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1.
Neural Regen Res ; 20(1): 29-40, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38767474

RESUMO

The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis. Microglia, as innate immune cells, play important roles in the maintenance of central nervous system homeostasis, injury response, and neurodegenerative diseases. Lactate has been considered a metabolic waste product, but recent studies are revealing ever more of the physiological functions of lactate. Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions, macrophage polarization, neuromodulation, and angiogenesis and has also been implicated in the development of various diseases. This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation, histone versus non-histone lactylation, and therapeutic approaches targeting lactate. Finally, we summarize the current research on microglia lactylation in central nervous system diseases. A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

2.
Int J Antimicrob Agents ; : 107235, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38851462

RESUMO

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3 multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin versus levofloxacin for treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: The eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at test of cure (TOC) visit in the modified intent-to-treat (mITT) population. The efficacy and safety were also compared between nemonoxacin and levofloxacin in terms of secondary efficacy and safety endpoints. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n=349) or levofloxacin (n=176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P> 0.05). The clinical efficacy of nemonoxacin was noninferior to levofloxacin in treatment of CAP. Nemonoxacin achieved microbiological success rate of 88.8% (95/107), while levofloxacin achieved 87.8% (43/49) (P > 0.05) at TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in nemonoxacin group and 22.2% in levofloxacin group, mostly local reactions at the infusion site, nausea, elevated ALT/AST, and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and noninferior to levofloxacin for treating CAP in adult patients.

3.
Nat Commun ; 15(1): 4746, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834546

RESUMO

Artificial photosynthesis is a promising approach to produce clean fuels via renewable solar energy. However, it is practically constrained by two issues of slow photogenerated carrier migration and rapid electron/hole recombination. It is also a challenge to achieve a 2:1 ratio of H2 and O2 for overall water splitting. Here we report a rational design of spatially differentiated two-dimensional Bi4Ti3O12 nanosheets to enhance overall water splitting. Such a spatially differentiated structure overcomes the limitation of charge transfer across different crystal planes in a single crystal semiconductor. The experimental results show a redistribution of charge within a crystal plane. The resulting photocatalyst produces 40.3 µmol h-1 of hydrogen and 20.1 µmol h-1 of oxygen at a near stoichiometric ratio of 2:1 and a solar-to-hydrogen efficiency of 0.1% under simulated solar light.

4.
BMC Pregnancy Childbirth ; 24(1): 406, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834957

RESUMO

BACKGROUND: Interpregnancy interval (IPI) is associated with the risk of GDM in a second pregnancy. However, an optimal IPI is still need to be determined based on the characteristics of the population. This study aimed to analyze the effect of interpregnancy interval (IPI) on the risk of gestational diabetes mellitus (GDM) in the Chinese population. METHODS: We conducted a retrospective cohort study on female participants who had consecutive deliveries at Peking University Shenzhen Hospital from 2013 to 2021. The IPI was categorized into 7 groups and included into the multivariate logistic regression model with other confound factors. Analysis was also stratified based on age of first pregnancy, BMI, and history of GDM. Adjusted OR values (aOR) and 95% confidence intervals (CI) calculated. The regression coefficient of IPI months on GDM prediction risk was analyzed using a linear regression model. RESULTS: A total of 2,392 participants were enrolled. The IPI of the GDM group was significantly greater than that of the non-GDM group (P < 0.05). Compared with the 18-24 months IPI category, participants with longer IPIs (24-36 months, 36-48 months, 48-60 months, and ≥ 60 months) had a higher risk of GDM (aOR:1.585, 2.381, 2.488, and 2.565; 95% CI: 1.021-2.462, 1.489-3.809, 1.441-4.298, and 1.294-5.087, respectively). For participants aged < 30 years or ≥ 30 years or without GDM history, all longer IPIs (≥ 36 months) were all significantly associated with the GDM risk in the second pregnancy (P < 0.05), while any shorter IPIs (< 18 months) was not significantly associated with GDM risk (P > 0.05). For participants with GDM history, IPI 12-18 months, 24-36 months, 36-48 months, and ≥ 60 months were all significantly associated with the GDM risk (aOR: 2.619, 3.747, 4.356, and 5.373; 95% CI: 1.074-6.386, 1.652-8.499, 1.724-11.005, and 1.078-26.793, respectively), and the slope value of linear regression (0.5161) was significantly higher compared to participants without a history of GDM (0.1891) (F = 284.168, P < 0.001). CONCLUSIONS: Long IPI increases the risk of GDM in a second pregnancy, but this risk is independent of maternal age. The risk of developing GDM in a second pregnancy for women with GDM history is more significantly affected by IPI.


Assuntos
Intervalo entre Nascimentos , Diabetes Gestacional , Humanos , Feminino , Diabetes Gestacional/epidemiologia , Gravidez , Estudos Retrospectivos , Intervalo entre Nascimentos/estatística & dados numéricos , Adulto , China/epidemiologia , Fatores de Risco , Número de Gestações
5.
BMC Public Health ; 24(1): 1490, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834959

RESUMO

The rapid development of digital technology has radically changed people's lives. Simultaneously, as the population is rapidly aging, academic research is focusing on the use of Internet technology to improve middle-aged and older people's health, particularly owing to the popularity of mobile networks, which has further increased the population's accessibility to the Internet. However, related studies have not yet reached a consensus. Herein, empirical analysis of the influence of mobile Internet use on the subjective health and chronic disease status of individuals in their Middle Ages and above was conducted utilizing ordered logit, propensity score matching (PSM), and ordered probit models with data from the 2020 China Health and Retirement Longitudinal Study. The study aimed to provide a theoretical basis and reference for exploring technological advances to empower the development of a healthy Chinese population and to advance the process of healthy aging. The health of middle-aged and older adults mobile Internet users was greatly improved, according to our findings. Further, the use of mobile Internet by these persons resulted in improvements to both their self-assessed health and the state of their chronic diseases. As per the findings of the heterogeneity analysis, the impact of mobile Internet use was shown to be more pronounced on the well-being of middle-aged persons aged 45-60 years compared to those aged ≥ 60 years. Further, the endogeneity test revealed that the PSM model could better eliminate bias in sample selection. The results suggest that the estimates are more robust after eliminating endogeneity, and that failure to disentangle sample selectivity bias would overestimate not only the facilitating effect of mobile Internet use on the self-assessed health impacts of middle-aged and older adults, but also the ameliorating effect of mobile Internet use on the chronic diseases of middle-aged and older adults. The results of the mechanistic analysis suggest that social engagement is an important mediating mechanism between mobile Internet use and the health of middle-aged and older adults. This implies that mobile Internet use increases opportunities for social participation among middle-aged and older adults, thereby improving their health.


Assuntos
Nível de Saúde , Humanos , China , Estudos Longitudinais , Pessoa de Meia-Idade , Masculino , Idoso , Feminino , Uso da Internet/estatística & dados numéricos , Doença Crônica , Aposentadoria/estatística & dados numéricos , Internet/estatística & dados numéricos
6.
Front Public Health ; 12: 1323820, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835614

RESUMO

Objective: To evaluate the long-term gastrointestinal (GI) symptoms and sleep quality sequelae in adolescents with COVID-19. Methods: Between June and July 2023, an online survey was done in Xiaoshan District, Hangzhou City, Zhejiang Province, China, using the GI Symptom Rating Scale (GSRS) and the Pittsburgh Sleep Quality Inventory (PSQI). Results: GI symptoms in COVID-19 patients increased by 11.86% compared to before infection, while sleep quality decreased by 10.9%. Over time, there was a significant increase in the cumulative incidence rate of GI symptoms and sleep disorders (p < 0.001). Follow-up of COVID-19 positive patients within 6 months of infection showed that GI symptoms and sleep quality began to ease starting from the first month after infection. Further analysis indicated a significant linear relationship between the severity of GI symptoms and sleep quality (R > 0.5, p < 0.001). Moreover, females, older age, and higher education were identified as risk factors influencing the long-term effects of COVID-19. Conclusion: SARS-CoV-2 affects GI symptoms and sleep quality in adolescents during both the acute phase and post-infection periods. Over time, these symptoms gradually alleviate. A significant correlation exists between GI symptoms and sleep quality.


Assuntos
COVID-19 , Gastroenteropatias , Qualidade do Sono , Transtornos do Sono-Vigília , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Adolescente , Feminino , Masculino , Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologia , China/epidemiologia , Estudos Retrospectivos , Transtornos do Sono-Vigília/epidemiologia , SARS-CoV-2 , Inquéritos e Questionários , Fatores de Risco
7.
Front Immunol ; 15: 1402724, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835783

RESUMO

Background and objective: Acute ischemic stroke (AIS) is a leading cause of mortality, severe neurological and long-term disability world-wide. Blood-based indicators may provide valuable information on identified prognostic factors. However, currently, there is still a lack of peripheral blood indicators for the prognosis of AIS. We aimed to identify the most promising prognostic indicators and establish prognostic models for AIS. Methods: 484 subjects enrolled from four centers were analyzed immunophenotypic indicators of peripheral blood by flow cytometry. Least absolute shrinkage and selection operator (LASSO) regression was applied to minimize the potential collinearity and over-fitting of variables measured from the same subject and over-fitting of variables. Univariate and multivariable Cox survival analysis of differences between and within cohorts was performed by log-rank test. The areas under the receiving operating characteristic (ROC) curves were used to evaluate the selection accuracy of immunophenotypic indicators in identifying AIS subjects with survival risk. The prognostic model was constructed using a multivariate Cox model, consisting of 402 subjects as a training cohort and 82 subjects as a testing cohort. Results: In the prospective study, 7 immunophenotypic indicators of distinct significance were screened out of 72 peripheral blood immunophenotypic indicators by LASSO. In multivariate cox regression, CTL (%) [HR: 1.18, 95% CI: 1.03-1.33], monocytes/µl [HR: 1.13, 95% CI: 1.05-1.21], non-classical monocytes/µl [HR: 1.09, 95% CI: 1.02-1.16] and CD56high NK cells/µl [HR: 1.13, 95% CI: 1.05-1.21] were detected to decrease the survival probability of AIS, while Tregs/µl [HR:0.97, 95% CI: 0.95-0.99, p=0.004], BM/µl [HR:0.90, 95% CI: 0.85-0.95, p=0.023] and CD16+NK cells/µl [HR:0.93, 95% CI: 0.88-0.98, p=0.034] may have the protective effect. As for indicators' discriminative ability, the AUC for CD56highNK cells/µl attained the highest of 0.912. In stratification analysis, the survival probability for AIS subjects with a higher level of Tregs/µl, BM/µl, CD16+NK cells/µl, or lower levels of CD56highNK cells/µl, CTL (%), non-classical monocytes/µl, Monocytes/µl were more likely to survive after AIS. The multivariate Cox model showed an area under the curve (AUC) of 0.805, 0.781 and 0.819 and 0.961, 0.924 and 0.982 in the training and testing cohort, respectively. Conclusion: Our study identified 7 immunophenotypic indicators in peripheral blood may have great clinical significance in monitoring the prognosis of AIS and provide a convenient and valuable predictive model for AIS.


Assuntos
Citometria de Fluxo , Imunofenotipagem , AVC Isquêmico , Humanos , Feminino , Masculino , AVC Isquêmico/sangue , AVC Isquêmico/mortalidade , AVC Isquêmico/diagnóstico , AVC Isquêmico/imunologia , Citometria de Fluxo/métodos , Prognóstico , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Biomarcadores/sangue , Idoso de 80 Anos ou mais
8.
World J Clin Oncol ; 15(5): 603-613, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38835843

RESUMO

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the type I receptor tyrosine kinase family. ROR1 is pivotal in embryonic development and cancer, and serves as a biomarker and therapeutic target. It has soluble and membrane-bound subtypes, with the latter highly expressed in tumors. ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms. Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis. Additionally, ROR1 may regulate the cell cycle, stem cell characteristics, and interact with other signaling pathways to affect cancer progression. This review explores the structure, expression and role of ROR1 in the development of gastrointestinal cancers. It discusses current antitumor strategies, outlining challenges and prospects for treatment.

9.
Front Plant Sci ; 15: 1404477, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835857

RESUMO

Abscisic acid (ABA) is a key phytohormone involved in wound healing in fruits and vegetables, while fluridone (FLD) is its synthetic inhibitor. However, it is unknown whether ABA signaling and downstream transcription factors are involved in the synthesis of phenolic acids and lignin monomers in muskmelon wounds, and the underlying mechanisms. In our study, exogenous ABA promoted endogenous ABA synthesis by increasing the levels of ß-carotenoid and zeaxanthin, activating 9-cis-epoxycarotenoid dioxygenase (NCED) and zeaxanthin epoxidase (ZEP), facilitated ABA signaling by increasing the expression levels of protein phosphatases type 2C (CmPP2C) and ABA-responsive element binding factors (CmABF), upregulated the expression levels of CmMYB1 and CmWRKY1, and ABA induced phenylpropanoid metabolism by activating phenylalanine ammonia-lyase (PAL), 4-coenzyme A ligase (4CL), and cinnamyl alcohol dehydrogenase (CAD), which further increased the synthesis of phenolic acids and lignin monomers in muskmelon wounds during healing. Taken together, exogenous ABA induced phenylpropanoid metabolism and increased the synthesis of phenolic acid and lignin monomer in muskmelon wounds during healing, and may be involved in endogenous ABA synthesis and signaling and related transcription factors.

10.
Sci Adv ; 10(23): eadm9631, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38838154

RESUMO

Short-wavelength infrared (SWIR) light detection plays a key role in modern technologies. Emerging solution-processed organic semiconductors are promising for cost-effective, flexible, and large-area SWIR organic photodiodes (OPDs). However, the spectral responsivity (R) and specific detectivity (D*) of SWIR OPDs are restricted by insufficient exciton dissociation and high noise current. In this work, we synthesized an SWIR small molecule with a spectral coverage of 0.3 to 1.3 micrometers peaking at 1100 nanometers. The photodiode, with optimized exciton dissociation, charge injection, and SWIR transmittance, achieves a record high R of 0.53 ampere per watt and D* of 1.71 × 1013 Jones at 1110 nanometers under zero bias. The D* at 1 to 1.2 micrometers surpasses that of the uncooled commercial InGaAs photodiode. Furthermore, large-area semitransparent all-organic upconversion devices integrating the SWIR photodiode realized static and dynamic SWIR-to-visible imaging, along with excellent upconversion efficiency and spatial resolution. This work provides alternative insights for developing sensitive organic SWIR detection.

11.
Front Vet Sci ; 11: 1359421, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38840631

RESUMO

Porcine circovirus disease (PCV) causes substantial economic losses in the pig industry, primarily from porcine circovirus type 2 (PCV2) and porcine circovirus type 3 (PCV3). Novel vaccines are necessary to prevent and control PCV infections. PCV coat proteins are crucial for eliciting immunogenic proteins that induce the production of antibodies and immune responses. A vaccine platform utilizing Semliki Forest virus RNA replicons expressing vesicular stomatitis virus glycoprotein (VSV-G), was recently developed. This platform generates virus-like vesicles (VLVs) containing VSV-G exclusively, excluding other viral structural proteins. In our study, we developed a novel virus-like vesicle vaccine by constructing recombinant virus-like vesicles (rVLVs) that also express EGFP. These rVLVs were created using the RNA replicon of Venezuelan equine encephalomyelitis (VEEV) and New Jersey serotype VSV-G. The rVLVs underwent characterization and safety evaluation in vitro. Subsequently, rVLVs expressing PCV2d-Cap and PCV3-Cap proteins were constructed. Immunization of C57 mice with these rVLVs led to a significant increase in anti-porcine circovirus type 2 and type 3 capsid protein antibodies in mouse serum. Additionally, a cellular immune response was induced, as evidenced by high production of IFN-γ and IL-4 cytokines. Overall, this study demonstrates the feasibility of developing a novel porcine circovirus disease vaccine based on rVLVs.

12.
Indian J Dermatol ; 69(2): 178-180, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38841217

RESUMO

In recent years, with the increased usage of tumour necrosis factor (TNF) inhibitors, more side effects have been revealed. Paradoxical psoriasis, including psoriasis vulgaris, palmoplantar pustulosis, scalp psoriasis and their combinations, is a common adverse effect. However, erythrodermic psoriasis associated with alopecia due to anti-TNF-α is rarely reported in the literature. We report a 44-year-old woman who developed erythrodermic psoriasis associated with diffuse alopecia during her treatment with adalimumab for palmoplantar pustulosis.

14.
Heliyon ; 10(11): e31782, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38841459

RESUMO

This study aimed to determine the association between sleep quality and mental health in COVID-19 carriers in China and evaluate the moderating effects of perceived social support. 1283 asymptomatic COVID-19 carriers were enrolled from March 2022 to April 2022 among Ruijin Jiahe Fangcang shelter hospital in Shanghai, China. They were assessed using the Pittsburgh Sleep Quality Index (PSQI), the General Health Questionnaire (GHQ), and the Perceived Social Support Scale (PSSS) respectively. Participants had an average age of 39.64 years and 59.6 % of whom were male. In total, 34.3 % of participants presented with poor sleep quality; 41.1 % showed bad mental health. Sleep quality was positively related to mental health (r = 0.321, P < 0.001, 95 %CI = 0.267, 0.369) and social support was negatively related to mental health (r = -0.414, P < 0.001, 95 %CI = -0.457, -0.367). Meanwhile, social support played a moderating role between sleep quality and mental health (ß = 0.066, P < 0.05, 95 %CI = 0.016, 0.117). These findings indicate that mental health resulting from the COVID-19 pandemic are increasingly apparent in China and provide a focus on sleep quality for the early prevention of mental health in asymptomatic carriers. And social support may be beneficial to the improvement of mental health, especially for people in crisis (e.g., COVID-19 pandemic).

15.
Front Public Health ; 12: 1402832, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846612

RESUMO

Introduction: The implementation of a hierarchical medical system holds significant practical importance in advancing the Healthy China strategy and elevating the overall health status of the population of China. Methods: This article empirically examines the influence of the implementation of a hierarchical medical system on the health of the population using the latest 2020 China Family Panel Studies database. Furthermore, it investigates the variability of this impact across distinct health insurance participation statuses and literacy groups. Results: The findings of the study demonstrate that the implementation of the hierarchical medical system substantially enhances the health of the population, not only in terms of self-assessed health but also through a notable positive effect on alleviating chronic diseases. These results maintain their validity even after conducting robustness tests utilizing a replacement estimation model. Heterogeneity analysis reveals that the impact of the hierarchical medical system on the population's health status exhibits significant variation concerning health insurance participation and literacy. Specifically, regarding health insurance participation, the hierarchical medical system effectively improves both self-assessed health and chronic disease status among the insured population. However, for those not enrolled in health insurance, the hierarchical medical system only demonstrates improvement in chronic disease status, with insignificant results observed in enhancing self-assessed health status. Moreover, propensity score matching (PSM) was also used to address endogeneity problems resulting from sample selectivity bias. The findings demonstrate that endogeneity issues can be suitably addressed by the PSM model. Additionally, they point out that an overestimation of the impact of the hierarchical medical system on the population's self-assessed health state would result from failing to take sample selectivity bias into account. On the other hand, it will lead to the underestimation of the effect of the hierarchical medical system on the status of chronic diseases. Discussion: Moving forward, steadfast efforts should be directed toward further enhancing the implementation of the hierarchical medical system. This includes the comprehensive promotion and using the pivotal role of the hierarchical medical system in improving the health of the population.


Assuntos
Seguro Saúde , Saúde da População , Humanos , China , Seguro Saúde/estatística & dados numéricos , Doença Crônica , Feminino , Masculino , Nível de Saúde , Adulto , Pessoa de Meia-Idade , Atenção à Saúde , Letramento em Saúde/estatística & dados numéricos
16.
Appl Clin Genet ; 17: 63-69, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828444

RESUMO

Optical Genome Mapping (OGM) technology has garnered growing interest for the identification of chromosomal structural variations (SVs), particularly complex ones that are implicated in genetic diseases in humans. In this study, we performed genetic diagnostics on a neonatal patient who presented with feeding difficulties, hypotonia, and an atrial septal defect. We utilized a combination of trio-whole exome sequencing and OGM for our analysis. The results revealed an unbalanced translocation between maternal chromosomes 4 and 6 in the proband, ogm[GRch38]t(4:6)(q35.2;q25.3), resulting in a 2.8 Mb deletion at the 4q35 terminal and a 10.2 Mb duplication at the 6q25 terminal. In summary, this study highlights how OGM, in conjunction with other genetic approaches, can unveil the genetic etiology of complex clinical syndromes. Neonatal patients often exhibit low specific phenotypes, underlining the significance of SV detection.

17.
Front Pharmacol ; 15: 1294668, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828446

RESUMO

Introduction: FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3 inhibitors are in clinical trials, and some have been applied in clinic. However, the safety, efficacy and pharmacodynamics of these FLT3 inhibitors have not been systemically analyzed before. Methods: We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023. Results: Our results showed the most common adverse events (AEs) were gastrointestinal adverse reactions, including diarrhea, hand-foot syndrome and nausea, while the most common hematological AEs were febrile neutropenia, anemia, and thrombocytopenia. Based on the published data, the mean overall survival (OS) and the mean progression-free survival (PFS) were 9.639 and 5.905 months, respectively. The incidence of overall response rate (ORR), complete remission (CR), partial response (PR), and stable disease (SD) for all these FLT3 inhibitors was 29.0%, 8.7%, 16.0%, and 42.3%, respectively. The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration (Tmax) in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life (T1/2) range was highly variable, from 6.8 to 151.8 h. Discussion: FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication.

18.
Rev Sci Instrum ; 95(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38832847

RESUMO

The core of electrostatic tomography (EST) is to solve the inverse problem, but the EST independent measurement data are much smaller than the value that needs to be reconstructed, resulting in a more serious inverse problem. This paper presents an improved ResNet-34 network (P-ResNet), which consists of an input layer, a residual feature extraction layer, and an output layer. The number of residual blocks is 3, 4, 4, and 3. After the second convolution in the main path of each residual block, a ReLU activation function is added to enhance the nonlinear expression ability of the network, and the generalization ability of the model is improved by introducing the L2 regularization loss function. A total of 15 930 sets of samples were simulated for the simulation test. After 200 rounds of iteration, the reconstruction results show that the network achieves high accuracy in EST image reconstruction tasks. In addition, the model is tested under different degrees of Gaussian white noise to verify its anti-noise ability. Compared with the traditional algorithms, the image correlation coefficients of this proposed model network are higher. In addition, this paper designs a small sensor to obtain the induced charge values through the principle of electrostatic induction. The reconstructed results obtained from the experimental data are consistent with the simulation results, which verifies the effectiveness and generalization ability of the proposed model.

19.
Brain Res ; 1840: 149049, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38825161

RESUMO

BACKGROUND: Previous studies have revealed structural brain abnormalities in individuals with depression, but the causal relationship between depression and brain structure remains unclear. METHODS: A genetic correlation analysis was conducted using summary statistics from the largest genome-wide association studies for depression (N = 674,452) and 1,265 brain structural imaging-derived phenotypes (IDPs, N = 33,224). Subsequently, a bidirectional two-sample Mendelian Randomization (MR) approach was employed to explore the causal relationships between depression and the IDPs that showed genetic correlations with depression. The main MR results were obtained using the inverse variance weighted (IVW) method, and other MR methods were further employed to ensure the reliability of the findings. RESULTS: Ninety structural IDPs were identified as being genetically correlated with depression and were included in the MR analyses. The IVW MR results indicated that reductions in the volume of several brain regions, including the bilateral subcallosal cortex, right medial orbitofrontal cortex, and right middle-posterior part of the cingulate cortex, were causally linked to an increased risk of depression. Additionally, decreases in surface area of the right middle temporal visual area, right middle temporal cortex, right inferior temporal cortex, and right middle-posterior part of the cingulate cortex were causally associated with a heightened risk of depression. Validation and sensitivity analyses supported the robustness of these findings. However, no evidence was found for a causal effect of depression on structural IDPs. CONCLUSIONS: Our findings reveal the causal influence of specific brain structures on depression, providing evidence to consider brain structural changes in the etiology and treatment of depression.

20.
iScience ; 27(6): 109983, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38827404

RESUMO

Recent studies have implicated a crucial role of Hippo signaling in cell fate determination by biomechanical signals. Here we show that mechanical loading triggers the activation of a Hippo-PKCζ-NFκB pathway in chondrocytes, resulting in the expression of NFκB target genes associated with inflammation and matrix degradation. Mechanistically, mechanical loading activates an atypical PKC, PKCζ, which phosphorylates NFκB p65 at Serine 536, stimulating its transcriptional activation. This mechanosensitive activation of PKCζ and NFκB p65 is impeded in cells with gene deletion or chemical inhibition of Hippo core kinases LATS1/2, signifying an essential role of Hippo signaling in this mechanotransduction. A PKC inhibitor AEB-071 or PKCζ knockdown prevents p65 Serine 536 phosphorylation. Our study uncovers that the interplay of the Hippo signaling, PKCζ, and NFκB in response to mechanical loading serves as a therapeutic target for knee osteoarthritis and other conditions resulting from mechanical overloading or Hippo signaling deficiencies.

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