Background: To evaluate the global burden of cataracts by year, age, region, gender, and socioeconomic status using disability-adjusted life years (DALYs) and prevalence from the Global Burden of Disease (GBD) study 2019. Methods: Global, regional, or national DALY numbers, crude DALY rates, and age-standardized DALY rates caused by cataracts, by year, age, and gender, were obtained from the Global Burden of Disease Study 2019. Socio-demographic Index (SDI) as a comprehensive indicator of the national or regional development status of GBD countries in 2019 was obtained from the GBD official website. Kruskal-Wallis test, linear regression, and Pearson correlation analysis were performed to explore the associations between the health burden with socioeconomic levels, Wilcoxon Signed-Rank Test was used to investigate the gender disparity. Results: From 1990 to 2019, global DALY numbers caused by cataracts rose by 91.2%, crude rates increased by 32.2%, while age-standardized rates fell by 11.0%. Globally, age-standardized prevalence and DALYs rates of cataracts peaked in 2017 and 2000, with the prevalence rate of 1283.53 [95% uncertainty interval (UI) 1134.46–1442.93] and DALYs rate of 94.52 (95% UI 67.09–127.24) per 100,000 population, respectively. The burden was expected to decrease to 1232.33 (95% UI 942.33–1522.33) and 91.52 (95% UI 87.11–95.94) by 2050. Southeast Asia had the highest blindness rate caused by cataracts in terms of age-standardized DALY rates (99.87, 95% UI: 67.18–144.25) in 2019. Gender disparity has existed since 1990, with the female being more heavily impacted. This pattern remained with aging among different stages of vision impairments and varied through GBD super regions. Gender difference (females minus males) of age-standardized DALYs (equation: Y = -53.2*X + 50.0, P < 0.001) and prevalence rates (equation: Y = − 492.8*X + 521.6, P < 0.001) was negatively correlated with SDI in linear regression. Conclusion: The global health of cataracts is improving but the steady growth in crude DALY rates suggested that health progress does not mean fewer demands for cataracts. Globally, older age, females, and lower socioeconomic status are associated with higher cataract burden. The findings of this study highlight the importance to make gender-sensitive health policies to manage global vision loss caused by cataracts, especially in low SDI regions.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease, and the molecular mechanisms remain poorly understood. Our findings demonstrated that pyruvate kinase M2 (PKM2) promoted fibrosis progression by directly interacting with Smad7 and reinforcing transforming growth factor–β1 (TGF-β1) signaling. Total PKM2 expression and the portion of the tetrameric form elevated in lungs and fibroblasts were derived from mice with bleomycin (BLM)–induced pulmonary fibrosis. Pkm2 deletion markedly alleviated BLM-induced fibrosis progression, myofibroblast differentiation, and TGF-β1 signaling activation. Further study showed that PKM2 tetramer enhanced TGF-β1 signaling by directly binding with Smad7 on its MH2 domain, and thus interfered with the interaction between Smad7 and TGF-β type I receptor (TβR1), decreased TβR1 ubiquitination, and stabilized TβR1. Pharmacologically enhanced PKM2 tetramer by TEPP-46 promoted BLM-induced pulmonary fibrosis, while tetramer disruption by compound 3k alleviated fibrosis progression. Our results demonstrate how PKM2 regulates TGF-β1 signaling and is a key factor in fibrosis progression.

The coronavirus disease 2019 (COVID-19) has spread widely around the world and has seriously affected the human health of tens of millions of people. In view of lacking anti-virus drugs target to SARS-CoV-2, there is an urgent need to develop effective new drugs. In this study, we reported our discovery of SARS-CoV-2 M^pro inhibitors. We selected 15 natural compounds, including 7 flavonoids, 3 coumarins, 2 terpenoids, one henolic, one aldehyde and one steroid compound for molecular docking and enzymatic screening. Myricetin were identified to have potent inhibit activity with IC₅₀ 3.684 ± 0.076 μM in the enzyme assay. The binding pose of Myricetin with SARS-CoV-2 M^pro was identified using molecular docking method. In the binding pocket of SARS-CoV-2 M^pro, the chromone ring of Myricetin interacts with His41 through π-π stacking, and the 3’-, 4’- and 7-hydroxyl of Myricetin interact with Phe140, Glu166and Asp187 through hydrogen bonds. Significantly, our results showed that Myricetin has potent effect on bleomycin-induced pulmonary inflammation by inhibiting the infiltration of inflammatory cells and the secretion of inflammatory cytokines IL-6, IL-1α, TNF-α and IFN-γ. Overall, Myricetin may be a potential drug for anti-virus and symptomatic treatment of COVID-19.

Rationale: Malignant ascites caused by cancer cells results in poor prognosis and short average survival time. No effective treatment is currently available for malignant ascites. In this study, the effects of lentinan (LNT)-functionalized selenium nanoparticles (Selene) on malignant ascites were evaluated. Furthermore, the mechanism of Selene targeting mitochondria of tumor cells were also investigated.

Anti-angiogenic therapies demonstrate anti-tumor effects by decreasing blood supply to tumors and inhibiting tumor growth. However, anti-angiogenic therapy may leads to changes in tumor microenvironment and increased invasiveness of tumor cells, which in turn promotes distant metastasis and increased drug resistance. The CO-IP assays, N-STORM and cytoskeleton analysis were used to confirm the mechanism that p-VEGFR2/VE-cadherin/β-catenin/actin complex regulates vascular remodeling and improves the tumor microenvironment. 6-gingerol (6G), the major bioactive component in ginger, stabilized this complex by enhancing the binding of VEGFa to VEGFR2 with non-pathway dependent. Biacore, pull down and molecular docking were employed to confirm the interaction between 6G and VEGFR2 and enhancement of VEGFa binding to VEGFR2. Here, we report that microvascular structural entropy (MSE) may be a prognostic factor in several tumor types and have potential as a biomarker in the clinic. 6G regulates the structural organization of the microvascular bed to decrease MSE via the p-VEGFR2/VE-cadherin/β-catenin/actin complex and inhibit tumor progression. 6G promotes the normalization of tumor vessels, improves the tumor microenvironment and decreases MSE, facilitating the delivery of chemotherapeutic agents into the tumor core and thereby reducing tumor growth and metastasis. This study demonstrated the importance of vascular normalization in tumor therapy and elucidated the mechanism of action of ginger, a medicinal compound that has been used in China since ancient times.