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Establishing a valid in vitro model to represent tumor heterogeneity and biology is critical but challenging. Tumor organoids are self‐assembled three‐dimensional cell clusters which are of great significance for recapitulating the histopathological, genetic, and phenotypic characteristics of primary tissues. The organoid has emerged as an attractive in vitro platform for tumor biology research and high‐throughput drug screening in cancer medicine. Organoids offer unique advantages over cell lines and patient‐derived xenograft models, but there are no standardized methods to guide the culture of organoids, leading to confusion in organoid studies that may affect accurate judgments of tumor biology. This review summarizes the shortcomings of current organoid culture methods, presents the latest research findings on organoid standardization, and proposes an outlook for organoid modeling. [ABSTRACT FROM AUTHOR]

Wood is favored by furniture and decorative materials due to its beautiful color and texture, lightweight and high strength, but the thermal stability and flame retardants of wood have not been well solved. In this paper, metal salt-doped ammonium polyphosphate silicon gel (Cu, Mn/APP/Gel) was trapped in the wood cell wall and cell cavity by vacuum-pressure infusion method and vacuum drying method. Compared with unmodified wood, Cu, Mn/APP/Gel impregnated wood can rapidly enhance the flame retardant and smoke suppression capability of wood due to the catalysis of Cu2+ and Mn2+, and the total heat release rate, heat release rate peak value, mean heat release rate, smoke produce rate, total smoke release, CO and CO2 yield (YCO, YCO2) are obviously reduced. The electronic microscope picture of the burned carbon layer shows that the Cu, Mn/APP/Gel doped wood no longer has a clear and beautiful carbon layer formed by cell structure, but completely forms a whole. It is this dense and firm carbon layer structure that effectively inhibits the thermal decomposition of wood and has a role in flame retardant and smoke suppression. This study proposed an environment-friendly and green scheme for flame retardant modification of wood. [ABSTRACT FROM AUTHOR]

A palladium-catalyzed selective B(3)–H arylation of o-carboranes at room temperature has been developed using readily available arylboronic acids as the aryl source, and the corresponding 3-aryl-o-carboranes were obtained in good to excellent yields. This method provides a powerful synthetic route for constructing polysubstituted o-carborane derivatives. [ABSTRACT FROM AUTHOR]

In this paper, we present an effective deep prediction framework based on robust recurrent neural networks (RNNs) to predict the likely therapeutic classes of medications a patient is taking, given a sequence of diagnostic billing codes in their record. Accurately capturing the list of medications currently taken by a given patient is extremely challenging due to undefined errors and omissions. We present a general robust framework that explicitly models the possible contamination through overtime decay mechanism on the input billing codes and noise injection into the recurrent hidden states, respectively. By doing this, billing codes are reformulated into its temporal patterns with decay rates on each medical variable, and the hidden states of RNNs are regularized by random noises which serve as dropout to improved RNNs robustness towards data variability in terms of missing values and multiple errors. The proposed method is extensively evaluated on real health care data to demonstrate its effectiveness in suggesting medication orders from contaminated values. [ABSTRACT FROM AUTHOR]

Circulating cells have a pathogenic role in the development of hypertensive nephropathy. However, how these cells infiltrate into the kidney are not fully elucidated. In this study, we investigated the role of CXCR6 in deoxycorticosterone acetate (DOCA)/salt-induced inflammation and fibrosis of the kidney. Following uninephrectomy, wild-type and CXCR6 knockout mice were treated with DOCA/salt for 3 weeks. Blood pressure was similar between wild-type and CXCR6 knockout mice at baseline and after treatment with DOCA/salt. Wild-type mice develop significant kidney injury, proteinuria, and kidney fibrosis after three weeks of DOCA/salt treatment. CXCR6 deficiency ameliorated kidney injury, proteinuria, and kidney fibrosis following treatment with DOCA/salt. Moreover, CXCR6 deficiency inhibited accumulation of bone marrow–derived fibroblasts and myofibroblasts in the kidney following treatment with DOCA/salt. Furthermore, CXCR6 deficiency markedly reduced the number of macrophages and T cells in the kidney after DOCA/salt treatment. In summary, our results identify a critical role of CXCR6 in the development of inflammation and fibrosis of the kidney in salt-sensitive hypertension. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is becoming one of the most emerging pathological process in the etiology of neurological disorders. Other common etiologies of the neurological disorders are aging and oxidative stress. Neurodegenerative disorders for instance Huntington's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Epilepsy, Schizophrenia, Multiple sclerosis, Neuropathic pain and Alzheimer's disease involves mitochondrial dysfunction and is regarded as the core of their pathological processes. Most central pathological feature of the neurodegenerative diseases is apoptosis which is regulated by mitochondria. Altered signaling of the apoptotic mechanisms are involved in neurodegeneration. Abnormal levels of these molecular apoptotic proteins promotes the pathogenesis of neurological disorders. Mitochondria are also implicated in the production of reactive oxygen species (ROS). Raised ROS levels initiates the cascade leading to the non-apoptotic death of cells. ROS produced in cells acts as signaling molecules, but when produced in abundance will result in cellular consequences to deoxyribonucleic acid, proteins and lipids, decreased effectiveness of cellular mechanisms, initiation of inflammatory pathways, excitotoxicity, protein agglomeration and apoptosis. Protecting mitochondrial function has been identified as the most effective therapeutic approach to attenuate the pathogenesis of neurodegenerative diseases. This review aims to provide an insight into the mitochondrial dysfunction in the pathogenesis of neurological disorders, alteration in signaling cascades of apoptosis in mitochondrial dysfunction and the therapeutic strategies (both natural and synthetic drugs) targeting these mitochondrial apoptotic pathways and oxidative stress that holds great promise. • Mitochondrial dysfunction is one of the most emerging pathological process in neurological disorders. • Most central pathological feature of the neurodegenerative diseases is apoptosis which is regulated by mitochondria. • Alteration in the apoptotic signaling in mitochondrial dysfunction is an insight of therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Cerebral ischemia/reperfusion (I/R) injury leads to cerebrovascular dysfunction characterized by endothelial cell injury or death. Metastasis-associated lung adenocarcinoma transcript 1(MALAT1) has been reported to be associated with endothelial dysfunction. Our study aimed to investigate the effect of MALAT1 on vascular endothelium. Methods: In this study, oxygen-glucose deprivation and reoxygenation (OGD-R) were used as in vitro studies to investigate the role of MALAT1 in I/R-induced apoptosis of cerebrovascular endothelial cells in an I/R injury model. Primary human brain microvascular endothelial cells were cultured on the condition of OGD-R and MALAT1 expression levels and apoptosis were measured at 6, 9, 12, 24 and 36 h after reoxygenation. The expression of MALAT1 and the apoptosis rate of cells exposed to OGD-R showed the trend of reoxygenation. The kit detected the expression of ROS and PI3K, and the change of Akt signal was detected by Western-blot. Results: After OGD-R, over-expression of MALAT1 lentivirus increased phosphatidylinositol 3-kinase (PI3K) activity and activation of Akt phosphorylation, while decreased apoptosis and caspase 3 activity. Moreover, these effects could be successfully eliminated by treating with a PI3K inhibitor (wortmannin). In contrast, knockdown of MALAT1 lentivirus reduced PI3K activity and Akt phosphorylation, while increased apoptosis and caspase 3 activity. Overexpression or knockdown of MALAT1 had no significant effect on that OGD-R-induced reactive oxygen species (ROS) production. Conclusions: This study first proposed that lncRNA MALAT1 can protect human cerebrovascular endothelial cells from OGD-R-induced apoptosis through a PI3K-dependent mechanism. These findings suggest that MALAT1 may be a potential new therapeutic target for brain I/R injury. [ABSTRACT FROM AUTHOR]

In this paper, the effects of heteropolyacids on pyrolysis process of poplar powder and is mechanism were studied by comparing the pyrolyiis process and characteiistic parameters of heat and smoke release of pop- ar powder treated with H3PMO12O40 (PMA), H3PW12O40 (PTA) and H3SiW12O40 (TSA). The TG and DTG curves of samples were determined by thermogravimetiic analyzer. And the heat release rate(HRR), total heat release (THR), smoke produce release (SPR) and total smoke produce (TSP) were measured by cone calorimetry (CONE). Besides, the FT-IR and Raman spectrometers were used to characterize the residual char. TGA results showed that three heteropolyacids could effectively decrease the initial pyrolylis temperature (Ti), the maximum weight loss temperature(Tmax) and the maximum weight loss rate(Rmax) of poplar wood and increase the char yeeld at 740 °C(CR740 °C). S-wood/PMA had the lowest Tmax and Rmax among all samples, which were decreased by 17.5% and 23.3% than S-wood, respeciively. And S-wood/PTA had the highest CR 740 °C, followed by S-wood/TSA. The CONE resuts ihowed that parameters of HRR, THR, SPR, TSP, and COY of the het- eropolyacid/poplar samples were significantly reduced. S-wood/PMA also had the lowest parameters of heat and smoke rdease, whose peak heat release rate(PHRR) and THR were decreased by 31.6% and 67.5% and the TSR and TSP were 86.01% and 87.5% lower than those of S-wood, respeciively. And FTIR and Roman spectrums showed that the content of assodated O--H and unsaturated C=C in the reiidual char of the heteropoly- acid/poplar samples were increased significantly, and ester bonds, MoO3, WO3 and SiO2 formed. Furthermore, A d/Ag of heteropolyacid/popaar samples was decreased. Therefore, heteropolyacids catalyze the dehydration of poplar powder into esters and the solidify of poplar powder into carbon by pyrolylis, which effectively llows down the pyrolylis rate and inhibits the pyrolylis process of poplar powder, exhibiting good lame retardancy and excellent smoke suppression effect. And H3PMO12O40 has the best flame retardant and smoke suppression effects on poplar powder among the three heteropolyacids. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the role of miR-192 in differentiation of T follicular helper cells in childhood asthma. Blood samples were taken from eighteen children with acute asthma attacks and fifteen healthy children (HC). Quantitative real-time PCR and Western blotting were used to detect the expression levels of miR-192, C-X-C chemokine receptor type 5 (CXCR5), B-cell lymphoma 6 (BCL-6) and inducible T-cell costimulator (ICOS). The flow cytometry was performed to detect the proportion of CD4 + CXCR5+ Tfh cells on CD4 + T lymphocytes. The enzyme-linked immunosorbent assay (ELISA) was carried out to determine the plasma concentrations of total IgE and IL-21. The effect of miR-192 on the T follicular helper cells differentiation by targeting CXCR5 was determined by dual-luciferase reporter assay. Children with asthma had lower levels of miR-192 than HC. The proportion of CD4 + CXCR + Tfh cells was significantly higher in the acute asthma group than HC. Similarly, the plasma concentration of total IgE and IL-21 in the acute group markedly increased compared with the HC, and IgE concentration was positively correlated with the proportion of CD4 + CXCR5 + Tfh cells. Furthermore, the expression levels of CXCR5, Bcl-6 and ICOS were significantly higher in the acute group than in the HC. While the proportion of CD4 + CXCR5 + Tfh cells, IL-21, CXCR5, Bcl-6 and ICOS were obviously lower in the CD4 + T cells transfected with miR-192 plasmid than that in miR-192 + CXCR5 group and control group. In conclusion, miR-192 blocks the activation pathway of Tfh cells by targeting CXCR5, which is a reasonable cellular target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Cerebral ischemia/reperfusion (I/R) injury leads to cerebrovascular dysfunction characterized by endothelial cell injury or death. Metastasis-associated lung adenocarcinoma transcript 1(MALAT1) has been reported to be associated with endothelial dysfunction. Our study aimed to investigate the effect of MALAT1 on vascular endothelium. Methods: In this study, oxygen–glucose deprivation and reoxygenation (OGD-R) were used as in vitro studies to investigate the role of MALAT1 in I/R-induced apoptosis of cerebrovascular endothelial cells in an I/R injury model. Primary human brain microvascular endothelial cells were cultured on the condition of OGD-R and MALAT1 expression levels and apoptosis were measured at 6, 9, 12, 24 and 36 h after reoxygenation. The expression of MALAT1 and the apoptosis rate of cells exposed to OGD-R showed the trend of reoxygenation. The kit detected the expression of ROS and PI3K, and the change of Akt signal was detected by Western-blot. Results: After OGD-R, over-expression of MALAT1 lentivirus increased phosphatidylinositol 3-kinase (PI3K) activity and activation of Akt phosphorylation, while decreased apoptosis and caspase 3 activity. Moreover, these effects could be successfully eliminated by treating with a PI3K inhibitor (wortmannin). In contrast, knockdown of MALAT1 lentivirus reduced PI3K activity and Akt phosphorylation, while increased apoptosis and caspase 3 activity. Overexpression or knockdown of MALAT1 had no significant effect on that OGD-R-induced reactive oxygen species (ROS) production. Conclusions: This study first proposed that lncRNA MALAT1 can protect human cerebrovascular endothelial cells from OGD-R-induced apoptosis through a PI3K-dependent mechanism. These findings suggest that MALAT1 may be a potential new therapeutic target for brain I/R injury. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction played an important role in the progression of diabetes mellitus (DM). miR-181c has been implicated in many diseases, including DM. However, the molecular mechanisms of miR-181c regulate this process remained poorly understood. Healthy ICR mice were divided into control group (n = 10) and db/db DM group (n = 10). The expression of miR-181c and FoxO1 were both investigated in diabetic db/db mice or high glucose-induced endothelial cells (MAECs and END-D). Here we found that down-regulation of miR-181c and the activation of FoxO1/iNOS were observed in mice and endothelial cells. Furthermore, we verified that miR-181c directly targeted and inhibited FoxO1 gene expression by targeting its 3′-UTR through luciferase reporter assay. Knockdown of FoxO1 reversed the up-regulation of iNOS, nitrotyrosine and the down-regulation of p-eNOS Ser1177 /eNOS in high glucose (30 mM)-induced MAECs cells. In addition, over-expression of miR-181c could reverse the enhanced nitration stress induced by high glucose, while this effect could be attenuated by pcDNA-FoxO1 in MAECs. These results shown that miR-181c attenuated nitration stress through regulating FoxO1 expression and affecting endothelial cell function, which offering a new target for the development of preventive or therapeutic agents against DM. [ABSTRACT FROM AUTHOR]

To improve the performance of pathological voice detection and classification, gammatone spectral latitude (GTSL) features were proposed. GTSL features are inspired by the nonlinear phenomena produced from the human phonation, presenting explicit physiological meaning. The features combine with human auditory perception characteristics. GTSL features quantify the turbulent noise by the nonlinear compression of peak value and dynamic range of the spectrums in each frequency channel. For pathological voice detection, gammatone spectral latitude (GTSL) features fitted better with traditional machine learning algorithms than traditional nonlinear features and gammatone ceptral coefficients (GTCCs). In the classification between healthy, neuromuscular and structural voices, the proposed features achieved average accuracy of 99.6% in the Massachusetts Eye and Ear Infirmary (MEEI) database, which is 35.6% higher than other gammatone features. The accuracies in other database, Saarbruecken Voice Database (SVD) and Hospital Universitario Prłncipe de Asturias (HUPA), were 89.9% and 97.4% respectively. The experimental results indicate that, GTSL features can provide objective evaluation of voice diseases with low computational complexity and database dependency. [ABSTRACT FROM AUTHOR]

Endothelial progenitor cells (EPCs) play a crucial role in maintaining vascular health and aiding in the repair of damaged blood vessels. However, the specific impact of EPCs-derived exosomes on vascular endothelial cell injury caused by lipopolysaccharide (LPS) remains inadequately understood. This study aims to explore the potential benefits of EPC-exosomes in mitigating LPS-induced vascular injury and to elucidate the underlying mechanism. Initially, EPCs were isolated from mouse peripheral blood, and their identity was confirmed through flow cytometry and immunocytochemistry. Subsequently, the exosomes derived from EPCs were identified using transmission electron microscopy (TEM) and western blot analysis. A sepsis model was induced by subjecting brain microvascular endothelial cells (BMECs) to LPS-induced injury. Both EPC and their exosomes demonstrated a significant increase in BMECs proliferation, reduced apoptosis, decreased levels of pro-inflammatory factors (TNF-α, IL-6, and caspase-3), and enhanced sprouting and angiogenesis of BMECs. Notable, the Exosomes demonstrated a more pronounced impact on these parameters. Furthermore, both EPCs and Exosomes exhibited significantly increased levels of miR-126a-5p, with the Exosomes showing a more substantial enhancement. These findings suggest that supplementing exosomal miR-126a-5p from EPCs can provide protective effects on BMECs, offering a potential therapeutic option for treating sepsis-induced microvascular endothelial cell injury. [ABSTRACT FROM AUTHOR]

Sodium-ion batteries (SIBs) have been recognized as one type of the most potential technologies for low-cost rechargeable batteries owing to the abundant resource of sodium. Herein, we present nanosized maricite NaFePO 4 nanoparticles encapsulated within carbon (NFP@NPCM) via a sol-gel method. The resultant NFP@NPCM nanocomposite as cathode material for SIBs exhibits a high capacity retention of more than 80% after 50 cycles at 0.1C and good rate capacity. The good electrochemical performances are attributed to the NaFePO 4 nanoparticles and the conductive carbon coating, which facilitate the fast access of Na+ ion and electron during the charging/discharging processes, respectively. Our result provides an alternative to prepare promising cathode material for SIBs toward practical application. [ABSTRACT FROM AUTHOR]

Although immunotherapy has revolutionized bladder cancer (BLCA) therapy, only few patients demonstrate durable clinical benefits due to the heterogeneity. Emerging evidence has linked pyroptosis to shaping tumor microenvironment (TME) and predicting therapy response. However, the relationship between pyroptosis and immunotherapy response in BLCA remains elusive. In this study, we performed a comprehensive bioinformatic analysis to dissect the role of pyroptosis in BLCA. Differentially expressed pyroptosis-related genes (DEPRGs) between tumor and normal tissues were identified using publicly available datasets. Kaplan–Meier analysis was performed to screen for DEPRGs associated with survival. Consensus clustering was used for BLCA subtyping. TME characteristics were evaluated by CIBERSORT, ESTIMATE and immune checkpoint genes (ICGs). Following univariate COX regression and LASSO analyses with pyroptosis-related DEGs, the risk model and nomogram were constructed with TCGA dataset and validated in the GEO dataset. Furthermore, therapeutic responses in high- and low-risk groups were compared using TIDE and GDSC databases. Two pyroptosis-related subtypes (Cluster 1 and 2) were identified based on expression patterns of GSDMA and CHMP4C. Bioinformatic analyses showed that cluster 1 had poor survival, more M0/M1/M2 macrophages, higher immune/stromal/ESTIMATE scores, and higher expression levels of ICGs. A 15-gene signature for predicting prognosis could classify patients into high- and low-risk groups. Furthermore, the correlation of risk scores with TIDE score and IC50 showed that patients in low-risk group were more sensitive to immunotherapy, whereas patients in high-risk group could better benefit from chemotherapy. Our study identified two novel pyroptosis-related subtypes and constructed a risk model, which can predict the prognosis, improve our understanding the role of PRGs in BLCA, and guide chemotherapy and immunotherapy. [ABSTRACT FROM AUTHOR]

Background & Aims: It has been reported that Wnt/β-catenin signalling pathway played a key role in liver fibrosis and that Pygo2 was an important mediator in β-catenin induced pathway. However, the role of Pygo2 in liver fibrogenesis was unknown. Our study was to investigate the expression of Pygo2 and its diagnostic value in patients with HBV-related liver fibrosis. Methods: Hundred and sixty-four patients with HBV infection underwent liver biopsy and liver stiffness measurement (LSM) by transient elastography (Fibroscan®; Echosens). Liver function was tested by routine biochemical examinations. Liver condition was assessed by haematoxylin and eosin (H&E) and Masson's trichrome staining. The expression of Pygo2 in liver tissue was measured by Real-time PCR and immunohistochemistry, respectively, while the serum levels of Pygo2 were detected by ELISA. The relationship between degree of liver fibrosis and Pygo2 expression was assessed by correlation analysis. Receiver operating characteristics (ROC) analysis was used to evaluate diagnostic accuracy of serum Pygo2, LSM and their combination. Results: The mRNA and protein levels of Pygo2 in HBV-infected patients were all higher than in normal persons (P < 0.05 respectively). Moreover, Pygo2 expression increased along with the progression of liver fibrosis (P < 0.05 respectively). The trend of serum Pygo2 agreed with its expression in liver tissue. The combination of serum Pygo2 and LSM had a significantly higher area under the curve than Pygo2 or LSM alone (P < 0.05 respectively). Conclusions: This study suggested that Pygo2 was involved in HBV-induced liver fibrogenesis. Pygo2 is a valuable biomarker for the evaluation of fibrosis in HBV-infected patients. [ABSTRACT FROM AUTHOR]

The ring with inner grid ribs (RWIGR) is a key mechanical part. Because of its light structure, high strength, high stiffness, and high carrying capacity, it is widely used in aerospace, special transporting equipment, and petrochemical and nuclear energy industries. Currently, the manufacturing of complex grid ribs mainly adopts cutting methods, which has low material utilization rate and low processing efficiency. Therefore, this paper proposes a novel forming method of radial constraining based on the current technical problem of the difficulty in integral forming of such RWIGR. That is, on the basis of the cylindrical ring rolling process, the continuous partial radial constraining squeezing process (CPRCSP) is adopted, so that the RWIGR can be integrally formed. The paper mainly does the following research work: (1) the process principle of the radial constraining squeezing forming is expounded, and the design method of squeezing molds is proposed. In addition, the squeezing deformation process of RWIGR is simulated and analyzed by the ABAQUS software. (2) Through the FE simulation results, the flow law and strain distribution of metal in the CPRCSP of RWIGR are analyzed. (3) The squeezing forming process of RWIGR is simulated under different squeezing process parameters, and the effects of different squeezing process parameters on RWIGR forming are revealed. (4) The experiment of CPRCSP is designed and implemented, which fully verifies the feasibility of the forming process. [ABSTRACT FROM AUTHOR]

• Energy-aware-correlation-filter tracker to adaptively adjust the target for tracking. • New strategy to reject low quality samples and ensure model discriminant ability. • Combining bottom-up and top-down optimal strategy for training and robust tracking. • Outperform many state-of-the-art trackers on several challenging datasets. Correlation filter based trackers attribute to its calculation in the frequency domain can efficiently locate targets in a relatively fast speed. This characteristic however also limits its generalization in some specific scenarios. The reasons that they still fail to achieve superior performance to state-of-the-art (SOTA) trackers are possibly due to two main aspects. The first is that while tracking the objects whose energy is lower than the background, the tracker may occur drift or even lose the target. The second is that the biased samples may be inevitably selected for model training, which can easily lead to inaccurate tracking. To tackle these shortcomings, a novel energy-aware correlation filter (EACOFT) based tracking method is proposed, in our approach the energy between the foreground and the background is adaptively balanced, which enables the target of interest always having a higher energy than its background. The samples' qualities are also evaluated in real time, which ensures that the samples used for template training are always helpful with tracking. In addition, we also propose an optimal bottom-up and top-down combined strategy for template training, which plays an important role in improving both the effectiveness and robustness of tracking. As a result, our approach achieves a great improvement on the basis of the baseline tracker, especially under the background clutter and fast motion challenges. Extensive experiments over multiple tracking benchmarks demonstrate the superior performance of our proposed methodology in comparison to a number of the SOTA trackers. [ABSTRACT FROM AUTHOR]