GD2Bi) armed T cells (GD2BATs). Preclinical studies demonstrated the high cytotoxicity of GD2BATs against GD2+cell lines, leading to the initiation of a phase I/II study in recurrent/refractory patients. METHODS: The 3+3 dose escalation phase I study (NCT02173093) encompassed nine evaluable patients with NB (n=5), osteosarcoma (n=3), and desmoplastic small round cell tumors (n=1). Patients received twice-weekly infusions of GD2BATs at 40, 80, or 160×106 GD2BATs/kg/infusion complemented by daily interleukin-2 (300,000 IU/m2) and twice-weekly granulocyte macrophage colony-stimulating factor (250 µg/m2). The phase II segment focused on patients with NB at the dose 3 level of 160×106 GD2BATs/kg/infusion. RESULTS: Of the 12 patients enrolled, 9 completed therapy in phase I with no dose-limiting toxicities. Mild and manageable cytokine release syndrome occurred in all patients, presenting as grade 2-3 fevers/chills, headaches, and occasional hypotension up to 72 hours after GD2BAT infusions. GD2-antibody-associated pain was minimal. Median overall survival (OS) for phase I and the limited phase II was 18.0 and 31.2 months, respectively, with a combined OS of 21.1 months. A phase I NB patient had a complete bone marrow response with overall stable disease. In phase II, 10 of 12 patients were evaluable: 1 achieved partial response, and 3 showed clinical benefit with prolonged stable disease. Over 50% of evaluable patients exhibited augmented immune responses to GD2+targets post-GD2BATs, as indicated by interferon-gamma (IFN-γ) EliSpots, Th1 cytokines, and/or chemokines. CONCLUSIONS: This study demonstrated the safety of GD2BATs up to 160×106 cells/kg/infusion. Coupled with evidence of post-treatment endogenous immune responses, our findings support further investigation of GD2BATs in larger phase II clinical trials.


Assuntos
Antineoplásicos , Neuroblastoma , Osteossarcoma , Criança , Humanos , Linfócitos T/patologia , Neuroblastoma/patologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Osteossarcoma/tratamento farmacológico
18.
Biochim Biophys Acta Mol Cell Res ; 1871(5): 119716, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38547933

RESUMO

BACKGROUND: The carcinogenic transcription factor c-Myc is the most aggressive oncogene, which drive malignant transformation and dissemination of triple-negative breast cancer (TNBC). Recruitment of many cofactors, especially WDR5, a protein that nucleates H3K4me chromatin modifying complexes, play a pivotal role in regulating c-Myc-dependent gene transcription, a critical process for c-Myc signaling to function in a variety of biological and pathological contexts. For this reason, interrupting the interaction between c-Myc and the transcription cofactor WDR5 may become the most promising new strategy for treating c-Myc driven TNBC. METHODS: Immunoprecipitation and mass spectrometry (IP-MS) is used to screen proteins that bind c-Myc/WDR5 interactions. The interaction of METTL3 with c-Myc/WDR5 in breast cancer tissues and TNBC cells was detected by Co-IP and immunofluorescence. Subsequently, we further analyzed the influence of METTL3 expression on c-Myc/WDR5 protein expression and its interaction stability by Western blot and Co-IP. The correlation between METTL3 and c-Myc pathway was analyzed by ChIP-seq sequencing and METTL3 knockdown transcriptome data. The effect of METTL3 expression on c-Myc transcriptional activity was detected by ChIP-qPCR and Dual Luciferase Reporter. At the same time, the overexpression vector METTL3-MUT (m6A) was constructed, which mutated the methyltransferase active site (Aa395-398, DPPW/APPA), and further explored whether the interaction between METTL3 and c-Myc/WDR5 was independent of methyltransferase activity. In addition, we also detected the changes of METTL3 expression on TNBC's sensitivity to small molecule inhibitors such as JQ1 and OICR9429 by CCK8, Transwell and clonal formation assays. Finally, we further verified our conclusions in spontaneous tumor formation mouse MMTV-PyMT and nude mouse orthotopic transplantation tumor models. RESULTS: METTL3 was found to bind mainly to c-Myc/WDR5 protein in the nucleus. It enhances the stability of c-Myc/WDR5 interaction through its methyltransferase independent mechanism, thereby enhancing the transcriptional activity of c-Myc on downstream glucose metabolism genes. Notably, the study also confirmed that METTL3 can directly participate in the transcription of glucose metabolism genes as a transcription factor, and knockdown METTL3 enhances the drug sensitivity of breast cancer cells to small molecule inhibitors JQ1 and OICR9429. The study was further confirmed by spontaneous tumor formation mouse MMTV-PyMT and nude mouse orthotopic transplantation tumor models. CONCLUSION: METTL3 binds to the c-Myc/WDR5 protein complex and promotes glycolysis, which plays a powerful role in promoting TNBC progression. Our findings further broaden our understanding of the role and mechanism of action of METTL3, and may open up new therapeutic avenues for effective treatment of TNBC with high c-Myc expression.

19.
Sci Rep ; 14(1): 6360, 2024 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493206

RESUMO

Parent-child and teacher-child relationship closeness have been shown to be crucial for children's development of socioemotional competencies from preschool to school-age stages. However, less is known about the importance of developing close relationships with young infants and toddlers attending childcare group settings for their early socioemotional development. The current study aimed to address this gap and to explore how child gender may influence the associations. Participants included 378 Hong Kong Chinese children (196 girls; Mage = 22.05 months, SD = 9.81 months) enrolled in childcare centres, along with their parents and teachers. Parents reported on children's socioemotional competencies as well as their relationship closeness with children; teachers reported on their relationship closeness with children. Multiple group structural equation modelling was used to analyse the results. The findings showed that both parent-child and teacher-child closeness were positively associated with children's social competence, while teacher-child closeness was negatively associated with children's anxiety behaviour. Parents of girls reported greater parent-child closeness, higher levels of social competence, and higher levels of anxiety behaviours compared to parents of boys. Furthermore, teacher-child closeness was significantly associated with social competence exclusively among girls, while parent-child closeness was significantly associated with anxiety behaviours solely among boys. Findings are discussed in terms of the role of child gender in influencing the associations between parent-child closeness, teacher-child closeness, and children's socioemotional competencies in the earliest years.


Assuntos
Relações Interpessoais , Professores Escolares , Masculino , Pré-Escolar , Lactente , Feminino , Humanos , Professores Escolares/psicologia , Pais , Habilidades Sociais , Ansiedade
20.
Huan Jing Ke Xue ; 45(2): 898-908, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471928

RESUMO

Magnetic phosphorous biochar (MPBC) was prepared from Camellia oleifera shells using phosphoric acid activation and iron co-deposition. The materials were characterized and analyzed through scanning electron microscopy (SEM), X-ray diffractometry (XRD), specific surface area and pore size analysis (BET), Fourier infrared spectroscopy (FT-IR), and X-ray photoelectron spectroscopy (XPS). MPBC had a high surface area (1 139.28 m2·g-1) and abundant surface functional groups, and it could achieve fast solid-liquid separation under the action of an external magnetic field. The adsorption behavior and influencing factors of sulfamethoxazole (SMX) in water were investigated. The adsorbent showed excellent adsorption properties for SMX under acidic and neutral conditions, and alkaline conditions and the presence of CO32- had obvious inhibition on adsorption. The adsorption process conformed to the quasi-second-order kinetics and Langmuir model. The adsorption rate was fast, and the maximum adsorption capacity reached 356.49 mg·g-1. The adsorption process was a spontaneous exothermic reaction, and low temperature was beneficial to the adsorption. The adsorption mechanism was mainly the chemisorption of pyrophosphate surface functional groups (C-O-P bond) between the SMX molecule and MPBC and also included hydrogen bonding, π-π electron donor-acceptor (π-πEDA) interaction, and a pore filling effect. The development of MPBC adsorbent provides an effective way for resource utilization of waste Camellia oleifera shells and treatment of sulfamethoxazole wastewater.


Assuntos
Sulfametoxazol , Poluentes Químicos da Água , Sulfametoxazol/química , Adsorção , Espectroscopia de Infravermelho com Transformada de Fourier , Água , Poluentes Químicos da Água/análise , Carvão Vegetal/química , Fósforo , Cinética , Fenômenos Magnéticos
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