The recent discovery of Dirac semimetals represents a new achievement in our fundamental understanding of topological states of matter. Due to their topological surface states, high mobility, and exotic properties associated with bulk Dirac points, these new materials have attracted significant attention and are believed to hold great promise for fabricating novel topological devices. For nanoscale device applications, effects from finite size usually play an important role. In this report, we theoretically investigate the electronic properties of Dirac semimetal nanostructures. Quantum confinement generally opens a bulk band gap at the Dirac points. We find that confinement along different directions shows strong anisotropic effects. In particular, the gap due to confinement along vertical c-axis shows a periodic modulation, which is absent for confinement along horizontal directions. We demonstrate that the topological surface states could be controlled by lateral electrostatic gating. It is possible to generate Rashba-like spin splitting for the surface states and to shift them relative to the confinement-induced bulk gap. These results will not only facilitate our fundamental understanding of Dirac semimetal nanostructures, but also provide useful guidance for designing all-electrical topological spintronics devices.

Diabetes Mellitus (DM)-induced bladder dysfunction is predominantly due to the long-term oxidative stress caused by hyperglycemia. Grape seed proanthocyanidin extract (GSPE) has been reported to possess a broad spectrum of pharmacological and therapeutic properties against oxidative stress. However, its protective effects against diabetic bladder dysfunction have not been clarified. This study focuses on the effects of GSPE on bladder dysfunction in diabetic rats induced by streptozotocin. After 8 weeks of GSPE administration, the bladder function of the diabetic rats was improved significantly, as indicated by both urodynamics analysis and histopathological manifestation. Moreover, the disordered activities of antioxidant enzymes (SOD and GSH-Px) and abnormal oxidative stress levels were partly reversed by treatment with GSPE. Furthermore, the level of apoptosis in the bladder caused by DM was decreased following the administration of GSPE according to the Terminal Deoxynucleotidyl Transferase (TdT)-mediated dUTP Nick-End Labeling (TUNEL) assay. Additionally, GSPE affected the expression of apoptosis-related proteins such as Bax, Bcl-2 and cleaved caspase-3. Furthermore, GSPE showed neuroprotective effects on the bladder of diabetic rats, as shown by the increased expression of nerve growth factor (NGF) and decreased expression of the precursor of nerve growth factor (proNGF). GSPE also activated nuclear erythroid2-related factor2 (Nrf2), which is a key antioxidative transcription factor, with the concomitant elevation of downstream hemeoxygenase-1 (HO-1). These findings suggested that GSPE could ameliorate diabetic bladder dysfunction and decrease the apoptosis of the bladder in diabetic rats, a finding that may be associated with its antioxidant activity and ability to activate the Nrf2 defense pathway.

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Long-term high salt intake exerts a negative impact on human health. The excessive use of sodium substitutes in the food industry can lead to decreased sensory quality of food. γ-Glutamyl peptides with pronounced taste-enhancing effects can offer an alternative approach to salt reduction. However, the content and yield of γ-glutamyl peptides in natural foods are relatively low. Enzyme-catalyzed synthesis of γ-glutamyl peptides provides a feasible solution. In this study, Pleurotus geesteranus was hydrolyzed by Flavourzyme to generate protein hydrolysates. Subsequently, they were modified by Bacillus amyloliquefaciens γ-glutamyl transpeptidase to generate γ-glutamyl peptides. The reaction conditions were optimized and their taste-enhancing effects were evaluated. Their peptide sequences were identified by parallel reaction monitoring with liquid chromatography–tandem mass spectrometry and analyzed using molecular docking. The optimal conditions for generation of γ-glutamyl peptides were a pH of 10.0, an enzyme condition of 1.2 U/g, and a reaction time of 2 h, which can elicit a strong kokumi taste. Notably, it exhibited a remarkable taste-enhancing effect for umami intensity (76.07%) and saltiness intensity (1.23-fold). Several novel γ-glutamyl peptide sequences were found by liquid chromatography–tandem mass spectrometry, whereas the binding to the calcium-sensing receptor was confirmed by molecular docking analysis. Overall, γ-glutamyl peptides from P. geesteranus could significantly enhance the umami and salt tastes, which can serve as promising taste enhancers.

We propose a graphene-based full valley- and spin-polarization device based on strained graphene with Rashba spin orbit coupling and magnetic barrier. The underlying mechanism is the coexistence of the valley and single spin band gaps in a certain Fermi energy. By aligning the Fermi energy in the valley and single spin band gaps, remarkable valley- and spin-polarization currents can be accessed.

Background Prostate cancer (PCa) shows racial disparity in clinical and genomic characteristics, and Asian patients with PCa often present with more aggressive phenotypes at diagnosis. The ability of TP53 to serve as a prognostic biomarker of PCa has been well studied in Western populations. However, no studies to date have examined the role of TP53 in the disparities of primary hormone-naïve prostate cancer (HNPC) between Chinese and Western populations. Methods We collected prostate tumors and matched normal tissues or blood samples to perform targeted next-generation sequencing of 94 Chinese primary localized HNPC samples, and correlated these genomic profiles with clinical outcomes. The OncoKB knowledge database was used to identify and classify actionable alterations. Results The aberrations of PTEN, CDK12, and SPOP in Chinese HNPC samples were similar to those in the Western samples. However, we demonstrated an association of a high frequency of TP53 alterations (21/94) with a relatively higher percentage of alterations in the Wnt signaling pathway (15/94) in Chinese HNPC. Additionally, we highlighted alterations of LRP1B as accounting for a high proportion of PCa and found more frequent alterations in CDH1 in Chinese PCa. Of these, only CDH1 alteration was associated with rapid biochemical recurrence (BCR). However, we verified that TP53 status was at the core of the genomic alteration landscape in Chinese HNPC with putative driver mutations because of the strong connections with other signaling pathways. The mutually exclusive relationship between alterations in TP53 and Wnt/ CTNNB1 further molecularly characterizes subsets of prostate cancers. Moreover, the alteration of KMT2C was more likely to co-occur with TP53 alteration, indicating a more aggressive phenotype of PCa, which was associated with sensitivity to treatment with poly ADT-ribose polymerase (PARP) inhibitors. Conclusions Detection of TP53 alterations has clinical utility for guiding precision cancer therapy for HNPC, especially in the Chinese population.

Background: Trametes robiniophila Murr (Huaier) has been used as an adjuvant therapy of tumor in traditional Chinese medicine for many years, but the underlying mechanisms are largely unknown. In the present study, we tested the inhibitory effect of Huaier extract on renal cancer 786-O cells and explored the possible mechanisms. Methods: 786-O cells were treated by gradient concentrations of Huaier extract, cell viability, invasion, migration and apoptosis were assessed by cell counting kit 8, cell scratch, transwell, and flow cytometry assay in vitro. The changes in protein level were detected by western blot analysis. Finally, the anticancer effect of Huaier was tested in vivo by nude mouse tumorigenicity assay. Results: Viability of 786-O cells was suppressed by Huaier in a time- and dose-dependent manner; cell invasion and migration were also dramatically inhibited. Flow cytometry assays showed that Huaier could induce cell apoptosis. Western blotting analysis indicated that Huaier suppressed the activation of PI3K/AKT/mTOR/p70S6K/4E-BP1 signaling pathway. We also found that Huaier could partly reverse the epithelialmesenchymal transition (EMT) process. In vivo experiment indicated that tumor growth in the xenograft mouse model was suppressed by Huaier. Conclusion: Huaier plays an anticancer effect partially through the suppression of the PI3K/AKT/mTOR/p70S6K/4E-BP1 pathway and by reversing the EMT process. Huaier may act as an effective agent for treating renal cell carcinoma.

Background The ETS transcription factor GABPA has long been thought of as an oncogenic factor and recently suggested as a target for cancer therapy due to its critical effect on telomerase activation, but the role of GABPA in clear cell renal cell carcinoma (ccRCC) is unclear. In addition, ccRCC is characterized by metabolic reprograming with aberrant accumulation of L-2-hydroxyglurate (L-2HG), an oncometabolite that has been shown to promote ccRCC development and progression by inducing DNA methylation, however, its downstream effectors remain poorly defined. Methods siRNAs and expression vectors were used to manipulate the expression of GABPA and other factors and to determine cellular/molecular and phenotypic alterations. RNA sequencing and ChIP assays were performed to identify GABPA target genes. A human ccRCC xenograft model in mice was used to evaluate the effect of GABPA overexpression on in vivo tumorigenesis and metastasis. ccRCC cells were incubated with L-2-HG to analyze GABPA expression and methylation. We carried out immunohistochemistry on patient specimens and TCGA dataset analyses to assess the effect of GABPA on ccRCC survival. Results GABPA depletion, although inhibiting telomerase expression, robustly enhanced proliferation, invasion and stemness of ccRCC cells, whereas GABPA overexpression exhibited opposite effects, strongly inhibiting in vivo metastasis and carcinogenesis. TGFBR2 was identified as the GABPA target gene through which GABPA governed the TGFβ signaling to dictate ccRCC phenotypes. GABPA and TGFBR2 phenocopies each other in ccRCC cells. Higher GABPA or TGFBR2 expression predicted longer survival in patients with ccRCC. Incubation of ccRCC cells with L-2-HG mimics GABPA-knockdown-mediated phenotypic alterations. L-2-HG silenced the expression of GABPA in ccRCC cells by increasing its methylation. Conclusions GABPA acts as a tumor suppressor by stimulating TGFBR2 expression and TGFβ signaling, while L-2-HG epigenetically inhibits GABPA expression, disrupting the GABPA-TGFβ loop to drive ccRCC aggressiveness. These results exemplify how oncometabolites erase tumor suppressive function for cancer development/progression. Restoring GABPA expression using DNA methylation inhibitors or other approaches, rather than targeting it, may be a novel strategy for ccRCC therapy.