Cutaneous melanoma is a highly aggressive and lethal malignant tumor, with an increasing incidence in recent years. Despite the advancements in various treatment approaches for cutaneous melanoma, achieving ideal treatment with conventional treatment strategies remains a big challenge due to factors such as the physicochemical properties of drugs, the complex tumor microenvironment, and surgical site infections. In the last decades, drug delivery systems have shown remarkable potential in the treatment of cancers, the nanoparticles (NPs) exhibit highly tunable capabilities, while hydrogels and microneedles excel in drug reservoirs, wound dressings, and transdermal delivery. This article introduces the latest research progress of these three drug delivery systems in the treatment of cutaneous melanoma, then functionally positions these delivery systems according to the requirements of different treatment stages, and further analyzes their clinical translation prospects, aiming to provide references for innovative drug development in this field.

Glycyrrhizae Radix et Rhizoma (GRR) is widely used in ancient and modern Chinese herbal compounds, which can moderate property of herbs with the effect of improving efficacy and reducing toxicity. Exploring the scientific connotation of GRR compatibility theory is of great significance for guiding the clinical application of GRR compatibility and related drug development. Based on summarizing the application and research status of GRR compatibility, this paper mainly reviews the research progress on the mechanisms of GRR compatibility in terms of enhancing efficiency, alleviating property, reducing toxicity, and incompatibility from the perspective of molecular self-assembly, and simultaneously expounds on the research progress of innovative formulation design and application of GRR components based on molecular self-assembly, so as to provide reference and guidance for further explaining and enriching the scientific connotation of GRR compatibility theory, and to provide certain theoretical and practical basis for the design and development of innovative formulations based on GRR component self-assembly.

Behçet's syndrome (BS) is a rare chronic immune/inflammatory disease characterized by recurrent oral aphthous ulcers and a variety of other systemic manifestations that can lead to many severe complications and even death. The exact pathogenesis of BS has not yet been fully elucidated. However, in recent years, several studies have identified neutrophil hyperfunction and enhanced chemotaxis as important components of the pathogenesis of BS. In this paper, the latest research progress on the involvement of neutrophil in the pathogenesis of BS is reviewed from three aspects: namely neutrophil hyperactivation, the release of neutrophil extracellular traps NETs (NETs), and the generation of excess reactive oxygen species (ROS), aiming to provide a theoretical basis for the pathogenesis and clinical diagnosis and treatment of BS. Furthermore, based on the key role of neutrophils in the disease process of BS, this paper also reviews the progress of research on neutrophil-targeted drug delivery systems, to provide a reference for the targeted regulation of neutrophils in treating BS.

Mitochondria, as the central hub regulating cellular metabolism and apoptosis, exhibit dynamic networks (fusion/fission, autophagy) whose dysregulation is closely linked to the pathogenesis of cancer, neurodegenerative diseases, and metabolic disorders. Conventional drug delivery systems fail to overcome the challenges of lysosomal escape and transmembrane delivery, resulting in systemic toxicity and targeting failures that severely limit clinical applicability. Recent mitochondrial-targeting strategies have achieved breakthroughs through an innovative tripartite framework—"precision delivery, dynamic responsiveness, and synergistic therapy" significantly enhancing delivery efficiency and therapeutic precision. However, heterogeneity in membrane potential, unclear mechanisms of carrier-biointerface interactions, and challenges in manufacturing scalability remain major bottlenecks for clinical translation. Future efforts must integrate pharmaceutics, synthetic biology, and computational materials science to develop closed-loop feedback-based intelligent carriers and establish standardized preclinical evaluation systems, thereby accelerating the implementation of precision medicine.

C-Glycosyltransferases (CGTs) are natural biocatalyst responsible for the formation of C-glycosides, transferring sugar moieties from activated nucleotide sugar donors to acceptor substrates and establishing C-C glycosidic bonds. C-glycosides show diverse pharmacological activities, such as antioxidant, anti-inflammatory, antibacterial, antiviral, and antitumor activities, and comparing with O-glycosides, C-glycosides exhibit better pharmacological properties due to their glycosidic bonds being more resistant to chemical and biological degradation. Thus, CGTs have shown considerable potential in drug research and development. Although research on CGTs has made significant progress, with respect to the number of identified CCTs and the understanding of catalytic mechanism, there is still a large distance between CGTs and extensively studied O-glycosyltransferases (OGTs). The reported crystal structures of CGTs have provided a good elucidation of the recognition of sugar donors. However, the limited acceptor-bound structure hinders the comprehensive understanding of their catalytic mechanisms, thereby affecting the application in the fields of bioengineering and pharmaceuticals. Here we summarize the information of identified CGTs for natural product regarding substrate types, protein structures, proposed catalytic mechanisms, and CGT-related engineering and applications, aiming to bring out some new ideas for future research and development.

The study aims to establish and validate a mouse model of depression with concurrent heart and spleen deficiency using a combined induction method involving neurobehavioral assessments and traditional Chinese medicine (TCM) syndrome evaluation. The model was constructed via modified electroshock and forced swimming protocols, and compared to a chronic unpredictable mild stress (CUMS)-induced depression model. Syndrome validation was performed using TCM prescriptions. Depression assessments revealed that the mice in the combined induction model exhibited significant depressive-like behaviors compared to controls. Moreover, the 5-hydroxytryptamine (5-HT) and dopamine (DA) levels in the brain tissue and serum were significantly decreased (P < 0.01, P < 0.05), while corticosterone (Cor) levels were significantly increased (P < 0.01). TCM syndrome evaluation demonstrated symptoms including mental fatigue, delayed responses, insomnia, reduced appetite (P < 0.01), and diminished tongue color intensity (P < 0.01). Cardiovascular and digestive functions were impaired (P < 0.01, P < 0.05), with a decreased spleen index (P < 0.01). Validation experiments indicated that paroxetine alleviated the depressive-like behaviors, while the classic TCM formula Guipi Decoction significantly modulated depression-related biomarkers and syndrome indicators. A mouse model of depression with both heart and spleen deficiency can be successfully established using the modified electroshock combined with forced swimming method. Animal experiments were conducted with the approval and supervision of the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine (ethics number: 2023031303).

This study aims to investigate the effects of nicotine exposure during puberty on cocaine addiction behaviors in adult rats and to investigate the underlying mechanisms. Male Wistar rats, aged 30 days, were divided into two groups: saline-exposed group and nicotine-exposed group. The nicotine-exposed group received subcutaneous injections (sc) of 0.3 mg·kg^-1 nicotine solution three times daily for 15 consecutive days, while the saline-exposed group received an equal volume of saline. On day 60 post-birth, blood was collected from the orbital sinus to separate serum. On day 62, rats underwent jugular vein catheterization surgery and self-administration (SA) training for cocaine, which lasted for 10 consecutive days. The fixed ratio (FR) schedule was gradually increased. After training, rats displayed stable nose-poke behavior for cocaine seeking. Dose-response tests (DR) and progressive ratio tests (PR) were performed to examine whether nicotine exposure during adolescence influenced cocaine addiction in adulthood. This experiment was approved by the Animal Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences (approval number: 00004401). In the DR test, nicotine-exposed rats showed significantly higher numbers of effective cocaine injections at doses of 0.03, 0.1, and 0.3 mg·kg^-1 compared to the saline-exposed group. The nicotine-exposed group exhibited more pronounced craving for cocaine. In the PR test, at 0.75 mg·kg^-1 cocaine dose, nicotine-exposed rats tended to have higher breakpoints (BP) than the saline-exposed group. Cytokine antibody array and ELISA of serum revealed that CCL5 level in the nicotine-exposed group was significantly higher than that in the saline-exposed group. Moreover, in the DR test, the number of cocaine injections obtained at 0 and 0.3 mg·kg^-¹ cocaine doses correlated significantly with CCL5 levels. In conclusion, nicotine administration during puberty in rats can significantly increase their addiction to cocaine and self-administration behavior in adulthood, exhibiting distinct drug dependence characteristics. The content of CCL5 in rat serum is positively correlated with cocaine addictive behavior.

The development of antitumor live microbial agents represents an emerging frontier in cancer immunotherapy. Attenuated Salmonella VNP20009 stands as one of the most extensively studied oncolytic bacterial strains, demonstrating remarkable tumor-targeting specificity with 10³–10⁴-fold higher distribution titers in tumor tissues compared to normal tissues, alongside significant antitumor efficacy. However, the molecular mechanisms underlying its tumor-targeting properties and antitumor activity remain elusive, hindering further strain optimization. As aromatic amino acids serve as essential nutrients for bacterial growth, their biosynthesis in Salmonella is primarily regulated by the aroC gene. To investigate the role of aromatic amino acid biosynthesis in VNP20009's antitumor activity, we constructed an aroC-deficient strain (VNP ΔaroC) using CRISPR/Cas9 technology. Systematic evaluations were performed to assess: ① tolerance to extracellular stresses (pH, H₂O₂) in vitro; ② invasive capacity against B16F10 melanoma cells; ③ proliferative capacity within tumor cells; ④ antitumor efficacy and biodistribution in B16F10 tumor-bearing mice. Experimental results revealed that VNP ΔaroC exhibited comparable growth profiles to wild-type VNP20009 under varying pH and H₂O₂ conditions. However, its colony growth rate on solid medium under identical pH and H₂O₂ conditions was significantly reduced relative to VNP20009. Furthermore, the invasive and proliferative capacities against B16F10 melanoma cells were markedly diminished compared to the wild-type strain. In murine models, VNP ΔaroC demonstrated reduced systemic toxicity but concurrently showed attenuated antitumor efficacy and tumor-targeting specificity. These findings establish aroC as a critical gene governing both therapeutic potency and tumor-targeting capability of VNP20009. This study provides valuable insights for further synthetic biological engineering of oncolytic bacterial strains. All animal experiments were approved by the Institutional Animal Care and Use Committee of the Nanjing University (approval No: IACUC-2003167).

This study employed an acute stress mouse model to systematically explore the regulatory effects of Pien Tze Huang (PTH) on myeloid and lymphoid immune cells in acutely stressed mice. C57BL/6J mice were randomly divided into a control group, an acute restraint stress group, and high dose and low dose Pien Tze Huang groups with acute restraint stress. Except for the control group, mice in the other groups were administered drugs by gavage for 7 consecutive days before the experiment. On the 7^th day, after drug administration, restraint stress was applied for 18 h, followed by an additional 2 days of drug administration. Mice were then sacrificed to measure the weights of the spleen and thymus and calculate organ indices. Flow cytometry was used to detect the numbers and proportion of myeloid and lymphoid immune cells in the spleen and peripheral blood of mice. The phagocytic capacity of peritoneal macrophages in mice was also measured. The results show that acute restraint stress increased the proportion of myeloid cells (eosinophils, macrophages) in peripheral blood and the spleen of mice, while decreasing the proportion of lymphoid immune cells (CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, natural killer T cells, B cells). It also reduced the phagocytic function of peritoneal macrophages in mice. After treatment with PTH, the proportion of myeloid cells (eosinophils) in peripheral blood and the spleen of stressed mice decreased, while the proportion of lymphoid immune cells (CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, natural killer T cells, B cells) increased. Additionally, the phagocytic function of peritoneal macrophages improved. This study shows that PTH can alleviate immune disorders caused by acute stress, providing experimental evidence for its use in treating psychosocial stress-related diseases. This experiment was approved by the Animal Ethics Committee of Jinan University (Approval No.: IACUC-20240220-14).

To evaluate the effect of tandospirone (TS) on fentanyl (FEN)-induced respiratory depression and its impact on fentanyl's analgesic and sedative effects, a rat model of respiratory depression was established using FEN. After drug administration, respiratory frequency (F), tidal volume (TV), expiratory volume (EV), and enhanced pause (PENH) were measured using plethysmography. Blood oxygen saturation (SaO₂) was measured using a non-invasive pulse meter. The acetic acid writhing test, hot-plate test, and spontaneous activity test were used to evaluate the number of writhes, reaction time, and locomotor activity in mice. The righting reflex test was used to measure the loss rate and immobility time in rats [this experiment was approved by the Institute of Military Medicine Experimental Animal Management and Utilization Committee (approval number: IACUC-2023-001C)]. Compared with the respiratory depression model group (FEN 160 μg·kg^-1), the changes of F, TV, EV, PENH, SaO₂ in rats at the same time points after pre-treatment and treatment of different doses of TS were improved. TS (2 mg·kg^-1) and TS+FEN groups reduced the number of writhing movements, total distance of spontaneous activity and increased the maximmal possible effect (MPE), indicating that TS has its own analgesic and sedative effect and enhances the analgesic and sedative effect of FEN. The increase in the median effective concentration (EC₅₀) of loss of the righting reflex (LORR) and the reduction in immobilization time confirm that preconditioning with TS has a protective effect against FEN poisoning. In conclusion, TS ameliorates FEN-induced respiratory depression, and it possesses inherent sedative and analgesic effects. When co-administered with FEN, TS can enhance the analgesic and sedative effects of FEN. TS could serve as a non-opioid medication to improve opioid-induced respiratory depression and warrants further development and research.