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ABSTRACT Retrieval and recommendation are two essential tasks in modern search tools. This paper introduces a novel retrieval‐reranking framework leveraging large language models to enhance the spatiotemporal and semantic associated mining and recommendation of relevant, unusual climate and environmental events described in news articles and web posts. This framework uses advanced natural language processing techniques to address the limitations of traditional manual curation methods in terms of high labor costs and lack of scalability. Specifically, we explore an optimized solution to employ cutting‐edge embedding models for semantically analyzing spatiotemporal events (news) and propose a Geo‐Time Re‐ranking strategy that integrates multi‐faceted criteria including spatial proximity, temporal association, semantic similarity, and category‐instructed similarity to rank and identify similar spatiotemporal events. We apply the proposed framework to a dataset of four thousand local environmental observer network events, achieving top performance on recommending similar events among multiple cutting‐edge dense retrieval models. The search and recommendation pipeline can be applied to a wide range of similar data search tasks dealing with geospatial and temporal data. We hope that by linking relevant events, we can better aid the general public to gain enhanced understanding on climate change and its impact on different communities. [ABSTRACT FROM AUTHOR]

Molybdenum carbide (MoC) integrated into a carbon matrix, known for its robust interfacial polarization, emerges as a promising ultra‐lightweight EM wave absorber. However, the fabrication of such materials remains a formidable challenge. Herein, a facile and scalable strategy for preparing MoC‐incorporated carbon matrix employing ZnMo‐HZIF foam material through ball‐milling foaming and calcination process as a promising electromagnetic wave materials (EWAMs). In detail, the 3D foam structure reaches impedance matching, and heterogeneous interfaces of N‐doped MoC‐incorporated carbon material (MoC/NC) promote the dipolar/interfacial polarization, confirmed by the hologram. Mo defects induced the charge transfers, displaying an enhanced interfacial polarization. At 15 wt.%, the minimum reflection loss of the obtained sample at 2.5 mm reaches −47.56 dB, and the effective absorption bandwidth spans 4.40 GHz, nearly covering the full X band. Additionally, the assembly device testing demonstrates their excellent self‐cleaning, heat‐insulation, flame retardancy, and infrared stealth properties. This work presents a new perspective on the synergistic effect of structure and components on electromagnetic wave absorption performance and provides a new approach for preparing lightweight and high‐performance MOF‐based electromagnetic wave absorbing materials. [ABSTRACT FROM AUTHOR]

Background. Arising from T progenitor cells, T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor, accounting for 15% of childhood ALL and 25% of adult ALL. Composing of putative enhancers in close genomic proximity, super enhancer (SE) is critical for cell identity and the pathogenesis of multiple cancers. Belonging to the cytosolute linker protein group, FYB1 is essential for TCR signaling and extensively studied in terms of tumor pathogenesis and metastasis. Dissecting the role of FYN binding protein 1 (FYB1) in T-ALL holds the potential to improve the treatment outcome and prognosis of T-ALL. Methods. In this study, SEs were explored using public H3K27ac ChIP-seq data derived from T-ALL cell lines, AML cell lines and hematopoietic stem and progenitor cells (HSPCs). Downstream target of FYB1 gene was identified by RNA-seq. Effects of shRNA-mediated downregulation of FYB1 and immunoglobulin lambda-like polypeptide 1 (IGLL1) on self-renewal of T-ALL cells were evaluated in vitro and/or in vivo. Results. As an SE-driven gene, overexpression of FYB1 was observed in T-ALL, according to the Cancer Cell Line Encyclopedia database. In vitro, knocking down FYB1 led to comprised growth and enhanced apoptosis of T-ALL cells. In vivo, downregulation of FYB1 significantly decreased the disease burden by suppressing tumor growth and improved survival rate. Knocking down FYB1 resulted in significantly decreased expression of IGLL1 that was also an SE-driven gene in T-ALL. As a downstream target of FYB1, IGLL1 exerted similar role as FYB1 in inhibiting growth of T-ALL cells. Conclusion. Our results suggested that FYB1 gene played important role in regulating self-renewal of T-ALL cells by activating IGLL1, representing a promising therapeutic target for T-ALL patients. [ABSTRACT FROM AUTHOR]

Fabric‐based materials have demonstrated promise for high‐performance wearable applications but are currently restricted by their deficient mechanical properties. Here, this work leverages the design freedom offered by additive manufacturing and a novel interlocking pattern to for the first time fabricate a dual‐faced chain mail structure consisting of 3D re‐entrant unit cells. The flexible structured fabric demonstrates high specific energy absorption and specific strength of up to 1530 J kg−1 and 5900 Nm kg−1, respectively, together with an excellent recovery ratio of ≈80%, thereby overcoming the strength–recoverability trade‐off. The designed dual‐faced structured fabric compares favorably against a wide range of materials proposed for wearable applications, attributed to the synergetic strengthening of the energy‐absorbing re‐entrant unit cells and their unique topological interlocking. This work advocates the combined design of energy‐absorbing unit cells and their interlocking to extend the application prospects of fabric‐based materials to shape‐adaptive protection. [ABSTRACT FROM AUTHOR]

Initiated by the University Consortium of Geographic Information Science (UCGIS), the GIS&T Body of Knowledge (BoK) is a community‐driven endeavor to define, develop, and document geospatial topics related to geographic information science and technologies (GIS&T). In recent years, GIS&T BoK has undergone rigorous development in terms of its topic re‐organization and content updating, resulting in a new digital version of the project. While the BoK topics provide useful materials for researchers and students to learn about GIS, the semantic relationships among the topics, such as semantic similarity, should also be identified so that a better and automated topic navigation can be achieved. Currently, the related topics are either defined manually by editors or authors, which may result in an incomplete assessment of topic relationships. To address this challenge, our research evaluates the effectiveness of multiple natural language processing (NLP) techniques in extracting semantics from text, including both deep neural networks and traditional machine learning approaches. Besides, a novel text summarization—KACERS (Keyword‐Aware Cross‐Encoder‐Ranking Summarizer)—is proposed to generate a semantic summary of scientific publications. By identifying the semantic linkages among key topics, this work guides the future development and content organization of the GIS&T BoK project. It also offers a new perspective on the use of machine learning techniques for analyzing scientific publications and demonstrates the potential of the KACERS summarizer in semantic understanding of long text documents. [ABSTRACT FROM AUTHOR]

With the high demand for basic resources such as electricity, communication, water supply, and gas in cities, most cities in my country are vigorously developing underground integrated pipe gallery. When constructing pipe gallery in coastal areas, it is necessary to consider the impact of groundwater level on structural calculations. There is still a lack of systematic research in domestic and foreign literature. Relying on the Qingdao West Coast New Area Project, this paper uses a combination of laboratory tests and MIDAS GTS/NX numerical simulation to study the influence of groundwater in the coastal area on the stress and deformation characteristics of the integrated pipe gallery. The results show that (1) the Mises stress on the roof and bottom of the integrated pipe gallery increases continuously with the rise of the groundwater level. Due to the effect of the effective stress, the Mises stress on the side wall shows a decreasing trend. (2) Due to the influence of the construction form of the cross-section interface, the maximum principal stress of each part of the M side is always smaller than that of the N side; with the continuous increase of groundwater level, the maximum principal stress at each part of the N and M sides of the pipe gallery structure joint gradually increases. (3) The overall structure of the pipe gallery floats up. Under the action of the buoyancy force, the bottom plate moves upward, and the surface displacement rises continuously with the rise of the groundwater level. (4) When the groundwater depth is the same, the analysis of the test results and the numerical simulation calculation results are basically consistent, which further verifies the validity of the numerical simulation calculation and has reference value. (5) The engineering example shows that in order to reduce the service life of the integrated pipe gallery, the impact of groundwater on the integrated pipe gallery cannot be ignored. [ABSTRACT FROM AUTHOR]

One of the advantages of sustainable competition for manufacturing systems is to make supply chain activities more efficient and effective. One of the major parts of these activities that can save a lot of costs is careful outsourcing. In this study, an approach based on decision-making policies in order to select suppliers and allocate order volume to them is introduced. The main contribution of this research is a comprehensive approach for optimizing both supplier evaluation and order allocation. In this regard, first, based on the evaluation, 39 key indicators were identified to evaluate the suppliers, and based on the content analysis, 25 key indicators were screened based on the Lavache method. Next, based on the fuzzy Delphi method, 11 indicators were selected from among the 25 key effective indicators. Finally, the Best-Worst Method (BWM) and a robust multi-objective formulation are proposed to find the weight of the effective criteria and the optimal order allocation to suppliers, respectively. Moreover, it is proved that the company under study faces a variety of suppliers and there is a need to analyze key indicators such as exchange rate changes and ease of communication. Based on the BWM results, it was shown that the exchange rate change trend with a weight of 0.24 is in the first place, and the quality system support index with a weight of 0.12 is in the second place. Moreover, based on the results of the proposed robust multi-objective mathematical model, it was revealed that in order to maintain the resilience of suppliers, the total demand should be distributed among all suppliers and the second supplier with a volume of 3600 units of raw materials has the largest share in delivering the required demand. [ABSTRACT FROM AUTHOR]

Background: AML (acute myeloid leukemia) is a common hematological malignancy in children with poor treatment effects and poor prognosis. Recent studies have shown that as a novel BRD4 (bromodomain containing 4) PROTACs (proteolysis targeting chimeras) degrader, GNE-987 can slow down the growth of various tumors and increase apoptosis, with promising clinical prospects. However, the function and molecular mechanism of GNE-987 in AML remain unclear. This study is aimed at investigating the therapeutic effect of GNE-987 on AML and its underlying mechanism.Methods: The association between BRD4 and AML was assessed by studying public databases. After GNE-987 was added to AML cells, cell proliferation slowed down, the cycle was disturbed, and apoptosis increased. Western blotting was used to detect BRD2 (bromodomain containing 2), BRD3 (bromodomain containing 3), BRD4, and PARP (poly ADP-ribose polymerase) proteins. The effect of GNE-987 on AML cells was analyzed in vivo. RNA-seq (RNA sequencing) and ChIP-seq (chromatin immunoprecipitation sequencing) validated the function and molecular pathways of GNE-987 in processing AML.Results: BRD4 expression was significantly elevated in pediatric AML samples compared with healthy donors. GNE-987 inhibited AML cell proliferation by inhibiting the cell cycle and inducing apoptosis. BRD2, BRD3, and BRD4 were consistent with decreased VHL (Von Hippel Lindau) expression in AML cells. In an AML xenograft model, GNE-987 significantly reduced the hepatosplenic infiltration of leukemia cells and increased the mouse survival time. Based on analysis of RNA-seq and ChIP-seq analyses, GNE-987 could target multiple SE- (super-enhancer-) related genes, including LYL1 (lymphoblastic leukemia 1), to inhibit AML.Conclusions: GNE-987 had strong antitumor activity in AML. GNE-987 could effectively inhibit the expression of SE-related oncogenes including LYL1 in AML. Our results suggested that GNE-987 had broad prospects in the treatment of AML. [ABSTRACT FROM AUTHOR]

Despite the widespread use of plastic bellows in prestressed channels, their poor bonding with concrete and mortar results in "layering," which limits their application in practical engineering. In this study, the bonding property between plastic bellows and concrete or grout material was investigated using a single-end compression test on plastic bellow concrete. The slip failure mode, ultimate load, and slip of plastic bellows were obtained. Furthermore, the analysis of the bond-slip properties of plastic bellows indicated that the bond strength decreased with increasing bond length. Moreover, the increase in the loading force was greater than the increase in the contact area. Based on the test data, a bond-slip constitutive relationship model was established, which accurately reflects the bond-slip process. The expressions of bond and slip were derived along with different bond positions of plastic bellow concrete specimens. Finally, a three-dimensional finite element model of a plastic bellow concrete specimen was established. The numerical simulation curve was compared with the experimental and fitting curves. The results indicated that the bond strength of the plastic bellow concrete specimen decreased with increasing bond length. The influence of bond strength on the contact area was comprehensively analyzed. This study effectively combines experimental research, theoretical analysis, and numerical simulation to analyze the bond performance between plastic bellows and concrete or grout material. [ABSTRACT FROM AUTHOR]

The present paper investigates the relationship between pressure (bond stress) and displacement at the failure load for different materials through testing and modeling. First, single-end tests were conducted on prebonded stressed and perforated concrete specimens with corrugated plastic, metal, and rubber extractive pipes. These tests reveal that corrugated plastic pipes provide good bonding performance with concrete and grout. Hence, they can be applied in the hole-forming process of posttensioned prestressed bonded structures, along with corrugated metal pipes and rubber extractive pipes. Based on the experimental observations and results, a theoretical approach for applying corrugated plastic pipes in projects such as China's high-speed rail has finally been demonstrated. [ABSTRACT FROM AUTHOR]

The use of polyenergy water pressure controlled blasting technology in tunnel construction is gradually being promoted, and the technology is often used in hard rock, and the mechanism of rock breaking in fractured sandstone strata is still lacking systematic research. The above mechanism was investigated using a combination of field experiments and ANSYS/LS-DYNA numerical simulation, and the results showed the following: (1) In the case of joint-hole blasting, the concentrating jet formed by the concentrating tube can effectively achieve controlled directional blasting of fractured sandstone. (2) The use of gun clay to seal the hole can effectively improve the stability of the blasting effect, reduce the waste of explosive gas, and effectively extend the duration of action. (3) The water bag enhances the blasting effect through the water wedge effect in the broken surrounding rock and also has the function of energy storage, which can effectively improve the blasting effect when combined with the gun clay. (4) The rock-breaking mechanism of polyenergy hydropressure smooth blasting in fractured sandstone geological conditions is the dual rock-breaking action of "polyenergy jet + water wedge action." (5) In this article, based on the analysis of blasting mechanism, the deployment method of polyenergy hydropressure smooth blasting is designed and has been well applied in engineering practice. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: Three diamines (1,8‐diaminooctane/p‐phenylenediamine/biphenylenediamine) with different alkyl groups were used to synthesize the functionalized graphene networks. Pd as the common metal catalyst was used to explore the effects of alkyl types of diamines on anti‐stacking, metal anchoring ability of functional graphene and hence the catalytic performance. The results were discussed by characterization of the material and its catalytic properties. All catalysts showed excellent catalytic performance on the Suzuki cross‐coupling reaction with a high yield of up to 100%. The p‐phenylenediamine and biphenylenediamine functionalized graphene with larger specific surface area was beneficial to improve the stability of the graphene catalyst and maintain good catalytic activity after 5 cycles. The Pd nanoparticles in 1,8‐octanediamine materials have smaller size and a smaller loading with the same or even better catalytic performance than p‐phenylenediamine, biphenylenediamine materials, due to the stronger electron donating ability of N of octanediamine than that of p‐phenylenediamine. [ABSTRACT FROM AUTHOR]

Gonadotropins (GtHs), including follicle‐stimulating hormone (FSH) and luteinizing hormone (LH), are important hormones involved in gametogenesis, gonadal steroidogenesis, and maturation. In this study, GtH subunits (FSHβ, LHβ and CGα) of largemouth bass (Micropterus salmoides) were cloned and characterized, and their regulation by luteinizing hormone‐releasing hormone analog (LHRHa2) and dopamine antagonist (DOM) treatment in vivo was investigated. The full‐length cDNA sequences of FSHβ, LHβ, and CGα were 683, 576, and 685bp, encoding 120, 152, and 132 amino acids, respectively. The deduced amino acid sequence analysis revealed that GtH subunits contain conserved cysteine residues and potential N‐linked glycosylation sites and showed high homology with the corresponding subunit sequences from other Perciformes by phylogenetic analysis. In the primary growth cortical alveoli stage of largemouth bass, the three GtH subunits were highly expressed in the pituitary, brain and ovary, but weakly in other tissues. After LHRHa2 and DOM injection, mRNA levels of FSHβ, LHβ, and CGα in the pituitary were significantly increased at 12 or 24 hr (p <.05), but significantly decreased at 48 hr; plasma FSH and LH levels showed a consistent trend. Histological analysis classified ovaries from LHRHa2‐ and DOM‐treated fish into the early oocyte maturation stage and late vitellogenesis stage, while those from the control group fish were classified into the early vitellogenesis stage. These results suggested that both LHRHa2 and DOM stimulated GtH subunit expression, increased plasma FSH and LH and accelerated ovary development of largemouth bass, providing a framework for a better understanding of the mechanisms of hormone‐mediated reproduction control in teleosts. [ABSTRACT FROM AUTHOR]

In real industrial scenarios, with the use of conventional machine learning techniques, data-driven diagnosis models have a limitation that it is difficult to achieve the desirable fault diagnosis performance, and the reason is that the training and testing datasets are assumed to have the same feature distributions. To address this problem, a novel bearing fault diagnosis framework based on domain adaptation and preferred feature selection is proposed, in that the model trained by the labeled data collected from a working condition can be applied to diagnose a new but similar target data collected from other working conditions. In this framework, an improved domain adaptation method, transfer component analysis with preserving local manifold structure (TCAPLMS), is proposed to reduce the differences in the data distributions between different domain datasets and, at the same time, take the label information of feature dataset and the local manifold structure of feature data into consideration. Furthermore, preferred feature selection by fault sensitivity and feature correlation (PSFFC) is embedded into this framework for selecting features which are more beneficial to fault pattern recognition and reduce the redundancy of feature set. Finally, vibration datasets collected from two test platforms are used for experimental analysis. The experimental results validate that the proposed method can obviously improve diagnosis accuracy and has significant potential benefits towards actual industrial scenarios. [ABSTRACT FROM AUTHOR]

Largemouth bass (LMB; Micropterus salmoides) has been an economically important fish in North America, Europe, and China. This study obtained a chromosome‐level genome assembly of LMB using PacBio and Hi‐C sequencing. The final assembled genome is 964 Mb, with contig N50 and scaffold N50 values of 1.23 Mb and 36.48 Mb, respectively. Combining with RNA sequencing data, we annotated a total of 23,701 genes. Chromosomal assembly and syntenic analysis proved that, unlike most Perciformes with the popular haploid chromosome number of 24, LMB has only 23 chromosomes (Chr), among which the Chr1 seems to be resulted from a chromosomal fusion event. LMB is phylogenetically closely related to European seabass and spotted seabass, diverging 64.1 million years ago (mya) from the two seabass species. Eight gene families comprising 294 genes associated with ionic regulation were identified through positive selection, transcriptome and genome comparisons. These genes involved in iron facilitated diffusion (such as claudin, aquaporins, sodium channel protein and so on) and others related to ion active transport (such as sodium/potassium‐transporting ATPase and sodium/calcium exchanger). The claudin gene family, which is critical for regulating cell tight junctions and osmotic homeostasis, showed a significant expansion in LMB with 27 family members and 68 copies for salinity adaptation. In summary, we reported the first high‐quality LMB genome, and provided insights into the molecular mechanisms of LMB adaptation to fresh and brackish water. The chromosome‐level LMB genome will also be a valuable genomic resource for in‐depth biological and evolutionary studies, germplasm conservation and genetic breeding of LMB. [ABSTRACT FROM AUTHOR]

Peony (Paeonia) has high ornamental, edible, and medicinal values. In order to distinguish seeds varieties, describe the proteomic profiles correlated with stress tolerance, and evaluate peony seed protein (PSP) as a functional food product, we characterized the seed protein profiles of these three species and their glucosidase inhibition activities. Results showed that the intensity of protein bands in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and specific protein ID (especially for specifically expressed proteins (SEPs)) was effective to distinguish these peony seed varieties. Proteomic analysis of the three species showed that P. ostii "Fengdan" has heat and pathogen tolerance-related proteins, while P. rockii has higher content of proteins related to cold resistance, which were all highly consistent with their adaptation of heat or cold habitat. Moreover, stress-related proteins were also accumulated in P. lactiflora Pall "Hangshao" seeds, showing its potential for stress resistance. Further protein analysis showed that the primary composition of PSP was albumin and globulin. And the solubility of PSP was good. Furthermore, PSP also showed high glucosidase inhibition activity, indicating that PSP might have some potential function for the remission of hyperglycemia. And P. ostii "Fengdan" seeds may be a better source for protein production than seeds of the other two species in terms of protein solubility and the content of total protein, albumin, and globulin. In addition, an optimal protocol of microwave-assisted alkali extraction was developed to produce PSP. In conclusion, the evaluated stress-related proteins in three peony seed species by proteomic analysis quite agreed with their adaptation of heat or cold stress; proteomics could also be a very useful tool for distinguishing species in the production; and peony seeds may be a good source for protein production. [ABSTRACT FROM AUTHOR]

The partial cDNA sequences of eight reference genes (actb, tuba1, gapdh58, gapdh59, eef1a1, RNA 18 s, pabpc1, ube2I) were cloned from largemouth bass Micropterus salmoides. The expression levels of these eight genes were compared in the various tissues (eye, spleen, kidney, gill, muscle, brain, liver, heart, gut and gonad) of M. salmoides fed on forage fish. The results showed that the candidate genes exhibited tissue‐specific expression to various degrees and the stability ranking order was eef1a1 > tuba1 > RNA 18 s > pabpc1 > ube2I > actb > gapdh58 > gapdh59 among tissue types. Four candidate genes eef1a1, tuba1, RNA 18 s and actb were used to analyse the stability in liver tissues of largemouth bass between the forage‐fish group and the formulated‐feed group. The candidate genes also showed some changes in expression levels in the livers, while eef1a1 and tuba1 had the most stable expression in livers of fish fed on alternative diets within 10 candidates. So eef1a1 and tuba1 were recommended as optimal reference gene in quantitative real‐time PCR analysis to normalise the expression levels of target genes in tissues and lives of the M. salmoides fed on alternative diets. In livers, the expression levels of gck normalised by eef1a1 and tuba1 showed the significant up‐regulation in formulated feed group (P < 0.05) than those in forage‐fish group. While sex difference has no significant effects on the expression levels of gck in both groups. [ABSTRACT FROM AUTHOR]

Impaired autophagic degradation of intracellular lipids is causally linked to the development of non‐alcoholic steatohepatitis (NASH). Pharmacological agents that can restore hepatic autophagic flux could therefore have therapeutic potentials for this increasingly prevalent disease. Herein, we investigated the effects of polydatin, a natural precursor of resveratrol, in a murine nutritional model of NASH and a cell line model of steatosis. Results showed that oral administration of polydatin protected against hepatic lipid accumulation and alleviated inflammation and hepatocyte damage in db/db mice fed methionine‐choline deficient diet. Polydatin also alleviated palmitic acid‐induced lipid accumulation in cultured hepatocytes. In both models, polydatin restored lysosomal function and autophagic flux that were impaired by NASH or steatosis. Mechanistically, polydatin inhibited mTOR signalling and up‐regulated the expression and activity of TFEB, a known master regulator of lysosomal function. In conclusion, polydatin ameliorated NASH through restoring autophagic flux. The polydatin‐regulated autophagy was associated with inhibition of mTOR pathway and restoration of lysosomal function by TFEB. Our study provided affirmative preclinical evidence to inform future clinical trials for examining the potential anti‐NASH effect of polydatin in humans. [ABSTRACT FROM AUTHOR]

An amine‐functionalized microporous metal‐organic framework (MOF)capable of thermodynamically capturing CO2 from flue gas/natural gas and kinetically separating n‐butane from iso‐butane is reported. The compound, Co2(abim)(im)3 (abim=2‐aminobenzimidazole, im=imidazole) is both thermally and chemically robust. According to our computational modeling, it has a sharp pore size distribution with a pore diameter of ∼4.9 Å. Two functionalities are proposed for this new compound: the basic amine groups provide higher affinity to acidic CO2 molecules than N2 and CH4 based on a thermodynamic mechanism which is demonstrated by the single component measurements and binary gas mixture breakthrough experiments; the pore aperture is optimal for the kinetic separation of n‐butane and iso‐butane which have kinetic diameters of 4.3 and 5.0 Å, respectively, which is confirmed from the pressure decay measurements and the breakthrough experiment. The new MOF is promising to simultaneously confront the challenges in both CO2 capture and the separation of n‐butane from iso‐butane in industrial practice. A stable amine‐functionalized microporous metal–organic framework was used to thermodynamically capturing CO2 from flue gas/natural gas and kinetically separating n‐butane from iso‐butane. [ABSTRACT FROM AUTHOR]

Abstract: Toxin B (TcdB) is a major pathogenic factor of Clostridum difficile. However, the mechanism by which TcdB exerts its cytotoxic action in host cells is still not completely known. Herein, we report for the first time that TcdB induced autophagic cell death in cultured human colonocytes. The induction of autophagy was demonstrated by the increased levels of LC3‐II, formation of LC3+ autophagosomes, accumulation of acidic vesicular organelles and reduced levels of the autophagic substrate p62/SQSTM1. TcdB‐induced autophagy was also accompanied by the repression of phosphoinositide 3‐kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) complex 1 activity. Functionally, pharmacological inhibition of autophagy by wortmannin or chloroquine or knockdown of autophagy‐related genes Beclin 1, Atg5 and Atg7 attenuated TcdB‐induced cell death in colonocytes. Genetic ablation of Atg5, a gene required for autophagosome formation, also mitigated the cytotoxic effect of TcdB. In conclusion, our study demonstrated that autophagy serves as a pro‐death mechanism mediating the cytotoxic action of TcdB in colonocytes. This discovery suggested that blockade of autophagy might be a novel therapeutic strategy for C. difficile infection. [ABSTRACT FROM AUTHOR]

Abstract: The incidence of Crohn's disease is increasing in many Asian countries, but considerable differences in genetic susceptibility have been reported between Western and Asian populations. This study aimed to fine‐map 23 previously reported Crohn's disease genes and identify their interactions in the Chinese population by Illumina‐based targeted capture sequencing. Our results showed that the genetic polymorphism A>G at rs144982232 in MST1 showed the most significant association (P = 1.78 × 10−5; odds ratio = 4.87). JAK2 rs1159782 (T>C) was also strongly associated with Crohn's disease (P = 2.34 × 10−4; odds ratio = 3.72). Gene‐gene interaction analysis revealed significant interactions between MST1 and other susceptibility genes, including NOD2, MUC19 and ATG16L1 in contributing to Crohn's disease risk. Main genetic associations and gene‐gene interactions were verified using ImmunoChip data set. In conclusion, a novel susceptibility locus in MST1 was identified. Our analysis suggests that MST1 might interact with key susceptibility genes involved in autophagy and bacterial recognition. These findings provide insight into the genetic architecture of Crohn's disease in Chinese and may partially explain the disparity of genetic signals in Crohn's disease susceptibility across different ethnic populations by highlighting the contribution of gene‐gene interactions. [ABSTRACT FROM AUTHOR]

Context The diagnosis of congenital hypogonadotropic hypogonadism ( CHH) in prepuberty has always been challenging. Here, we aimed at studying the clinical and genetic features of paediatric CHH, especially the phenotype of hypospadias and dual defects (patients showing hypothalamic and/or pituitary defects and testicular hypoplasia), so as to have a better understanding of CHH. Design The clinical and genetic features of patients with CHH were analysed, and the relationships between hypospadias, dual defects and genetics were investigated. Patients Patients who visited Beijing Children's Hospital and were positively diagnosed with CHH. Measurements The collected data included sex hormones, MRI of the olfactory bulb, human chorionic gonadotrophin ( hCG) test and genetic testing. We analysed clinical features and genetic results, especially hypospadias and dual defects, and compared the stimulated testosterone (T) levels in patients with and without cryptorchidism. Results Sixty-four patients were positively diagnosed, and forty-seven (73.4%) had Kallmann syndrome ( KS). Four patients (6.3%) had hypospadias, including 2 KS. Micropenis combined with cryptorchidism was the most common phenotype (39%). Approximately two-third of patients showed a poor response to hCG; 15 cases were diagnosed with dual defects, and there were no significant differences between those with and without cryptorchidism. Twenty-six cases (51%) of 51 patients were identified as having classical HH mutations, affecting 10 different genes, with oligogenic mutations in 5 cases (9.8%). The most common mutations were in PROKR2 (17.6%), FGFR1 (13.7%) and CHD7 (7.8%). The frequency of PROKR2 mutations was higher in dual HH when compared to other HH cases (6/15 vs 3/36, P = .021). Conclusions Micropenis and/or cryptorchidism can serve as important signs for the diagnosis of HH in paediatrics, and the coexistence of hypospadias does not exclude the diagnosis of CHH, including KS or normosmic isolated HH (nHH). Testicular function may be impaired earlier than expected, and PROKR2 mutations need to be evaluated to identify presumed dual defects. [ABSTRACT FROM AUTHOR]

Shale gas is an effective gas resource all over the world. The evaluation of pore structure plays a critical role in exploring shale gas efficiently. Nitrogen adsorption experiment is one of the significant approaches to analyze pore size structure of shale. Shale is extremely heterogeneous due to component diversity and structure complexity. Therefore, adsorption isotherms for homogeneous adsorbents and empirical isotherms may not apply to shale. The shape of adsorption-desorption curve indicates that nitrogen adsorption on shale includes monolayer adsorption, multilayer adsorption, and capillary condensation. Usually, Langmuir isotherm is a monolayer adsorption model for ideal interfaces; BET (Brunauer, Emmett, Teller) adsorption isotherm is a multilayer adsorption model based on specific assumptions; Freundlich isotherm is an empirical equation widely applied in liquid phase adsorption. In this study, a new nitrogen adsorption isotherm is applied to simultaneously depict monolayer adsorption, multilayer adsorption, and capillary condensation, which provides more real and accurate representation of nitrogen adsorption on shale. In addition, parameters are discussed in relation to heat of adsorption which is relevant to the shape of the adsorption isotherm curve. The curve fitting results indicate that our new nitrogen adsorption isotherm can appropriately describe the whole process of nitrogen adsorption on shale. [ABSTRACT FROM AUTHOR]

Microcystins (MCs), produced by freshwater cyanobacteria, can be serious water pollutants, so it is important to monitor their concentration in drinking water. We have developed a method for rapid and accurate determination of microcystin levels in environmental water, using magnetic solid-phase extraction and high-performance liquid chromatography with UV detection. The magnetic composite material, which was combined with cetylpyridinium chloride, was prepared by hydrothermal synthesis. The optimal extraction of microcystins in water sample was achieved by optimizing the amount of adsorbent, time of adsorption, ratio of eluting solvent, and volume of eluent. Under the optimal conditions, the limit of detection of MC-LR was 0.001 μg/L, and the limit of quantification was 0.0028 μg/L. The limit of detection of MC-RR was 0.001 μg/L, and the limit of quantification was 0.003 μg/L. These values are far lower than those established by the International Health Organization for the maximum concentration of microcystins in drinking water. The magnetic solid-phase extraction adsorbent used in this method has the advantages of simple preparation, low price, and easy solid-liquid separation, and it can be used for the rapid and sensitive monitoring of trace microcystins in environmental water samples. [ABSTRACT FROM AUTHOR]

Herein, we report the first case of successful term delivery of twins in a patient with bicorporeal septate uterus via natural conception. The patient had been diagnosed with complete septate, didelphys and bicornuate uterus during different phases of her three pregnancies. Based on follow-up data at six weeks and then six months post-partum of the last pregnancy, we found that the abnormalities presented in our case did not fit the criteria of any categories following American Fertility Society and European Society of Human Reproduction and Embryology-European Society for Gynaecological Endoscopy classification systems. After comprehensive review of the uterine morphologic characteristics, embryology and pregnancy outcome, we considered 'bicorporeal septate uterus' the most appropriate diagnosis. This case emphasized the atypical changes of uterine shape as twin pregnancy advances and its influence on productive performance and pregnancy outcome in uterine malformation. It also raised concern regarding the usability and comprehensiveness of the two most popular classification systems. [ABSTRACT FROM AUTHOR]

Many studies showed that RhoC-GTPases are central molecules in oncogenic transformation. The expression of RhoC is significantly increased in hepatocellular carcinoma (HCC). HBV is the major risk factor for HCC. However, it is unknown whether HBV regulating RhoC expression. In this study, we showed the RhoC expression was significantly higher in HepG2.2.15 than that in HepG2 cells. HBV could up-regulate RhoC expression through enhancing the activity of its promoter, and HBs and HBx may involve in this process. After silencing HBs and HBx expressions by using RNA interference, the expression of RhoC in HepG2.2.15 cells could be obviously inhibited. These results would provide useful information for understanding mechanism of HCC induced by HBV infection. [ABSTRACT FROM AUTHOR]

Recent genome-wide association study (GWAS) has identified that the prostate stem cell antigen ( PSCA) rs2294008 is involving in regulating gastric epithelial-cell proliferation, influencing the risk of diffuse-type gastric cancer. We hypothesized that PSCA rs2294008 is also associated with gastric cancer survival. We genotyped PSCA rs2294008 using TaqMan method in 943 patients with surgically resected gastric cancer. Analyses of genotype association with survival outcomes were assessed by the Kaplan-Meier method, Cox proportional hazards models and the log-rank test. There was no significant association between rs2294008 and survival of gastric cancer (log-rank p = 0.085 for CT/TT versus CC). However, in the stratification analysis of histology, we found that rs2294008 CT/TT genotypes were associated with significantly improved survival among diffuse-type gastric cancer (log-rank p = 0.025, hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.59-0.96), compared to the CC genotype. Moreover, this protective effect was more predominant for diffuse-type gastric cancer patients with tumor size >5 cm and distant metastasis. If validated in further studies, PSCA rs2294008 could be useful marker of survival assessment and individualized clinical therapy for gastric cancer, particularly among the diffuse-type gastric cancer. [ABSTRACT FROM AUTHOR]

( Cancer Sci 2010; 101: 782–786) Methylenetetrahydrofolate reductase (MTHFR), involved in DNA methylation and nucleotide synthesis, is thought to be associated with a decreased risk of adult and childhood acute lymphoblastic leukemia (ALL). Accumulating evidence has indicated that two common genetic variants, C677T and A1298C, are associated with cancer risk. We hypothesized that these two variants were associated with childhood ALL susceptibility and influence serum MTHFR levels. We genotyped these two polymorphisms and detected MTHFR levels in a case–control study of 361 cases and 508 controls. Compared with the 677CC and 677CC/CT genotypes, the 677TT genotype was associated with a statistically significantly decreased risk of childhood ALL (odds ratio = 0.53, 95% confidence interval = 0.32–0.88, and odds ratio = 0.55, 95% confidence interval = 0.35–0.88, respectively). In addition, a pronounced reduced risk of ALL was observed among low-risk ALL and B-phenotype ALL. Moreover, the mean serum MTHFR level was 8.01 ng/mL (±4.38) in cases and 9.27 ng/mL (±4.80) in controls ( P < 0.001). MTHFR levels in subjects with 677TT genotype was significantly higher than those with 677CC genotype ( P = 0.010) or 677CT genotype ( P = 0.043) in controls. In conclusion, our results provide evidence that the MTHFR polymorphisms might contribute to reduced childhood ALL risk in this population. [ABSTRACT FROM AUTHOR]

Runt-related transcription factor 3 ( RUNX3) is a well known gene for its functions in gastric cancer suppression, but the effect of its genetic variations on the risk of gastric cancer remains unclear. In this study, ten tagging single nucleotide polymorphisms (tSNPs) of the RUNX3 gene were selected and genotyped in a hospital-based case-control study of 312 gastric cancer patients and 329 cancer-free controls in a Chinese population. In the single-locus analysis, three RUNX3 intronic tSNPs associated with significantly increased risk of gastric cancer were observed: the SNP3 rs11249206 CC genotype (adjusted odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.03–2.99), compared with the TT genotype; the SNP7 rs760805 AA genotype (adjusted OR = 1.82, 95% CI = 1.14–2.92), compared with the TT genotype; and the SNP8 rs2236852 GG genotype (adjusted OR = 1.69, 95% CI = 1.05–2.72), compared with the AA genotype. In the combined analyses of these three tSNPs, we found that the combined genotypes with four to six variant (risk) alleles (i.e. SNP3 C, SNP7 A, and SNP8 G alleles) were associated with an increased risk of gastric cancer compared with those with one to three variant (risk) alleles (adjusted OR = 2.00, 95% CI = 1.41–2.85), and this increased risk was more pronounced among subgroups of age ≥65 years, never smokers, and never drinkers. However, no significant association was observed in the clinicopathological features analyses. In conclusion, the RUNX3 genetic variants may modulate the risk of gastric cancer in a Chinese population. Further larger and functional studies are warranted to validate the findings. ( Cancer Sci 2009; 100: 1688–1694) [ABSTRACT FROM AUTHOR]

The incidence of Crohn's disease is increasing in many Asian countries, but considerable differences in genetic susceptibility have been reported between Western and Asian populations. This study aimed to fine-map 23 previously reported Crohn's disease genes and identify their interactions in the Chinese population by Illumina-based targeted capture sequencing. Our results showed that the genetic polymorphism A>G at rs144982232 in MST1 showed the most significant association (P = 1.78 × 10 -5 ; odds ratio = 4.87). JAK2 rs1159782 (T>C) was also strongly associated with Crohn's disease (P = 2.34 × 10 -4 ; odds ratio = 3.72). Gene-gene interaction analysis revealed significant interactions between MST1 and other susceptibility genes, including NOD2, MUC19 and ATG16L1 in contributing to Crohn's disease risk. Main genetic associations and gene-gene interactions were verified using ImmunoChip data set. In conclusion, a novel susceptibility locus in MST1 was identified. Our analysis suggests that MST1 might interact with key susceptibility genes involved in autophagy and bacterial recognition. These findings provide insight into the genetic architecture of Crohn's disease in Chinese and may partially explain the disparity of genetic signals in Crohn's disease susceptibility across different ethnic populations by highlighting the contribution of gene-gene interactions., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Toxin B (TcdB) is a major pathogenic factor of Clostridum difficile. However, the mechanism by which TcdB exerts its cytotoxic action in host cells is still not completely known. Herein, we report for the first time that TcdB induced autophagic cell death in cultured human colonocytes. The induction of autophagy was demonstrated by the increased levels of LC3-II, formation of LC3 + autophagosomes, accumulation of acidic vesicular organelles and reduced levels of the autophagic substrate p62/SQSTM1. TcdB-induced autophagy was also accompanied by the repression of phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) complex 1 activity. Functionally, pharmacological inhibition of autophagy by wortmannin or chloroquine or knockdown of autophagy-related genes Beclin 1, Atg5 and Atg7 attenuated TcdB-induced cell death in colonocytes. Genetic ablation of Atg5, a gene required for autophagosome formation, also mitigated the cytotoxic effect of TcdB. In conclusion, our study demonstrated that autophagy serves as a pro-death mechanism mediating the cytotoxic action of TcdB in colonocytes. This discovery suggested that blockade of autophagy might be a novel therapeutic strategy for C. difficile infection., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)