Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.

Puerarin, a known isoflavone, is commonly found as a Chinese herb medicine. It is widely used in China to treat cardiac diseases such as angina, cardiac infarction and arrhythmia. However, its cardioprotective mechanism remains unclear. In this study, puerarin significantly prolonged ventricular action potential duration (APD) with a dosage dependent manner in the micromolar range on isolated rat ventricular myocytes. However, submicromolar puerarin had no effect on resting membrane potential (RMP), action potential amplitude (APA) and maximal velocity of depolarization (Vmax) of action potential. Only above the concentration of 10 mM, puerarin exhibited more aggressive effect on action potential, and shifted RMP to the positive direction. Millimolar concentrations of puerarin significantly inhibited inward rectified K⁺ channels in a dosage dependent manner, and exhibited bigger effects upon Kir2.1 vs Kir2.3 in transfected HEK293 cells. As low as micromolar range concentrations of puerarin significantly inhibited Kv7.1 and IKs. These inhibitory effects may due to the direct inhibition of puerarin upon channels not via the PKA-dependent pathway. These results provided direct preclinical evidence that puerarin prolonged APD via its inhibitory effect upon Kv7.1 and IKs, contributing to a better understanding the mechanism of puerarin cardioprotection in the treatment of cardiovascular diseases.

Shuganjieyu (SGJY) capsule is a classical formula widely used in Chinese clinical application. In this paper, an ultra-performance liquid chromatography coupled with electrospray ionization and ion trap mass spectrometry has been established to separate and identify the chemical constituents of SGJY and the multiple constituents of SGJY in rats. The chromatographic separation was performed on a C₁₈ RRHD column (150 × 2.1 mm, 1.8 μm), while 0.1% formic acid–water and 0.1% formic acid–acetonitrile was used as mobile phase. Mass spectral data were acquired in both positive and negative modes. On the basis of the characteristic retention time (R_t) and mass spectral data with those of reference standards and relevant references, 73 constituents from the SGJY and 15 ingredients including 10 original constituents and 5 metabolites from the rat plasma after oral administration of SGJY were identified or tentatively characterized. This study provided helpful chemical information for further pharmacology and active mechanism research on SGJY.

Antibody–drug conjugates (ADC) that utilize DNA topoisomerase I inhibitors, such as deruxtecan and SN-38, have significantly enhanced the efficacy of cancer treatment. However, the development of more effective ADCs to combat drug-resistant tumors remains a critical challenge. ADCs covalently link the topoisomerase I inhibitor exatecan and the RNA polymerase II inhibitor triptolide to the same antibody, thereby establishing a dual-killing mechanism against tumor cells. Through optimization of the linker design, this dual-payload ADC achieved precise drug delivery in vivo. Specifically, triptolide is initially released to downregulate the expression of the stress response protein heat shock protein 70 and the efflux pump P-glycoprotein in tumor cells, thereby significantly enhancing drug sensitivity and effectively overcoming resistance, followed by gradual exatecan release, further inhibiting tumor cell proliferation and survival. Experimental results demonstrated that this dual-payload ADC exhibits significant antitumor activity in both in vitro cell models and in vivo xenograft models, including cell line–derived xenograft and patient-derived xenograft models, successfully addressing the challenge of drug resistance encountered in traditional monotherapy. Additionally, non-Good Laboratory Practice–compliant toxicity studies have confirmed the favorable safety profile of this ADC. In summary, this study provides an innovative strategy for overcoming tumor resistance, demonstrating substantial potential for clinical translation, and offering promising therapeutic outcomes and prognosis for patients with cancer.

Pine needles have been widely used in the development of anti-hypertensive and anti-hyperlipidemic agents and health food. However, the widespread distribution of this tree poses great obstacles to the quality control and efficacy evaluation. To facilitate the effective and rational exploitation of Masson’s pine (Pinus massoniana Lamb), as well as ensure effective development of Masson’s pine needles as a medicinal agent, we investigated the spatial distribution of habitat suitability and evaluated the optimal ranges of ecological factors of P. massoniana with 280 samples collected from 12 provinces in China through the evaluation of four constituents known to be effective medicinally. The results of habitat suitability evaluation were also verified by Root Mean Square Error (RMSE). Finally, five ecological factors were chosen in the establishment of a habitat suitability evaluation system. The most suitable areas for P. massoniana growth were mainly concentrated in the middle and lower reaches of the Yangtze River basin, such as Sichuan, Guizhou, and Jiangxi provinces, while the best quality needles were from Guizhou, Sichuan, and the junction area of Chongqing, Hunan, and Hubei provinces. This information revealed that suitable areas for effective constituent accumulation of Masson’s pine needles accounted for only 7.41% of its distribution area.

H. perforatum, as one of the Traditional Chinese Medicinal materials, possesses a variety of pharmacological activities and high medicinal value. However, in recent years, the wild resources of H. perforatum have been severely depleted due to global climate change and human activities, and artificial cultivation faces problems such as unstable yield and active ingredient content. This poses a serious obstacle to the development and utilization of its resources. Therefore, this experiment took H. perforatum as the research object and used 894 distribution records of H. perforatum and 36 climatic environmental factors, using the MaxEnt model and GIS technology to explore the main climatic factors affecting the distribution of H. perforatum. Additionally, by utilizing the principles of ecological niche theory, the potential suitable distribution regions of H. perforatum across past, present, and future timelines were predicted, which can ascertain the dynamics of its spatial distribution patterns and the trend of centroid migration. The results indicate that the main environmental factors affecting the geographical distribution of H. perforatum are solar radiation in April (Srad4), solar radiation in September (Srad9), mean temperature of driest quarter (Bio9), solar radiation in November (Srad11), annual mean temperature (Bio1), and annual precipitation (Bio12). Under future climate scenarios, there is a remarkable trend of expansion in the suitable distribution areas of H. perforatum. The centroid migration indicates a trend of migration towards the northwest direction and high-altitude areas. These results can provide a scientific basis for formulating conservation and sustainable use management strategies for H. perforatum resources.