Norcantharidin Enhances the Antitumor Effect of 5-Fluorouracil by Inducing Apoptosis of Cervical Cancer Cells: Network Pharmacology, Molecular Docking, and Experimental Validation.

The high recurrence rate of cervical cancer is a leading cause of cancer deaths in women. 5-Fluorouracil (5-FU) is an antitumor drug used to treat many types of cancer, but its diminishing effectiveness and side effects limit its use. Norcantharidin (NCTD), a demethylated derivative of cantharidin, exhibits various biological activities. Here, we investigated whether NCTD could potentiate 5-FU to induce cervical cancer cell death. To assess the cell viability and synergistic effects of the drugs, cell counting kit-8 and colony formation assays were performed using HR-HPV-positive cervical cancer cell lines. Annexin V-FITC/PI staining and TUNEL assays were performed to confirm the induction of apoptosis. The synergistic effect of NCTD on the antitumor activity of 5-FU was analyzed using network pharmacology, molecular docking, and molecular dynamics simulations. Apoptosis-related proteins were examined using immunoblotting. The combination of NCTD and 5-FU was synergistic in cervical cancer cell lines. Network pharmacological analysis identified 10 common targets of NCTD and 5-FU for cervical cancer treatment. Molecular docking showed the strong binding affinity of both compounds with CA12, CASP9, and PTGS1. Molecular dynamics simulations showed that the complex system of both drugs with caspase-9 could be in a stable state. NCTD enhanced 5-FU-mediated cytotoxicity by activating apoptosis-related proteins. NCTD acts synergistically with 5-FU to inhibit cervical cancer cell proliferation. NCTD enhances 5-FU-induced apoptosis in cervical cancer cell lines via the caspase-dependent pathway.

Multimodal contrastive representation learning for drug-target binding affinity prediction.

In the biomedical field, the efficacy of most drugs is demonstrated by their interactions with targets, meanwhile, accurate prediction of the strength of drug-target binding is extremely important for drug development efforts. Traditional bioassay-based drug-target binding affinity (DTA) prediction methods cannot meet the needs of drug R&D in the era of big data. Recent years we have witnessed significant success on deep learning-based models for drug-target binding affinity prediction task. However, these models only considered a single modality of drug and target information, and some valuable information was not fully utilized. In fact, the information of different modalities of drug and target can complement each other, and more valuable information can be obtained by fusing the information of different modalities. In this paper, we introduce a multimodal information fusion model for DTA prediction that is called FMDTA, which fully considers drug/target information in both string and graph modalities and balances the feature representations of different modalities by a contrastive learning approach. In addition, we exploited the alignment information of drug atoms and target residues to capture the positional information of string patterns, which can extract more useful feature information in SMILES and target sequences. Experimental results on two benchmark datasets show that FMDTA outperforms the state-of-the-art model, demonstrating the feasibility and excellent feature capture capability of FMDTA. The code of FMDTA and the data are available at: https://github.com/bestdoubleLin/FMDTA.

LSM14B controls oocyte mRNA storage and stability to ensure female fertility.

Controlled mRNA storage and stability is essential for oocyte meiosis and early embryonic development. However, how to regulate mRNA storage and stability in mammalian oogenesis remains elusive. Here we showed that LSM14B, a component of membraneless compartments including P-body-like granules and mitochondria-associated ribonucleoprotein domain (MARDO) in germ cell, is indispensable for female fertility. To reveal loss of LSM14B disrupted primordial follicle assembly and caused mRNA reduction in non-growing oocytes, which was concomitant with the impaired assembly of P-body-like granules. 10× Genomics single-cell RNA-sequencing and immunostaining were performed. Meanwhile, we conducted RNA-seq analysis of GV-stage oocytes and found that Lsm14b deficiency not only impaired the maternal mRNA accumulation but also disrupted the translation in fully grown oocytes, which was closely associated with dissolution of MARDO components. Moreover, Lsm14b-deficient oocytes reassembled a pronucleus containing decondensed chromatin after extrusion of the first polar body, through compromising the activation of maturation promoting factor, while the defects were restored via WEE1/2 inhibitor. Together, our findings reveal that Lsm14b plays a pivotal role in mammalian oogenesis by specifically controlling of oocyte mRNA storage and stability.

Effects of resveratrol on DLD and NDUFB9 decrease in frozen semen of Mongolian sheep.

Mongolian sheep are a breed of sheep in China known for their excellent cold and drought resistance. Sperm from Mongolian sheep are often cryopreserved to improve breeding outcomes. However, cryopreservation of sperm often results in issues such as reduced vitality and altered morphology. Therefore, the objective of this study was to investigate the impact of the cryoprotectant resveratrol on frozen sperm from Mongolian sheep, specifically examining its effects on key proteins during cryopreservation. In this study, sperm samples were obtained from three adult Mongolian rams and processed through semen centrifugation. The sperm motility parameters of Fresh Sperm Group (FR), Resveratrol added before freezing group (FF-Res), Resveratrol-free frozen sperm group (FT), and Resveratrol added after freeze-thawing group (FA-Res) were determined. The tandem mass tags (TMT) peptide labeling combined with LC-MS/MS was used for proteomic analysis of the total proteins in FR and FT groups. A total of 2651 proteins were identified, among which 41 proteins were upregulated and 48 proteins were downregulated after freezing. In-depth bioinformatics analysis of differentially abundant proteins (DAPs) revealed their close association with the tricarboxylic acid cycle (TCA) and oxidative phosphorylation pathway. The energy-related protein dihydrolipoamide dehydrogenase (DLD) and the reactive oxygen species (ROS)-related protein NADH dehydrogenase 1 beta subcomplex subunit 9 (NDUFB9) exhibited significant decreases, indicating their potential role as key proteins contributing to reduced sperm vitality. The study demonstrated that the addition of resveratrol (RES) to semen could elevate the expression levels of DLD and NDUFB9 proteins. This study represents the pioneering proteomic analysis of Mongolian ram sperm before and after cryopreservation, establishing the significance of DLD and NDUFB9 as key proteins influencing the decline in vitality following cryopreservation of Mongolian ram sperm. These findings clarify that resveratrol can enhance the levels of DLD and NDUFB9 proteins in cryopreserved Mongolian ram sperm, consequently enhancing their vitality.

Progress on CRISPR/Cas9 system in the genetic improvement of livestock and poultry.

CRISPR/Cas9 gene editing technology, as a highly efficient genome editing method, has been extensively employed in the realm of animal husbandry for genetic improvement. With its remarkable efficiency and precision, this technology has revolutionized the field of animal husbandry. Currently, CRISPR/Cas9-based gene knockout, gene knock-in and gene modification techniques are widely employed to achieve precise enhancements in crucial production traits of livestock and poultry species. In this review, we summarize the operational principle and development history of CRISPR/Cas9 technology. Additionally, we highlight the research advancements utilizing this technology in muscle growth and development, fiber growth, milk quality composition, disease resistance breeding, and animal welfare within the livestock and poultry sectors. Our aim is to provide a more comprehensive understanding of the application of CRISPR/Cas9 technology in gene editing for livestock and poultry.

Single-cell RNA sequencing of the Mongolia sheep testis reveals a conserved and divergent transcriptome landscape of mammalian spermatogenesis.

Spermatogenesis is a highly coordinated and complex process, and is pivotal for transmitting genetic information between mammalian generations. In this study, we investigated the conservation, differences, and biological functions of homologous genes during spermatogenesis in Mongolia sheep, humans, cynomolgus monkey, and mice using single-cell RNA sequencing technology. We compared X chromosome meiotic inactivation events in Mongolia sheep, humans, cynomolgus monkey, and mice to uncover the concerted activity of X chromosome genes. Subsequently, we focused on the dynamics of gene expression, key biological functions, and signaling pathways at various stages of spermatogenesis in Mongolia sheep and humans. Additionally, the ligand-receptor networks of Mongolia sheep and humans in testicular somatic and germ cells at different developmental stages were mapped to reveal conserved germ cell-soma communication using single-cell resolution. These datasets provided novel information and insights to unravel the molecular regulatory mechanisms of Mongolia sheep spermatogenesis and highlight conservation in gene expression during spermatogenesis between Mongolia sheep and humans, providing a foundation for the establishment of a large mammalian disease model of male infertility.

Clearance of bacteria from lymph nodes in sheep immunized with Brucella suis S2 vaccine is associated with M1 macrophage activation.

Ovine brucellosis is a global zoonotic disease of sheep caused by Brucella melitensis, which inflicts a significant burden on human and animal health. Brucella suis strain S2 (B. suis S2) is a smooth live attenuated vaccine for the prevention of ovine brucellosis in China. However, no previous studies have assessed the immunogenicity of B. suis S2 vaccine after oral immunization in sheep. Here, we attempted to evaluate the ovine immune response over the course of B. suis S2 immunization and to identify in vivo predictors for vaccine development. Body temperature, serum Brucella antibodies, serum cytokines (IL-12p70 and interferon [IFN]-γ), and bacterial load in the mandibular lymph nodes (LN), superficial cervical LN, superficial inguinal LN, and spleen were investigated to determine the safety and efficacy of the vaccine. The abnormal body temperature of sheep occurred within 8 days post-infection (dpi). Brucella suis S2 persisted for a short time (< 21 dpi) in the mandibular LN. The highest level of IL-12p70 was observed at 9 dpi, whereas serum IFN-γ levels peaked at 12 dpi. Transcriptome analysis and quantitative reverse transcription PCR were performed to determine gene expression profiles in the mandibular LN of sheep. Antigen processing and presentation pathway was the dominant pathway related to the dataset. Our studies suggest that the immune response in ovine LN resembled type 1 immunity with the secretion of IL-12p70 and IFN-γ after B.suis S2 immunization and the vaccine may eliminate Brucella via stimulation of M1 macrophages through the course of Th cells.

The Sympathetic Nervous System Modulates Cancer Vaccine Activity through Monocyte-Derived Cells.

The sympathetic nervous system (SNS) is an important regulator of immune cell function during homeostasis and states of inflammation. Recently, the SNS has been found to bolster tumor growth and impair the development of antitumor immunity. However, it is unclear whether the SNS can modulate APC function. Here, we investigated the effects of SNS signaling in murine monocyte-derived macrophages (moMФ) and dendritic cells (DCs) and further combined the nonspecific ß-blocker propranolol with a peptide cancer vaccine for the treatment of melanoma in mice. We report that norepinephrine treatment dramatically altered moMФ cytokine production, whereas DCs were unresponsive to norepinephrine and critically lack ß2-adrenergic receptor expression. In addition, we show that propranolol plus cancer vaccine enhanced peripheral DC maturation, increased the intratumor proportion of effector CD8+ T cells, and decreased the presence of intratumor PD-L1+ myeloid-derived suppressor cells. Furthermore, this combination dramatically reduced tumor growth compared with vaccination alone. Taken together, these results offer insights into the cell-specific manner by which the SNS regulates the APC immune compartment and provide strong support for the use of propranolol in combination with cancer vaccines to improve patient response rates and survival.

Glutathione ameliorates the meiotic defects of copper exposed ovine oocytes via inhibiting the mitochondrial dysfunctions.

Regardless of the essential role of copper (Cu) in the physiological regulation process of mammalian reproduction, excessive exposure to Cu triggers the meiotic defects of porcine oocytes via compromising the mitochondrial functions. However, the connections between the excessive Cu exposure and meiotic defects of ovine oocytes have not been reported. In this study, the effect of copper sulfate (CuSO4) exposure on the meiotic potentials of ovine oocytes was analyzed. Subsequently, the ameliorative effect of glutathione (GSH) supplementation on the meiotic defects of CuSO4 exposed ovine oocytes was investigated. For these purposes, the in vitro maturation (IVM) of ovine cumulus oocyte complexes (COCs) was conducted in the presence of 5, 10, 20 and 40 µg/mL of CuSO4 supplementation. Subsequently, different concentrations of GSH (2, 4 and 8 mM) were added to the IVM medium containing CuSO4 solution. After IVM, the assay, including nuclear maturation, spindle organization, chromosome alignment, cytoskeleton assembly, cortical granule (CGs) dynamics, mitochondrial function, reactive oxygen species (ROS) generation, apoptosis, epigenetic modification and fertilization capacity of ovine oocytes were performed. The results showed that excessive Cu exposure triggered the meiotic defects of ovine oocytes via promoting the mitochondrial dysfunction related oxidative stress damage. Moreover, the GSH supplementation, not only ameliorated the decreased maturation potential and fertilization defect of CuSO4 exposed oocytes, but inhibited the mitochondrial dysfunction related oxidative stress damage, ROS generation, apoptosis and altered H3K27me3 expression in the CuSO4 exposed oocytes. Combined with the gene expression pattern, the finding in the present study provided fundamental bases for the ameliorative effect of GSH supplementation on the meiotic defects of CuSO4 exposed oocytes via inhibiting the mitochondrial dysfunctions, further benefiting these potential applications of GSH supplementation in the mammalian IVM system and livestock breeding suffering from the excessive Cu exposure.

Underwater image enhancement using adaptive color restoration and dehazing.

Underwater images captured by optical cameras can be degraded by light attenuation and scattering, which leads to deteriorated visual image quality. The technique of underwater image enhancement plays an important role in a wide range of subsequent applications such as image segmentation and object detection. To address this issue, we propose an underwater image enhancement framework which consists of an adaptive color restoration module and a haze-line based dehazing module. First, we employ an adaptive color restoration method to compensate the deteriorated color channels and restore the colors. The color restoration module consists of three steps: background light estimation, color recognition, and color compensation. The background light estimation determines the image is blueish or greenish, and the compensation is applied in red-green or red-blue channels. Second, the haze-line technique is employed to remove the haze and enhance the image details. Experimental results show that the proposed method can restore the color and remove the haze at the same time, and it also outperforms several state-of-the-art methods on three publicly available datasets. Moreover, experiments on an underwater object detection dataset show that the proposed underwater image enhancement method is able to improve the accuracy of the subsequent underwater object detection framework.

Three-step irradiance schedule versus two-step irradiance schedule for pain control during topical 5-aminolevulinic acid-photodynamic therapy of facial acne in Chinese patients: A prospective randomized comparative study.

BACKGROUND: A two-step irradiance schedule has been found to be useful for pain control during photodynamic therapy (PDT) on nonmelanotic skin cancer and condyloma acuminatum. OBJECTIVES: To evaluate the efficacy of a new three-step irradiance schedule derived from the psychological "peak-end rule" and two-step irradiance schedule in relieving pain during 5-aminolevulinic acid PDT (ALA-PDT) on acne. METHODS: A total of 90 moderate to severe acne patients were enrolled in our study and randomly divided into two groups with a ratio of 1:1. They were treated by a light-emitting diode light source of 633 ± 10 nm after being incubated with 5% ALA for an hour using a two-step or three-step irradiance schedule, respectively. The total irradiance intensity was 84 J/cm2 of each session and the treatment interval was 2 weeks. Pain was recorded 30 min after each PDT using a visual analog scale (VAS). Follow-up was done at baseline and 2 weeks after each treatment. The numbers of lesions were counted after the third treatment through the pictures taken before and all the side effects were recorded at each follow-up visit. RESULTS: Eighty-seven subjects completed the total three treatments (44 cases in Group A and 43 cases in Group B). The average VAS of Group B (1.61 ± 0.67) was significantly lower than that of Group A (3.14 ± 0.67), with a difference of 1.52 ± 0.08 (p < 0.0001) between them. Both groups received a similar effective rate after the total three sessions (88.64% vs. 88.37%, p > 0.05). CONCLUSIONS: The new three-step irradiance method could relieve pain during ALA-PDT more significantly than the two-step schedule with a similar effective rate.

Performance Degradation Prediction Using LSTM with Optimized Parameters.

Predicting the degradation of mechanical components, such as rolling bearings is critical to the proper monitoring of the condition of mechanical equipment. A new method, based on a long short-term memory network (LSTM) algorithm, has been developed to improve the accuracy of degradation prediction. The model parameters are optimized via improved particle swarm optimization (IPSO). Regarding how this applies to the rolling bearings, firstly, multi-dimension feature parameters are extracted from the bearing's vibration signals and fused into responsive features by using the kernel joint approximate diagonalization of eigen-matrices (KJADE) method. Then, the between-class and within-class scatter (SS) are calculated to develop performance degradation indicators. Since network model parameters influence the predictive accuracy of the LSTM model, an IPSO algorithm is used to obtain the optimal prediction model via the LSTM model parameters' optimization. Finally, the LSTM model, with said optimal parameters, was used to predict the degradation trend of the bearing's performance. The experiment's results show that the proposed method can effectively identify the trends of degradation and performance. Moreover, the predictive accuracy of this proposed method is greater than that of the extreme learning machine (ELM) and support vector regression (SVR), which are the algorithms conventionally used in degradation modeling.

Identification of piRNAs in the testes of Sunite and Small-tailed Han sheep.

P-element-induced wimpy testis-interacting RNAs (piRNAs) are small RNAs that are essential for mammalian spermatogenesis and testicular development. Comparative analyses of the molecular mechanisms of spermatogenesis among different organisms are therefore dependent on accurate piRNA characterizations. In this study, we identified piRNAs in the testes of two breeds of Mongolian sheep: the Sunite (SN), which has a low reproductive rate, and Small-tailed Han (STH), which has a high reproductive rate. A thorough understanding of the mechanisms underlying the differences in fecundity between the two breeds might provide insights for the improvement of fertility and reproductive success in these and other sheep breeds. We identified 835 piRNAs and 206 piRNA clusters across the two breeds. Of these, 29 putative piRNAs were expressed in the SN samples only, and 229 putative piRNAs were expressed in the STH samples only. In addition, 206 piRNA clusters were upregulated in STH sheep as compared to the SN sheep. Functional pathway analysis indicated that the genes neighboring the predicted piRNAs were likely associated with spermatogenesis. piRNAs might thus be linked to male fecundity in sheep. Our results increase knowledge of the association between piRNAs and male fertility.

Association between novel variants in BMPR1B gene and litter size in Mongolia and Ujimqin sheep breeds.

Prolificacy is an important trait of animals, specifically for sheep. The Bone morphogenetic protein receptor 1B (BMPR1B) is a major gene affecting the litter size of many sheep breeds. The well-known FecB mutation (Q249R) was associated fully with the hyper prolific phenotype of Booroola Merino. However, the identification of variation in all exonic regions of BMPR1B was rare. In this study, we sequenced all exonic regions of BMPR1B gene of Mongolia sheep breed, and ten novel variants were detected by direct sequencing. Among them, the litter size of the Mongolia ewes with the CC genotype was significantly higher (0.34 additional lambs, p < .05) than those with the TT genotype of the g.29346567C>T single nucleotide polymorphism (SNP). The litter size of the Mongolia ewes with the TT genotype was significantly higher (0.19 additional lambs, p < .05 and .31 additional lambs, p < .01, respectively) than those with the GT and GG genotypes of the c.1470G>T SNP. The silent c.1470G>T mutation is predicted to increase the stability of the mRNA secondary structure through reducing minimum free energy and is predicted to change the mRNA secondary structure of BMPR1B. Our findings may give potentially useful genetic markers for increasing litter size in sheep.

Multiple omics analysis reveals that high fiber diets promote gluconeogenesis and inhibit glycolysis in muscle.

BACKGROUND: Meat quality is a complex trait affected by genotypic and environmental factors. In a previous study, it was found that feedstuffs have various effects on the growth rate and meat quality of lambs. However, the underlying mechanisms are still not entirely clear. RESULTS: In this study, to investigate the mechanisms that impact meat quality in twin sheep fed either with high fiber low protein (HFLP) forage (Ceratoides) or low fiber high protein (LFHP) forage (alfalfa) diets, multi omics techniques were utilized for integration analysis based on the feed nutritional value and the sheep microbiome, transcriptome, metabolome, and fatty acid profile. Results showed that the production performance and the muscle components of lambs were significantly affected by feeds. The essential fatty acid (linoleic acid and arachidonic acid) content of the muscle, based on gas chromatography-mass spectrometry analysis, was increased when lambs were fed with HFLP. The microbes in the lambs' rumen fed a HFLP diet were more diverse than those of the LFHP fed group. Besides, the ratio of Bacteroidetes and Firmicutes in the rumen of the sheep fed a LFHP diet was 2.6 times higher than that of the HFLP fed group. Transcriptome analysis of the muscle revealed that the genes related to glucose metabolic processes and fatty acid biosynthesis were significantly differentially expressed between the two groups. Potential cross talk was found between the sfour omics data layers, which helps to understand the mechanism by which feedstuffs affect meat quality of lambs. CONCLUSION: Feed systems may affect the epigenetic regulation of genes involved in the glucose metabolic pathway. HFLP feeds could induce gluconeogenesis to maintain glucose levels in blood, resulting in decreased fat content in muscle. The multiple omics analysis showed that the microbiota structure is significantly correlated with the metabolome and gene expression in muscle. This study laid a theoretical foundation for controlling the nutrient intake of sheep; it suggested that its fatty acid spectrum modifications and the removal of meat quality detrimental material could guide sheep feeding for functional mutton.

HKF-SVR Optimized by Krill Herd Algorithm for Coaxial Bearings Performance Degradation Prediction.

In real industrial applications, bearings in pairs or even more are often mounted on the same shaft. So the collected vibration signal is actually a mixed signal from multiple bearings. In this study, a method based on Hybrid Kernel Function-Support Vector Regression (HKF-SVR) whose parameters are optimized by Krill Herd (KH) algorithm was introduced for bearing performance degradation prediction in this situation. First, multi-domain statistical features are extracted from the bearing vibration signals and then fused into sensitive features using Kernel Joint Approximate Diagonalization of Eigen-matrices (KJADE) algorithm which is developed recently by our group. Due to the nonlinear mapping capability of the kernel method and the blind source separation ability of the JADE algorithm, the KJADE could extract latent source features that accurately reflecting the performance degradation from the mixed vibration signal. Then, the between-class and within-class scatters (SS) of the health-stage data sample and the current monitored data sample is calculated as the performance degradation index. Second, the parameters of the HKF-SVR are optimized by the KH (Krill Herd) algorithm to obtain the optimal performance degradation prediction model. Finally, the performance degradation trend of the bearing is predicted using the optimized HKF-SVR. Compared with the traditional methods of Back Propagation Neural Network (BPNN), Extreme Learning Machine (ELM) and traditional SVR, the results show that the proposed method has a better performance. The proposed method has a good application prospect in life prediction of coaxial bearings.

Enhanced Temperature Stability of High Energy Density Ferroelectric Polymer Blends: The Spatial Confinement Effect.

Thermal stability of polymer structure is a key to achieve stable energy density at elevated temperature for ferroelectric-polymer-based capacitors. Here, a poly (vinylidene fluoride) / polymethyl methacrylate (PMMA) blend with a stabilized spherulite structure displaying steady energy density around 7.8-9.8 J cm-3 across the temperature range up to 70 °C is reported, which outperforms most neat ferroelectric polymers at elevated temperature. The microstructure of the blend observed by atomic force microscopy exhibits an alternating lamellar structure (crystalline/mixed amorphous layers) within spherulites, which might be rationalized by PMMA being gradually expelled from the spherulite and finally staying between PVDF lamellae during crystallization. The structure with rigid amorphous layers can induce a spatial confinement effect of chain motion and structural change under thermal stress, which is evidenced by temperature-insensitive long period in small-angle X-ray scattering measurements. The enhanced thermal stability of energy storage can be attributed to the constraint on free volume and carrier transportation caused by the spatial confinement. Our findings provide a strategy to attain temperature-stable high-energy-density ferroelectric polymers for energy storage capacitors.

Relationship between burnout and intention to leave amongst clinical nurses: The role of spiritual climate.

AIM: This study aims to identify the role that spiritual climate has in reducing burnout and intentions to leave amongst clinical nurses. BACKGROUND: Both shortages and the high turnover of nurses are challenging problems worldwide. Enhancing the spiritual climate amongst nurses can enhance teamwork, organisational commitment and job satisfaction and can play a role in reducing burnout and turnover intention. METHODS: A total of 207 clinical nurses working at a tertiary university hospital were included in this cross-sectional, single-site study. Independent-samples t test and ANOVA, Pearson correlation analysis and hierarchical regression analysis were used to explore the relationships amongst related factors. RESULTS: Most clinical departments showed a moderate spiritual climate (60.24 ± 0.82) with high job burnout (33.62 ± 0.28) and turnover intention (2.37 ± 0.57). A good spiritual climate was correlated with high job satisfaction (r = 0.412, p < 0.01), low burnout and turnover intention (r = -0.423, p < 0.01 and r = -0.292, p < 0.01, respectively). Spiritual climate could also indirectly influence nurses' job burnout and turnover intention (R2  = 10.31%). CONCLUSIONS: Different departments have different spiritual climates. The findings from this study indicate that spiritual climate may impact nursing burnout and turnover. IMPLICATIONS FOR NURSING MANAGEMENT: Using a spiritual climate scale provides health care decision-makers with clear information about staff spirituality well-being. Interventions to improve spiritual climate can benefit teamwork in clinical departments.

A Method for Detecting Dynamic Mutation of Complex Systems Using Improved Information Entropy.

In this study, a nonlinear analysis method called improved information entropy (IIE) is proposed on the basis of constructing a special probability mass function for the normalized analysis of Shannon entropy for a time series. The definition is directly applied to several typical time series, and the characteristic of IIE is analyzed. This method can distinguish different kinds of signals and reflects the complexity of one-dimensional time series of high sensitivity to the changes in signal. Thus, the method is applied to the fault diagnosis of a rolling bearing. Experimental results show that the method can effectively extract the sensitive characteristics of the bearing running state and has fast operation time and minimal parameter requirements.

Downregulation of RIF1 Enhances Sensitivity to Platinum-Based Chemotherapy in Epithelial Ovarian Cancer (EOC) by Regulating Nucleotide Excision Repair (NER) Pathway.

BACKGROUND/AIMS: Rap1 interacting factor 1 (RIF1) was deemed to be involved in replication timing regulation and DNA damage response. However, little is known about the role of RIF1 in malignancies. Thus, this study aimed to investigate whether the expression of RIF1 is relevant to the response of epithelial ovarian cancer (EOC) patients to cisplatin chemotherapy and its underlying mechanism. METHODS: Immunohistochemistry was used for detecting the expression of RIF1 in 72 human ovarian cancer tissues followed by association analysis of RIF1 expression with patients' responses to platinum-based chemotherapy. The survival analysis of ovarian patients based on platinum chemotherapy was analyzed using online databases. RNA interference of RIF1 was carried out in OVCAR3 and A2780 cell lines, to determine the effect of lacking RIF1 expression on cellular responses to cisplatin by using MTS assay. The nucleotide excision repair (NER) capacity of these cells was assessed by using host-cell reactivation and UV sensitivity assay. Western Blot analysis was carried out to determine the effect of RIF1 on the proteins of NER and apoptosis signaling pathway by using RIF1 knockdown cells. BALB/c nude mice model was used for detection of response to cisplatin in vivo. RESULTS: RIF1 expression was significantly associated with the response of ovarian patients to platinum-based chemotherapy (P< 0.01). In cohorts from online databases, high expression of RIF1 was associated with higher mortality of EOC patients based on platinum chemotherapy (P < 0.01). RIF1 knockdown increased sensitivity to cisplatin in EOC in vitro and in vivo. Deletion of RIF1 impaired the NER activity by inhibiting the NER proteins in ovarian cancer cells. Besides, knockdown of RIF1 enhanced cisplatin-induced apoptosis. CONCLUSIONS: RIF1 plays an important role in regulating the expression of NER proteins, which in turn contributes to cellular response to cisplatin and EOC patients' response to platinum-based chemotherapy. RIF1 knockdown also promotes cisplatin-induced apoptosis. RIF1 may serve as a novel biomarker for predicting platinum-based chemosensitivity and the prognosis of EOC patients.