Vulnerable atherosclerotic plaque rupture is the principal mechanism that accounts for myocardial infarction and stroke. High matrix metalloproteinase-9 (MMP-9) expression and activity have been proven to lead to plaque instability. Metformin, a first-line treatment for type 2 diabetes, is beneficial to plaque vulnerability. However, the mechanism underlying its anti-atherogenic effect remains unclear. Molecular docking and surface plasmon resonance experiments showed that metformin directly interacts with MMP-9, and incubated MMP-9 overexpressing HEK293A cells with metformin (1 μmol·L⁻¹) significantly attenuates MMP-9’s activity using zymography and MMP activity assays. Moreover, metformin treatment drives MMP-9 degradation. Next, we constructed a carotid artery atherosclerotic plaque model and administered consecutive 14-day metformin (200 mg·kg⁻¹·d⁻¹) treatment by intragastric gavage. Immunofluorescence staining of the right carotid common artery and serum MMP activity assay results showed that metformin treatment decreased local plaque MMP-9 protein level and circulating MMP-9 activity, respectively. Histochemical staining revealed that after metformin treatment, the collagen content in plaque was significantly preserved, and the plaque vulnerability index decreased. These findings suggested that metformin improved atherosclerotic plaque stability by directly binding to MMP-9 and driving its degradation.

Background: Healthcare workers (HCWs) are pivotal in influenza containment, serving as both high-risk individuals and vaccine advocates. However, influenza vaccination coverage among Chinese HCWs remains suboptimal. Existing research is often constrained by limited geographic representativeness or non-robust designs. This study provides a robust, nationwide assessment of influenza vaccine uptake and recommendation behaviors among HCWs in China. Methods: A multicenter cross-sectional survey was conducted in late 2025 across four Chinese provinces (Shanghai, Shandong, Chongqing, and Hubei). A total of 390 frontline HCWs—only those defined as directly engaged in influenza management and prevention—from 48 hospitals (primary, secondary, and tertiary levels) completed validated electronic questionnaires. A multinomial logistic regression model was employed to identify determinants of personal vaccine uptake behavior among HCWs. Results: Overall influenza knowledge was moderate, with notable gaps in recognizing typical symptoms (29.23%), southern China’s peak season (31.03%), and optimal vaccination timing (55.38%). A striking “recommendation-uptake disparity” was observed: while 93.6% of HCWs recommended the vaccine to patients, only 22.3% received it annually themselves. A multinomial regression revealed that being a nurse (vs. doctor: OR = 3.11, 95% CI: 1.28–7.53) or female (vs. male: OR = 3.08, 95% CI: 1.28–7.44) was positively associated with annual vaccination, whereas clinical technicians (vs. doctors: OR = 0.18, 95% CI: 0.03–0.94) showed lower odds. Primary barriers to personal vaccination included inconvenience (49.5%), perceived high cost (16.2%), and efficacy concerns (19.5%). Conclusions: This study highlights a significant gap between high recommendation rates and low personal uptake among HCWs in China. The findings underscore the need for multifaceted interventions, including workplace-based reminder systems, free vaccination policies, and tailored education, to optimize coverage and strengthen the role of HCWs in national influenza prevention.

Upon chronic stress, β-adrenergic receptor activation induces cardiac fibrosis and leads to heart failure. The small molecule compound IMM-H007 has demonstrated protective effects in cardiovascular diseases via activation of AMP-activated protein kinase (AMPK). This study aimed to investigate IMM-H007 effects on cardiac fibrosis induced by β-adrenergic receptor activation. Because adenosine analogs also exert AMPK-independent effects, we assessed AMPK-dependent and -independent IMM-H007 effects in murine models of cardiac fibrosis. Continual subcutaneous injection of isoprenaline for 7 days caused cardiac fibrosis and cardiac dysfunction in mice in vivo. IMM-H007 attenuated isoprenaline-induced cardiac fibrosis, diastolic dysfunction, α-smooth muscle actin expression, and collagen I deposition in both wild-type and AMPKα2^−/− mice. Moreover, IMM-H007 inhibited transforming growth factor β1 (TGFβ1) expression in wild-type, but not AMPKα2^−/− mice. By contrast, IMM-H007 inhibited Smad2/3 signaling downstream of TGFβ1 in both wild-type and AMPKα2^−/− mice. Surface plasmon resonance and molecular docking experiments showed that IMM-H007 directly interacts with TGFβ1, inhibits its binding to TGFβ type II receptors, and downregulates the Smad2/3 signaling pathway downstream of TGFβ1. These findings suggest that IMM-H007 inhibits isoprenaline-induced cardiac fibrosis via both AMPKα2-dependent and -independent mechanisms. IMM-H007 may be useful as a novel TGFβ1 antagonist.

BCR-ABL1 kinase is a critical driver of chronic myeloid leukemia (CML) pathophysiology. The approval of allosteric inhibitor asciminib brings new hope for overcoming drug resistance caused by mutations in the ATP-binding site. To expand the chemical diversity of BCR-ABL1 kinase inhibitors with positive anti-tumor effect with asciminib, structure-based virtual screening and molecular dynamics simulations were employed to discover novel scaffolds. This approach led to the identification of a series of N-(2-acetamidobenzo[d]thiazol-6-yl)-2-phenoxyacetamide derivatives as new BCR-ABL1 inhibitors. The most potent compound, 10m, demonstrated inhibition of BCR-ABL-dependent signaling and showed an anti-tumor effect against K562 cells, with an IC₅₀ value of 0.98 μM. Compound 10m displayed powerful synergistic anti-proliferation and pro-apoptotic effects when combined with asciminib, highlighting its potential as a promising lead for the development of potential BCR-ABL inhibitors.

Multiple subtypes of avian influenza virus (AIV), including H5N1, H5N6, and H5N8 viruses, are currently co-circulating in wild birds and poultry and causing sporadic human infections. Vaccine development is essential for pandemic preparedness. In this study, we constructed a candidate vaccine virus (CVV) using reverse genetics (RG) based on the sequence of the first human-infected H5N8 subtype AIV, A/Astrakhan/3212/2020 (H5N8). We evaluated the immunogenicity of the rH5N8/PR8 vaccine strain in combination with Alum, ISA51, and MF59 adjuvants, and we optimized immunization strategies including dosage, administration route, and immunization interval in BALB/c mice. Our results demonstrated that a 10 μg dose of inactivated rH5N8/PR8 with MF59 adjuvant, administered intramuscularly twice at 7-day intervals, induced the strongest immune response and effectively protected mice against challenge with wild-type H5N8 AIVs. Since pandemic influenza vaccines typically require tailored vaccination doses and routes specific to their characteristics, this study provides valuable insights for the development of similar vaccine strains with pandemic potential.