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With an estimated global prevalence of 32.4%, non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent chronic liver condition. The marine ecosystem, distinguished by its distinctive environmental characteristics, is a treasure trove of novel lead compounds possessing unique chemical structures, offering promising avenues for the development of new therapeutic agents or dietary supplement targeting NAFLD. Marine bioactive substances from natural products, such as polysaccharides, polyphenols, polyunsaturated fatty acids, and peptides, have been shown to benefit liver health by alleviating metabolic dysfunction through multiple mechanisms. This paper reviews the effects of marine bioactive substances from various marine entities, including marine fauna, flora, and microorganisms, on the regulation of NAFLD. A brief overview of the predominant pathogenic mechanisms underlying the disease is also provided, thereby establishing a critical link between the therapeutic potential of marine bioactive substances and the management of NAFLD.

Shrimp body had to face with spoilage and melanosis when it come to food preservation. In this study, a kind of composite edible film (CEF) composed of hydroxypropyl methyl cellulose (HPMC) and shrimp-derived bioactive peptide microcapsule (SBPM), was developed to preserve the body of Penaeus vannamei. First of all, single-factor experiments were conducted by monitoring the mechanical performance and the water vapor permeability (WVP) of CEF, in order to investigate the influence of the dosages of HPMC, glycerol and SBPM, upon the formulation properties and mechanical strength of the film. The FTIR and free radical scavenging capacity of CEF were also determined when the SBPM addition changed and then, the optimum preparation process of CEF was ascertained based on the results mentioned above. In addition, the preservation-effect of CEF on fresh Penaeus vannamei was evaluated by inspecting some important items such as the sensory evaluation, pH, total volatile basic nitrogen (TVB-N) and aerobic bacterial count of shrimp flesh. The results of the single-factor experiments indicated the optimum amounts of HPMC, glycerol and SBPM were 12%, 0.4% and 3%, respectively, and the comprehensive performance of CEF was satisfied under this optimum condition. The antioxidant ability of CEF was excellent when the dosage of SBPM was not less than 3% and, the interaction between SBPM and other membrane fractions was powerful when the addition amount of SBPM came to be 3%~4%, which was indicated by the FTIR results. More importantly, the spoilage of shrimp body could be controlled by covering the body with CEF and, the sensory of seafood might be maintained by this film, as evidenced by the inhibitory effects of CEF on the raising of body pH, the jump of TVB-N and the increase of aerobic bacterial count in shrimp fresh. The quality guarantee period of fresh body in CEF group could be prolonged by 3~4 days as compared with that in unprotected group, while the overall freshness-keeping ablility of CEF was superior to that of HPMC film even PE film, indicating the potent protective effect of CEF on the fresh of Penaeus vannamei.

The combined effect of curcumin and docosahexaenoic acid (DHA) on liver injury has not yet been reported. We determined the synergistic effect of curcumin and DHA on the protection of WRL-68 cells from palmitic acid-induced injury, and on the inhibition of LX2 cells. A microemulsion to co-deliver both compounds was prepared by ultrasonic emulsification. Mice were fed a high-fat diet for 10 weeks to induce mild non-alcoholic fatty liver disease (NAFLD). At a dose of 5 mg/kg curcumin and 30 mg/kg DHA, the microemulsion successfully lowered serum triacylglycerol (TG) and low-density lipoprotein cholesterol levels, and significantly attenuated NAFLD. A pharmacokinetic study in rats showed that the microemulsion had a higher Cmax value for curcumin, a greater AUC0–24 value and a longer t1/2 value for both curcumin and DHA. This investigation provides a novel application of a combination of functional food ingredients to treat chronic liver disease.

Ulcerative colitis (UC) is a kind of inflammatory bowel condition characterized by inflammation within the mucous membrane, rectal bleeding, diarrhea, and pain experienced in the abdominal region. Existing medications for UC have limited treatment efficacy and primarily focus on symptom relief. Limonium bicolor (LB), an aquatic traditional Chinese medicine (TCM), exerts multi-targeted therapeutic effects with few side effects and is used to treat anemia and hemostasis. Nevertheless, the impact of LB on UC and its mechanism of action remain unclear. Therefore, the objective of this study was to investigate the anti-inflammatory effects and mechanism of action of ethanol extract of LB (LBE) in lipopolysaccharide-induced RAW 264.7 macrophages and dextran sulfate sodium (DSS)-induced UC. The results showed that LBE suppressed the secretion of cytokines in LPS-stimulated RAW 264.7 cells in a dose-dependent manner. LBE had protective effects against DSS-induced colitis in mice, decreased the disease activity index (DAI) score, alleviated symptoms, increased colon length, and improved histological characteristics, thus having protective effects against DSS-induced colitis in mice. In addition, it reversed disturbances in the abundance of proteobacteria and probiotics such as Lactobacillus and Blautia in mice with DSS-induced UC. Based on the results of network pharmacology analysis, we identified four main compounds in LBE that are associated with five inflammatory genes (Ptgs2, Plg, Ppar-γ, F2, and Gpr35). These results improve comprehension of the biological activity and functionality of LB and may facilitate the development of LB-based compounds for the treatment of UC.

In this study, a novel and simple strategy is proposed based on 3D network formed by easily blending polysaccharide carrageenan (Car) and fucoidan (Fuc) without a crosslinker. The Fuc/Car dual coating effectively assists the self-assembly of soy protein-isolated (SPI)/curcumin (Cur, C) composite microcapsules (SPI/C) and achieves an excellent curcumin encapsulation efficiency (EE) up to 95.28% with a 4.16% loading capacity (LC) under optimal conditions. The resulting nanocomposites achieved a satisfying redispersibility in aqueous solution and enhanced the water solubility with a lower size dispersity index (PDI) of 0.12 and a larger zeta potential of −29.67 mV. The Fuc/Car double-layer network not only dramatically improved its thermal stability and photostability, but also provided controlled release and enhanced antioxidant activity in in vitro conditions. The underlying mechanism of the self-assembly of the curcumin-loaded nanoparticles was also addressed. The results proved the feasibility of the encapsulation of unstable hydrophobic bioactive substances (curcumin) with the dual anionic polysaccharide Fuc/Car co-stabilized SPI nanoparticles. This study paves the way for an alternative way of developing novel curcumin delivery systems and will have broad prospects in the pharmaceutical industries.

Abstract Phosphoprotein enriched in astrocytes, 15 kDa (PEA-15) is a death-effector domain (DED) containing protein involved in regulating mitogen-activated protein kinase and apoptosis pathways. In this molecular dynamics study, we examined how phosphorylation of the PEA-15 C-terminal tail residues, Ser-104 and Ser-116, allosterically mediates conformational changes of the DED and alters the binding specificity from extracellular-regulated kinase (ERK) to Fas-associated death domain (FADD) protein. We delineated that the binding interfaces between the unphosphorylated PEA-15 and ERK2 and between the doubly phosphorylated PEA-15 and FADD are similarly composed of a scaffold that includes both the DED and the C-terminal tail residues of PEA-15. While the unphosphorylated serine residues do not directly interact with ERK2, the phosphorylated Ser-116 engages in strong electrostatic interactions with arginine residues on FADD DED. Upon PEA-15 binding, FADD repositions its death domain (DD) relative to the DED, an essential conformational change to allow the death-inducing signaling complex (DISC) assembly.

An obese mouse model induced by high-fat diet (HFD) feeding was used to reveal the role of piperine in modulating gut microbiota (GM). Piperine was administrated at 20 and 40 mg/kg body weight every day. As a result, piperine at 40 mg/kg significantly decreased body weight, liver weight, perirenal fat weight, and lowered serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, and glucose levels in HFD-fed mice. Additionally, piperine significantly attenuated fatty liver and modulated hepatic mRNA expressions of SREBP-1c, SREBP2, and HMGCR. In perirenal fat, FAS, C/EBPα, MCP1, and IL-6 expressions were significantly downregulated by piperine. 16S rRNA sequencing revealed that piperine elevated GM diversity. The relative abundance of Muribaculaceae and Ruminococcaceae were significantly elevated, while Dubosiella and Enterorhabdus genera were suppressed by piperine. The Pearson correlation analysis showed that the altered phylotypes were highly correlated with obesity phenotypes. These findings suggest that piperine modulates energy homeostasis and inflammation to alleviate obesity associated with GM regulation.

Collagen has been ubiquitously applied in the food, cosmetic, biomedical, and pharmaceutical industries. However, the existing collagen in the market cannot meet the demand of consumers. In this study, double-spotted pufferfish collagen (DPC) was extracted from the skin of the pufferfish and characterized as type I collagen, which maintains a native triple helical structure. Liquid chromatography-tandem mass spectrometry analysis revealed that α1 and α2 subunits of DPC comprised 378 and 372 uninterrupted Gly-X-Y triplets, respectively, which were 78.3 % and 78.4 % of the total amino acid content. Secondary structure analysis revealed that DPC consisted of 50.23 % α-helices, 26.51 % β-sheets, 23.26 % β-turns, and 0 % random coils. Using XRD, the distance between collagen molecular chains was found to be 11.45 Å. The yield of DPC was 49.83 % ± 1.85 % (dry weight basis), which was higher than that of pigskin collagen. Dynamic sweep and steady-state shear of DPC were significantly affected by temperature and concentration. DPC solutions exhibited shear-thinning rheological behavior. DPC exhibited water holding and oil absorption capacities superior to terrestrial collagen, such as that of chicken feet collagen. The foaming properties and emulsifying properties of DPC were superior to commercial collagen, such as that of black ruff collagen. DPC was nontoxic to MC3T3-E1 cells and had good cytocompatibility. These results suggest that DPC is a new alternative for collagen with potential for further applications in food, cosmetic, and biomedical fields.

A simple and symmetrical parallel mechanism with three translations is designed according to the theory and method of topological design of parallel mechanism based on Position and Orientation Characteristic （POC） equation. The topological characteristics of mechanism，such as position and orientation characteristic set，degree of freedom and coupling degree，are calculated respectively by POC equation to verify the kinematics characteristics of the mechanism with three translations. The kinematics equation of the mechanism is established，and the analytical expression of positive and inverse kinematics solution of the mechanism are derived，the singularity，workspace and dexterity of the mechanism are studied. Finally，a multi-objective optimization design model is established，with elite retention strategy of rapid and dominate the multi-objective optimization algorithm （NSGA-Ⅱ），the scale synthesis of the structural parameters is carried out，a set of Pareto optimal solutions are obtained by optimization. The results show that the workspace volume and global dexterity can’t be maximized at the same time. Pareto optimal solution can be selected according to the actual needs to meet the needs of the two goals.

The brain is a highly complex organ consisting of numerous types of cells with ample diversity at the epigenetic level to achieve distinct gene expression profiles. During neuronal cell specification, transcription factors (TFs) form regulatory modules with chromatin remodeling proteins to initiate the cascade of epigenetic changes. Currently, little is known about brain epigenetic regulatory modules and how they regulate gene expression in a cell-type specific manner. To infer TFs involved in neuronal specification, we applied a recursive motif search approach on the differentially methylated regions identified from single-cell methylomes. The epigenetic transcription regulatory modules (ETRM), including EGR1 and MEF2C, were predicted and the co-expression of TFs in ETRMs were examined with RNA-seq data from single or sorted brain cells using a conditional probability matrix. Lastly, computational predications were validated with EGR1 ChIP-seq data. In addition, methylome and RNA-seq data generated from Egr1 knockout mice supported the essential role of EGR1 in brain epigenome programming, in particular for excitatory neurons. In summary, we demonstrated that brain single cell methylome and RNA-seq data can be integrated to gain a better understanding of how ETRMs control cell specification. The analytical pipeline implemented in this study is freely accessible in the Github repository (https://github.com/Gavin-Yinld/brain_TF).

It is unclear why neuronal activity induced methylation changes are limited to specific loci in the genome. Here, authors show that the DNA demethylation enzyme, TET1, gains its specificity via the interaction with EGR1, a sequence specific DNA binding protein.

Four undescribed phenolic compounds, namely asperpropanols A–D (1–4), along with two known congeners 5 and 6, were isolated from Aspergillus puniceus A2, a deep-sea-derived fungus. The gross structures of the compounds were established by detailed analyses of the HRESIMS and NMR data, and their absolute configurations were resolved by modified Mosher’s method and calculations of ECD data. Compounds 1–6 were found to have excellent anti-inflammatory effect on lipopolysaccharide (LPS)-induced RAW264.7 cells at 20 μM, evidenced by the reduced nitric oxide (NO), tumor necrosis factor α, and interleukin 6 production. Among them, 5 and 6 showed inhibitory effects on NO production comparable with the positive control (BAY11-7083 at 10 μM). Additionally, the LPS-induced mRNA expressions of inducible nitric oxide synthase and cyclooxygenase-2 were also decreased. Interestingly, mRNA expression of nuclear factor erythroid 2–related factor 2 (Nrf2) was downregulated by LPS and recovered by 1–6, suggesting a vital role of Nrf2 in their effect. We further found that pharmacological inhibition of Nrf2 by ML385 largely abrogated the effects of 1–6 on RAW264.7 cells. Therefore, 1–6 may share a common anti-inflammatory mechanism via Nrf2 upregulation and activation.

The objective of this study was to develop aquatic collagen production from fish processing by-product skin as a possible alternative to terrestrial sources. Silver carp skin collagen (SCSC) was isolated and identified as type I collagen, and LC-MS/MS analysis confirmed the SCSC as Hypophthalmichthys molitrix type I collagen, where the yield of SCSC was 40.35 ± 0.63% (dry basis weight). The thermal denaturation temperature (Td) value of SCSC was 30.37 °C, which was superior to the collagen of deep-sea fish and freshwater fish. Notably, SCSC had higher thermal stability than human placental collagen, and the rheological experiments showed that the SCSC was a shear-thinning pseudoplastic fluid. Moreover, SCSC was functionally superior to some other collagens from terrestrial sources, such as sheep, chicken cartilage, and pig skin collagen. Additionally, SCSC could provide a suitable environment for MC3T3-E1 cell growth and maintain normal cellular morphology. These results indicated that SCSC could be used for further applications in food, cosmetics, and biomedical fields.

Chemical examination of the fermented broth of the mangrove-derived fungus Phaeosphaeriopsis sp. S296 resulted in the isolation of two new cyclodecadepsipeptides, namely phaeosphamides A (1) and B (2), as well as one known congener Sch 217048 (3). The structures of new metabolites, including absolute configurations, were established on the basis of extensive spectroscopic data analyses, chemical conversion, and Marfey’s method. The 2-hydroxy-3-methylpentanoic acid (Hmp) moiety and pipecolic acid (Pip) unit in structures were rarely discovered in nature. Interestingly, compounds 1–3 are examples of peptides discovered from the fungal genus Phaeosphaeriopsis for the first time. All identified compounds were evaluated for their cytotoxicity against five tumor cell lines of AGS, BEL-7402, HepG2, B16, and BIU87. Among them, compound 1 showed inhibitory activities against these tumor cell lines with IC50 values ranging from 5.14 to 66.38 μM. A further mechanistic investigation found that 1 arrested AGS cells in the G2 phase and induced their apoptosis in a dose-dependent manner.

Abstract DNA methylation plays important roles in the regulation of nervous system development and in cellular responses to environmental stimuli such as light-derived signals. Despite great efforts in understanding the maturation and refinement of visual circuits, we lack a clear understanding of how changes in DNA methylation correlate with visual activity in the developing subcortical visual system, such as in the dorsal lateral geniculate nucleus (dLGN), the main retino-recipient region in the dorsal thalamus. Here, we explored epigenetic dynamics underlying dLGN development at ages before and after eye opening in wild-type mice and mutant mice in which retinal ganglion cells fail to form. We observed that development-related epigenetic changes tend to co-localize together on functional genomic regions critical for regulating gene expression, while retinal-input-induced epigenetic changes are enriched on repetitive elements. Enhancers identified in neurons are prone to methylation dynamics during development, and activity-induced enhancers are associated with retinal-input-induced epigenetic changes. Intriguingly, the binding motifs of activity-dependent transcription factors, including EGR1 and members of MEF2 family, are enriched in the genomic regions with epigenetic aberrations in dLGN tissues of mutant mice lacking retinal inputs. Overall, our study sheds new light on the epigenetic regulatory mechanisms underlying the role of retinal inputs on the development of mouse dLGN.

In this study, the effects of a polysaccharide derived from Laminaria japonica (LJP) on obesity were investigated in mice fed a high-fat diet (HFD). LJP significantly attenuated obesity-related features, lowering serum triglycerides, glucose, total cholesterol and low-density lipoprotein cholesterol levels. HFD-induced liver steatosis and hepatocellular ballooning were significantly attenuated by LJP. Additionally, LJP was found to significantly modulate hepatic gene expressions of AMPK and HMGCR, which are key regulators of lipid and cholesterol metabolism. We further found that LJP ameliorated HFD-induced gut microbiota (GM) dysbiosis by significantly reducing the obesity-related Firmicutes to Bacteroidetes ratio, meanwhile promoting the growth of Verrucomicrobia at the phylum level. At the genus level, propionate-producing bacteria Bacteroides and Akkermansia were elevated by LJP, which might explain the result that LJP elevated fecal propionate concentration. Taken together, these findings suggest that dietary intake of LJP modulates hepatic energy homeostasis to alleviate obesity-related nonalcoholic fatty liver disease associated with GM regulation.

Abstract Phosphoinositide 3‐kinases, delta (PI3Kδ) and gamma (PI3Kγ) are enriched in immune cells and regulate the development and function of innate and adaptive immunity. Dual PI3Kδγ inhibitors are considered high value targets for their potential to treat a variety of immune‐mediated diseases, but their discovery has been challenging. Here we describe the preclinical pharmacology of HM5023507, an orally active dual inhibitor of δγ isoforms in immune signaling. HM5023507 inhibited PI3Kδ and PI3Kγ isoforms with greater than 100‐fold selectivity against PI3Kα and PI3Kβ in recombinant enzymatic assays and in primary human immune cells with an exquisite selectivity against other targets. HM5023507 attenuated the PI3Kδ/γ signaling in human basophils (IC50: 42/340 nmol/L; selectivity ratio ~1:8). HM5023507 attenuated the activation and function of human B and T cells, Th17 differentiation of CD4 T cells in the blood of healthy donors and rheumatoid arthritis patients, and cytokine and IgG production in human T and B cell cocultures, in vitro. Orally dosed HM5023507 attenuated PI3K δ/γ‐mediated immune signaling in the rat in a dose‐related manner. In addition, HM5023507 inhibited semiestablished collagen‐induced arthritic inflammation in the rats (ED50 of 0.25mg/kg, p.o. BID or 0.5 mg/kg, QD, AUC: 1422 ng/mL*h), improved histopathology‐ and micro‐computed tomography (µCT)‐based indices of joint damage, bone destruction, and attenuated the levels of anti‐collagen antibody, with an overall anti‐inflammatory profile matching that of a TNFα neutralizing antibody. The PI3K δγ inhibitory profile of HM5023507 and its selectivity make it a useful tool to further delineate immunobiology of dual PI3K δγ targeting.

In recent years, a large number of pharmacologically active compounds containing a butenolide functional group have been isolated from secondary metabolites of marine microorganisms. Butyrolactone I was found to be produced by Aspergillus terreus isolated from several marine-derived samples. The hypoglycemic activity of butyrolactone I has aroused our great interest. In this study, we synthesized six racemic butenolide derivatives (namely BL-1–BL-6) by modifying the C-4 side chain of butyrolactone I. Among them, BL-3 and BL-5 improved the insulin resistance of HepG2 cells and did not affect the proliferation of RIN-m5f cell line, which indicated the efficacy and safety of BL-3 and BL-5. Furthermore, BL-3, BL-4, BL-5, and BL-6 displayed a significant protein tyrosine phosphatase 1B (PTP1B) inhibitory effect, while the enantiomers of BL-3 displayed different 50% percentage inhibition concentration (IC50) values against PTP1B. The results of molecular docking simulation of the BLs and PTP1B explained the differences of biological consequences observed between the enantiomers of BL-3, which supported BLs as PTP1B inhibitors, and also indicated that the chirality of C-4 might influence the inhibitory effect of the BLs. Our findings provide a novel strategy for the development of butyrolactone derivatives as potential PTP1B inhibitors for the treatment of type 2 diabetes mellitus.

Embryonic stem cells (ESCs) consist of a population of self-renewing cells displaying extensive phenotypic and functional heterogeneity. Research towards the understanding of the epigenetic mechanisms underlying the heterogeneity among ESCs is still in its initial stage. Key issues, such as how to identify cell-subset specifically methylated loci and how to interpret the biological meanings of methylation variations remain largely unexplored. To fill in the research gap, we implemented a computational pipeline to analyze single-cell methylome and to perform an integrative analysis with single-cell transcriptome data. According to the origins of variation in DNA methylation, we determined the genomic loci associated with allelic-specific methylation or asymmetric DNA methylation, and explored a beta mixture model to infer the genomic loci exhibiting cell-subset specific methylation (CSM). We observed that the putative CSM loci in ESCs are significantly enriched in CpG island (CGI) shelves and regions with histone marks for promoter and enhancer, and the genes hosting putative CSM loci show wide-ranging expression among ESCs. More interestingly, the putative CSM loci may be clustered into co-methylated modules enriching the binding motifs of distinct sets of transcription factors. Taken together, our study provided a novel tool to explore single-cell methylome and transcriptome to reveal the underlying transcriptional regulatory networks associated with epigenetic heterogeneity of ESCs.

Selenium nanoparticles (SeNPs) have attracted attention due to their favorable properties, unique bioactivities, and potential for use in nutritional supplements and nanomedicine applications. However, the application of SeNPs in the clinic has been greatly hindered by their poor stability, and their potential to protect against alcohol-induced oxidative stress has not been fully investigated. Herein, SeNPs were synthesized in the presence of chitosan (CS) or chitooligosaccharide (COS), and a mixture of SeNPs, CS, and COS was spray-dried to prepare selenium-nanoparticles-loaded chitosan/chitooligosaccharide microparticles (SeNPs-CS/COS-Ms). Their physicochemical properties, including morphology, elemental state, size distribution, surface potential, and characteristic structure, were investigated. The release of SeNPs from the vehicle and the free radical scavenging ability of SeNPs-CS/COS-Ms were also studied. Furthermore, the safety of SeNPs-CS/COS-Ms and their antioxidant activity against alcohol were evaluated in mice. The results indicate that SeNPs-CS/COS-Ms, with a novel structure characterized by their smooth or wrinkled surface, hollow core, and COS body filled with SeNPs-CS nanobeads, were able to release SeNPs and scavenge DPPH and superoxide anion radicals. SeNPs-CS/COS-Ms were found to be much safer than selenite, and they might protect mice from ethanol-induced oxidative stress by reducing lipid and protein oxidation and by boosting glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT). In conclusion, SeNPs-CS/COS-Ms offer a new way to develop stable SeNPs with higher efficacy and better biosafety, and the antioxidant potential of SeNPs-CS/COS-Ms against ethanol deserves further development.

Tetrodotoxin (TTX) was identified as a latent neurotoxin that has a significant analgesia effect. It was rapidly absorbed and excreted in rat after intramuscular (i.m.) injection. To maintain the effect, frequent injections were required. The enteric sustained-release TTX pellets with sucrose pellets as a drug carrier was prepared by fluidized bed spray irrigation, coated in sequence with Eudragit NE30D as a sustained-release layer, hydroxypropyl methylcellulose (HPMC) as a barrier layer and Eudragit L30D-55 as an enteric coating. TTX in the pellets could be sustained released for 12 h in dissolution test. In vivo, TTX pellets reached Cmax at 5 h, and t1/2 was 14.52 ± 2.37 h after intragastrically (i.g.) administration in rat. In acetic acid induced writhing test in rat, the pellets at the dosages of 20, 40, 60 and 80 μg·kg−1 produced analgesic effect at about 1.5 h to 9 h and the strongest effect was at about 3 h to 6 h. Simultaneously, the LD50 of the enteric sustained-release TTX pellets was 840.13 μg·kg−1, and the ED50 was about 30 μg·kg−1. Thus, the therapeutic index was about 25. The enteric sustained-release TTX pellets with absolute analgesia effect and greatly enhanced safety was prepared.

Postherpetic neuralgia (PHN) is nerve pain caused by a reactivation of the varicella zoster virus. Medications are used to reduce PHN but their use is limited by serious side effects. Tetrodotoxin (TTX) is a latent neurotoxin that can block neuropathic pain, but its therapeutic index is only 3–5 times with intravenous or intramuscular injection. Therefore, we prepared oral TTX pellets and examined their effect in a rat model of PHN induced by resiniferatoxin (RTX). Oral TTX pellets were significantly effective at preventing RTX-induced mechanical and thermal allodynia, and similar to pregabalin. Moreover, oral administration of TTX pellets dose-dependently inhibited RTX-induced PHN compared with intramuscular administration of TTX injection. We also studied the pharmacokinetic profile of TTX pellets. Our results showed that the blood concentration of TTX reached a maximum plasma concentration (Cmax) at around 2 h, with an elimination half-life time (t1/2) of 3.23 ± 1.74 h after intragastric administration. The median lethal dose (LD50) of TTX pellets was 517.43 μg/kg via oral administration to rats, while the median effective dose (ED50) was approximately 5.85 μg/kg, and the therapeutic index was 88.45. Altogether, this has indicated that oral TTX pellets greatly enhance safety when compared with TTX injection.

Context A first-principles approach based on density functional theory was used to explore the effect of bending deformation on the electrical structure of molybdenum ditelluride doped with nonmetallic atoms X (X = B, C, N, and O). The study included alternate doping of nonmetallic atoms, as well as a comparison of the effects of intrinsic bending deformation and nonmetallic doping deformation. The results demonstrate that boron atom doping raises the Fermi energy level. Examining the energy band structure indicates that the intrinsic molybdenum ditelluride is a direct band gap semiconductor, which is transformed from a direct band gap to an indirect band gap after doping. We selected boron-doped systems for bending deformation and compared them with the intrinsic systems. With increasing deformation, all systems start to shift from semiconductor to metal. When the deformation reaches 8°, the energy levels fill and the electron energy increases. The intrinsically bent systems transition from direct band gap to indirect band gap and eventually to metal. The indirect band gap semiconductor-to-metal transition process occurs after the bending deformation of the boron-doped atoms. The analytical results show that the absorption and reflection peaks of the molybdenum ditelluride system are blue-shifted after the bending deformation of the boron-doped atoms. Methods Under fundamental principles, this research depends on the density functional theory framework (DFT) using the CASTEP module in the Materials-Studio software. The plane-wave pseudopotential approach with modified gradient approximation and the Perdew-Burke-Ernzerhof (PBE) generalized function is used for structure optimization and total energy calculations of the X-doped (X = B, C, N, O) MoTe2 system at different shape variables. Geometry optimization of the 27-atom superlattice MoTe2 was carried out, followed by alternative doping of tellurium atoms in the molybdenum ditelluride with B, C, N, and O. In this paper, the intrinsic bending deformation and B-doping of molybdenum ditelluride were selected for deformation analysis. Intrinsic bending deformations and boron-doped molybdenum ditelluride with bending angles ranging from 2° to 8° were employed for deformation investigation. In Fig. 1, pink is used to represent doped B atoms, orange is used to describe Te atoms, and green is used to represent Mo atoms. For the degree of deformation of molybdenum ditelluride, in this paper, it is expressed by the bending angle, i.e., the angle of the plane of molybdenum ditelluride after bending and deformation of a single layer of molybdenum ditelluride concerning the angle of the plane folded for the deformed plane. How to do it: For ease of presentation, the atomic chains are set to different colors. The purple part on both sides of the figure is bent and deformed, 3–5 atoms are fixed appropriately, and the middle part is deformed. On this basis, the bending deformation of intrinsically doped and boron-doped MoTe2 is comparatively analyzed. The effect of boron-doped atoms on the structure of MoTe2 is systematically investigated to study its structural stability and electronic structure. [ABSTRACT FROM AUTHOR]

Chemical examination of the rice solid fermented cultures of the fungus Penicillium pinophilum J70 isolated from the fresh leaves of Hypericum japonicum Thumb led to the isolation of one new polyketide, namely penioctadecatrienoic A (1), together with two known compounds (2 and 3). The structure of the new metabolite 1 was resolved on the basis of extensive spectroscopic analysis (NMR and HRESIMS data), in association with the modified Mosher's method for the absolute configurational assignment. All isolated metabolites were evaluated for their cytotoxic activity against ECA-109, the anti-inflammatory activity against NO production in lipopolysaccharides (LPS) stimulated RAW264.7 cells, and the antibacterial activity on Staphylococcus aureus ATCC 29213. As a result, compounds 1-3 showed moderately anti-inflammatory effects with the inhibitory rates ranging from 44.5% to 60.7% at the concentration of 20 μM. In addition, compound 1 exhibited weakly antibacterial effect with an MIC value of 32 µg/mL. [ABSTRACT FROM AUTHOR]