Salvia miltiorrhiza Bunge （Lamiaceae） is a medicinal plant widely used in Traditional Chinese Medicine for treating cardiovascular and cerebrovascular diseases. Chloroplasts are double-membrane-bound, chlorophyll-containing organelles and responsible for photosynthesis in plant cells. The structural information of chloroplast genomes serves as the foundation for precise exogenous gene insertion, site selection, and chloroplast genome modification. In this study, a comprehensive analysis and comparison of 125 chloroplast genomes from S. miltiorrhiza and 76 congeneric species were conducted, focusing on sequence characteristics, codon usage bias, simple sequence repeats （SSRs）, contraction/expansion of chloroplast genome boundaries, and phylogenetic relationships, which could provide a theoretical foundation for advancing chloroplast genetic engineering, genetic diversity analysis, molecular breeding, and species identification within the Salvia genus.

Paclitaxel (PTX), a valuable natural product derived from Taxus species, exhibits remarkable anti-cancer properties. It penetrates nanopores in microtubule walls, interacting with tubulin on the lumen surface and disrupting microtubule dynamics, thereby inducing cytotoxic effects in cancer cells. PTX and its derivatives have gained approval for treating various diseases due to their low toxicity, high efficiency, and broad-spectrum application. The widespread success and expanding applications of PTX have led to increased demand, raising concerns about accessibility. Consequently, researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability. This review examines the challenges and advancements in PTX sourcing, production, physicochemical properties, anti-cancer mechanisms, clinical applications, trials, and chemo-immunotherapy. It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.
Humans ; Paclitaxel/pharmacology* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Neoplasms/drug therapy* ; Animals ; Taxus/chemistry*

ObjectiveTo explore the possible mechanism of Osteoking （OK） on postmenopausal osteoporosis （PMOP）. MethodForty adult female mice were randomly divided into a sham operation （Sham） group， osteoporosis model （OVX） group， estradiol intervention （E₂） group， and OK group， with 10 mice in each group. The modeling was completed by conventional back double incision ovariectomy， and the corresponding drugs were given one week later. After 12 weeks， the body mass and uterine index of mice were measured， and the pathological changes of bone tissue and the number of osteoclasts （OCs） were determined by hematoxylin-eosin （HE） and tartrate-resistant acid phosphatase （TRAP） staining， respectively. Bone mineral density （BMD）， trabecular number （Tb.N）， trabecular separation （Tb.Sp）， and bone volume fraction （BV/TV） were measured by microcomputed tomography （Micro-CT）. The maximum load of the femur was detected by a three-point bending test. The contents of tumor necrosis factor-α （TNF-α） and bone resorption marker C-terminal telopeptide of type Ⅰ collagen （CTX-1） were measured by enzyme linked immunosorbent assay （ELISA）. The protein expression levels of nuclear factor-kappa B p65 （NF-κB p65）， phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65）， nuclear factor kappa B inhibitor alpha （IκBα）， phosphorylated nuclear factor kappa B alpha （p-IκBα）， nuclear factor of activated T cells 1 （NFATc1）， and proto-oncogene （c-Fos） were detected by Western blot. The mRNA expressions of OCs-related specific genes matrix metalloproteinase-9 （MMP-9）， NFATc1， TRAP， cathepsin K （CTSK）， and c-Fos were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the Sham group， the uterine index decreased significantly in the OVX group， and the body mass （BMI） increased significantly. The structure of bone trabeculae was completely damaged， and the number of OCs increased. BMD， Tb.N， BV/TV， and maximum load decreased， while Tb.Sp was up-regulated. The levels of TNF-α and CTX-1 in serum were up-regulated. The protein expressions of c-Fos， p-NF-κB p65/NF-κB p65， NFATc1， and p-IκBα/IκBα were increased. The mRNA expressions of NFATc1， c-Fos， CTSK， TRAP， and MMP-9 were up-regulated （P<0.05， P<0.01）. Compared with the OVX group， the body mass of the OK and E₂ groups decreased， and the uterine index increased. The bone trabeculae increased， and the number of OCs decreased. BMD， Tb.N， BV/TV， and maximum load increased， while Tb.Sp decreased. The levels of TNF-α and CTX-1 in serum were decreased. The protein expressions of c-Fos， p-NF-κB p65/NF-κB p65， NFATc1， and p-IκBα/IκBα were decreased， and the mRNA expressions of NFATc1， c-Fos， CTSK， TRAP， and MMP-9 were decreased （P<0.05， P<0.01）. ConclusionOK can inhibit the NF-κB/NFATc1 signaling pathway and reduce bone mass loss by reducing the level of inflammatory injury factors in PMOP mice， which is one of the mechanisms for treating PMOP.

Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

Obesity has become a growing epidemic that seriously affects the quality of human life. Obesity not only adds the burden to the body but may have negative impacts on various body systems and organs, such as the cardiovascular and metabolic systems. In recent years, some studies have shown that obesity also negatively affects the reproductive system and influences male reproductive health. Male reproductive health is not only related to the normalization of male reproductive function but also plays a role in the ability to conceive healthy offspring. This article summarizes research progress on the effects of obesity on male reproductive health, including endocrine hormone disruption, reproductive organ structural damage, increased oxidative stress, and reproductive cell epigenetic alterations, providing insights for a deeper understanding of the influence of obesity on male reproduction and potential treatments.

Plant diterpenoids are widely distributed and abundant natural products with diverse structures and functions in nature, which have been commonly used in pharmaceutical, agricultural and industrial production. In recent years, plant diterpenoids have attracted increasing attention, including their biosynthetic pathways, transcriptional regulatory networks, and biological functions. Herein, the biosynthetic pathways of diterpenoids are summarized in a modular fashion. Further, the regulatory network between diterpene biosynthesis and environmental factors is reviewed. Insights into diterpene metabolism may drive elucidation of complex active diterpene pathways and serve as a knowledge repository for metabolic engineering and cell factory construction.
Plants, Medicinal/metabolism* ; Diterpenes/chemistry* ; Metabolic Engineering ; Biosynthetic Pathways ; Biological Products/metabolism*

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.

Objective To investigate the effect of butylphthalide and sodium chloride injection on patients who received endovascular treatment for acute anterior circulation large vessel occlusive stroke.Methods A total of 173 patients were identified from February 2015 to December 2017 in the Department of Neurology of Jingling Hospital in this retrospective observational study.Propensity score-matching analysis was performed to balance differences in baseline characteristics between patients who received butylphthalide injection (butylphthalide group) and those who did not (control group).The modified Rankin Scale scores at 90 days were compared between the butylphthalide and control groups.Results A total of 144 patients who received endovascular treatment for acute anterior circulation large vessel occlusive stroke were finally analyzed,54 cases in the butylphthalide group and 90 cases in the control group.The proportion of good functional outcome at 90 days in the butylphthalide group was higher than that in the control group (63.0％ (34/54) vs 44.4％ (40/90);x2=4.633,P=0.031).Thirty-six pairs were matched successfully by the propensity score matching,36 patients in the butylphthalide group and 36 in the control group.There was no statistically significant difference in the 90-day functional outcome between the two groups (66.7％ (24/36) vs 44.4％ (16/36);x2=3.600,P=0.058).One hundred and fifteen patients were recanalized,47 cases in the butylphthalide group and 68 cases in the control group,and after the propensity score matching,30 pairs were analyzed.The proportion of good functional outcome at 90 days in the butylphthalide group was higher than that in the control group (73.3％ (22/30) vs 46.7％ (14/30);x2=4.444,P=0.035).Conclusion After propensity score-matching,butylphthalide and sodium chloride injection could improve 90-day functional outcome in patients with acute anterior circulation large vessel occlusive stroke and obtained recanalization by endovascular treatment while could not before propensity score-matching.

Neuropeptides play an important role in the physiological functions of the human body. The physiological activities such as pain, sleep, mood, learning and memory are affected by neuropeptides. Neuropeptides mainly exist in the nerve tissue of the body, and a small amount of them are distributed in body fluid and organs. At present, analysis of large-scale identification of neuropeptides in whole brain tissue is still challenging. Therefore, high-throughput detection of these neuropeptides is greatly significant to understand the composition and function of neuropeptides. In this study, 1 830 endogenous peptides and 99 novel putative neuropeptides were identified by extraction of endogenous peptides from whole brain tissue of mice by liquid phase tandem mass spectrometry (LC-MS / MS). The identification of these endogenous peptides provides not only a reference value in the treatment and mechanism studies of diseases and the development of drugs, but also the basis for the study of a new neuropeptides and their functions.

Objective Ischemic stroke with elevated serum immunoglobulin E ( IgE) in some young patients is regarded as cerebral vasculitis clinically though without sufficient pathological evidence .This study was to investigate the characteristics of vascular lesions in these patients by temporal artery biopsy . Methods We performed histopathologic examinations on the temporal arteries of 32 young ischemic stroke patients with unknown etiology , 16 with normal and the other 16 with elevated serum IgE .We observed inflammatory cells infiltration and mast cells by HE staining and toluidine blue stai-ning respectively and determined the expressions of matrix metalloproteinase -9 (MMP-9), monocyte chemotaxis protein -1 (MCP-1) and serum IgE by immunohistochemistry . Results Compared with the patients with normal IgE , those of the elevated IgE group showed a significantly higher rate of inflammatory cells infiltration (12.5%vs 62.5%, P<0.01), with 1 case of focal necrosis and fi-brinous exudation in the adventitia in the latter group .The average optical density ( OD) of monocyte chemotaxis protein-1 ( MCP-1) in the temporal artery was also dramatically higher in the elevated IgE group than in the normal controls ([9.25 ±5.79] ×10 -5 vs [4.41 ±2.87] ×10 -5, P<0.01).The average OD of matrix metalloproteinase 9 (MMP-9) and intima-media thickness were both increased in the elevated IgE group ([32.79 ±21.38] ×10 -4 and [0.25 ±0.06] mm) but showed no statistically significant differ-ence from those in the normal IgE group ([25.23 ±12.78] ×10 -4 and [0.22 ±0.06] mm) (both P>0.05).Nor was any signifi-cant difference observed in the number of the mast cells between the normal and elevated IgE groups (2.8 ±1.5 vs 3.6 ±2.3, P>0.05). Conclusion The infiltration and necrosis of inflammatory cells and fibrin exudation in the temporal artery of the young pa-tient with elevated serum IgE are likely to be the manifestations of vasculitis , and MCP-1 may play a role in the pathogenesis of the disease.