Cytochrome P450 Mining for Bufadienolide Diversification.

Bufadienolides are a class of steroids with a distinctive α-pyrone ring at C17, mostly produced by toads and consisting of over 100 orthologues. They exhibit potent cardiotonic and antitumor activities and are active ingredients of the traditional Chinese medicine Chansu and Cinobufacini. Direct extraction from toads is costly, and chemical synthesis is difficult, limiting the accessibility of active bufadienolides with diverse modifications and trace content. In this work, based on the transcriptome and genome analyses, using a yeast-based screening platform, we obtained eight cytochrome P450 (CYP) enzymes from toads, which catalyze the hydroxylation of bufalin and resibufogenin at different sites. Moreover, a reported fungal CYP enzyme Sth10 was found functioning in the modification of bufalin and resibufogenin at multiple sites. A total of 15 bufadienolides were produced and structurally identified, of which six were first discovered. All of the compounds were effective in inhibiting the proliferation of tumor cells, especially 19-hydroxy-bufalin (2) and 1ß-hydroxy-bufalin (3), which were generated from bufalin hydroxylation catalyzed by CYP46A35. The catalytic efficiency of CYP46A35 was improved about six times and its substrate diversity was expanded to progesterone and testosterone, the common precursors for steroid drugs, achieving their efficient and site-specific hydroxylation. These findings elucidate the key modification process in the synthesis of bufadienolides by toads and provide an effective way for the synthesis of unavailable bufadienolides with site-specific modification and active potentials.

DNA Bloom Filter enables anti-contamination and file version control for DNA-based data storage.

DNA storage is one of the most promising ways for future information storage due to its high data storage density, durable storage time and low maintenance cost. However, errors are inevitable during synthesizing, storing and sequencing. Currently, many error correction algorithms have been developed to ensure accurate information retrieval, but they will decrease storage density or increase computing complexity. Here, we apply the Bloom Filter, a space-efficient probabilistic data structure, to DNA storage to achieve the anti-error, or anti-contamination function. This method only needs the original correct DNA sequences (referred to as target sequences) to produce a corresponding data structure, which will filter out almost all the incorrect sequences (referred to as non-target sequences) during sequencing data analysis. Experimental results demonstrate the universal and efficient filtering capabilities of our method. Furthermore, we employ the Counting Bloom Filter to achieve the file version control function, which significantly reduces synthesis costs when modifying DNA-form files. To achieve cost-efficient file version control function, a modified system based on yin-yang codec is developed.

Glabridin reduces neuroinflammation by modulating inflammatory signals in LPS-induced in vitro and in vivo models.

OBJECTIVES: Chronic neuroinflammation has become one of the important causes of common neurodegeneration disease. Therefore, the target of this study was to explore the protective action of glabridin on lipopolysaccharide (LPS)-induced neuroinflammation in vivo and in vitro and its mechanism. METHODS: The neuroinflammation model was established by LPS-induced BV2 cells. The cell viability with various concentrations of glabridin was determined by MTT assay, and the content of NO in each group was detected. A neuroinflammatory model was established in male C57BL/6J mice for a water maze test. Subsequently, NF-κB and SOD indices were measured by ELISA, GFAP and IBA-1 indices were measured by immunofluorescence, and Nissl staining was used to explore the Nissl bodies in the hippocampus of mice. RESULTS: In vitro experiments, our results expressed that glabridin could markedly increase the cell activity of LPS-induced BV2 cells and reduce the NO expression in cells. It indicated that glabridin had a remarkable impact on the neuroinflammation of LPS-induced BV2 cell protection. In vivo neuroinflammation experiments, mice treated with different doses of glabridin showed significantly improved ability of memory compared with the LPS group in the Morris water maze test. The levels of NF-κB, GFAP, and the number of positive cells in Nissl staining were decreased. High-dose glabridin significantly increased the SOD content in the brain tissue and decreased the IBA-1 levels. CONCLUSION: Glabridin can significantly reduce or even reverse LPS-induced neuroinflammation, which may be related to the fact that glabridin can reduce the NO expression, NF-κB, IBA-1, GFAP, and other inflammatory mediators, upregulate the expression of SOD to relieve oxidative stress of brain and inhibit the activation of gliocyte in brain tissue.

Daith piercing: Revisited from the perspective of auricular acupuncture systems. A narrative review.

BACKGROUND: Daith piercing is a special ear-piercing method that punctures the crus of the helix. The penetrated site at the ear's innermost point is assumed to stimulate a pressure point associated with the vagus nerve. It has been reported that the pierced spot relieves migraine and tension-type headaches by activating vagal afferents, leading to the inhibition of neurons in the caudal trigeminal nucleus via the nucleus tractus solitarii. OBJECTIVE: The objective of this narrative literature review is to summarize the current state of knowledge concerning daith piercing for the treatment of migraine and tension-type headaches from the perspectives of the Chinese and Western auricular systems. METHODS: PubMed and China National Knowledge Infrastructure databases were searched using the keywords "daith piercing," "auricular points," "headache," and "acupuncture" from database inception to September 1, 2023. Only studies on humans were eligible; otherwise, no further restrictions were applied to the study designs, type of headache, or patient population of the identified articles. Bibliographies of all eligible studies were screened for further eligible studies. The main outcome of interest was a quantitative measure of pain relief by daith piercing. Secondary outcomes were relapse time of headache and further outcomes related to daith piercing, if available. RESULTS: From a total of 186 identified articles, one retrospective study and three case reports fulfilled the inclusion criteria. No clinical trial was identified. The obtained studies describe patients experiencing chronic headaches undergoing daith piercing without changing or reducing their usual medication. In all case studies and the retrospective study, patients reported substantial reductions in pain immediately after daith piercing; however, headache symptoms recurred several weeks to months thereafter. From the perspective of the Chinese and Western auricular systems, no sufficient explanation for the described treatment effect of daith piercing was found. CONCLUSION: The available literature, combined with the reported recurrence of pain as well as the associated side effects of daith piercing, indicate that current evidence does not support daith piercing for the treatment of migraine, tension-type headaches, or other headache disorders. PLAIN LANGUAGE SUMMARY: This paper summarizes what we know about Daith piercing (DP) for chronic migraine and tension-type headache and discusses how DP might work. Current evidence does not support DP as an effective treatment of chronic migraine and tension-type headache. These findings might assist clinicians in discussing this subject with patients as well as guide future research.

Veronica linariifolia subsp. dilatata ameliorates LPS-induced acute lung injury by attenuating endothelial cell barrier dysfunction via EGFR/Akt/ZO-1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried aerial parts of Veronica linariifolia subsp. dilatata (Nakai & Kitag.) D.Y.Hong named Shui Man Jing (SMJ) is a traditional Chinese medicine with a long history of clinical use in the treatment of chronic bronchitis and coughing up blood, however, its role on acute lung injury (ALI) has not been revealed yet. AIM OF THE STUDY: To assess the efficiency of SMJ on ALI and to investigate whether it inhibited endothelial barrier dysfunction by regulating the EGFR/Akt/ZO-1 pathway to alleviate ALI in vivo and in vitro based on the result of network pharmacology. MATERIALS AND METHODS: An in vivo model of ALI was established using inhalation of atomized lipopolysaccharide (LPS), and the effects of SMJ on ALI were evaluated through histopathological examination and inflammatory cytokines, lung histology and edema, vascular and alveolar barrier disruption. Network pharmacology was applied to predict the mechanism of SMJ in the treatment of ALI. The crucial targets were validated by RT-PCR, Western Blotting, molecular docking, immunohistochemistry and immunofluorescence methods in vivo and in virto. RESULTS: Administration of SMJ protected mice against LPS-induced ALI, including ameliorating the histological alterations in the lung tissues, and decreasing lung edema, protein content of bronchoalveolar lavage fluid, infiltration of inflammatory cell and secretion of cytokines. SMJ exerted protective effects in ALI by inhibiting endothelial barrier dysfunction in mice and bEnd.3 cell. SMJ relieved endothelial barrier dysfunction induced by LPS through upregulating the EGFR expression. SMJ also increased the phosphorylation of Akt, and ZO-1 expression both in vivo and in vitro. CONCLUSION: SMJ attenuates vascular endothelial barrier dysfunction for LPS-induced ALI via EGFR/Akt/ZO-1 pathway, and is a promising novel therapeutic candidate for ALI.

Ent-labdane-type diterpene glycosides obtained from Rubus chingii Hu and their inhibitory effects on PDE5A activity.

In this study, 16 new ent-labdane-type diterpene glycosides, designated as goshonosides J1-J16 (1-16), along with nine previously known diterpene glycosides (17-25) were extracted from the fruits of Rubus chingii Hu. The structures of goshonosides J1-J16 were elucidated using various analytical techniques, such as nuclear magnetic resonance, electron capture detector ECD, high-resolution electrospray ionization mass spectrometry HREIMS, single-crystal X-ray diffraction, and hydrolysis. Furthermore, the isolates' efficacy in inhibiting the activity of phosphodiesterase type 5 A was evaluated. Goshonosides J1, J2, and G effectively inhibited the activity of the aforementioned enzyme (IC50 values: 6.15 ± 1.76, 3.27 ± 0.65, and 9.61 ± 2.36 µM, respectively). Our findings highlight the remarkable structural diversity of bioactive compounds in R. chingii Hu and offer insights into the use of this shrub.

[A comparative study of raw Aurantii Fructus Immaturus and bran-fried products on dryness of rats with slow-transit constipation].

The differences in dryness between raw Aurantii Fructus Immaturus(AFI) and bran-fried products were investigated based on a slow-transit constipation(STC) model. Seventy healthy SPF-grade rats were randomly divided into a blank group(K), a positive drug group(Y), a model group(M), low-and high-dose raw AFI groups(SD and SG), and low-and high-dose bran-fried AFI groups(FD and FG). During the experiment, it was found that compared with the K group, the groups with drug treatment had little effect on the daily body weight of the STC rats. The first defecation time of black stool in the M group was significantly higher than that in the K group, and the 24-hour fecal output significantly decreased starting from the 13th day, indicating successful modeling. The SG group showed a significant increase in the first defecation time, fecal water content, urine output, and water intake than other groups with drug treatment. The FG group had the highest fecal output than other groups with drug treatment. The FD group had the highest salivary secretion than other groups with drug treatment. The levels of cAMP/cGMP, VIP, 5-HT, AQP1, and AQP5 were measured in each group with drug treatment, and the expression of c-Kit and SCF mRNA in gastric antrum tissue and AQP3 mRNA in the kidney and colon were detected by RT-PCR. The results showed that the SD and SG groups had a more significant impact on AQP1, AQP5, and other water channel indexes in STC rats than the FD and FG groups. The FD and FG groups had a more significant impact on c-Kit, SCF, VIP, 5-HT, and other gastrointestinal motility indicators than the SD and SG groups. This study, through in vitro biological observations, immunological detection, and gene expression analysis, found that raw AFI had strong dryness property, while bran-fried AFI could alleviate its dryness property.

Effects of dietary melatonin on antioxidant and immune function of the Pacific white shrimp (Litopenaeus vannamei), as determined by transcriptomic analysis.

Melatonin (MT) is regarded as an antioxidant and immunostimulant that can efficiently scavenge free radicals and activate antioxidant enzymes. The aim of this study was to investigate the effects of dietary MT on the growth performance and immune function of the Pacific white shrimp (Litopenaeus vannamei). Six groups of L. vannamei were supplemented with dietary MT at 0, 22.5, 41.2, 82.7, 165.1, and 329.2 mg/kg levels for 2 months. RNA-Seq analysis was performed to obtain transcriptome data of the control group and the group supplemented with dietary MT at 82.7 mg/kg BW. In total, 1220 DEGs (799 up-regulated and 421 down-regulated) were identified. Pathways and genes related to growth performance and immune function were verified by real-time quantitative polymerase chain reaction. The total hemocyte count, phagocytosis rate, and respiratory burst were significantly increased in the MT (82.7 mg/kg BW) group as compared to the control group. Analysis of antioxidant-related enzymes in the hepatopancreas showed that dietary MT (82.7 mg/kg BW) significantly increased activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase, while dietary MT at 41.2 mg/kg BW significantly increased activities of glutathione S-transferase, lysozyme (LZM), and phenoloxidase (PO). At the transcriptional level, dietary MT up-regulated expression levels of genes associated with antioxidant immunity and growth, which included PO, SOD, LZM, GPx, chitin synthase, ecdysone receptor, calcium-calmodulin dependent protein kinase I, and retinoid X receptor. In conclusion, dietary MT may improve the growth performance and immune function of L. vannamei to some extent.

Transcriptomic analysis of the antioxidant responses and immunomodulatory effects of dietary melatonin in red swamp crayfish (Procambarus clarkii).

This study aimed to investigate the effects of dietary melatonin (MT) levels on the antioxidant capacity, immunomodulatory, and transcriptional regulation of red swamp crayfish. Six experimental diets with different levels of MT (0, 22.5, 41.2, 82.7, 165.1, and 329.2 mg/kg diet) were fed to juvenile crayfish for 60 d. The transcriptome data of the control group and the group supplemented with dietary MT at 165.1 mg/kg were obtained using RNA-seq. In total, 3653 differentially expressed genes (2082 up-regulated and 1571 down-regulated) were identified. Pathways and genes related to antioxidant immune and growth performance were verified by qRT-PCR. The total hemocyte count, phagocytosis rate, and respiratory burst were significantly increased in the MT (165.1 mg/kg) group compared to the control group. Analysis of antioxidant immune-related enzymes in the hepatopancreas demonstrated that dietary MT (165.1 mg/kg) significantly increased activities of catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase and significantly decreased aspartate aminotransferase and alanine aminotransferase activity. At the transcriptional level, dietary MT up-regulated expression levels of genes associated with antioxidant immune and development, which included toll-like receptors, Crustin, C-type lectin, and so on. To conclude, MT could be used as a supplement in crayfish feed to increase immunity and antioxidant capacity and according to the broken line regression, the ideal MT concentration was the 159.02 mg/kg. Overall, this study demonstrates the role of melatonin in the antioxidant responses and immunomodulatory of Procambarus clarkii, laying the foundation for the development of melatonin as a feed additive in the aquaculture of this species.

Constituents of the fruits of Rubus chingii Hu and their neuroprotective effects on human neuroblastoma SH-SY5Y cells.

Rubi fructus (Rubus chingii Hu) is a fruit of Rubus genus and is used in medicine and food applications. In this study, eight new phenylpropanoids (1-8) and seven known compounds (9-15) were isolated from the dried fruits of Rubus chingii Hu, and their structures were characterized through high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopy. Electronic circular dichroism (ECD) experiments were performed, and the results were compared with ECD spectra. Compound 3 was characterized through extensive single crystal X-ray diffraction. Evaluation of the neuroprotective pharmacological activities revealed that compounds 6, 7, 9, and 14 exerted protective effects against H2O2-induced neurotoxicity by reducing the reactive oxygen species levels at concentrations of 50 and 100 µM. Moreover, the three compounds 6, 9, and 14 significantly inhibited the expression of the Casp3 gene at a concentration of 50 µM. Compounds 7 and 9 effectively repressed the expression of the MYC gene. Compounds 6 and 9 obviously upregulated the ratio of Bcl2/Bax in SH-SY5Y cells and inhibited cell apoptosis. The study results can be used as a reference for the development of R. chingii products to realize their neuroprotective functions in the future.

Comparative metabolomics analysis investigating the impact of melatonin-enriched diet on energy metabolism in the crayfish, Cherax destructor.

Melatonin is a multifunctional bioactive molecule present in almost all organisms and has been gradually used in the aquaculture industry in recent years. Energy metabolism is an essential process for individuals to maintain their life activities; however, the process through which melatonin regulates energy metabolism in aquatic animals remains unclear. The present study aimed to conduct a comprehensive analysis of the regulatory mechanism of melatonin for energy metabolism in Cherax destructor by combining metabolomics analysis with the detection of the key substance content, enzymatic activity, and gene expression levels in the energy metabolism process after culturing with dietary melatonin supplementation for 8 weeks. Our results showed that dietary melatonin increased the content of glycogen, triglycerides, and free fatty acids; decreased lactate levels; and promoted the enzymatic activity of pyruvate kinase (PK), malate dehydrogenase (MDH), and acetyl-CoA carboxylase. The results of gene expression analysis showed that dietary melatonin also increased the expression levels of hexokinase, PK, MDH, lactate dehydrogenase, lipase, and fatty acid synthase genes. The results of metabolomics analysis showed that differentially expressed metabolites were significantly enriched in lysine degradation and glycerophospholipid metabolism. In conclusion, our study demonstrates that dietary melatonin increased oxidative phosphorylation, improved glucose utilization, and promoted storage of glycogen and lipids in C. destructor. These lipids are used not only for energy storage but also to maintain the structure and function of cell membranes. Our results further add to the understanding of the mechanisms of energy regulation by melatonin in crustaceans.

Bibliometric analysis of acupuncture and moxibustion treatment for mild cognitive impairment.

Objective: This study aims to analyze the current research status of acupuncture in the treatment of mild cognitive impairment (MCI) using bibliometric methods, explore current research hotspots, and predict future research trends. Methods: Literature on acupuncture for MCI in China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) databases were searched from their inception to December 31, 2022. Articles were then filtered using inclusion and exclusion criteria and imported into VOSviewer 1.6.11 and CiteSpace 6.1.6msi software for descriptive analysis of publication numbers, network analysis of author/institution collaborations, and cluster analysis of keywords, as well as analysis of keyword emergence and linear relationships with time. Results: The Chinese and English databases included 243 and 565 relevant articles, respectively. The overall volume of Chinese and English literature was stable, with the annual volume generally increasing. In terms of countries, institutions, and authors, China had the highest number of English-language publications; however, the number of joint publications among institutions/authors was low. Research institutions were independent and dispersed, with no collaborative teams formed around a single institution/author. The hotspots in Chinese literature were "needling, treatment, electric acupuncture, nimodipine, cognitive training" and other clinical research directions. The hotspots in English literature were "acupuncture, electro-acupuncture, Alzheimer's disease, dementia, cognitive impairment, memory, vascular dementia, mild cognitive impairment, stroke, hippocampus, injury," and other mechanisms of action. Conclusion: The popularity of acupuncture for MCI is increasing year by year. Acupuncture for MCI, along with cognitive training, can help improve cognitive function. "Inflammation" is the frontier of acupuncture for MCI research. In the future, strengthening effective communication and cooperation among institutions, especially international cooperation, is essential for conducting high-quality research on acupuncture for MCI. This will help obtain high-level evidence and improve the output and translation of research results.

Iridoids and derivatives from Catalpa ovata with their antioxidant activities.

Six new iridoid derivatives (1-6)，together with twelve known compounds (7-18), were isolated and identified from the dried fruits of Catalpa ovata G. Don. Their chemical structures were mainly established through the relative spectroscopic data, while the absolute configurations of compounds 2 and 3 were elucidated on the electronic circular dichroism calculations. Their antioxidant activities were evaluated by activating the Nrf2 transcriptional pathway in 293 T cells in vitro. Among them, Compounds 1, 3, 4, 6-8, 10-12, 14, 15, 17 and 18 showed significant Nrf2 agonistic effect compared with the control group at 25 µM. Finally, The hypothetical biosynthetic pathway for 1-13 was discussed.

Bavachinin selectively modulates PPAR γ and maintains bone homeostasis in Type 2 Diabetes.

Full peroxisome proliferator-activated receptor (PPAR) γ agonists, Thiazolidinediones (TZDs), effectively prevent the process of Type 2 Diabetes Mellitus (T2DM), but their side effects have curtailed use in the clinic, including weight gain and bone loss. Here, we identified that a selective PPAR γ modulator, Bavachinin (BVC), isolated from the seeds of Psoralea Corylifolia L., could potently regulate bone homeostasis. MC3T3-E1 pre-osteoblast cells and C3H10T1/2 mesenchymal stem cells were assessed for osteogenic differentiation activities, and receptor activator of NF-κB ligand (RANKL)-induced RAW 264.7 cells were assessed osteoclasts formation. Leptin receptor-deficient mice and diet-induced obesity mice were applied to evaluate the effect of BVC on bone homeostasis in vivo. Compared to full PPAR γ agonist rosiglitazone, BVC significantly increased the osteogenesis differentiation activities under normal and high glucose conditions in MC3T3-E1 cells. Moreover, BVC could alleviate osteoclast differentiation in RANKL-induced RAW 264.7 cells. In vivo, synthesized BVC prodrug (BN) has been applied to improve water solubility, increase the extent of oral absorption of BVC and prolong its residence time in blood circulation. BN could prevent weight gain, ameliorate lipid metabolism disorders, improve insulin sensitivity, and maintain bone mass and bone biomechanical properties. BVC, a unique PPAR γ selective modulator, could maintain bone homeostasis, and its prodrug (BN) exhibits insulin sensitizer activity while circumventing the side effects of the TZDs, including bone loss and undesirable weight gain.

SETD7 promotes metastasis of triple-negative breast cancer by YY1 lysine methylation.

Breast cancer has gradually become the predominant cause for cancer-associated death in women. The metastatic dissemination and underlying mechanisms of triple-negative breast cancer (TNBC) are not sufficiently understood. (Su(var)3-9, enhancer of zeste, Trithorax) domain-containing protein 7 (SETD7) is vital for promoting the metastasis of TNBC, as demonstrated in this study. Clinical outcomes were significantly worse in primary metastatic TNBC with upregulated SETD7. Overexpression of SETD7 in vitro and in vivo promotes migration of TNBC cells. Two highly conserved lysine (K) residues K173 and K411 of Yin Yang 1 (YY1) are methylated by SETD7. Further, we found that SETD7-mediated K173 residue methylation protects YY1 from the ubiquitin-proteasome degradation. Mechanistically, it was found that the SETD7/YY1 axis regulates epithelial-mesenchymal transition (EMT) and tumor cell migration via the ERK/MAPK pathway in TNBC. The findings indicated that TNBC metastasis is driven by a novel pathway, which may be a promising target for advanced TNBC treatment.

A step closer to real practice: Integrated tandem photocatalysis-biofilm process towards degradation of crude oil.

Intimately coupled photocatalysis and biodegradation (ICPB) systems represent a promising wastewater treatment technology. The implementation of ICPB systems for oil spill treatment is a pressing concern. In this study, we developed an ICPB system comprising BiOBr/modified g-C3N4 (M-CN) and biofilms for the treatment of oil spills. The results demonstrate that the ICPB system achieved the rapid degradation of crude oil, outperforming the single photocatalysis and biodegradation methods by degrading 89.08 ± 5.36% within 48 h. The combination of BiOBr and M-CN formed a Z-scheme heterojunction structure, enhancing the redox capacity. The interaction between the holes (h+) and the negative charge on the biofilm surface promoted the separation of electrons (e-) and h+, thereby accelerating the degradation process of crude oil. Moreover, ICPB system maintained an excellent degradation ratio after three cycles and its biofilms progressively adapted to the adverse effects of crude oil and light. The microbial community structure remained stable throughout the degradation of crude oil, with Acinetobacter and Sphingobium identified as the dominant genera in biofilms. The proliferation of the Acinetobacter genus appeared to be the main factor contributing to the promotion of crude oil degradation. Our work demonstrates that the integrated tandem strategies perhaps represent a feasible pathway toward practical crude oil degradation.

Effects of dietary melatonin on growth performance, antioxidant capacity, and nonspecific immunity in crayfish, Cherax destructor.

Melatonin (MT) is an indole hormone widely found in plants and animals. Many studies have shown that MT promotes the growth and immunity of mammals, fish, and crabs. However, the effect on commercial crayfish has not been demonstrated. The purpose of this study was to evaluate the effects of dietary MT on growth performance and innate immunity of Cherax destructor from three aspects of individual level, biochemical level, and molecular level after 8 weeks of culture. In this study, we found that MT supplementation increased weight gain rate, specific growth rate, and digestive enzyme activity in C. destructor compared to the control group. Dietary MT not only promoted the activity of T-AOC, SOD, and GR, increased the content of GSH, and decreased the content of MDA in the hepatopancreas, but also increased the content of hemocyanin and copper ions and AKP activity in hemolymph. Gene expression results showed that MT supplementation at appropriate doses increased the expression of cell cycle-regulated genes (CDK, CKI, IGF, and HGF) and non-specific immune genes (TRXR, HSP60, and HSP70). In conclusion, our study showed that adding MT to the diet improved growth performance, enhanced the antioxidant capacity of hepatopancreas, and immune parameters of hemolymph in C. destructor. In addition, our results showed that the optimal dietary supplementation dose of MT in C. destructor is 75-81 mg/kg.

Effects of dietary soluble ß-1,3-glucan on the growth performance, antioxidant status, and immune response of the river prawn (Macrobrachium nipponense).

The effects of dietary ß-1,3-glucan on the growth performance, body composition, hepatopancreas tissue structure, antioxidant activities, and immune response of the river prawn (Macrobrachium nipponense) were investigated. In total, 900 juvenile prawns were fed one of five diets with different contents of ß-1,3-glucan (0%, 0.1%, 0.2%, and 1.0%) or 0.2% curdlan for 6 weeks. The growth rate, weight gain rate, specific growth rate, specific weight gain rate, condition factor, and hepatosomatic index of juvenile prawns fed 0.2% ß-1,3-glucan were significantly higher than those fed 0% ß-1,3-glucan and 0.2% curdlan (p < 0.05). The whole-body crude lipid content of prawns supplemented with curdlan and ß-1,3-glucan was significantly higher than that of the control group (p < 0.05). The antioxidant and immune enzyme activities of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), catalase (CAT), lysozyme (LZM), phenoloxidase (PO), acid phosphatase (ACP), and alkaline phosphatase (AKP) in the hepatopancreas of juvenile prawns fed 0.2% ß-1,3-glucan were significantly higher than those of the control and 0.2% curdlan groups (p < 0.05), and tended to increase and then decrease with increasing dietary ß-1,3-glucan. The highest malondialdehyde (MDA) content was observed in juvenile prawns without ß-1,3-glucan supplementation. The results of real-time quantitative PCR indicated that dietary ß-1,3-glucan promoted expression of antioxidant and immune-related genes. Binomial fit analysis of weight gain rate and specific weight gain rate showed that the optimum ß-1,3-glucan requirement of juvenile prawns was 0.550%-0.553%. We found that suitable dietary ß-1,3-glucan improved juvenile prawns growth performance, antioxidant capacity, and non-specific immunity, which provide reference for shrimp healthy culture.

Structures, Sources, Identification/Quantification Methods, Health Benefits, Bioaccessibility, and Products of Isorhamnetin Glycosides as Phytonutrients.

In recent years, people have tended to consume phytonutrients and nutrients in their daily diets. Isorhamnetin glycosides (IGs) are an essential class of flavonoids derived from dietary and medicinal plants such as Opuntia ficus-indica, Hippophae rhamnoides, and Ginkgo biloba. This review summarizes the structures, sources, quantitative and qualitative analysis technologies, health benefits, bioaccessibility, and marketed products of IGs. Routine and innovative assay methods, such as IR, TLC, NMR, UV, MS, HPLC, UPLC, and HSCCC, have been widely used for the characterization and quantification of IGs. All of the therapeutic effects of IGs discovered to date are collected and discussed in this study, with an emphasis on the relevant mechanisms of their health-promoting effects. IGs exhibit diverse biological activities against cancer, diabetes, hepatic diseases, obesity, and thrombosis. They exert therapeutic effects through multiple networks of underlying molecular signaling pathways. Owing to these benefits, IGs could be utilized to make foods and functional foods. IGs exhibit higher bioaccessibility and plasma concentrations and longer average residence time in blood than aglycones. Overall, IGs as phytonutrients are very promising and have excellent application potential.

Size-optimized nuclear-targeting phototherapy enhances the type I interferon response for "cold" tumor immunotherapy.

There is growing interest in the effect of innate immune silencing in "cold" tumors, which always fail in the immune checkpoint blockade monotherapy using PD-L1 monoclonal antibodies (aPD-L1). Combination of aPD-L1 with photodynamic therapy, i.e., photoimmunotherapy, is a promising strategy to improve the mono immunotherapy. Nuclear-targeting nanoparticles could elicit a type I interferon (IFN)-mediated innate immune response and reverse the immunosuppressive microenvironment for long-term immunotherapy of "cold" tumors. Photosensitizers such as zinc phthalocyanine (ZnPc) have limited ability to target the nucleus and activate innate sensing pathways to minimize tumor recurrence. Additionally, the relationship between nanoparticle size and nuclear entry capacity remains unclear. Herein, graphene quantum dots (GQDs) were employed as aPD-L1 and ZnPc carriers. Three particle sizes (200 nm, 32 nm and 5 nm) of aPD-L1/ZnPc/GQD-PEG (PZGE) were synthesized and tested. The 5 nm nanoparticles achieved the best nuclear enrichment capacity contributing to their ultrasmall size. Notably, 5 nm PZGE-based photodynamic therapy enabled an amplification of the type I IFN-mediated innate immune response and could convert "immune-cold" tumors into "immune-hot" ones. Utilizing their size advantage to target the nucleus, 5 nm nanoparticles induced DNA damage and activated the type I IFN-mediated innate immune response, subsequently promoting cytotoxic T-lymphocyte infiltration and reversing negative PD-L1 expression. Furthermore, the nanoplatform we designed is promising for the effective suppression of distant oral squamous cell carcinoma. Thus, for the first time, this study presents a size design strategy for nuclear-targeted photo-controlled immune adjuvants and the nuclear-targeted phototherapy-mediated immunomodulatory functions of type I IFN innate immune signalling for "immune-cold" tumors. STATEMENT OF SIGNIFICANCE: The potential of commonly used photosensitizers to activate innate sensing pathways for producing type I IFNs is limited due to the lack of nuclear targeting. Facilitating the nuclear-targeting of photosensitizers to enhance innate immune response and execute long-term tumor killing effect would be a promising strategy for "cold" tumor photoimmunotherapy. Herein, we report an optimal size of PZGE nanoparticles that enable the nuclear-targeting of ZnPc, which reinforces the type I IFN-mediated innate immune response, synergistically reversing "cold tumors" to "hot tumors" for effective primary and distant tumor photoimmunotherapy. This work highlights the marked efficacy of ultrasmall nuclear-located nanocarriers and offers new insight into "immune-cold tumors" via prominent innate immune activation mediated by nuclear-targeting photoimmunotherapy.