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1.
Sci Total Environ ; 927: 172366, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38614325

RESUMO

BACKGROUND: Concerns remain about the neurotoxic properties of the ubiquitous organophosphate esters (OPEs), the replacement of the toxicant polybrominated diphenyl ethers. OBJECTIVES: We examined the associations of prenatal exposure to OPEs and their mixtures with early-life neurodevelopment trajectories. METHODS: Totally 1276 mother-child pairs were recruited from the Shanghai Maternal-Child Pairs Cohort. A high-performance liquid chromatography-triple quadrupole mass spectrometer was used to measure the levels of 7 OPEs in cord serum. Ages and Stages Questionnaires was used to examine children's neuropsychological development at 2, 6, 12, and 24 months of age. Group-based trajectory models were applied to derive the neurodevelopmental trajectories. Multiple linear regression and logistic regression model were performed to assess the relationships between OPEs exposure and neurodevelopment and trajectories. Mixtures for widely detected OPEs (n = 4) were investigated using quantile-based g-computation. RESULTS: Tributyl phosphate (TBP), tris (2-butoxy ethyl) phosphate (TBEP), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and 2-ethylhexyl diphenyl phosphate (EHDPP), had detection rates >50 %. TDCPP had the highest median concentration (1.02 µg/L) in cord serum. EHDPP concentrations were negatively associated with scores in most domains at 12 months of age, with effect values (ß) ranging from -1.89 to -0.57. EHDPP could negatively affect the total ASQ (OR = 1.07, 95 % CI: 1, 1.15) and gross-motor (OR = 1.09, 95 % CI: 1.02, 1.17) trajectory in infancy. Joint exposure to OPEs was associated with decreased scores in the total ASQ, gross-motor, fine-motor and problem-solving domain of 12-month-old infants, with ß ranging from -5.93 to -1.25. In addition, the qgcomp models indicated significant positive associations between the concentrations of OPEs mixtures and risks of the persistently low group of the total ASQ, gross-motor and fine-motor development in early childhood. The impact of OPEs was more pronounced in boys. DISCUSSION: Our findings suggested OPEs, especially EHDPP, had a persistently negative effect on neurodevelopment during the first 2 years.


Assuntos
Desenvolvimento Infantil , Ésteres , Organofosfatos , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , China , Organofosfatos/toxicidade , Lactente , Gravidez , Desenvolvimento Infantil/efeitos dos fármacos , Exposição Materna/estatística & dados numéricos , Masculino , Poluentes Ambientais , Pré-Escolar , Estudos de Coortes , Adulto
2.
Sci Rep ; 14(1): 8574, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615094

RESUMO

Pure self-management model, pure aggregation business model and Self-support + aggregation model are three commonly used business modes on ride-hailing platforms. We use an analytical model to study these three business models and give the optimal business model decision of the platform. The research shows that the heterogeneity ratio of drivers, the cost of the platform under the Self-support model, the franchise fee received by the platform under the aggregation model and the dissatisfaction of the original users on the platform play a key role in the selection of the platform's business model. When the difference between the franchise fee under the aggregation mode and the platform cost under the Self-support mode fails to generate positive feedback on the platform profit, the platform should choose the pure Self-support mode. When riders are more sensitive to the heterogeneity of service quality of the platform and user stickiness can be ensured, the platform should choose the pure aggregation business model. When user stickiness can be guaranteed and the cost of the platform under the self-run model is controllable, the platform should choose the Self-support + aggregation business model.

3.
Laryngoscope ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501703

RESUMO

OBJECTIVES: The purpose of this study is to determine the predictors of neck lymphedema and to explore its association with symptoms and patient-reported outcomes (PROs) in Head and Neck Cancer (HNC) patients who underwent non-operative treatment. METHODS: This study involved a cross-sectional secondary analysis of data from patients diagnosed with head and neck squamous cell carcinoma who underwent radiation therapy (±chemotherapy). Patients with visits <6 weeks or >2 years following completion of radiation and those with recurrent or metastatic cancer were excluded. Presence of post-treatment lymphedema, demographics, clinical characteristics, health-related behaviors, and symptoms were collected. PROs were obtained using validated questionnaires that assessed depression, anxiety, swallowing dysfunction, and quality of life (QOL). Multivariable regression models were used to examine the relationship between lymphedema with predictors and symptoms. RESULTS: Of the 203 patients included, 88 (43.4%) developed post-treatment lymphedema. In multivariable analysis, pre-treatment Body Mass Index (BMI) (odds ratio [OR] = 1.07, 95% confidence interval [CI] [1.01, 1.14] p = 0.016) and N stage (OR = 1.96, 95% CI [1.06, 3.66], p = 0.032) were found to be independently associated with lymphedema. Regarding PROs, lymphedema was associated with greater swallowing dysfunction (3.48, 95% CI [0.20, 6.75], p = 0.038), decreased mouth opening (-3.70, 95% CI [-7.31, -0.10], p = 0.044), and increased fatigue (1.88, 95% CI [1.05, 3.38], p = 0.034). CONCLUSION: Higher pre-treatment BMI and greater N stage are identified as independent predictors for lymphedema development in non-operative HNC patients. Additionally, patients experiencing lymphedema reported worsening swallowing dysfunction and increased symptoms related to trismus and fatigue. Recognizing patients at elevated risk for lymphedema allows for early intervention, alleviation of symptom burden, and optimization of health care resources. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

4.
Talanta ; 273: 125902, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38508126

RESUMO

Current genotoxicity assessment methods are mainly employed to verify the genotoxic safety of drugs, but do not allow for rapid screening of specific genotoxic impurities (GTIs). In this study, a new approach for the recognition of GTIs has been proposed. It is to expose the complex samples to an in vitro nucleoside incubation model, and then draw complete DNA adduct profiles to infer the structures of potential genotoxic impurities (PGIs). Subsequently, the genotoxicity is confirmed in human by 3D bioprinted human liver organoids. To verify the feasibility of the approach, lansoprazole chloride compound (Lanchlor), a PGI during the synthesis of lansoprazole, was selected as the model drug. After confirming genotoxicity by Comet assay, it was exposed to different models to map and compare the DNA adduct profiles by LC-MS/MS. The results showed Lanchlor could generate diverse DNA adducts, revealing firstly its genotoxicity at molecular mechanism of action. Furthermore, the largest variety and content of DNA adducts were observed in the nucleoside incubation model, while the human liver organoids exhibited similar results with rats. The results showed that the combination of DNA adductomics and 3D bioprinted organoids were useful for the rapid screening of GTIs.


Assuntos
Adutos de DNA , Nucleosídeos , Humanos , Ratos , Animais , Nucleosídeos/toxicidade , Cromatografia Líquida , Espectrometria de Massas em Tandem , Dano ao DNA , Fígado , DNA , Organoides , Lansoprazol
5.
Exp Ther Med ; 27(4): 142, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38476910

RESUMO

Currently, no antifibrotic drug in clinical use can effectively treat renal fibrosis. Fluorofenidone (AKFPD), a novel pyridone agent, significantly reduces renal fibrosis by inhibiting the activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome; however, the underlying mechanism of this inhibition is not fully understood. The present study aimed to reveal the molecular mechanism underlying the suppression of NLRP3 inflammasome activation by AKFPD. It investigated the effect of AKFPD on NLRP3 activation and lysosomal cathepsins in a unilateral ureteral obstruction (UUO) rat model, and hypoxia/reoxygenation (H/R)-treated HK-2 cells and murine peritoneal-derived macrophages (PDMs) stimulated with lipopolysaccharide (LPS) and ATP. The results confirmed that AKFPD suppressed renal interstitial fibrosis and inflammation by inhibiting NLRP3 inflammasome activation in UUO rat kidney tissues. In addition, AKFPD reduced the production of activated caspase-1 and maturation of IL-1ß by suppressing NLRP3 inflammasome activation in H/R-treated HK-2 cells and murine PDMs stimulated with LPS and ATP. AKFPD also decreased the activities of cathepsins B, L and S both in vivo and in vitro. Notably, AKFPD downregulated cathepsin B expression and NLRP3 colocalization in the cytoplasm after lysosomal disruptions. Overall, the results suggested that AKFPD attenuates renal fibrosis by inhibiting lysosomal cathepsin-mediated activation of the NLRP3 inflammasome.

6.
JAMA Otolaryngol Head Neck Surg ; 150(4): 295-302, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38386337

RESUMO

Importance: Socioeconomic deprivation is associated with increased risk of poor health and quality-of-life (QOL) outcomes in head and neck cancer (HNC) survivors. However, there are few data on how neighborhood deprivation affects patient-reported outcome measures (PROMs) in HNC survivors. Objective: To investigate whether neighborhood socioeconomic deprivation is associated with symptom burden, psychological distress, and QOL among HNC survivors. Design, Setting, and Participants: This cross-sectional study used prospectively collected data from patients seen in a university-affiliated multidisciplinary HNC survivorship clinic between September 2018 and September 2021 who received radiotherapy for squamous cell carcinoma of the oral cavity, oropharynx, and larynx or hypopharynx. Exposure: Neighborhood socioeconomic deprivation, measured using the Area Deprivation Index (ADI). Main Outcomes and Measures: The PROMs pertaining to symptom burden and severity of psychological distress were measured using the Neck Disability Index, Insomnia Severity Index, the 10-item Eating Assessment Tool, the Generalized Anxiety Disorder 7-item scale, and the 8-item Patient Health Questionnaire. Physical and social-emotional QOL were obtained using the University of Washington QOL questionnaire. Multivariable linear regression analysis adjusting for individual-level sociodemographic, comorbidity, and treatment characteristics investigated the association between ADI and PROMs. A subgroup analysis was performed to compare the lowest (most affluent areas: ADI, 0%-20%) and highest (most deprived areas: ADI, 80%-100%) ADI quintiles. Results: A total of 277 patients were included in the final analysis (mean [SD] age, 64.18 [9.60] years; 215 [77.6%] male). Cancer sites were the oral cavity (52 [18.8%]), oropharyngeal area (171 [61.7%]), and larynx or hypopharynx (54 [19.5%]). Multivariable analysis showed that for every 1-point increase in ADI, social-emotional QOL changed by -0.14 points (95% CI, -0.24 to -0.05 points), anxiety increased by 0.03 points (95% CI, 0.01-0.06 points), and neck disability worsened by 0.05 points (95% CI, 0.01-0.10 points). Compared with patients in the most affluent areas, those in the most deprived areas had significantly lower physical (-15.89 points; 95% CI, -25.96 to -2.31 points; Cohen d = -0.83) and social-emotional (-13.57 points; 95% CI, -22.79 to -3.49 points; Cohen d = -0.69) QOL and higher depression (2.60 points; 95% CI, 0.21-4.40 points; Cohen d = 0.52), anxiety (3.12 points; 95% CI, 1.56-4.66 points; Cohen d = 0.61), insomnia (3.55 points; 95% CI, 0.33-6.41 points; Cohen d = 0.54), and neck disability (5.65 points; 95% CI, 1.66-9.55 points; Cohen d = 0.66) scores. Conclusions and Relevance: In this cross-sectional study, a higher ADI score was associated with higher risk of increased psychological distress, higher symptom burden, and decreased QOL after treatment among HNC survivors. These findings suggest that proactive, patient-centered interventions are needed to address these disparities.


Assuntos
Neoplasias de Cabeça e Pescoço , Angústia Psicológica , Distúrbios do Início e da Manutenção do Sono , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Qualidade de Vida/psicologia , Estudos Transversais , Neoplasias de Cabeça e Pescoço/terapia , Sobreviventes
7.
Angew Chem Int Ed Engl ; 63(16): e202319981, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38381713

RESUMO

Chemoradiotherapy combines radiotherapy with concurrent chemotherapy to potentiate antitumor activity but exacerbates toxicities and causes debilitating side effects in cancer patients. Herein, we report the use of a nanoscale metal-organic layer (MOL) as a 2D nanoradiosensitizer and a reservoir for the slow release of chemotherapeutics to amplify the antitumor effects of radiotherapy. Coordination of phosphate-containing drugs to MOL secondary building units prolongs their intratumoral retention, allowing for continuous release of gemcitabine monophosphate (GMP) for effective localized chemotherapy. In the meantime, the MOL sensitizes cancer cells to X-ray irradiation and provides potent radiotherapeutic effects. GMP-loaded MOL (GMP/MOL) enhances cytotoxicity by 2-fold and improves radiotherapeutic effects over free GMP in vitro. In a colon cancer model, GMP/MOL retains GMP in tumors for more than four days and, when combined with low-dose radiotherapy, inhibits tumor growth by 98 %. The synergistic chemoradiotherapy enabled by GMP/MOL shows a cure rate of 50 %, improves survival, and ameliorates cancer-proliferation histological biomarkers.


Assuntos
Neoplasias , Fosfatos , Humanos , Gencitabina , Quimiorradioterapia , Neoplasias/tratamento farmacológico
8.
Natl Sci Rev ; 11(2): nwad324, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38314400

RESUMO

Iron catalysts are ideal transition metal catalysts because of the Earths abundant, cheap, biocompatible features of iron salts. Iron catalysts often have unique open-shell structures that easily undergo spin crossover in chemical transformations, a feature rarely found in noble metal catalysts. Unfortunately, little is known currently about how the open-shell structure and spin crossover affect the reactivity and selectivity of iron catalysts, which makes the development of iron catalysts a low efficient trial-and-error program. In this paper, a combination of experiments and theoretical calculations revealed that the iron-catalyzed hydrosilylation of alkynes is typical spin-crossover catalysis. Deep insight into the electronic structures of a set of well-defined open-shell active formal Fe(0) catalysts revealed that the spin-delocalization between the iron center and the 1,10-phenanthroline ligand effectively regulates the iron center's spin and oxidation state to meet the opposite electrostatic requirements of oxidative addition and reductive elimination, respectively, and the spin crossover is essential for this electron transfer process. The triplet transition state was essential for achieving high regioselectivity through tuning the nonbonding interactions. These findings provide an important reference for understanding the effect of catalyst spin state on reaction. It is inspiring for the development of iron catalysts and other Earth-abundant metal catalysts, especially from the point of view of ligand development.

9.
Chemistry ; 30(19): e202303739, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38287793

RESUMO

To expand the market capacity of p-diethylbenzene (PDEB), core-shell zeolite (TS-1@MCM-48) is designed as a catalyst for PDEB oxidation. TS-1@MCM-48 catalyst is synthesized by in-situ crystallization method and characterized by X-ray diffraction (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), N2 adsorption-desorption, in-situ electron paramagnetic resonance (EPR) and 29Si nuclear magnetic resonance (29Si MAS-NMR). Oxidation of PDEB by H2O2 was investigated systematically in liquid phase. The conversion of PDEB over TS-1@MCM-48 was 28.1 % and the total selectivity was 72.6 %, where the selectivity of EAP (p-ethylacetophenone) and EPEA (4-ethyl-α-methylbenzyl alcohol) was 28.6 % and 44.0 %, respectively. Compared with TS-1 and MCM-48 zeolite, the conversion rate of reactants and the selectivity of products have been significantly improved. The catalytic performance of TS-1@MCM-48 is derived from its well-crystallized microporous core and mesoporous shell with regular channels, which make active sites of TS-1 zeolite in the catalyst be fully utilized and mass transfer resistance be largely reduced. Further through theoretical calculation, we propose that the oxidation of PDEB is the result of the combination and mutual transformation of free radical process and carbocation process. Core-shell structure ensures the conversion rate of raw materials and improves the selectivity of products.

10.
Exp Cell Res ; 436(2): 113924, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38280435

RESUMO

Cervical cancer (CC), as a common female malignant tumor in the world, is an important risk factor endangering women's health worldwide. The purpose of this study was to investigate the role of RBM15 in CC. The TCGA database was used to screen differentially expressed m6A genes in normal and tumor tissues. QRT-PCR was used to quantify HEIH, miR-802, EGFR, cell stemness, and epithelial-mesenchymal transition (EMT)-related genes. The interaction between HEIH and miR-802 was verified by dual-luciferase reporter assay and RIP assay. The occurrence of tumor cells after different treatments was detected by CCK-8, transwell and EdU staining. BALB/c nude mice were used to examine the effects of different treatments on tumor growth and cell stemness in vivo. RBM15 was upregulated in tumor tissues and cells. M6A was highly enriched in HEIH and enhances its RNA stability. HEIH acts as an oncogenic lncRNA to promote CC cell proliferation, migration and tumor growth. Mechanistically, HEIH regulates tumor cell stemness and promotes the proliferation and migration of CC cells by competitively adsorbing miR-802 and up-regulating the expression of EGFR. In short, our data shown that the m6A methyltransferase RBM15 could affect tumor cell proliferation, metastasis and cell stemness by stabilizing HEIH expression.


Assuntos
Adenina/análogos & derivados , MicroRNAs , RNA Longo não Codificante , Neoplasias do Colo do Útero , Animais , Camundongos , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/patologia , Camundongos Nus , Receptores ErbB/genética , Receptores ErbB/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
11.
Nat Struct Mol Biol ; 31(1): 115-124, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38177687

RESUMO

The subcortical maternal complex (SCMC) plays a crucial role in early embryonic development. Malfunction of SCMC leads to reproductive diseases in women. However, the molecular function and assembly basis for SCMC remain elusive. Here we reconstituted mouse SCMC and solved the structure at atomic resolution using single-particle cryo-electron microscopy. The core complex of SCMC was formed by MATER, TLE6 and FLOPED, and MATER embraced TLE6 and FLOPED via its NACHT and LRR domains. Two core complexes further dimerize through interactions between two LRR domains of MATERs in vitro. FILIA integrates into SCMC by interacting with the carboxyl-terminal region of FLOPED. Zygotes from mice with Floped C-terminus truncation showed delayed development and resembled the phenotype of zygotes from Filia knockout mice. More importantly, the assembly of mouse SCMC was affected by corresponding clinical variants associated with female reproductive diseases and corresponded with a prediction based on the mouse SCMC structure. Our study paves the way for further investigations on SCMC functions during mammalian preimplantation embryonic development and reveals underlying causes of female reproductive diseases related to SCMC mutations, providing a new strategy for the diagnosis of female reproductive disorders.


Assuntos
Desenvolvimento Embrionário , Oócitos , Gravidez , Feminino , Humanos , Camundongos , Animais , Microscopia Crioeletrônica , Zigoto , Camundongos Knockout , Mamíferos
12.
Small ; : e2309633, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38282381

RESUMO

Low-cost bifunctional electrocatalysts capable of efficiently driving the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are needed for the growth of a green hydrogen economy. Herein, a Ru/Co3 O4 heterojunction catalyst rich in oxygen vacancies (VO ) and supported on carbon cloth (RCO-VO @CC) is prepared via a solid phase reaction (SPR) strategy. A RuO2 /Co9 S8 @CC precursor (ROC@CC) is first prepared by loading Co9 S8 nanosheets onto CC, following the addition of RuO2 nanoparticles (NPs). After the SPR process in an Ar atmosphere, Ru/Co3 O4 heterojunctions with abundant VO are formed on the CC. The compositionally optimized RCO-VO @CC electrocatalyst with a Ru content of 0.55 wt.% exhibits very low overpotential values of 11 and 253 mV at 10 mA cm-2 for HER and OER, respectively, in 1 m KOH. Further, a low cell voltage of only 1.49 V is required to achieve a current density of 10 mA cm-2 . Density functional theoretical calculations verify that the outstanding bifunctional electrocatalytic performance originates from synergistic charge transfer between Ru metal and VO -rich Co3 O4 . This work reports a novel approach toward a high-efficiency HER/OER electrocatalyst for energy storage and conversion.

13.
Laryngoscope ; 134 Suppl 1: S1-S12, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37178050

RESUMO

OBJECTIVES: (1) To determine tumor control rates for treating growing vestibular schwannoma (VS) with CyberKnife stereotactic radiosurgery (CK SRS); (2) to determine hearing outcomes after CK SRS; (3) to propose a set of variables that could be used to predict hearing outcomes for patients receiving CK SRS for VS. STUDY DESIGN: Retrospective case series review. METHODS: 127 patients who received CK SRS for radiographically documented growing VS were reviewed. Tumors were monitored for post-procedure growth radiographically with linear measurements and three-dimensional segmental volumetric analysis (3D-SVA). Hearing outcomes were reviewed for 109 patients. Cox proportional hazard modeling was used to identify variables correlated with hearing outcomes. RESULTS: Tumor control rate was 94.5% for treating VS with CK SRS. Hearing outcomes were categorized using the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) classification system. As of their last available audiogram, 33.3% of patients with pre-treatment class A and 26.9% of patients with class B retained their hearing in that class. 15.3% of patients starting with class A or B with extended follow-up (>60 months), maintained hearing within this same grouping. Our final model proposed to predict hearing outcomes included age, fundal cap distance (FCD), tumor volume, and maximum radiation dose to the cochlea; however, FCD was the only statistically significant variable. CONCLUSION: CK SRS is an effective treatment for control of VS. Hearing preservation by class was achieved in a third of patients. Finally, FCD was found to be protective against hearing loss. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:S1-S12, 2024.


Assuntos
Perda Auditiva , Neuroma Acústico , Radiocirurgia , Humanos , Neuroma Acústico/radioterapia , Neuroma Acústico/cirurgia , Estudos Retrospectivos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Audição , Perda Auditiva/etiologia , Perda Auditiva/prevenção & controle , Perda Auditiva/cirurgia , Resultado do Tratamento , Seguimentos
14.
J Neurosci ; 44(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37945348

RESUMO

The auditory steady-state response (ASSR) is a cortical oscillation induced by trains of 40 Hz acoustic stimuli. While the ASSR has been widely used in clinic measurement, the underlying neural mechanism remains poorly understood. In this study, we investigated the contribution of different stages of auditory thalamocortical pathway-medial geniculate body (MGB), thalamic reticular nucleus (TRN), and auditory cortex (AC)-to the generation and regulation of 40 Hz ASSR in C57BL/6 mice of both sexes. We found that the neural response synchronizing to 40 Hz sound stimuli was most prominent in the GABAergic neurons in the granular layer of AC and the ventral division of MGB (MGBv), which were regulated by optogenetic manipulation of TRN neurons. Behavioral experiments confirmed that disrupting TRN activity has a detrimental effect on the ability of mice to discriminate 40 Hz sounds. These findings revealed a thalamocortical mechanism helpful to interpret the results of clinical ASSR examinations.Significance Statement Our study contributes to clarifying the thalamocortical mechanisms underlying the generation and regulation of the auditory steady-state response (ASSR), which is commonly used in both clinical and neuroscience research to assess the integrity of auditory function. Combining a series of electrophysiological and optogenetic experiments, we demonstrate that the generation of cortical ASSR is dependent on the lemniscal thalamocortical projections originating from the ventral division of medial geniculate body to the GABAergic interneurons in the granule layer of the auditory cortex. Furthermore, the thalamocortical process for ASSR is strictly regulated by the activity of thalamic reticular nucleus (TRN) neurons. Behavioral experiments confirmed that dysfunction of TRN would cause a disruption of mice's behavioral performance in the auditory discrimination task.


Assuntos
Córtex Auditivo , Vigília , Feminino , Masculino , Camundongos , Animais , Camundongos Endogâmicos C57BL , Núcleos Talâmicos/fisiologia , Corpos Geniculados/fisiologia , Córtex Auditivo/fisiologia , Estimulação Acústica/métodos , Neurônios GABAérgicos/fisiologia
15.
Tohoku J Exp Med ; 262(2): 63-74, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-37438122

RESUMO

Cuproptosis can serve as potential prognostic predictors in patients with cancer. However, the role of this relationship in ovarian serous cystadenocarcinoma (OV) remains unclear. 376 OV tumor samples were obtained from the Cancer Genome Atlas (TCGA) database, and long non-coding RNAs (lncRNAs) related to cuproptosis were obtained through correlation analysis. The risk assessment model was further constructed by univariate Cox regression analysis and LASSO Cox regression. Bioinformatics was used to analyze the regulatory effect of relevant risk assessment models on tumor mutational burden (TMB) and immune microenvironment. We obtained 5 lncRNAs (AC025287.2, AC092718.4, AC112721.2, LINC00996, and LINC01639) and incorporated them into the Cox proportional hazards model. Kaplan-Meier (KM) curve analysis of the prognosis found that the high-risk group was associated with a poorer prognosis. The receiver operating characteristic (ROC) curve showed stronger predictive power compared to other clinicopathological features. Immune infiltration analysis showed that high-risk scores were inversely correlated with CD8+ T cells, CD4+ T cells, macrophages, NK cells, and B cells. Functional enrichment analysis found that they may act via the extracellular matrix (ECM)-interacting proteins and other pathways. We successfully constructed a reliable cuproptosis-related lncRNA model for the prognosis of OV.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , RNA Longo não Codificante , Feminino , Humanos , RNA Longo não Codificante/genética , Cistadenocarcinoma Seroso/genética , Prognóstico , Carcinoma Epitelial do Ovário , Imunoterapia , Neoplasias Ovarianas/genética , Microambiente Tumoral
16.
Mater Horiz ; 11(4): 930-938, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38093700

RESUMO

The low photosensitivity of phenanthraquinone-doped poly(methyl methacrylate) (PQ/PMMA) severely limits its recording speed for holographic data storage. A high-performance holographic recording medium based on a unique combination of N-methylpyrrolidone (NMP) regulated PQ/PMMA has been developed. A NMP-PQ/PMMA photopolymer with high sensitivity, high diffraction efficiency and negligible volume shrinkage was successfully fabricated by tuning the composition of the PMMA matrix by varying the ratio of NMP to monomers. The photosensitivity is increased by 6.9 times (from 0.27 cm J-1 to 1.86 cm J-1), the diffraction efficiency is increased from 60% to > 80%, and volume shrinkage is decreased by a factor of 2 (from 0.4% to 0.2%). Further investigation revealed that the addition of NMP significantly reduced the molecular weight of PMMA and increased the amount of MMA residuals, while also improving the solubility of PQ molecules. More interestingly, for the first time, the NMP-PQ/PMMA material could record data information repeatedly at least 6 times. The present study elucidates that the introduction of NMP not only modulates the molecular weight of PMMA but also enables the residual monomer MMA to more easily combine with PQ to form a photoproduct for improved holographic performance.

17.
Front Neurosci ; 17: 1224479, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38027496

RESUMO

Introduction: Auditory change detection is a pre-attentive cortical auditory processing ability. Many neurological and psychological disorders can lead to defects in this process. Some studies have shown that phase synchronization may be related to auditory discrimination. However, the specific contributions of phase synchronization at different frequencies remain unclear. Methods: We analyzed the electroencephalogram (EEG) data of 29 healthy adults using an oddball paradigm consisting of a standard stimulus and five deviant stimuli with varying frequency modulation patterns, including midpoint frequency transitions and linear frequency modulation. We then compared the peak amplitude and latency of inter-trial phase coherence (ITC) at the theta(θ), alpha(α), and beta(ß) frequencies, as well as the N1 component, and their relationships with stimulus changes. At the same time, the characteristics of inter-trial phase coherence in response to the pure tone stimulation and chirp sound with a fine time-frequency structure were also assessed. Result: When the stimulus frequency did not change relative to the standard stimulus, the peak latency of phase coherence at ß and α frequencies was consistent with that of the N1 component. The inter-trial phase coherence at ß frequency (ß-ITC)served as a faster indicator for detecting frequency transition when the stimulus frequency was changed relative to the standard stimulus. ß-ITC demonstrates temporal stability when detecting pure sinusoidal tones and their frequency changes, and is less susceptible to interference from other neural activities. The phase coherence at θ frequency could integrate the frequency and temporal characteristics of deviant into a single representation, which can be compared with the memory trace formed by the standard stimulus, thus effectively identifying auditory changes. Pure sinusoidal tone stimulation could induce higher inter-trial phase coherence in a smaller time window, but chirp sounds with a fine time-frequency structure required longer latencies to achieve phase coherence. Conclusion: Phase coherence at theta, alpha, and beta frequencies are all involved in auditory change detection, but play different roles in this automatic process. Complex time-frequency modulated stimuli require longer processing time for effective change detection.

18.
Environ Sci Pollut Res Int ; 30(53): 114438-114451, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37858030

RESUMO

Fumonisin B1 (FB1) is a widely present mycotoxin that accumulates in biological systems and poses a health risk to animals. However, few studies have reported the molecular mechanism by which FB1 induces nephrotoxicity. The aim of this study was to assess the extent of nephrotoxicity during FB1 exposure and the possible molecular mechanisms behind it. Therefore, 180 young quails were equally divided into two groups. The control group was fed typical quail food, while the experimental group was fed quail food containing 30 mg·kg-1 FB1. Various parameters were assessed, which included histopathological, ultrastructural changes, levels of biochemical parameters, oxidative indicators, inflammatory factors, possible target organelles mitochondrial and endoplasmic reticulum (ER)-related factors, nuclear xenobiotic receptors (NXR) response, and cytochrome P450 system (CYP450s)-related factors in the kidneys on days 14, 28, and 42. The results showed that FB1 can induce oxidative stress through NXR response and disorder of the CYP450s system, leading to mitochondrial dysfunction and ER stress, promoting the expression of inflammatory factors (including IL-1ß, IL-6, and IL-8) and causing kidney damage. This study elucidated the possible molecular mechanism by which FB1 induces nephrotoxicity in young quails.


Assuntos
Fumonisinas , Micotoxinas , Animais , Codorniz , Fígado/metabolismo , Fumonisinas/toxicidade , Micotoxinas/toxicidade , Sistema Enzimático do Citocromo P-450/metabolismo
19.
Opt Express ; 31(21): 34088-34099, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37859173

RESUMO

Based on the cross-spectral density (CSD) function, the coherence-orbital angular momentum (COAM) matrix of twisted Gaussian Schell-model (TGSM) beam is proposed, and the COAM matrix is used to describe the correlation between OAM modes in TGSM optical field. The COAM matrix characteristics of TGSM beam are analyzed by numerical simulation. The results show that the COAM matrix characteristics of TGSM beam depend on the initial parameters of the beam. In addition, a method of generating TGSM beam by superposition of COAM matrix element modes is described, and the influence of different initial parameters on the superposition characteristics is studied. The results reveal the internal relationship between the coherent structure of the optical field, the twist phase and the OAM modes. Our work helps to explore new expressions of partially coherent beams and promote the practical application of optimizing partially coherent beams.

20.
Front Oncol ; 13: 1179897, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711200

RESUMO

Background: Kinesin is a molecular motor for transporting "goods" within cells and plays a key role in many types of tumors. The multi-angle study of kinesin at the pan-cancer level is conducive to understanding its role in tumorigenesis and development and clinical treatment potential. Methods: We evaluated the expression of KIF genes, performed differential analysis by using the R package limma, and explored the pan-cancer prognosis of KIF genes by univariate Cox regression analysis. To evaluate the pan-cancer role of KIF genes as a whole, we defined the KIFscore with the help of gene set variation analysis (GSVA) and explored the KIFscores across normal tissues, tumor cell lines, and 33 tumor types in TCGA. Next, we used spearman correlation analysis to extensively study the correlation between the KIFscore and tumor prognosis and be-tween the KIFscore and clinical indicators. We also identified the relationship between the KIFscore and genomic variation and immune molecular signatures by multiplatform analysis. Finally, we identified the key genes in clear cell renal cell carcinoma (ccRCC) through machine learning algorithms and verified the candidate genes by CCK8, wound healing assay, Transwell assay, and flow cytometry. Results: In most cancers, KIFscores are high and they act as a risk factor for cancer. The KIFscore was significantly associated with copy number variation (CNV), tumor mutation burden (TMB), immune subtypes, DNA repair deficiency, and tumor stemness indexes. Moreover, in almost all cancer species, the KIFscore was positively correlated with T cell CD4+ TH2, the common lymphoid pro-genitor, and the T cell follicular helper. In addition, it was negatively correlated with CXCL16, CCL14, TNFSF13, and TNFRSF14 and positively correlated with ULBP1, MICB, and CD276. Machine learning helped us to identify four hub-genes in ccRCC. The suitable gene, KIF14, is highly expressed in ccRCC and promotes tumor cell proliferation, migration, and invasion. Conclusion: Our study shows that the KIF genes play an important pan-cancer role and may become a potential new target for a variety of tumor treatments in the future. Furthermore, KIF14, a key molecule in the KIF genes, can provide a new idea for the ccRCC treatment.

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