Tumor microenvironment in pancreatic ductal adenocarcinoma: Implications in immunotherapy

Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers. Surgical resection is the only curable treatment option, but it is available for only a small fraction of patients at the time of diagnosis. With current therapeutic regimens, the average 5-year survival rate is less than 10% in pancreatic cancer patients. Immunotherapy has emerged as one of the most promising treatment options for multiple solid tumors of advanced stage. However, its clinical efficacy is suboptimal in most clinical trials on pancreatic cancer. Current studies have suggested that the tumor microenvironment is likely the underlying barrier affecting immunotherapy drug efficacy in pancreatic cancer. In this review, we discuss the role of the tumor microenvironment in pancreatic cancer and the latest advances in immunotherapy on pancreatic cancer

The role of lithium in the aging precipitation process of al-zn-mg-cu alloys and its effect on the properties

It is well known that the development of lightweight alloys with improved comprehensive performance and application value are the future development directions for the ultra-high-strength 7xxx series Al-Zn-Mg-Cu alloys used in the aircraft field. As the lightest metal element in nature, lithium (Li) has outstanding advantages in reducing the density and increasing the elastic modulus in aluminum alloys, so Al-Zn-Mg-Cu alloys containing Li have gained widespread attention. Furthermore, since the Al-Zn-Mg-Cu alloy is usually strengthened by aging treatment, it is crucial to understand how Li addition affects its aging precipitation process. As such, in this article, the effects and mechanism of Li on the aging precipitation behavior and the impact of Li content on the aging precipitation phase of Al-Zn-Mg-Cu alloys are briefly reviewed, and the influence of Li on the service properties, including mechanical properties, wear resistance, and fatigue resistance, of Al-Zn-Mg-Cu alloys are explained. In addition, the corresponding development prospects and challenges of the Al-Zn-Mg-Cu-Li alloy are also proposed. This review is helpful to further understand the role of Li in Al-Zn-Mg-Cu alloys and provides a reference for the development of high-strength aluminum alloys containing Li with good comprehensive properties

The Edge Effects Boosting Hydrogen Evolution Performance of Platinum/Transition Bimetallic Phosphide Hybrid Electrocatalysts

Platinum (Pt) is regarded as a promising electrocatalyst for hydrogen evolution reaction (HER). However, its application in an alkaline medium is limited by the activation energy of water dissociation, diffusion of H+, and desorption of H*. Moreover, the formation of effective structures with a low Pt usage amount is still a challenge. Herein, guided by the simulation discovery that the edge effect can boost local electric field (LEF) of the electrocatalysts for faster proton diffusion, platinum nanocrystals on the edge of transition metal phosphide nanosheets are fabricated. The unique heterostructure with ultralow Pt amount delivered an outstanding HER performance in an alkaline medium with a small overpotential of 44.5 mV and excellent stability for 80 h at the current density of −10 mA cm−2. The mass activity of as-prepared electrocatalyst is 2.77 A mg−1Pt, which is 15 times higher than that of commercial Pt/C electrocatalysts (0.18 A mg−1Pt). The density function theory calculation revealed the efficient water dissociation, fast adsorption, and desorption of protons with hybrid structure. The study provides an innovative strategy to design unique nanostructures for boosting HER performances via achieving both synergistic effects from hybrid components and enhanced LEF from the structural edge effect

Long Non-coding RNAs: A New Regulatory Code for Osteoporosis

Osteoporosis is a metabolic bone disease characterized by a decrease in bone mass and degradation of the bone microstructure, which increases bone fragility and fracture risk. However, the molecular mechanisms of osteoporosis remain unclear. Long non-coding RNAs (lncRNAs) have become important epigenetic regulators controlling the expression of genes and affecting multiple biological processes. Accumulating evidence of the involvement of lncRNAs in bone remolding has increased understanding of the molecular mechanisms underlying osteoporosis. This review aims to summarize recent progress in the elucidation of the role of lncRNAs in bone remodeling, and how it contributes to osteoblast and osteoclast function. This knowledge will facilitate the understanding of lncRNA roles in bone biology and shed new light on the modulation and potential treatment of osteoporosis

Corotational Instability, Magnetic Resonances and Global Inertial-Acoustic Oscillations in Magnetized Black-Hole Accretion Discs

Low-order, non-axisymmetric p-modes (also referred as inertial-acoustic modes) trapped in the inner-most region of hydrodynamic accretion discs around black holes, are plausible candidates for high-frequency quasi-periodic oscillations (QPOs) observed in a number of accreting black-hole systems. These modes are subject to global instabilities due to wave absorption at the corotation resonance (where the wave pattern frequency $\omega/m$ equals the disc rotation rate $\Omega$), when the fluid vortensity, $\zeta=\kappa^2/(2\Omega\Sigma)$ (where $\kappa$ and $\Sigma$ are the radial epicyclic frequency and disc surface density, respectively), has a positive gradient. We investigate the effects of disc magnetic fields on the wave absorption at corotation and the related wave super-reflection of the corotation barrier, and on the overstability of disc p-modes. For discs with a pure toroidal field, the corotation resonance is split into two magnetic resonances, where the wave frequency in the corotating frame of the fluid, \tomega=\omega-m\Omega, matches the slow magnetosonic wave frequency. Significant wave energy/angular momentum absorption occurs at both magnetic resonances, but with opposite signs. The combined effect of the two magnetic resonances is to reduce the super-reflection and the growth rate of the overstable p-modes. We show that even a subthermal toroidal field may suppress the overstability of hydrodynamic (B=0) p-modes. For accretion discs with mixed (toroidal and vertical) magnetic fields, two additional Alfven resonances appear, where \tomega matches the local Alfven wave frequency. They further reduce the growth rate of p-modes. Our results suggest that in order for the non-axisymmetric p-modes to be a viable candidate for the observed high-frequency QPOs, the disc magnetic field must be appreciably subthermal, or other mode excitation mechanisms are at work.Comment: 21 pages, 11 figures, MNRAS accepte

Intravitreal injection of Huperzine A promotes retinal ganglion cells survival and axonal regeneration after optic nerve crush

Traumatic optic neuropathy (TON) is a condition that causes massive loss of retinal ganglion cells (RGCs) and their axonal fibers, leading to visual insufficiency. Several intrinsic and external factors can limit the regenerative ability of RGC after TON, subsequently resulting in RGC death. Hence, it is important to investigate a potential drug that can protect RGC after TON and enhance its regenerative capacity. Herein, we investigated whether Huperzine A (HupA), extracted from a Chinese herb, has neuroprotective effects and may enhance neuronal regeneration following the optic nerve crush (ONC) model. We compared the three modes of drug delivery and found that intravitreal injection of HupA could promote RGC survival and axonal regeneration after ONC. Mechanistically, HupA exerted its neuroprotective and axonal regenerative effects through the mTOR pathway; these effects could be blocked by rapamycin. To sum up, our findings suggest a promising application of HupA in the clinical treatment of traumatic optic nerve