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This paper studies the internal control of the one-dimensional wave equation in domains with moving boundary. The equation characterizes the motion of a string with a fixed endpoint and the other moving one. We derive the interior controllability for wave equation by using the multiplier method. Moreover, the sharper estimate on the controllability time that only depends on the speed of the moving endpoint is given. [ABSTRACT FROM AUTHOR]

Background. In this research, programmed cell death protein 1 (PD-1) inhibitors, including toripalimab, sintilimab, and camrelizumab, were evaluated for the treatment of non-small-cell lung cancer (NSCLC). Methods. This retrospective research was conducted on patients with locally advanced and advanced NSCLC receiving various PD-1 inhibitors including toripalimab, sintilimab, and camrelizumab, between April 2019 and March 2023. Results. In total, the ORR and DCR of 167 patients included in this research were 40.72% (68/167) and 92.81% (155/167), respectively, while the statistical median PFS was 13.90 months (95% CI, 10.657–17.143), and the median OS was 30.10 months (95% CI, 22.142–38.058). Multifactorial analysis showed that two factors, line of treatment and history of smoking, had a statistically significant benefit on the patients' PFS benefit P < 0.05 , while the factor that had a statistically significant benefit on the patients' OS benefit was the presence of serious adverse events (AEs) during treatment. 83.83% and 24.55% of patients experienced any grade AEs and grade 3–5 AEs, respectively. Conclusions. In our research, therapy lines and history of smoking had influence on the efficacy of immunotherapy, while serious AEs during treatment were prognostic factors that affected the OS benefit of immunotherapy. Patients we studied did not die from treatment-related causes, and PD-1 inhibitors did not cause additional toxicity in elderly patients. However, further investigations and multicenter studies are needed. [ABSTRACT FROM AUTHOR]

Lipid metabolism plays a key role in erectile dysfunction. Our purpose was to evaluate the influence of lipid-lowering drugs on erectile dysfunction employing a two-sample Mendelian randomization (MR) study. Genetic instruments were employed to represent the exposure of lipid-lowering drugs. Inverse variance-weighted MR (IVWMR) was employed to calculate the estimation of effects. IVW-MR analysis showed that the positive relationship between the expression of HMGCR and the risk of erectile dysfunction (odds ratio [OR] = 1.27, 95% confidence interval [CI] 1.03–1.57; p = 0.028). No significant relationship was detected between NPC1L1, PSK9 expression and erectile dysfunction. This MR study suggested that HMGCR inhibitors are a more desirable treatment modality for patients with ED. [ABSTRACT FROM AUTHOR]

The Maf proteins (Mafs) belong to basic leucine zipper transcription factors and are members of the activator protein-1 (AP-1) superfamily. There are two subgroups of Mafs: large Mafs and small Mafs, which are involved in a wide range of biological processes, such as the cell cycle, proliferation, oxidative stress, and inflammation. Therefore, dysregulation of Mafs can affect cell fate and is closely associated with diverse diseases. Accumulating evidence has established both large and small Mafs as mediators of tumor development. In this review, we first briefly describe the structure and physiological functions of Mafs. Then we summarize the upstream regulatory mechanisms that control the expression and activity of Mafs. Furthermore, we discuss recent studies on the critical role of Mafs in cancer progression, including cancer proliferation, apoptosis, metastasis, tumor/stroma interaction and angiogenesis. We also review the clinical implications of Mafs, namely their potential possibilities and limitations as biomarkers and therapeutic targets in cancer. [ABSTRACT FROM AUTHOR]

Gametophytic self-incompatibility (SI) is regulated by S-allele recognition; that is, pollen in a style with the same S-genotype will undergo programmed cell death and stop growing so that it is unable to complete double fertilization, ultimately resulting in the SI response. S-RNase is the female determinant of SI in pear (Pyrus). In the Pyrus genome, there are two different S-RNase alleles at the S-locus, which generate two different S-RNase products in the pistil. The extracted S-glycoprotein is actually a protein complex. In this study, artificial self-pollination was conducted at the bud stage to overcome SI in 'Huanghua' (S1S2) pear. Seven plants homozygous for S1-RNase and four homozygous for S2-RNase were selected from the selfed progeny of 'Huanghua' by S-gene molecular identification biotechnology. We investigated the function of single S-RNases isolated from the pistils of S-gene homozygous Pyrus germplasm. The pollen of 'Huanghua' could smoothly pass through the style of the S-gene homozygous germplasm and complete fertilization. S-RNases were extracted from flower styles of different genotypes and used to treat different types of pollen. The S-RNase from 'Huanghua' completely inhibited the growth of S1S2, S1S1, and S2S2 pollen, while the S-RNase from homozygous germplasm allowed some S1S2 pollen and different single genotypes of pollen to continue growing. These results further validate the core events of SI including cytoskeleton depolymerization and programmed cell death. By iTRAQ-based proteomic analysis of style proteins, a total of 13 S-RNase-related proteins were identified. In summary, we have created reliable S-RNase gene homozygous germplasm, which will play a crucial role in further research on SI in pear and in the development of the pear industry. [ABSTRACT FROM AUTHOR]

SUMMARY: Seed abortion is an important process in the formation of seedless characteristics in citrus fruits. However, the molecular regulatory mechanism underlying citrus seed abortion is poorly understood. Laser capture microdissection‐based RNA‐seq combined with Pacbio‐seq was used to profile seed development in the Ponkan cultivars 'Huagan No. 4' (seedless Ponkan) (Citrus reticulata) and 'E'gan No. 1' (seeded Ponkan) (C. reticulata) in two types of seed tissue across three developmental stages. Through comparative transcriptome and dynamic phytohormone analyses, plant hormone signal, cell division and nutrient metabolism‐related processes were revealed to play critical roles in the seed abortion of 'Huagan No. 4'. Moreover, several genes may play indispensable roles in seed abortion of 'Huagan No. 4', such as CrWRKY74, CrWRKY48 and CrMYB3R4. Overexpression of CrWRKY74 in Arabidopsis resulted in severe seed abortion. By analyzing the downstream regulatory network, we further determined that CrWRKY74 participated in seed abortion regulation by inducing abnormal programmed cell death. Of particular importance is that a preliminary model was proposed to depict the regulatory networks underlying seed abortion in citrus. The results of this study provide novel insights into the molecular mechanism across citrus seed development, and reveal the master role of CrWRKY74 in seed abortion of 'Huagan No. 4'. Significance Statement: The seedless character of citrus has important economic value and is favored by consumers, but the formation process of its internal mechanism still lacks understanding. In this study, the molecular mechanism of seed abortion in seedless Ponkan caused by abnormal programmed cell death was preliminarily analyzed by functional genomics, cytological morphological observation, physiological and biochemical assays, as well as stable genetic transformation. [ABSTRACT FROM AUTHOR]

Background: Necroptosis has been reported to play a critical role in occurrence and progression of cancer. The dysregulation of long non-coding RNAs (lncRNAs) is associated with the progression and metastasis of clear cell renal cell carcinoma (CCRCC). However, research on necroptosis-related lncRNAs in the tumor heterogeneity and prognosis of CCRCC is not completely unclear. This study aimed to analysis the tumor heterogeneity among CCRCC subgroups and construct a CCRCC prognostic signature based on necroptosis-related lncRNAs. Methods: Weighted gene co-expression network analysis (WGCNA) was performed to identify necroptosis-related lncRNAs. A preliminary classification of molecular subgroups was performed by non-negative matrix factorization (NMF) consensus clustering analysis. Comprehensive analyses, including fraction genome altered (FGA), tumor mutational burden (TMB), DNA methylation alterations, copy number variations (CNVs), and single nucleotide polymorphisms (SNPs), were performed to explore the potential factors for tumor heterogeneity among the three subgroups. Subsequently, we constructed a predictive signature by multivariate Cox regression. Nomogram, calibration curves, decision curve analysis (DCA), and time-dependent receiver-operating characteristics (ROC) were used to validate and evaluate the signature. Finally, immune correlation analyses, including immune-related signaling pathways, immune cell infiltration status and immune checkpoint gene expression level, were also performed. Results: Seven necroptosis-related lncRNAs were screened out by WGCNA, and three subgroups were classified by NMF consensus clustering analysis. There were significant differences in survival prognosis, clinicopathological characteristics, enrichments of immune-related signaling pathway, degree of immune cell infiltration, and expression of immune checkpoint genes in the various subgroups. Most importantly, we found that 26 differentially expressed genes (DEGs) among the 3 subgroups were not affected by DNA methylation alterations, CNVs and SNPs. On the contrary, these DEGs were associated with the seven necroptosis-related lncRNAs. Subsequently, the identified RP11-133F8.2 and RP11-283G6.4 by multivariate Cox regression analysis were involved in the risk model, which could serve as an independent prognostic factor for CCRCC. Finally, qRT-PCR confirmed the differential expression of the two lncRNAs. Conclusions: These findings contributed to understanding the function of necroptosis-related lncRNAs in CCRCC and provided new insights of prognostic evaluation and optimal therapeutic strategy for CCRCC. [ABSTRACT FROM AUTHOR]

Objective: Colon cancer (CC) is one of the most common cancers worldwide and has a poor prognosis. Surgery followed by adjuvant chemotherapy is the standard treatment strategy for stage III CC patients. Primary tumor location (PTL) is an important factor for the long-term survival of CC. However, the difference in the prognosis between the histological subtypes of mucinous adenocarcinoma (MAC) and nonspecific adenocarcinoma (AC) in stage III CC patients is unclear. The correlation of chemotherapy, PTL and histological subtype with the overall survival (OS) of stage III CC patients has not yet been explored. Methods: Patients diagnosed with stage III CC from 2010 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. The clinicopathological features and OS were analyzed according to the chemotherapy, PTL and histological subtype. Results: A total of 28,765 eligible stage III CC patients were enrolled in this study. The results showed that chemotherapy, left-sided CC (LCC) and AC were favorable prognostic factors for OS. Right-sided CC (RCC) had worse OS than LCC regardless of chemotherapy. MAC had worse OS than AC in the patients with chemotherapy, but the survival benefits disappeared in the patients without chemotherapy. Additionally, in LCC, MAC had worse OS than AC regardless of chemotherapy. However, in RCC, MAC had worse OS than AC in patients with chemotherapy but had similar OS to AC in patients without chemotherapy. In the AC group, RCC had worse OS than LCC regardless of chemotherapy. In the MAC group, RCC had comparable OS to LCC regardless of chemotherapy. Four subgroups, i.e., RCC/MAC, RCC/AC, LCC/MAC and LCC/AC, all showed benefits from chemotherapy. Among them, LCC/AC had the best OS, and RCC/MAC had the worst OS compared with the other three subgroups. Conclusion: The prognosis of MAC is worse than that of AC in stage III CC. LCC/AC has the best OS, while RCC/MAC has the worst OS but still benefits from chemotherapy. The impact of chemotherapy on survival is greater than that of histological subtype, but the impact of histological subtype on survival is similar to that of PTL. [ABSTRACT FROM AUTHOR]

Background: Although significant progress has been made in immunotherapy for lung adenocarcinoma (LUAD), there is an urgent need to identify effective indicators to screen patients who are suitable for immunotherapy. Systematically investigating the cuproptosis-related genes (CRGs) in LUAD may provide new ideas for patients' immunotherapy stratification. Method: We comprehensively analyzed the landscape of 12 CRGs in a merged TCGA and GEO LUAD cohort. We investigated the associations between tumor microenvironment and immunophenotypes. We utilized a risk score to predict the prognosis and immunotherapy response for an individual patient. Additionally, we conducted CCK-8 experiments to evaluate the impact of DLGAP5 knockdown on A549 cell proliferation. Result: We utilized an integrative approach to analyze 12 CRGs and differentially expressed genes (DEGs) in LUAD samples, resulting in the identification of two distinct CRG clusters and two gene clusters. Based on these clusters, we generated immunophenotypes and observed that the inflamed phenotype had the most abundant immune infiltrations, while the desert phenotype showed the poorest immune infiltrations. We then developed a risk score model for individual patient prognosis and immunotherapy response prediction. Patients in the low-risk group had higher immune scores and ESTIMATE scores, indicating an active immune state with richer immune cell infiltrations and higher expression of immune checkpoint genes. Moreover, the low-risk group exhibited better immunotherapy response according to IPS, TIDE scores, and Imvigor210 cohort validation results. In addition, our in vitro wet experiments demonstrated that DLGAP5 knockdown could suppress the cell proliferation of A549. Conclusion: Novel cuproptosis molecular patterns reflected the distinct immunophenotypes in LUAD patients. The risk model might pave the way to stratify patients suitable for immunotherapy and predict immunotherapy response. [ABSTRACT FROM AUTHOR]

Cuproptosis is a newly form of cell death. Cuproptosis related lncRNA in lung adenocarcinoma (LUAD) has also not been fully elucidated. In the present study, we aimed to construct a prognostic signature based on cuproptosis-related lncRNA in LUAD and investigate its association with immunotherapy response. The RNA-sequencing data, clinical information and simple nucleotide variation of LUAD patients were obtained from TCGA database. The LASSO Cox regression was used to construct a prognostic signature. The CIBERSORT, ESTIMATE and ssGSEA algorithms were applied to assess the association between risk score and TME. TIDE score was applied to reflect the efficiency of immunotherapy response. The influence of overexpression of lncRNA TMPO-AS1 on A549 cell was also assessed by in vitro experiments. The lncRNA prognostic signature included AL606834.1, AL138778.1, AP000302.1, AC007384.1, AL161431.1, TMPO-AS1 and KIAA1671-AS1. Low-risk group exhibited much higher immune score, stromal score and ESTIMATE score, but lower tumor purity compared with high-risk groups. Also, low-risk group was associated with a much higher score of immune cells and immune related function sets, indicating an immune activation state. Low-risk patients had relative higher TIDE score and lower TMB. External validation using IMvigor210 immunotherapy cohort demonstrated that low-risk group had a better prognosis and might more easily benefit from immunotherapy. Overexpression of lncRNA TMPO-AS1 promoted the proliferation, migration and invasion of A549 cell line. The novel cuproptosis-related lncRNA signature could predict the prognosis of LUAD patients, and helped clinicians stratify patients appropriate for immunotherapy and determine individual therapeutic strategies. [ABSTRACT FROM AUTHOR]

The Maf proteins (Mafs) belong to basic leucine zipper transcription factors and are members of the activator protein-1 (AP-1) superfamily. There are two subgroups of Mafs: large Mafs and small Mafs, which are involved in a wide range of biological processes, such as the cell cycle, proliferation, oxidative stress, and inflammation. Therefore, dysregulation of Mafs can affect cell fate and is closely associated with diverse diseases. Accumulating evidence has established both large and small Mafs as mediators of tumor development. In this review, we first briefly describe the structure and physiological functions of Mafs. Then we summarize the upstream regulatory mechanisms that control the expression and activity of Mafs. Furthermore, we discuss recent studies on the critical role of Mafs in cancer progression, including cancer proliferation, apoptosis, metastasis, tumor/stroma interaction and angiogenesis. We also review the clinical implications of Mafs, namely their potential possibilities and limitations as biomarkers and therapeutic targets in cancer. [ABSTRACT FROM AUTHOR]

Multiple proteins are involved in network regulation through the crosstalk of different signaling pathways in cancers. Here, we propose a novel strategy of genome therapy with branch-PCR-assembled gene nanovectors to perform network-based gene regulation at multiple levels for cancer therapy. To validate network-based multiplex-gene regulation for genome therapy, we chose to simultaneously target one tumor suppressor gene (TP53) and one oncogene (MYC) in two different signaling pathways. The results showed that, compared to gene nanovectors targeting single genes (NP-TP53 and NP-shMYC), branch-PCR-assembled gene nanovectors simultaneously expressing p53 proteins and MYC shRNA arrays (NP-TP53-shMYC) showed enhanced antitumor efficacy in both MDA-MB-231 cancer cells and an MDA-MB-231-tumor-bearing mouse model. These findings indicate the feasibility and effectiveness of genome therapy in cancer therapy. [ABSTRACT FROM AUTHOR]

Purpose: Pancreatic adenocarcinoma (PAAD) is one of the most common causes of death among solid tumors, and its pathogenesis remains to be clarified. This study aims to elucidate the value of immune/stromal-related genes in the prognosis of PAAD through comprehensive bioinformatics analysis based on the immune microenvironment and validated in Chinese pancreatic cancer patients. Methods: Gene expression profiles of pancreatic cancer patients were obtained from TCGA database. Differentially expressed genes (DEGs) were identified based on the ESTIMATE algorithm. Gene co-expression networks were constructed using WGCNA. In the key module, survival analysis was used to reveal the prognostic value. Subsequently, we performed functional enrichment analysis to construct a protein–protein interaction (PPI) network. The relationship between tumor immune infiltration and hub genes was analyzed by TIMER and CIBERSORT. Finally, it was validated in the GEO database and in tissues of Chinese pancreatic cancer patients. Results: In the TCGA pancreatic cancer cohort, a low immune/stromal score was associated with a good prognosis. After bioinformatic analysis, 57 genes were identified to be significantly associated with pancreatic cancer prognosis. Among them, up-regulation of four genes (COL6A3, PLAU, MMP11 and MMP14) indicated poor prognosis and was associated with multiple immune cell infiltration. IHC results showed that PLAU protein levels from Chinese pancreatic cancer tissues were significantly higher than those from adjacent non-tumor tissues and were also associated with tumor TNM stage and lymph node metastasis. Conclusion: In conclusion, this study demonstrates that PLAU may serve as a new diagnostic and therapeutic target, which is highly expressed in Chinese pancreatic cancer tissues and associated with lymph node metastasis. [ABSTRACT FROM AUTHOR]

Background: Colon adenocarcinoma (COAD) is one of the most common malignant tumors and is diagnosed at an advanced stage with a poor prognosis worldwide. Pyroptosis is involved in the initiation and progression of tumors. This research focused on constructing a pyroptosis-related ceRNA network to generate a reliable risk model for risk prediction and immune infiltration analysis of COAD. Methods: Transcriptome data, miRNA-sequencing data, and clinical information were downloaded from the TCGA database. First, differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) were identified to construct a pyroptosis-related ceRNA network. Second, a pyroptosis-related lncRNA risk model was developed applying univariate Cox regression analysis and least absolute shrinkage and selection operator method (LASSO) regression analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were utilized to functionally annotate RNAs contained in the ceRNA network. In addition, Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, univariate and multivariate Cox regression, and nomogram were applied to validate this risk model. Finally, the relationship of this risk model with immune cells and immune checkpoint blockade (ICB)-related genes was analyzed. Results: A total of 5373 DEmRNAs, 1159 DElncRNAs, and 355 DEmiRNAs were identified. A pyroptosis-related ceRNA regulatory network containing 132 lncRNAs, 7 miRNAs, and 5 mRNAs was constructed, and a ceRNA-based pyroptosis-related risk model including 11 lncRNAs was built. The tumor tissues were classified into high- and low-risk groups according to the median risk score. Kaplan-Meier analysis showed that the high-risk group had a shorter survival time; ROC analysis, independent prognostic analysis, and nomogram further indicated the risk model was a significant independent prognostic factor what had an excellent ability to predict patients’ risk. Moreover, immune infiltration analysis indicated that the risk model was related to immune infiltration cells (i.e., B cell naïve, T cell follicular helper, macrophage M1) and ICB-related genes (i.e., PD-1, CTLA4, HAVCR2). Conclusions: This pyroptosis-related lncRNA risk model possessed good prognostic value, and the ability to predict the outcome of ICB immunotherapy in COAD. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most general malignant tumors. Hypoxia is a critical clinical characteristic and acts as a significant part in the development and cancers' prognosis. The prognostic value and biological functions of hypoxia-related lncRNAs in hepatocellular carcinoma is little known. Thus, we aim to establish a hypoxia-related lncRNA signature to predict the HCC patients' survival. First, we extracted the hypoxia-related genes and expression of lncRNAs from the MSigDB and TCGA database, respectively. The co-expression analysis among hypoxia-related mRNAs and lncRNAs was employed to identify hypoxia-related lncRNAs. Then, comprehensive analyses of lncRNAs expression level and survival data were applied to establish the signature. We built a prognostic signature on the foundation of the three differently expressed hypoxia-related lncRNAs. Kaplan-Meier curves indicated the low-risk group is associated with better survival. The 1−, 3−, and 5 years AUC values of the signature were 0.805, 0.672 and 0.63 respectively. The test set performed consistent outcomes. A nomogram was built grounded on the risk score and clinicopathological features. GSEA showed the immune-related pathways in high-risk group, while metabolism-related pathways in low-risk group. Besides, we found this model was correlated with the clinical features, tumor immune cell infiltration, immune checkpoints, and m6A-related genes. Finally, a novel signature based on hypoxia-related lncRNAs was established and validated for predicting HCC patients' survival and may offer some useful information for immunotherapies. [ABSTRACT FROM AUTHOR]

Summary: Citrus fruit has a unique structure with soft leathery peel and pulp containing vascular bundles and several segments with many juice sacs. The function and morphology of each fruit tissue are different. Therefore, analysis at the organ‐wide or mixed‐tissue level inevitably obscures many tissue‐specific phenomena. High‐throughput RNA sequencing was used to profile Citrus sinensis fruit development based on four fruit tissue types and six development stages from young fruits to ripe fruits. Using a coexpression network analysis, modules of coexpressed genes and hub genes of tissue‐specific networks were identified. Of particular, importance is the discovery of the regulatory network of phytohormones during citrus fruit development and ripening. A model was proposed to illustrate how ABF2 mediates the ABA signalling involved in sucrose transport, chlorophyll degradation, auxin homoeostasis, carotenoid and ABA biosynthesis, and cell wall metabolism during citrus fruit development. Moreover, we depicted the detailed spatiotemporal expression patterns of the genes involved in sucrose and citric acid metabolism in citrus fruit and identified several key genes that may play crucial roles in sucrose and citric acid accumulation in the juice sac, such as SWEET15 and CsPH8. The high spatial and temporal resolution of our data provides important insights into the molecular networks underlying citrus fruit development and ripening. [ABSTRACT FROM AUTHOR]

In this paper, we are concerned with a wave equation on a time-dependent domain with a Dirichlet boundary condition at the endpoint x = 0 and a boundary feedback at the moving endpoint x = k t . We discuss the stabilization and exact boundary observability of the 1-dimensional wave equation with moving boundary feedback. By using generalized Fourier series and Parseval's equality in weighted L 2 − spaces, we derive a precise polynomial asymptotic stability for the energy function of the solution. Moreover, the exact boundary observabilities of the solution are established in minimal time. The observability constants are explicitly given at each endpoint. [ABSTRACT FROM AUTHOR]

RNA interference (RNAi) has been extensively used to downregulate abnormal excessive mRNA in treating intractable diseases like cancers. Albeit with the success of siRNA drugs, the development of shRNA (small hairpin RNA) as RNAi drugs still meets the great challenge in clinical treatments for lacking the suitable delivery vector to express numerous shRNAs in cells. Considering our previously established branch‐PCR (branched polymerase chain reaction) technology, we herein introduced a multisite‐targeting c‐Myc shRNA array into DNA nanovectors via branch‐PCR. The results indicated that this kind of DNA nanovector retained better serum stability than plasmids and linear DNA. The cell viability test further showed that the transcription of c‐Myc shRNA arrays greatly enhanced the anti‐cancer activity by eliminating approximately 98.2 % c‐Myc mRNA, which posed a technical advance in augmenting the gene silencing efficiency of vector‐expressed shRNAs in cells. Hence, it would be promising to use this customizable and stable shRNA array‐based DNA nanovectors to enhance the curable efficacy of shRNAs in cancer treatment. [ABSTRACT FROM AUTHOR]

The Navier–Stokes–Voigt equations are a regularization of the Navier–Stokes equations. Sharing some asymptotic and statistical properties, they have been used in direct numerical simulations of the latter. In this article, we characterize the decay rate of the solutions to the Navier–Stokes–Voigt equations with damping. Applying the Fourier splitting method, we prove the H1 decay of weak solutions for α > 0, β > 2, and μ > ν2. [ABSTRACT FROM AUTHOR]

What is known and objective: There have been concerns about a potential link between long‐term use of bisphosphonates (BPs) for the treatment of osteoporosis and rare serious adverse effects, such as atypical femoral fractures. However, many reviews exist with conflicting conclusions about this issue. The aim of this overview of reviews was to systematically evaluate the risk of rare serious adverse effects of long‐term use of BPs for the treatment of osteoporosis. Methods: We identified systematic reviews with meta‐analyses of randomized controlled trials (RCTs) and (or) observational studies published in English or Chinese that evaluated the safety of BPs through to December 2018. The Cochrane library, PubMed, Web of Science and hand‐searching of reference lists and clinical practice guidelines were electronically searched for data sources. Carcinogenicity, atypical fracture, osteonecrosis of jaw (ONJ) and fracture union time were specified as the primary outcomes. The methodological quality of each systematic review was assessed by two reviewers using the Assessment of Multiple Systematic Reviews (AMSTAR) tool, and the quality of evidence for key outcomes was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Results and discussion: In total, 1376 potentially relevant citations were identified, of which only 8 systematic reviews with meta‐analyses met the eligibility criteria. All the included reviews were published between 2012 and 2015 and documented the pooled estimates of effect size (relative risk [RR], odds ratio [OR] or hazard ratio [HR] and their 95% confidence intervals [95% CI]) for the incidence of adverse events. All included systematic reviews were of moderate or high quality. The median AMSTAR score was 7.5 (interquartile range, 5‐10). However, evidence of the key outcomes was mainly of very low or moderate quality. BP treatment only increased the risk of atypical fracture and ONJ, and prolonged union time compared with placebo or other anti‐osteoporosis drugs (P ＜.05). What is new and conclusion: This study indicated that long‐term use of BPs could increase the risk of rare serious adverse effects, but the relationship between long‐term use of BPs and carcinogenicity was often uncertain. Therefore, high‐quality research and more complete inclusion criteria are needed. [ABSTRACT FROM AUTHOR]

Histone deacetylase inhibitors (HDACIs) cause oncogene‑transformed mammalian cell death. Our previous study indicated that HDACIs activate forkhead box O1 (FOXO1) and induce autophagy in liver and colon cancer cells. However, whether FOXO1 is involved in HDACI‑mediated oncogene‑transformed mammalian cell death remains unclear. In the present study, H‑ras transformed MCF10A cells were used to investigate the role of FOXO1 in this pathway. Results showed that trichostatin A (TSA), a HDACI, activated apoptosis in MCF10A‑ras cells, but not in MCF10A cells. Furthermore, TSA activated FOXO1 via P21 upregulation, whereas the knockdown of FOXO1 reduced TSA‑induced cell death. In addition, TSA induced autophagy in MCF10A and MCF10A‑ras cells by blocking the mammailian target of rapamycin signaling pathway. Furthermore, autophagy inhibition lead to higher MCF10A‑ras cell death by TSA, thus indicating that autophagy is essential in cell survival. Taken together, the present study demonstrated that TSA causes oncogene‑transformed cell apoptosis via activation of FOXO1 and HDACI‑mediated autophagy induction, which served as important cell survival mechanisms. Notably, the present findings imply that a combination of HDACIs and autophagy inhibitors produce a synergistic anticancer effect. [ABSTRACT FROM AUTHOR]

The history of religious thought and the history of human thought are closely interrelated, so the study of Chinese psychology of religion should pay attention to the study of Chinese history. In this paper, we summarize the history of Han Chinese psychology of religion in three stages from the perspectives of the history of Chinese thought, the history of Chinese religion, and the history of Chinese psychology. In the accumulation stage during the Spring and Autumn and Warring States periods, debates about 'human nature' were central to a psychology of religion. We hope that this will be helpful for the further study of Chinese psychology of religion. [ABSTRACT FROM AUTHOR]

In this paper, a physical model for a SiC Junction Field Effect Transistor (JFET) is presented. The novel feature of the model is that the mobility dependence on both temperature and electric field is taken into account. This is particularly important for high-current power devices where the maximum conduction current is limited by drift velocity saturation in the channel. The model equations are described in detail, emphasizing the differences introduced by the field-dependent mobility model. The model is then implemented in Pspice. Both static and dynamic simulation results are given. The results are validated with experimental results under static conditions and under resistive and inductive switching conditions. [ABSTRACT FROM AUTHOR]

An existing physics-based insulated gate bipolar transistor (IGBT) model, which has been proven accurate for both inductive turn-off and inductive turn-on simulations, is modified to account for planar-gate IGBT 2-D effects at the MOS end of the drift region. The modification is based on a steady-state solution of carrier distribution in the JFET region of the IGBT. The accuracy of this solution is verified through a set of finite element simulations. The improved accuracy of the modified model in terms of on-state forward drop and voltage tail at turn-on is verified through comparison with experimental results. [ABSTRACT FROM PUBLISHER]

In this paper, a parameter extraction procedure for high-voltage diodes with local lifetime control is proposed. It is designed for use with the physics-based diode model described in Part I, which is capable of simulating diodes with local lifetime control. The parameter extraction procedure described requires a forward characteristic and a reverse recovery measurement. The parameter extraction procedure is illustrated using finite-element simulations. The physics-based model using the parameters extracted is then compared with experimental results. [ABSTRACT FROM AUTHOR]

This paper presents the development and implementation of a physics-based diode model which can simulate aspects of high-voltage diodes such as snappy recovery during punch-through and the modified carrier density profile due to local lifetime control. It uses a Fourier series solution for the ambipolar diffusion equation in the lightly doped base region. The model is compared with finite-element device simulations. A parameter extraction procedure for the diode with lifetime control is proposed in Part II. [ABSTRACT FROM AUTHOR]

Based on the studies that have been done in the field of psychology of religion since the 1980s in mainland China, this article attempts to reveal the achievements and problems of the studies during this course. The article also expounds on how to carry out the developing tactics on theoretical study and practical application in the future. These goals include the following: to strengthen the study about the history of psychology of religion in western countries and to establish a solid foundation for this discipline's building, to emphasize a combination between the quantitative method and qualitative one and try to construct a methodological system in accord with the character of the psychology of religion, and to make psychology of religion play an important role in society. [ABSTRACT FROM AUTHOR]