Search

Human physiological signal processing is one of the research fields widely used in recent years. Research on human physiological signals plays a vital role in predicting human health and detecting and classifying certain disease outbreaks. The network of human physiological signals is difficult to determine because it contains a lot of information about human activities. To this end, a variety of feature extraction, feature selection, and classification algorithms have been implemented in the anomaly prediction process. However, it has the main disadvantage of classification results, using a large number of features and increasing complexity. In order to solve these problems, this paper proposes a convolutional neural network-based extraction technique for human physiological signal features and uses an MPL classifier to detect whether the ECG signal is normal or not, taking the ECG signal as an example. In this paper, the signal preprocessing method based on wavelet transform and morphological filtering is adopted, and the high-frequency signal is removed by wavelet transform, and the low-frequency signal is removed by morphological filtering. A wide range of tests on ECG signals obtained from the MIT-BIH-AR databank and INCART database showed that the method has good detection performance with sensitivity Sen = 99.54%, positive prediction rate PPR = 99.65%, detecting mistake ratio DER = 0.35% and precision Acc = 99.55%, which is an improved performance compared to other techniques, proving the superiority of the present technique.

Defects causing concomitant loss of CD25 expression in regulatory T cells (Tregs) have been identified in systemic lupus erythematosus (SLE). However, the cause of this deficiency is not fully understood. Carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), an immune co-receptor, contributes to general T-cell function and activation. Our previous study revealed that CEACAM1 expression was upregulated in peripheral blood mononuclear cells (PBMCs) from patients with SLE. However, its role remains unclear. Herein, we confirmed CEACAM1, especially CEACAM1-S, was upregulated in PBMCs from patients with SLE. CEACAM1-S over-expression inhibits CD4+ CD25+ Treg differentiation, whereas knockdown of CEACAM1 had the opposite effect in vitro. CEACAM1-S is the target of miR-31. MiR-31 mimic inhibits CEACAM1 expression and enhances CD4+ CD25+ Treg differentiation, which was reversed by CEACAM1-S over-expression. Moreover, the circulating TGF-β level was upregulated in SLE patients and TGF-β reduced miR-31 expression via enhancing NF-κB activity. Importantly, CEACAM1 and TGF-β mRNA levels were downregulated, while the miR-31 level and the abundance of CD4+ CD25+ Tregs were increased in inactive patients compared with that in patients with active SLE. In addition, CEACAM1-S expression was positively correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, while CD4+ CD25+ Treg abundance and miR-31 level were negatively correlated with the SLEDAI score. In conclusion, reduced activity of miR-31 by TGF-β, via the inhibition of NF-ᴋB, acted to inhibit the differentiation of CD4+ CD25+ Tregs by directly targeting CEACAM1-S and to promote autoimmunity.

Turtles are characterized by their typical carapace, which is primarily composed of corneous beta proteins in the horny part and collagen in the dermal part. The formation of the extracellular matrix in the dermis of the carapace in a hard-shelled and a soft-shelled turtle has been compared. The study examines carapace development, with an emphasis on collagen accumulation, in the soft-shelled turtle Pelodiscus sinensis and hard-shelled turtle Trachemys scripta elegans, using comparative morphological and embryological analyses. The histological results showed that collagen deposition in the turtle carapace increased as the embryos developed. However, significant differences were observed between the two turtle species at the developmental stages examined. The microstructure of the dermis of the carapace of P. sinensis showed light and dark banding of collagen bundles, with a higher overall collagen content, whereas the carapacial matrix of T. scripta was characterized by loosely packed and thinner collagenous fiber bundles with a lower percentage of type I collagen. Overall, the formation and distribution of collagen fibrils at specific developmental stages are different between the soft-and hard-shelled turtles. These results indicate that the pliable epidermis of the soft-shelled turtle is supported by a strong dermis that is regularly distributed with collagen and that it allows improved maneuvering, whereas a strong but inflexible epidermis as observed in case of hard-shelled turtles limits movement. This article is protected by copyright. All rights reserved.

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), which are pivotal sensors of RNA virus invasions, mediate the transcriptional induction of genes encoding type I interferons (IFNs) and proinflammatory cytokines, successfully establishing host antiviral immune response. A few excellent reviews have elaborated on the structural biology of RLRs and the antiviral mechanisms of RLR activation. In this review, we give a basic understanding of RLR biology and summarize recent findings of how RLR signaling cascade is strictly controlled by host regulatory mechanisms, which include RLR-interacting proteins, post-translational modifications and microRNAs (miRNAs). Furthermore, we pay particular attention to the relationship between RLRs and diseases, especially how RLRs participate in SARS-CoV-2, malaria or bacterial infections, how single-nucleotide polymorphisms (SNPs) or mutations in RLRs and antibodies against RLRs lead to autoinflammatory diseases and autoimmune diseases, and how RLRs are involved in anti-tumor immunity. These findings will provide insights and guidance for antiviral and immunomodulatory therapies targeting RLRs.

The Chinese Materia Medica can be divided into four classes: cold, cool, warm, and hot, which mainly exhibits two opposite properties: cold and hot. This study aimed to explore the scientific essence involved in the cold and hot features of Chinese Materia Medica. The microarray data of twelve cold/hot herbs with typical cold and hot properties (six for each group) were analyzed on the Gene-Cloud of Biotechnology Information. First, we compared the differences in total gene expression profiles and identified differentially expressed genes (DEGs) between two classes of herbs. Subsequently, gene ontology (GO) enrichment analysis, pathway analysis, and gene signal network analysis were performed to screen out related pathways and core genes. This study reveals that the upregulated genes in cold herbs are downregulated in hot herbs, and the genes downregulated in cold herbs were upregulated in hot herbs. The gene expression of the two types of herbs has apparent differences, and the DEGs enrich in six systems, including metabolism, immune system, nervous system, endocrine system, cell proliferation and apoptosis, and hemorheology. PRKACA, PRKACB, PRKCA, ADCY7, PIK3R1, and MAPK1 are the core genes. These results elucidated the objectivity of the differences between cold and hot herbs at a genetic level, and identified related pathways and core genes, which may be a feasible approach for solving the qualitative and even quantitative problems of the cold and hot properties of herbs.

In this paper, we derive that every n-dimensional ( $$2\le n\le 7$$ ) special Lagrangian cones in $${\mathbb {R}}^{n}\times {\mathbb {R}}^{n}$$ with flat normal bundle must be flat. And we also derive a rigidity result under a certain restriction on Gauss map.

Background A long noncoding RNA (lncRNA), ZNFX1 antisense RNA 1 (ZFAS1), was increased in multiple cancers, including hepatocellular carcinoma (HCC), resulting in malignancy development and progression. However, the mechanisms involving the interaction between ZFAS1 and microRNA-624 (miRNA-624) remain largely unknown. Therefore, the goal of this study was to probe the functional role of ZFAS1 in the development of HCC and its underlying mechanism. Methods Firstly, differentially expressed lncRNAs in HCC tissues were screened out by microarray. Subsequently, the prognostic effect of ZFAS1 patients with HCC was analyzed by the Kaplan-Meier analysis and The Cancer Genome Atlas database. ZFAS1 regulation on miRNA-624 was determined after si-ZFAS1 and/or miRNA-624 inhibitor were transfected into HepG2 and SMMC7721 cell lines. Finally, the effects of ZFAS1 on the growth and metastasis of HCC were observed by in vivo tumorigenesis and metastasis tests. Results ZFAS1 was overexpressed in HCC tissues and cells and indicated worse prognosis and shorter survival in patients with HCC. Silencing of ZFAS1 inhibited the malignancy of HCC cells, but miR-624 inhibitor could partially reverse the repressive role of si-ZFAS1. Moreover, ZFAS1 induced the extracellular-regulated protein kinases/c-Jun N-terminal kinase (ERK/JNK)/P38 pathway by binding to midkine (MDK) through miR-624, thus promoting the occurrence of HCC. Conclusion Collectively, ZFAS1 depletion inhibited the occurrence of HCC by downregulating the MDK/ERK/JNK/P38 pathway through restoring miR-624 expression. Inhibition of ZFAS1 may act as an innovative target to suppress occurrence in HCC.

Fubrick tea aqueous extract (FTEs) has been reported to improve lipid metabolism and gut microbiota communities in mice and humans. However, it is still unclear how FTEs prevents obesity through gut microbiota, and whether some other regulatory mechanisms are involved in the process. Here, we found that FTEs supplementation effectively alleviated the body weight gain, visceral fat accumulation, dyslipidemia, and impaired glucose tolerance induced by a high-fat diet (HFD), and fecal microbiota transplantation (FMT) from FTEs-treated mice showed similar protective effects as FTEs supplementation in mice fed with a HFD. The results confirmed that gut microbiota played key roles in attenuating HFD-induced fat deposition and metabolic disorder. In particular, FTEs reversed HFD-induced gut microbiota dysbiosis via increasing the relative abundances of Bacteroides, Adlercreutzia, Alistipes, Parabacteroides, and norank_f_Lachnospiraceae, and reducing that of Staphylococcus. Interestingly, FTEs could still alleviate HFD-induced lipid accumulation in mice treated with antibiotics, which had increased relative abundances of Bacteroidetes, Bacteroides, and Bacteroides_uniformis sp. In addition, supplementation with FTEs also modified the serum metabolome, especially the "caffeine metabolism" pathway. Furthermore, FTEs supplementation increased the concentrations of caffeine, theophylline, and theobromine in serum, which were positively correlated with an abundance of norank_f_Lachnospiraceae. Overall, FTEs exerts beneficial effects against obesity induced by HFD, and the underlying mechanism is partially related to the reprogramming of intestinal microbiota, while the metabolism of caffeine in FTEs also played an important role in the process. This study provides a theoretical basis for the further study of the anti-obesity effects of FTEs and the consideration of gut microbiota as a potential target for the treatment of obesity induced by a HFD.

We derive interior Hessian estimates for special Lagrangian equations with supercritical phase in general dimension through a compactness approach.

Matrix metalloproteinases 9 (MMP9) is a member of the zinc-ion-dependent proteinases family and plays a pathogenic role in chronic inflammatory autoimmune diseases. However, its roles in the pathogenesis of myositis have not been elucidated. In this study, we aimed to determine the gene expression and serum level of MMP9 and their relationship with clinical features and serological parameters in myositis. Our results showed that MMP9 mRNA in peripheral blood mononuclear cells (PBMC) was upregulated in myositis patients compared to that in healthy controls. Myositis patients positive for anti-Jo1 antibodies exhibited significantly higher serum MMP9 than anti-MDA5 positive or antibody-negative patients and healthy controls. However, the presence of interstitial lung disease (ILD) did not affect MMP9 levels. We further identified that anti-Jo1-positive myositis patients showed higher numbers of white blood cells (WBC), lymphocytes and neutrophils; increased levels of creatine kinase (CK), lactate dehydrogenase (LDH), and C-reactive protein (CRP); and higher erythrocyte sedimentation rate (ESR) than anti-MDA5 positive patients. In addition, serum MMP-9 levels were positively correlated with WBCs, neutrophils, CK, CRP, ESR, and LDH in myositis patients. In vitro experiments showed that purified serum IgG from Jo-1-positive patients could stimulate PBMCs to release more MMP9 than the IgG from MDA-5-positive sera. These results indicated that increased MMP9 in anti-Jo1-positive myositis patients was associated with the extent of muscle involvement, but not pulmonary damage. The distinct pattern of serum MMP9 perhaps clarifies the differences in pathophysiology between anti-Jo1 and anti-MDA5 in patients with myositis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used drugs due to their values in attenuating pain, fever and inflammation. Unfortunately, conspicuous adverse effects, such as gastrointestinal (GI) damage and/or cardiovascular events have impeded their application in clinic. M378 is a novel hydrogen sulfide-releasing NSAIDs with uncompromised potency and negligible toxicity compared to the existing NSAIDs. However, its anti-inflammatory activity and mechanism are still an enigma. Here we investigated the effect of M378 on the NLRP3 inflammasome signaling pathway and addressed the underlying molecular mechanism. Our data in vitro showed that M378 dose-dependently inhibited the cleavage of Caspase-1 and the secretion of active IL-1β and blocked NLRP3-dependent pyroptosis in LPS-primed J774A.1 macrophages. Furthermore, M378 remarkably inhibited upstream ASC oligomerization and ROS production regarding the process of NLRP3 inflammasome assembly. Our data in vivo demonstrated that M378 protected mice from acute liver injury, reducing the levels of ALT/AST and IL-1β and improving hepatic pathological damages. Immunoblot analysis revealed that M378 inhibited the expressions of Caspase-1 and IL-1β in liver tissues of ALI mice. We also showed that M378 alleviated IL-1β secretion and peritoneal neutrophils infiltration in MSU-elicited acute peritonitis mice. In conclusion, M378 exerted its anti-inflammatory effect both in vitro and in vivo and its mechanisms are at least connected to its inhibitory performance on the generation of ASC oligomers and ROS production. These findings give an insight. into the molecular mechanism of hydrogen sulfide-releasing NSAIDs and support a potent therapeutic role of M378 in the treatment of NLRP3-driven inflammatory diseases.

We construct certain non-polynomial entire solutions to $$\sigma _k$$ equations on $${\mathbb {R}}^n$$ .

During the HH-19-2 flight mission of the Chinese Scientific Experimental System, dried Nostoc sp. cells were exposed to the stratosphere environment (32,508 m altitude) for 3 h and 22 min. The atmospheric pressure, temperature, relative humidity, and ionizing and non-ionizing radiation levels at that altitude are similar to those on the surface of Mars. Although analyses revealed decreased photosynthetic activity, a decline in autofluorescence, and damage to the cellular morphology in the flight-exposed sample, the death rate was low (28%). Physiological changes were not obvious after the exposure to the Mars-like vacuum conditions. The ground-exposed samples showed a similar trend to the flight-exposed samples, but the damage was relatively slight. RNA-sequencing data revealed a number of affected metabolic pathways: photosynthetic system and CO2 fixation function, activation of antioxidant systems, heat shock protein, DNA repair, and protein synthesis. Results suggest that Nostoc sp. has the potential to survive in a Mars-like environment and that it may be a suitable pioneer species to colonize Mars in the future in closed life-support systems (base) or in localities with relatively suitable conditions for life, such as localities with water available.

The rhythm gene BMAL1 (Brain and Muscle ARNT-Like 1) may play an important role in glioma tolerance for anti-angiogenesis therapy. In humans with glioma of different pathological grades, BMAL1 expression was significantly different, and the expression of ANG2 (Angiopoietin 2) and VEGF (Vascular endothelial growth factor) was positively correlated with the expression of BMAL1. Additionally, BMAL1 expression is positively correlated with the microvascular density and peritumoral edema of glioma. According to in vitro experiments, silencing the expression of BMAL1 in primary glioma cells results in a decrease in the expression of VEGF. In contrast, overexpression of BMAL1 promotes the expression of ANG2 and VEGF via HIF-1a pathway. Therefore, BMAL1 likely participates in the angiogenesis of glioma by modulating ANG2 and VEGF expression, alters the therapeutic effect of anti-angiogenic treatments, and promotes peritumoral brain edema of glioma.

Objectives Clinically amyopathic dermatomyositis (CADM) is a subtype of dermatomyositis (DM) characterized by low-grade or absent muscle inflammation but frequent and rapidly progressive interstitial lung disease (RP-ILD) and skin ulcers with anti-melanoma differentiation-associated gene 5 (anti-MDA5) autoantibodies. Basic leucine zipper transcription factor ATF-like 2 (BATF2) is thought to function as an inhibitor of tumours and inflammation. Here, we aimed to investigate the roles of BATF2 in Th cell differentiation of CADM with an anti-MDA5 autoantibody (anti-MDA5+ CADM). Methods Naive CD4+ T cells from human peripheral blood mononuclear cells (PBMCs) of healthy controls (HCs) were isolated and then cultured with IL-12, TGF-β or TGF-β plus IL-6 following anti-CD3 and anti-CD28 stimulations. The expression of BATF2 was measured by real-time PCR. The percentages of Th1, Th17 and Treg CD4+ T cells were detected by flow cytometry. BATF2 knockdown of CD4+ T cells was performed using small interfering RNAs (siRNAs). Results The expression of BATF2 in PBMCs was higher in anti-MDA5+ CADM patients than in healthy controls. The BATF2 mRNA expression was increased under Th1 and Treg polarization but decreased under Th17 polarization. Th17 cell activation-associated genes were possibly increased while Th1 and Treg cell differentiation-associated genes were inhibited by posttranscriptional gene silencing of BATF2 in CD4+ T cells. Conclusions BATF2 promoted Th1 and Treg cell differentiation but suppressed Th17 cell activation in anti-MDA5+ CADM.

Defects causing concomitant loss of CD25 expression in regulatory T cells (Tregs) have been identified in systemic lupus erythematosus (SLE). However, the cause of this deficiency is not fully understood. Carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), an immune co-receptor, contributes to general T-cell function and activation. Our previous study revealed that CEACAM1 expression was upregulated in peripheral blood mononuclear cells (PBMCs) from patients with SLE. However, its role remains unclear. Herein, we confirmed CEACAM1, especially CEACAM1-S, was upregulated in PBMCs from patients with SLE. CEACAM1-S over-expression inhibits CD4

Background. The modernization of traditional Chinese medicine (TCM) demands systematic data mining using medical records. However, this process is hindered by the fact that many TCM symptoms have the same meaning but different literal expressions (i.e., TCM synonymous symptoms). This problem can be solved by using natural language processing algorithms to construct a high-quality TCM symptom normalization model for normalizing TCM synonymous symptoms to unified literal expressions. Methods. Four types of TCM symptom normalization models, based on natural language processing, were constructed to find a high-quality one: (1) a text sequence generation model based on a bidirectional long short-term memory (Bi-LSTM) neural network with an encoder-decoder structure; (2) a text classification model based on a Bi-LSTM neural network and sigmoid function; (3) a text sequence generation model based on bidirectional encoder representation from transformers (BERT) with sequence-to-sequence training method of unified language model (BERT-UniLM); (4) a text classification model based on BERT and sigmoid function (BERT-Classification). The performance of the models was compared using four metrics: accuracy, recall, precision, and F1-score. Results. The BERT-Classification model outperformed the models based on Bi-LSTM and BERT-UniLM with respect to the four metrics. Conclusions. The BERT-Classification model has superior performance in normalizing expressions of TCM synonymous symptoms.

Sepsis is a life-threatening complication of infection and is closely associated with coagulation abnormalities. Heat shock factor 1 (HSF1) is an important transcription factor involved in heat shock response and other biological processes. However, whether HSF1 plays regulatory roles in blood coagulation is still unclear. In this study, a sepsis model was generated in HSF1-knockout mice using caecal ligation and puncture, and the role of HSF1 in microthrombosis and multiple organ dysfunction was evaluated. Notably, lung, liver, and kidney tissues were significantly damaged, fibrin/fibrinogen deposition in the lungs and kidneys was increased, and coagulation activity was gradually increased over time in mice with sepsis; these changes were more obvious in HSF-/- mice than in HSF1+/+ mice. RNA-seq analysis of lung tissues showed that tissue-type plasminogen activator (t-PA) was upregulated in septic mice and was significantly lower in HSF1-knockout mice than in wild-type mice. The effects of HSF1 on t-PA expression were further validated in HSF1-knockout mice with sepsis and in bEnd.3 mouse brain microvascular endothelial cells in vitro using HSF1 RNA interference or overexpression under lipopolysaccharide stimulation. Bioinformatics analysis of the t-PA promoter sequence, combined with electromobility shift and luciferase reporter assays, showed that HSF1 directly up-regulated t-PA at the transcriptional level. Therefore, our results revealed, for the first time, that HSF1 suppressed coagulation activity and microthrombosis by directly up-regulating t-PA, thereby playing a protective role against multiple organ dysfunction in sepsis.

The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, China, introduced the third highly pathogenic coronavirus into humans in the 21st century. Scientific advance after the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic and Middle East respiratory syndrome coronavirus (MERS-CoV) emergence enabled clinicians to understand the epidemiology and pathophysiology of SARS-CoV-2. In this review, we summarize and discuss the epidemiology, clinical features, and virology of and host immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2 and the pathogenesis of coronavirus-induced acute respiratory distress syndrome (ARDS)., SUMMARY The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, China, introduced the third highly pathogenic coronavirus into humans in the 21st century. Scientific advance after the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic and Middle East respiratory syndrome coronavirus (MERS-CoV) emergence enabled clinicians to understand the epidemiology and pathophysiology of SARS-CoV-2. In this review, we summarize and discuss the epidemiology, clinical features, and virology of and host immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2 and the pathogenesis of coronavirus-induced acute respiratory distress syndrome (ARDS). We especially highlight that highly pathogenic coronaviruses might cause infection-associated hemophagocytic lymphohistiocytosis, which is involved in the immunopathogenesis of human coronavirus-induced ARDS, and also discuss the potential implication of hemophagocytic lymphohistiocytosis therapeutics for combating severe coronavirus infection.

The expression and localization of different isoforms of creatine kinase in Pelodiscus sinensis (PSCK) were studied to reveal the role of PSCK isozymes (PSCK-B, PSCK-M, PSCK-S) under bacterial infection-induced immunologic stress. The computational molecular dynamics simulations predicted that PSCK-S would mostly possess a kinase function in a structural aspect when compared to PSCK-B and PSCK-M. The assay of biochemical parameters such as total superoxide dismutase (T-SOD), lactate dehydrogenase (LDH), malondialdehyde (MDA), catalase (CAT), and the content of ATP were measured along with total PSCK activity in different tissue samples under bacterial infection. The expression detections of PSCK isozymes in vitro and in vivo were overall well-matched where PSCK isozymes were expressed differently in P. sinensis tissues. The results showed that PSCK-B mostly contributes to the spleen, followed by the liver and myocardium; PSCK-M mostly contributes to the liver, followed by the myocardium and skeletal muscle, while PSCK-S contributes to the spleen and is uniquely expressed in skeletal muscle. Our study suggests that the various alterations of PSCK isozymes in tissues of P. sinensis are prone to defense the bacterial infection and blocking energetic imbalance before severe pathogenesis turned on in P. sinensis.

The objective of this study was to investigate changes in intestinal histopathology and expression of heat-shock proteins (HSPs) in the small intestinal tissue of mouse after acute exposure to dibutyl phthalate (DBP). Forty-eight 60-day-old Institute of Cancer Research (ICR) mice were administered DBP by gavage once a day for 10 days. The mice were divided into three groups of 16 mice each: the high-dose group was administered 500 mg/kg body weight (BW) DBP; the low-dose group was administered 50 mg/kg BW; and the control group was not administered DBP. Significant increases in the uterine index, ovary index, and testicular index were observed in the DBP-exposed groups compared to those in the control group. Villus height and V/ C ratio significantly increased ( p < 0.05) in the duodenum and decreased ( p < 0.05) in the jejunum after the administration of DBP. The goblet cell number decreased in both the duodenum and the jejunum of mice exposed to DBP ( p < 0.05) compared to the number in the control group mice. Damage to the structure of the small intestine was accompanied by a marked increase in HSP27 expression and a decrease in the expression of HSP70 and HSP90 in both high-dose and low-dose groups. These results indicate that elevated HSP27 levels in the duodenum and jejunum may be important markers for acute DBP exposure and that HSP27 may act as a protective protein involved in intestinal mucosa repair.

Heat-shock protein B1 (HSPB1) is a multifunctional protein that protects against oxidative stress; however, its function in antioxidant pathways remains largely unknown. Here, we sought to determine the roles of HSPB1 in H9c2 cells subjected to oxidative stress. Using nonreducing sodium dodecyl sulfate polyacrylamide gel electrophoresis, we found that increased HSPB1 expression promoted the reduced states of glutathione reductase (GR), peroxiredoxin 1 (Prx1), and thioredoxin 1, whereas knockdown of HSPB1 attenuated these responses following oxidative stress. Increased HSPB1 expression promoted the activation of GR and thioredoxin reductase. Conversely, knockdown of HSPB1 attenuated these responses following oxidative stress. Importantly, overexpression of HSPB1 promoted the complex formation between HSPB1 and oxidized Prx1, leading to dephosphorylation of STE-mammalian STE20-like kinase 1 (MST1) in H9c2 cells exposed to H2 O 2 , whereas downregulation of HSPB1 induced the opposite results. Mechanistically, HSPB1 regulated the Hippo pathway by enhancing the dephosphorylation of MST1, resulting in reduced phosphorylation of LATS1 and Yes-associated protein (YAP). Moreover, HSPB1 regulated YAP-dependent gene expression. Thus, HSPB1 promoted the reduced state of endogenous antioxidant pathways following oxidative stress in H9c2 cells and improved the redox state of the cytoplasm via modulation of the Hippo signaling pathway.

In this study, paclitaxel and etoposide-loaded lipid–polymer hybrid nanoparticles (PE-LPN) was successful prepared and evaluated for physicochemical and anticancer effect. Nanosized PE-LPN was obtained with a perfect spherical morphology. PE-LPN exhibited a controlled release of two drugs in a sequential manner. The nanoparticles exhibited a typical endocytosis-mediated cellular uptake in cancer cells. The ratiometric combination of paclitaxel (PTX) and etoposide (ETP) were significantly more cytotoxic than individual drugs. Importantly, superior cytotoxic effect was observed for dual-drug-loaded PE-LPN than cocktail combination at a much lower dose. Similarly, PE-LPN exhibited a significantly higher apoptosis of cancer cells (∼45%) compared to that of any other groups with higher caspase-3 and -8 activity. Importantly, PE-LPN showed a remarkable tumor regression effect and exhibited a 2-fold superior efficacy than free drugs. PE-LPN treated group showed significantly less Ki-67 positive cells (less than 25%) than PTX/ETP and single drug treated groups, suggesting less active cell proliferation and a considerably higher tumor growth inhibition effect. The results collectively showed that combination of drugs could greatly improve the therapeutic property of chemotherapeutic drugs. By combining ETP with PTX (a powerful anticancer drug) in a polymer–lipid hybrid nanoparticle system, therapeutic efficacy could be improved in osteosarcoma treatments.

A time-adjustable pulsatile release system (TAPS) containing ketoprofen (KF) as an active pharmaceutical agent was developed having been designed for bedtime dosing and releasing drug in the early morning to control the symptoms of rheumatoid arthritis (RA). The formulation involved a tablet core (KF) and a control-release layer, and the coating membrane was composed of EC and Eudragit L100. A single-factor study, a central composite design and a response surface method were selected to optimize the formula and the optimum prescription was as follows: tablet core (KF 50mg, MCC 70mg, lactose 40mg, L-HPC 38mg), and film (EC 7.8g, Eudragit L100 4.2g, PEG 6000 1.8g in 95% alcohol each 200ml). The in vivo release behavior of the tablets was evaluated in Beagle dogs after a parallel oral administration of KF TAPS tablets and commercial KF capsules, when it was found that the KF TAPS tablets released the drug after a lag-time of 3.458h and the Tmax was 5.833h. The relative bioavailability was 85.01%, and the two formulations were bioequivalent in terms of Cmax and AUC0-t and the in vitro- in vivo correlations indicated that test formulation had a good in vivo-in vitro correlation (r=0.9703). These results show that the novel drug delivery system (TAPS) has the potential to be used as a KF preparation with chronophamacokinetics characteristics.

A heterojunction PIN Diode in which an I-layer of GaAs is placed between P-layer of Al 0.11 Ga 0.89 As and N-layer of GaAs is discussed. The performance of a PIN diode depends to a large extent on the semiconductor material and the geometry of the chip, particularly the intrinsic layer [1]. In this paper, the PIN switching diode model is established by Sentaurus TCAD software and the simulation of different thickness of I- layer is carried out to find the most optimal thickness of I-layer. I-V characteristics and the S-parameters of the PIN device are also measured to verify the experiments.