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Tanshinone IIA (Tan IIA), a neuroprotective natural compound extracted from Salvia miltiorrhiza, is used in stroke treatment. However, elucidating Tan IIA's neuroprotective mechanisms remains challenging due to limitations in assessing drug efficacy and biochemical parameters in clinical studies. This study investigated Tan IIA's impact on neuroinflammatory responses and its neuroprotective mechanisms using HMGB1- or TNF-α-stimulated BV2 microglia in a co-culture system with primary neuron cells. The results indicated that Tan IIA significantly reduced microglial activation induced by TNF-α or HMGB1. Concurrently, Tan IIA disrupted the interactions between HMGB1 and toll-like receptor 4 (TLR4), and between TNF-α and TNF receptor 1 (TNFR1), modulating the HMGB1/TLR4/nuclear factor-kappa B (NF-κB) and TNF-α/TNFR1/NF-κB signaling pathways and related protein expressions. Moreover, co-culture experiments showed that neuronal apoptosis induced by microglial activation was reversed by Tan IIA. In conclusion, Tan IIA provides neuroprotection by modulating signaling pathways in microglia, thus preventing neuronal apoptosis. This study offers new insights into therapeutic targets for ischemic stroke.

RESUMO

Ammonia-oxidizing archaea (AOA) play crucial roles in marine carbon and nitrogen cycles by fixing inorganic carbon and performing the initial step of nitrification. Evaluation of carbon and nitrogen metabolism popularly relies on functional genes such as amoA and accA. Increasing studies suggest that quorum sensing (QS) mainly studied in biofilms for bacteria may serve as a universal communication and regulatory mechanism among prokaryotes; however, this has yet to be demonstrated in marine planktonic archaea. To bridge this knowledge gap, we employed a combination of metabolic activity markers (amoA, accA, and grs) to elucidate the regulation of AOA-mediated nitrogen, carbon processes, and their interactions with the surrounding heterotrophic population. Through co-transcription investigations linking metabolic markers to potential key QS genes, we discovered that QS molecules could regulate AOA's carbon, nitrogen, and lipid metabolisms under different conditions. Interestingly, specific AOA ecotypes showed a preference for employing distinct QS systems and a distinct QS circuit involving a typical population. Overall, our data demonstrate that QS orchestrates nitrogen and carbon metabolism, including the exchange of organic metabolites between AOA and surrounding heterotrophic bacteria, which has been previously overlooked in marine AOA research.

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OBJECTIVE: To observe the clinical efficacy of medical education combined with extended care in patients with bronchial asthma and its effect on adherence to inhaled glucocorticoids. METHODS: Ninety-eight patients with bronchial asthma were divided into the control group and the experimental group, n = 49, by utilizing the random number table method. The control group was given routine education and care as well as routine out-of-hospital instructions, and the experimental group was given medical education and extended care based on the control group. Asthma disease knowledge mastery, asthma control, quality of life, medication adherence and lung function were compared between both groups, and the number of asthma attacks and re-hospitalizations were recorded. RESULTS: The experimental group performed higher scores of health knowledge, asthma control test and quality of life, rate of complete adherence, forced expiratory volume in one second (FEV1), peak expiratory flow rate, and FEV1/forced vital capacity. The number of asthma attacks and the times of re-hospitalizations were lower in the experimental group (all P < 0.05). CONCLUSION: Medical education combined with extended care can improve bronchial asthma patients' mastery of asthma disease knowledge, effectively control patients' conditions, enhance patients' quality of life and lung function, increase patients' adherence to inhaled glucocorticoids, and reduce the recurrence of bronchial asthma patients.

RESUMO

PURPOSE: To explore the value of tissue quantitative diffusion analysis of ultrasound elastography in the diagnosis of early-stage chronic kidney disease (CKD). METHODS: The observation group comprised 54 patients with early-stage CKD treated at Fuzhou No 7 Hospital, and the control group consisted of 40 healthy individuals who underwent physical examinations at the same hospital. The renal parenchyma of the participants were examined using ultrasonography, color Doppler ultrasonography, and tissue quantitative diffusion analysis of ultrasound elastography. Renal dimensions (diameter, thickness, and renal parenchyma thickness), interlobar artery blood flow parameters, and 11 elastic characteristic values were analyzed and compared between the two groups. The area under the receiver-operating characteristic (ROC) curve, cut-off values, sensitivity, and specificity were calculated using the ROC curve analysis. RESULTS: There were no significant differences in the blood flow parameters of the interlobar artery and the dimensions of renal meridians between the two groups. In the observation group, the mean (MEAN) decreased, while the blue area ratio and skewness, increased, compared to the control group (p < 0.05). In addition, the ROC curve revealed that the blue area ratio, MEAN, and skewness had significant diagnostic value (the area under the curve > 0.7). Notably, the best cut-off value of the MEAN was found to be 106, indicating that a MEAN value less than 106 represented early-stage CKD. Also, this cutoff value had a sensitivity of 80% and a specificity of 81%. CONCLUSION: Tissue quantitative diffusion analysis of ultrasound elastography can quantitatively evaluate renal parenchymal damage in early-stage CKD using quantitative diffusion parameters, with the MEAN parameter, having a cutoff of 106, being particularly effective. This parameter and cutoff value offer a valuable tool for the early detection and diagnosis of CKD, potentially improving patient outcomes through earlier intervention. CLINICAL TRIAL NUMBER: Not applicable.

Assuntos

Técnicas de Imagem por Elasticidade , Insuficiência Renal Crônica , Humanos , Técnicas de Imagem por Elasticidade/métodos , Masculino , Feminino , Insuficiência Renal Crônica/diagnóstico por imagem , Pessoa de Meia-Idade , Adulto , Idoso , Diagnóstico Precoce , Rim/diagnóstico por imagem , Rim/irrigação sanguínea , Curva ROC , Sensibilidade e Especificidade

RESUMO

Coral-associated bacteria are sensitive to the health status of coral and proven biomarker(s) of the coral bleaching. However, whether coral specificity or health status play a key role when coral-associated bacteria responding to coral bleaching is not known. Therefore, the bacterial communities of five species of healthy and bleached corals, Acropora millepora, Favites abdita, Galaxea fascicularis, Dipsastraea speciosa and Pocillopora damicornis, were collected along the coast of Sanya, South China Sea and targeted for associated bacterial studies. The relative abundance of the dominant class Gammaproteobacteria tended to be higher in healthy corals, while Alphaproteobacteria were more abundant in bleached corals. Dominant genus Achromobacter demonstrated higher relative abundance in healthy corals (0.675) than in bleached corals (0.151). Most of the bleached corals had high α diversity, ß dispersion, heterogeneity and complexity of the co-occurrence network of bacterial communities, which support the 'Anna Karenina Principle (AKP)' of diverse in threatened objects and conserved in healthy ones. The bacterial communities in the bleached corals were mostly involved in the selection process, and communities in the healthy corals were involved in the undominated process, which is obtained based on the null model test of ß nearest-taxon-index (ßNTI) and Bray-Curtis-based Raup-Crick (RCBray). This evidence further confirmed the AKP and revealed that the bacterial communities in the bleached corals were driven by deterministic factors. These findings provide valuable insights into the connection between bacterial and coral status, and the application of the AKP in the changing patterns of bacterial communities during coral bleaching.

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BACKGROUND: The development of the human vermiform appendix at the cellular level, as well as its function, is not well understood. Appendicitis in preschool children, although uncommon, is associated with a high perforation rate and increased morbidity. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on the human appendix during fetal and pediatric stages as well as preschool-age inflammatory appendices. Transcriptional features of each cell compartment were discussed in the developing appendix. Cellular interactions and differentiation trajectories were also investigated. We compared scRNA-seq profiles from preschool appendicitis to those of matched healthy controls to reveal disease-associated changes. Bulk transcriptomic data, immunohistochemistry, and real-time quantitative PCR were used to validate the findings. RESULTS: Our analysis identified 76 cell types in total and described the cellular atlas of the developing appendix. We discovered the potential role of the BMP signaling pathway in appendiceal epithelium development and identified HOXC8 and PITX2 as the specific regulons of appendix goblet cells. Higher pericyte coverage, endothelial angiogenesis, and goblet mucus scores together with lower epithelial and endothelial tight junction scores were found in the preschool appendix, which possibly contribute to the clinical features of preschool appendicitis. Preschool appendicitis scRNA-seq profiles revealed that the interleukin-17 signaling pathway may participate in the inflammation process. CONCLUSIONS: Our study provides new insights into the development of the appendix and deepens the understanding of appendicitis in preschool children.

Assuntos

Apendicite , Apêndice , Análise de Célula Única , Humanos , Apendicite/genética , Apendicite/patologia , Pré-Escolar , Análise de Célula Única/métodos , Feminino , Masculino , Análise de Sequência de RNA/métodos , Lactente , Proteínas de Homeodomínio/genética

RESUMO

In fringe projection profilometry based on temporal phase unwrapping, determining a fringe order map commonly requires a large number of fringes. To reduce the fringe number, this paper proposes a concise absolute phase retrieval algorithm just by projecting four fringes. The first two orthogonal fringes with relatively large frequency can collect reliable height information. The second two fringes are designed the same as the first two, but the only difference is that each 2π-phase of them is shifted by a unique amount, which can robustly label a large number of fringe orders. For decoding the fringes, we develop an average intensity one-time extraction algorithm, which allows for the rapid acquisition of the two pairs of alternating current components. From this, the wrapped phase containing height information and the stair-coded phase providing fringe orders can be directly extracted by arctangent operation in a point-to-point manner. Furthermore, we also develop a universal fringe order correction algorithm that can simultaneously correct the common errors and the misalignment between the wrapped phase and fringe orders. Experiment results demonstrate that this method achieves comparable accuracy and adaptability to the phase-coding method, while utilizing two fewer fringes.

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Peeling wheat yields higher-quality flour. During processing in a flaking machine, wheat kernels undergo continuous compression within the machine's chamber. As this compression persists, damage to the kernels intensifies and accumulates, eventually leading to kernel breakage. To study the damage characteristics of wheat kernels during peeling, this study established a continuous damage model based on Hertzian contact theory and continuous damage theory. The model's accuracy was validated through experiments, culminating in the calculation of critical parameters for wheat peeling. This study focused on different wheat varieties (Ningmai 22 and Jichun 1) and kernel sizes (the thicknesses of the small, medium, and large kernels were standardized as follows: Ningmai 22-2.67 ± 0.07 mm, 2.81 ± 0.07 mm, and 2.95 ± 0.07 mm; Jichun 1-2.98 ± 0.11 mm, 3.20 ± 0.11 mm, and 3.42 ± 0.11 mm). Continuous compression tests were conducted using a mass spectrometer, and critical damage parameters were analyzed and calculated by integrating the theoretical model with experimental data. The test results showed that the average maximum crushing force (Fc) for small, medium, and large-sized kernels of Ningmai 22 was 96.71 ± 2.27 N, 110.17 ± 2.68 N, and 128.41 ± 2.85 N, respectively. The average maximum crushing deformation (αc) was 0.65 ± 0.08 mm, 0.68 ± 0.13 mm, and 0.77 ± 0.17 mm, respectively. The average elastic-plastic critical pressure (Fs) was 50.21 N, 60.13 N, and 59.08 N, respectively, and the average critical values of elastic-plastic deformation (αs) were 0.37 mm, 0.38 mm, and 0.39 mm, respectively. For Jichun 1, the average maximum crushing force (Fc) for small-, medium-, and large-sized kernels was 113.34 ± 3.15 N, 125.28 ± 3.64 N, and 136.15 ± 3.29 N, respectively. The average maximum crushing deformation (αc) was 0.75 ± 0.11 mm, 0.83 ± 0.15 mm, and 0.88 ± 0.18 mm, respectively. The average elastic-plastic critical pressure (Fs) was 58.11 N, 64.17 N, and 85.05 N, respectively, and the average critical values of elastic-plastic deformation (αs) were 0.45 mm, 0.47 mm, and 0.52 mm, respectively. The test results indicated that during mechanical compression, if the deformation is less than αs, the continued application of the compression load will not result in kernel crushing. However, if the deformation exceeds αs, continued compression will lead to kernel crushing, with the required number of compressions decreasing as the deformation increases. If the deformation surpasses αc, a single compression load is sufficient to cause kernel crushing. Since smaller wheat kernels are more susceptible to breakage during processing, the peeling pressure (F) within the chamber should be controlled to remain below the average elastic-plastic critical pressure (Fs) of small-sized wheat kernels. Additionally, the kernel deformation (α) induced by the flow rate and loading in the chamber should be kept below the average elastic-plastic critical deformation (αs) of small-sized wheat kernels. This paper provides a theoretical foundation for the structural design and optimization of processing parameters for wheat peeling machines.

RESUMO

Methods based on deep learning have achieved great success in the field of video action recognition. When these methods are applied to real-world scenarios that require fine-grained analysis of actions, such as being tested on a tea ceremony, limitations may arise. To promote the development of fine-grained action recognition, a fine-grained video action dataset is constructed by collecting videos of tea ceremony actions. This dataset includes 2745 video clips. By using a hierarchical fine-grained action classification approach, these clips are divided into 9 basic action classes and 31 fine-grained action subclasses. To better establish a fine-grained temporal model for tea ceremony actions, a method named TSM-ConvNeXt is proposed that integrates a TSM into the high-performance convolutional neural network ConvNeXt. Compared to a baseline method using ResNet50, the experimental performance of TSM-ConvNeXt is improved by 7.31%. Furthermore, compared with the state-of-the-art methods for action recognition on the FineTea and Diving48 datasets, the proposed approach achieves the best experimental results. The FineTea dataset is publicly available.

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Biodegradable microplastics (Bio-MPs) are a hot topic in soil research due to their potential to replace conventional microplastics. Biofertilizers are viewed as an alternative to inorganic fertilizers in agriculture due to their potential to enhance crop yields and food safety. The use of both can have direct and indirect effects on rhizosphere microorganisms. However, the influence of the coexistence of "Bio-MPs and biofertilizers" on rhizosphere microbial characteristics remains unclear. We investigated the effects of coexisting biofertilizers and Bio-MPs on the structure, function, and especially the carbon metabolic properties of crop rhizosphere bacteria, using a pot experiment in which polyethylene microplastics (PE-MPs) were used as a reference. The results showed that the existence of both microplastics (MPs) changed the physicochemical properties of the rhizosphere soil. Exposure to MPs also remarkably changed the composition and diversity of rhizosphere bacteria. The network was more complex in the Bio-MPs group. Additionally, metagenomic analyses showed that PE-MPs mainly affected microbial vitamin metabolism. Bio-MPs primarily changed the pathways related to carbon metabolism, such as causing declined carbon fixation/degradation and inhibition of methanogenesis. After partial least squares path model (PLS-PM) analysis, we observed that both materials influenced the rhizosphere environment through the bacterial communities and functions. Despite the degradability of Bio-MPs, our findings confirmed that the coexistence of biofertilizers and Bio-MPs affected the fertility of the rhizosphere. Regardless of the type of plastic, its use in soil requires an objective and scientifically grounded approach.

RESUMO

PURPOSE: This study aims to analyze whether undergoing amniocentesis during pregnancy in women diagnosed with hepatitis B virus (HBV) infection leads to HBV transmission to newborns. METHODS: Retrospective data collection was conducted from June 2019 to November 2022 on expectant mothers positive for hepatitis B surface antigen (HBsAg) who underwent amniocentesis at The Third Affiliated Hospital of Sun Yat-sen University, along with data on their newborns. The study summarized the HBV infection status of newborns born to mothers with different expressions of hepatitis B e antigen (HBeAg), antiviral treatment versus no treatment, and different HBV DNA viral loads before delivery. RESULTS: In this study, 346 expectant mothers tested positive for HBsAg, along with 351 newborns (including 5 sets of twins, with 8 infants (2.28%) testing HBsAg-positive at birth. All newborns received dual immunotherapy and were followed up. At 7-12 months, retesting for HBsAg positivity and HBV DNA positivity among infants revealed that out of the infants born with HBsAg positivity, 7 cases had seroconverted to negative, while the remaining infant, who was positive for both HBsAg and HBeAg at birth, tested positive for both HBsAg and HBV DNA at 7-12 months. Thus, one case of vertical transmission of hepatitis B from mother to child occurred in this study. The proportion of infants born with HBsAg + among newborns born to HBeAg-positive mothers (4 cases, 6.06%) was significantly higher than that among newborns born to HBeAg-negative mothers (4 cases, 1.41%) (P < 0.05). The proportion of infants born with HBsAg + showed no significant difference between newborns born to mothers receiving antiviral therapy (2 cases, 2.90%) and those born to mothers not receiving antiviral therapy (6 cases, 2.13%) (P > 0.05). Among expectant mothers with viral load ≥ 6 log 10 IU/mL before delivery, 3 newborns (30.00%) were manifesting HBsAg positivity at birth, significantly higher than the group with viral load < 6 log 10 IU/mL before delivery (5 cases, 1.47%) (P < 0.05). CONCLUSION: Among HBsAg-positive expectant mothers, only a small number of infants are infected with the hepatitis B virus at birth, the proportion of which is relatively low. Infants born to mothers who are HBeAg-positive or have a viral load ≥ 6 log10 IU/mL have a higher risk of being born positive.

Assuntos

Amniocentese , DNA Viral , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Vírus da Hepatite B , Hepatite B , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez , Carga Viral , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Recém-Nascido , Hepatite B/transmissão , Adulto , Antígenos de Superfície da Hepatite B/sangue , Complicações Infecciosas na Gravidez/virologia , Complicações Infecciosas na Gravidez/tratamento farmacológico , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , DNA Viral/sangue , Antígenos E da Hepatite B/sangue , Antivirais/uso terapêutico , Masculino , Mães , Adulto Jovem

RESUMO

A series of arylsulfones and heteroarylsulfones have previously been demonstrated to dysregulate the conserved bacterial ClpP protease, causing the unspecific degradation of essential cellular housekeeping proteins and ultimately resulting in cell death. A cocrystal structure of a 2-ß-sulfonylamide analog, ACP1-06, with Escherichia coli ClpP showed that its 2-pyridyl sulfonyl substituent adopts two orientations in the binding site related through a sulfone bond rotation. From this, a new bis-aryl phosphine oxide scaffold, designated as ACP6, was designed based on a "conformation merging" approach of the dual orientation of the ACP1-06 sulfone. One analog, ACP6-12, exhibited over a 10-fold increase in activity over the parent ACP1-06 compound, and a cocrystal X-ray structure with ClpP confirmed its predicted binding conformation. This allowed for a comparative analysis of how different ligand classes bind to the hydrophobic binding site. The study highlights the successful application of structure-based rational design of novel phosphine oxide-based antibiotics.

Assuntos

Antibacterianos , Desenho de Fármacos , Endopeptidase Clp , Escherichia coli , Óxidos , Fosfinas , Fosfinas/química , Fosfinas/farmacologia , Endopeptidase Clp/metabolismo , Endopeptidase Clp/antagonistas & inibidores , Endopeptidase Clp/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Óxidos/química , Escherichia coli/enzimologia , Escherichia coli/efeitos dos fármacos , Relação Estrutura-Atividade , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/antagonistas & inibidores , Cristalografia por Raios X , Modelos Moleculares , Sítios de Ligação , Estrutura Molecular

RESUMO

Acetyl CoA acetyltransferase 1 (ACAT1), a mitochondrial enzyme, is mainly involved in the formation and decomposition of ketones, isoleucine, and fatty acids. Previous clinical studies showed that mutations in the ACAT1 gene lead to ketoacidosis, Notably the role of ACAT1 in human cancer' pathogenesis varies depending on cancer type, and its specific role in gastric cancer remains largely unknown. In the current study, we found that the expression of ACAT1 in primary late-stage gastric cancer tumor tissues was significantly lower than in early-stage tumors. This observation was further confirmed in high-grade gastric cancer cell line MKN45. The expression of CD44 and OCT4 was decreased, while CD24 expression was increased by overexpressing ACAT1 in MKN45 gastric cancer cells. Moreover, the ability of gastric cancer cells to form colonies on soft agar was also reduced by ACAT1 overexpression. Likewise, overexpression of ACAT1 inhibited epithelial mesenchymal transition (EMT) in gastric cancer cells evidenced by increased expression of the epithelial marker E-Cadherin, decreased expression of mesenchymal marker vimentin, and decreased expression levels of SNAI 1/3. In addition, ACAT1 overexpression inhibited cell migration and invasion, improved the response to 5-Fluorouracil (5-FU) and etoposide. In contrast, inhibition of ACAT1 activity promoted the proliferation of gastric cancer cells. The xenotransplantation results in nude mice showed that overexpression of ACAT1 in gastric cancer cells inhibited tumor growth in vivo. In addition, the low expression of ACAT1 in gastric cancer was further validated by searching public databases and conducting bioinformatic analyses. Mechanistically, bioinformatic analysis found that the inhibitory effect of ACAT1 in gastric cancer may be related to the Adipocytokine Signaling Pathway, Ppar Signaling Pathway, Propanoate Metabolism and P53 Signaling Pathway. Correlation analysis indicated ACAT1 mRNA expression was correlated with immune infiltrates. Collectively, our data show that ACAT1 induces pronounced inhibitory effects on gastric cancer initiation and development, which may impact future strategies to treat this aggressive cancer.

Assuntos

Acetil-CoA C-Acetiltransferase , Transição Epitelial-Mesenquimal , Mitocôndrias , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Acetil-CoA C-Acetiltransferase/metabolismo , Acetil-CoA C-Acetiltransferase/genética , Mitocôndrias/metabolismo , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Movimento Celular , Proliferação de Células , Feminino , Masculino , Ensaios Antitumorais Modelo de Xenoenxerto , Fluoruracila/farmacologia

RESUMO

Marine algal toxins have garnered significant attention in the research community for their unique biochemical properties and potential medical applications. These bioactive compounds, produced by microalgae, pose significant risks due to their high toxicity, yet offer promising therapeutic benefits. Despite extensive research identifying over 300 marine algal toxins, including azaspiracids, brevetoxins, cyclic imines, and yessotoxins, gaps remain in the understanding of their pharmacological potential. In this paper, we critically review the classification, bioactive components, toxicology, pharmacological activities, and mechanisms of these toxins, with a particular focus on their clinical applications. Our motivation stems from the increasing interest in marine algal toxins as candidates for drug development, driven by their high specificity and affinity for various biological receptors. We aim to bridge the gap between toxicological research and therapeutic application, offering insights into the advantages and limitations of these compounds in comparison to other bioactive substances. This review not only enhances the understanding of marine algal toxins' complexity and diversity, but also highlights their extensive application potential in medicine and bioscience, providing a foundation for future research and development in this field.

Assuntos

Toxinas Marinhas , Toxinas Marinhas/toxicidade , Toxinas Marinhas/química , Toxinas Marinhas/farmacologia , Humanos , Animais , Oxocinas/toxicidade , Oxocinas/química , Oxocinas/farmacologia , Microalgas/química , Toxinas de Poliéter , Venenos de Moluscos

RESUMO

Deep multiview clustering provides an efficient way to analyze the data consisting of multiple modalities and features. Recently, the autoencoder (AE)-based deep multiview clustering algorithms have attracted intensive attention by virtue of their rewarding capabilities of extracting inherent features. Nevertheless, most existing methods are still confronted by several problems. First, the multiview data usually contains abundant cross-view information, thus parallel performing an individual AE for each view and directly combining the extracted latent together can hardly construct an informative view-consensus feature space for clustering. Second, the intrinsic local structures of multiview data are complicated, hence simply embedding a preset graph constraint into multiview clustering models cannot guarantee expected performance. Third, current methods commonly utilize the Kullback-Leibler (KL) divergence as clustering loss and accordingly may yield appalling clusters that lack discriminate characters. To solve these issues, in this article we propose two new AE-based deep multiview clustering algorithms named AE-based deep multiview clustering model incorporating graph embedding (AG-DMC) and deep discriminative multiview clustering algorithm with adaptive graph constraint (ADG-DMC). In AG-DMC, a novel cross-view representation learning model is established delicately by performing decoding processes based on the cascaded view-specific latent to learn sound view-consensus features for inspiring clustering results. In addition, an entropy-regularized adaptive graph constraint is imposed on the obtained soft assignments of data to precisely preserve potential local structures. Furthermore, in the improved model ADG-DMC, the adversarial learning mechanism is adopted as clustering loss to strengthen the discrimination of different clusters for better performance. In the comprehensive experiments carried out on eight real-world datasets, the proposed algorithms have achieved superior performance in the comparison with other advanced multiview clustering algorithms.

RESUMO

Engineered hydrogel patches have shown promising therapeutic effects in the treatment of myocardial infarction (MI), especially anisotropic patches that mimic the characteristics of native myocardium have attracted widespread attention. However, it remains a great challenge to develop cardiac patches with long-range and orderly electrical conduction based on an effective, mild, and rapid strategy. Here, a multifunctional anisotropic cardiac patch is presented based on microfluidic manipulation. The anisotropic alginate-gelatin methacrylate hydrogel patches are easily and rapidly prepared through microfluidic focusing, ion-photocrosslinking, and parallel packing processes. The fluid-based anisotropic realization process does not involve complex machining and strong field stimulation and is compatible with the loading of macromolecular biological agents. The anisotropic hydrogel patch can mimic the anisotropy of the myocardium and guide the directional polarization of cardiomyocytes. In animal model experiments, it also exhibits significant effects in inhibiting ventricular remodeling, fibrosis, and enhancing cardiac function recovery after MI. These comprehensive features make the multifunctional hydrogel patch a promising candidate for cardiac tissue repair and future provide a new paradigm for expanding microfluidic technology to solve tissue engineering challenges.

RESUMO

Background: Angioimmunoblastic T-cell lymphoma (AITL) is known for its unfavorable survival prognosis. Chidamide has shown efficacy in relapsed/refractory AITL, but its efficacy in newly diagnosed AITL is uncertain. Objective: This retrospective research aimed to evaluate the effectiveness and safety of chidamide when used with doxorubicin, cyclophosphamide, prednisone, and vincristine (CHOP) in comparison to CHOP by itself for individuals newly diagnosed with AITL, and to examine the impact of transplantation. Method: This was an analysis that compared outcomes among patients who received chidamide + CHOP on a clinical trial vs. historical controls who received CHOP alone, enrolling a total of sixty-six treatment-naive AITL patients between April 2014 and November 2022. Among them, thirty-three received chidamide in addition to CHOP (chidamide group), while thirty-three received CHOP alone (control group). The clinical characteristics were balanced between the two groups. All patients were scheduled to undergo up to six courses of treatment before transplantation. Results: The chidamide group had a significantly longer median overall survival (OS) compared to the control group, with a median OS that was not reached, as opposed to 20 months in the control group (p = 0.002). In the control group, the median progression-free survival (PFS) was 11 months, while in the chidamide group, it was 22 months (p = 0.080). In the high-risk group (IPI ≥ 3), the chidamide group demonstrated notably superior complete response (CR) and overall response rate (ORR) compared to the control cohort (p = 0.002, p = 0.034). The PFS and OS in the chidamide group were not reached, and there were significant differences compared to the control group (p = 0.007, p = 0.003). The median OS of the transplanted group was longer than the non-transplanted group (p = 0.004). On multivariate analysis, chidamide group reduced the hazards of death in the total cohort. Conclusion: As the study was non-random and retrospective, Chidamide combined with chemotherapy should be tested in randomized trials given its potential to improve prognosis in treatment-naive AITL patients. Furthermore, autologous hematopoietic stem cell transplantation (auto-HSCT) has demonstrated enhanced overall survival in individuals with AITL. Clinical trial registration: https://clinicaltrials.gov/, NCT03268889.

Assuntos

Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aminopiridinas/uso terapêutico , Aminopiridinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzamidas/uso terapêutico , Benzamidas/administração & dosagem , Benzamidas/efeitos adversos , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Linfoma de Células T/mortalidade , Linfoma de Células T/terapia , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/diagnóstico , Prednisona/uso terapêutico , Prednisona/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/uso terapêutico , Vincristina/administração & dosagem

RESUMO

Age-related osteoporosis manifests as a complex pathology that disrupts bone homeostasis and elevates fracture risk, yet the mechanisms facilitating age-related shifts in bone marrow macrophages/osteoclasts (BMMs/OCs) lineage are not fully understood. To decipher these mechanisms, we conducted an investigation into the determinants controlling BMMs/OCs differentiation. We performed single-cell multi-omics profiling on bone marrow samples from mice of different ages (1, 6, and 20 months) to gain a holistic understanding of cellular changes across time. Our analysis revealed that aging significantly instigates OC differentiation. Importantly, we identified Cebpd as a vital gene for osteoclastogenesis and bone resorption during the aging process. Counterbalancing the effects of Cebpd, we found Irf8, Sox4, and Klf4 to play crucial roles. By thoroughly examining the cellular dynamics underpinning bone aging, our study unveils novel insights into the mechanisms of age-related osteoporosis and presents potential therapeutic targets for future exploration.

RESUMO

AIM: To investigate whether retinal nerve fiber layer defects (RNFLDs) is a potential risk factor for chronic kidney disease (CKD) in Chinese adults. METHODS: The Kailuan Eye Study was a population-based study that included 14 440 participants. All participants underwent detailed assessments, RNFLDs were diagnosed using color fundus photographs. RESULTS: Overall, 12 507 participants [8533 males (68.23%)] had complete systemic examination data and at least one evaluable fundus photograph. RNFLDs were found in 621 participants [5.0%; 95% confidence interval (CI): 4.6%-5.34%], and 70 cases of multiple RNFLDs were found (11.27%). After adjusting multiple factors, RNFLDs was significantly associated with CKD severity, the ORs of CKD stage 3, stage 4 and stage 5 were 1.698, 4.167, and 9.512, respectively. Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors, the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively. Furthermore, 2294 participants had CKD (18.34%, 95%CI: 17.68%-18.99%). After adjusting for other factors, CKD presence was significantly correlated with the presence of RNFLDs. CONCLUSION: The strongest risk factors for RNFLDs are CKD and hypertension. Conversely, RNFLDs can be an ocular feature in patients with CKD. Fundoscopy can help detect systemic diseases, and assessment for RNFLDs should be considered in CKD patients.