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Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones. [ABSTRACT FROM AUTHOR]

With the increasing penetration of wind and solar energies, the accompanying uncertainty that propagates in the system places higher requirements on the expansion planning of power systems. A source-grid-load-storage coordinated expansion planning model based on stochastic programming was proposed to suppress the impact of wind and solar energy fluctuations. Multiple types of system components, including demand response service entities, converter stations, DC transmission systems, cascade hydropower stations, and other traditional components, have been extensively modeled. Moreover, energy storage systems are considered to improve the accommodation level of renewable energy and alleviate the influence of intermittence. Demand-response service entities from the load side are used to reduce and move the demand during peak load periods. The uncertainties in wind, solar energy, and loads were simulated using stochastic programming. Finally, the effectiveness of the proposed model is verified through numerical simulations. [ABSTRACT FROM AUTHOR]

Glycolysis has a major role in cancer progression and can affect the tumor immune microenvironment, while its specific role in lung adenocarcinoma (LUAD) remains poorly studied. We obtained publicly available data from The Cancer Genome Atlas and Gene Expression Omnibus databases and used R software to analyze the specific role of glycolysis in LUAD. The Single Sample Gene Set Enrichment Analysis (ssGSEA) indicated a correlation between glycolysis and unfavorable clinical outcome, as well as a repression effect on the immunotherapy response of LUAD patients. Pathway enrichment analysis revealed a significant enrichment of MYC targets, epithelial-mesenchymal transition (EMT), hypoxia, G2M checkpoint, and mTORC1 signaling pathways in patients with higher activity of glycolysis. Immune infiltration analysis showed a higher infiltration of M0 and M1 macrophages in patients with elevated activity of glycolysis. Moreover, we developed a prognosis model based on six glycolysis-related genes, including DLGAP5, TOP2A, KIF20A, OIP5, HJURP, and ANLN. Both the training and validation cohorts demonstrated the high efficiency of prognostic prediction in this model, which identified that patients with high risk may have a poorer prognosis and lower sensitivity to immunotherapy. Additionally, we also found that Th2 cell infiltration may predict poorer survival and resistance to immunotherapy. The study indicated that glycolysis is significantly associated with poor prognosis in patients with LUAD and immunotherapy resistance, which might be partly dependent on the Th2 cell infiltration. Additionally, the signature comprised of six genes related to glycolysis showed promising predictive value for LUAD prognosis. [ABSTRACT FROM AUTHOR]

Siniperca undulata and S. obscura (Centrarchiformes: Sinipercidae) are small Chinese perches, living in creeks and streams in southern China. While they have sympatric distribution and occupy similar macrohabitat, their body sizes and ecological niches have many differences. Determining the genome sequences of S. undulata and S. obscura would provide us an essential data set for better understanding their genetic makeup and differences that may play important roles in their adaptation to different niches. We determined the genome sequences of both S. undulata and S. obscura using 10× genomics technology and the next-generation sequencing. The assembled genomes of S. undulata and S. obscura were 744 and 733 Mb, respectively. Gene family analysis revealed that there were no overlap between S. undulata and S. obscura in terms of rapid expanding and rapid contracting genes families, which were related to growth, immunity, and mobility. Positive selection analyses also cooperated that the function of selected genes involve growth, athletic ability, and immunity, which may explain the preference of different niches by S. undulata and S. obscura. Pairwise sequentially Markovian coalescent analyses for the two species suggested that populations of both S. undulata and S. obscura showed a rising trend between 90 and 70 Ka probably due to the mild environment during the last interglacial period. A stage of population shrinking occurred from 70 to 20 Ka, which was in with the Tali glacial period in eastern China (57-16 Ka). [ABSTRACT FROM AUTHOR]

As a new type of flexible retaining structure, reinforced soil retaining wall is widely used in civil engineering and highway engineering because of good seismic performance and economy. The residual displacement under seism is one of the most important parameters to evaluate the seismic performance of reinforced soil retaining wall. The related theoretical research is rare. Taking the pseudo-dynamic method and kinematic differential equation as the theoretical basis, considering the residual deformation under large magnitude, a theoretical method is proposed to calculate the residual displacement of reinforced soil retaining wall under seismic. The rationality and accuracy of the theoretical method is verified by centrifuge model test. The results would provide some reference for the performance design and damage evaluation of reinforced soil retaining wall. [ABSTRACT FROM AUTHOR]

In the era of big data, there are numerous duplicate code snippets on the Internet, it is especially necessary to make use of them to build new software projects. In this paper, we present a toolkit (KG4Py) for generating a knowledge graph of Python files in GitHub repositories and conducting semantic search with the knowledge graph. In KG4Py, we remove all duplicate files in 317 K Python files and perform static code analyses of these files by using a concrete syntax tree (CST) to build a code knowledge graph of Python functions. We integrate a pre-trained model with an unsupervised model to generate a new model, and combine this new model with a code knowledge graph for the purpose of searching code snippets with natural language descriptions. The experimental results show that KG4Py achieves good performance in both the construction of the code knowledge graph and the semantic search of code snippets. [ABSTRACT FROM AUTHOR]

Effective phage cocktails consisting of multiple virus types are essential for successful phage therapy against pandrug-resistant pathogens, including Salmonella enterica serovar (S.) Typhimurium. Here we show that a Salmonella phage, F118P13, with non-productive infection and a lytic phage, PLL1, combined to inhibit pandrug-resistant S. Typhimurium growth and significantly limited resistance to phages in vitro. Further, intraperitoneal injection with this unique phage combination completely protected mice from Salmonella-induced death and inhibited bacterial proliferation rapidly in various organs. Furthermore, the phage combination treatment significantly attenuated the inflammatory response, restored the generation of CD4+ T cells repressed by Salmonella, and allowed macrophages and granulocytes to participate in immunophage synergy to promote bacterial clearance. Crucially, the non-productive phage F118P13 is less likely to be cleared by the immune system in vivo, thus providing an alternative to phage cocktail against bacterial infections. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is one of the fatal cancers worldwide, and over 60% of patients are lung adenocarcinoma (LUAD). Our clinical data demonstrated that DNA methylation of the promoter region of miR-126-3p was upregulated, which led to the decreased expression of miR-126-3p in 67 cases of lung cancer tissues, implying that miR-126-3p acted as a tumor suppressor. Transduction of miR-126-3p is a potential therapeutic strategy for treating LUAD, yet the physiological environment and properties of miRNA challenge current transduction approaches. Methods: We evaluated the expression of miR-126-3p in 67 pairs of lung cancer tissues and the corresponding adjacent non-tumorous tissues by Reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The relationship between the overall survival of lung cancer patients and miR-126-3p was analyzed by the Cancer Genome Atlas cohort database (Oncolnc, http://www.oncolnc.org). We analyzed DNA methylation Methylation-specific PCR (MSP) analysis. To determine whether ADAM9 is the direct target of miR-126-3p, we performed the 3′-UTR luciferase reporter assay. The protein levels in the cells or tissues were evaluated with western blotting (WB) analysis. The biodistribution of nanoparticles were monitored by in vivo tracking system. Results: We describe the development of novel stealth and matrix metalloproteinase 2 (MMP2)-activated biomimetic nanoparticles, which are constructed using MMP2-responsive peptides to bind the miR-126-3p (known as MAIN), and further camouflaged with red blood cell (RBC) membranes (hence named REMAIN). REMAIN was able to effectively transduce miRNA into lung cancer cells and release them via MMP2 responsiveness. Additionally, REMAIN possessed the advantages of the natural RBC membrane, including extended circulation time, lower toxicity, better biocompatibility, and immune escape. Moreover, in vitro and in vivo results demonstrated that REMAIN effectively induced apoptosis of lung cancer cells and inhibited LUAD development and progression by targeting ADAM9. Conclusion: The novel style of stealth and MMP2-activated biomimetic nanoparticles show great potential in miRNA delivery. [ABSTRACT FROM AUTHOR]

Background: Osimertinib-based therapy effectively improves the prognosis of lung adenocarcinoma (LUAD) patients with epidermal growth factor receptor mutations. However, patients will have cancer progression after approximately one year due to the occurrence of drug resistance. Extensive evidence has revealed that lipid metabolism and tumor-associated macrophage (TAM) are associated with drug resistance, which deserves further exploration. Methods: An osimertinib resistance index (ORi) was built to investigate the link between lipid metabolism and osimertinib resistance. The ORi was constructed and validated using TCGA and GEO data, and the relationship between ORi and immune infiltration was discussed. Weighted gene co-expression network analysis based on the M2/M1 macrophage ratio determined the hub gene TIAM2 and the biological function of TIAM2 in LUAD was verified in vitro. Results: ORi based on nine lipid metabolism-related genes was successfully constructed, which could accurately reflect the resistance of LUAD patients to osimertinib, predict the prognosis, and correlate with M2-like TAM. Additionally, TIAM2 was found to increase osimertinib tolerance, enhance cell motility, and promote M2-like TAM polarization in LUAD. Conclusions: The lipid metabolism gene is strongly connected with osimertinib resistance. TIAM2 contributes to osimertinib resistance, enhances cell motility, and induces M2-like TAM polarization in LUAD. [ABSTRACT FROM AUTHOR]

Natural products (NPs) and their derivatives are important resources for drug discovery. There are many in silico target prediction methods that have been reported, however, very few of them distinguish NPs from synthetic molecules. Considering the fact that NPs and synthetic molecules are very different in many characteristics, it is necessary to build specific target prediction models of NPs. Therefore, we collected the activity data of NPs and their derivatives from the public databases and constructed four datasets, including the NP dataset, the NPs and its first-class derivatives dataset, the NPs and all its derivatives and the ChEMBL26 compounds dataset. Conditions, including activity thresholds and input features, were explored to access the performance of eight machine learning methods of target prediction of NPs, including support vector machines (SVM), extreme gradient boosting, random forests, K-nearest neighbor, naive Bayes, feedforward neural networks (FNN), convolutional neural networks and recurrent neural networks. As a result, the NPs and all their derivatives datasets were selected to build the best NP-specific models. Furthermore, the consensus models, as well as the voting models, were additionally applied to improve the prediction performance. More evaluations were made on the external validation set and the results demonstrated that (1) the NP-specific model performed better on the target prediction of NPs than the traditional models training on the whole compounds of ChEMBL26. (2) The consensus model of FNN + SVM possessed the best overall performance, and the voting model can significantly improve recall and specificity. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer (LC) and one of the leading causes of cancer-related death worldwide. LUAD has a low survival rate owing to tumour invasion and metastasis. Circulating tumour cells (CTCs) are precursors of distant metastasis, which are considered to adopt the characteristics of cancer stem cells (CSCs). Therefore, analysing the risk factors of LUAD from the perspective of CTCs may provide novel insights into the metastatic mechanisms and may help to develop diagnostic and therapeutic strategies.Methods: A total of 447 patients from TCGA dataset were included in the training cohort, and 460 patients from the GEO dataset were included in the validation cohort. A CTC-related-gene risk model was constructed using LASSO penalty-Cox analysis, and its predictive value was further verified. Functional enrichment analysis was performed on differentially expressed genes (DEGs), followed by immune correlation analysis based on the results. In addition, western blot, CCK-8 and colony formation assays were used to validate the biological function of RAB26 in LUAD.Results: A novel in-silico CTC-related-gene risk model, named the CTCR model, was constructed, which successfully divided patients into the high- and low-risk groups. The prognosis of the high-risk group was worse than that of the low-risk group. ROC analysis revealed that the risk model outperformed traditional clinical markers in predicting the prognosis of patients with LUAD. Further study demonstrated that the identified DEGs were significantly enriched in immune-related pathways. The immune score of the low-risk group was higher than that of the high-risk group. In addition, RAB26 was found to promote the proliferation of LUAD.Conclusion: A prognostic risk model based on CTC-related genes was successfully constructed, and the relationship between DEGs and tumour immunity was analysed. In addition, RAB26 was found to promote the proliferation of LUAD cells. [ABSTRACT FROM AUTHOR]

Background. Pyroptosis is a form of programmed cell death, playing a significant role in cancer. Glioblastoma multiforme (GBM) is the most common malignant brain tumor. The poor prognosis in GBM due to temozolomide (TMZ) resistance has been widely discussed. Such being the case, the correlation between TMZ resistance and pyroptosis is seldom investigated. On this basis, this paper aims to explore the potential prognostic value of genes related to TMZ resistance and pyroptosis as well as their relationship to the immune microenvironment in GBM. Methods. A total of 103 patients from TCGA were assigned to a training cohort; 190 from CGGA were assigned to a validation cohort. The prognostic risk model reflecting pyroptosis and TMZ resistance was built from the training cohort using multivariate Cox regression and performed validation. RT-qPCR was used to examine the expression of 4 genes from the risk signature. FOXP3 was selected for overexpression and verified using the western blot. The TMZ IC50 of FOXP3-overexpressed cell lines was determined by CCK8. Results. A four genes-based risk signature was established and validated, separating GBM patients into high- and low-risk groups. Compared with the low-risk group, the high-risk group presented worse clinical survival outcomes. Its differential expressed genes were enriched in immune-related pathways and closely related to the immune microenvironment. Moreover, RT-qPCR results suggested that FOXP3, IRF3, and CD274 were significantly upregulated in TMZ-resistant strains, while TP63 was downregulated. FOXP3-overexpressed GBM cell lines had higher TMZ IC50, implying an increased resistance of TMZ. Conclusion. A novel gene signature relevant to pyroptosis and TMZ resistance was constructed and could be used for the prognosis of GBM. The four genes from the risk model might play a potential role in antitumor immunity and serve as therapeutic targets for GBM. [ABSTRACT FROM AUTHOR]

In the era of big data, there are numerous duplicate code snippets on the Internet, it is especially necessary to make use of them to build new software projects. In this paper, we present a toolkit (KG4Py) for generating a knowledge graph of Python files in GitHub repositories and conducting semantic search with the knowledge graph. In KG4Py, we remove all duplicate files in 317 K Python files and perform static code analyses of these files by using a concrete syntax tree (CST) to build a code knowledge graph of Python functions. We integrate a pre-trained model with an unsupervised model to generate a new model, and combine this new model with a code knowledge graph for the purpose of searching code snippets with natural language descriptions. The experimental results show that KG4Py achieves good performance in both the construction of the code knowledge graph and the semantic search of code snippets. [ABSTRACT FROM AUTHOR]

Rhinogobius similis is distributed in East and Southeast Asia. It is an amphidromous species found mostly in freshwater and sometimes brackish waters.We have obtained a high-resolution assembly of the R. similis genome using nanopore sequencing, high-throughput chromosome conformation capture (Hi-C), and transcriptomic data. The assembled genome was 890.10Mb in size and 40.15% in GC content. Including 1373 contigs with contig N50 is 1.54Mb, and scaffold N50 is 41.51Mb. All of the 1373 contigs were anchored on 22 pairs of chromosomes. The BUSCO evaluation score was 93.02% indicating high quality of genome assembly. The repeat sequences accounted for 34.92% of the whole genome, with retroelements (30.13%), DNA transposons (1.64%), simple repeats (2.34%), and so forth. A total of 31,089 protein-coding genes were predicted in the genome and functionally annotated using Maker, of those genes, 26,893 (86.50%) were found in InterProScan5. There were 1910 gene families expanded in R. similis, 1171 gene families contracted and 170 gene families rapidly evolving. We have compared one rapidly change gene family (PF05970) commonly found in four species (Boleophthalmus pectinirostris, Neogobius melanostomus, Periophthalmus magnuspinnatus, and R. similis), which was found probably related to the lifespan of those species. During 400–10Ka, the period of the Guxiang Ice Age, the population of R. similis decreased drastically, and then increased gradually following the last interglacial period. A high-resolution genome of R. similis should be useful to study taxonomy, biogeography, comparative genomics, and adaptive evolution of the most speciose freshwater goby genus, Rhinogobius. [ABSTRACT FROM AUTHOR]

Research on direct targets of traditional Chinese medicine (TCM) is the key to study the mechanism and material basis of it, but there is still no effective methods at present. We took Compound Danshen dropping pills (CDDP) as a study case to establish a strategy to identify significant direct targets of TCM. As a result, thirty potential active kinase targets of CDDP were identified. Nine of them had potential dose-dependent effects. In addition, the direct inhibitory effect of CDDP on three kinases, AURKB, MET and PIM1 were observed both on biochemical level and cellular level, which could not only shed light on the mechanisms of action involved in CDDP, but also suggesting the potency of drug repositioning of CDDP. Our results indicated that the research strategy including both in silico models and experimental validation that we built, were relatively efficient and reliable for direct targets identification for TCM prescription, which will help elucidating the mechanisms of TCM and promoting the modernization of TCM. [ABSTRACT FROM AUTHOR]

Visceral pain is a common clinical symptom, which is caused by mechanical stretch, spasm, ischemia and inflammation. Fragile X syndrome (FXS) with lack of fragile X mental retardation protein (FMRP) protein is an inherited disorder that is characterized by moderate or severe intellectual and developmental disabilities. Previous studies reported that FXS patients have self-injurious behavior, which may be associated with deficits in nociceptive sensitization. However, the role of FMRP in visceral pain is still unclear. In this study, the FMR1 knock out (KO) mice and SH-SY5Y cell line were employed to demonstrate the role of FMRP in the regulation of visceral pain. The data showed that FMR1 KO mice were insensitive to zymosan treatment. Recording in the anterior cingulate cortex (ACC), a structure involved in pain process, showed less presynaptic glutamate release and postsynaptic responses in the FMR1 KO mice as compared to the wild type (WT) mice after zymosan injection. Zymosan treatment caused enhancements of adenylyl cyclase 1 (AC1), a pain-related enzyme, and NMDA GluN2B receptor in the ACC. However, these up-regulations were attenuated in the ACC of FMR1 KO mice. Last, we found that zymosan treatment led to increase of FMRP levels in the ACC. These results were further confirmed in SHSY5Y cells in vitro. Our findings demonstrate that FMRP is required for NMDA GluN2B and AC1 upregulation, and GluN2B/ AC1/FMRP forms a positive feedback loop to modulate visceral pain. [ABSTRACT FROM AUTHOR]

Aim: Circular RNAs (circRNAs) play important roles in the progression of human cancers. circRNA nuclear receptor interacting protein 1 (circNRIP1) has been reported to play as an oncogene in gastric cancer. However, the mechanism underlying circNRIP1 in gastric cancer progression is far from understood. Patients and Methods: Forty-five gastric cancer patients were recruited and overall survival of patients was analyzed. Gastric cancer cell lines MGC-803 and AGS cells were cultured for study in vitro. The expression levels of circNRIP1, microRNA (miR)-182 and rho-associated protein kinase 1 (ROCK1) were detected by quantitative real-time polymerase chain reaction or Western blot. Cell migration, invasion, cell cycle distribution and apoptosis were determined by transwell, flow cytometry and Western blot assays, respectively. The target association between miR-182 and circNRIP1 or ROCK1 was assessed by luciferase reporter assay and RNA immunoprecipitation. Results: circNRIP1 expression was enhanced in gastric cancer tissues and cells and high expression of circNRIP1 indicated poor survival of patients. Knockdown of circNRIP1 suppressed cell migration and invasion, arrested cell cycle at G0-G1 phase and promoted apoptosis in gastric cancer cells. miR-182 was a target of circNRIP1 and its deficiency reversed the effect of circNRIP1 silence on cell migration, invasion, cell cycle distribution and apoptosis in gastric cancer cells. Moreover, ROCK1 was validated as a target of miR-182 and competitively regulated by circNRIP1. Conclusion: Silence of circNRIP1 inhibited progression of gastric cancer by increasing miR-182 and decreasing ROCK1, providing a novel target for the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

The big-eye mandarin fish (Siniperca knerii) is an endemic species of southern China. It belongs to the family Sinipercidae, which is closely related to the well-known North American sunfish family Centrarchidae. Determining the genome sequence of S. knerii would provide a foundation for better examining its genetic diversity and population history. A novel sequenced genome of the Sinipercidae also would help in comparative study of the Centrarchidae using Siniperca as a reference. Here, we determined the genome sequence of S. knerii using 10x Genomics technology and next-generation sequencing. Paired-end sequencing on a half lane of HiSeq X platform generated 56 Gbp of raw data. Read assembly using Supernova assembler resulted in two haplotype genomes with 732.1 Mb in size and an average GC content of 40.4%, which is consistent with genome size previously reported or estimated using k-mer counting. A total of 7,989 scaffolds with an N50 score of 12.64 Mb were obtained. The longest scaffold was 30.54 Mb. Evaluation of the genome completeness using BUSCO confirmed that 96.5% genes of the Actinopterygii Benchmarking Universal Single-Copy Orthologs were found in the assembled genome of S. knerii. Gene prediction using Maker annotation kit resulted in 28,440 genes, of which 25,899 genes had at least one hit comparing to the NCBI Nr database, KEGG or InterProScan5. Pairwise sequentially Markovian coalescent (PSMC) analysis of the genome showed that there was a bottleneck event of the population of S. knerii between 70 ka -- 20 ka, which was concordant with the Tali glacier period, suggesting a population decline of S. knerii probably due to climate conditions. [ABSTRACT FROM AUTHOR]

Using the ERA-5 monthly reanalysis data and precipitation observations, this paper analyses the interdacal dry-wet transition and its mechanism in the Tarim Basin(TB) during summer. From the long-term perspective(1961–2021), TB is in a trend of "wet in the west and dry in the east". By taking a nine-year moving average of the precipitation(PRE), the research period is divided into three subperiods: P1(1961–1987), P2(1988–2009) and P3(2010−2021). From P1 to P3, the regional averaged Standardized Precipitation Evapotranspiration Index(SPEI) demonstrates an interdecadal turning of "wetting to drying". During P2(1988–2009), the dynamic component of water vapor increases the zonal moisture transport, causing a slight increase in PRE. The potential evapotranspiration(PET) is weakened by the increase in PRE and relative humidity(RH), the decrease in 2-m temperature(T2m) and 10-m wind speed(10UV), resulting in the humidification of the TB. In the P3(2010–2021), the non-linear component of water vapor increases moisture convergence in the western TB, causing a significant increase in PRE. However, the decrease in RH, accompanied by increases in T2m and UV10, results in a rapid increase in PET. The TB gets dry. The South Asian high(SAH) develops southeastward, guiding more water vapor transport from the upstream westerly and the tropical Indian Ocean. The Western Pacific subtropical high(WPSH) extends northwestward, increasing water vapor convergence in the western TB. The main reason for the increased precipitation changes from increased water vapor advection to enhanced water vapor convergence. The differences in PRE formation and T2m amplitude cause the interdecadal change in RH, deriving an interdecadal transition of wet and dry in the TB. Our findings may deepen the understanding of climate change, and provide a scientific support for ecological development, and global climate governance in arid/semi-arid regions. • TB has been presented an interdacal dry-wet transition in summer. • The summer SPEI in the TB is consistent with the interdacadal variations of PET. • The SAH and the WPSH modulate the moisture transport pathways and precipitation formation, influence the dry-wet transition in the TB. [ABSTRACT FROM AUTHOR]

The application of bacteriophages to control foodborne bacterial pathogens in foods has gained traction in recent years. Poultry meat is a major source of Campylobacter jejuni, and a target for the application of bacteriophages. To offer the prospect of a post-harvest control measure, the bacteriophage must function at refrigeration temperatures, where C. jejuni does not grow but can survive. Here, we report actions of three classes of Campylobacter bacteriophage at 4 °C. The pre-incubation of broth cultures at 4 °C before a shift to 42 °C under conditions that support the growth of the host bacteria revealed differences in the time to lysis compared with cultures incubated at 42 °C. The pre-adsorption of the bacteriophage to a sub-population of bacteria is consistent with the observation of asynchronous infection. To ascertain whether the bacteriophages adsorb and infect (the commitment to replicate), we investigated bacteriophage transcription at 4 °C. RNA transcripts for all the bacteriophage host combinations were detected after 15 min, indicating that the interaction is not merely passive. Bacteriophages can infect C. jejuni at refrigeration temperatures, but the infection does not proceed to lysis in the absence of host cell division. [ABSTRACT FROM AUTHOR]

Extreme weather events affect the development and survival of disease pathogens and vectors. Our aim was to investigate the potential effects of heat waves on the population dynamics of Asian tiger mosquito (Aedes albopictus), which is a major vector of dengue and Zika viruses. We modeled the population abundance of blood-fed mosquito adults based on a mechanistic population model of Ae. albopictus with the consideration of diapause. Using simulated heat wave events derived from a 35-year historical dataset, we assessed how the mosquito population responded to different heat wave characteristics, including the onset day, duration, and the average temperature. Two important observations are made: (1) a heat wave event facilitates the population growth in the early development phase but tends to have an overall inhibitive effect; and (2) two primary factors affecting the development are the unusual onset time of a heat wave and a relatively high temperature over an extended period. We also performed a sensitivity analysis using different heat wave definitions, justifying the robustness of the findings. The study suggests that particular attention should be paid to future heat wave events with an abnormal onset time or a lasting high temperature in order to develop effective strategies to prevent and control Ae. albopictus-borne diseases. [ABSTRACT FROM AUTHOR]

Summary: The carrier state is an alternative bacteriophage life cycle by which virulent bacteriophage can persist in association with host bacteria. Campylobacter jejuni carrier state strains exhibit growth phase dependent motility due to a truncated flagella phenotype. Genome sequencing identified a T368A substitution in the G3 domain of the SRP‐like GTPase FlhF from C. jejuni PT14CP30A carrier state strains, which we hypothesized to be the cause of the complex motility phenotype. We have analyzed the role of this mutation in C. jejuni PT14 and demonstrated that flhF(T368A) leads to a large proportion of cells unable to synthesize flagella, while the remaining cells form a single flagellum at one pole leading to significantly reduced motility. The flhF(T368A) mutation causes a reduction in the phage adsorption constant, which leads to a decrease in infection efficiency. Down‐regulation of σ28 and σ54 dependent flagellar genes were observed as responses to the flhF(T368A) mutation. FlhF(T368A) protein is impaired in GTPase activity and exhibits reduced stability. C. jejuni carrying flhF(T368A) are less sensitive to bacteriophage infection and formation of the carrier state. The acquisition of flhF(T368A) in carrier state strains acts to prevent super‐infection and maintain association with the bacteriophage that provoked the interaction. Campylobacters are enteric bacteria that cause foodborne disease. Bacteriophages are viruses that kill specific bacteria. Understanding how virulent bacteriophages interact with bacteria is of importance for pathogen control, and the extra‐intestinal transmission of bacteriophage and bacteria. The carrier state is an alternative bacteriophage life cycle by which virulent bacteriophages can persist in association with the host. Carrier state campylobacters acquire the mutation FlhF(T368A) that impairs GTPase activity to modulate cell motility and bacteriophage resistance. [ABSTRACT FROM AUTHOR]

Cervical cancer is the fourth most common gynecological cancer worldwide. Although prophylactic vaccination presents the most effective method for cervical cancer prevention, chemotherapy is still the primary invasive intervention. It is urgent to exploit low-toxic natural anticancer drugs on account of high cytotoxicity and side-effects of conventional agents. As a natural product, (-)-epigallocatechingallate (EGCG) has abilities in anti-proliferation, anti-metastasis and pro-apoptosis of cervical cancer cells. Moreover, EGCG also has pharmaceutical synergistic effects with conventional agents such as cisplatin (CDDP) and bleomycin (BLM). The underlying mechanisms of EGCG suppressive effects on cervical cancer are reviewed in this article. Further research directions and ambiguous results are also discussed. [ABSTRACT FROM AUTHOR]

Multi-spectral photometric stereo can recover pixel-wise surface normal from a single RGB image. The difficulty lies in that the intensity in each channel is the tangle of illumination, albedo and camera response; thus, an initial estimate of the normal is required in optimization-based solutions. In this paper, we propose to make a rough depth estimation using the deep convolutional neural network (CNN) instead of using depth sensors or binocular stereo devices. Since high-resolution ground-truth data is expensive to obtain, we designed a network and trained it with rendered images of synthetic 3D objects. We use the model to predict initial normal of real-world objects and iteratively optimize the fine-scale geometry in the multi-spectral photometric stereo framework. The experimental results illustrate the improvement of the proposed method compared with existing methods. [ABSTRACT FROM AUTHOR]

Cellular automata (CA) is a powerful tool for modeling the evolution of macroscopic scale phenomena as it couples time, space, and variables together while remaining in a simplified form. However, such application has remained challenging in forest insect epidemics due to the highly dynamic nature of insect behavior. Recent advances in temporal trajectory-based image analysis offer an alternative way to obtain high-frequency model calibration data. In this study, we propose an insect-CA modeling framework that integrates cellular automata, remote sensing, and Geographic Information System to understand the insect ecological processes, and tested it with measured data of mountain pine beetle (MPB) in the Rocky Mountains. The overall accuracy of the predicted MPB mortality pattern in the test years ranged from 88% to 94%, which illuminates its effectiveness in modeling forest insect dynamics. We further conducted sensitivity analysis to examine responses of model performance to various parameter settings. In our case, the ensemble random forest algorithm outperforms the traditional linear regression in constructing the suitability surface. Small neighborhood size is more effective in simulating the MPB movement behavior, indicating that short-distance is the dominating dispersal mode of MPB. The introduction of a stochastic perturbation component did not improve the model performance after testing a broad range of randomness degree, reflecting a relative compact dispersal pattern rather than isolated outbreaks. We conclude that CA with remote sensing observation is useful for landscape insect movement analyses; however, consideration of several key parameters is critical in the modeling process and should be more thoroughly investigated in future work. [ABSTRACT FROM AUTHOR]

The life cycles and transmission of most infectious agents are inextricably linked with climate. In spite of a growing level of interest and progress in determining climate change effects on infectious disease, the debate on the potential health outcomes remains polarizing, which is partly attributable to the varying effects of climate change, different types of pathogen-host systems, and spatio-temporal scales. We summarize the published evidence and show that over the past few decades, the reported negative or uncertain responses of infectious diseases to climate change has been growing. A feature of the research tendency is the focus on temperature and insect-borne diseases at the local and decadal scale. Geographically, regions experiencing higher temperature anomalies have been given more research attention; unfortunately, the Earth's most vulnerable regions to climate variability and extreme events have been less studied. From local to global scales, agreements on the response of infectious diseases to climate change tend to converge. So far, an abundance of findings have been based on statistical methods, with the number of mechanistic studies slowly growing. Research gaps and trends identified in this study should be addressed in the future. [ABSTRACT FROM AUTHOR]

Ample evidence suggests that social support, self-efficacy, and adherence significantly, independently, and together affect glycemic control in patients with type 2 diabetes mellitus (T2DM), but the pathway from social support to glycemic control remains unclear. This study hypothesized that the effect of social support on glycemic control was mediated sequentially by self-efficacy and adherence. Patients with T2DM were recruited from two hospitals in Guangzhou, China, from January 1 to July 31, 2014, and their sociodemographic clinical data and their assessments on social support, self-efficacy, and adherence were obtained from medical records and self-completed questionnaires. Of the 532 patients who participated, 35% achieved glycemic control (i.e., HbA1c < 7%). Social support, self-efficacy, and adherence had significant correlations with each other and with glycemic control (P<0.05). Regression analyses and structural equation modeling showed that better social support was associated to better patient self-efficacy, which, in turn, was associated with better medical adherence, which was associated with improved glycemic control, and the relationship between social support and glycemic control was sequentially and completely mediated by self-efficacy and adherence. The five goodness-of-fit indices confirmed that our data fitted the hypothesized pathway model strongly. [ABSTRACT FROM AUTHOR]

The short-term photovoltaic (PV) power prediction is mainly used to prevent photovoltaic power generation fluctuations, grid overvoltage, reverse current, and islanding effects. At the same time, the mid-term PV power forecast is of great significance to improving the availability of PV power generation and the benefit of PV grid connection. Because of the significant differences in time scales between mid-term and short-term power prediction, the short-term power prediction model or method cannot be directly applied to mid-term power prediction. Therefore, few scholars have developed effective short-to-mid-term power forecasting strategies for photovoltaics. As a result, this research proposes a prediction model based on a fast cull outlier algorithm (FC), a decision tree (DT), least squares support vector regression (LSSVR), and an improved whale bat optimization algorithm (IWBOA), which is used for the prediction of the short-to-mid-term photovoltaic power on different time scales, one day and one month in advance. The FC algorithm is used to analyze the difference between the overall data and the abnormal data in the local density and distance to remove the outliers in the original data set. The revised DT model differentiates the data according to climate characteristics to obtain different input data subsets with the best correlation and constructs an independent LSSVR-based model corresponding to the data subsets. The WOA algorithm is improved by independently designing the Chebyshev chaotic initialization strategy, chaotic adaptive inertia weight and BOA algorithm, and the kernel function width and penalty factor of each short-to-mid-term independent sub-PV power prediction model are optimized by IWBOA, thereby improving the computational speed and prediction accuracy of the LSSVR model. Finally, the effectiveness of the proposed strategy is evaluated using actual data from photovoltaic power plants in China. The regression coefficient (R2), mean square error (MSE), root mean square error (RMSE), and mean absolute error (MAE) of short-term forecasting ability of the FCDT-IWBOA-LSSVR model established in this paper are 0.99657, 0.22009, 0.32515, and 0.20959, respectively, while the R2, MSE, RMSE, and MAE of medium-term forecasting ability are 0.98374, 1.91371, 1.38336, and 0.6256. The calculation results show that the prediction accuracy of the FCDT-IWBOA-LSSVR model is higher than that of the WOA-LSSVR, PSO-LSSVR, PSO-BP, I-ACO-SVR, ANN, EMS-DSM-RT, 5 ML, and ELM models. • Short-to-mid-term photovoltaic power generation prediction model established. • The FC algorithm analyze local density and distance for data and remove outliers. • The DT model differentiates the data according to climate characteristics. • The IWBOA was used to optimize the parameters of the LSSVR prediction model. [ABSTRACT FROM AUTHOR]

The thalassospiramide lipopeptides have great potential for therapeutic applications; however, their structural and functional diversity and biosynthesis are poorly understood. Here, by cultivating 130 Rhodospirillaceae strains sampled from oceans worldwide, we discovered 21 new thalassospiramide analogues and demonstrated their neuroprotective effects. To investigate the diversity of biosynthetic gene cluster (BGC) architectures, we sequenced the draft genomes of 28 Rhodospirillaceae strains. Our family-wide genomic analysis revealed three types of dysfunctional BGCs and four functional BGCs whose architectures correspond to four production patterns. This correlation allowed us to reassess the "diversity-oriented biosynthesis" proposed for the microbial production of thalassospiramides, which involves iteration of several key modules. Preliminary evolutionary investigation suggested that the functional BGCs could have arisen through module/domain loss, whereas the dysfunctional BGCs arose through horizontal gene transfer. Further comparative genomics indicated that thalassospiramide production is likely to be attendant on particular genes/pathways for amino acid metabolism, signaling transduction, and compound efflux. Our findings provide a systematic understanding of thalassospiramide production and new insights into the underlying mechanism. [ABSTRACT FROM AUTHOR]

Thermal acclimatory adjustments of locomotor performance and thermal tolerance occur commonly in ectothermic animals. However, few studies have investigated ontogenetic differences in these acclimatory responses, and thus, their causes remain unclear. In this study, juvenile and adult Chinese fire-bellied newts (Cynops orientalis) were acclimated to one of two temperatures (16 or 24 °C) for 4 weeks to examine ontogenetic differences in acclimation effect on burst swimming speed, and critical thermal minimum (CTMin) and maximum (CTMax). Swimming performance was thermally acclimated in both juvenile and adult C. orientalis. Adult newts had greater absolute swimming speeds than juveniles, which may simply result from their larger sizes. Cold acclimation enhanced low-temperature resistance, and warm acclimation enhanced high-temperature resistance in both juveniles and adults. Despite no ontogenetic difference in CTMin, adult newts had greater CTMax and acclimation response ratio than juveniles, indicating their greater abilities to withstand extreme high temperatures and manage rapid temperature shifts. Ontogenetic change in the thermal acclimatory responses of newts may be related to changes in the thermal environment they experience. [ABSTRACT FROM AUTHOR]

Objective: Cuproptosis‐related genes are closely related to lung adenocarcinoma (LUAD), which can be analyzed via the analysis of long noncoding RNA (lncRNA). To date, the clinical significance and function of cuproptosis‐related lncRNAs are still not well elucidated. Further analysis of cuproptosis‐related prognostic lncRNAs is of great significance for the treatment, diagnosis, and prognosis of LUAD. Methods: In this study, a multiple machine learning (ML)‐based computational approach was proposed for the identification of the cuproptosis‐related lncRNAs signature (CRlncSig) via comprehensive analysis of cuproptosis, lncRNAs, and clinical characteristics. The proposed approach integrated multiple ML algorithms (least absolute shrinkage and selection operator regression analysis, univariate and multivariate Cox regression) to effectively identify the CRlncSig. Results: Based on the proposed approach, the CRlncSig was identified from the 3450 cuproptosis‐related lncRNAs, which consist of 13 lncRNAs (CDKN2A‐DT, FAM66C, FAM83A‐AS1, AL359232.1, FRMD6‐AS1, AC027237.4, AC023090.1, AL157888.1, AL627443.3, AC026355.2, AC008957.1, AP000346.1, and GLIS2‐AS1). Conclusions: The CRlncSig could well predict the prognosis of different LUAD patients, which is different from other clinical features. Moreover, the CRlncSig was proved to be an effective indicator of patient survival via functional characterization analysis, which is relevant to cancer progression and immune infiltration. Furthermore, the results of RT‐PCR assay indicated that the expression level of FAM83A‐AS1 and AC026355.2 in A549 and H1975 cells (LUAD) was significantly higher than that in BEAS‐2B cells (normal lung epithelial). [ABSTRACT FROM AUTHOR]

The herbal tea made from the leaves and stems of Cyclocarya paliurus is thought to be more flavorful than those made from the leaves only. However, evidence supporting this view is not available yet. 53 VOCs and 54 non-VOCs were identified via HS-SPME-GC-MS and UPLC-Q-TOF/MS, respectively, which were found to vary dramatically in three groups of samples (combination of stems and leaves, separated leaves, and separated stems). 11 VOCs and 18 non-VOCs potential markers are responsible for the change of metabolic effects through the biosynthesis of flavonoids, the synthesis of terpenoids, and the oxidation of fatty acids and carotenoids. In response, the stems were effective to enhance fatty odors, the initial astringency and bitterness and the aftertaste of sweetness of the leaves. Stems are conducive to increasing total phenolic content, total flavonoid content and antioxidant capacity of Cyclocarya paliurus herbal extract because of the increase in polyphenols. In addition, the stems have the potential to be used as raw materials for nerolidol and polyphenols extraction. This study has been the first to determine the contribution of stem to the flavor of Cyclocarya paliurus herbal tea and these results provide the theoretical basis for making Cyclocarya paliurus herbal tea with stems. [Display omitted] • An untargeted metabolomics approach was applied to C. paliurus herbal tea. • The first study to determine the contribution of stems to C. paliurus herbal tea. • 29 characteristic metabolites were obtained by using OPLS-DA analysis. • Metabolic pathways of VOCs and non-VOCs in C. paliurus herbal tea were studied. • The stems of C. paliurus are rich in flavonoids and nerolidol. [ABSTRACT FROM AUTHOR]

An optimization strategy combining global semiempirical quantum mechanical search with all-electron density functional theory was adopted to determine the lowest energy structure of (GaSb)n clusters up to n = 9. The growth pattern of the clusters differed from those of previously reported group III-V binary clusters. A cagelike configuration was found for cluster sizes n ≤ 7. The structure of (GaSb)6 deviated from that of other III-V clusters. Competition existed between core-shell and hollow cage structures of (GaSb)7. Novel noncagelike structures were energetically preferred over the cages for the (GaSb)8 and (GaSb)9 clusters. Electronic properties, such as vertical ionization potential, adiabatic electron affinities, HOMO-LUMO gaps, and average on-site charges on Ga or Sb atoms, as well as binding energies, were computed. [ABSTRACT FROM AUTHOR]

Background: The mosquito Aedes albopitus is a competent vector for the transmission of many blood-borne pathogens. An important factor that affects the mosquitoes' development and spreading is climate, such as temperature, precipitation and photoperiod. Existing climate-driven mechanistic models overlook the seasonal pattern of diapause, referred to as the survival strategy of mosquito eggs being dormant and unable to hatch under extreme weather. With respect to diapause, several issues remain unaddressed, including identifying the time when diapause eggs are laid and hatched under different climatic conditions, demarcating the thresholds of diapause and non-diapause periods, and considering the mortality rate of diapause eggs. Methods: Here we propose a generic climate-driven mechanistic population model of Ae. albopitus applicable to most Ae. albopictus-colonized areas. The new model is an improvement over the previous work by incorporating the diapause behaviors with many modifications to the stage-specific mechanism of the mosquitoes' life-cycle. monthly Container Index (CI) of Ae. albopitus collected in two Chinese cities, Guangzhou and Shanghai is used for model validation. Results: The simulation results by the proposed model is validated with entomological field data by the Pearson correlation coefficient r2 in Guangzhou (r2 = 0.84) and in Shanghai (r2 = 0.90). In addition, by consolidating the effect of diapause-related adjustments and temperature-related parameters in the model, the improvement is significant over the basic model. Conclusions: The model highlights the importance of considering diapause in simulating Ae. albopitus population. It also corroborates that temperature and photoperiod are significant in affecting the population dynamics of the mosquito. By refining the relationship between Ae. albopitus population and climatic factors, the model serves to establish a mechanistic relation to the growth and decline of the species. Understanding this relationship in a better way will benefit studying the transmission and the spatiotemporal distribution of mosquito-borne epidemics and eventually facilitating the early warning and control of the diseases. [ABSTRACT FROM AUTHOR]

Background: After the earthquake on 14, April 2010 at Yushu in China, a plague epidemic hosted by Himalayan marmot (Marmota himalayana) became a major public health concern during the reconstruction period. A rapid assessment of the distribution of Himalayan marmot in the area was urgent. The aims of this study were to analyze the relationship between environmental factors and the distribution of burrow systems of the marmot and to predict the distribution of marmots.Methods: Two types of marmot burrows (hibernation and temporary) in Yushu County were investigated from June to September in 2011. The location of every burrow was recorded with a global positioning system receiver. An ecological niche model was used to determine the relationship between the burrow occurrence data and environmental variables, such as land surface temperature (LST) in winter and summer, normalized difference vegetation index (NDVI) in winter and summer, elevation, and soil type. The predictive accuracies of the models were assessed by the area under the curve of the receiving operator curve.Results: The models for hibernation and temporary burrows both performed well. The contribution orders of the variables were LST in winter and soil type, NDVI in winter and elevation for the hibernation burrow model, and LST in summer, NDVI in summer, soil type and elevation in the temporary burrow model. There were non-linear relationships between the probability of burrow presence and LST, NDVI and elevation. LST of 14 and 23 °C, NDVI of 0.22 and 0.60, and 4100 m were inflection points. A substantially higher probability of burrow presence was observed in swamp soil and dark felty soil than in other soil types. The potential area for hibernation burrows was 5696 km(2) (37.7% of Yushu County), and the area for temporary burrows was 7711 km(2) (51.0% of Yushu County).Conclusions: The results suggested that marmots preferred warm areas with relatively low altitudes and good vegetation conditions in Yushu County. Based on these results, the present research is useful in understanding the niche selection and distribution pattern of marmots in this region. [ABSTRACT FROM AUTHOR]

In this paper, we investigate a class of stochastic evolution inclusions of Clarke's subdifferential type in Hilbert spaces. The existence of mild solutions and controllability results are given and proved by using stochastic analysis techniques, semigroup of operators theory, a fixed point theorem of multivalued maps and properties of generalized Clarke subdifferential. An example is included to illustrate the applicability of the main results. [ABSTRACT FROM AUTHOR]

With the rapid development of renewable energy, the primary frequency control (PFC) is becoming more critical and significant to ensure the stability of the electrical power system. As the main role of PFC, the thermal power unit tends to in a wide operation interval, and the changes in PFC characteristics along with working conditions are inevitable. By decomposing and quantifying the dynamic energy conversion process, this paper proposes a novel mechanism to evaluate the PFC capability for the supercritical thermal power plants that covered 30%–100% of the rated load. In the mechanism, a refined steam turbine model is established to reflect the short‐term dynamic response of PFC by combining it with the coupling characteristics of the main steam valve and main steam pressure in the later phase. Meanwhile, as a new prior assessment index, the equivalent electricity has been put forward to quantify the PFC capability for the power plant. In a case study of a 600 MW supercritical power plant, the capacities of PFC under 30%–50% of the rated load are quantified for the first time. Comparison results between theoretical calculation and real PFC test show that the proposed PFC capability assessment mechanism has acceptable accuracy of 96.1%, which could be effective to assess the frequency response reserve and stability margin in the grid. [ABSTRACT FROM AUTHOR]

Posttranscriptional gene regulation is governed by a network of RNA-binding proteins (RBPs) that interact with regulatory elements in the mRNA to modulate multiple molecular processes, including splicing, RNA transport, RNA stability, and translation. Mounting evidence indicates that there is a hierarchy within this network whereby certain RBPs cross-regulate other RBPs to coordinate gene expression. HuR, an RNA-binding protein we linked previously to aberrant VEGF mRNA metabolism in models of SOD1-associated amyotrophic lateral sclerosis, has been identified as being high up in this hierarchy, serving as a regulator of RNA regulators. Here we investigated the role of HuR in regulating two RBPs, TDP-43 and FUS/TLS, that have been linked genetically to amyotrophic lateral sclerosis. We found that HuR promotes the expression of both RBPs in primary astrocytes and U251 cells under normal and stressed (hypoxic) conditions. For TDP-43, we found that HuR binds to the 3' untranslated region (UTR) and regulates its expression through translational efficiency rather than RNA stability. With HuR knockdown, there was a shift of TDP-43 and FUS mRNAs away from polysomes, consistent with translational silencing. The TDP-43 splicing function was attenuated upon HuR knockdown and could be rescued by ectopic TDP-43 lacking the 3' UTR regulatory elements. Finally, conditioned medium from astrocytes in which HuR or TDP-43 was knocked down produced significant motor neuron and cortical neuron toxicity in vitro. These findings indicate that HuR regulates TDP-43 and FUS/TLS expression and that loss of HuR-mediated RNA processing in astrocytes can alter the molecular and cellular landscape to produce a toxic phenotype. [ABSTRACT FROM AUTHOR]

Marine bacteria are the most widely distributed organisms in the ocean environment and produce a wide variety of secondary metabolites. However, traditional screening for bioactive natural compounds is greatly hindered by the lack of a systematic way of cataloguing the chemical profiles of bacterial strains found in nature. Here we present a chemical fingerprint database of marine bacteria based on their secondary metabolite profiles, acquired by high-resolution LC-MS. Till now, 1,430 bacterial strains spanning 168 known species collected from different marine environments were cultured and profiled. Using this database, we demonstrated that secondary metabolite profile similarity is approximately, but not always, correlated with taxonomical similarity. We also validated the ability of this database to find species-specific metabolites, as well as to discover known bioactive compounds from previously unknown sources. An online interface to this database, as well as the accompanying software, is provided freely for the community to use. [ABSTRACT FROM AUTHOR]

Simple Summary: New-born piglets often fail to thrive during suckling without any obvious signs of clinical disease, which causes significant economic loss and suffering. This is, in part, caused by enhanced production values, with too many piglets produced for the sow to provide adequate nutrition to its offspring. These piglets may not be receiving enough milk from the sow and may be removed to controlled environment pens and fed a complete commercial milk replacer to provide adequate nutrition and enhanced care. However, milk replacers do not traditionally contain the milk sugars found in sow milk that stimulate the development of a healthy immune system and gut microbiota. In this study, the effects of supplementing milk replacer with simple milk sugars on gut health, the microbiome and immune-protective goblet cells were investigated. Commercial milk replacer supplemented with milk sugars significantly increased the abundance of beneficial gut bacteria, improved gut health and the numbers of protective immune goblet cells. Results indicate that milk sugars given in milk replacer may be a useful addition in the husbandry of non-thriving, poorly performing piglets when moved to environmentally controlled pens away from sows and fit siblings by modulating their microbiome and gut health performance. Poorly performing piglets receiving commercial milk replacers do not benefit from the naturally occurring probiotic galacto-oligosaccharides otherwise found in sow milk. Study objectives were to investigate the effects of complete milk replacer supplemented with galacto-oligosaccharides on the microbiome, gut architecture and immunomodulatory goblet cell expression of poorly performing piglets that could benefit from milk replacement feeding when separated from sows and housed with fit siblings in environmentally controlled pens. The study is novel in that it is one of the first to investigate the effects of supplementing complete milk replacer with galacto-oligosaccharides in poorly performing piglets. Gastrointestinal tract samples were collected from piglets, and the microbiome composition was assessed by 16s ribosomal ribonucleic acid gene sequencing. Gut architectural features, villus/crypt ratio and enumeration of goblet cells in tissues were assessed by histopathological techniques. The most abundant taxa identified at the genus level were Lactobacillus, Streptococcus, Prevotella, Lactococcus and Leuconostoc. Milk replacer plus galacto-oligosaccharides significantly improved gut architectural features and villus/crypt ratio throughout the gastrointestinal tract, increased the number of goblet cells and revealed a differential abundance of beneficial probiotic bacteria, particularly Lactobacillus and Bifidobacterium. In these respects, galacto-oligosaccharide-supplemented milk replacer may be a useful addition to animal husbandry in poorly performing, non-thriving animals when moved to environmentally controlled pens away from sows and fit siblings, thereby modulating the microbiome and gastrointestinal tract performance. [ABSTRACT FROM AUTHOR]

Pullorum disease caused by Salmonella Pullorum remains an important disease for the poultry industry due to high morbidity and mortality in many countries. Phage therapy is becoming an alternative strategy to control multidrug-resistant Salmonella infections in young chicks. However, how bacteriophages affect the growth performance of chicks infected with S. Pullorum remains poorly understood. Herein, we assessed the therapeutic efficacy of Salmonella phage CKT1 against hypervirulent arthritis - causing S. Pullorum. The results showed that single phage treatment after hypervirulent S. Pullorum infection significantly improved body weight loss of chicks. Compared with enlarged liver and spleen in only Salmonella challenged group, phage administration substantially reduced the liver/body and spleen/body weight ratios, bacterial loads in organs and the degree of hepatic sinusoidal dilatation and congestion. Moreover, phage CKT1 can enter the organs of chicks and stay for at least 3 d in liver and spleen, and promote higher serum levels of IL-6 production within 6 d postinfection, indicating phage-induced bacterial lysis may be involved in inflammatory immune response to S. Pullorum infection. Analysis of the microbiome of gastrointestinal tract of chicks demonstrated that Salmonella challenge significantly reduced the relative abundances of Lachnoclostridium and Blautia, resulting in remarkably increased Escherichia-Shigella and Klebsiella becoming the predominant bacterial taxa. In contrast, the use of phage CKT1 significantly reduced Escherichia-Shigella and Klebsiella populations in intestine, permitting the proliferation of beneficial microbiota in Firmicutes including Lachnoclostridium, Ruminococcus, Lactobacillus , and Pseudoflavonifractor. In addition, phage alone treatments did not affect the normal gut microbiota structure of chicks, and phage therapy on Salmonella infected chicks increased bacteria species richness in the cecum. These results suggest that Salmonella phage CKT1 could improve growth performance of chicks challenged with S. Pullorum by normalizing the abnormal intestinal microbiome. [ABSTRACT FROM AUTHOR]

The results of laboratory model tests for simulating the slope failure due to vibration, including un reinforced slope and the slope reinforced by using geo textile, show that the slope failure occurs when a cumulative plastic displacement exceeds a certain critical value. To overcome the defects of conventional stability analysis, which evaluates the slope characteristics only by its strength parameters, a numerical procedure considering the stiffness and deformation of materials and geo synthetics is proposed to evaluate the seismic slope stability. In the proposed procedure, the failure of slope is defined when the cumulative plastic displacement calculated by a dynamic response analysis using actual seismic wave exceeds the critical value of displacement estimated by a static stability analysis considering seismic coefficient. The proposed procedure is applied to the laboratory model tests and an actual failure of slope in earthquake. The case study shows the possibility that the proposed procedure gives the realistic evaluation of seismic slope stability. [ABSTRACT FROM AUTHOR]

We report a new type of memory device based on insulating LaAlO3/SrTiO3 (LAO/STO) hetero-interface. The microstructures of the LAO/STO interface are characterized by Cs-corrected scanning transmission electron microscopy, which reveals the element intermixing at the interface. The inhomogeneous element distribution may result in carrier localization, which is responsible for the insulating state. The insulating state of such interface can be converted to metallic state by light illumination and the metallic state maintains after light off due to giant persistent photoconductivity (PPC) effect. The on/off ratio between the PPC and the initial dark conductance is as large as 105. The metallic state also can be converted back to insulating state by applying gate voltage. Reversible and reproducible resistive switching makes LAO/STO interface promising as a nonvolatile memory. Our results deepen the understanding of PPC phenomenon in LAO/STO, and pave the way for the development of all-oxide electronics integrating information storage devices [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in western world. However, NAFLD shows an increasing trend in China every year, which has attracted the attention of national health authorities. The previous studies have shown that NAFLD caused severe gastrointestinal motor disorders, but little is known about the interstitial cells of Cajal (ICC) role in gastrointestinal motor disorders. Objectives: The aim of this study was to observe the ICC in jejunum of nonalcoholic fatty liver mice by immunohistochemistry and assessed the relationship between intestinal motility and ICC. Materials and Methods: Thirty five Sprague-Dawley (SD) rats were randomly divided into nonalcoholic fatty liver (n = 25) and control groups (n = 10), rats were housed individually in cages and had free access to food and water, nonalcoholic fatty liver group was duplicated by high-fat diet (consisted of ordinary food, 20 g/kg cholesterol and 100 g/kg fat) feeding. Dextran blue-2000 was used to monitor the intestinal motility. The proximal small intestine was harvested to investigate the C-kit positive ICC. The hepatic tissue slices were used for pathological observation. Results: Nonalcoholic fatty liver disease was successfully established. The intestinal motility in nonalcoholic fatty liver group (49.5 ± 10.9) was weaker compared to the control group (57.3 ± 8.9), P < 0.05. The rate of ICC also have shown statistically significant differences between nonalcoholic fatty liver (4.87 ± 2.97/mm 2) and control groups (6.54 ± 3.13/mm 2), P < 0.05. Conclusions: ICC may be related to the intestinal motility in nonalcoholic fatty liver mice. [ABSTRACT FROM AUTHOR]

Background: Non-steroidal anti-inflammatory drugs (NSAIDs), the most widely prescribed drugs in the world, can cause gastrointestinal damage, including colitis. However, the prevalence of NSAID-induced colitis is unknown because the disease is often asymptomatic. Case presentation: We report the case of a 64-year-old female patient with a history of long-term NSAID use, who was hospitalized with septic shock caused by Klebsiella pneumoniae bacteremia. Computed tomography revealed multiple renal and splenic abscesses with diffuse colon wall thickening. A colonoscopy confirmed colitis with diffuse ulcers. NSAIDs were discontinued after this hospitalization. The abscesses improved after antibiotic treatment. A short course of balsalazide treatment was given under the suspicion of ulcerative colitis. Balsalazide was discontinued four months later due to a non-compatible clinical course. A follow-up colonoscopy two years later revealed a normal colon mucosa, and NSAID-induced colitis was diagnosed. Conclusion: This is the first reported case of combined bacterial splenic and renal abscesses without intestinal manifestations as the initial presentation of NSAID-induced colitis. In contrast to cases of K. pneumoniae bacteremia with primary liver abscesses in patients with diabetes mellitus in Taiwan, we presented the first case with abscesses caused by community-acquired K. pneumoniae in the kidneys and spleen without liver invasion. In conclusion, our case report alerts clinicians to the possibility that K. pneumoniae bacteremia combined with multiple abscesses can be associated with severe NSAID-induced colitis. [ABSTRACT FROM AUTHOR]

The in vitro oxygen microenvironment profoundly affects the capacity of cell cultures to model physiological and pathophysiological states. Cell culture is often considered to be hyperoxic, but pericellular oxygen levels, which are affected by oxygen diffusivity and consumption, are rarely reported. Here, we provide evidence that several cell types in culture actually experience local hypoxia, with important implications for cell metabolism and function. We focused initially on adipocytes, as adipose tissue hypoxia is frequently observed in obesity and precedes diminished adipocyte function. Under standard conditions, cultured adipocytes are highly glycolytic and exhibit a transcriptional profile indicative of physiological hypoxia. Increasing pericellular oxygen diverted glucose flux toward mitochondria, lowered HIF1α activity, and resulted in widespread transcriptional rewiring. Functionally, adipocytes increased adipokine secretion and sensitivity to insulin and lipolytic stimuli, recapitulating a healthier adipocyte model. The functional benefits of increasing pericellular oxygen were also observed in macrophages, hPSC-derived hepatocytes and cardiac organoids. Our findings demonstrate that oxygen is limiting in many terminally-differentiated cell types, and that considering pericellular oxygen improves the quality, reproducibility and translatability of culture models. Synopsis: Cell culture is considered a microenvironment with high oxygen. Here, terminally-differentiated cells are shown to be deprived of pericellular oxygen in standard culture systems. mandating tight control of oxygen provision and consumption conditions to ensure experimental reproducibility and translatability to physiology. Cells of various types cultured in standard medium volumes are hypoxic due to oxygen consumption exceeding diffusion rates. Increasing oxygen supply to cultured cells enhances glucose oxidation and anabolic reactions, and causes widespread transcriptional changes. Increased oxygen supply improves the differentiation and function of differentiated cellular models such as adipocytes, macrophages, hPSC-derived hepatocytes and cardiac organoids. Transcriptional responses to limited oxygen in cultured cells match those driven by hypoxia in vivo. Standard cell culture medium volumes dictate a hypoxic pericellular in vitro microenvironment due to oxygen consumption exceeding diffusion rates. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) refer to a certain subpopulation within the tumor entity that is characterized by restricted cellular proliferation and multipotent differentiation potency. The existence of CSCs has been proven to contribute to the heterogeneity of malignancies, accounting for intensified tumorigenesis, treatment resistance, and metastatic spread. Dormancy was proposed as a reversible state of cancer cells that are temporarily arrested in the cell cycle, possessing several hallmarks that facilitate their survival within a devastating niche. This transient period is evoked to enter an actively proliferating state by multiple regulatory alterations, and one of the most significant and complex factors comes from local and systemic inflammatory reactions and immune components. Although CSCs and dormant cancer cells share several similarities, the clear relationship between these two concepts remains unclear. Thus, the detailed mechanism of immune cells interacting with CSCs and dormant cancer cells also warrants elucidation for prevention of cancer relapse and metastasis. In this review, we summarize recent findings and prospective studies on CSCs and cancer dormancy to conclude the relationship between these two concepts. Furthermore, we aim to outline the mechanism of immune components in interfering with CSCs and dormant cancer cells to provide a theoretical basis for the prevention of relapse and metastasis. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) and migraine are distinct clinical disorders. Apart from the characteristics of chronic and recurrent pain in nature, these pain-related disorders apparently share many similarities. For example, IBS is female predominant with community prevalence about 5-10%, whereas that of migraine is 1-3% also showing female predominance. They are often associated with many somatic and psychiatric comorbidities in terms of fibromyaglia, chronic fatigue syndrome, interstitial cystitis, insomnia and depression etc., even the IBS subjects may have coexisted migraine with an estimated odds ratio of 2.66. They similarly reduce the quality of life of victims leading to the social, medical and economic burdens. Their pathogeneses have been somewhat addressed in relation to biopsychosocial dysfunction, heredity, genetic polymorphism, central/visceral hypersensitivity, somatic/cutaneous allodynia, neurolimbic pain network, gonadal hormones and abuses etc. Both disorders are diagnosed according to the symptomatically based criteria. Multidisciplinary managements such as receptor target new drugs, melantonin, antispasmodics, and psychological drugs and measures, complementary and alternatives etc. are recommended to treat them although the used agents may not be necessarily the same. Finally, the prognosis of IBS is pretty good, whereas that of migraine is less fair since suicide attempt and stroke are at risk. In conclusion, both distinct chronic pain disorders to share many similarities among various aspects probably suggest that they may locate within the same spectrum of a pain-centered disorder such as central sensitization syndromes. The true pathogenesis to involve these disorders remains to be clarified in the future. [ABSTRACT FROM AUTHOR]

Bats and cetaceans (i.e., whales, dolphins, porpoises) are two kinds of mammals with unique locomotive styles and occupy novel niches. Bats are the only mammals capable of sustained flight in the sky, while cetaceans have returned to the aquatic environment and are specialized for swimming. Associated with these novel adaptations to their environment, various development changes have occurred to their body plans and associated structures. Given the importance of Hox genes in many aspects of embryonic development, we conducted an analysis of the coding regions of all Hox gene family members from bats (represented by Pteropus vampyrus, Pteropus alecto, Myotis lucifugus and Myotis davidii) and cetaceans (represented by Tursiops truncatus) for adaptive evolution using the available draft genome sequences. Differences in the selective pressures acting on many Hox genes in bats and cetaceans were found compared to other mammals. Positive selection, however, was not found to act on any of the Hox genes in the common ancestor of bats and only upon Hoxb9 in cetaceans. PCR amplification data from additional bat and cetacean species, and application of the branch-site test 2, showed that the Hoxb2 gene within bats had significant evidence of positive selection. Thus, our study, with genomic and newly sequenced Hox genes, identifies two candidate Hox genes that may be closely linked with developmental changes in bats and cetaceans, such as those associated with the pancreatic, neuronal, thymus shape and forelimb. In addition, the difference in our results from the genome-wide scan and newly sequenced data reveals that great care must be taken in interpreting results from draft genome data from a limited number of species, and deep genetic sampling of a particular clade is a powerful tool for generating complementary data to address this limitation. [ABSTRACT FROM AUTHOR]

The physical environment of myo- cardium, featuring excitation-con- traction coupling, constant and efficient provision of nutrient/oxygen and deli- cate integration of cardiomyocytes and supporting cell population (fibro- blasts, endothelial cells), is one of the most complex systems in human body. Numerous studies have demonstrated the significance of physical stimulation in cardiac cell physiology, including the maintenance of contractile function in cardiomyocytes,1 cell alignment and extracellular matrix secretion in fibro- blasts and endothelial cells.2,3 In effort to reconstruct the physical environment found in the cardiac niche for routine cell culture use, we have devised a biore- actor system to account for three major forms of physical stimuli, namely, cyclic stretch, electrical stimulation and fluid perfusion.4 [ABSTRACT FROM AUTHOR]