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1.
Biostatistics ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39002144

RESUMO

High-dimensional omics data often contain intricate and multifaceted information, resulting in the coexistence of multiple plausible sample partitions based on different subsets of selected features. Conventional clustering methods typically yield only one clustering solution, limiting their capacity to fully capture all facets of cluster structures in high-dimensional data. To address this challenge, we propose a model-based multifacet clustering (MFClust) method based on a mixture of Gaussian mixture models, where the former mixture achieves facet assignment for gene features and the latter mixture determines cluster assignment of samples. We demonstrate superior facet and cluster assignment accuracy of MFClust through simulation studies. The proposed method is applied to three transcriptomic applications from postmortem brain and lung disease studies. The result captures multifacet clustering structures associated with critical clinical variables and provides intriguing biological insights for further hypothesis generation and discovery.

2.
JAMA Surg ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39018053

RESUMO

Importance: Choosing Wisely recommendations advocate against routine use of axillary staging in older women with early-stage, clinically node-negative (cN0), hormone receptor-positive (HR+), and HER2-negative breast cancer. However, rates of sentinel lymph node biopsy (SLNB) in this population remain persistently high. Objective: To evaluate whether an electronic health record (EHR)-based nudge intervention targeting surgeons in their first outpatient visit with patients meeting Choosing Wisely criteria decreases rates of SLNB. Design, Setting, and Participants: This nonrandomized controlled trial was a hybrid type 1 effectiveness-implementation study with subsequent postintervention semistructured interviews and lasted from October 2021 to October 2023. Data came from EHRs at 8 outpatient clinics within an integrated health care system; participants included 7 breast surgical oncologists. Data were collected for female patients meeting Choosing Wisely criteria for omission of SLNB (aged ≥70 years with cT1 and cT2, cN0, HR+/HER2- breast cancer). The study included a 12-month preintervention control period; baseline surveys assessing perceived acceptability, appropriateness, and feasibility of the designed intervention; and a 12-month intervention period. Intervention: A column nudge was embedded into the surgeon's schedule in the EHR identifying patients meeting Choosing Wisely criteria for potential SLNB omission. Main Outcomes and Measures: The primary outcome was rate of SLNB following nudge deployment into the EHR. Results: Similar baseline demographic and tumor characteristics were observed before (control period, n = 194) and after (intervention period, n = 193) nudge deployment. Patients in both the control and intervention period had a median (IQR) age of 75 (72-79) years. Compared with the control period, unadjusted rates of SLNB decreased by 23.1 percentage points (46.9% SLNB rate prenudge to 23.8% after; 95% CI, -32.9 to -13.8) in the intervention period. An interrupted time series model showed a reduction in the rate of SLNB following nudge deployment (adjusted odds ratio, 0.26; 95% CI, 0.07 to 0.90; P = .03). The participating surgeons scored the intervention highly on acceptability, appropriateness, and feasibility. Dominant themes from semistructured interviews indicated that the intervention helped remind the surgeons of potential Choosing Wisely applicability without the need for additional clicks or actions on the day of the patient visit, which facilitated use. Conclusions and Relevance: This study showed that a nudge intervention in the EHR significantly decreased low-value axillary surgery in older women with early-stage, cN0, HR+/HER2- breast cancer. This user-friendly and easily implementable EHR-based intervention could be a beneficial approach for decreasing low-value care in other practice settings or patient populations. Trial Registration: ClinicalTrials.gov Identifier: NCT06006910.

3.
Sci Rep ; 14(1): 16263, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009655

RESUMO

Through preferential treatment by education officials or through bribery, some adolescents can obtain admission to a junior high school. However, it is unclear whether it affects the mental health of adolescents. This study used Propensity Score Matching to examine the effects of corruption on adolescent mental health. A total of 17,254 junior high school students sample (11-18 years old; 48.7% girls and 53.1% boys) were used from the China Education Panel Survey. 14.1% of adolescents attended a junior high school by corrupt means, corruption had a significantly negative effect on the mental health of these adolescents (ATT = -0.388, p < 0.01), the reasons grounded in the fact that they received more criticisms from teachers and wanted to leave their current school. In general, corruption in the admissions process can have detrimental effects on the mental health of adolescents. This study extends the previous articles on how to improve adolescent mental health and complements the application of cognitive dissonance theory. Findings from this study revealed that anti-corruption in the education sector is necessary, and the institutional design to ensure fair enrolment in basic education will contribute to the mental health of adolescents.


Assuntos
Saúde Mental , Humanos , Adolescente , Feminino , Masculino , China , Criança , Estudantes/psicologia , Critérios de Admissão Escolar , Instituições Acadêmicas , População do Leste Asiático
4.
Pest Manag Sci ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847471

RESUMO

BACKGROUND: Body-color polymorphisms in insects are often explained by environmental selective advantages. Differential fitness related to body coloration has been demonstrated in Myzus persicae (Sulzer): performance of the red morph is in general better than that of the green morph on tobacco plants. However, the molecular mechanism involved is largely unclear. RESULTS: Here we showed that the red morph of M. persicae had higher expression of a carotenoid desaturase CarD763 in the whole body, salivary gland and saliva relative to the green morph. Also, 18% individuals displayed faded red body color 5 days post dsCarD763 treatment. Furthermore, knockdown of CarD763 in the red morph significantly prolonged the time needed to locate phloem and shortened the duration of phloem feeding. Honeydew production and survival rate decreased as well. In contrast, overexpression of CarD763 in tobacco leaves facilitated aphid feeding, enhanced honeydew production and improved the survival rate of aphids. Compared with those fed by dsGFP aphids, plants infested by dsCarD763-treated aphids had higher ROS accumulation, lower lycopene content and photosynthetic rate, and maximum photon quantum yield. The reverse was true when plants overexpressed CarD763. CONCLUSION: These findings demonstrated that CarD763, a red morph-specific salivary protein, could enhance aphid feeding and early colonization by promoting plant photosynthesis. © 2024 Society of Chemical Industry.

5.
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.

6.
Fa Yi Xue Za Zhi ; 40(2): 118-127, 2024 Apr 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38847025

RESUMO

In the study of age estimation in living individuals, a lot of data needs to be analyzed by mathematical statistics, and reasonable medical statistical methods play an important role in data design and analysis. The selection of accurate and appropriate statistical methods is one of the key factors affecting the quality of research results. This paper reviews the principles and applicable principles of the commonly used medical statistical methods such as descriptive statistics, difference analysis, consistency test and multivariate statistical analysis, as well as machine learning methods such as shallow learning and deep learning in the age estimation research of living individuals, and summarizes the relevance and application prospects between medical statistical methods and machine learning methods. This paper aims to provide technical guidance for the age estimation research of living individuals to obtain more scientific and accurate results.


Assuntos
Aprendizado de Máquina , Humanos , Determinação da Idade pelo Esqueleto/métodos , Análise Multivariada , Determinação da Idade pelos Dentes/métodos
7.
Adv Mater ; : e2405079, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38922998

RESUMO

Solid-state batteries (SSBs) have garnered significant attention in the critical field of sustainable energy storage due to their potential benefits in safety, energy density, and cycle life. The large-scale, cost-effective production of SSBs necessitates the development of high-performance solid-state electrolytes. However, the manufacturing of SSBs relies heavily on the advancement of suitable solid-state electrolytes. Composite polymer electrolytes (CPEs), which combine the advantages of ordered microporous materials (OMMs) and polymer electrolytes, meet the requirements for high ionic conductivity/transference number, stability with respect to electrodes, compatibility with established manufacturing processes, and cost-effectiveness, making them particularly well-suited for mass production of SSBs. This review delineates how structural ordering dictates the fundamental physicochemical properties of OMMs, including ion transport, thermal transfer, and mechanical stability. The applications of prominent OMMs are critically examined, such as metal-organic frameworks, covalent organic frameworks, and zeolites, in CPEs, highlighting how structural ordering facilitates the fulfillment of property requirements. Finally, an outlook on the field is provided, exploring how the properties of CPEs can be enhanced through the dimensional design of OMMs, and the importance of uncovering the underlying "feature-function" mechanisms of various CPE types is underscored.

8.
Eur Phys J E Soft Matter ; 47(6): 41, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38880801

RESUMO

In recent years, the problem of traffic congestion has become increasingly serious, and research on traffic system control has become a new hotspot. Studying the bifurcation characteristics of traffic flow systems and designing control schemes for unstable support points can alleviate traffic congestion from a new perspective. This article improves the full speed differential model considering strong wind models from the perspective of bifurcation control to adjust traffic flow. This article theoretically proves the existence conditions of Hopf bifurcation and saddle node bifurcation in the model and finds the stability mutation point of the transportation system stability. A nonlinear system feedback controller was designed for unstable bifurcation points using Chebyshev polynomial approximation and random feedback control methods. Without changing the system equilibrium point, the advance, delay, and elimination of Hopf bifurcation were achieved, and the abrupt behavior of the transportation system was controlled, thereby alleviating traffic congestion. This article explains the changes in the stability of complex transportation systems from the perspective of bifurcation analysis, which can better capture the characteristics of traffic flow. By adjusting the control parameters in the feedback controller, the influence of boundary conditions on the stability of the transportation system is fully described, and the influence of unstable focal points and saddle points on the system is suppressed, thereby slowing down the traffic flow. In addition, unstable bifurcation points can be eliminated, and the Hopf bifurcation can be controlled to advance, delay, and disappear, thereby achieving control over the stable behavior of the transportation system. This helps alleviate traffic congestion and also helps describe actual traffic phenomena.

9.
Foods ; 13(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38928787

RESUMO

In the realm of analysis, the lateral flow immunoassay (LFIA) is frequently utilized due to its capability to be fast and immediate. However, the biggest challenge of the LFIA is its low detection sensitivity and tolerance to matrix interference, making it impossible to enable accurate, qualitative analyses. In this study, we developed a new LFIA with higher affinity and sensitivity, based on a nanobody (G8-DIG) and CuS nanoflowers-Au (CuS NFs-Au), for the detection of aflatoxin B1 (AFB1) in maize. We synthesized the immunoprobe G8-DIG@CuS NFs-Au, stimulated the in situ development of Au nanoparticles (Au NPs) on Cu NFs by electrical displacement, and obtained Cu NFs-Au for fixing the G8-DIG. G8-DIG@CuS NFs-Au probe-based LFIAs may, in ideal circumstances, use a strip chromatography reader to accomplish sensitive quantitative detection and qualitative visualization. AFB1 has a detection range of 2.82-89.56 µg/L and a detection limit of 0.87 µg/L. When compared with an LFIA based on CuS NFs, this sensitivity is increased by 2.76 times. The practical application of this method in corn flour demonstrated a recovery rate of 81.7% to 117%. Therefore, CuS NFs-Au show great potential for detecting analytes.

11.
Cancer ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781433

RESUMO

BACKGROUND: Effective systemic therapy remains limited for advanced esophageal squamous cell carcinoma (ESCC) and hepatocellular carcinoma (HCC), particularly after prior failed treatment with immune checkpoint inhibitors (ICIs). Theoretically, a combination of tyrosine kinase inhibitors (TKIs) with ICIs may restore immunotherapy sensitivity. METHODS: In this phase 1b study, patients received AL2846, an antiangiogenic TKI with multiple targets (c-MET, VEGFR1, c-KIT, Axl, RET, KDR, and VEGFR3), in combination with an anti-PD-L1 antibody (TQB2450) until disease progression, intolerable toxicity, death, or discontinuation for any cause. The primary end points included overall response rate (ORR) and safety, with secondary end points encompassing progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response. RESULTS: Between November 2021 and September 2022, 18 patients with ESCC and 15 patients with HCC, whose ORR was 11.1% (95% confidence interval [CI], 3.1%-32.8%) and 0%, respectively, were enrolled. Adverse events (AEs) of any grade and treatment-related AEs were documented in 32 patients (97.0%) and 31 patients (93.9%), respectively. Grade 3 or higher AEs were observed in 10 patients (30.3%), with vomiting (6.1%) and infectious pneumonia (9.1%) being the most prevalent. Median PFS and OS values were 3.22 months (95% CI, 1.35-5.68 months) and 5.98 months (95% CI, 3.71-8.87 months), respectively, in patients with ESCC, and 5.55 months (95% CI, 2.66 months to not evaluable [NE]) and 16.72 months (95% CI, 4.86 months to NE), respectively, in patients with HCC. The DCRs were 66.7% (95% CI, 43.75%-83.72%) in patients with ESCC and 73.3% (95% CI, 48.05%-89.10%) in patients with HCC. CONCLUSIONS: Combined TQB2450 and AL2846 therapy exhibited a favorable safety profile in immunotherapy-refractory patients with advanced ESCC and HCC.

12.
PLoS One ; 19(5): e0303983, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38781264

RESUMO

Despite accumulating evidence that blood flow restriction (BFR) training promotes muscle hypertrophy and strength gain, the underlying neurophysiological mechanisms have rarely been explored. The primary goal of this study is to investigate characteristics of cerebral cortex activity during BFR training under different pressure intensities. 24 males participated in 30% 1RM squat exercise, changes in oxygenated hemoglobin concentration (HbO) in the primary motor cortex (M1), pre-motor cortex (PMC), supplementary motor area (SMA), and dorsolateral prefrontal cortex (DLPFC), were measured by fNIRS. The results showed that HbO increased from 0 mmHg (non-BFR) to 250 mmHg but dropped sharply under 350 mmHg pressure intensity. In addition, HbO and functional connectivity were higher in M1 and PMC-SMA than in DLPFC. Moreover, the significant interaction effect between pressure intensity and ROI for HbO revealed that the regulation of cerebral cortex during BFR training was more pronounced in M1 and PMC-SMA than in DLPFC. In conclusion, low-load resistance training with BFR triggers acute responses in the cerebral cortex, and moderate pressure intensity achieves optimal neural benefits in enhancing cortical activation. M1 and PMC-SMA play crucial roles during BFR training through activation and functional connectivity regulation.


Assuntos
Córtex Cerebral , Córtex Motor , Treinamento Resistido , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Masculino , Treinamento Resistido/métodos , Adulto Jovem , Córtex Cerebral/fisiologia , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/metabolismo , Córtex Cerebral/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Córtex Motor/fisiologia , Córtex Motor/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/irrigação sanguínea , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/diagnóstico por imagem
13.
PLoS Biol ; 22(5): e3002628, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38814940

RESUMO

The peptidoglycan (PG) layer is a critical component of the bacterial cell wall and serves as an important target for antibiotics in both gram-negative and gram-positive bacteria. The hydrolysis of septal PG (sPG) is a crucial step of bacterial cell division, facilitated by FtsEX through an amidase activation system. In this study, we present the cryo-EM structures of Escherichia coli FtsEX and FtsEX-EnvC in the ATP-bound state at resolutions of 3.05 Å and 3.11 Å, respectively. Our PG degradation assays in E. coli reveal that the ATP-bound conformation of FtsEX activates sPG hydrolysis of EnvC-AmiB, whereas EnvC-AmiB alone exhibits autoinhibition. Structural analyses indicate that ATP binding induces conformational changes in FtsEX-EnvC, leading to significant differences from the apo state. Furthermore, PG degradation assays of AmiB mutants confirm that the regulation of AmiB by FtsEX-EnvC is achieved through the interaction between EnvC-AmiB. These findings not only provide structural insight into the mechanism of sPG hydrolysis and bacterial cell division, but also have implications for the development of novel therapeutics targeting drug-resistant bacteria.


Assuntos
Trifosfato de Adenosina , Divisão Celular , Proteínas de Escherichia coli , Escherichia coli , Peptidoglicano , Peptidoglicano/metabolismo , Hidrólise , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/química , Escherichia coli/metabolismo , Escherichia coli/genética , Trifosfato de Adenosina/metabolismo , Microscopia Crioeletrônica , Parede Celular/metabolismo , Conformação Proteica , Modelos Moleculares , N-Acetil-Muramil-L-Alanina Amidase/metabolismo , N-Acetil-Muramil-L-Alanina Amidase/genética , Proteínas da Membrana Bacteriana Externa , Transportadores de Cassetes de Ligação de ATP , Regulador de Condutância Transmembrana em Fibrose Cística , Lipoproteínas , Proteínas de Ciclo Celular
14.
Biosens Bioelectron ; 259: 116369, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38781695

RESUMO

Accurate and effective detection is essential to against bacterial infection and contamination. Novel biosensors, which detect bacterial bioproducts and convert them into measurable signals, are attracting attention. We developed an artificial intelligence (AI)-assisted smartphone-based colorimetric biosensor for the visualized, rapid, sensitive detection of pathogenic bacteria by measuring the bacteria secreted hyaluronidase (HAase). The biosensor consists of the chlorophenol red-ß-D-galactopyranoside (CPRG)-loaded hyaluronic acid (HA) hydrogel as the bioreactor and the ß-galactosidase (ß-gal)-loaded agar hydrogel as the signal generator. The HAase degrades the bioreactor and subsequently determines the release of CPRG, which could further react with ß-gal to generate signal colors. The self-developed YOLOv5 algorithm was utilized to analyze the signal colors acquired by smartphone. The biosensor can provide a report within 60 min with an ultra-low limit of detection (LoD) of 10 CFU/mL and differentiate between gram-positive (G+) and gram-negative (G-) bacteria. The proposed biosensor was successfully applied in various areas, especially the evaluation of infections in clinical samples with 100% sensitivity. We believe the designed biosensor has the potential to represent a new paradigm of "ASSURED" bacterial detection, applicable for broad biomedical uses.


Assuntos
Técnicas Biossensoriais , Colorimetria , Smartphone , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Colorimetria/instrumentação , Limite de Detecção , Humanos , Inteligência Artificial , beta-Galactosidase/química , Bactérias/isolamento & purificação
15.
Biol Trace Elem Res ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789898

RESUMO

Polycystic ovary syndrome (PCOS) severely affects women's fertility and accompanies serious metabolic disturbances, affecting 5%-20% of women of reproductive age globally. We previously found that exposure to toxic metals in the blood raised the risk of PCOS, but the association between exposure to toxic metals and the risk of PCOS in the follicular fluid, the microenvironment for oocyte growth and development in females, and its effect on metabolism has not been reported. This study aimed to evaluate the associations between the concentrations of cadmium (Cd), mercury (Hg), barium (Ba) and arsenic (As) in FF and the risk of PCOS, and to explore the mediating effect of metabolic markers in FF on the above relationship. We conducted a case-control study, including 557 women with PCOS and 651 controls. Ba, Cd, Hg and As levels in FF were measured by ICP-MS, metabolites levels in FF was measured by LC-MS/MS among 168 participants randomly selected from all the participants. Logistic regression models were used to assess the association of a single metal level with the PCOS risk, and linear regression models were used to assess the relationships of a single metal level with clinical phenotype parameters and metabolites levels. Combined effect of metals mixture levels on the risk of PCOS were assessed via weighted quantile sum (WQS) regression and bayesian kernel machine regression (BKMR). Medication analysis was performed to explore the role of metabolic markers on the relationship of toxic metals levels with the risk of PCOS. The exposure levels of Cd, Hg, Ba and As in FF were all positively and significantly associated with the PCOS risk (with respect to the highest vs. lowest tertile group: OR = 1.57, 95% CI = 1.17 ~ 2.12 for Cd, OR = 1.69, 95% CI = 1.22 ~ 2.34 for Hg, OR = 1.76, 95% CI = 1.32 ~ 2.34 for Ba, OR = 1.42, 95% CI = 1.05 ~ 1.91 for As). In addition, levels of metal mixture also significantly correlated with the risk of PCOS, Cd level contributed most to it. Moreover, we observed significant positive relationships between Cd level and LH (ß = 0.048, 95% CI = 0.002 ~ 0.094), T (ß = 0.077, 95% CI = 0.029 ~ 0.125) and HOMA-IR value (ß = 0.060, 95% CI = 0.012 ~ 0.107), as well as Hg level with LH, FSH/LH ratio and TC. Furthermore, we revealed that estrone sulfate, LysoPE 22:6 and N-Undecanoylglycine were significantly and positively mediating the association between Cd level and the risk of PCOS (with mediated proportion of 0.39, 0.24 and 0.35, respectively), and between Hg level and the risk of PCOS (with mediated proportion of 0.29, 0.20 and 0.46, respectively). These highly expressed metabolites significantly enriched in the fatty acid oxidation, steroid hormone biosynthesis and glycerophospholipids metabolism, which may explain the reason why the levels of Cd and Hg in FF associated with the phenotype of PCOS. Ba and As in FF was not found the above phenomenon. Our results suggested that exposure to multiple toxic metals (Cd, Hg, Ba and As) in FF associated with the increased risk of PCOS, Cd was a major contributor. Levels of Cd and Hg in FF significantly associated with the phenotype of PCOS. The above association may result from that Cd and Hg in FF related with the disturbance of fatty acid oxidation, steroid hormone biosynthesis and the glycerophospholipids metabolism.

16.
Int J Biol Macromol ; 270(Pt 2): 132231, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38735603

RESUMO

Mpox virus has wildly spread over 108 non-endemic regions in the world since May 2022. DNA replication of mpox is performed by DNA polymerase machinery F8-A22-E4, which is known as a great drug target. Brincidofovir and cidofovir are reported to have broad-spectrum antiviral activity against poxviruses, including mpox virus in animal models. However, the molecular mechanism is not understood. Here we report cryogenic electron microscopy structures of mpox viral F8-A22-E4 in complex with a DNA duplex, or dCTP and the DNA duplex, or cidofovir diphosphate and the DNA duplex at resolution of 3.22, 2.98 and 2.79 Å, respectively. Our structural work and DNA replication inhibition assays reveal that cidofovir diphosphate is located at the dCTP binding position with a different conformation to compete with dCTP to incorporate into the DNA and inhibit DNA synthesis. Conformation of both F8-A22-E4 and DNA is changed from the pre-dNTP binding state to DNA synthesizing state after dCTP or cidofovir diphosphate is bound, suggesting a coupling mechanism. This work provides the structural basis of DNA synthesis inhibition by brincidofovir and cidofovir, providing a rational strategy for new therapeutical development for mpox virus and other pox viruses.


Assuntos
Antivirais , Cidofovir , Citosina , Replicação do DNA , Organofosfonatos , Replicação Viral , Cidofovir/farmacologia , Cidofovir/química , Organofosfonatos/farmacologia , Organofosfonatos/química , Citosina/análogos & derivados , Citosina/farmacologia , Citosina/química , Replicação do DNA/efeitos dos fármacos , Humanos , Antivirais/farmacologia , Antivirais/química , Replicação Viral/efeitos dos fármacos , DNA Viral , Modelos Moleculares
17.
Sci Total Environ ; 937: 173482, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38795982

RESUMO

Extensive application of rare earth element oxide nanoparticles (REE NPs) has raised a concern over the possible toxic health effects after human exposure. Once entering the body, REE NPs are primarily processed by phagocytes in particular macrophages and undergo biotic phosphate complexation in lysosomal compartment. Such biotransformation affects the target organs and in vivo fate of REE NPs after escaping the lysosomes. However, the immunomodulatory effects of intraphagolysosomal dissolved REE NPs remains insufficient. Here, europium oxide (Eu2O3) NPs were pre-incubated with phagolysosomal simulant fluid (PSF) to mimic the biotransformation of europium oxide (p-Eu2O3) NPs under acid phagolysosome conditions. We investigated the alteration in immune cell components and the hematopoiesis disturbance on adult mice after intravenous administration of Eu2O3 NPs and p-Eu2O3 NPs. Our results indicated that the liver and spleen were the main target organs for Eu2O3 NPs and p-Eu2O3 NPs. Eu2O3 NPs had a much higher accumulative potential in organs than p-Eu2O3 NPs. Eu2O3 NPs induced more alterations in immune cells in the spleen, while p-Eu2O3 NPs caused stronger response in the liver. Regarding hematopoietic disruption, Eu2O3 NPs reduced platelets (PLTs) in peripheral blood, which might be related to the inhibited erythrocyte differentiation in the spleen. By contrast, p-Eu2O3 NPs did not cause significant disturbance in peripheral PLTs. Our study demonstrated that the preincubation with PSF led to a distinct response in the immune system compared to the pristine REE NPs, suggesting that the potentially toxic effects induced by the release of NPs after phagocytosis should not be neglected, especially when evaluating the safety of NPs application in vivo.


Assuntos
Európio , Hematopoese , Lisossomos , Nanopartículas Metálicas , Óxidos , Animais , Európio/toxicidade , Camundongos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Óxidos/toxicidade , Hematopoese/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Baço/efeitos dos fármacos , Nanopartículas/toxicidade
18.
Angew Chem Int Ed Engl ; : e202409094, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806443

RESUMO

Supramolecular artificial light-harvesting system with highly efficient host-guest energy transfer pathway provides an ideal platform for optimizing the photochemistry process. The consecutive photo-induced electron transfer (conPET) process overcomes the energy limitation of visible-light photocatalysis, but is often compromised by mismatching between the absorption of ground state dye and its radical, weakening the efficiency of photoredox reaction. By encapsulating a conPET photocatalyst rhodamine 6G into metal-organic cage, the supramolecular approach was undertaken to tackle the intrinsic difficulty of matching the light absorption of photoexcitation between rhodamine 6G and its radical. The highly efficient Förster resonance energy transfer from the photoexcited cage to rhodamine 6G forced by host-guest encapsulation facilitates the conPET process for the single-wavelength light-driven activation of aryl halides by stabilizing and accelerating the production and accumulation of the rhodamine 6G radical intermediate. The tunable and flexible nature of the supramolecular host-guest complex renders the cage-based encapsulation strategy promising for the development of ideal photocatalysts toward the better utilization of solar energy.

19.
Materials (Basel) ; 17(8)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38673213

RESUMO

The dynamic mechanical behavior and cushioning performance of honeycomb sandwich panels, which are extensively employed in product cushioning packaging due to their exceptional energy absorption capabilities, were examined using a combination of experimental and numerical methods. Several factors, such as maximum acceleration-static stress, cushioning coefficient-static stress, and other curves, were analyzed under various impact conditions. The simulated stress-strain, deformation modes, cushioning coefficients, and other parameters demonstrate consistency with the experimental results. The acceleration, maximum compression, and cushioning coefficient obtained from the experiment and simulation calculation were 30.68 g, 15.44 mm, and 2.65, and 31.96 g, 14.91 mm, and 2.79, respectively. The results indicate that all error values were less than 5%, confirming the precision and reliability of the model. Furthermore, the model was utilized to simulate and predict the cushioning performance of honeycomb sandwich panels with different cell structures and paper thicknesses. These results provide a solid basis for enhancing the design of subsequent honeycomb element structures.

20.
Proc Natl Acad Sci U S A ; 121(17): e2314353121, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38635634

RESUMO

Auxin regulates plant growth and development through downstream signaling pathways, including the best-known SCFTIR1/AFB-Aux/IAA-ARF pathway and several other less characterized "noncanonical" pathways. Recently, one SCFTIR1/AFB-independent noncanonical pathway, mediated by Transmembrane Kinase 1 (TMK1), was discovered through the analyses of its functions in Arabidopsis apical hook development. Asymmetric accumulation of auxin on the concave side of the apical hook triggers DAR1-catalyzed release of the C-terminal of TMK1, which migrates into the nucleus, where it phosphorylates and stabilizes IAA32/34 to inhibit cell elongation, which is essential for full apical hook formation. However, the molecular factors mediating IAA32/34 degradation have not been identified. Here, we show that proteins in the CYTOKININ INDUCED ROOT WAVING 1 (CKRW1)/WAVY GROWTH 3 (WAV3) subfamily act as E3 ubiquitin ligases to target IAA32/34 for ubiquitination and degradation, which is inhibited by TMK1c-mediated phosphorylation. This antagonistic interaction between TMK1c and CKRW1/WAV3 subfamily E3 ubiquitin ligases regulates IAA32/34 levels to control differential cell elongation along opposite sides of the apical hook.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas F-Box , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Transdução de Sinais , Ubiquitinas/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas F-Box/genética , Proteínas F-Box/metabolismo
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