Schistura rara, a small stream-dwelling fish of the family Nemacheilidae, is endemic to headwater streams of the Beijiang River in Shaoguan, China. Here, we report the first complete mitochondrial genome (mitogenome) of S. rara, which is 16,563 bp in length and contains 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and a single non-coding control region (D-loop). The mitogenome has a GC content of 42.8% and shows a clear bias toward A/C-ending codons in PCGs. Maximum-likelihood (ML) phylogenetic analyses based on complete mitogenome sequences indicate that Schistura is non-monophyletic. Within this framework, S. rara is recovered as the sister species to S. incerta and, together with one lineage of S. fasciolata, forms a well-supported clade. These three species are the only Schistura taxa recorded from the upper Beijiang River. The newly generated mitogenomic data provide an important genetic resource for clarifying the phylogenetic position and taxonomic status of S. rara within Nemacheilidae.

Transarterial chemoembolisation (TACE) is an important treatment method for solid tumors, such as liver cancer. Its main advantages are precise treatment and reduced trauma. However, limitations including inadequate drug loading, burst release and ectopic embolization still exist in clinical practice. In this study, we developed sodium alginate sulfate microspheres (AM) with multiple types of drug-loading groups and self-expanding behavior, achieving superior drug loading capacity and embolization stability. The framework material sodium alginate sulfate (SAS) contains various drug-loading groups, resulting in fast drug loading (30 min, Doxorubicin hydrochloride), high loading capacity (68.0 mg/g, Irinotecan hydrochloride), sustained release (>30 days, Doxorubicin hydrochloride) and compatibility with multi-drug loading types (including gemcitabine hydrochloride and procaine hydrochloride). The fatty acid/sodium fatty acid buffer system formed at the aqueous-oil phase interface facilitated the formation of a gradient cross-linked structure, which conferred self-expansion behavior to the microspheres. In pig renal artery embolization (n = 9), the AM stabilizes the embolized artery, resulting in tissue necrosis without vascular recanalization or ectopic embolization (**p = 0.002 on 90 days). Therefore, AM with high drug-loading capacity and self-expansion has great potential to enhance the safety and efficacy of TACE treatment.

Thrombosis remains a leading cause of cardiovascular and cerebrovascular mortality worldwide. Plasminogen activators, notably urokinase and alteplase, have been established as standard thrombolytic agents in clinical practice. However, their therapeutic potential is severely compromised by rapid metabolic clearance, non-specific biodistribution, and associated hemorrhagic complications. Here, we designed a dual-functional nano drug delivery platform that leverages P-selectin overexpression on activated platelets and the characteristic hypoxic microenvironment at thrombotic sites for precision thrombolytic intervention. Specifically, we developed a hypoxia-responsive block (PAC) by conjugating polyguluronate sulfate (PGS, P-selectin targeting motif) with azobenzene-modified cholesterol, enabling urokinase encapsulation within PAC@UK liposomes. Under hypoxic conditions that mimic the thrombotic microenvironment, the reductive cleavage of azobenzene moieties initiated sustained urokinase release (96.41% cumulative release), while maintaining exceptional biocompatibility and demonstrating preferential targeting of activated platelets. Comprehensive in vivo validation across zebrafish, murine mesenteric, and carotid artery thrombosis models revealed markedly enhanced thrombolytic efficacy compared to free UK. This biomimetic nanoplatform represents a paradigm shift toward intelligent, site-specific thrombolytic intervention, offering substantial clinical promise for safer and more effective treatment of thrombotic disorders.

Hyperlipidemia is a chronic metabolic disorder in humans, contributing to the onset of cardiovascular diseases (CVDs) that remain the leading cause of death worldwide. Current clinical antihyperlipidemic agents are often accompanied by diverse adverse side effects. Therefore, developing safer novel lipid regulators is an urgent and challenging task. Marine polysaccharides exhibit remarkable antihyperlipidemic activity owing to their distinctive physicochemical properties, multi-target mechanisms, and system-level modulation. This review systematically summarizes recent progress regarding the antihyperlipidemic efficacy of marine polysaccharides and provides comprehensive insights into their sources, structural features, structure–activity relationships, mechanisms of action, and application potential. Furthermore, this review also highlights the existing limitations and challenges in translational research of marine polysaccharides, and puts forward future research directions to advance marine polysaccharides into safe, effective, and sustainable natural therapeutics for hyperlipidemia.

Periodontitis, a prevalent and progressive infectious inflammatory disease, is characterized by alveolar bone resorption and loss of periodontal attachment, presenting a formidable challenge for complete tissue regeneration. This study develops a biomimetic dual-layer scaffold (d-ACT@MIC/SIM) featuring synchronized minocycline (MIC) release and liposome-encapsulated simvastatin (SIM) delivery for optimal periodontal repair. The scaffold featured an asymmetric architecture, comprising a dense upper layer of chitosan (CS) and sodium alginate (AL) designed to prevent epithelial downgrowth, and a porous osteoconductive lower layer of CS, AL, and β-tricalcium phosphate (β-TCP) to support cell infiltration and bone ingrowth. Physicochemical characterization confirmed that d-ACT@MIC/SIM possessed favorable biocompatibility, robust antimicrobial efficacy against periodontal pathogens, and requisite mechanical integrity. In vivo studies, following the implantation of the biomimetic dual-layer drug-loading scaffold (d-ACT@MIC/SIM) into alveolar bone defects in a rat periodontitis model for 10 weeks, demonstrated significantly enhanced alveolar bone regeneration, with a bone volume/tissue volume (BV/TV) ratio of 80.6%. Furthermore, this multifunctional scaffold exhibited synergistic capabilities in promoting osteogenic differentiation, exerting sustained antibacterial activity, and mitigating local inflammatory responses. These findings highlight the substantial therapeutic potential of this asymmetrically structured, dual drug-loading biomimetic scaffold as a promising strategy for periodontal tissue engineering and the clinical management of periodontitis.

Pathological cardiac hypertrophy is one of the main causes of heart failure, with a highly complex pathogenesis. Currently, there is no specific therapeutic drugs available in clinical practice. Propylene glycol alginate sodium sulfate (PSS) is a heparin-like drug, which plays an important role in anticoagulation, antithrombosis and lipid-lowering. Here, PSS-loaded multivesicular liposomes coated with trimethyl chitosan were developed and their therapeutic effects on ameliorating myocardial hypertrophy were investigated. The PSS-loaded multivesicular liposomes achieved high encapsulation efficiency and sustained-release of PSS. Animal-level results showed that the new PSS formulation could delay the progression of myocardial hypertrophy. Additionally, the cell-level studies identified that PSS could inhibit myocardial cell hypertrophy and prevent fibrosis through MAPK and TGF-β/Smad signaling pathways. Our research have confirmed the potential of PSS as a candidate drug for improving myocardial hypertrophy, providing an early intervention strategy to delay the progression of cardiac hypertrophy to heart failure.

Diabetic wounds are prone to bacterial infection and difficult to heal due to chronic inflammation and hyperglycemic microenvironment. Here we developed a novel bioactive hydrogel with multifunctional tunable properties, including biocompatibility, pH-response, anti-inflammatory activity, and the ability to promote diabetic wound healing. The injectable and self-healing hydrogel was prepared by cross-linking sulfated oxidized sodium alginate (S-OSA) with adipic dihydrazide (ADH) and subsequently loading with the angiogenic drug desferrioxamine (DFO). Under acidic microenvironment in diabetic wounds during the early stage, the hydrogel presented a pH-responsive and sustained release of DFO due to unstable acylhydrazone bonds. The hydrogel also exhibited good cytocompatibility and hemocompatibility. Furthermore, the in vivo experiments demonstrated that the hydrogel significantly promoted diabetic wounds healing by reducing the inflammatory response, accelerating collagen deposition, and promoting vascular regeneration. These findings suggested that sulfated alginate-based hydrogel holds considerable promise for treating diabetic wounds complicated by chronic inflammation.

Cardiac hypertrophy is a critical contributor to cardiac dysfunction and the development of heart failure, yet effective therapeutic strategies remain limited. Propylene glycol alginate sulfate sodium (PSS) is a marine sulfated polysaccharide drug used in the treatment of cardiovascular diseases and has shown cardiac function benefits. Here, we designed a pH-responsive PSS-loaded nanoparticle drug delivery system. It was self-assembled by negatively charged PSS with positively charged trimethyl chitosan glycocholic acid (TMC-GA) via electrostatic interaction, and further stabilized the nanoparticles with Hydroxypropyl methylcellulose phthalate (HP55) excipients. The prepared TMC-GA/HP55@PSS nanoparticles were spherical, with a mean particle size of 361.5 ± 1.26 nm, zeta potential of −30.3 ± 0.9 mV, and encapsulation efficiency of 92.52 ± 2.4%. In vitro release study demonstrated the pH-responsive property of TMC-GA/HP55@PSS under intestinal conditions and facilitated nanoparticles absorption in the intestinal epithelium. In vitro experiments confirmed the biocompatibility of PSS and its ability to improve myocardial cell hypertrophy. In vivo, both PSS and its nanoparticles significantly ameliorated pressure overload–induced cardiac hypertrophy in mice, with TMC-GA/HP55@PSS exhibiting better cardioprotective efficacy. This study is the first to integrate pH-responsiveness and bile acid transport-mediated uptake into PSS nanocarrier systems. The findings provide valuable data and enlightenment for designing novel formulations and expanding the clinical applications of PSS.

Hyperlipidemia has become a major global health challenge and one of the leading causes of mortality. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a circulating plasma protein, promotes the lysosomal degradation of hepatic low-density lipoprotein receptors (LDLR), thereby reducing the clearance of low-density lipoprotein (LDL) from blood plasma. PCSK9 has increasingly become a prominent therapeutic target for the development of lipid-lowering agents. In this study, we firstly identified polyguluronate sulfate (PGS) as a novel PCSK9 inhibitor. PGS could bind to the positively charged domain of PCSK9 with a KD value of 3.198 μM, effectively blocking its mediated LDLR degradation. This interaction leads to increase in LDLR levels on hepatocyte surface, enhancing LDL clearance. Furthermore, we demonstrated that PGS more effectively activates the AMP-activated protein kinase (AMPK) pathway compared to polymannuronate sulfate (PMS) at 200 μg/mL, resulting in about 2-fold greater lipid-lowering effect. In summary, our findings highlight PGS as a promising candidate for the development of novel lipid-lowering drugs, offering new insights into the therapeutic potential of sulfate polysaccharides targeting PCSK9.

Thrombolytic therapy for cardiovascular and cerebrovascular diseases is significantly limited by the short half-life, inadequate targeting specificity, and hemorrhagic complications of conventional therapeutic agents. To overcome these challenges, we developed a dual-functional nanogel (PGS-SP@UK) that integrates P-selectin-mediated thrombus targeting with ROS-responsive drug release. Taking advantage of the P-selectin targeting capability of polyguluronate sulfate (PGS), we synthesized the sulfated polysaccharide with selenocystamine and pinacol phenylboronate (PBAP) to construct an amphiphilic copolymer capable of encapsulating urokinase (UK). Notably, this nanogel exhibited H2O2-triggered UK release (85.79 %) while maintaining great stability under physiological conditions. In vitro studies confirmed its neuroprotective effects through modulation of the ferroptosis signaling pathway in an OGD/R-induced model. In vivo studies revealed efficient blood-brain barrier penetration and thrombus-specific accumulation, achieving 84.3 % recovery in cerebral infarct area through synergistic thrombolysis and oxidative stress mitigation. Our study presents an innovative drug delivery system with significant potential for clinical ischemic stroke treatment. STATEMENT OF SIGNIFICANCE: Conventional thrombolytic agents suffer from poor targeting specificity and severe bleeding complications, limiting their clinical efficacy in ischemic stroke treatment. We designed a dual-functional nanogel (PGS-SP@UK) that uniquely integrates P-selectin-mediated active targeting with ROS-responsive drug release mechanisms. This innovative design represents a system to combine polyguluronate sulfate-based thrombus recognition with oxidative stress-triggered urokinase liberation. Our nanogel achieves unprecedented selectivity through dual targeting: bioactive targeting via P-selectin binding and microenvironmental responsiveness to pathological ROS levels. In vivo validation demonstrated exceptional therapeutic outcomes with 84.3 % cerebral infarct recovery while eliminating systemic hemorrhagic risks. This breakthrough establishes a new therapeutic paradigm that transcends current limitations through synergistic thrombolysis and neuroprotection, offering transformative potential for precision medicine in thrombotic disorders.

ZnO/Ag nanocomposite was prepared via in situ method by using silver nitrate and ZnSO4 as the raw material. ZnO and ZnO/Ag were characterized by utilizing SEM, UV-vis, XRD, FTIR, and so on. The photocataytic degradation behaviors of ZnO and ZnO/Ag for trimethylamine (TEA) in air and solution were studied. The results indicated that ZnO/Ag had better photocatalytic degradation properties on trimethylamine under the condition of 0.06 g catalyst, 2 h photocatalytic time, and 15 A light intensity, and the degradation rates of TEA were up to 44 and 67% in air and solution, respectively. Furtherly, ZnO and ZnO/Ag also indicated perfect photocatalytic degradation properties toward to organic compounds in wastewater. Especially, the harmless treatment of triethylamine was achieved by using photocatalytic degradation method that provided a novel method for treating triethylamine. In all the above results leaded to a good application prospect of ZnO/Ag in the degradation of organic compounds in air and solution.

The exploration of efficient and safe chemodynamic therapy (CDT)-based cancer treatment is expected but still faces challenges. Herein, a kind of multifunctional nanomicelles was constructed for CDT, combined with biocompatible polysaccharides as nanocarriers, pH responsiveness and active targeting of P-selectin overexpressed tumors. The P-selectin-targeted ligand, polyguluronate sulfate (PGS), complexed with copper peroxide to form PGS-Cu nanomicelles by electrostatic interactions. Under acidic conditions, PGS-Cu nanomicelles released copper ions with H2O2 and were able to produce •OH by Fenton-like reaction. In vitro data demonstrated PGS-Cu nanomicelles had high selectivity targeting P-selectin over-expressed cancer cells and induced cell death via CDT. In vivo evaluation showed PGS-Cu nanomicelles were enriched in tumor tissues and significantly inhibited tumor growth. This study identified that PGS-Cu nanomicelles could be a highly effective strategy for CDT cancer treatment.

Atrial fibrosis is the hallmark of structural remodeling in the pathogenesis of atrial fibrillation (AF). Meanwhile, AF causes a hypercoagulable state, and then provokes pro-fibrotic response. To discover a potential effective AF treatment targeting both coagulation and atrial fibrosis, this study investigated the structure–activity relationship of propylene glycol alginate sodium sulfate (PSS) derivatives with heparin-like activity on TGF-β1-induced atrial fibrosis. We found that PSS derivatives had significantly inhibitory effects on proliferation, migration, phenotypic transformation, and secretion/deposition of extracellular matrix of atrial fibroblasts. Among them, PGGS showed the optimal anti-atrial fibrotic activity by suppressing TGF-β1-induced activation of Smad2/3 signaling pathway. Furthermore, the study in vivo indicated that PGGS treatment displayed a reduced atrial fibrosis and AF inducibility, and attenuated the hypercoagulable state by decreasing D-dimer level and thrombin (FIIa) activity in MHC-TGF-β1 cys33ser transgenic mice, which had increased fibrosis in atrium but not in the ventricles. Our results demonstrated that PSS derivatives, especially PGGS, were potential anti-atrial fibrosis and anti-coagulant agents for AF prevention. Our study is beneficial in extending the current understandings of the function of PSS on atrial fibrosis and vulnerability to AF.

Fucosylated chondroitin sulfate is a unique glycosaminoglycan isolated from sea cucumbers, with excellent anticoagulant activity. The fucosyl branch in FCS is generally located at the 3-OH of D-glucuronic acid but, recently, a novel structure with α-L-fucose linked to the 6-OH of N-acetyl-galactosamine has been found. Here, using functionalized monosaccharide building blocks, we prepared novel FCS tetrasaccharides with fucosyl branches both at the 6-OH of GalNAc and 3-OH of GlcA. In the synthesis, the protective group strategy of selective O-sulfation, as well as stereoselective glycosylation, was established, which enabled the efficient synthesis of the specific tetrasaccharide compounds. This research enriches knowledge on the structural types of FCS oligosaccharides and facilitates the exploration of the structure–activity relationship in the future.

P-selectin has been shown to enhance growth and metastasis of mouse tumors by promoting regulatory T cell (Treg) infiltration into the tumors. Theoretically, a P-selectin antagonist could suppress the process. Popylene glycol alginate sodium sulfate (PSS) is a heparin-like marine drug, which was originally approved to treat cardiovascular disease in China. Previously, we reported that PSS was an effective P-selectin antagonist in vitro. However, it is unknown whether PSS can regulate Treg infiltration and its effect on lung metastasis in vivo. Our results showed that PSS at 30 mg/kg significantly suppressed lung metastasis and improved overall survival, with potency comparable to the positive control LMWH. Mechanistic study indicated that PSS blocked tumor cells adhesion and activated platelets by directly binding with activated platelet's P-selectin. Compared to the model group, PSS decreased the percent of Tregs by 63 % in lungs after treating for 21 days while increasing CD8+ T cells (1.59-fold) and Granzyme B+ CD8 T cells (2.08-fold)' percentage for generating an adaptive response for systemic tumor suppression. The study indicated that the P-selectin antagonist, PSS, suppressed lung metastasis by inhibiting the infiltration of regulatory T cells (Treg) into the tumors.

Numerous disseminated tumor cells specifically overexpress P-selectin. Therefore, it was thought to be a potential target for tumor therapy. Herein, we described a novel P-selectin-targeted glycosyl ligand-sulfated polyguluronic acid (PGS), as an oriented carrier of P-selectin-targeted drug delivery system. Specifically, the PGS-SS-DOX polymeric micelles were constructed to confirm the practicability of the PGS carrier as a new P-selectin-targeted ligand. PGS-SS-DOX micelles comprised P-selectin-targeted PGS, doxorubicin (DOX) as an anticarcinogen, and pH/redox dual-sensitive bio-linker facilitating drug release in tumor tissues. In vitro and in vivo data showed that PGS-SS-DOX micelles significantly increased tumor cell killing capacity and exhibited a favorable biocompatibility comparison with Free-DOX. This work proved that PGS was an ideal low immunogenic, biodegradable drug carrier for the delivery of anti-cancer drugs. The facile PGS-SS-drug micelle system provided enormous opportunities for treating disseminated tumors utilizing many irreplaceable anticarcinogens.

生药学是药学专业核心课程之一,实验教学在生药学课程中占有重要地位.通过实验教学,不仅培养学生的科学思维能力、实践操作能力以及严谨扎实的科研态度,学生还掌握了生药鉴定的基本方法,初步具备了鉴别生药的能力.2022年秋季学期笔者参加了学校组织的生药学实验课程教学评估工作,教学质量和效果得到了评估专家和学生的一致好评,本文总结了教学评估中的经验.