Inside and Outside Flank Alternate Meshing Silent Chain and Experimental Evaluation of Dynamic Performance

Abstract: A new silent chain with inside and outside flank alternating meshing mechanism and sprockets were designed, and the main technical parameters and structure type of the plate and sprocket profile were described. In order to verify the good meshing transmission performance of the new silent chain, we did the performance comparison test for inside and outside flank alternate meshing silent chain and the ANSI standard silent chain with regard to transverse displacement vibration and wear extension. The results show that the new silent chain transmits smoothly, with standard silent chain compared to significantly reduce vibration quantity of transverse displacement, and it has good wear resistance properties, which is much superior to the standard silent chain. The results also verify low impact characteristics of the new silent chain and the rationality of design method. Because of its special meshing mechanism and structure type of alternate load, the new silent chain reduces meshing impact, vibration and polygon effect when chain and sprocket meshes, and fundamentally improves silent chain transmission performance, then extends the life of the chain

Phosphatidylinositol 3-Kinase- Signaling Promotes Campylobacter jejuni-Induced Colitis through Neutrophil Recruitment in Mice

Crypt abscesses caused by excessive neutrophil accumulation are prominent features of human campylobacteriosis and its associated pathology. The molecular and cellular events responsible for this pathological situation are currently unknown. We investigated the contribution of PI3Kγ signaling in Campylobacter jejuni-induced neutrophil accumulation and intestinal inflammation. Germ-free and specific pathogen free Il10−/−and germ-free Il10−/−; Rag2−/− mice were infected with C. jejuni (109 CFU/mouse). PI3Kγ signaling was manipulated using either the pharmacological PI3Kγ inhibitor AS252424 (i.p. 10 mg/kg daily) or genetically using Pi3γ−/− mice. After up to 14 days, inflammation was assessed histologically and by measuring levels of colonic Il1β, Cxcl2 and Il17a mRNA. Neutrophils were depleted using anti-Gr1 antibody (i.p. 0.5 mg/mouse/every 3 days). Using germ-free Il10−/−; Rag2−/− mice, we observed that innate immune cells are the main cellular compartment responsible for campylobacteriosis. Pharmacological blockade of PI3Kγ signaling diminished C. jejuni-induced intestinal inflammation, neutrophil accumulation and NF-κB activity, which correlated with reduced Il1β (77%), Cxcl2 (73%) and Il17a (72%) mRNA accumulation. Moreover, Pi3kγ−/− mice pretreated with anti-IL-10R were resistant to C. jejuni-induced intestinal inflammation compared to Wt mice. This improvement was accompanied by a reduction of C. jejuni translocation into the colon and extra-intestinal tissues and by attenuation of neutrophil migratory capacity. Furthermore, neutrophil depletion attenuated C. jejuni-induced crypt abscesses and intestinal inflammation. Our findings indicate that C. jejuni-induced PI3Kγ signaling mediates neutrophil recruitment and intestinal inflammation in Il10−/− mice. Selective pharmacological inhibition of PI3Kγ may represent a novel means to alleviate severe cases of campylobacteriosis, especially in antibiotic-resistant strains

Interferon-alpha responsible EPN3 regulates hepatitis B virus replication

Hepatitis B virus (HBV) infection remains a major health problem worldwide, and the current antiviral therapy, including nucleoside analogs, cannot achieve life-long cure, and clarification of antiviral host immunity is necessary for eradication. Here, we found that a clathrin-binding membrane protein epsin3 (EPN3) negatively regulates the expression of HBV RNA. EPN3 expression was induced by transfection of an HBV replicon plasmid, and reduced HBV-RNA level in hepatic cell lines and murine livers hydrodynamically injected with the HBV replicon plasmid. Viral RNA reduction by EPN3 was dependent on transcription, and independent from epsilon structure of viral RNA. Viral RNA reduction by overexpression of p53 or IFN-α treatment, was attenuated by knockdown of EPN3, suggesting its role downstream of IFN-α and p53. Taken together, this study demonstrates the anti-HBV role of EPN3. The mechanism how it decreases HBV transcription is discussed

Experimental Study on Flexural Behaviour of Prestressed Specified Density Concrete Composite Beams

To solve the problem of poor seismic resistance due to the disadvantages of traditional concrete composite beams, such as heavy self-weight in prefabricated buildings, prestressed specified-density concrete composite beams are proposed herein. First, a mix ratio test of specified-density concrete was performed. Second, five prestressed specified-density composite beams, a prestressed ordinary concrete composite beam, and a prestressed semi lightweight concrete cast-in-situ beam were tested. The influence of the precast concrete height, reinforcement ratio, and concrete materials on the failure mechanism, flexural bearing capacity, and short-term stiffness of the composite beams were analysed. From the results, the specified-density concrete composite beams and the ordinary composite beam had similar ultimate bearing capacities, but the average distance between crack spacings of the former was smaller. The precast concrete height affected the bending performance of the prestressed specified density concrete composite beam insignificantly, but the maximum ultimate bearing capacity of the composite beam could be increased by 35.6% by increasing the reinforcement ratio. The composite beam and the cast-in-place beam exhibited similar load-carrying capabilities and deformation properties. The average crack spacing, cracking load, and ultimate load value of the specified density concrete composite beams calculated according to the China national standard “Code for design of concrete structures” were consistent with the measured values

Experimental Study on Flexural Behaviour of Prestressed Specified Density Concrete Composite Beams

To solve the problem of poor seismic resistance due to the disadvantages of traditional concrete composite beams, such as heavy self-weight in prefabricated buildings, prestressed specified-density concrete composite beams are proposed herein. First, a mix ratio test of specified-density concrete was performed. Second, five prestressed specified-density composite beams, a prestressed ordinary concrete composite beam, and a prestressed semi lightweight concrete cast-in-situ beam were tested. The influence of the precast concrete height, reinforcement ratio, and concrete materials on the failure mechanism, flexural bearing capacity, and short-term stiffness of the composite beams were analysed. From the results, the specified-density concrete composite beams and the ordinary composite beam had similar ultimate bearing capacities, but the average distance between crack spacings of the former was smaller. The precast concrete height affected the bending performance of the prestressed specified density concrete composite beam insignificantly, but the maximum ultimate bearing capacity of the composite beam could be increased by 35.6% by increasing the reinforcement ratio. The composite beam and the cast-in-place beam exhibited similar load-carrying capabilities and deformation properties. The average crack spacing, cracking load, and ultimate load value of the specified density concrete composite beams calculated according to the China national standard “Code for design of concrete structures” were consistent with the measured values

An integrative evaluation of circadian gene TIMELESS as a pan-cancer immunological and predictive biomarker

Abstract Background The gene TIMELESS, which is involved in the circadian clock and the cell cycle, has recently been linked to various human cancers. Nevertheless, the association between TIMELESS expression and the prognosis of individuals afflicted with pan-cancer remains largely unknown. Objectives The present study aims to exhaustively scrutinize the expression patterns, functional attributes, prognostic implications, and immunological contributions of TIMELESS across diverse types of human cancer. Methods The expression of TIMELESS in normal and malignant tissues was examined, as well as their clinicopathologic and survival data. The characteristics of genetic alteration and molecular subtypes of cancers were also investigated. In addition, the relationship of TIMELESS with immune infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), and drug sensitivity was illustrated. Immunohistochemistry (IHC) was used to validate the expression of TIMELESS in clinical patients with several types of cancer. Results In contrast to the matching normal controls, most tumor types were found to often overexpress TIMELESS. Abnormal expression of TIMELESS was significantly related to more advanced tumor stage and poorer prognosis of breast cancer, as well as infiltrating immune cells such as cancer-associated fibroblast infiltration in various tumors. Multiple cancer types exhibited abnormal expression of TIMELESS, which was also highly correlated with MSI and TMB. More crucially, TIMELESS showed promise in predicting the effectiveness of immunotherapy and medication sensitivity in cancer therapy. Moreover, cell cycle, DNA replication, circadian rhythm, and mismatch repair were involved in the functional mechanisms of TIMELESS on carcinogenesis. Furthermore, immunohistochemical results manifested that the TIMELESS expression was abnormal in some cancers. Conclusions This study provides new insights into the link between the circadian gene TIMELESS and the development of various malignant tumors. The findings suggest that TIMELESS could be a prospective prognostic and immunological biomarker for pan-cancer

Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway

Resveratrol, a natural compound in grapes and red wine, has drawn attention due to potential cardiovascular-related health benefits. However, its effect on vascular inflammation at physiologically achievable concentrations is largely unknown. In this study, resveratrol in concentrations as low as 1 μm suppressed TNF-α-induced monocyte adhesion to human EA.hy926 endothelial cells (ECs), a key event in the initiation and development of atherosclerosis. Low concentrations of resveratrol (0.25–2 μm) also significantly attenuated TNF-α-stimulated mRNA expressions of MCP-1/CCL2 and ICAM-1, which are vital mediators of EC-monocyte adhesion molecules and cytokines for cardiovascular plaque formation. Additionally, resveratrol diminished TNF-α-induced IκB-α degradation and subsequent nuclear translocation of NF-κB p65 in ECs. In the animal study, resveratrol supplementation in diet significantly diminished TNF-α-induced increases in circulating levels of adhesion molecules and cytokines, monocyte adhesion to mouse aortic ECs, F4/80-positive macrophages and VCAM-1 expression in mice aortas and restored the disruption in aortic elastin fiber caused by TNF-α treatment. The animal study also confirmed that resveratrol blocks the activation of NF-κB In Vivo. In conclusion, resveratrol at physiologically achievable concentrations displayed protective effects against TNF-α-induced vascular endothelial inflammation in vitro and In Vivo. The ability of resveratrol in reducing inflammation may be associated with its role as a down-regulator of the NF-κB pathway

Investigation of <italic>&#x03C7;</italic>⁽²⁾-Translated Optical Frequency Combs Tunability in Gallium Phosphide-on- Insulator Resonators

We describe a synergistic optimization approach that enables highly efficient frequency translation of a Kerr optical frequency comb (OFC) from 1550 nm to 775 nm in a gallium phosphide-on-insulator (GaP-OI) microresonator. Key distinctions from previous GaP-OI works which focused on individual optical nonlinearity are that this work not only emphasizes the interaction between the second- and third-order nonlinearity, but also explores the tunability of the &#x03C7;(2)-translated OFC through geometric and temperature tuning. We apply this approach to the burgeoning GaP-OI platform and demonstrate that a 50 &#x03BC;m-radius ring resonator with a cross-section of 555 nm &#x00D7; 600 nm has an intracavity second harmonic (SH) generation efficiency as high as 71.5&#x0025;&#x002F;W, 3 times larger compared to the state-of-the-art designs. The sum-frequency (SF) comb at 775 nm has a geometric tuning sensitivity of 354 GHz&#x002F;nm, and a thermal tuning sensitivity of 24.8 GHz&#x002F;K, paving the way for post-fabrication trimming and in-situ spectral shaping, with a broader potential to realize highly efficient, wide-spectrum, and tunable on-chip nonlinear sources