Stimulus of Work Function on Electron Transfer Process of Intermetallic Nickel-Antimonide Toward Bifunctional Electrocatalyst for Overall Water Splitting.

Engineering the intermetallic nanostructures as an effective bifunctional electrocatalyst for hydrogen and oxygen evolution reactions (HER and OER) is of great interest in green hydrogen production. However, a few non-noble metals act as bifunctional electrocatalysts, exhibiting terrific HER and OER processes reported to date. Herein the intermetallic nickel-antimonide (Ni─Sb) dendritic nanostructure via cost-effective electro-co-deposition method is designed and their bifunctional electrocatalytic property toward HER and OER is unrevealed. The designed Ni─Sb delivers a superior bifunctional activity in 1 m KOH electrolyte, with a shallow overpotential of ≈119 mV at -10 mA for HER and ≈200 mV at 50 mA for OER. The mechanism behind the excellent bifunctional property of Ni─Sb is discussed via "interfacial descriptor" with the aid of Kelvin probe force microscopy (KPFM). This study reveals the rate of electrocatalytic reaction depends on the energy required for electron and proton transfer from the catalyst's surface. It is noteworthy that the assembled Ni─Sb-90 electrolyzer requires only a minuscule cell voltage of ≈1.46 V for water splitting, which is far superior to the art of commercial catalysts.

GV1001 modulates neuroinflammation and improves memory and behavior through the activation of gonadotropin-releasing hormone receptors in a triple transgenic Alzheimer's disease mouse model.

GV1001 protects neural cells from amyloid-ß (Aß) toxicity and other stressors in in vitro studies and demonstrates clinically beneficial effects in patients with moderate to severe Alzheimer's disease (AD). Here, we investigated the protective effects and mechanism of action of GV1001 in triple transgenic AD (3xTg-AD) mice. We found that GV1001 improved memory and cognition in middle- and old-aged 3xTg-AD mice. Additionally, it reduced Aß oligomer and phospho-tau (Ser202 and Thr205) levels in the brain, and mitigated neuroinflammation by promoting a neuroprotective microglial and astrocyte phenotype while diminishing the neurotoxic ones. In vitro, GV1001 bound to gonadotropin releasing hormone receptors (GnRHRs) with high affinity. Levels of cyclic adenosine monophosphate, a direct downstream effector of activated GnRHRs, increased after GV1001 treatment. Furthermore, inhibition of GnRHRs blocked GV1001-induced effects. Thus, GV1001 might improve cognitive and memory functions of 3xTg-AD mice by suppressing neuroinflammation and reducing Aß oligomers levels and phospho-tau by activating GnRHRs and their downstream signaling pathways.

Bursal Acromial Resurfacing Improves Shoulder Biomechanics in a Cadaveric Model of Massive Rotator Cuff Tear.

PURPOSE: To investigate the effectiveness of bursal acromial resurfacing (acromiograft) on acromiohumeral distance, subacromial contact area, and pressure in a cadaveric model of massive rotator cuff tear. METHODS: Eight fresh-frozen cadaveric shoulders were tested using a customized shoulder testing system. Humeral head translation, subacromial contact pressure, and the subacromial contact area were evaluated across 4 conditions: (1) intact shoulder; (2) simulated massive rotator cuff tear, (3) 3-mm acromiograft condition, and (4) 6-mm acromiograft condition. The acromiografts were simulated using Teflon and a reported technique. The values were measured at 0°, 20°, and 40° abduction and 0°, 30°, 60°, and 90° external rotation for each abduction status. RESULTS: Compared with a massive cuff tear, the 6-mm acromiograft significantly reduced the superior translation of the humeral head at all abduction/external rotation angles (P < .05). The 3-mm acromiograft also decreased superior translation of the humeral head compared with massive cuff tear, but not all differences were significant. The 3- and 6-mm acromiografts significantly decreased the subacromial contact pressure and increased the subacromial contact area in almost all positions (P < .05). The 3-mm acromiograft maintained biomechanical properties similar to the intact condition, whereas the 6-mm acromiograft increased the contact area. CONCLUSIONS: This biomechanical study demonstrated that both 3- and 6-mm acromiografts using Teflon in a cadaveric model of a massive cuff tear resulted in recentering of the superiorly migrated humeral head, increased the subacromial contact area, and decreased the subacromial contact pressure. The 3-mm graft was sufficient for achieving the intended therapeutic effects. CLINICAL RELEVANCE: The acromiograft can normalize altered biomechanics and may aid in the treatment of massive cuff tears. Because grafting the acromion's undersurface is new with limited clinical outcomes, further observation is crucial. Using a Teflon instead of an acellular dermal matrix allograft for bursal acromial resurfacing could yield different results, requiring careful interpretation.

Varus-valgus alignment of humeral short stem in reverse total shoulder arthroplasty: does it really matter?

BACKGROUND: The utilization of short humeral stems in reverse total shoulder arthroplasty has gained attention in recent times. However, concerns regarding the risk of misalignment during implant insertion are associated with their use. METHODS: Eight fresh-frozen cadaveric shoulders were prepared for dissection and biomechanical testing. A bespoke humeral implant was fabricated to facilitate assessment of neutral, varus, and valgus alignments using a single stem, and 10° was established as the maximum permissible angle for misalignments. Shift in humerus position and changes in deltoid length attributable to misalignments relative to the neutral position were evaluated using a Microscribe 3DLx system. The impingement-free range of motion, encompassing abduction, adduction, internal rotation, and external rotation (ER), was gauged using a digital goniometer. The capacity for abduction was evaluated at maximal abduction angles under successive loading on the middle deltoid. A specialized traction system coupled with a force transducer was employed to measure anterior dislocation forces. RESULTS: Relative to the neutral alignment, valgus alignment resulted in a more distal (10.5 ± 2.4 mm) and medial (8.3 ± 2.2 mm) translation of the humeral component, whereas the varus alignment resulted in the humerus shifting more superiorly (11.2 ± 1.3 mm) and laterally (9.9 ± 0.9 mm) at 0° abduction. The valgus alignment exhibited the highest abduction angle than neutral alignment (86.2°, P < .001). Conversely, the varus alignment demonstrated significantly higher adduction (18.4 ± 7.4°, P < .001), internal rotation (68.9 ± 15.0°, P = .014), and ER (45.2 ± 10.5°, P = .002) at 0° abduction compared to the neutral alignments. Anterior dislocation forces were considerably lower (23.8 N) in the varus group compared to the neutral group at 0°ER (P = .047). Additionally, abduction capability was markedly higher in varus alignment at low deltoid loads than the neutral alignment (5N, P = .009; 7.5 N, P = .007). CONCLUSIONS: The varus position enhances rotational range of motion (ROM) but increases instability, while the valgus position does not significantly impact ROM or instability compared to the neutral position.

hTERT Peptide Fragment GV1001 Prevents the Development of Porphyromonas gingivalis-Induced Periodontal Disease and Systemic Disorders in ApoE-Deficient Mice.

GV1001, an anticancer vaccine, exhibits other biological functions, including anti-inflammatory and antioxidant activity. It also suppresses the development of ligature-induced periodontitis in mice. Porphyromonas gingivalis (Pg), a major human oral bacterium implicated in the development of periodontitis, is associated with various systemic disorders, such as atherosclerosis and Alzheimer's disease (AD). This study aimed to explore the protective effects of GV1001 against Pg-induced periodontal disease, atherosclerosis, and AD-like conditions in Apolipoprotein (ApoE)-deficient mice. GV1001 effectively mitigated the development of Pg-induced periodontal disease, atherosclerosis, and AD-like conditions by counteracting Pg-induced local and systemic inflammation, partly by inhibiting the accumulation of Pg DNA aggregates, Pg lipopolysaccharides (LPS), and gingipains in the gingival tissue, arterial wall, and brain. GV1001 attenuated the development of atherosclerosis by inhibiting vascular inflammation, lipid deposition in the arterial wall, endothelial to mesenchymal cell transition (EndMT), the expression of Cluster of Differentiation 47 (CD47) from arterial smooth muscle cells, and the formation of foam cells in mice with Pg-induced periodontal disease. GV1001 also suppressed the accumulation of AD biomarkers in the brains of mice with periodontal disease. Overall, these findings suggest that GV1001 holds promise as a preventive agent in the development of atherosclerosis and AD-like conditions associated with periodontal disease.

Unravelling the Bi-Functional Electrocatalytic Properties of {Mo72Fe30} Polyoxometalate Nanostructures for Overall Water Splitting Using Scanning Electrochemical Microscope and Electrochemical Gating Methods.

This study reports the use of Keplerate-type {Mo72Fe30} polyoxometalate (POMs) nanostructures as a bi-functional-electrocatalyst for HER and OER in an alkaline medium with a lower overpotential (135 mV for HER and 264 mV for OER), and excellent electrochemical stability. The bi-functional catalytic properties of {Mo72Fe30} POM are studied using a scanning electrochemical microscope (SECM) via current mapping using substrate generation and tip collection mode. Furthermore, the bipolar nature of the {Mo72Fe30} POM nano-electrocatalysts is studied using the electrochemical gating via simultaneous monitoring of the electrochemical (cell) and electrical ({Mo72Fe30} POM) signals. Next, a prototype water electrolyzer fabricated using {Mo72Fe30} POM electrocatalysts showed they can drive 10 mA cm-2 with a low cell voltage of 1.62 V in lab-scale test conditions. Notably, the {Mo72Fe30} POM electrolyzers' performance assessment based on recommended conditions for industrial aspects shows that they require a very low overpotential of 1.89 V to drive 500 mA cm-2, highlighting their promising candidature toward clean-hydrogen production.

Investigating composite electrode materials of metal oxides for advanced energy storage applications.

Electrochemical energy systems mark a pivotal advancement in the energy sector, delivering substantial improvements over conventional systems. Yet, a major challenge remains the deficiency in storage technology to effectively retain the energy produced. Amongst these are batteries and supercapacitors, renowned for their versatility and efficiency, which depend heavily on the quality of their electrode materials. Metal oxide composites, in particular, have emerged as highly promising due to the synergistic effects that significantly enhance their functionality and efficiency beyond individual components. This review explores the application of metal oxide composites in the electrodes of batteries and SCs, focusing on various material perspectives and synthesis methodologies, including exfoliation and hydrothermal/solvothermal processes. It also examines how these methods influence device performance. Furthermore, the review confronts the challenges and charts future directions for metal oxide composite-based energy storage systems, critically evaluating aspects such as scalability of synthesis, cost-effectiveness, environmental sustainability, and integration with advanced nanomaterials and electrolytes. These factors are crucial for advancing next-generation energy storage technologies, striving to enhance performance while upholding sustainability and economic viability.

GV1001 reduces neurodegeneration and prolongs lifespan in 3xTg-AD mouse model through anti-aging effects.

GV1001, which mimics the activity of human telomerase reverse transcriptase, protects neural cells from amyloid beta (Aß) toxicity and other stressors through extra-telomeric function, as noted in our prior in vitro studies. As per a recent phase II clinical trial, it improves cognitive function in patients with moderate to severe dementia. However, the underlying protective mechanisms remain unclear. This study aimed to investigate the effects of GV1001 on neurodegeneration, senescence, and survival in triple transgenic Alzheimer's disease (3xTg-AD) mice. GV1001 (1 mg/kg) was subcutaneously injected into old 3xTg-AD mice thrice a week until the endpoint for sacrifice, and survival was analysed. Magnetic resonance imaging (MRI) and Prussian blue staining (PBS) were performed to evaluate entry of GV1001 entrance into the brain. Diverse molecular studies were performed to investigate the effect of GV1001 on neurodegeneration and cellular senescence in AD model mice, with a particular focus on BACE, amyloid beta1-42 (Aß1-42), phosphorylated tau, volume of dentate gyrus, ß-galactosidase positive cells, telomere length, telomerase activity, and ageing-associated proteins. GV1001 crossed the blood-brain barrier, as confirmed by assessing the status of ferrocenecarboxylic acid-conjugated GV1001 using magnetic resonance imaging and PBS. GV1001 increased the survival of 3xTg-AD mice. It decreased BACE and Aß1-42 levels, neurodegeneration (i.e., reduced CA1, CA3 and dentate gyrus volume, decreased levels of senescence-associated ß-galactosidase positive cells, and increased telomere length and telomerase activity), and levels of ageing-associated proteins. We suggest that GV1001 exerts anti-ageing effects in 3xTg-AD mice by reducing neurodegeneration and senescence, which contributes to improved survival.

Retrospective Analysis of the Clinical Characteristics of Patients with Breast Cancer Treated with Telomerase Peptide Immunotherapy Combined with Cytotoxic Chemotherapy.

Purpose: Telomerase activation, a critical step in cancer progression, occurs in approximately 95% of breast cancer cases. Telomerase is an attractive therapeutic target for breast cancer owing to its unique expression pattern. GV1001, a telomerase-derived peptide, is loaded onto human leukocyte antigen (HLA) class II antigen-presenting cells and binds to CD4+ T cell activating immune responses. This study aimed to evaluate the effectiveness and safety of co-administration of GV1001 and cytotoxic chemotherapy in patients with heavily-treated metastatic breast cancer. Patients and methods: We analyzed 63 patients with breast cancer who received both GV1001 and cytotoxic chemotherapy. The GV 1001 administration methods involves 0.56 mg intradermal injection three times during the first week, one time at weeks 2, 3, 4, and 6, and then once every 28 days. The primary endpoint of this study was quality of life according to EORTC QLO-C30 and EQ-5D, while the secondary endpoint was the antitumor response according to RECIST 1.1, progression-free survival, overall survival, and toxicity profile. Results: In 34 patients with HR+ breast cancer evaluable for tumor response, the disease control rate (DCR) and overall response rate (ORR) were 58.8% and 26.4%, respectively. The DCR and ORR were 66.6% and 28.5% in 21 patients with HER-2+ and 50% and 25% in patients with triple-negative breast cancer (TNBC), respectively. The median progression free survival was 10.4, 8.7, and 5.6 months in HR+, HER-2+, TNBC, respectively. The overall survival was 19.7, 13.2, and 9.4 months for patients with HR+, HER-2+, and TNBC, respectively. Most patients had an improved quality of life with statistically significant differences in some variables. The patients in this study experienced no additional toxicities other than the cytotoxic chemotherapy-associated side effects. Conclusion: GV1001 is a relatively safe anticancer vaccine for patients with heavily-treated breast cancer and can to improve the quality of life.