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Granulosa cells are crucial for the establishment and maintenance of bidirectional communication among oocytes. Various intercellular material exchange modes, including paracrine and gap junction, are used between them to achieve the efficient delivery of granulosa cell structural components, energy substrates, and signaling molecules to oocytes. Glucose metabolism and lipid metabolism are two basic energy metabolism pathways in granulosa cells; these are involved in the normal development of oocytes. Pyruvate, produced by granulosa cell glycolysis, is an important energy substrate for oocyte development. Granulosa cells regulate changes in intrafollicular hormone levels through the processing of steroid hormones to control the development process of oocytes. This article reviews the material exchange between oocytes and granulosa cells and expounds the significance of granulosa cells in the development of oocytes through both glucose metabolism and lipid metabolism. In addition, we discuss the effects of glucose and lipid metabolism on oocytes under pathological conditions and explore its relationship to polycystic ovary syndrome (PCOS). A series of changes were found in the endogenous molecules and ncRNAs that are related to glucose and lipid metabolism in granulosa cells under PCOS conditions. These findings provide a new therapeutic target for patients with PCOS; additionally, there is potential for improving the fertility of patients with PCOS and the clinical outcomes of assisted reproduction.

A bstract The Kramers-Wannier self-duality of critical quantum chains is examined from the perspective of model wave functions. We demonstrate, using the transverse-field Ising chain and the 3-state Potts chain as examples, that the symmetry operator for the Kramers-Wannier self-duality follows in a simple and direct way from a ‘generalised’ translation symmetry of the model wave function in the anyonic fusion basis. This translation operation, in turn, comprises a sequence of F -moves in the underlying fusion category. The symmetry operator thus obtained naturally admits the form of a matrix product operator and obeys non-invertible fusion rules. The findings reveal an intriguing connection between the (non-invertible) translation symmetry on the lattice and topological aspects of the conformal field theory describing the scaling limit.

Esophageal squamous dysplasia is believed to be the precursor lesion of esophageal squamous cell carcinoma (ESCC); however, the genetic evolution from dysplasia to ESCC remains poorly understood. Here, we applied multi-region whole-exome sequencing to samples from two cohorts, 45 ESCC patients with matched dysplasia and carcinoma samples, and 13 tumor-free patients with only dysplasia samples. Our analysis reveals that dysplasia is heavily mutated and harbors most of the driver events reported in ESCC. Moreover, dysplasia is polyclonal, and remarkable heterogeneity is often observed between tumors and their neighboring dysplasia samples. Notably, copy number alterations are prevalent in dysplasia and persist during the ESCC progression, which is distinct from the development of esophageal adenocarcinoma. The sharp contrast in the prevalence of the ‘two-hit’ event on TP53 between the two cohorts suggests that the complete inactivation of TP53 is essential in promoting the development of ESCC. The pathogenesis of oesophageal squamous cell carcinoma is a multi-step process but the genetic determinants behind this progression are unknown. Here the authors use multi-region exome sequencing to comprehensively investigate the genetic evolution of precursor dysplastic lesions and untransformed oesophagus.

Background Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) present unique molecular signatures, but the tumorigenesis of EBVaGCs and the role EBV plays during this process remain poorly understood. Methods We applied whole-exome sequencing, EBV genome sequencing, and whole-genome bisulfite sequencing to multiple samples ( n = 123) derived from the same patients ( n = 25), which covered saliva samples and different histological stages from morphologically normal epithelial tissues to dysplasia and EBVaGCs. We compared the genomic landscape between EBVaGCs and their precursor lesions and traced the clonal evolution for each patient. We also analyzed genome sequences of EBV from samples of different histological types. Finally, the key molecular events promoting the tumor evolution were demonstrated by MTT, IC50, and colony formation assay in vitro experiments and in vivo xenograft experiments. Results Our analysis revealed increasing mutational burden and EBV load from normal tissues and low-grade dysplasia (LD) to high-grade dysplasia (HD) and EBVaGCs, and oncogenic amplifications occurred late in EBVaGCs. Interestingly, within each patient, EBVaGCs and HDs were monoclonal and harbored single-strain-originated EBV, but saliva or normal tissues/LDs had different EBV strains from that in EBVaGCs. Compared with precursor lesions, tumor cells showed incremental methylation in promotor regions, whereas EBV presented consistent hypermethylation. Dominant alterations targeting the PI3K-Akt and Wnt pathways were found in EBV-infected cells. The combinational inhibition of these two pathways in EBV-positive tumor cells confirmed their synergistic function. Conclusions We portrayed the (epi) genomic evolution process of EBVaGCs, revealed the extensive genomic diversity of EBV between tumors and normal tissue sites, and demonstrated the synergistic activation of the PI3K and Wnt pathways in EBVaGCs, offering a new potential treatment strategy for this disease.

Tensile fatigue tests were designed to study the relation between the tangential magnetic memory signal and dislocations. According to experimental results, in the early stage of fatigue, the magnetic signal and the dislocation density rapidly increase; while in the middle stage, the magnetic signal gradually increases, the dislocation density remains steady, and only the dislocation structure develops. On the other hand, in the later stage, the magnetic signal once again increases rapidly, the dislocation structure continues to develop, and microscopic cracks are formed. Analysis reveals that the dislocations block the movement of the domain wall, and the area of dislocation accumulation thus becomes an internal magnetic source and scatters a field outward. In addition, the magnetic memory field strengthens with increasing dislocation density and complexity of the dislocation structure. Accordingly, the dislocation pinning factor related with the dislocation density and the dislocation structure has been proposed to characterize the effect of dislocations on the magnetic memory signal. The magnetic signal strengthens with an increase in the dislocation pinning factor.

Based on the Gurson-Tvergaard-Needleman （GTN） model and Hill＇s quadratic anisotropic yield criterion, a combined experimental-numerical study on fracture initiation in the process of thermal stamping of Mg alloy AZ31 sheets was carried out. The aim is to predict the formability of thermal stamping of the Mg alloy sheets at different temperatures. The presented theoretical framework was implemented into a VUMAT subroutine for ABAQUS/EXPLICIT. Internal damage evolution due to void growth and coalescence developed at different temperatures in the Mg alloy sheets was observed by scanning electron microscopy （SEM）. Moreover, the thermal effects on the void growth, coalescence, and fracture behavior of the Mg alloy sheets were analyzed by the extended GTN model and forming limit diagrams （FLD）. Parameters employed in the GTN model were determined from tensile tests and numerical iterative computation. The distribution of major and minor principal strains in the specimens was determined from the numerical results. Therefore, the corresponding forming limit diagrams at different stress levels and temperatures were drawn. The comparison between the predicted forming limits and the experimental data shows a good agreement.

SET7, serving as the only histone methyltransferase that monomethylates ‘Lys-4’ of histone H3, has been proved to function as a key regulator in diverse biological processes, such as cell proliferation, transcriptional network regulation in embryonic stem cell, cell cycle control, protein stability, heart morphogenesis and development. What′s more, SET7 is involved inthe pathogenesis of alopecia aerate, breast cancer, tumor and cancer progression, atherosclerosis in human carotid plaques, chronic renal diseases, diabetes, obesity, ovarian cancer, prostate cancer, hepatocellular carcinoma, and pulmonary fibrosis. Therefore, there is urgent need to develop novel SET7 inhibitors. In this paper, based on DC-S239 which has been previously reported in our group, we employed scaffold hopping- and 2D fingerprint-based similarity searches and identified DC-S285 as the new hit compound targeting SET7 (IC50 = 9.3 μM). Both radioactive tracing and NMR experiments validated the interactions between DC-S285 and SET7 followed by the second-round similarity search leading to the identification ofDC-S303 with the IC50 value of 1.1 μM. In cellular level, DC-S285 retarded tumor cell proliferation and showed selectivity against MCF7 (IC50 = 21.4 μM), Jurkat (IC50 = 2.2 μM), THP1 (IC50 = 3.5 μM), U937 (IC50 = 3.9 μM) cell lines. Docking calculations suggested that DC-S303 share similar binding mode with the parent compoundDC-S239. What′s more, it presented good selectivity against other epigenetic targets, including SETD1B, SETD8, G9a, SMYD2 and EZH2. DC-S303 can serve as a drug-like scaffold which may need further optimization for drug development, and can be used as chemical probe to help the community to better understand the SET7 biology.

Overload-exercise （OE） causes myocardial injury through inducing autophagy and apoptosis. In this study we examined whether an autophagy inhibitor 3-methyladenine （3-MA） could alleviate OE-induced cardiac injury. Rats were injected with 3-MA （15 mg/kg, iv） or saline before subjected to various intensities of OE, including no swim （control）, 2 h swim （mild-intensity exercise, MIE）, 2 h swim with 2.5% body weight overload （moderate OE; MOE）, 5% overload （intensive OE; IOE） or 2.5% overload until exhausted （exhaustive OE; EOE）. After OE, the hearts were harvested for morphological and biochemiacal analysis. The cardiac morphology, autophagosomes and apoptosis were examined with H＆E staining, transmission electron microscopy and TUNEL analysis, respectively. Autophagyrelated proteins to （LC3-Ⅱ/Ⅰ and Beclin-1） and apoptosis-related proteins （Bci-2/Bax） were assessed using Western blotting. Our results showed that compared with the control, MIE did not change the morphological structures of the heart tissues that exhibited intact myocardial fibers and neatly arranged cardiomyocytes. However, IOE resulted in irregular arrangement of cardiomyocytes and significantly increased width of cardiomyocytes, whereas EOE caused more swollen and even disrupted cardiomyocytes. In parallel with the increased OE intensity （MOE, IOE, EOE）, cardiomyocyte autophagy and apoptosis became more and more prominent, evidenced by the increasing number of autophagosomes and expression levels of LC3-Ⅱ/Ⅰ and Beclin-1 as well as the increasing apoptotic cells and decreasing Bcl-2/Bax ratio. 3-MA administration significantly attenuated OE-induced morphological changes of cardiomyocytes as well as all the autophagy- and apoptosis-related abnormalities in MOE, IOE and EOE rats. Thus, the autophagy inhibitor 3-MA could alleviate OE-induced heart injury in rats.

Histone deacetylases (HDACs), especially HDAC1, 2, 3 and 4, are abundantly expressed and over-activated in prostate cancer that is correlated with the poor prognosis. Thus, inhibition of HDAC activity has emerged as a potential alternative option for prostate cancer therapy. Chromopeptide A is a depsipeptide isolated from the marine sediment-derived bacterium Chromobacterium sp. HS-13-94; it has a chemical structure highly similar to FK228, a class I HDAC inhibitor that is approved by FDA for treating T-cell lymphoma. In this study, we determined whether chromopeptide A, like FK228, acted as a class I HDAC inhibitor, and whether chromopeptide A could inhibit the growth and migration of human prostate cancer in vitro and in vivo . HDAC enzyme selectivity and kinetic analysis revealed that chromopeptide A selectively inhibited the enzymatic activities of HDAC1, 2, 3 and 8 in a substrate non-competitive manner with comparable IC 50 values for each HDAC member as FK228 in vitro . Importantly, chromopeptide A dose-dependently suppressed the proliferation of human prostate cancer cell lines PC3, DU145 and LNCaP with IC 50 values of 2.43±0.02, 2.08±0.16, and 1.75±0.06 nmol/L, respectively, accompanied by dose-dependent inhibition of HDAC enzymatic activity in PC3 and DU145 cells. Chromopeptide A (0.2–50 nmol/L) caused G 2 /M phase arrest and induced apoptosis in the prostate cancer cell lines. Moreover, chromopeptide A dose-dependently inhibited the migration of PC3 cells. In mice bearing PC3 prostate cancer xenografts, intravenous injection of chromopeptide A (1.6, 3.2 mg/kg, once a week for 18 d) significantly suppressed the tumor growth, which was associated with increased expression levels of Ac-H3 and p21 in tumor tissues. Our results identify chromopeptide A as a novel class I HDAC inhibitor and provide therapeutic strategies that may be implemented in prostate cancer.

Background： Patients on hemodialysis have a high-mortality risk. Tiffs study analyzed factors associated with death in patients on maintenance hemodialysis （MHD）. While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to iliad the characteristics of patients preceding death.Methods： Participants were selected from 16 blood purification centers in China from January 2012 to December 2014, Patients＇ data were collected retrospectively. Based on survival status, the participants were divided into two groups： survival group and the death group. Logistic regression analysis was performed to determine/＇actors associated with all-cause mortality.