Blood-Pressure-Lowering and Endothelium-Dependent Vasorelaxant Effects of Nutgall Tree in Rats.

Hypertension is the crucial modifiable risk factor for cardiovascular diseases, and efforts to identify functional foods that are effective for hypertension control are increasing. The nutgall tree (NT, Rhus chinensis Mill.) is used in traditional medicine and food because of its medicinal value. However, the role of NT in hypertension has not been investigated. Therefore, the hypotensive effect of NT leaf ethanol extract (NTE) was investigated in spontaneously hypertensive rats (SHRs). SHRs were allocated to three groups (control, 300, or 1000 mg/kg NTE), and blood pressure was measured before and after oral administration. Systolic and diastolic blood pressure significantly decreased in the NTE 1000 mg/kg group and was the lowest at 2 h after administration (-26.4 ± 10.3, -33.5 ± 9.8%, respectively). Daily NTE administration for five days also resulted in a similar effect. Further, the vasorelaxant effects and related mechanisms were investigated in the aortas of Sprague Dawley rats. NTE showed the dose-dependent blood-vessel-relaxing effect, and its mechanism involves the NO-sGC-cGMP pathway, activation of K+ channels, and reduction in the vasoconstrictive action of angiotensin II. Therefore, our study provides basic data indicating the potential use of NTE as a functional food for high blood pressure.

Vasorelaxant and Blood Pressure-Lowering Effects of Cnidium monnieri Fruit Ethanol Extract in Sprague Dawley and Spontaneously Hypertensive Rats.

Cnidium monnieri (L.) Cusson, a member of the Apiaceae family, is rich in coumarins, such as imperatorin and osthole. Cnidium monnieri fruit (CM) has a broad range of therapeutic potential that can be used in anti-bacterial, anti-cancer, and sexual dysfunction treatments. However, its efficacy in lowering blood pressure through vasodilation remains unknown. This study aimed to assess the potential therapeutic effect of CM 50% ethanol extract (CME) on hypertension and the mechanism of its vasorelaxant effect. CME (1-30 µg/mL) showed a concentration-dependent vasorelaxation on constricted aortic rings in Sprague Dawley rats induced by phenylephrine via an endothelium-independent mechanism. The vasorelaxant effect of CME was inhibited by blockers of voltage-dependent and Ca2+-activated K+ channels. Additionally, CME inhibited the vascular contraction induced by angiotensin II and CaCl2. The main active compounds of CM, i.e., imperatorin (3-300 µM) and osthole (1-100 µM), showed a concentration-dependent vasorelaxation effect, with half-maximal effective concentration values of 9.14 ± 0.06 and 5.98 ± 0.06 µM, respectively. Orally administered CME significantly reduced the blood pressure of spontaneously hypertensive rats. Our research shows that CME is a promising treatment option for hypertension. However, further studies are required to fully elucidate its therapeutic potential.

Sakuranetin as a Potential Regulator of Blood Pressure in Spontaneously Hypertensive Rats by Promoting Vasorelaxation through Calcium Channel Blockade.

Natural compounds, known for diverse pharmacological properties, have attracted attention as potential sources for hypertension treatment. Previous studies have revealed the hypotensive effect and vascular relaxation of prunetin, a natural compound derived from Prunus yedoensis. However, the potential blood pressure-lowering and vasorelaxant effects of sakuranetin, another representative compound found in plants belonging to the genus Prunus, have remained unexplored. We aimed to fill this gap by investigating the hypotensive and vasorelaxant effects of sakuranetin in rats. Results indicated that sakuranetin, particularly in the sakuranetin 20 mg/kg group, led to significant reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) by -14.53 ± 5.64% and -19.83 ± 6.56% at 4 h after administration. In the sakuranetin 50 mg/kg group, the SBP and DBP decreased by -13.27 ± 6.86% and -16.62 ± 10.01% at 2 h and by -21.61 ± 4.49% and -30.45 ± 5.21% at 4 h after administration. In addition, we identified the vasorelaxant effects of sakuranetin, attributing its mechanisms to the inhibition of calcium influx and the modulation of angiotensin II. Considering its hypotensive and vasorelaxant effects, sakuranetin could potentially serve as an antihypertensive agent. However, further research is required to evaluate the safety and long-term efficacy.

Hormone Replacement Therapy and Risks of Various Cancers in Postmenopausal Women with De Novo or a History of Endometriosis.

This study examined the impact of hormone replacement therapy (HRT) on the occurrence of various cancers in postmenopausal women with de novo or a history of endometriosis. In the datasets for ten cancers (cervical, uterine, ovarian, breast, colon, gastric, liver, lung, pancreatic, and thyroid), women who received HRT (the HRT group) and those who did not (the control group) were selected by a 1:1 matching with those who met the study criteria. In the dataset for each cancer, the incidence of each cancer was very low (0.2% to 1.5% in the HRT group and 0.2% to 1.3% in the control group). The duration of HRT was 1.3 ± 2.1 years. After adjusting for co-variables, HRT was a significant risk factor for uterine cancer (p < 0.05). However, the risk of liver cancer decreased significantly with duration of HRT (p < 0.05). Moreover, combined estrogen and progesterone decreased the risks of liver and thyroid cancers significantly (p < 0.05), and estrogen alone decreased the risks of breast and lung cancers significantly (p < 0.05). Tibolone was not associated with the risk of any of the cancers assessed. These results can help guide the use of HRT in women with de novo or a history of endometriosis.

Field-free spin-orbit torque switching in ferromagnetic trilayers at sub-ns timescales.

Current-induced spin torques enable the electrical control of the magnetization with low energy consumption. Conventional magnetic random access memory (MRAM) devices rely on spin-transfer torque (STT), this however limits MRAM applications because of the nanoseconds incubation delay and associated endurance issues. A potential alternative to STT is spin-orbit torque (SOT). However, for practical, high-speed SOT devices, it must satisfy three conditions simultaneously, i.e., field-free switching at short current pulses, short incubation delay, and low switching current. Here, we demonstrate field-free SOT switching at sub-ns timescales in a CoFeB/Ti/CoFeB ferromagnetic trilayer, which satisfies all three conditions. In this trilayer, the bottom magnetic layer or its interface generates spin currents with polarizations in both in-plane and out-of-plane components. The in-plane component reduces the incubation time, while the out-of-plane component realizes field-free switching at a low current. Our results offer a field-free SOT solution for energy-efficient scalable MRAM applications.

Field-free switching of perpendicular magnetization by two-dimensional PtTe2/WTe2 van der Waals heterostructures with high spin Hall conductivity.

The key challenge of spin-orbit torque applications lies in exploring an excellent spin source capable of generating out-of-plane spins while exhibiting high spin Hall conductivity. Here we combine PtTe2 for high spin conductivity and WTe2 for low crystal symmetry to satisfy the above requirements. The PtTe2/WTe2 bilayers exhibit a high in-plane spin Hall conductivity σs,y ≈ 2.32 × 105 × h/2e Ω-1 m-1 and out-of-plane spin Hall conductivity σs,z ≈ 0.25 × 105 × h/2e Ω-1 m-1, where h is the reduced Planck's constant and e is the value of the elementary charge. The out-of-plane spins in PtTe2/WTe2 bilayers enable the deterministic switching of perpendicular magnetization at room temperature without magnetic fields, and the power consumption is 67 times smaller than that of the Pt control case. The high out-of-plane spin Hall conductivity is attributed to the conversion from in-plane spin to out-of-plane spin, induced by the crystal asymmetry of WTe2. Our work establishes a low-power perpendicular magnetization manipulation based on wafer-scale two-dimensional van der Waals heterostructures.

Hypotensive and Vasorelaxant Effects of Sanguisorbae Radix Ethanol Extract in Spontaneously Hypertensive and Sprague Dawley Rats.

Hypertension requires proper management because of the increased risk of cardiovascular disease and death. For this purpose, functional foods containing tannins have been considered an effective treatment. Sanguisorbae radix (SR) also contains various tannins; however, there have been no studies on its vasorelaxant or antihypertensive effects. In this study, the vasorelaxant effect of the ethanol extract of SR (SRE) was investigated in the thoracic aorta of Sprague Dawley rats. SRE (1, 3, 10, 30, and 100 µg/mL) showed this effect in a dose-dependent manner, and its mechanisms were related to the NO/cGMP pathway and voltage-gated K+ channels. Concentrations of 300 and 1000 µg/mL blocked the influx of extracellular Ca2+ and inhibited vasoconstriction. Moreover, 100 µg/mL of SRE showed a relaxing effect on blood vessels constricted by angiotensin II. The hypotensive effect of SRE was investigated in spontaneously hypertensive rats (SHR) using the tail-cuff method. Blood pressure significantly decreased 4 and 8 h after 1000 mg/kg of SRE administration. Considering these hypotensive effects and the vasorelaxant mechanisms of SRE, our findings suggests that SRE can be used as a functional food to prevent and treat hypertension. Further studies are needed for identifying the active components and determining the optimal dosage.

Evaluating the Efficacy of Tension Band Wiring Fixation for Chaput Tubercle Fractures.

BACKGROUND: Chaput tubercle fractures, located at the attachment site of the anterior inferior tibiofibular ligament (AITFL) on the distal tibia, have the potential to destabilize the syndesmosis joint. This study aims to assess the effectiveness of tension band wiring (TBW) as a surgical intervention for managing Chaput fractures and the consequent syndesmosis instability. METHODS: A retrospective review of patient charts was undertaken for those who had undergone ankle fracture surgery from April 2019 through May 2022. The surgical procedure involved direct fixation of the Chaput fractures using the TBW method. Radiological assessments were performed using postoperative simple radiographs and computed tomography (CT) scans, while clinical outcomes were evaluated using the Olerud-Molander Ankle Score (OMAS) and the visual analog scale (VAS). RESULTS: The study included 21 patients. The average OMAS improved significantly, rising from 5.95 preoperatively to 83.57 postoperatively. Similarly, the average VAS score dropped from 7.95 before the surgery to 0.19 thereafter. Minor wound complications were reported by three patients, and one case of superficial infection was resolved with antibiotic therapy. CONCLUSIONS: Our findings suggest that the TBW technique is an effective surgical approach for treating Chaput fractures and associated syndesmosis instability. It provides reliable fixation strength and leads to improved long-term functional outcomes. Further research is needed to compare the TBW technique with alternative methods and optimize the treatment strategies for these complex ankle fractures.

Spin current driven by ultrafast magnetization of FeRh.

Laser-induced ultrafast demagnetization is an important phenomenon that probes arguably the ultimate limits of the angular momentum dynamics in solid. Unfortunately, many aspects of the dynamics remain unclear except that the demagnetization transfers the angular momentum eventually to the lattice. In particular, the role and origin of electron-carried spin currents in the demagnetization process are debated. Here we experimentally probe the spin current in the opposite phenomenon, i.e., laser-induced ultrafast magnetization of FeRh, where the laser pump pulse initiates the angular momentum build-up rather than its dissipation. Using the time-resolved magneto-optical Kerr effect, we directly measure the ultrafast-magnetization-driven spin current in a FeRh/Cu heterostructure. A strong correlation between the spin current and the magnetization dynamics of FeRh is found even though the spin filter effect is negligible in this opposite process. This result implies that the angular momentum build-up is achieved by an angular momentum transfer from the electron bath (supplier) to the magnon bath (receiver) and followed by the spatial transport of angular momentum (spin current) and dissipation of angular momentum to the phonon bath (spin relaxation).

Escherichia coli RimI Encodes Serotonin N-Acetyltransferase Activity and Its Overexpression Leads to Enhanced Growth and Melatonin Biosynthesis.

Serotonin N-acetyltransferase (SNAT) functions as the penultimate or final enzyme in melatonin biosynthesis, depending on the substrate. The Escherichia coli orthologue of archaeal SNAT from Thermoplasma volcanium was identified as RimI (EcRimI), with 42% amino acid similarity to archaeal SNAT. EcRimI has been reported to be an N-acetyltransferase enzyme. Here, we investigated whether EcRimI also exhibits SNAT enzyme activity. To achieve this goal, we purified recombinant EcRimI and examined its SNAT enzyme kinetics. As expected, EcRimI showed SNAT activity toward various amine substrates including serotonin and 5-methoxytryptamine, with Km and Vmax values of 531 µM and 528 pmol/min/mg protein toward serotonin and 201 µM and 587 pmol/min/mg protein toward 5-methoxytryptamine, respectively. In contrast to the rimI mutant E. coli strain that showed no growth defect, the EcRimI overexpression strain exhibited a 2-fold higher growth rate than the control strain after 24 h incubation in nutrient-rich medium. The EcRimI overexpression strain produced more melatonin than the control strain in the presence of 5-methoxytryptamine. The enhanced growth effect of EcRimI overexpression was also observed under cadmium stress. The higher growth rate associated with EcRimI expression was attributed to increased protein N-acetyltransferase activity, increased synthesis of melatonin, or the combined effects of both.

Enhanced spin Seebeck effect via oxygen manipulation.

Spin Seebeck effect (SSE) refers to the generation of an electric voltage transverse to a temperature gradient via a magnon current. SSE offers the potential for efficient thermoelectric devices because the transverse geometry of SSE enables to utilize waste heat from a large-area source by greatly simplifying the device structure. However, SSE suffers from a low thermoelectric conversion efficiency that must be improved for widespread application. Here we show that the SSE substantially enhances by oxidizing a ferromagnet in normal metal/ferromagnet/oxide structures. In W/CoFeB/AlOx structures, voltage-induced interfacial oxidation of CoFeB modifies the SSE, resulting in the enhancement of thermoelectric signal by an order of magnitude. We describe a mechanism for the enhancement that results from a reduced exchange interaction of the oxidized region of ferromagnet, which in turn increases a temperature difference between magnons in the ferromagnet and electrons in the normal metal and/or a gradient of magnon chemical potential in the ferromagnet. Our result will invigorate research for thermoelectric conversion by suggesting a promising way of improving the SSE efficiency.

Human Naa50 Shows Serotonin N-Acetyltransferase Activity, and Its Overexpression Enhances Melatonin Biosynthesis, Resulting in Osmotic Stress Tolerance in Rice.

A new clade of serotonin N-acetyltransferase (SNAT), the penultimate enzyme in the melatonin biosynthetic pathway, has been reported in the archaeon Thermoplasma volcanium. The closest homolog of archaea SNAT in human was an N-alpha-acetyltransferase50 (Naa50). To determine whether human Naa50 (hNaa50) shows SNAT enzyme activity, we chemically synthesized and expressed the hNaa50 gene in Escherichia coli, followed by Ni2+ affinity purification. Purified recombinant hNaa50 showed SNAT activity (Km and Vmax values of 986 µM and 1800 pmol/min/mg protein, respectively). To assess its in vivo function, hNaa50 was overexpressed in rice (hNaa50-OE). The transgenic rice plants produced more melatonin than nontransgenic wild-type rice, indicating that hNaa50 is functionally coupled with melatonin biosynthesis. Due to its overproduction of melatonin, hNaa50-OE had a higher tolerance against osmotic stress than the wild type. Enhanced expression of the chaperone genes BIP1 and CNX in hNaa50-OE plants was responsible for the increased tolerance. It is concluded that hNaa50 harbors serotonin N-acetyltransferase enzyme activity in addition to its initial N-alpha-acetyltransferase, suggesting the bifunctionality of the hNaa50 enzyme toward serotonin and protein substrates. Consequently, ectopic overexpression of hNaa50 in rice enhanced melatonin synthesis, indicating that hNaa50 is in fact involved in melatonin biosynthesis.

Evaluation of dental status using a questionnaire before administration of general anesthesia for the prevention of dental injuries.

Background: Dental evaluation and protection are important for preventing traumatic dental injuries when patients are under general anesthesia. The objective of the present study was to develop a questionnaire based on dentition-related risk factors that could serve as a valuable tool for dental evaluation and documentation. Methods: We developed a questionnaire for dental evaluation before administration of general anesthesia, investigated the association between patient-and-dentist responses and mouthguard fabrication, and assessed response agreement between 100 patients. Results: Protective mouthguards were fabricated for 27 patients who were identified as having a high risk of dental injury. There was a strong association between dentists' responses and mouthguard fabrication, depending on the general oral health status, use of ceramic prosthesis, presence of masticatory pain related to periodontal diseases, gingival edema, and implants (P < 0.05). Response agreement between patients and dentists for items related to dental pain, loss of dental pulp vitality, root canal therapy, dental trauma, aesthetic prosthesis, tooth mobility, and implant prosthesis was high (Cohen's kappa coefficient κ ≥ 0.6). Conclusions: A high agreement was observed between patient-dentist responses and a strong association with mouthguard fabrication for items pertaining to ceramic prosthesis, masticatory pain, and dental implants. Patients with a "yes" response to these items are recommended to undergo a dental evaluation and use a dental protective device while under general anesthesia.

Vascular Relaxation and Blood Pressure Lowering Effects of Prunus mume in Rats.

Prunus mume Siebold et Zuccarini is mainly consumed as processed fruits in beverages, vinegar, alcohol, or fruit syrup; studies have reported various functional effects. Many pharmacological and functional studies exist on fruit extracts or processed foods using fruits, however, efficacy studies on various parts of P. mume, including the bark, branches, flowers, and leaves, have not been sufficiently conducted. A previous study revealed that a 70% ethanol extract of P. mume branches induced vascular endothelium-dependent vasorelaxant effects in rat thoracic aortic rings. Therefore, we hypothesized that various parts (the fruits, flowers, leaves, and bark) might have vasorelaxant effects. We evaluated the effects of P. mume extracts on the vascular relaxation of isolated rat thoracic aorta and hypotensive effects in spontaneous hypertensive rats (SHR). A 70% ethanol extract of P. mume bark (PBaE) was the most effective, thus, we investigated its vasorelaxant mechanisms and hypotensive effects. PBaE lowered the blood pressure in SHR and induced the vascular endothelium-dependent relaxation of isolated rat aortic rings via the NO/sGC/cGMP and the PGI2 pathways in the vascular smooth muscle. Potassium channels, such as KCa, KATP, KV, and Kir, were partially associated with a PBaE-induced vasorelaxation. Therefore, PBaE might help prevent and treat hypertension.

Hypotensive and Endothelium-Dependent Vasorelaxant Effects of Grayblue Spicebush Ethanol Extract in Rats.

Hypertension is one of the most common chronic diseases, and its prevalence is increasing worldwide. Lindera glauca (Siebold & Zucc.) Blume, known as grayblue spicebush (GS), has been used as food and for medicinal purposes; however, studies about its hypotensive or vasorelaxant effects are lacking. Therefore, the hypotensive effect of an ethanolic extract of the GS branch (GSE) was investigated in 15-week-old spontaneously hypertensive rats (SHRs) using the tail cuff method. The GSE administration group (1000 mg/kg SHR body weight) showed a decrease in their systolic and diastolic blood pressure measured 4 h after its administration. In addition, we investigated its vasorelaxant effect using the thoracic aorta dissected from Sprague-Dawley rats. The GSE (0.5, 1, 2, 5, 10, and 20 µg/mL) showed an endothelium-dependent vasorelaxant effect, and its mechanisms were found to be relevant to the inward rectifier, voltage-dependent, and non-selective K+ channels. Moreover, the GSE (20 µg/mL) showed an inhibitory effect on aortic rings constricted with angiotensin II. Considering its hypotensive and vasorelaxant effects, GSE has potential as a functional food to help treat and prevent high blood pressure. However, further studies on the identification of the active components of GSE and safety evaluations of its use are needed.

Cereblon Deficiency Contributes to the Development of Elastase-Induced Emphysema by Enhancing NF-κB Activation.

Cereblon (CRBN) has been shown to play an essential role in regulating inflammatory response and endoplasmic reticulum stress, thus mediating the development of various diseases. However, little is known about the roles of CRBN in chronic obstructive pulmonary disease (COPD) pathogenesis. We found that the protein levels of CRBN in lung homogenates from patients with COPD were lower than those from never smokers and smokers. The CRBN protein level was positively correlated with the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). To investigate the role of CRBN in modulating elastase-induced emphysema, we used Crbn knockout (KO) mice. Elastase-induced emphysematous changes were significantly aggravated in Crbn KO mice. Neutrophil infiltration, lung cell injury, and protein leakage into the bronchoalveolar space were more severe in Crbn KO mice than in wild-type (WT) mice. Furthermore, Crbn KO resulted in the elevated release of neutrophilic chemokines and inflammatory cytokines in lung epithelial cells and macrophages. The transcriptional activity of nuclear factor-κB (NF-κB) was significantly increased in Crbn knocked-down cells. In conclusion, Crbn deficiency might be involved in the development of emphysema by enhancing NF-κB activation, suggesting that targeting CRBN might be an effective therapeutic approach for the treatment of COPD.

Postoperative Hormone Replacement Therapy and Survival in Women with Ovarian Cancer.

The effect of postoperative hormone replacement therapy (HRT) on survival in women with ovarian cancer remains unclear. This study aimed to investigate the impact of postoperative HRT on survival in women with ovarian cancer using the nationwide cohort study. Women aged ≤60 and diagnosed with ovarian cancer that received primary surgery were followed-up for 5.6 ± 2.9 years. Mean ages of women administered HRT (the HRT group; n = 263) or not administered HRT (the control group; n = 1521) were 41.5 ± 8.5 and 41.0 ± 11.4 years, respectively. After adjustment for covariables, OS was significantly greater in the HRT group (HR 0.618; 95% CI 0.414−0.922; p = 0.018). Kaplan−Meier curve analysis showed OS was significantly higher in the HRT group (85.3% vs. 76.6%; p = 0.016). The ratio of women with HRT to women without HRT increased significantly with time (restricted mean survival times for OS, p < 0.001). In addition, OS was significantly greater for those that received HRT for >5 years than for those that received HRT for ≤0.5 years (HR 0.234; 95% CI 0.059−0.936; p = 0.040). Postoperative HRT improved survival among women with ovarian cancer. The impact of HRT on survival increased with time and treatment duration.

Spin Swapping Effect of Band Structure Origin in Centrosymmetric Ferromagnets.

We theoretically demonstrate the spin swapping effect of band structure origin in centrosymmetric ferromagnets. It is mediated by an orbital degree of freedom but does not require inversion asymmetry or impurity spin-orbit scattering. Analytic and tight-binding models reveal that it originates mainly from k points where bands with different spins and different orbitals are nearly degenerate, and thus it has no counterpart in normal metals. First-principle calculations for centrosymmetric 3d transition-metal ferromagnets show that the spin swapping conductivity of band structure origin can be comparable in magnitude to the intrinsic spin Hall conductivity of Pt. Our theory generalizes transverse spin currents generated by ferromagnets and emphasizes the important role of the orbital degree of freedom in describing spin-orbit-coupled transport in centrosymmetric materials.

Voltage-driven gigahertz frequency tuning of spin Hall nano-oscillators.

Spin Hall nano-oscillators (SHNOs) exploiting current-driven magnetization auto-oscillation have recently received much attention because of their potential for neuromorphic computing. Widespread applications of neuromorphic devices with SHNOs require an energy-efficient method of tuning oscillation frequency over broad ranges and storing trained frequencies in SHNOs without the need for additional memory circuitry. While the voltage-driven frequency tuning of SHNOs has been demonstrated, it was volatile and limited to megahertz ranges. Here, we show that the frequency of SHNOs is controlled up to 2.1 GHz by an electric field of 1.25 MV/cm. The large frequency tuning is attributed to the voltage-controlled magnetic anisotropy (VCMA) in a perpendicularly magnetized Ta/Pt/[Co/Ni]n/Co/AlOx structure. Moreover, the non-volatile VCMA effect enables cumulative control of the frequency using repetitive voltage pulses which mimic the potentiation and depression functions of biological synapses. Our results suggest that the voltage-driven frequency tuning of SHNOs facilitates the development of energy-efficient neuromorphic devices.