Grape Seed Proanthocyanidins Protect Pancreatic ß Cells Against Ferroptosis via the Nrf2 Pathway in Type 2 Diabetes.

Pancreatic ß cell damage is the primary contributor to type 2 diabetes mellitus (T2DM); however, the underlying mechanism remains nebulous. This study explored the role of ferroptosis in pancreatic ß cell damage and the protective effects of grape seed proanthocyanidin extract (GSPE). In T2DM model rats, the blood glucose, water intake, urine volume, HbA1c, and homeostasis model assessment-insulin resistance were significantly increased, while the body weight and the insulin level were significantly decreased, indicating the successful establishment of the T2DM model. MIN6 mouse insulinoma ß cells were cultured in high glucose and sodium palmitate conditions to obtain a glycolipid damage model, which was administered with GSPE, ferrostatin-1 (Fer-1), or nuclear factor erythroid 2-related factor 2 (Nrf2) small interfering (si) RNA. GSPE and Fer-1 treatment significantly improved pancreatic ß-cell dysfunction and protected against cell death. Both treatments increased the superoxide dismutase and glutathione activity, reduced the malondialdehyde and reactive oxygen species levels, and improved iron metabolism. Furthermore, the treatments reversed the expression of ferroptosis markers cysteine/glutamate transporter (XCT) and glutathione peroxidase 4 (GPX4) caused by glycolipid toxicity. GSPE treatments activated the expression of Nrf2 and related proteins. These effects were reversed when co-transfected with si-Nrf2. GSPE inhibits ferroptosis by activating the Nrf2 signaling pathway, thus reducing ß-cell damage and dysfunction in T2DM. Therefore, GSPE is a potential treatment strategy against T2DM.

Physical exercise habits are related with reduced prevalence of falling among elderly women in China.

BACKGROUND: Although some studies have examined the association between exercise and falls, most have focused on specific exercises, and the results have been inconsistent. In addition, there is a lack of evidence on elderly Chinese women who have different living and exercise habits compared to those in other countries. Therefore, this study aimed to investigate whether physical exercise is associated with falls in elderly Chinese women. METHODS: This cross-sectional study included 1429 elderly Chinese women with a mean age of 69.2 years. Information on physical exercise habits and fall experiences was collected using a self-report questionnaire. Logistic regression models were used to analyze the association between physical exercise habits and falls. RESULTS: The results showed that 15% participants had a fall in the past year. After adjusting for confounding factors, the odd ratios (ORs) and 95% Confidence Intervals (CIs) for fall experiences across categories of exercise frequency were as follow: 1 (reference) for no exercise behavior, 0.50 (0.29, 0.85) for exercise 1 to 5 times a week, and 0.37 (0.25, 0.55) for exercise more than 6 times a week. Furthermore, the ORs (95% CIs) across categories of exercise insistence were 1 (reference) for less than 1 year, 0.78 (0.37, 1.65) for 1 to 3 years, and 0.38 (0.20, 0.74) for more than 3 years. In terms of exercise duration, the ORs (95% CIs) for < 1 h/day, 1-2 h/day, and > 2 h/day were 1 (reference), 0.85 (0.53, 1.36), and 2.80 (1.30, 6.05). Unlike other variables, longer exercise duration was associated unfavorably with falls. CONCLUSION: Physical exercise habits were associated with falls in elderly Chinese women. Keeping a proper exercise habit may contribute to lower risk of falling in elderly women.

Comparative analysis of ankle injury kinematics and dynamics in basketball players: forefoot landing vs. rearfoot landing modes.

OBJECTIVE: To compare the differences in ankle joint parameters of basketball athletes between the forefoot and rearfoot landing and to investigate the injury mechanism of ankle joints in different landing modes. METHODS: Twenty level II male basketball athletes were selected as subjects in this study. The landing movements of these athletes were assigned into a forefoot landing mode and a rearfoot landing mode. The former includes movements such as running emergency stop, two-leg jump and forefoot landing, while the latter includes actions such as running emergency stop, two-leg jump and rearfoot landing. The motion capture system and three-dimensional force measuring table were used for collecting the kinematic and dynamic data of the subjects. RESULTS: The initial landing angles, including ankle dorsiflexion and medial ankle rotation of the forefoot were larger than those of the rearfoot (all P<0.05). Compared to those in the rearfoot landing mode, the forefoot landing exhibited a greater peak angle of ankle plantar flexion and ankle varus, as well as a smaller peak angle of ankle dorsiflexion and ankle internal rotation (all P<0.05). In comparison to the rearfoot landing mode, the forefoot landing showed a larger range of ankle varus and valgus, as well as a smaller range of ankle dorsiflexion and plantar flexion (all P<0.05). The ankle plantar flexion torque of forefoot landing was higher than that of rearfoot landing, while the peak ankle dorsiflexion torque of forefoot landing was smaller than that of rearfoot landing (all P<0.05). Compared to those in the rearfoot landing mode, the outward peak ground reaction force was smaller and the forward peak ground reaction was larger in forefoot landing mode (all P<0.05). No obvious differences were observed in other indicators between two landing modes. CONCLUSIONS: There are kinematic and dynamic differences between the forefoot and rearfoot landing. Forefoot landing may increase the risk of ankle injury during landing.

Ultrasensitive optical modulation in hybrid metal-perovskite and metal-graphene metasurface THz devices.

Implementation of efficient terahertz (THz) wave control is essential for THz technology development for applications including sixth-generation communications and THz sensing. Therefore, realization of tunable THz devices with large-scale intensity modulation capabilities is highly desirable. By integrating perovskite and graphene with a metallic asymmetric metasurface, two ultrasensitive devices for dynamic THz wave manipulation through low-power optical excitation are demonstrated experimentally here. The perovskite-based hybrid metadevice offers ultrasensitive modulation with a maximum modulation depth for the transmission amplitude reaching 190.2% at the low optical pump power of 5.90 mW/cm2. Additionally, a maximum modulation depth of 227.11% is achieved in the graphene-based hybrid metadevice at a power density of 18.87 mW/cm2. This work paves the way toward design and development of ultrasensitive devices for optical modulation of THz waves.

Multispectral higher-order Fano resonant metasurface based on periodic twisted DNA-like split ring arrays with three modulation methods.

The active modulation of the Fano resonance is rare but desirable. However, recent studies mostly focused on a single modulation method and few reported the use of three photoelectric control methods. A tunable graphene DNA-like metamaterial modulator with multispectral Fano resonance is demonstrated. In experimentally fabricated metamaterials with six photoelectric joint modulation patterns, each joint shows different optoelectrical response characteristics. Ultrahigh modulation depth (MD) up to 982% was achieved at 1.5734 THz with a 1.040 A external laser pump by involving combined optoelectrical methods. These results show that the metasurface modulator is a promising platform for higher-order Fano resonance modulation and communication fields.

Graphene-integrated toroidal resonance metasurfaces used for picogram-level detection of chlorothalonil in the terahertz region.

Toroidal dipole resonance can significantly reduce radiation loss of materials, potentially improving sensor sensitivity. Generally, toroidal dipole response is suppressed by electric and magnetic dipoles in natural materials, making it difficult to observe experimentally. However, as 2D metamaterials, metasurfaces can weaken the electric and magnetic dipole, enhancing toroidal dipole response. Here, we propose a new graphene-integrated toroidal resonance metasurface as an ultra-sensitive chemical sensor, capable of qualitative detection of chlorothalonil in the terahertz region, down to a detection limit of 100 pg/mL. Our results demonstrate graphene-integrated toroidal resonance metasurfaces as a promising basis for ultra-sensitive, qualitative detection in chemical and biological sensing.

Protective Effects of Grape Seed Proanthocyanidins on the Kidneys of Diabetic Rats through the Nrf2 Signalling Pathway.

BACKGROUND: Diabetic nephropathy (DN) is the most common cause of end-stage renal failure. Grape seed proanthocyanidin extract (GSPE) is a powerful antioxidant that is believed to protect the kidney through antioxidant action. However, the underlying mechanism of GSPE protection against DN remains unclear. OBJECTIVE: To explore if GSPE can improve DN by activating nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response element signalling and to clarify its possible mechanism. Materials and methods. Ten healthy Sprague-Dawley rats were randomly selected as controls. Rats with streptozotocin-induced diabetes were randomly divided into three groups (10 animals/group): type 2 diabetes mellitus (T2DM) group (untreated), L-GSPE group (treated with 125-mg/kg/day GSPE for 8 weeks), and H-GSPE group (treated with 250 mg/kg/day GSPE for 8 weeks). RESULTS: Renal histopathological results indicated limited pathological damage in GSPE-treated groups. Compared with the T2DM group, the H-GSPE group had significantly reduced kidney weight and renal index. Similarly, the levels of fasting blood glucose, serum creatinine, blood urea nitrogen, uric acid, urinary albumin, and renal malondialdehyde (p < 0.05) were also significantly decreased. In addition, GSPE significantly increased the levels of superoxide dismutase, total antioxidative capability, and glutathione (p < 0.05) as well as the protein levels of Nrf2, HO-1, glutathione S-transferase, and NAD (P)H quinone oxidoreductase 1 (p < 0.05). CONCLUSION: The results indicate that GSPE reduced renal damage in rats with diabetes by activating the Nrf2 signalling pathway, which consequently increased the antioxidant capacity of the tissue. Therefore, GSPE is a potential natural agent for the treatment of diabetic nephropathy.

Tunable bifunctional polarization-independent metamaterial device based on Dirac semimetal and vanadium dioxide.

In this study, a tunable bifunctional polarization-independent metamaterial device based on Dirac semimetal films (DSFs) and vanadium dioxide (VO2) is investigated. At the VO2 insulator state, a polarization-independent electromagnetically induced reflectance effect can be achieved via destructive interference between bright and dark modes. When VO2 transitions to a metallic state, the proposed device behaves as a dual-band polarization-independent absorber with 99.9% and 94.5% absorptance at 9.06 and 10.9 THz, respectively, and is insensitive over a wide range of incidence angles. In both cases, refractive index sensing is achieved, and the response can be dynamically tuned by changing the Fermi energy of the DSF.

Tunable bifunctional terahertz metamaterial device based on Dirac semimetals and vanadium dioxide.

A tunable bifunctional terahertz (THz) metamaterial device based on Dirac semimetal films (DSFs) and VO2 is presented. The insulator-to-metal phase transition of VO2 enables bifunctional asymmetric transmission and dual-directional absorption to be switched in the THz range. When VO2 serves as a dielectric, tunable broadband asymmetric transmission of linearly polarized THz waves can be achieved. When VO2 is in a metallic state, the proposed device acts as a tunable dual-directional absorber with perfect absorption in both illumination directions. In each case, the response can be tuned by varying the Fermi energy of the DSFs. This offers a new pathway for the development of tunable multifunctional THz metamaterial devices.

Mammotome-assisted removal with minimal incision of large juvenile fibroadenoma of breast: A case report.

INTRODUCTION: Giant juvenile breast fibroadenoma can cause deformity and should be excised. Cosmesis is an important consideration in young patients. PATIENT CONCERNS: The patient was admitted to our hospital for a mass of 6 × 6 cm in her left breast. DIAGNOSE: A giant juvenile fibroadenoma. INTERVENTIONS: With the help of Mammotome, we translated the larger mass to smaller one and removed it via a small circumareolar incision with no residual tumor. OUTCOMES: There was no recurrence of disease after 2 years. CONCLUSION: Mammotome-combined resection is a new approach that can be used to excise giant fibroadenomas with a minimal incision, and provides a favorable contour to the breast.

Tunable terahertz metamaterial absorber based on Dirac semimetal films.

In this paper, the tunable properties of metamaterial absorbers based on 3D Dirac semimetal films (DSFs) in the terahertz (THz) regime are discussed in theory. We consider the absorbers with square-shaped, circular-patch, and cross-shaped resonators. These resonances are theoretically polarization-insensitive at normal incidence because of their 90° rotational symmetry and can achieve perfect absorption in numerical simulation. We then introduce dual-band and broadband absorbers by combining two DSF-based square-shaped (or circular-patch) resonators into one unit cell with different sizes. Unlike with a conventional metal-based absorber, the absorption of a DSF-based absorber can be dynamically tuned by varying the Fermi energy instead of refabricating the structures. Moreover, the DSFs can be regarded as a "Salisbury screen" of an absorber to block the transmission at the THz frequencies, which can be more convenient than graphene in the application of a tunable absorber. Our designs have potential applications in various fields such as sensors, thermal detectors, and imagers.

[Expression of hypoxia inducible factor-1α and insulin in pancreatic cancer and their correlation].

OBJECTIVE: To explore the correlation between the expressions of hypoxia inducible factor-1α (HIF-1α) and insulin in pancreatic cancer. METHODS: HIF-1α and insulin expression was detected by immunohistochemistry in the center and the edge of pancreatic adenocarcinoma specimens of 65 cases. Western blot was used to detect HIF-1α expression and insulin level in the center and the edge of pancreatic adenocarcinoma specimens of 28 cases. The relationship between HIF-1α expression and insulin level in the pancreatic cancer was analyzed. RESULTS: The results of immunohistochemistry and Western blot showed that HIF-1α protein expression was high in both the center and the edge of pancreatic cancers (P > 0.05), and insulin level was significantly higher at the edge of specimen than that in the center (P < 0.05). HIF-1α protein and insulin levels were positively correlated at the edge of cancer tissue (r = 0.374, P < 0.05), but no significant correlation between them in the center of cancerous tissue (r = -0.145, P > 0.05). CONCLUSION: Insulin may promote the local invasion and metastasis of pancreatic cancer by up-regulating HIF-1α.

ShRNA silencing glycogen synthase kinase-3 beta inhibits tumor growth and angiogenesis in pancreatic cancer.

Glycogen synthase kinase-3 beta (GSK-3ß), a serine/threonine protein kinase, plays a vital role in the tumorigenesis of many cancers, but its role in pancreatic cancer remains unknown. In this study, we showed that GSK-3ß was aberrantly activated in pancreatic cancer. GSK-3ß knockdown resulted in arrested proliferation and increased apoptosis in pancreatic cancer cell lines. Expression of Bcl-2 and vascular endothelial growth factor (VEGF) decreased significantly in a GSK-3ß knockdown group. In a xenograft tumor model, GSK-3ß knockdown inhibited tumor growth and angiogenesis. Our study showed that GSK-3ß may become a promising therapeutic target for human pancreatic cancer.

Insulin promotes proliferative vitality and invasive capability of pancreatic cancer cells via hypoxia-inducible factor 1alpha pathway.

This study examined whether insulin-stimulated hypoxia-inducible factor 1alpha (HIF-1alpha) expression plays a crucial role in promoting the proliferative vitality and invasive capability in human pancreatic cancer cells. PANC-1 cells were divided into three groups: Control group, insulin group and insulin+YC-1 (a pharmacological inhibitor of HIF-1alpha) group in terms of different treatments. Cells in the insulin group or insulin+YC-1 group were treated with insulin (0.1, 1, 10 and 100 nmol/L) alone or combined with 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1, 0.1, 1, 10 and 100 micromol/L). HIF-1alpha mRNA and protein expression in PANC-1 cells was determined by real-time RT-PCR and Western blotting respectively. Cell proliferation and invasion were measured by using growth curve and invasion assay, respectively. Western blot analysis demonstrated that insulin dose-dependently increased the HIF-1alpha protein expression, and YC-1 could dose-dependently block this effect. However, neither insulin nor YC-1 altered HIF-1alpha mRNA levels in PANC-1 cells. Moreover, insulin could enhance the proliferation and invasion of PANC-1 cells, while YC-1 could weaken this effect. It was concluded that the malignant proliferation and local invasion of pancreatic cancer cells may be related to high-insulin microenvironment. The tumor biological behavior change resulting from high-insulin microenvironment may be associated with the increased expression of HIF-1alpha protein.