Cold stress is a key environmental constraint in aquaculture, but integrated host responses linking oxidative status, intestinal microbiota, and hepatic metabolism remain insufficiently characterized in Luciobarbus capito. This study aimed to evaluate the biochemical, microbial, and metabolic responses of L. capito to acute low-temperature exposure. Fish were exposed to 12 °C for 96 h, with fish maintained at 22 °C as controls; hepatic antioxidant indices, serum biochemical parameters, intestinal microbiota based on 16S rRNA gene sequencing, and liver metabolomic profiles were analyzed. Cold exposure reduced hepatic total superoxide dismutase (T-SOD) and catalase (CAT) activities and increased malondialdehyde (MDA) content, while serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities increased and acid phosphatase (ACP) activity decreased. The intestinal microbiota showed reduced richness and compositional shifts, including decreased Cetobacterium and increased Pseudomonas. Liver metabolomics identified 172 differential metabolites, with enriched pathways related to glycerophospholipid metabolism, α-linolenic acid metabolism, pantothenate and CoA biosynthesis, and ascorbate and aldarate metabolism. Correlation analysis indicated significant associations between altered bacterial genera and hepatic metabolites. These results suggest that acute cold stress disrupts oxidative balance, intestinal microbial composition, and hepatic metabolism in L. capito, providing an integrated view of associated physiological and metabolic responses to low-temperature stress.

The management of endometrial cancer (EC) remains challenging due to metastatic risk, therapeutic resistance, and the modest durability of standard regimens. Nanotechnology offers a promising avenue to overcome these limitations by enhancing tumor-selective drug delivery, enabling controlled release, and facilitating multimodal approaches that integrate therapy and imaging. This review systematically summarizes recent advances in nanoparticle applications for EC, focusing on strategies that target key molecular drivers, such as TP53, PI3K/PTEN, and immune checkpoints, and evaluates localized administration routes such as vaginal delivery. Preclinical studies, including the demonstration of JX06-loaded nanoparticles combined with metformin achieving approximately 86

Pyroptosis holds great promise for evoking robust anti-tumor immunity, but many pyroptosis induction strategies rely on caspase-3 (Casp-3) activation and face challenges of the immunosuppressive nature of apoptosis and the frequent silencing of gasdermin E (GSDME), a substrate of Casp-3, in tumors. Here, we report a strategy to rewire the pyroptotic pathway by bypassing Casp-3 to directly activate gasdermin D (GSDMD). We identify a small-molecule agonist, (E)-2,3-diiodobut-2-ene-1,4-diol (DIBDO), which undergoes deiodination to release iodide ions upon activation by the tumor-abundant nucleophile glutathione, thereby catalytically generating singlet oxygen and molecular iodine. This cascade induces oxidative damage that downregulates key mediators of caspase-9 and caspase-8 pathways, thereby down-regulating Casp-3 activation. This mechanism selectively triggers GSDMD-mediated pyroptosis, provoking robust immunogenic cell death and inflammatory cytokine release to reconfigure the tumor immune microenvironment. In murine tumor models, DIBDO enhances tumor infiltration of cytotoxic T cells and synergizes with checkpoint blockade therapy to suppress both primary and distal tumors. It can also serve as an in situ or exogenous vaccine to elicit potent and durable antitumor immunity. This work presents a paradigm-shifting approach to cancer immunotherapy by decoupling pyroptosis from Casp-3 dependence, offering a promising avenue to expand the scope of immunogenic cell death-based treatments.

Photodynamic therapy (PDT) stands out as a promising alternative for cancer treatment due to its low invasiveness and low side effects. Additionally, photosensitizers often exhibit photoluminescent properties, which provide valuable diagnostic guidance for preoperative planning and drug delivery. However, current assessment of therapeutic efficacy largely relies on auxiliary imaging techniques to track tumor volume changes, which fail to provide real-time feedback on treatment outcomes. In this study, a DNA-specific dual-emissive photosensitizer, TPBT, was identified for photodynamic theranostics with red fluorescence serving for preoperative guidance and green fluorescence enabling real-time therapeutic evaluation. Notably, TPBT can behave as a cell-membrane permeable dye to stain the nuclei of early apoptosis cells. Moreover, TPBT exhibits a unique "light-induced emission enhancement" phenomenon, where its green fluorescence intensity is amplified by approximately three-fold under light exposure, enabling more accurate signal reporting and reducing photobleaching. The dual-emissive TPBT integrates diagnostic imaging, personalized treatment, and real-time therapeutic monitoring into a single molecule, offering an innovative strategy for developing efficient and precise theranostic systems.

Benzo(a)pyrene (B[a]P) is a pervasive freshwater pollutant, yet its toxicity to the fish gallbladder remains poorly understood. This study investigated the toxicological impacts of 2.5 and 25 μg/L B[a]P on common carp (Cyprinus carpio) using histological, transcriptomic, and single-cell RNA sequencing (scRNA-seq) analyses. Results showed that the gallbladder is a primary site for B[a]P accumulation. High B[a]P concentrations caused vacuolar degeneration of mucosal epithelial cells and nuclear deformities. Transcriptomic analysis revealed that B[a]P stress triggered autoimmune homeostasis imbalance and overinhibited apoptosis. scRNA-seq identified cellular heterogeneity changes, specifically T-cell impairment and epithelial cell (EC) proliferation. Mechanistically, T-cell reduction was linked to the T-cell 2 subset, while EC proliferation involved EC 0 and EC 4 subsets, all participating in the apoptosis pathway. These findings demonstrate that the apoptosis pathway is a key target of B[a]P toxicity in the gallbladder. This work provides a cellular-level framework for assessing environmental polycyclic aromatic hydrocarbon (PAH) risks in aquaculture.

Hemoperfusion has become an important blood-purification modality in critical illnesses, renal failure, liver disorders and sepsis. Due to its ability to remove different toxins from the blood using special adsorbents, hemoperfusion has therapeutic advantages over other technologies, such as hemodialysis. Innovations in adsorbent materials and application systems have led to the advancement of clinical applications of hemoperfusion. In this review, technological innovations in both traditional (activated carbon, natural and synthetic polymers) and novel adsorbent materials (carbon nanomaterials, two-dimensional materials, and ordered porous materials) are evaluated. The performance of these adsorbents in terms of adsorption capacity, biocompatibility, and adsorption mechanism is further introduced and compared. In addition, emerging hemoperfusion adsorbent application systems are discussed, including catalytic systems, adsorption systems integrated with monitoring functions, microfluidic platforms for precise toxin removal, and wearable devices for continuous treatment. This review devotes particular attention to the material innovations and application systems of hemoperfusion adsorbents, highlighting hemoperfusion's potential as a pivotal technology in personalized and precision medicine for the management of complex diseases.

Radiation proctitis (RP), the most prevalent complication of pelvic radiotherapy, remains therapeutically challenging due to rapid drug clearance and the lack of strategies that simultaneously address oxidative stress, inflammation, and impaired epithelial repair. Inspired by the intrinsic mucosal retention of Auricularia auricula (AA), we develop a polydiacetylene-pullulan microgel (PPMG) that integrates prolonged bioadhesion, potent reactive oxygen species (ROS) scavenging, and pathology-responsive epidermal growth factor (EGF) release into a single platform. EGF-loaded PPMG (EGF@PPMG) exhibits a wrinkled microstructure mimicking that of AA, enabling extended mucosal retention through physical interlocking, electrostatic interactions, and hydrogen bonding at the damaged colorectal epithelium. Its polydiacetylene backbone acts as a sacrificial antioxidant, efficiently eliminating radiation-induced ROS while protecting the structural integrity and bioactivity of EGF. In a murine RP model, a single enema of EGF@PPMG markedly attenuated oxidative stress, suppressed pro-inflammatory cytokine expression, alleviated colorectal shortening, and accelerated epithelial regeneration, outperforming the clinical standard of EGF-sucralfate combination. Comprehensive biosafety evaluations confirmed the excellent biocompatibility of PPMG without systemic toxicity. This work establishes a biomimetic, microenvironment-modulating microgel platform that integrates antioxidant, anti-inflammatory, and pro-healing functions into a single long-acting formulation, offering a broadly applicable strategy for the localized management of RP and other mucosal inflammatory diseases.

The phototheranostic system has garnered significant attention due to its dual functionality of combining imaging and treatment. Moreover, while achieving non-invasive, real-time imaging and precise spatiotemporal controlled treatment, it also maintains low toxicity to normal tissues. Among the phototheranostic systems, cyanine dyes are a kind of ideal near-infrared (NIR) photosensitizer for phototheranostics. However, challenges still remain in terms of photostability, tumor selectivity, and diagnostic and treatment efficiency. This review summarizes advances of cyanine dye-based phototheranostics in tumor diagnosis and treatment over the past five years, with a focus on molecular modifications and nanostructure construction, delivery strategies, and synergistic mechanisms in integrated platforms for enhancing functionality. The review also looks ahead to future opportunities and challenges of cyanine dyes in tumor theranostics.

Raman imaging,as a molecular spectroscopy technique,has been widely studied and applied in research fields such as life sciences and food safety due to its excellent specificity and high resolution.However,its development still faces challenges such as weak signals,slow acquisition speed,and insufficient penetration depth.In recent years,the rapid development of aggregate science has provided new insights for addressing these limitations.Aggregation-induced emission(AIE)materials exhibit enhanced signals in the aggregated state,which may compensate for the inherent weak Raman signals.This article reviews the cutting-edge progress of Raman imaging technology and its current status in cross-disciplinary research with aggregate science,emphasizing the strategy of constructing AIE-Raman dual-responsive probes through molecular engineering to achieve functional complementarity between fluorescence localization and Raman quantification,thereby significantly improving detection sensitivity and specificity.These probes have demonstrated single-cell resolution and high spatiotemporal accuracy in applications such as tumor surgical navigation,diagnosis and treatment of drug-resistant bacteria,and dynamic monitoring of organelles.We also analyze the bottlenecks in this field,such as biological safety and the complexity of molecular design,and outline the future development directions,including intelligent responsive probes,artificial intelligence-assisted analysis,and multimodal fusion platforms.The integration of Raman imaging and AIE sheds new light in the field of medical imaging.

"Milk disease", a relatively serious disease with a high infection and mortality rate, frequently threatens the aquaculture of the Chinese mitten crab area, especially in northern China in recent years. To explore effective measures on the "milky disease" control, gradient temperature and pH were designed for the aquaculture of the infected crabs according to the reproductive characteristics of the pathogens. Then, the tissue slice and the immune capacity were detected to analyze the treatment resulting response on the organism immune system; and the bacterial and fungal flora distribution of the hepatopancreas was analyzed to judge the trend of disease development. The results found that low temperature (16 degrees C) significantly increased the survival percentage of the infected crabs (p < 0.05), which weakened the damage of the immune system and enhanced immunoenzyme activities (p < 0.05), but without any significant change in the microbial flora structure, indicating low temperature delayed the onset of disease and can effectively gain time for further treatment and cure measures. High temperature decreased the survival percentage (p < 0.05), but the only survived crabs showed a much higher immunocompetence and a reduced percent of community abundance of the pathogen in vivo (p < 0.05). These crabs prompted the characteristics of the "cured" crabs and suggested immunity promotion and the competition/inhibition of the pathogen in vivo would be significant for the prophylaxis and treatment of the milky disease. The survival percentage and fluctuant enzyme activities of alkali-pH groups manifested that alkali pH brought a positive response in the preliminary stage but damaged the immune system of the infected crabs, indicating it is essential to reappraise the adaptability to environmental factors in the infected crabs for disease control. This study is of crucial meaning for establishing new strategies for prevention and control of the "milky disease".

Bioflocculant is considered to have broad application prospect in multi fields for the nontoxic and biodegradation properties. Screening new bioflocculant-producing bacteria with high flocculating activity, stress resistance characteristics, and application security is a significant action in the development of the biofloc technique. A novel bioflocculant-producing species, Metabacillus hrfriensis CT-WN-B3, was isolated from alkali-tolerant strains distributing in Daqing, Heilongjiang Province, China. A strong activity flocculant was detected in the extracellular polymeric substance (EPS) of CT-WN-B3, which could form biofloc more effectively under alkali conditions, with a flocculating rate of more than 70 %. The principal component of the bioflocculant was identified as the polysaccharide of extracellular polymeric substance (EPS) because of its 75.183 +/- 2.268 % flocculation contribution, which was very significantly higher than that of the protein and the lipid (p < 0.01). Basing on the whole-genome sequencing analysis of CT-WN-B3, none gene encodes a known virulence factor, but two genes correspond to antibiotic resistance. Antibiotic resistance tests showed CT-WN-B3 was resistant to clindamycin. In the assessment of the antimicrobial spectrum, no antibacterial active substance was detected in the supernatant of CT-WN-B3 culture. Totally, the results of the safety assessment had eliminated the doubts about the application risk of CT-WN-B3. These results indicated that CT-WN-B3 is an alkali-suitable flocculant-producing bacterium for application in multiple fields, under alkali conditions especially.

The blood-brain barrier (BBB) is a substantial impediment to effectively delivering central nervous system (CNS) therapies. In this review, we provide a comprehensive dissection of the BBB's elaborate structure and function and discuss the inherent limitations of conventional drug delivery mechanisms due to its impermeability. We summarized the creative deployment of nanocarriers, the astute modification of small molecules to bolster their CNS penetration capabilities as well as the burgeoning potential of magnetic nanoparticles and optical techniques that are positioned to enable more precise and targeted drug delivery across the BBB and we discuss the current clinical application of some nanomedicines. In addition, we emphasize the indispensable role of artificial intelligence in designing novel materials and the paramount significance of interdisciplinary research in surmounting clinical challenges associated with BBB penetration. Our review meticulously integrates these insights to accentuate the impact of nanotechnological innovations in BBB research and CNS disease management. It presents a promising trajectory for the evolution of patient care in neurological disorders and suggests that these scientific strides could lead to more efficacious treatments and improved outcomes for those afflicted with such conditions.

Paraptosis emerges as a new promising form of programmed nonapoptotic cell death in chemotherapeutic anticancer therapy. However, current paraptosis agents face critical challenges, including poor targeting specificity, limited imaging capability, and low therapeutic efficacy. To overcome these limitations, we developed a novel approach by functionalizing the tetraphenylethylene (TPE) unit at the meso position of xanthene dyes, enabling the synthesis of two sterically hindered regioisomeric fluorescent paraptosis-inducing agents (m-TSX and p-TSX) for mitochondria-targeted chemo-photodynamic anticancer therapy. These agents exhibited strong near-infrared (NIR) emissions (∼663 nm) with a quantum yield of up to 82.9%. The TPE substitution, in contrast to the phenyl group, allowed for precise modulation of triplet excited state energy levels, boosting type I/II reactive oxygen species (ROS) generation, and notable enhancement of the paraptotic anticancer activity. Comparative studies of the meta- and para-substituted regioisomers revealed that the meta-substituted m-TSX exhibited superior ROS generation and anticancer behavior. m-TSX effectively induced Alix/ATF4-regulated paraptosis, along with apoptosis and necrosis, while also triggering GPX4/SLC7A11-regulated ferroptosis under low-power 655 nm laser (0.1 W/cm2) irradiation, leading to effective cancer cell growth inhibition. Furthermore, in vivo chemo-photodynamic therapy against HeLa tumor by inducing multiple cell death pathways was successfully achieved. This innovative strategy of steric hindrance regulation represents a breakthrough in developing bright NIR xanthene-based anticancer agents for synergistic cancer therapy.

In this study, we aimed to explore the biological characteristics and quality of crayfish (Procambarus clarkii) reared in different modes and fill in the research gap regarding assessments of Procambarus clarkii quality in the cold regions of China. To achieve this, typical rice–crayfish coculture (RCCC) and pond culture (PC) modes were established in Northeast China to evaluate the chelae proportion (CP), hepatosomatic index (HSI), abdominal meat yield (MY), proximate composition, fatty acids, free amino acids, and mineral elements of Procambarus clarkii. Extremely significantly higher CP (32.50%) but lower HSI (6.22%) and MY (9.54%) were observed in P. clarkii reared in the RCCC compared with those reared in the PC. The RCCC contained higher levels of total lipids, ∑MUFA, ∑EFA, h/H, ∑EFAA, ∑FAA, ∑TUV, ∑TBV, and ∑TME but lower levels of crude protein, ∑SFA, DHA + EPA, DHA/EPA, AI, and ∑TSV in the hepatopancreas. In addition, the RCCC had higher levels of ∑SFA, ∑EFA, AI, TI, ∑EFAA, ∑FAA, ∑TUV, and ∑TBV but lower levels of ∑HUFA, ∑n-6 PUFA, DHA/EPA, h/H, ∑TSV, and ∑TME in muscle. In summary, the culture modes of P. clarkii reared in the cold regions of China have an influence on the biological characteristics and quality of this species.

Polydiacetylene (PDA) materials are a class of conjugated polymeric materials with alternating carbon-carbon double (C=C) and triple (C equivalent to C) bonds, synthesized by the oriented regular arrangement of DA monomers using solid-state topochemical polymerization, which have unique optical properties and colorimetric capabilities. The newly synthesized PDA exhibits blue color and non-fluorescent properties, and when it is exposed to environmental stimuli, such as changes in pH, temperature, electrical stress, mechanical stress, etc., it will undergo a transition from blue to red, generating PDA with red phase and obvious fluorescence, which is a characteristic that makes it widely used in the field of biosensing. Meanwhile, the Raman spectrum of PDA is located in the cellular silent region (1800-2800 cm-1), which is not interfered by biological macromolecules such as proteins and nucleic acids, etc. The molecular structure of the traditional PDA restricts the enhancement of its Raman signal, and to obtain effective SRS imaging in living cells, it is necessary to couple the imaging technique with intrinsically Raman-active molecular probes. In this paper, a water-soluble and functionalizable PDA material is introduced, which exhibits superb Raman signal and ultra-high sensitivity, and can target different cells after surface modification, and also performs deep tissue imaging after synergizing the Raman imaging technique with two-photon imaging, highlighting its great application prospects in the imaging field. Due to the easy modification of PDA, coupling the target with PDA can realize direct biosensing or improve the targeting effect of drug delivery; PDA also shows good biomimetic properties, through the doping of biomolecules or the design of its molecular structure, it is prepared into liposomes, nanofibers and other forms, which can respond to changes in the biological environment, and has good potential for use in the fields of indirect biosensing, tissue engineering, and drug delivery. Meanwhile, we also found that PDA materials generate reactive oxygen species under photo-oxidation conditions and degrade themselves into non-toxic small molecules such as succinic acid, which are ROS-responsive and degradable, and can be made into smart microenvironmental drug delivery systems or degradable tissue scaffolds, which have obvious advantages in the fields of in vivo tumor therapy, cardiovascular therapy, and tissue repair. In this review, we introduce the synthesis methods, structural properties, and excellent biochemical and optoelectronic properties of PDA materials, summarize their recent progress in the fields of Raman imaging, biosensing, tissue engineering, and drug delivery, and reveal the multifunctionality of PDA materials as well as their advantages in the diagnosis and treatment of diseases to show the value of the application of PDA materials in the biomedical field.

Cationic photosensitizers (PSs) offer many intriguing advantages, in addition to generating heat or reactive oxygen species for cancer phototherapy. However, the preparation of cationic PSs with enhanced near-infrared (NIR) absorption remains a significant challenge. In this work, we have synthesized a PS TPBBT, which incorporates a strong electron-withdrawing unit, benzobisthiadiazole, and four terminal pyridinium groups. It self-assembles into a mixed H/J aggregated state with a maximal absorption peak at 620 nm but coassembles with negatively charged planar small molecules to form sole J-aggregates. Following this strategy, we coassemble TPBBT with rhein, a planar, anionic traditional Chinese medicine with an anticancer activity, which allows for a near 100 nm bathochromic shift of the maximal absorption of TPBBT and improves the photothermal conversion efficiency (PCE) of TPBBT from 6.4 to 60.4% under 808 nm laser irradiation. Additionally, coassembling with TPBBT significantly enhances the cellular uptake of rhein through the photothermal effect. The coassembly of TPBBT and rhein (TPBBTein) can completely eliminate 4T1 tumors on mouse models, validating that this facile strategy not only can tune the NIR J-aggregate of cationic PS through molecular coassembly but also promotes the efficient, symbiotic combination of photothermal therapy and chemotherapy.

Atherosclerosis(AS)is a complex cardiovascular disease characterized by the buildup of plaque in the arteries.The development of effective diagnostic and therapeutic strategies is crucial for the management of AS.Polymeric nanomaterials,due to their unique properties such as biocompatibility,versatility,and ease of functionalization,have emerged as promising materials for the diagnosis and treatment of AS.This review summarizes the pathogenesis,mechanisms,and microenvironment features changes in AS,as well as the polymeric nanomaterial treatment strategies targeting these changes.It also provides a detailed overview of the applications of polymeric nanomaterials in various imaging techniques and therapy strategies for AS.In addition,this review discusses the biosafety evaluation systems for polymeric nanomaterials,encompassing in vivo distribution and metabolism assessment,biological evaluation,immunological evaluation,and toxicological evaluation.It aims to compile the current state of research and applications of polymeric nanomaterials in AS diagnosis and treatment,highlighting their potential for translation into clinical practice.

Air exposure stress can induce stress response of Eriocheir sinensis and affect its normal life activities. The goal of this study was to investigate the effects of water immersion on the recovery of hepatopancreas immune-related enzyme activity, intestinal microbial diversity and metabolic level of Chinese mitten crabs after exposure to air. The results show that immersion can effectively alleviate the adverse effects of air exposure on the antioxidant capacity and immune capacity of Chinese mitten crabs, and the longer the time of immersion, the more obvious the recovery effect. Among them, the levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and acid phosphatase significantly increased after exposure to air (P < 0.05), reached a peak at 3 h, began to decline after immersion, and returned to a level close to the initial value at 24 h (P < 0.05). In addition, after exposure to air, the glucose and total cholesterol in haemolymph of Eriocheir sinensis were significantly different from the initial values (P < 0.05), gradually recovered to the initial level after re-immersion. However, changes in intestinal flora and hepatopancreas metabolism caused by air exposure did not fully recover after water exposure, and its negative effects did not completely disappear. The sequencing results showed that the species composition and diversity of intestinal microorganisms of Chinese mitten crab changed after air exposure and immersion treatment. The relative abundance of Actinomycetes increased significantly, while that of Proteobacteria and Firmicutes decreased significantly. Metabolomics analysis showed that air exposure and immersion destroyed the metabolic balance of amino acids and carnitine, reduced the level of carnitine metabolism, hindered the absorption of nutrients, and led to the accumulation of harmful substances.

α‐Synuclein (α‐Syn) amyloidogenesis is considered a promising diagnostic marker and therapeutic target for Parkinson's disease (PD). Simultaneously visualizing and mitigating α‐Syn amyloidogenesis are essential for future PD theranostics, yet they continue to pose an insurmountable challenge. This study have herein developed a nanobody‐decorated polydiacetylene to approach a straightforward solution. Grafting α‐Syn61‐95 segment into the third complementary determining region of a parent nanobody generates an engineered nanobody X30 that can bind with α‐Syn and prevent its amyloidogenesis through homotypic interaction. It next use X30 to decorate poly(deca‐4,6‐diynedioic acid) (PDDA), a polydiacetylene with an ultrastrong alkyne Raman signal (2120 cm −1 ) in the cellular silent region, to create an α‐Syn targeting Raman probe PX30. The binding affinity between X30 and α‐Syn can be further boosted for over 150 times attributed to the rigidity of PDDA backbone and the multivalent effect. Therefore, PX30 not only enables real‐time Raman visualization of α‐Syn amyloidogenesis with a high signal‐to‐noise ratio in living zebrafish, but also alleviates amyloidogenesis‐mediated damage to zebrafish embryos by effectively inhibiting α‐Syn amyloidogenesis at low stoichiometric concentrations and scavenging pathologic reactive oxygen species.