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Abstract Terahertz modulators play a critical role in high-speed wireless communication, non-destructive imaging, and so on, which have attracted a large amount of research interest. Nevertheless, all-optical terahertz modulation, an ultrafast dynamical control approach, remains to be limited in terms of encoding and multifunction. Here we experimentally demonstrated an optical-programmed terahertz switching realized by combining optical metasurfaces with the terahertz metasurface, resulting in 2-bit dual-channel terahertz encoding. The terahertz metasurface, made up of semiconductor islands and artificial microstructures, enables effective all-optical programming by providing multiple frequency channels with ultrafast modulation at the nanosecond level. Meanwhile, optical metasurfaces covered in terahertz metasurface alter the spatial light field distribution to obtain color code. According to the time-domain coupled mode theory analysis, the energy dissipation modes in terahertz metasurface can be independently controlled by color excitation, which explains the principle of 2-bit encoding well. This work establishes a platform for all-optical programmed terahertz metadevices and may further advance the application of composite metasurface in terahertz manipulation.

Abstract Flexible thermoelectric devices show great promise as sustainable power units for the exponentially increasing self-powered wearable electronics and ultra-widely distributed wireless sensor networks. While exciting proof-of-concept demonstrations have been reported, their large-scale implementation is impeded by unsatisfactory device performance and costly device fabrication techniques. Here, we develop Ag2Se-based thermoelectric films and flexible devices via inkjet printing. Large-area patterned arrays with microscale resolution are obtained in a dimensionally controlled manner by manipulating ink formulations and tuning printing parameters. Printed Ag2Se-based films exhibit (00 l)-textured feature, and an exceptional power factor (1097 μWm−1K−2 at 377 K) is obtained by engineering the film composition and microstructure. Benefiting from high-resolution device integration, fully inkjet-printed Ag2Se-based flexible devices achieve a record-high normalized power (2 µWK−2cm−2) and superior flexibility. Diverse application scenarios are offered by inkjet-printed devices, such as continuous power generation by harvesting thermal energy from the environment or human bodies. Our strategy demonstrates the potential to revolutionize the design and manufacture of multi-scale and complex flexible thermoelectric devices while reducing costs, enabling them to be integrated into emerging electronic systems as sustainable power sources.

Abstract Non‐Hermitian degeneracies, also known as exceptional points (EPs), have presented remarkable singular characteristics such as the degeneracy of eigenvalues and eigenstates and enable limitless opportunities for achieving fascinating phenomena in EP photonic systems. Here, the general theoretical framework and experimental verification of a non‐Hermitian metasurface that holds a pair of anti‐chiral EPs are proposed as a novel approach for efficient terahertz (THz) switching. First, based on the Pancharatnam–Berry (PB) phase and unitary transformation, it is discovered that the coupling variation of ±1 spin eigenstates will lead to asymmetric modulation in two orthogonal linear polarizations (LP). Through loss‐induced merging of a pair of anti‐chiral EPs, the decoupling of ±1 spin eigenstates are then successfully realized in a non‐Hermitian metasurface. Final, the efficient THz modulation is experimentally demonstrated, which exhibits modulation depth exceeding 70% and Off‐On‐Off switching cycle less than 9 ps in one LP while remains unaffected in another one. Compared with conventional THz modulation devices, the metadevice shows several figures of merits, such as a single frequency operation, high modulation depth, and ultrafast switching speed. The proposed theory and loss‐induced non‐Hermitian device are general and can be extended to numerous photonic systems varying from microwave, THz, infrared, to visible light.

In recent years, due to growing interest in gut health, the potential benefits of probiotics on the gut have received much attention. Probiotics, now readily available in both dietary supplements and a variety of foods, have become a focal point of consumer health choices. This study aims to explore the impact of consumer-related factors, including socio-demographic profiles, health status, and probiotics knowledge, on the acceptance of probiotics products in Hong Kong. A total of 385 participants engaged in a survey, providing data for an in-depth analysis of how these factors influence attitudes toward probiotics. Findings revealed a general confidence in the safety of probiotics products among respondents; however, there was a noticeable gap in probiotics understanding. The study highlighted a correlation between probiotics knowledge and specific socio-demographic attributes, with higher educational attainment positively linked to greater probiotics awareness. Furthermore, the research indicated that women exhibit higher health consciousness and a greater propensity for probiotics consumption compared to men. Consequently, promoting enhanced probiotics education and fostering increased health awareness are crucial steps to prevent the misuse of probiotics and optimize health outcomes.

GeSb2Te4 (GST124), one of the well‐known phase‐change materials for nonvolatile memory and rewritable optical storage, has been recently found to be promising thermoelectric materials with low lattice thermal conductivity and high electrical conductivity. However, its thermoelectric performance is greatly restricted by the excessively high hole concentration. Herein, the impact of a series of group IIIA (Al, Ga, In) and group VIA (S, Se) dopants on the electrical transport properties of polycrystalline GST124 has been studied. It is found that element sulfur (S) has the best doping efficiency because the GeS bonds are very strong and ionic that are beneficial for suppressing Ge vacancies to reduce the carrier concentration. Meanwhile, element indium (In) also shows decent doping efficiency because its ionic radius is close to the Ge ion and the InTe bonds have moderate bonding strength. Moreover, In doping introduces a resonant level in the valence band, leading to enhanced Seebeck coefficient and power factor. A high figure of merit (zT)of 0.73 at 700 K and an average zT of 0.48 over 300–750 K are obtained in Ge0.92In0.08Sb2Te4, which are 26% and 66% higher than pristine GST124. This study will advance the understanding and development of high‐performance GeSbTe‐based thermoelectric materials.

Abstract Background To compare the surgical effects of lateral transperitoneal approach (LTA) and posterior retroperitoneal approach (PRA) for pheochromocytoma of different sizes. Methods Data on patients with pheochromocytoma from 2014 to 2023 were collected from our hospital. According to different surgical approaches and tumor size, all patients were divided into four groups: tumor size

Abstract Non‐Hermitian degeneracies, also known as exceptional points (EPs), have attracted considerable attention due to their unique physical properties. In particular, metasurfaces related to EPs can open the way to unprecedented devices with functionalities such as unidirectional transmission and ultra‐sensitive sensing. Herein, an active non‐Hermitian metasurface with a loss‐induced parity‐time symmetry phase transition for ultrafast terahertz metadevices is demonstrated. Specifically, the eigenvalues of the non‐Hermitian transmission matrix undergo a phase transition under optical excitation and are degenerate at EPs in parameter space, which is accompanied by the collapse of chiral transmission. Ultrafast EP modulation on a picosecond time scale can be realized through variations in the transient loss at a non‐Hermitian metasurface pumped by pulsed excitation. Furthermore, by exploiting the physical characteristics of chiral transmission EPs, a switchable quarter‐wave plate based on the photoactive metasurface is designed and experimentally verified and realized the corresponding function of polarization manipulation. This work opens promising possibilities for designing functional terahertz metadevices and fuses EP physics with active metasurfaces.

Abstract Annexin-A6 (ANXA6), a Ca2+-dependent membrane binding protein, is the largest of all conserved annexin families and highly expressed in the plasma membrane and endosomal compartments. As a multifunctional scaffold protein, ANXA6 can interact with phospholipid membranes and various signaling proteins. These properties enable ANXA6 to participate in signal transduction, cholesterol homeostasis, intracellular/extracellular membrane transport, and repair of membrane domains, etc. Many studies have demonstrated that the expression of ANXA6 is consistently altered during tumor formation and progression. ANXA6 is currently known to mediate different patterns of tumor progression in different cancer types through multiple cancer-type specific mechanisms. ANXA6 is a potentially valuable marker in the diagnosis, progression, and treatment strategy of various cancers. This review mainly summarizes recent findings on the mechanism of tumor formation, development, and drug resistance of ANXA6. The contents reviewed herein may expand researchers’ understanding of ANXA6 and contribute to developing ANXA6-based diagnostic and therapeutic strategies.

Mounting evidence suggests that the gut microbiota plays a crucial role in the development and treatment of various cancers. Recent research on the urinary microbiota challenges the long-standing belief that urine is sterile, as urinary microbiota has been implicated in the development of bladder and prostate cancers, similar to the role of gut microbiota in cancer development. Although the precise involvement of microbiota in the proliferation and differentiation of renal cell carcinoma (RCC) remains unclear, dysbiosis is considered one possible mechanism by which microbiota may contribute to RCC development and treatment. This review summarizes potential mechanisms by which gut microbiota may contribute to the development of RCC, and provides evidence for the involvement of urinary microbiota in RCC. We also explore the role of gut microbiota in RCC treatment and propose that the composition of gut microbiota could serve as a predictive marker for the potential efficacy of immune checkpoint inhibitors (ICIs) in RCC patients. Additionally, evidence suggests that modulating the abundance and distribution of microbiota can enhance the therapeutic effects of drugs, suggesting that microbiota may serve as a promising adjuvant therapy for RCC. Overall, we believe that further investigation into the gut and urinary microbiome of RCC patients could yield valuable insights and strategies for the prevention and personalized treatment of RCC.

Capacitive deionization (CDI) is a promising technique for brackish water desalination. However, its salt electrosorption capacity is insufficient for practical application yet, and little information is available on hardness ion (Mg2+, Ca2+) removal in CDI. Herein, hierarchical porous carbon (HPC) was prepared from low-cost and renewable microalgae via a simple one-pot approach, and both MnO2/HPC and polyaniline/HPC (PANI/HPC) composites were then synthesized using a facile, one-step hydrothermal method. Compared with the MnO2 electrode, the MnO2/HPC electrode presented an improved hydrophilicity, higher specific capacitance, and lower electrode resistance. The electrodes exhibited pseudocapacitive behaviors, and the maximum salt electrosorption capacities of MnO2/HPC-PANI/HPC CDI cell was up to 0.65 mmol g−1 NaCl, 0.71 mmol g−1 MgCl2, and 0.76 mmol g−1 CaCl2, respectively, which were comparable and even higher than those of the previously reported CDI cells. Additionally, the MnO2/HPC electrode presented a selectivity order of Ca2+ ≥ Mg2+ > Na+, and the divalent cation selectivity was found to be attributed to their stronger binding strength in the cavity of MnO2. Multiscale simulations further reveal that the MnO2/HPC electrodes with the unique luminal configuration of MnO2 and HPC as supportive framework could offer a great intercalation selectivity of the divalent cations and exhibit a great promise in hardness ion removal.

COVID-19 pandemic, caused by the SARS-CoV-2 virus, is still affecting the entire world via the rapid emergence of new contagious variants. Vaccination remains the most effective prevention strategy for viral infection, yet not all countries have sufficient access to vaccines due to limitations in manufacturing and transportation. Thus, there is an urgent need to develop an easy-to-use, safe, and low-cost vaccination approach. Genetically modified microorganisms, especially probiotics, are now commonly recognized as attractive vehicles for delivering bioactive molecules via oral and mucosal routes. In this study, Lactobacillus casei has been selected as the oral vaccine candidate based on its’ natural immunoadjuvant properties and the ability to resist acidic gastric environment, to express antigens of SARS-CoV-2 Omicron variant B.1.1.529 with B-cell and T-cell epitopes. This newly developed vaccine, OMGVac, was shown to elicit a robust IgG systemic immune response against the spike protein of Omicron variant B.1.1.529 in Golden Syrian hamsters. No adverse effects were found throughout this study, and the overall safety was evaluated in terms of physiological and histopathological examinations of different organs harvested. In addition, this study illustrated the use of the recombinant probiotic as a live delivery vector in the initiation of systemic immunity, which shed light on the future development of next-generation vaccines to combat emerging infectious diseases.

Background: Pyroptosis is a form of programmed cell death accompanied by specific inflammatory and immune responses, and it is closely related to the occurrence and progression of various cancers. However, the roles of pyroptosis-related genes (PRGs) in the prognosis, treatment response, and tumor microenvironment (TME) of prostate cancer (PCa) remain to be investigated.Methods: The mRNA expression data and clinical information of PCa patients were obtained from the Cancer Genome Atlas database (TCGA) and the cBioPortal for Cancer Genomics website, and the 52 PRGs were obtained from the published papers. The univariate, multivariate, and LASSO Cox regression algorithms were used to obtain prognostic hub PRGs. Meanwhile, qRT-PCR was used to validate the expression of hub genes between PCa lines and normal prostate epithelial cell lines. We then constructed and validated a risk model associated with the patient’s disease-free survival (DFS). Finally, the relationships between risk score and clinicopathological characteristics, tumor immune microenvironment, and drug treatment response of PCa were systematically analyzed.Results: A prognostic risk model was constructed with 6 hub PRGs (CHMP4C, GSDMB, NOD2, PLCG1, CYCS, GPX4), and patients were divided into high and low-risk groups by median risk score. The risk score was confirmed to be an independent prognostic factor for PCa in both the training and external validation sets. Patients in the high-risk group had a worse prognosis than those in the low-risk group, and they had more increased somatic mutations, higher immune cell infiltration and higher expression of immune checkpoint-related genes. Moreover, they were more sensitive to cell cycle-related chemotherapeutic drugs and might be more responsive to immunotherapy.Conclusion: In our study, pyroptosis played a significant role in the management of the prognosis and tumor microenvironment of PCa. Meanwhile, the established model might help to develop more effective individual treatment strategies.

With a close pathogenetic resemblance to human diabetes, canine Diabetes Mellitus, a chronic metabolic disease featuring abnormally high blood sugar levels, is increasing in prevalence worldwide. Unlike humans, canine glycemic control requires life-long insulin injections and dietary control in most cases, thereby jeopardizing diabetic dogs’ quality of life and increasing the difficulty of disease control. While many research studies have focused on elucidating the relationship between the canine gut microbiome and diseases, there is currently no research on the subject of diabetes mellitus in dogs. We hypothesized that the gut microbiome of canines with diabetes mellitus is different from that of healthy controls. Thus, we performed targeted 16S rRNA sequencing and comprehensive bioinformatic analysis to compare the gut microbiome profiles of 16 diabetic dogs with those of 32 healthy dogs. Clostridioides difficile, Phocaeicola plebeius, Lacrimispora indolis, and Butyricicoccus pullicaecorum were found to be enriched in diabetic dogs. A distinct shift towards carbohydrate degradation metabolic pathways was found to be differentially abundant in the diabetic subjects. Alteration of the co-occurrence network was also evident in the diabetic group. In conclusion, our study suggests that the gut microbial landscape differs in diabetic canines at the genera, species, functional, and network levels. These findings have significant implications for disease management, and thus warrant further research.

Al2O3-based self-lubricating ceramics are cutting tool materials that meet the extreme working conditions of dry cutting. However, due to the soft lubricating components, the mechanical properties of composites are dramatically reduced. In this paper, Al2O3-cBN-hBN self-lubricating material was designed. High density, fine grain ceramics were synthesized by high-pressure technology. The influence of thermodynamic condition, cBN/hBN addition on mechanical and thermal properties of sintered composites was analyzed. Friction and wear tests were carried out. It is found that the addition of cBN particles can significantly improve the mechanical and thermal properties of the composites. However, the truss effect caused by excessive volume fraction of cBN can reduce the pressure transfer efficiency, and then affect the properties of sintered composites. The different hBN content can change the wear mechanism of the composites. The release efficiency of hBN particles in composites was enhanced due to the large modulus difference between cBN and hBN. The well-sintered Al2O3-cBN-hBN bulks present an excellent mechanical property. The hardness of the composites is improved at least by 54% compared with the traditional self-lubricating material on the premise of ensuring fracture toughness and lubrication performance.

Human cell division cycle-related protein 8 (CDCA8) is an essential component of the vertebrate chromosomal passenger complex (CPC). CDCA8 was confirmed to play a role in promoting malignant tumor progression. However, the exact function of CDCA8 in the development and progression of prostate cancer (PCa) remains unclear. In this study, the database GSE69223 was downloaded by the gene expression omnibus (GEO) database, as well as CDCA8 expression differences in multiple tumor tissues and normal tissues were detected by The Cancer Genome Atlas (TCGA), TIMER, Oncomine, and Ualcan databases. Kaplan-Meier and Cox regression methods were used to analyze the correlation between CDCA8 expression and prognosis in PCa. We confirmed the expression of CDCA8 in PCa tissues by HPA. We also analyzed the association of CDCA8 expression with PCa clinical characteristics in the TCGA database. To further understand the role of CDCA8 in PCa, we assessed the effects of CDCA8 on PCa cell growth, proliferation, and migration in vitro studies. As a result, CDCA8 was significantly overexpressed in PCa cells compared with normal prostate cells. High CDCA8 expression predicts poor prognosis in PCa patients, and CDCA8 expression was higher in high-grade PCa. In addition, silencing of CDCA8 significantly inhibited PCa cell proliferation and migration. In summary, CDCA8 promoted the proliferation and migration of PCa cells.

Thinning the buffer layer thickness between the GaN epilayer and Si substrate without introducing large residual stress is persistently desired for GaN-on-Si devices to promote their thermal budgets and low-cost, multifunctional applications. In this work, the GaN-on-Si heterostructures were directly bonded at room temperature by surface activated bonding (SAB) and the therein residual stress states were investigated by confocal micro-Raman. The effects of thermal annealing process on the residual stress and interfacial microstructure in SAB fabricated GaN-on-Si heterostructures were also systematically investigated by in situ micro-Raman and transmission electron microscopy. It was found that a significant relaxation and a more uniform stress distribution was obtained in SAB bonded GaN-on-Si heterostructure in comparison with that of MOCVD grown sample; however, with increasing annealing temperature, the residual stresses at the SAB bonded GaN layer and Si layer evolute monotonically in different trends. The main reason can be ascribed to the amorphous layer formed at the bonding interface, which played a critical stress relaxation role and transformed into a much thinner crystallized interlayer without any observable structural defects after 1000 °C annealing.

A broad tunability of the thermoelectric and mechanical properties of CoSb3 has been demonstrated by adjusting the composition with the addition of an increasing number of elements. However, such a strategy may negatively impact processing repeatability and composition control. In this work, single-element-filled skutterudite is engineered to have high thermoelectric and mechanical performances. Increased Yb filling fraction is found to increase phonon scattering, whereas cryogenic grinding contributes additional microstructural scattering. A peak zT of 1.55 and an average zT of about 1.09, which is comparable to the reported results of multiple-filled SKDs, are realized by the combination of simple composition and microstructure engineering. Furthermore, the mechanical properties of Yb single-filled CoSb3 skutterudite are improved by manipulation of the microstructure through cryogenic grinding. These findings highlight the realistic prospect of producing high-performance thermoelectric materials with reduced compositional complexity. Keywords: Skutterudites, Thermoelectric material, Compositional complexity, Microstructure engineering, Cryogenic grinding

Lumbar disc herniation (LDH) with radicular pain is a common and complicated musculoskeletal disorder. Our previous study showed that LDH-induced methylglyoxal (MG) accumulation contributed to radicular pain. The underlying mechanisms through which MG accumulates are poorly understood. In the present study, we found that both MG and tumor necrosis factor-alpha (TNF-ɑ) levels in the herniated disc of patients with radicular pain were significantly increased, and the activity of Glyoxalase 1 (GLO1), the rate-limiting enzyme that metabolizes MG, was decreased. In rats, the LDH model was mimicked by implantation of autologous nucleus pulposus (NP) to the left lumbar five spinal nerve root. The mechanical allodynia was observed in LDH rats. Besides, MG and TNF-ɑ levels were increased, and GLO1 activity was significantly decreased in the implanted NP. In cultured rat NP cells, stimulation with the inflammatory mediator TNF-ɑ reduced GLO1 activity and expression. These results suggested that TNF-ɑ-induced GLO1 activity decrease contributed to MG accumulation in the herniated disc of patients with radicular pain.

BACKGROUND:The use of abacavir has been linked with increased cardiovascular risk in patients with human immunodeficiency virus infection; however, the mechanism involved remains unclear. We hypothesize that abacavir may impair endothelial function. In addition, based on the structural similarity between abacavir and adenosine, we propose that abacavir may affect vascular contractility through endogenous adenosine release or adenosine receptors in blood vessels. METHODS:The relaxation effect of abacavir on rat basilar arteries was studied using the myograph technique. Cyclic GMP and AMP levels were measured by immunoassay. The effects of abacavir on nucleoside transporters were studied using radiolabeled nucleoside uptake experiments. Ecto-5' nucleotidase activity was determined by measuring the generation of inorganic phosphate using adenosine monophosphate as the substrate. RESULTS:Abacavir induced the relaxation of rat basilar arteries in a concentration-dependent manner. This relaxation was abolished when endothelium was removed. In addition, the relaxation was diminished by the nitric oxide synthase inhibitor, L-NAME, the guanylyl cyclase inhibitor, ODQ, and the protein kinase G inhibitor, KT5820. Abacavir also increased the cGMP level in rat basilar arteries. Abacavir-induced relaxation was also abolished by adenosine A2 receptor blockers. However, abacavir had no effect on ecto-5' nucleotidase and nucleoside transporters. Short-term and long-term treatment of abacavir did not affect acetylcholine-induced relaxation in rat basilar arteries. CONCLUSION:Abacavir induces acute endothelium-dependent relaxation of rat basilar arteries, probably through the activation of adenosine A2 receptors in endothelial cells, which subsequently leads to the release of nitric oxide, resulting in activation of the cyclic guanosine monophosphate/protein kinase G-dependent pathway in vascular smooth muscle cells. It is speculated that abacavir-induced cardiovascular risk may not be related to endothelial dysfunction as abacavir does not impair relaxation of blood vessels. The most likely explanation of increased cardiovascular risk may be increased platelet aggregation as suggested by other studies.

The hypocholesterolemic protective effect of the dried seed of Astragalus complanatus (ACS) was investigated in rats fed with normal diet, high cholesterol diet (HCD), and HCD plus 70% ethanol extract of ACS (600 mg/kg/day) by oral gavage for four weeks. ACS extract was tested to be rich in antioxidants, which may be contributed to its high content of phenolic compounds. Consumption of ACS remarkably suppressed the elevated total cholesterol (p < 0.01) and LDL-C (p < 0.001) induced by HCD. Chemical constituents of ACS extract were analyzed by ultra-performance liquid chromatography coupled with electrospray ionization orbitrap mass spectrometry and the results showed that the ACS extract mainly consisted of phenolic compounds including flavonoids and flavonoid glycosides. In addition, based on the serum fatty acid profiles, elucidated using gas chromatography-mass spectrometry, free and esterified fatty acids including docosapentaenoic acid, adrenic acid, dihomo-γ-linolenic acid and arachidonic acid were regulated in ACS treatment group. Western blot results further indicated the protein expression of peroxisome proliferator-activated receptor alpha (PPARα) (p < 0.05) in liver was upregulated in ACS treatment group. To conclude, our results clearly demonstrated that ACS provides beneficial effect on lowering HCD associated detrimental change.

BackgroundStatins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors) consumption provides beneficial effects on cardiovascular systems. However, effects of statins on vascular KATP channel gatings are unknown.MethodsPig left anterior descending coronary artery and human left internal mammary artery were isolated and endothelium-denuded for tension measurements and Western immunoblots. Enzymatically-dissociated/cultured arterial myocytes were used for patch-clamp electrophysiological studies and for [Ca(2+)]i, [ATP]i and [glucose]o uptake measurements.ResultsThe cromakalim (10 nM to 10 µM)- and pinacidil (10 nM to 10 µM)-induced concentration-dependent relaxation of porcine coronary artery was inhibited by simvastatin (3 and 10 µM). Simvastatin (1, 3 and 10 µM) suppressed (in okadaic acid (10 nM)-sensitive manner) cromakalim (10 µM)- and pinacidil (10 µM)-mediated opening of whole-cell KATP channels of arterial myocytes. Simvastatin (10 µM) and AICAR (1 mM) elicited a time-dependent, compound C (1 µM)-sensitive [(3)H]-2-deoxy-glucose uptake and an increase in [ATP]i levels. A time (2-30 min)- and concentration (0.1-10 µM)-dependent increase by simvastatin of p-AMPKα-Thr(172) and p-PP2A-Tyr(307) expression was observed. The enhanced p-AMPKα-Thr(172) expression was inhibited by compound C, ryanodine (100 µM) and KN93 (10 µM). Simvastatin-induced p-PP2A-Tyr(307) expression was suppressed by okadaic acid, compound C, ryanodine, KN93, phloridzin (1 mM), ouabain (10 µM), and in [glucose]o-free or [Na(+)]o-free conditions.ConclusionsSimvastatin causes ryanodine-sensitive Ca(2+) release which is important for AMPKα-Thr(172) phosphorylation via Ca(2+)/CaMK II. AMPKα-Thr(172) phosphorylation causes [glucose]o uptake (and an [ATP]i increase), closure of KATP channels, and phosphorylation of AMPKα-Thr(172) and PP2A-Tyr(307) resulted. Phosphorylation of PP2A-Tyr(307) occurs at a site downstream of AMPKα-Thr(172) phosphorylation.

BACKGROUND: Angiogenesis plays an important role in a wide range of physiological processes, and many diseases are associated with the dysregulation of angiogenesis. Radix Astragali is a Chinese medicinal herb commonly used for treating cardiovascular disorders and has been shown to possess angiogenic effect in previous studies but its active constituent and underlying mechanism remain unclear. The present study investigates the angiogenic effects of calycosin, a major isoflavonoid isolated from Radix Astragali, in vitro and in vivo. METHODOLOGY: Tg(fli1:EGFP) and Tg(fli1:nEGFP) transgenic zebrafish embryos were treated with different concentrations of calycosin (10, 30, 100 microM) from 72 hpf to 96 hpf prior morphological observation and angiogenesis phenotypes assessment. Zebrafish embryos were exposed to calycosin (10, 100 microM) from 72 hpf to 78 hpf before gene-expression analysis. The effects of VEGFR tyrosine kinase inhibitor on calycosin-induced angiogenesis were studied using 72 hpf Tg(fli1:EGFP) and Tg(fli1:nEGFP) zebrafish embryos. The pro-angiogenic effects of calycosin were compared with raloxifene and tamoxifen in 72 hpf Tg(fli1:EGFP) zebrafish embryos. The binding affinities of calycosin to estrogen receptors (ERs) were evaluated by cell-free and cell-based estrogen receptor binding assays. Human umbilical vein endothelial cell cultures (HUVEC) were pretreated with different concentrations of calycosin (3, 10, 30, 100 microM) for 48 h then tested for cell viability and tube formation. The role of MAPK signaling in calycosin-induced angiogenesis was evaluated using western blotting. CONCLUSION: Calycosin was shown to induce angiogenesis in human umbilical vein endothelial cell cultures (HUVEC) in vitro and zebrafish embryos in vivo via the up-regulation of vascular endothelial growth factor (VEGF), VEGFR1 and VEGFR2 mRNA expression. It was demonstrated that calycosin acted similar to other selective estrogen receptor modulators (SERMs), such as raloxifene and tamoxifen, by displaying selective potency and affinity to estrogen receptors ERalpha and ERbeta. Our results further indicated that calycosin promotes angiogenesis via activation of MAPK with the involvement of ERK1/2 and ER. Together, this study revealed, for the first time, that calycosin acts as a selective estrogen receptor modulator (SERM) to promote angiogenesis, at least in part through VEGF-VEGFR2 and MAPK signaling pathways.

In recent years, due to growing interest in gut health, the potential benefits of probiotics on the gut have received much attention. Probiotics, now readily available in both dietary supplements and a variety of foods, have become a focal point of consumer health choices. This study aims to explore the impact of consumer-related factors, including socio-demographic profiles, health status, and probiotics knowledge, on the acceptance of probiotics products in Hong Kong. A total of 385 participants engaged in a survey, providing data for an in-depth analysis of how these factors influence attitudes toward probiotics. Findings revealed a general confidence in the safety of probiotics products among respondents; however, there was a noticeable gap in probiotics understanding. The study highlighted a correlation between probiotics knowledge and specific socio-demographic attributes, with higher educational attainment positively linked to greater probiotics awareness. Furthermore, the research indicated that women exhibit higher health consciousness and a greater propensity for probiotics consumption compared to men. Consequently, promoting enhanced probiotics education and fostering increased health awareness are crucial steps to prevent the misuse of probiotics and optimize health outcomes. [ABSTRACT FROM AUTHOR]

Solanaceae, commonly known as nightshade, is a diverse family of flowering plants comprising around 90 genera and an estimated 3000–4000 species. Solanaceae spp. and its various fruits, including pepino (Solanum muricatum), commonly known as pepino melon, are widely recognized by the public for their nutritional value and pharmacological effects. Pepino melon, in particular, is often enjoyed as a fresh dessert or salad due to its juicy flesh. Given its beneficial properties, the potential of pepino melon to be developed as a functional food has been extensively studied. This review aims to provide a comprehensive summary of the reported pharmacological effects of the active compounds found in pepino plant and melon. Among these compounds, polyphenols, notably quercetin, and vitamin C have demonstrated notable antioxidant properties such as scavenging free radicals, effectively protecting against free-radical damage. Moreover, these active ingredients provide pepino with anti-inflammatory properties by inhibiting the expression of proinflammatory cytokines and enzymes, thereby reducing nitric oxide production. Additionally, they have shown promise in selectively targeting cancer cells, exhibiting anti-cancer properties. Furthermore, the active compounds such as quercetin in pepino have been associated with anti-diabetic effects, improving insulin sensitivity and inhibiting insulin resistance. Overall, this review highlights the diverse and significant pharmacological effects of the active compounds found in pepino melon, emphasizing its potential as a valuable functional food. [ABSTRACT FROM AUTHOR]

Background: This study aimed to conduct a pooled analysis to compare the outcomes of patients with metastatic renal cell carcinoma who received presurgical systemic therapy [(ST); including immunotherapy and/or targeted therapy] followed by cytoreductive nephrectomy (CN) [(deferred CN; (dCN)] with those who underwent upfront CN (uCN) followed by ST. Methods: The present study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A comprehensive search was conducted in PubMed, Embase, Web of Science, Scopus, and the Cochrane Library database to identify eligible comparative studies up to April 2023. To evaluate their relevance, pooled hazard ratio with 95% CIs were calculated. Results: A total of 3157 patients were included in nine studies. The dCN group was observed to be correlated with superior overall survival (OS) compared to the uCN group (hazard ratio =0.71, 95% CI 0.57-0.89, P=0.003). Moreover, the authors conducted subgroup analyses according to the type of ST, sample size, sex, age, and risk score, and observed similar outcomes for OS across most subgroups. Conclusions: The results of this study demonstrated that dCN may be associated with improved OS compared to uCN in patients with metastatic renal cell carcinoma receiving ST. However, no significant differences were found between the uCN and dCN groups in the immunotherapy-based combinations subgroup. Further research is needed to confirm these results. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the differences in manual acupuncture effectiveness at sensitized points by investigating the mechanisms of local skin action at different sensitization points in rats with knee osteoarthritis (KOA). Methods: Forty Sprague–Dawley rats were equally divided into control, model (1 mg of monoiodoacetate into the right knee joint cavity), sham operation, manual acupuncture at right Tianjing acupoint (MAR-SJ 10), and left SJ 10 groups. Safranine-O and fast green staining were used to assess the modeling. The morphological and functional changes in mast cells (MCs) were assessed during acupoint sensitization using toluidine blue and immunofluorescence staining. The levels of serotonin, histamine, substance P (SP), and tryptase at skin acupoints and serum levels of IL-β, IL-6, and TNF-α were detected using ELISA. Results: After 14 days of treatment, the number of MCs and their degranulation rates were statistically higher in the model group than in the control group (both P

Abstract Centrosymmetric materials with site inversion asymmetries possess hidden spin polarization, which remains challenging to be converted into spin currents because the global inversion symmetry is still conserved. This study demonstrates the spin-polarized circular photocurrents in centrosymmetric transition metal dichalcogenide semiconductors at normal incidence without applying electric bias. The global inversion symmetry is broken by using a spatially-varying circularly polarized light beam, which could generate spin gradient owing to the hidden spin polarization. The dependence of the circular photocurrents on electrode configuration, illumination position, and beam spot size indicates an emergence of circulating electric current under spatially inhomogeneous light, which is associated with the deflection of spin-polarized current through the inverse spin Hall effect. The circular photocurrents is subsequently utilized to probe the spin polarization and the inverse spin Hall effect under different excitation wavelengths and temperatures. The results of this study demonstrate the feasibility of using centrosymmetric materials with hidden spin polarization and non-vanishing Berry curvature for spintronic device applications.

Abstract Background The syncytiotrophoblast (SCT) layer in the placenta serves as a crucial physical barrier separating maternal-fetal circulation, facilitating essential signal and substance exchange between the mother and fetus. Any abnormalities in its formation or function can result in various maternal syndromes, such as preeclampsia. The transition of proliferative villous cytotrophoblasts (VCT) from the mitotic cell cycle to the G0 phase is a prerequisite for VCT differentiation and their fusion into SCT. The imprinting gene P57Kip2, specifically expressed in intermediate VCT capable of fusion, plays a pivotal role in driving this key event. Moreover, aberrant expression of P57Kip2 has been linked to pathological placental conditions and adverse fetal outcomes. Methods Validation of STK40 interaction with P57Kip2 using rigid molecular simulation docking and co-immunoprecipitation. STK40 expression was modulated by lentivirus in BeWo cells, and the effect of STK40 on trophoblast fusion was assessed by real-time quantitative PCR, western blot, immunofluorescence, and cell viability and proliferation assays. Co-immunoprecipitation, transcriptome sequencing, and western blot were used to determine the potential mechanisms by which STK40 regulates P57Kip2. Results In this study, STK40 has been identified as a novel interacting protein with P57Kip2, and its expression is down-regulated during the fusion process of trophoblast cells. Overexpressing STK40 inhibited cell fusion in BeWo cells while stimulating mitotic cell cycle activity. Further experiments indicated that this effect is attributed to its specific binding to the CDK-binding and the Cyclin-binding domains of P57Kip2, mediating the E3 ubiquitin ligase COP1-mediated ubiquitination and degradation of P57Kip2. Moreover, abnormally high expression of STK40 might significantly contribute to the occurrence of preeclampsia. Conclusions This study offers new insights into the role of STK40 in regulating the protein-level homeostasis of P57Kip2 during placental development.

Abstract Background Evidence is scarce on the effect of free fatty acid (FFA) level in the prognosis of coronary artery disease (CAD) patients with hypertension. This study. Methods A large prospective cohort study with a follow-up period of average 2 years was conducted at Xinjiang Medical University Affiliated First Hospital from December 2016 to October 2021. A total of 10,395 CAD participants were divided into groups based on FFA concentration and hypertension status, and then primary outcome mortality and secondary endpoint ischemic events were assessed in the different groups. Results A total of 222 all-cause mortality (ACMs), 164 cardiac mortality (CMs), 718 major adverse cardiovascular events (MACEs) and 803 major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded during follow-up period. A nonlinear relationship between FFA and adverse outcomes was observed only in CAD patients with hypertension. Namely, a “U -shape” relationship between FFA levels and long-term outcomes was found in CAD patients with hypertension. Lower FFA level (