Graphene Enhances the Loading Capacity and Lubrication Performance of Ionic Liquids: A Molecular Dynamics Study.

Ionic liquid (IL) combined with graphene additives have garnered extensive attention in the field of high-performance lubricating materials. However, the ambiguous mechanism of graphene influencing the load-carrying and anti-wear capacity of ILs needs further study. In this work, friction simulation shows that adding graphene causes friction coefficient to reduce by up to 88% compared with pure ILs, but lubrication performance is lost due to the destruction of graphene under high stress. Meanwhile, multilayer graphene has better friction-reducing performance and friction durability as compared to the monolayer structure, which is attributed to the easy-shear property and the reduction in the percentage of high tensile stress sites in multilayer graphene structure. In addition, it was found that excessively thick ILs film would form a three-body abrasive wear structure with graphene, which accelerated the structural destruction of graphene and caused a decline in its tribological properties. It is believed these findings can be valuable for designing of high-performance lubricating oil for practical engineering.

Microstructural Evolution, Mechanical Properties and Tribological Behavior of B4C-Reinforced Ti In Situ Composites Produced by Laser Powder Bed Fusion.

Based on the advantage of rapid net-shape fabrication, laser powder bed fusion (LPBF) is utilized to process B4C-reinforced Ti composites. The effect of volumetric energy density (VED) on the relative density, microstructural evolution, tensile properties and wear behaviors of B4C-reinforced Ti composites were systematically investigated. The LPBF-ed samples with high relative density (>99%) can be achieved, while the pores and un-melted powders can be observed in the sample owing to the low energy input (33 J/mm3). The additive particulates B4C were transformed into needle-like TiB whiskers with nano-scale while C dissolved in the Ti matrix. Fine-scale grains (<10 µm) with random crystallographic orientation can be achieved and the residual stress shows a downtrend as the VED increases. Through the analysis of the tensile and wear tests, the sample at 61 J/mm3 VED showed a good combination of strength and wear performance, with an ultimate tensile strength of 951 MPa and a wear rate of 3.91 × 10-4 mm3·N-1m-1. The microstructural evolution in VED changes and the corresponding underlying strengthening mechanisms of LPBF-ed Ti + B4C composites are conducted in detail.

Beyond canonical PROTAC: biological targeted protein degradation (bioTPD).

Targeted protein degradation (TPD) is an emerging therapeutic strategy with the potential to modulate disease-associated proteins that have previously been considered undruggable, by employing the host destruction machinery. The exploration and discovery of cellular degradation pathways, including but not limited to proteasomes and lysosome pathways as well as their degraders, is an area of active research. Since the concept of proteolysis-targeting chimeras (PROTACs) was introduced in 2001, the paradigm of TPD has been greatly expanded and moved from academia to industry for clinical translation, with small-molecule TPD being particularly represented. As an indispensable part of TPD, biological TPD (bioTPD) technologies including peptide-, fusion protein-, antibody-, nucleic acid-based bioTPD and others have also emerged and undergone significant advancement in recent years, demonstrating unique and promising activities beyond those of conventional small-molecule TPD. In this review, we provide an overview of recent advances in bioTPD technologies, summarize their compositional features and potential applications, and briefly discuss their drawbacks. Moreover, we present some strategies to improve the delivery efficacy of bioTPD, addressing their challenges in further clinical development.

Upper limb movement characteristics in volleyball athletes / Características do movimento dos membros superiores em atletas de voleibol / Características del movimiento de las extremidades superiores en atletas de voleibol

ABSTRACT Introduction Passing and serving are the most direct and efficient tactics for scoring points in volleyball. The recoil of the upper limbs in dominating the ball requires strength and muscular explosion, where the effect of the body's angular momentum accompanies a joint and rhythmic action. Objective This study aims to analyze muscle strength in upper limb movements in volleyball athletes. Methods Several volleyball players volunteered for the research. The movement when the athlete hits the ball was analyzed using kinematic analysis. The relationship between muscle strength and ball movement was also analyzed. Results Body muscle tissue can be effectively trained during volleyball practice. The compound movements also help in the elasticity of the abdominal muscles. The stimulation of other muscle groups was observed in the participation of the movements. Conclusion In modern volleyball training, athletes should strengthen their training with rapid trunk muscle swing exercises to improve the coordination ability of the sets of muscle groups. The protocols presented can assist in improving players' skills and performance. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução Passar e servir são as táticas mais diretas e eficientes de marcar pontos no voleibol. O recuo dos membros superiores no domínio da bola requer força e explosão muscular onde o efeito do momento angular do corpo acompanha uma ação conjunta e rítmica. Objetivo O objetivo deste estudo é analisar a força muscular no movimento dos membros superiores em atletas de voleibol. Métodos Vários jogadores de voleibol voluntariaram-se para a pesquisa. Foi analisado o movimento quando o atleta acerta a bola utilizando o recurso de análise cinemática. Também foi analisada a relação entre a força muscular e o movimento da bola. Resultados O tecido muscular corporal pode ser efetivamente treinado durante a prática do voleibol. Os movimentos compostos também auxiliam na elasticidade da musculatura abdominal. O estímulo de outros grupos musculares foi observado na participação dos movimentos. Conclusão No treinamento moderno de voleibol, os atletas devem fortalecer o treinamento com exercício rápido de balanço dos músculos do tronco para melhorar a capacidade de coordenação dos conjuntos de grupos musculares. Os protocolos apresentados podem auxiliar na melhoria das habilidades e no desempenho dos jogadores. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El pase y el saque son las tácticas más directas y eficaces para conseguir puntos en el voleibol. El retroceso de los miembros superiores en el dominio del balón requiere fuerza y explosión muscular donde el efecto del momento angular del cuerpo acompaña una acción conjunta y rítmica. Objetivo El objetivo de este estudio es analizar la fuerza muscular en el movimiento de las extremidades superiores en atletas de voleibol. Métodos Varios jugadores de voleibol se ofrecieron como voluntarios para la investigación. El movimiento cuando el atleta golpea la pelota se analizó mediante la función de análisis cinemático. También se analizó la relación entre la fuerza muscular y el movimiento del balón. Resultados El tejido muscular del cuerpo puede entrenarse eficazmente durante la práctica del voleibol. Los movimientos compuestos también ayudan a la elasticidad de los músculos abdominales. Se observó la estimulación de otros grupos musculares en la participación de los movimientos. Conclusión En el entrenamiento moderno de voleibol, los atletas deben reforzar su entrenamiento con ejercicios de balanceo rápido de los músculos del tronco para mejorar la capacidad de coordinación de los conjuntos de grupos musculares. Los protocolos presentados pueden ayudar a mejorar las habilidades y el rendimiento de los jugadores. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Effect of Na-ion intercalation on the thermal conductivity of carbon honeycomb nanostructure.

This work studies the thermal conductivity of Na-ion intercalated carbon honeycomb (CHC) via the combination of first-principles calculation and molecular dynamics simulation. The effects of ion concentration, ion charge, temperature, and strain are explored. The simulation results show that the thermal conductivity of CHC presents a nonmonotonic dependence on the ion concentration. The enhanced phonon scattering and increased phonon group velocities of CHC induced by its interaction with the Na ions are responsible for the nonmonotonic dependence. Both the increases in the ion charge and temperature reduce the thermal conductivity. In contrast, a compressive strain of around -3% can increase the thermal conductivity by eliminating the phonon softening effect caused by the volume expansion of CHC during the ion intercalation. However, further increasing the strain negatively or positively from -3% leads to a decrease in the thermal conductivity. The simulation results presented in this work are beneficial in understanding the thermal properties of CHC when it is used as an electrode in ion batteries and supercapacitors.

Reciprocal positive regulation between BRD4 and YAP in GNAQ-mutant uveal melanoma cells confers sensitivity to BET inhibitors.

Uveal melanoma (UM) is the most common intraocular cancer in adults. UMs are usually initiated by a mutation in GNAQ or GNA11 (encoding Gq or G11, respectively), unlike cutaneous melanomas (CMs), which usually carry a BRAF or NRAS mutation. Currently, there are no clinically effective targeted therapies for UM carrying Gq/11 mutations. Here, we identified a causal link between Gq activating mutations and hypersensitivity to bromodomain and extra-terminal (BET) inhibitors. BET inhibitors transcriptionally repress YAP via BRD4 regardless of Gq mutation status, independently of Hippo core components LATS1/2. In contrast, YAP/TAZ downregulation reduces BRD4 transcription exclusively in Gq-mutant cells and LATS1/2 double knockout cells, both of which are featured by constitutively active YAP/TAZ. The transcriptional interdependency between BRD4 and YAP identified in Gq-mutated cells is responsible for the preferential inhibitory effect of BET inhibitors on the growth and dissemination of Gq-mutated UM cells compared to BRAF-mutated CM cells in both culture cells and animal models. Our findings suggest BRD4 as a viable therapeutic target for Gq-driven UMs that are addicted to unrestrained YAP function.

Recent Progress on Wear-Resistant Materials: Designs, Properties, and Applications.

There has been tremendous interest in the development of different innovative wear-resistant materials, which can help to reduce energy losses resulted from friction and wear by ≈40% over the next 10-15 years. This paper provides a comprehensive review of the recent progress on designs, properties, and applications of wear-resistant materials, starting with an introduction of various advanced technologies for the fabrication of wear-resistant materials and anti-wear structures with their wear mechanisms. Typical strategies of surface engineering and matrix strengthening for the development of wear-resistant materials are then analyzed, focusing on the development of coatings, surface texturing, surface hardening, architecture, and the exploration of matrix compositions, microstructures, and reinforcements. Afterward, the relationship between the wear resistance of a material and its intrinsic properties including hardness, stiffness, strength, and cyclic plasticity is discussed with underlying mechanisms, such as the lattice distortion effect, bonding strength effect, grain size effect, precipitation effect, grain boundary effect, dislocation or twinning effect. A wide range of fundamental applications, specifically in aerospace components, automobile parts, wind turbines, micro-/nano-electromechanical systems, atomic force microscopes, and biomedical devices are highlighted. This review is concluded with prospects on challenges and future directions in this critical field.

Management of post-traumatic long bone defects: A comparative study based on long-term results.

BACKGROUND: Reconstruction of post-traumatic long bone defects is a formidable problem. To date, the approaches for bony reconstruction remain controversial. Thus, we aimed to compare the different methods in the treatment of patients with post-traumatic long bone defects, based on the long-term functional and self-evaluation results. METHODS: We retrospectively reviewed data on patients with post-traumatic long bone defects of the lower extremities from January 2006 to January 2015. The patients were divided into three groups according to the surgical method used to treat the defects (group 1, free vascularized fibular transfer; group 2, distraction osteogenesis; group 3, the induced membrane technique). Data including the complication rates, entire treatment period, long-term visual analog scale scores, and Sickness Impact Profile (SIP) scores during follow-up were recorded. RESULTS: A total of 317 patients were included, with 106, 132, and 79 patients in groups 1, 2, and 3, respectively. The major complication rates were 22.6%, 25.8%, and 26.6% for the groups (P > 0.05), respectively. The mean treatment durations for bony defects, from surgery to non-protected weight-bearing, were 65.1, 46.5, and 56.6 weeks for each group, respectively. At 2 years postoperatively, the average SIP scores for each group were 10.5, 11.7, and 11.5, respectively (P > 0.05). CONCLUSION: Patients who sustained long bone defects can be advised that either one of these three methods which typically results in long-term outcomes equivalent to others. LEVEL OF EVIDENCE: retrospective study.

Association of Nonalcoholic Fatty Liver Disease With Osteoporotic Fractures: A Cross-Sectional Retrospective Study of Chinese Individuals.

Objective: Nonalcoholic fatty liver disease (NAFLD) is related to several inflammatory or metabolic diseases. However, findings of previous studies investigating the association between NAFLD and BMD are inconsistent. Only one study reported a potential association between NAFLD and osteoporotic fracture. This study investigated whether NAFLD in older participants (>55 years) was associated with osteoporotic fracture risk. Materials and Methods: This cross-sectional, observational study included 2,695 participants (35.7% men, 614 cases of NAFLD, and 383 fractures). Standardized questionnaires, laboratory tests, and physical and ultrasonic examinations were completed. Results: After adjusting for various factors including serum triglycerides (TG), high-density cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), multivariate logistic regression models revealed a marginal association between NAFLD and osteoporotic fracture risk in men (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.06-3.27; P = 0.030) but no association in women (OR, 1.05; 95% CI, 0.74-1.48; P = 0.800). Further stratified analyses showed a significant association between NAFLD and osteoporotic fracture risk in men without high TG, low HDL-C, and high LDL-C. Conclusions: There was a significant association between NAFLD and osteoporotic fracture risk in older Chinese men, particularly men without dyslipidemia.

Association of gout with osteoporotic fractures.

PURPOSE: Previous studies have shown that serum uric acid levels and inflammation are associated with bone mineral density. Gout, a disease characterized by hyperuricemia and inflammation, contributes to the risk of osteoporotic fractures. However, this association is controversial. Therefore, this study investigated whether gout in older people (age > 55 years) is associated with osteoporotic fracture risk. METHODS: This population-based, cross-sectional study included 2674 participants (147 cases of gout and 388 fractures). Standardized and self-administered questionnaires were employed and physical examinations, blood tests, and bone mineral density examinations were performed; multivariate-adjusted logistic regression models were used to evaluate associations between gout and osteoporotic fracture risk. RESULTS: The data were adjusted for age; smoking status; alcohol status; physical activity; body mass index; waist circumference; hypertension; cardiovascular events; diabetes mellitus; rheumatoid arthritis; serum levels of total cholesterol (TC), triglycerides, and high- and low-density lipids; and T-scores. We found a significant association between gout and osteoporotic fracture risk in women (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.12-3.56; P = 0.019), but no such association in men (OR, 1.30; 95% CI, 0.58-2.88; P = 0.525). Further stratified analyses showed a significant association between gout and osteoporotic fracture risk in women without rheumatic arthritis and in those with high TC levels or with osteoporosis (all, P < 0.05). CONCLUSIONS: In older Chinese adults, gout is significantly associated with the risk of osteoporotic fractures in women, especially those without rheumatic arthritis and in those with high TC levels or with osteoporosis.

Geraniin inhibits migration and invasion of human osteosarcoma cancer cells through regulation of PI3K/Akt and ERK1/2 signaling pathways.

Geraniin, an active compound isolated from Geranium sibiricum, was found to inhibit proliferation and induce apoptosis of tumor cells. However, the antimetastatic effects of geraniin remain elusive. Our study found the potential antitumor mechanisms of geraniin through inhibiting the migration and invasion of human osteosarcoma U2OS cells. The western blot, gelatin zymography, and reversed transcription-PCR analysis showed that geraniin suppressed matrix metalloproteinase-9 (MMP-9) expression in a concentration-dependent manner. Geraniin potently suppressed the phosphorylation of extracellular signal regulating kinase (ERK)1/2, phosphatidylinositide-3-kinase (PI3K), and Akt, but did not affect phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. Furthermore, when transforming growth factor-ß1 (TGF-ß1) was used as an agonist, geraniin inhibited TGF-ß1-mediated cell invasion and upregulation of MMP-9. These results suggested that geraniin inhibited U2OS cell migration and invasion by reducing the expression of MMP-9 through the PI3K/Akt and ERK1/2 signaling pathways.

Baicalin inhibits human osteosarcoma cells invasion, metastasis, and anoikis resistance by suppressing the transforming growth factor-ß1-induced epithelial-to-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) plays an important role in inducing cancer metastasis. Baicalin, a flavone derivative isolated from Scutellaria spp., shows a series of pharmacological and physiological activities. However, the possible role of baicalin in the EMT is unclear. In this study, we attempted to investigate the potential use of baicalin as an inhibitor of transforming growth factor-ß1 (TGF-ß1)-induced EMT in U2OS cells. We found that TGF-ß1 induced the EMT to promote U2OS cells migration, invasion, and anoikis resistance. Western blotting showed that baicalin inhibited U2OS cells' invasion and migration, increased the expression of the epithelial phenotype marker E-cadherin, repressed the expression of the mesenchymal phenotype marker vimentin, as well as decreased the level of EMT-inducing transcription factors Snail1 and Slug during the initiation of TGF-ß1-induced EMT. Baicalin also inhibited the TGF-ß1-induced increase in cell migration, invasion, and anoikis resistance in TGF-ß1-induced U2OS cells. In addition, the TGF-ß1-mediated phosphorylated levels of Smad2/3 were inhibited by baicalin pretreatment. Above all, we conclude that baicalin suppresses human osteosarcoma cells' migration, invasion, and anoikis resistance in vitro through suppression of TGF-ß1-induced EMT.

[Effect of parthenolide on serum expressions of interleukin-1beta and tumor necrosis factor-alpha in rabbits with knee osteoarthritis].

OBJECTIVE: To observe the therapeutic effect of parthenolide (PTL) on rabbit knee arthritis (KOA) and its effects on serum expression of interleukin-1beta (IL-1beta) and contents of tumor necrosis factor-alpha (TNF-alpha). METHODS: Eight rabbits were randomly selected from 40 healthy pure-bred New Zealand rabbits as the normal control group. The KOA model was established in the rest 32 rabbits by plaster cast fixation of the right hind limb extension position. After modeling they were randomly divided into 4 groups, i.e., the model control group, the high dose PTL group, the middle dose PTL group, and the low dose PTL group, 8 in each group. Serum contents of IL-1beta and TNF-alpha were detected using enzyme-linked immunosorbent assay. RESULTS: Compared with the model group, IL-1beta and TNF-alpha concentration decreased in the 3 PTL groups (P < 0.01). The decrement was positively correlated with PTL concentrations (IL-1beta: r = 0.55, P < 0.01; TNF-alpha: r = 0.56, P < 0.01). The inhibition reached the peak when the PTL concentration arrived at 20 micromol/L. CONCLUSIONS: PTL could down-regulate the blood IL-1beta and TNF-alpha concentrations of KOA rabbits. Besides, the decrement was positively correlated with the PTL concentration.

[The effect of cyclophosphamide on cytokines in patients with primary Sjögren's syndrome-associated interstitial lung disease].

OBJECTIVE: To investigate the mechanisms of cyclophosphamide sequential therapy for patients with primary Sjögren's syndrome-associated interstitial lung disease (PSS-ILD). METHODS: This was a retrospective review of 15 patients (2005 - 2008) with PSS-ILD who underwent cyclophosphamide sequential therapy. Peripheral blood and bronchoalveolar lavage (BALF) were obtain before and 3, 6, 12, 24 months after the treatment. The TNF-α and TGF-ß(1)mRNA levels in peripheral blood were measured using reverse transcription-polymerase chain reaction (RT-PCR). Serum and BALF TNF-α, TGF-ß(1)and MMP-9 levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: (1) The average levels of serum TNF-α (0.39 ± 0.22) and TGF-ß(1) (0.31 ± 0.18) mRNA in patients with PSS-ILD were higher compared with that in patients with PSS without ILD. TNF-α level (0.23 ± 0.19) was significantly decreased 3 months after cyclophosphamide treatment (t = 2.533, P < 0.05), and TGF-ß(1) (0.31 ± 0.18) level markedly decreased after 6 months of treatment (t = 2.617, P < 0.05). (2) The levels of serum TNF-α (11.2 ± 2.6) µg/L, TGF-ß(1) (72 ± 19) µg/L and MMP-9 (38 ± 9) µg/L in patients with PSS-ILD were higher than that in patients with PSS without ILD. TGF-ß(1) (36 ± 12) µg/L level decreased significantly after 3 months of treatment (t = 2.526, P < 0.05), and TNF-α level (7.1 ± 1.3) µg/L markedly decreased after 6 months of therapy (t = 2.578, P < 0.05). MMP-9 level (18 ± 4) µg/L decreased significantly after 12-month treatment (t = 2.329, P < 0.05). (3) The levels of BALF TNF-α (17.1 ± 3.5) µg/L, TGF-ß(1) (36 ± 17) µg/L and MMP-9 (27 ± 10) µg/L in patients with PSS-ILD were higher than that in patients with PSS without ILD. TGF-ß(1) (21 ± 14) µg/L level decreased significantly after 3-month treatment, and TNF-α level (9.4 ± 1.7) µg/L was decreased after 6 months of cyclophosphamide treatment (t = 2.215, P < 0.05). MMP-9 level (13 ± 5) µg/L decreased after 12 months of cyclophosphamide treatment (t = 2.576, P < 0.05). CONCLUSION: The mechanisms of cyclophosphamide treatment may be associated with its inhibition on production of TNF-α, TGF-ß(1)and MMP-9.