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Galactic cosmic rays suffer from solar modulation when they propagate through the heliosphere. The transfer of the local interstellar spectrum (LIS) to the top-of-atmosphere spectra is influenced by solar wind convection, and diffusion on the heliospheric magnetic field (HMF), among other factors. In this work, we derive the LIS of proton (p) and helium (He) covering energies from a few MeV/n to TeV/n, using a nonparameterization method. The study utilizes monthly AMS-02 data on proton and helium fluxes and their ratio to examine the evolution of solar modulation from 2011 May to 2017 May. To improve the fitting, the force-field approximation is modified by assigning different solar modulation potentials for high (ϕ h ) and low (ϕ l ) energy ranges. A sigmoid function is employed to describe the transition between these energy ranges. The analysis reveals that the break in proton and helium fluxes occurs at the same rigidity value, with a mean of approximately 6 GV and this break is more pronounced during the HMF reversal period. The ϕ l is close to the result of Advanced Composition Explorer while the ϕ h is close to the result of neutron monitor data. Furthermore, the long-term behavior of the proton-to-helium ratio ratio is found to naturally arise from the model when considering different Z/A values and the LISs for proton and helium.

Cardiac lymphangiogenesis plays an important physiological role in the regulation of interstitial fluid homeostasis, inflammatory, and immune responses. Impaired or excessive cardiac lymphatic remodeling and insufficient lymph drainage have been implicated in several cardiovascular diseases including atherosclerosis and myocardial infarction (MI). Although the molecular mechanisms underlying the regulation of functional lymphatics are not fully understood, the interplay between lymphangiogenesis and immune regulation has recently been explored in relation to the initiation and development of these diseases. In this field, experimental therapeutic strategies targeting lymphangiogenesis have shown promise by reducing myocardial inflammation, edema and fibrosis, and improving cardiac function. On the other hand, however, whether lymphangiogenesis is beneficial or detrimental to cardiac transplant survival remains controversial. In the light of recent evidence, cardiac lymphangiogenesis, a thriving and challenging field has been summarized and discussed, which may improve our knowledge in the pathogenesis of cardiovascular diseases and transplant biology.

The lymphatic system provides important functions for tissue fluid homeostasis and immune response. Lymphangiogenesis, the formation of new lymphatics, comprises a series of complex cellular events in vitro or in vivo, e.g., proliferation, differentiation, and sprouting. Recent evidence has implied that macrophages act as a direct structural contributor to lymphatic endothelial walls or secret VEGF-C/-D and VEGF-A to initiate lymphangiogenesis in inflamed or tumor tissues. Bone marrow-derived macrophages are versatile cells that express different functional programs in response to exposure to microenvironmental signals, and can be identified by specific expression of a number of proteins, F4/80, CD11b, and CD68. Several causative factors, e.g., NF-κB, IL-1β, TNF-α, SDF-1, M-CSF, especially TonEBP/VEGF-C signaling, may be actively involved in macrophage-induced lymphangiogenesis. Alteration of macrophage phenotype and function has a profound effect on the development and progression of inflammation and malignancy, and macrophage depletion for controlling lymphangiogenesis may provide a novel approach for prevention and treatment of lymphatic-associated diseases.

As galactic cosmic rays (GCRs) propagate through the turbulent plasma environment within the heliosphere, they undergo a process of diffusion, drift, and energy loss, leading to a notable reduction in their flux. This is the solar modulation impact. Recently, the cosmic-ray experiment AMS-02 published daily fluxes of proton and helium for the period from 2011 May 20 to 2019 October 29 in the rigidity interval from about 1 to 100 GV, exhibiting fine time structures that correlate with solar wind properties on a daily basis. In this work, we employ three different modified force field approximation models to fit the data. By fitting to the daily proton and helium fluxes, we get the time series of solar modulation potential. We find good agreement of data and model predictions for both proton and helium with the same parameters in two modified force field approximation models. The results in this study verify that the modified force-field approximation model is a valid parameterization of the GCR spectrum also at daily timescales.

We systematically investigate the mass spectrum and two-body open-charm strong decays of charmonium states in a coupled-channel model where the 3 P 0 quark-antiquark pair creation mechanism is employed. The results of masses, mass shifts, proportions of the c c ¯ component, and open-charm decay widths are provided. The S - D wave mixing angles and di-electric decay widths for vector mesons are also presented. Based on our results, we find that the ψ ( 3770 ) , ψ ( 4040 ) , ψ ( 4160 ) , ψ ( 4360 ) , and ψ ( 4415 ) can be assigned as the 1 3 D 1 -, 3 3 S 1 -, 2 3 D 1 -, 4 3 S 1 -, and 3 3 D 1 -dominated charmonium states, respectively. The ψ 3 ( 3842 ) is a good candidate of the ψ 3 ( 1 D ) charmonium state. The calculated mass and strong decay width of χ c 1 ( 2 P ) with significant continuum contribution ( ∼ 57%) favor the charmonium interpretation for the mysterious χ c 1 ( 3872 ) . When considering the large uncertainty in the observed decay width, the possibility to assign the χ c 0 ( 3860 ) as the χ c 0 ( 2 P ) charmonium state cannot be ruled out. One may describe well the properties of χ c 2 ( 3930 ) with the χ c 2 ( 2 P ) charmonium. The predictions on properties of other c c ¯ states can be tested by future experiments.

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome that elevates the risk of hepatocellular carcinoma (HCC). Although alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells, the deregulated metabolic modulation of HCC cells in the NAFLD progression remains obscure. Here, we discovers an endoplasmic reticulum-residential protein, Nogo-B, as a highly expressed metabolic modulator in both murine and human NAFLD-associated HCCs, which accelerates high-fat, high-carbohydrate diet-induced metabolic dysfunction and tumorigenicity. Mechanistically, CD36-mediated oxLDL uptake triggers CEBPβ expression to directly upregulate Nogo-B, which interacts with ATG5 to promote lipophagy leading to lysophosphatidic acid-enhanced YAP oncogenic activity. This CD36-Nogo-B-YAP pathway consequently reprograms oxLDL metabolism and induces carcinogenetic signaling for NAFLD-associated HCCs. Targeting the Nogo-B pathway may represent a therapeutic strategy for HCC arising from the metabolic syndrome. Non alcoholic fatty liver disease (NAFLD) associates with an elevated risk of developing hepatocellular carcinoma (HCC). Here, the authors find that Nogo-B, an endoplasmic reticulum resident protein, is upregulated by lipid uptake and acts as an oncogene in NAFLD-associated HCC by promoting lipid droplet breakdown by lipophagy and triggering Hippo pathway dysregulation

The spectra of Galactic cosmic rays (GCRs) contain crucial information about their origin and propagation through the interstellar medium. When GCRs reach Earth, they are significantly influenced by the solar wind and the heliospheric magnetic field, a phenomenon known as solar modulation. This effect introduces time-dependent variations in GCR fluxes. The AMS-02 experiment has released time-dependent flux data for protons, electrons, and positrons, revealing clear correlations with solar modulation. Studies suggest that cosmic rays with the same charge, such as protons and helium nuclei, exhibit similar or the same solar modulation parameters. In this work, we derive the local interstellar spectrum (LIS) for protons and positrons under the assumption of a common solar modulation potential, using data from Voyager 1 and a 7 yr average from AMS-02. Similarly, the LIS for antiprotons and electrons is derived by assuming they are governed by a separate solar modulation potential. We demonstrate that the time-dependent fluxes of positrons and protons can be accurately modeled using the same set of solar modulation parameters within a modified force-field approximation framework. Based on this, we predict the time-dependent fluxes of antiprotons using the corresponding electron flux data.

Osteoarthritis (OA) is a chronic, degenerative joint disease presenting a significant global health threat. While current therapeutic approaches primarily target symptom relief, their efficacy in repairing joint damage remains limited. Recent research has highlighted mesenchymal stem cells (MSCs) as potential contributors to cartilage repair, anti-inflammatory modulation, and immune regulation in OA patients. Notably, MSCs from different sources and their derivatives exhibit variations in their effectiveness in treating OA. Moreover, pretreatment and gene editing techniques of MSCs can enhance their therapeutic outcomes in OA. Additionally, the combination of novel biomaterials with MSCs has shown promise in facilitating the repair of damaged cartilage. This review summarizes recent studies on the role of MSCs in the treatment of OA, delving into their advantages and exploring potential directions for development, with the aim of providing fresh insights for future research in this critical field.

Background The emergence of the novel, pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global health emergency. SARS-CoV-2 is highly contagious and has a high mortality rate in severe patients. However, there is very limited information on the effect of SARS-CoV-2 infection on the integrity of the blood–brain barrier (BBB). Methods RNA-sequencing profiling was performed to analyze the transcriptomic changes in human brain microvascular endothelial cells (hBMECs) after SARS-CoV-2 infection. Bioinformatic tools were used for differential analysis. Immunofluorescence, real-time quantitative PCR, and Western blotting analysis were used to explore biological phenotypes. Results A total of 927 differentially expressed genes were identified, 610 of which were significantly upregulated while the remaining 317 were downregulated. We verified the significant induction of cytokines, chemokines, and adhesion molecules in hBMECs by SARS-CoV-2, suggesting an activation of the vascular endothelium in brain. Moreover, we demonstrated that SARS-CoV-2 infection could increase the BBB permeability, by downregulating as well as remodeling the intercellular tight junction proteins. Conclusions Our findings demonstrated that SARS-CoV-2 infection can cause BBB dysfunction, providing novel insights into the understanding of SARS-CoV-2 neuropathogenesis. Moreover, this finding shall constitute a new approach for future prevention and treatment of SARS-CoV-2-induced CNS infection.

The cost of fuel cell systems can be largely reduced by developing hydroxide exchange membrane fuel cells (HEMFCs) based on platinum group metal-free (PGM-free) catalysts. However, the sluggish hydrogen oxidation reaction (HOR) in alkaline electrolytes forces HEMFCs to use higher PGM loadings at the anode than proton exchange membrane fuel cells to sustain the desired power densities. Here we report nickel–molybdenum–niobium metallic glasses as PGM-free HOR catalysts. The optimal Ni 52 Mo 13 Nb 35 metallic glass exhibits an intrinsic exchange current density of 0.35 mA cm −2 , outperforming that of a Pt disk catalyst (0.30 mA cm −2 ). This catalyst also shows remarkable robustness in alkaline electrolyte with a wide stability window up to 0.8 V versus the reversible hydrogen electrode. When used as the anode, this catalyst enables power densities of 390 mW cm −2 in H 2 /O 2 fuel cells and 253 mW cm −2 in H 2 /air fuel cells, and shows negligible performance degradation over 50 h and 30 h, respectively. Hydroxide exchange membrane fuel cells operating in alkaline electrolyte are more cost-effective than their proton exchange membrane counterparts, but their performance is still considerably lower. Now, a Ni–Mo–Nb metallic glass is put forward as a hydrogen oxidation reaction catalyst with high activity and stability in alkaline electrolyte.