Pure spin current generation in a Rashba-Dresselhaus quantum channel

We demonstrate a spin pump to generate pure spin current of tunable intensity and polarization in the absence of charge current. The pumping functionality is achieved by means of an ac gate voltage that modulates the Rashba constant dynamically in a local region of a quantum channel with both static Rashba and Dresselhaus spin-orbit interactions. Spin-resolved Floquet scattering matrix is calculated to analyze the whole scattering process. Pumped spin current can be divided into spin-preserved transmission and spin-flip reflection parts. These two terms have opposite polarization of spin current and are competing with each other. Our proposed spin-based device can be utilized for non-magnetic control of spin flow by tuning the ac gate voltage and the driving frequency.Comment: 6 pages, 3 figure

Biological actions and molecular effects of resveratrol, pterostilbene, and 3′-hydroxypterostilbene

AbstractStilbenes are a class of polyphenolic compounds, naturally found in a wide variety of dietary sources such as grapes, berries, peanuts, red wine, and some medicinal plants. There are several well-known stilbenes including trans-resveratrol, pterostilbene, and 3′-hydroxypterostilbene. The core chemical structure of stilbene compounds is 1,2-diphenylethylene. Recently, stilbenes have attracted extensive attention and interest due to their wide range of health-beneficial effects such as anti-inflammation, -carcinogenic, -diabetes, and -dyslipidemia activities. Moreover, accumulating in vitro and in vivo studies have reported that stilbene compounds act as inducers of multiple cell-death pathways such as apoptosis, cell cycle arrest, and autophagy for chemopreventive and chemotherapeutic agents in several types of cancer cells. The aim of this review is to highlight recent molecular findings and biological actions of trans-resveratrol, pterostilbene, and 3′-hydroxypterostilbene

Targeted deletion of GSNOR in hepatocytes of mice causes nitrosative inactivation of O6-alkylguanine-DNA alkyltransferase and increased sensitivity to genotoxic diethylnitrosamine

S-nitrosoglutathione reductase (GSNOR), a ubiquitously expressed protein central to the control of protein S-nitrosylation, plays critical roles in many biological systems. We showed recently that GSNOR is often deficient in human hepatocellular carcinoma and that germ line deletion of the GSNOR gene in mice causes hepatocellular carcinoma through S-nitrosylation and proteasomal degradation of the key DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT). We report here the generation of mice with targeted deletion of GSNOR in hepatocytes or in cells of the hematopoietic lineage. We found that during inflammatory responses induced by intraperitoneal injection of diethylnitrosamine (DEN) or lipopolysaccharide, the amount of liver AGT was not changed in mice with GSNOR deletion in hematopoietic cells but was almost completely depleted in mice with GSNOR deletion in hepatocytes. In livers of DEN-challenged mice, GSNOR deletion in hepatocytes but not hematopoietic cells resulted in an increase in phosphorylated histone H2AX, a well-established marker of DNA double-strand breaks. Hepatocyte deletion of GSNOR increased DEN-induced mortality, which was abolished in mice deficient in both GSNOR and inducible nitric oxide synthase. Thus, protection of AGT and resistance to nitrosamine-induced genotoxicity critically depends on GSNOR in hepatocytes. In addition, our findings suggest that nitrosative inactivation of AGT from GSNOR deficiency might sensitize cancerous cells to alkylating drugs in cancer treatment

Major adverse cardiovascular events of enzalutamide versus abiraterone in prostate cancer: a retrospective cohort study.

Background While the cardiovascular risks of androgen receptor pathway inhibitors have been studied, they were seldom compared directly. This study compares the risks of major adverse cardiovascular events (MACE) between enzalutamide and abiraterone among prostate cancer (PCa) patients. Methods Adult PCa patients receiving either enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between 1 December 1999 and 31 March 2021 were identified in this retrospective cohort study. Patients who switched between enzalutamide and abiraterone, initiated abiraterone used without steroids, or experienced prior cardiac events were excluded. Patients were followed-up until 30 September 2021. The primary outcomes were MACE, a composite of stroke, myocardial infarction (MI), Heart failure (HF), or all-cause mortality and a composite of adverse cardiovascular events (CACE) not including all-cause mortality. The secondary outcomes were individual components of MACE. Inverse probability treatment weighting was used to balance covariates between treatment groups. Results In total, 1015 patients were analyzed (456 enzalutamide users and 559 abiraterone users; mean age 70.6 ± 8.8 years old) over a median follow-up duration of 11.3 (IQR: 5.3–21.3) months. Enzalutamide users had significantly lower risks of 4P-MACE (weighted hazard ratio (wHR) 0.71 [95% confidence interval (CI) 0.59–0.86], p < 0.001) and CACE (wHR 0.63 [95% CI: 0.42–0.96], p = 0.031), which remained consistent in multivariable analysis. Such an association may be stronger in patients aged ≥65 years or without diabetes mellitus and was independent of bilateral orchidectomy. Enzalutamide users also had significantly lower risks of MI (wHR 0.57 [95% CI: 0.33–0.97], p = 0.040) and all-cause mortality (wHR 0.71 [95% CI: 0.59–0.85], p < 0.001). Conclusion Enzalutamide was associated with lower cardiovascular risks than abiraterone in PCa patients

Association between duration of gonadotrophin-releasing hormone agonist use and cardiovascular risks: A population-based competing-risk analysis

Background Although androgen deprivation therapy has known cardiovascular risks, it is unclear if its duration is related to cardiovascular risks. This study thus aimed to investigate the associations between gonadotrophin-releasing hormone (GnRH) agonist use duration and cardiovascular risks. Methods This retrospective cohort study included adult patients with prostate cancer receiving GnRH agonists in Hong Kong during 1999–2021. Patients who switched to GnRH antagonists, underwent bilateral orchidectomy, had <6 months of GnRH agonist, prior myocardial infarction (MI), or prior stroke was excluded. All patients were followed up until September 2021 for a composite endpoint of MI and stroke. Multivariable competing-risk regression using the Fine-Gray subdistribution model was used, with mortality from any cause as the competing event. Results In total, 4038 patients were analyzed (median age 74.9 years old, interquartile range (IQR) 68.7–80.8 years old). Over a median follow-up of 4.1 years (IQR 2.1–7.5 years), longer GnRH agonists use was associated with higher risk of the endpoint (sub-hazard ratio per year 1.04 [1.01–1.06], p = 0.001), with those using GnRH agonists for ≥2 years having an estimated 23% increase in the sub-hazard of the endpoint (sub-hazard ratio 1.23 [1.04–1.46], p = 0.017). Conclusion Longer GnRH agonist use may be associated with greater cardiovascular risks

Post-stroke upper limb recovery is correlated with dynamic resting-state network connectivity

Motor recovery is still limited for people with stroke especially those with greater functional impairments. In order to improve outcome, we need to understand more about the mechanisms underpinning recovery. Task-unbiased, blood flow–independent post-stroke neural activity can be acquired from resting brain electrophysiological recordings and offers substantial promise to investigate physiological mechanisms, but behaviourally relevant features of resting-state sensorimotor network dynamics have not yet been identified. Thirty-seven people with subcortical ischaemic stroke and unilateral hand paresis of any degree were longitudinally evaluated at 3 weeks (early subacute) and 12 weeks (late subacute) after stroke. Resting-state magnetoencephalography and clinical scores of motor function were recorded and compared with matched controls. Magnetoencephalography data were decomposed using a data-driven hidden Markov model into 10 time-varying resting-state networks. People with stroke showed statistically significantly improved Action Research Arm Test and Fugl-Meyer upper extremity scores between 3 weeks and 12 weeks after stroke (both P < 0.001). Hidden Markov model analysis revealed a primarily alpha-band ipsilesional resting-state sensorimotor network which had a significantly increased life-time (the average time elapsed between entering and exiting the network) and fractional occupancy (the occupied percentage among all networks) at 3 weeks after stroke when compared with controls. The life-time of the ipsilesional resting-state sensorimotor network positively correlated with concurrent motor scores in people with stroke who had not fully recovered. Specifically, this relationship was observed only in ipsilesional rather in contralesional sensorimotor network, default mode network or visual network. The ipsilesional sensorimotor network metrics were not significantly different from controls at 12 weeks after stroke. The increased recruitment of alpha-band ipsilesional resting-state sensorimotor network at subacute stroke served as functionally correlated biomarkers exclusively in people with stroke with not fully recovered hand paresis, plausibly reflecting functional motor recovery processes

Statin use and mortality risk in Asian patients with prostate cancer receiving androgen deprivation therapy: A population-based cohort study

Background This study aimed to examine the associations between the use of statins concurrent with androgen deprivation therapy (ADT) and the risks of mortality in Asian patients diagnosed with prostate cancer (PCa). Methods Adult patients (≥18 years old) diagnosed with PCa who were receiving any form of ADT and were being treated at public hospitals in Hong Kong from December 1999 to March 2021 were retrospectively identified, with follow-up conducted until September 2021. Patients who had received medical castration for <180 days without subsequent bilateral orchidectomy, those who had used statins concurrently with ADT for <180 days, and those with missing baseline total cholesterol levels were excluded. Statin users were defined as individuals who had used statins for ≥180 days concurrent with ADT, while non-users were those who had not used any statins. PCa-related mortality was the primary outcome, while all-cause mortality served as the secondary outcome. Inverse probability treatment weighting was employed to balance the covariates. Results A total of 4920 patients were included, consisting of 2578 statin users and 2342 non-users (mean age 76.1 ± 8.2 years). Over a mean follow-up period of 4.2 ± 3.3 years, it was observed that statin users had significantly lower risks of both PCa-related mortality (weighted hazard ratio [wHR] 0.56 [95% confidence interval (CI) 0.48, 0.65], p < 0.001) and all-cause mortality (wHR 0.57 [95% CI 0.51, 0.63], p < 0.001), regardless of the type of ADT used. Notably, these associations were more pronounced among patients with less advanced PCa, as indicated by the absence of androgen receptor antagonist or chemotherapy usage (p value for interaction <0.001 for both outcomes). Conclusion(s) The use of statins concurrent with ADT was associated with reduced mortality risks among Asian patients with PCa. These findings suggest the need for additional research to explore the potential role of statins in the treatment of PCa patients

Spin Injection and Inverse Edelstein Effect in the Surface States of Topological Kondo Insulator SmB6

There has been considerable interest in exploiting the spin degrees of freedom of electrons for potential information storage and computing technologies. Topological insulators (TI), a class of quantum materials, have special gapless edge/surface states, where the spin polarization of the Dirac fermions is locked to the momentum direction. This spin-momentum locking property gives rise to very interesting spin-dependent physical phenomena such as the Edelstein and inverse Edelstein effects. However, the spin injection in pure surface states of TI is very challenging because of the coexistence of the highly conducting bulk states. Here, we experimentally demonstrate the spin injection and observe the inverse Edelstein effect in the surface states of a topological Kondo insulator, SmB6. At low temperatures when only surface carriers are present, a clear spin signal is observed. Furthermore, the magnetic field angle dependence of the spin signal is consistent with spin-momentum locking property of surface states of SmB6.Comment: 15 pages, 5 figures, Accepted to Nature Communications (In Press

Triggering Apoptotic Death of Human Malignant Melanoma A375.S2 Cells by Bufalin: Involvement of Caspase Cascade-Dependent and Independent Mitochondrial Signaling Pathways

Bufalin was obtained from the skin and parotid venom glands of toad and has been shown to induce cytotoxic effects in various types of cancer cell lines, but there is no report to show that whether bufalin affects human skin cancer cells. The aim of this investigation was to study the effects of bufalin on human malignant melanoma A375.S2 cells and to elucidate possible mechanisms involved in induction of apoptosis. A375.S2 cells were treated with different concentrations of bufalin for a specific time period and investigated for effects on apoptotic analyses. Our results indicated that cells after exposure to bufalin significantly decreased cell viability, and induced cell morphological changes and chromatin condensation in a concentration-dependent manner. Flow cytometric assays indicated that bufalin promoted ROS productions, loss of mitochondrial membrane potential (ΔΨm), intracellular Ca2+ release, and nitric oxide (NO) formations in A375.S2 cells. Additionally, the apoptotic induction of bufalin on A375.S2 cells resulted from mitochondrial dysfunction-related responses (disruption of the ΔΨm and releases of cytochrome c, AIF, and Endo G), and activations of caspase-3, caspase-8 and caspase-9 expressions. Based on those observations, we suggest that bufalin-triggered apoptosis in A375.S2 cells is correlated with extrinsic- and mitochondria-mediated multiple signal pathways