Red ginseng ameliorates lipotoxicity-induced renal fibrosis in hyperuricemia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic kidney disease can be caused by numerous diseases including obesity and hyperuricemia (HUA). Obesity may exacerbate the renal injury caused by HUA. Red ginseng, a steamed products of Panax ginseng Meyer root, is known for its remarkable efficacy in improving metabolic syndrome, such as maintaining lipid metabolic balance. However, the role of red ginseng on hyperuricemia-induced renal injury in obese cases remains unclear. AIM OF THE STUDY: This study aimed to investigate the action of red ginseng extract (RGE) on lipotoxicity-induced renal injury in HUA mice. MATERIALS AND METHODS: A high-fat diet (HFD)-induced obesity model was employed to initially investigate the effects of RGE on body weight, TC, OGTT, renal lipid droplets, and renal function indices such as uric acid, creatinine, and urea nitrogen. Renal structural improvement was demonstrated by H&E staining. Subsequently, an animal model combining obesity and HUA was established to further study the impact of RGE on OAT1 and ACC1 expression levels. The mechanisms underlying renal injury regulation by RGE were postulated on the basis of RNA sequencing, which was verified by immunohistochemical (including F4/80, Ki67, TGF-ß1, α-SMA, and E-cadherin), Masson, and Sirius red staining. RESULTS: RGE modulated HFD-induced weight gain, glucose metabolism, and abnormalities of uric acid, urea nitrogen, and creatinine. RGE alleviated the more severe renal histopathological changes induced by obesity combined with HUA, with down-regulated the protein levels of ACC1, F4/80, Ki67, TGF-ß1, and α-SMA, and up-regulated OAT1 and E-cadherin. CONCLUSIONS: RGE has ameliorative effects on chronic kidney disease caused by obesity combined with HUA by maintaining lipid balance and reducing renal inflammation and fibrosis.

Repairing the intestinal mucosal barrier of traditional Chinese medicine for ulcerative colitis: a review.

Damage to the intestinal mucosal barrier play an important role in the pathogenesis of ulcerative colitis (UC). Discovering the key regulators and repairing the disturbed barrier are crucial for preventing and treating UC. Traditional Chinese medicine (TCM) has been proved to be effective on treating UC and has exhibited its role in repairing the intestinal mucosal barrier. We summarized the evidence of TCM against UC by protecting and repairing the physical barrier, chemical barrier, immune barrier, and biological barrier. Mechanisms of increasing intestinal epithelial cells, tight junction proteins, and mucins, promoting intestinal stem cell proliferation, restoring the abundance of the intestinal microbiota, and modulating the innate and adaptive immunity in gut, were all involved in. Some upstream proteins and signaling pathways have been elucidated. Based on the existing problems, we suggested future studies paying attention to patients' samples and animal models of UC and TCM syndromes, conducting rescue experiments, exploring more upstream regulators, and adopting new technical methods. We hope this review can provide a theoretical basis and novel ideas for clarifying the mechanisms of TCM against UC via repairing the intestinal mucosal barrier.

Efficacy of omega-3 fatty acids for hospitalized COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Emerging expert consensuses and guidelines recommend that omega-3 fatty acids may have anti-inflammatory effects in hospitalized patients with coronavirus disease (COVID-19). However, these recommendations are based on pathophysiological studies of inflammation rather than direct clinical evidence. We conducted this systematic review and meta-analysis to evaluate the efficacy of omega-3 fatty acid supplementation in hospitalized patients with COVID-19. METHODS AND STUDY DESIGN: We retrieved literature from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), WANFANG, Chinese Biomedical Literature Database, and Cochrane Library databases up to May 1, 2023. Data from studies comparing omega-3 fatty acids with a placebo or other pharmaceutical nutrients were analyzed. RESULTS: Of 3032 records, 42 full-text articles were reviewed, five eligible studies were identified, and one study was found in the references. In total of six studies involving 273 patients were included, pooled, and analyzed. Compared to the control group, omega-3 fatty acid intervention reduced the overall mortality of hospitalized patients with COVID-19 (RR=0.76; 95% CI, [0.61, 0.93]; p=0.010). No serious or unexpected drug-related adverse events were observed. No statistical significance was observed in inflammatory markers such as CRP (MD=-9.69; 95% CI, [-22.52, 3.15]; p=0.14; I2=97%) and IL-6; however, the neutrophil/lymphocyte ratio was significantly lower in the omega-3 FAs group on day 7 of intervention (p < 0.001). CONCLUSIONS: Omega-3 fatty acid administration may be associated with reduced mortality in hospitalized patients with COVID-19. Given the small sample size of enrolled studies, more rigorous and large-scale trials are urgently needed in the future to verify its efficacy.

Meta-analysis of Huangqi (Astragalus membranaceus) and Chinese Yam (Rhizoma Dioscoreae) for Diabetic Nephropathy.

Context: Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), has caused enormous economic pressure and serious health problems worldwide. TCM practitioners commonly use a combination of Astragalus membranaceus (A. membranaceus) and Rhizoma Dioscoreae (R. Dioscoreae) in the treatment of DN. Research is still lacking on the therapeutic effects of TCM for DN. Objective: The systematic review and meta-analysis intended to evaluate whether the combination of A. membranaceus and R. Dioscoreae together with Western medicine can provide better efficacy against DN than treatment with traditional Western medicine alone, to provide a clinical medical basis for the use of the TCM combination. Design: The research team performed a performed a systematic narrative review by searching the Web of Science, Science Direct, Pubmed, China National Knowledge Infrastructure (CNKI), VIP, Wanfang, Chinese Science and Technology Journal Database, and Biomedical Literature Chinese Database from databases' inceptions to May 2023. The team used the keywords astragalus and yam, diabetic nephropathy, antidiabetic, and 24-h urinary protein. Setting: The review and meta-analysis occurred at Jiangxi Hospital of Integrated Traditional China and Western Medicine in Nanchang, Jiangxi, China. Intervention: To perform a subgroup analysis, the research team divided the studies into two groups based on the TCM treatment course, with one subgroup receiving treatment for ≤4 weeks and the second receiving treatment for >4 weeks, to judge whether a time-dependence existed for the effects of the TCM combination on UP. Outcome Measure: All studies used 24-h urinary protein (UP) as the outcome measure. Results: In all studies, all heterogeneous (P < .01, I2 = 94%, the intervention groups had a significantly greater reduction in 24-h UP than the control groups did (P < .05). The heterogeneity for a treatment course of ≤4 weeks was P < .01, I2 = 97%, and for a course of >4 weeks was P < .01, I2 = 87%. For both ≤4 weeks and >4 weeks, the intervention groups had a significantly greater reduction in 24-h UP than the control groups did, with P < .01 and P < .01, respectively. The protein effect wasn't time dependent. Conclusions: A. membranaceus and R. Dioscoreae can significantly reduce UP production, and inhibition of UP wasn't time-dependent.

Can vitamin B6 alleviate the adverse reactions of quadruple anti-Helicobacter pylori regimen? : randomized controlled trial.

BACKGROUND: Vitamin B6 is an essential water-soluble vitamin for humans. It is often used to prevent a variety of neuropathies, relieve vomiting, and relieve symptoms such as hand and foot neuritis. AIM: To evaluate whether vitamin B6 can alleviate the adverse reactions caused by the quadruple anti-Helicobacter pylori treatment regimen containing minocycline and metronidazole. METHODS: In this randomized controlled trial, 280 patients with H. pylori infection were randomly placed into one of two treatment groups-the conventional treatment group and the vitamin B6 supplement treatment group-for 2 weeks. The primary endpoint was the total incidence of adverse reactions up to 2 weeks after treatment initiation. The study was designed according to CONSORT Medicinal Interventions. And it was registered with Chinese Clinical Trial Registry under the number ChiCTR2100053833. RESULTS: In terms of efficacy, vitamin B6 does not affect the efficacy of conventional regimen. In the vitamin B6 supplement treatment group, the incidence of adverse reactions was 56.92%, which was significantly lower than the 74.62% observed in the conventional treatment group. In addition, the severity of adverse reactions was also significantly reduced. The proportion of moderate to severe central nervous system symptoms decreased from 58.7 to 14.63%. And, the proportion of moderate to severe gastrointestinal reactions decreased from 33.33 to 0%. We speculate that the mechanism of vitamin B6 of reducing adverse reaction may be related to the production of GABA in the brain. CONCLUSIONS: Vitamin B6 can alleviate adverse reactions of the quadruple anti-H. pylori regimen containing minocycline and metronidazole.

Activation of Pyroptosis Using AIEgen-Based sp2 Carbon-Linked Covalent Organic Frameworks.

Covalent organic frameworks (COFs) have emerged as a promising class of crystalline porous materials for cancer phototherapy, due to their exceptional characteristics, including light absorption, biocompatibility, and photostability. However, the aggregation-caused quenching effect and apoptosis resistance often limit their therapeutic efficacy. Herein, we demonstrated for the first time that linking luminogens with aggregation-induced emission effect (AIEgens) into COF networks via vinyl linkages was an effective strategy to construct nonmetallic pyroptosis inducers for boosting antitumor immunity. Mechanistic investigations revealed that the formation of the vinyl linkage in the AIE COF endowed it with not only high brightness but also strong light absorption ability, long lifetime, and high quantum yield to favor the generation of reactive oxygen species for eliciting pyroptosis. In addition, the synergized system of the AIE COF and αPD-1 not only effectively eradicated primary and distant tumors but also inhibited tumor recurrence and metastasis in a bilateral 4T1 tumor model.

[Alcohol extract of root and root bark of Toddalia asiatica alleviates CIA in rats through anti-inflammatory and proapoptotic effects].

This study aims to investigate the therapeutic effect of alcohol extract of root and root bark of Toddalia asiatica(TAAE) on collagen-induced arthritis(CIA) in rats through phosphatidylinoinosidine-3 kinase/protein kinase B(PI3K/Akt) signaling pathway. To be specific, CIA was induced in rats, and then the rats were treated(oral, daily) with TAAE and Tripterygium Glycoside Tablets(TGT), respectively. The swelling degree of the hind leg joints was scored weekly. After 35 days of administration, the histopathological changes were observed based on hematoxylin and eosin(HE) staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the levels of cytokines [tumor necrosis factor-α(TNF-α), interleukin(IL)-6)]. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) staining was performed to detect the apoptosis of synoviocytes in rats. Western blot was used to detect the expression levels of apoptosis-related proteins B-cell lymphoma 2(Bcl-2)-associated X(Bax), Bcl-2, and caspase-3 and pathway-related proteins phosphoinositide 3-kinase(PI3K), phosphorylated(p)-PI3K, protein kinase B(Akt), and p-Akt. RT-qPCR was conducted to examine the mRNA levels of Bax, Bcl-2, caspase-3, TNF-α, IL-6, and IL-1ß and pathway-related proteins PI3K, p-PI3K, Akt, and p-Akt. TAAE can alleviate the joint swelling in CIA rats, reduce serum levels of inflammatory cytokines, improve synovial histopathological changes, promote apoptosis of synoviocytes, and inhibit synovial inflammation. In addition, RT-qPCR and Western blot results showed that TAAE up-regulated the level of Bax, down-regulated the level of Bcl-2, and activated caspase-3 to promote apoptosis in synoviocytes. TAAE effectively down-regulated the protein levels of p-PI3K and p-Akt. In this study, TAAE shows therapeutic effect on CIA in rats and reduces the inflammation. The mechanism is that it suppresses PI3K/Akt signaling pathway and promotes synoviocyte apoptosis. Overall, this study provides a new clue for the research on the anti-inflammatory mechanism of TAAE and lays a theoretical basis for the better clinical application of TAAE in the treatment of inflammatory and autoimmune diseases.

Advances in Biotechnological Production and Metabolic Regulation of Astragalus membranaceus.

Legume medicinal plants Astragalus membranaceus are widely used in the world and have very important economic value, ecological value, medicinal value, and ornamental value. The bioengineering technology of medicinal plants is used in the protection of endangered species, the rapid propagation of important resources, detoxification, and the improvement of degraded germplasm. Using bioengineering technology can effectively increase the content of secondary metabolites in A. membranaceus and improve the probability of solving the problem of medicinal plant resource shortage. In this review, we focused on biotechnological research into A. membranaceus, such as the latest advances in tissue culture, including callus, adventitious roots, hairy roots, suspension cells, etc., the metabolic regulation of chemical compounds in A. membranaceus, and the research progress on the synthetic biology of astragalosides, including the biosynthesis pathway of astragalosides, microbial transformation of astragalosides, and metabolic engineering of astragalosides. The review also looks forward to the new development trend of medicinal plant biotechnology, hoping to provide a broader development prospect for the in-depth study of medicinal plants.

Pyroelectric Janus nanomotors to promote cell internalization and synergistic tumor therapy.

The tumor diffusion and cell internalization are the major obstacles to improving delivery efficacy of therapeutic agents. External electric fields have shown strong effect on the cell membrane polarization and fluidity, but usually need complicated power management circuits. Herein, in situ generation of microelectric field on nanoparticles (NPs) is proposed to overcome these delivery barriers. Janus tBT@PDA-CPT NPs were developed through partially coating of polydopamine (PDA) caps on pyroelectric tetragonal BaTiO3 (tBT) NPs and then camptothecin (CPT) conjugation via disulfide linkages. For comparison, cBT@PDA-CPT NPs were prepared from non-pyroelectric cubic BaTiO3 (cBT) as control. Near-infrared (NIR) illumination on PDA caps of the Janus NPs produces asymmetric thermophoretic force to drive NP motion for tumor accumulation, deep tissue penetration and effective cell interaction. Photothermally created temperature variations on tBT NPs build pyroelectric potentials to selectively change the membrane potential of tumor cells other than normal cells and exhibit a dominated role in enhancing tumor cell internalization and cytotoxicity. The combination index analysis confirms the synergistic effect of pyroelectric dynamic therapy (PEDT), chemotherapy and photothermal therapy (PTT), leading to full inhibition of tumor growth and noticeable extension of animal survival at significant lower CPT doses. The mild PTT/PEDT, the reduced CPT dose and the selective toxicity to tumor cells have achieved favorable treatment safety after tBT@PDA-CPT/NIR treatment. Therefore, in response to the differences in membrane potentials and glutathione levels between tumor and normal cells, we have demonstrated a concise design to achieve thermophoresis-driven motion, pyroelectric potential-enhanced cell internalization and PTT/PEDT/chemotherapy-synergized antitumor treatment.

Photothermal Propelling and Pyroelectric Potential-Promoted Cell Internalization of Janus Nanoparticles and Pyroelectrodynamic Tumor Therapy.

Cancer phototherapy experiences limitations in tissue diffusion and cell internalization of phototherapeutic agents and dose-dependent side effects. Herein, Janus pyroelectric nanoparticles (NPs) are designed to generate self-powered motion and built-in electric fields to overcome the delivery barriers. Polydopamine (PDA) layers are partially coated on tetragonal BaTiO3 (tBT) NPs to prepare Janus tBT@PDA, and Au NPs are deposited on the PDA caps to obtain Janus tBT@PDA-Au NPs. Near-infrared (NIR) illumination of tBT@PDA-Au builds in situ pyroelectric potentials on NPs, which selectively affect the membrane potential of tumor cells rather than normal cells to enhance tumor cell internalization and produce reactive oxygen species (ROS) for pyroelectric dynamic therapy (PEDT). The asymmetric photothermal effect of the Janus NPs creates thermophoretic force to propel NP motion, which enhances tumor diffusion and cellular uptake of NPs and boosts cytotoxicity and intracellular ROS levels. The inoculation of Au NPs increases the photothermal effect, exhibits larger motion velocities, produces higher pyroelectric potentials, and elevates cellular uptake rates, resulting in significant induction of tumor cell apoptosis, suppression of tumor growth, and extension of animal survival. Thus, the concise design of tBT@PDA-Au/NIR treatment has achieved thermophoretic motion-promoted tissue diffusion, built-in electric field-enhanced cell internalization, and photothermal/PEDT-synergized antitumor efficacy.

Pyroelectric Janus nanomotors for synergistic electrodynamic-photothermal-antibiotic therapies of bacterial infections.

Antibacterial electrotherapy is currently activated by external electric field or self-powered generators, but usually needs complicated power management circuits. Herein, near-infrared illumination (NIR) of pyroelectric nanoparticles (NPs) produces a built-in electric field to address the effectiveness and safety concerns in the antibacterial treatment. Janus tBT@PDA NPs were obtained by capping polydopamine (PDA) on tetragonal BaTiO3 (tBT) NPs through defining the polymerization time, followed by ciprofloxacin (CIP) loading on the PDA caps to fabricate Janus tBT@PDA-Cip NPs. NIR illumination of PDA caps creates temperature variations on tBT NPs to generate photothermal and pyroelectric effects. Finite element simulation reveals a pyroelectric potential of over 1 V and sufficient reactive oxygen species (ROS) are produced to exhibit pyroelectric dynamic therapy (PEDT). The elevated temperature on one side of the Janus NPs produces thermophoretic force to drive NP motion, which enhances interactions with bacteria and overcomes limitations in the short action distance and lifespan of ROS. The pyroelectric field accelerates CIP release through weakening the π-π stacking and electrostatic interaction with PDA and also interrupts membrane potentials of bacteria to enhance CIP invasion into bacteria. The synergistic antibacterial effect of pyroelectric tBT@PDA-Cip NPs causes the fully recovery of S. aureus-infected skin wounds and regeneration of intact epidermis, blood vessels and hair follicles, while no obvious pathological change or inflammatory lesion is detected in the major organs. Thus, the pyroelectric Janus nanomotors demonstrate synergistic PEDT/photothermal/antibiotic effects to enhance antibacterial efficacy while avoiding the necessity of excessive heat, ROS and antibiotic doses. STATEMENT OF SIGNIFICANCE: Antibacterial treatment is challenged by antibiotics-derived side effects and the evolution of resistant strains. Phototherapy is commonly associated with excessive heat and oxidative stress, and their combinations with other agents are especially encouraged to strengthen antibacterial efficacy while alleviating the associated side effects. Electric field is another activator to generate antibacterial abilities, but usually requires complicated power management and bulk electrodes, making it inconvenient in a biological setup. To address these challenges, we propose a strategy to generate microelectric field on nanoparticles themselves and achieve synergistic electrodynamic-photothermal-antibiotic therapies. The pyroelectric effect weakens interactions between nanoparticles and antibiotics to accelerate drug release, and the built-in pyroelectric field increases membrane fluidity to enhance bacterial uptake of antibiotics.

[Effects of electroacupuncture pretreatment on NLRP3 inflammasome in mice with ventilator-induced lung injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment on inflammatory response in ven-tilator-induced lung injury (VILI) mice, so as to explore the underlying mechanism of EA pretreatment on prevention of VILI. METHODS: C57BL/6 mice were randomly divided into sham-operation group, model group, EA group and sham-acupoint group，with 8 mice in each group. The VILI model was established by ventilation with high tidal volume. Mice in the EA group and sham-acupoint group were given EA at "Zusanli" (ST36)and "Feishu"(BL13) or non-acupoints (located at 1-2 cm on both sides of the tail root of the proximal trunk) before mechanical ventilation, 30 min each time, once a day for 5 days. Arterial blood was collec-ted for blood gas analysis, the total protein content in bronchoalveolar lavage fluid (BALF) was detected by BCA method. The contents of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in BALF were detected by ELISA. Lung injury score was determined after HE staining. The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and Caspase-1 in lung tissue was detected by Western blot. RESULTS: Compared with the sham-operation group, the arterial partial pressure of oxygen and oxygenation index were decreased(P<0.05), the levels of total protein, IL-1ß and IL-18 in BALF, the W/D value and the pathological injury score of lung tissue and the protein expression levels of NLRP3, Caspase-1 and ASC were increased(P<0.05)in the model group. Following the interventions, the above mentioned increased or decreased indicators were reversed(P<0.05) in the EA group rather than in the sham-acupoint group. CONCLUSION: EA pretreatment of ST36 and BL13 can reduce the damage of lung tissue caused by mechanical ventilation, which may be related to its effect in reducing the expression of NLPR3 inflammasome related proteins, reducing the activation of inflammasome, and thereby reducing the inflammatory response.

Transcriptome profiling Revealed the potential mechanisms of Shen Lin Bai Zhu San n-butanol extract on DSS induced Colitis in Mice and LC-MS analysis.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disorder in gastrointestinal tract. Shen Ling Bai Zhu San (SLBZS), which has a long history of use in Traditional Chinese Medicine (TCM), has been widely used to treat gastrointestinal diseases. The isolated fractions of TCM have also been proved to possess an important potential for treating diseases, which are due to their effective components. PURPOSE: In this study, we examined the possibility that SLBZS and its isolated active fractions may prevent DSS-induced colitis, and investigated the potential mechanisms by regulating genetic profile of colon. METHODS: Colitis mice were induced by 2.5% DSS for 7 days, and then SLBZS and different SLBZS extracts were administrated to protect the mice for 7 days. Body weight, diarrhea, bleeding in stool, colon length, spleen weight, cytokines of serum and colon and pathology of colon were assessed. The level of Ginsenoside Rg1, Re and Rb1 in different SLBZS extracts and qualitative analysis of n-butanol extract of SLBZS (S-Nb) was performed by HPLC and LC-MS, respectively. And the effects of S-Nb on the transcriptome in colitis were investigated. RESULTS: Our results showed that SLBZS and S-Nb significantly regained body weight, reduced DAI, splenomegaly and the length of colon and attenuated histological damage of the colon. Meanwhile, SLBZS and S-Nb markedly reduced the levels of TNF-α, IL-1ß and IL-6 and increased the level of IL-10 in serum and colon. These effects may be associated with the high levels of Ginsenoside Rg1, Re and Rb1 and rich variety of compounds in S-Nb including 6 ginsenosides, glycyrrhizin, L-tryptophan, and so on. Transcriptome analysis revealed that S-Nb selectively regulated 103 differentially expressed genes (DEGs), 36 of which were changed in DSS-induced mice. And the genes of Per2, Per3, Npy and Serpina3m were closely related to colitis and also restored by S-Nb with different extent. Remarkably, these DEGs modulated the biological functions of colitis mice, including extracellular region, response to external stimulus, MAPK signaling pathway and arginine and proline metabolism. CONCLUSIONS: These data indicated that SLBZS and S-Nb blunted DSS-induced colitis by modulating differentially expression gene profile and biological functions based on their ginsenosides and rich compounds.

Two new iridoid glycosides from Odontites vulgaris.

Two new iridoid glycosides, named 3'-O-benzoyl-dolichocymboside D (1) and dolichocymboside E (2), along with ten known glycosides (3-12), were isolated from the ethanol extract of the whole plants of Odontites vulgaris Moench. The structures of the isolated compounds were elucidated by 1D and 2D NMR and HR-ESI-MS spectra and by comparison with those reported in the literature. This is the first report on compounds 11 and 12 isolated from the family Scrophulariaceae, and compounds 8-10 were isolated from the genus Odontites.

Effects of Dietary Riboflavin Supplementation on the Growth Performance, Body Composition and Anti-Oxidative Capacity of Coho Salmon (Oncorhynchus kisutch) Post-Smolts.

The present study investigated the effects of dietary riboflavin on growth performance, body composition and anti-oxidative capacity of coho salmon (Oncorhynchus kisutch) post-smolts. Seven experimental diets were formulated with graded riboflavin levels of 0.00, 3.96, 8.07, 16.11, 31.81, 63.67 and 126.69 mg/kg, respectively. Each diet was fed to triplicate groups of 10 fish with an individually initial mean body weight of 186.22 ± 0.41 g in 21 cages (water volume, 1000-L/cage) and fed three times daily (7:30, 12:30 and 17:30) to apparent satiation for 12 weeks. Fish fed a diet with 31.81 mg/kg riboflavin had the highest specific growth rate (SGR), which was significantly higher than fish-fed diets with 0.00, 3.96, 8.07 and 126.69 mg/kg riboflavin (p < 0.05). Feed conversion ratio showed an inverse trend with SGR. No significant differences were observed in condition factor, hepatosomatic index, viscerosomatic index, muscle moisture, crude protein and ash contents among dietary groups. Muscle lipid had the highest content in the 31.81 mg/kg group and was significantly higher (p < 0.05) than those in the 0.00, 3.96 and 8.07 mg/kg groups. The alanine aminotransferase, aspartate aminotransferase and malondialdehyde contents in the liver and serum of fish were significantly decreased with the increase in dietary riboflavin level up to 31.81 mg/kg, and then increased as dietary riboflavin level further increased. An inverse trend was observed for total superoxide dismutase and catalase activities. Serum total cholesterol and triglyceride levels were significantly decreased with the dietary of riboflavin levels up to 31.81 and 63.67 mg/kg, respectively. The cubic curve regression analysis based on SGR indicated that the optimum dietary riboflavin level was estimated to be 35.26 mg/kg for coho salmon post-smolts.

[Effect of Biantie pretreatment on serum level of PHD2/HIF-1α and brain tissue damage in rats during acute hypobaric hypoxia exposure].

OBJECTIVE: To observe the effect of Biantie (bian stone plaste) pretreatment on serum level of prolyl hydroxylase domain 2 (PHD2) and hypoxia-inducible factor-1α (HIF-1α) in rats with acute hypobaric hypoxia induced-brain injury, and to explore the possible mechanism of Biantie on preventing brain injury at high altitude. METHODS: Forty-five male SD rats were randomly divided into a blank group, a model group, a Biantie group, a medication group and a Biantie+inhibitor group, 9 rats in each group. The rats in the Biantie group the and the Biantie+inhibitor group were pretreated with Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9), 2 h each time, once a day; the rats in the medication group were treated with intragastric administration of rhodiola capsule solution (280 mg/kg) for 14 d; the rats in the Biantie+inhibitor group were intraperitoneally injected with the PHD inhibitor dimethyloxalyl glycine (DMOG) at a dose of 40 mg/kg 24 h before the establishment of the model. After the intervention, except for the blank group, the rats in the remaining 4 groups were placed in the oxygen chamber to simulate a high-altitude environment to establish the acute hypobaric hypoxia brain injury model. The arterial blood-gas analysis indexes [blood oxygen saturation (SaO2), lactic acid (Lac), blood sodium (Na+), blood potassium (K+)] and brain water content were detected in each group; the histomorphology of cerebral cortex was observed by HE staining; the serum levels of PHD2 and HIF-1α as well as vascular endothelial growth factor (VEGF) were detected by ELISA; the VEGF protein expression in brain tissue was detected by Western blot; the VEGF mRNA expression in brain tissue was detected by real-time fluorescent quantitative PCR. RESULTS: Compared with the blank group, the levels of SaO2 and Na+ in the model group were decreased (P<0.05), while the levels of Lac and K+ as well as the water content of brain tissue were increased (P<0.05). Compared with the model group, the level of SaO2 in the Biantie group and the medication group was increased (P<0.05), while the levels of Lac, K+ and the water content of brain tissue were decreased (P<0.05); the level of Na+ in the Biantie group was increased (P<0.05). Compared with the Biantie group, the level of SaO2 in the Biantie+inhibitor group was decreased (P<0.05), and the level of Lac and the water content of brain tissue were increased (P<0.05). In the model group, the cortical tissue cells were loose and disordered, the cortical blood vessels were dilated, and the cells were obviously swollen; the anoxic injury in the Biantie group and the medication group was lighter, and the anoxic injury in the Biantie+inhibitor group was more obvious than that in the Biantie group. Compared with the blank group, the serum PHD2 content in the model group was decreased and the HIF-1α content was increased (P<0.05), and the content of VEGF in serum and VEGF protein and mRNA expressions in brain were increased (P<0.05). Compared with the model group, the content of PHD2 in serum in the Biantie group and the medication group was increased (P<0.05), and the level of HIF-1α was decreased (P<0.05), and the content of VEGF in serum as well as VEGF protein and mRNA expressions in brain were decreased (P<0.05). Compared with the Biantie group, the serum PHD2 content in the Biantie+inhibitor group was decreased and HIF-1α level were increased (P<0.05), and the content of VEGF in serum as well as VEGF mRNA expression in brain were increased (P<0.05). CONCLUSION: Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9) could regulate serum PHD2/HIF-1α to down-regulate VEGF expression, reduce brain edema and enhance anti-hypoxia ability, so as to achieve the purpose of preventing brain injury at high altitude.

Deep Learning-Based Universal Expert-Level Recognizing Pathological Images of Hepatocellular Carcinoma and Beyond.

Background and Aims: We aim to develop a diagnostic tool for pathological-image classification using transfer learning that can be applied to diverse tumor types. Methods: Microscopic images of liver tissue with and without hepatocellular carcinoma (HCC) were used to train and validate the classification framework based on a convolutional neural network. To evaluate the universal classification performance of the artificial intelligence (AI) framework, histological images from colorectal tissue and the breast were collected. Images for the training and validation sets were obtained from the Xiamen Hospital of Traditional Chinese Medicine, and those for the test set were collected from Zhongshan Hospital Xiamen University. The accuracy, sensitivity, and specificity values for the proposed framework were reported and compared with those of human image interpretation. Results: In the human-machine comparisons, the sensitivity, and specificity for the AI algorithm were 98.0, and 99.0%, whereas for the human experts, the sensitivity ranged between 86.0 and 97.0%, while the specificity ranged between 91.0 and 100%. Based on transfer learning, the accuracies of the AI framework in classifying colorectal carcinoma and breast invasive ductal carcinoma were 96.8 and 96.0%, respectively. Conclusion: The performance of the proposed AI framework in classifying histological images with HCC was comparable to the classification performance achieved by human experts, indicating that extending the proposed AI's application to diagnoses and treatment recommendations is a promising area for future investigation.

Transcriptome and metabolome reveal the accumulation of secondary metabolites in different varieties of Cinnamomum longepaniculatum.

BACKGROUND: Cinnamomum longepaniculatum (Gamble) N. Chao ex H. W. Li, whose leaves produce essential oils, is a traditional Chinese medicine and economically important tree species. In our study, two C. longepaniculatum varieties that have significantly different essential oil contents and leaf phenotypes were selected as the materials to investigate secondary metabolism. RESULT: The essential oil content and leaf phenotypes were different between the two varieties. When the results of both transcriptome and metabolomic analyses were combined, it was found that the differences were related to phenylalanine metabolic pathways, particularly the metabolism of flavonoids and terpenoids. The transcriptome results based on KEGG pathway enrichment analysis showed that pathways involving phenylpropanoids, tryptophan biosynthesis and terpenoids significantly differed between the two varieties; 11 DEGs (2 upregulated and 9 downregulated) were associated with the biosynthesis of other secondary metabolites, and 12 DEGs (2 upregulated and 10 downregulated) were related to the metabolism of terpenoids and polyketides. Through further analysis of the leaves, we detected 196 metabolites in C. longepaniculatum. The abundance of 49 (26 downregulated and 23 upregulated) metabolites differed between the two varieties, which is likely related to the differences in the accumulation of these metabolites. We identified 12 flavonoids, 8 terpenoids and 8 alkaloids and identified 4 kinds of PMFs from the leaves of C. longepaniculatum. CONCLUSIONS: The combined results of transcriptome and metabolomic analyses revealed a strong correlation between metabolite contents and gene expression. We speculate that light leads to differences in the secondary metabolism and phenotypes of leaves of different varieties of C. longepaniculatum. This research provides data for secondary metabolite studies and lays a solid foundation for breeding ideal C. longepaniculatum plants.

Conduction of a chemical structure-guided metabolic phenotype analysis method targeting phenylpropane pathway via LC-MS: Ginkgo biloba and soybean as examples.

The phenylpropane pathway (PPP) is one of the most extensively investigated metabolic routes. This pathway biosynthesizes many important active ingredients such as phenylpropanoids and flavonoids that affect the flavor, taste and nutrients of food. How to elucidate the metabolic phenotype of PPP is fundamental in food research and development. In this study, we designed a structural periodical table filled with 103 metabolites produced from PPP. All of them especially the 62 structural isomers were qualified and quantified with high resolution and sensitivity via multiple reaction mode in liquid chromatography tandem triple quadrupole mass spectrometry. Ginkgo biloba and soybean were used as samples for the practical application of this method: The delicate spatial-temporal metabolic balance of PPP from ginkgo biloba has been first elucidated; It is first confirmed that the salt and draught stresses could redirect the biosynthesis trend of PPP to produce more isoflavones in soybean leaves.

Discovery of honokiol thioethers containing 1,3,4-oxadiazole moieties as potential α-glucosidase and SARS-CoV-2 entry inhibitors.

Honokiol, isolated from a traditional Chinese medicine (TCM) Magnolia officinalis, is a biphenolic compound with several biological activities. To improve and broaden its biological activity, herein, two series of honokiol thioethers bearing 1,3,4-oxadiazole moieties were prepared and assessed for their α-glucosidase and SARS-CoV-2 entry inhibitory activities. Among all the honokiol thioethers, compound 7l exhibited the strongest α-glucosidase inhibitory effect with an IC50 value of 18.9 ± 2.3 µM, which was superior to the reference drug acarbose (IC50 = 24.4 ± 0.3 µM). Some interesting results of structure-activity relationships (SARs) have also been discussed. Enzyme kinetic study demonstrated that 7l was a noncompetitive α-glucosidase inhibitor, which was further supported by the results of molecular docking. Moreover, honokiol thioethers 7e, 9a, 9e, and 9r exhibited potent antiviral activity against SARS-CoV-2 pseudovirus entering into HEK-293 T-ACE2h. Especially 9a displayed the strongest inhibitory activity against SARS-CoV-2 pseudovirus entry with an IC50 value of 16.96 ± 2.45 µM, which was lower than the positive control Evans blue (21.98 ± 1.98 µM). Biolayer interferometry (BLI) binding and docking studies suggested that 9a and 9r may effectively block the binding of SARS-CoV-2 to the host ACE2 receptor through dual recognition of SARS-CoV-2 spike RBD and human ACE2. Additionally, the potent honokiol thioethers 7l, 9a, and 9r displayed relatively no cytotoxicity to normal cells (LO2). These findings will provide a theoretical basis for the discovery of honokiol derivatives as potential both α-glucosidase and SARS-CoV-2 entry inhibitors.