Nationwide law enforcement impact on the pet bird trade in China.

Conservation enforcement is a direct strategy to combat illegal wildlife trade in open markets. Yet, its large-scale effectiveness has not been widely assessed due to the lack of extensive market data. Between August 2016 and June 2017, a national coordinated enforcement campaign led by the leading Chinese authority to combat illegal migratory bird trade coincided with the largest-ever pet bird market survey across China by voluntary birdwatchers before and after the enforcement, which served as a unique natural experiment. Across 73 markets from 22 Chinese provinces, the dataset contains 140,723 birds of 346 species from 48 families and recorded a drastic decline in bird abundance traded after enforcement. Notably, species protected under China's Wildlife Protection Law declined significantly, while commercially bred species increased, although responses to enforcement were spatially heterogeneous. Our model showed that the national protection level was the best predictor for the trend of traded species, even after accounting for confounding factors such as regional baseline enforcement pressure and wild native bird populations. However, the widely traded native songbirds were not offered adequate national protection. Future policies should consider the pet bird trade patterns, target key areas of trade, and develop a more systematic market survey design to monitor trade.

Small molecule inhibitors targeting regulatory T cells for cancer treatment.

Regulatory T cells (Tregs) are important controllers of the immune system homeostasis by preventing disproportionate immune responses. In the context of cancer, Tregs contribute to tumor development by suppressing other immune cells in the tumor microenvironment (TME). Infiltration of Tregs in the TME has been associated with poor prognosis in cancer patients. Thus, understanding the mechanisms underlying Treg recruitment and suppressive functions is essential for developing cancer immunotherapies to boost antitumor immune responses. While antibody-based strategies targeting Tregs have shown promise, small molecule inhibitors offer distinct advantages, including oral bioavailability and the ability to penetrate the TME and target intracellular proteins. Here, we provide an overview of small molecule inhibitors that have demonstrated efficacy in modulating Tregs activity in cancer and highlight the need for phenotypic assays to characterize therapeutic compounds.

Competitive Coordination of Sodium Ions for High-Voltage Sodium Metal Batteries with Fast Reaction Speed.

The unstable electrode-electrolyte interface and the narrow electrochemical window of normal electrolytes hinder the potential application of high-voltage sodium metal batteries. These problems are actually related to the solvation structure of the electrolyte, which is determined by the competition between cations coordinated with anions or solvent molecules. Herein, we design an electrolyte incorporating ethyl (2,2,2-trifluoroethyl) carbonate and fluoroethylene carbonate, which facilitates a pronounced level of cation-anion coordination within the solvation sheath by enthalpy changes to reduce the overall coordination of cation-solvents and increase sensitivity to salt concentration. Such an electrolyte regulated by competitive coordination leads to highly reversible sodium plating/stripping with extended cycle life and a high Coulombic efficiency of 98.0%, which is the highest reported so far in Na||Cu cells with ester-based electrolytes. Moreover, 4.5 V high-voltage Na||Na3V2(PO4)2F3 cells exhibit a high rate capability up to 20 C and an impressive cycling stability with an 87.1% capacity retention after 250 cycles with limited Na. The proposed strategy of solvation structure modification by regulating the competitive coordination of the cation provides a new direction to achieve stable sodium metal batteries with high energy density and can be further extended to other battery systems by controlling enthalpy changes of the solvation structure.

MiR-141-3p-Functionalized Exosomes Loaded in Dissolvable Microneedle Arrays for Hypertrophic Scar Treatment.

Hypertrophic scar (HS) is a common fibroproliferative disease caused by abnormal wound healing after deep skin injury. However, the existing approaches have unsatisfactory therapeutic effects, which promote the exploration of newer and more effective strategies. MiRNA-modified functional exosomes delivered by dissolvable microneedle arrays (DMNAs) are expected to provide new hope for HS treatment. In this study, a miRNA, miR-141-3p, which is downregulated in skin scar tissues and in hypertrophic scar fibroblasts (HSFs), is identified. MiR-141-3p mimics inhibit the proliferation, migration, and myofibroblast transdifferentiation of HSFs in vitro by targeting TGF-ß2 to suppress the TGF-ß2/Smad pathway. Subsequently, the engineered exosomes encapsulating miR-141-3p (miR-141-3pOE -Exos) are isolated from adipose-derived mesenchymal stem cells transfected with Lv-miR-141-3p. MiR-141-3pOE -Exos show the same inhibitive effects as miR-141-3p mimics on the pathological behaviors of HSFs in vitro. The DMNAs for sustained release of miR-141-3pOE -Exos are further fabricated in vivo. MiR-141OE -Exos@DMNAs effectively decrease the thickness of HS and improve fibroblast distribution and collagen fiber arrangement, and downregulate the expression of α-SMA, COL-1, FN, TGF-ß2, and p-Smad2/3 in the HS tissue. Overall, a promising, effective, and convenient exosome@DMNA-based miRNA delivery strategy for HS treatment is provided.

Precise, fast and comprehensive analysis of intact glycopeptides and modified glycans with pGlyco3.

Great advances have been made in mass spectrometric data interpretation for intact glycopeptide analysis. However, accurate identification of intact glycopeptides and modified saccharide units at the site-specific level and with fast speed remains challenging. Here, we present a glycan-first glycopeptide search engine, pGlyco3, to comprehensively analyze intact N- and O-glycopeptides, including glycopeptides with modified saccharide units. A glycan ion-indexing algorithm developed for glycan-first search makes pGlyco3 5-40 times faster than other glycoproteomic search engines without decreasing accuracy or sensitivity. By combining electron-based dissociation spectra, pGlyco3 integrates a dynamic programming-based algorithm termed pGlycoSite for site-specific glycan localization. Our evaluation shows that the site-specific glycan localization probabilities estimated by pGlycoSite are suitable to localize site-specific glycans. With pGlyco3, we confidently identified N-glycopeptides and O-mannose glycopeptides that were extensively modified by ammonia adducts in yeast samples. The freely available pGlyco3 is an accurate and flexible tool that can be used to identify glycopeptides and modified saccharide units.

Genomic profiling informs therapies and prognosis for patients with hepatocellular carcinoma in clinical practice.

Hepatocellular carcinoma (HCC) genomic research has discovered actionable genetic changes that might guide treatment decisions and clinical trials. Nonetheless, due to a lack of large-scale multicenter clinical validation, these putative targets have not been converted into patient survival advantages. So, it's crucial to ascertain whether genetic analysis is clinically feasible, useful, and whether it can be advantageous for patients. We sequenced tumour tissue and blood samples (as normal controls) from 111 Chinese HCC patients at Qingdao University Hospital using the 508-gene panel and the 688-gene panel, respectively. Approximately 95% of patients had gene variations related to targeted treatment, with 50% having clinically actionable mutations that offered significant information for targeted therapy. Immune cell infiltration was enhanced in individuals with TP53 mutations but decreased in patients with CTNNB1 and KMT2D mutations. More notably, we discovered that SPEN, EPPK1, and BRCA2 mutations were related to decreased median overall survival, although MUC16 mutations were not. Furthermore, we found mutant MUC16 as an independent protective factor for the prognosis of HCC patients after curative hepatectomy. In conclusion, this study connects genetic abnormalities to clinical practice and potentially identifies individuals with poor prognoses who may benefit from targeted treatment or immunotherapy.

When will the immune-stimulating antibody conjugates (ISACs) be transferred from bench to bedside?

Immunostimulatory antibody conjugates (ISACs) as a promising new generation of targeted therapeutic antibody-drug conjugates (ADCs), that not only activate innate immunity but also stimulate adaptive immunity, providing a dual therapeutic effect to eliminate tumor cells. However, several ISACs are still in the early stages of clinical development or have already failed. Therefore, it is crucial to design ISACs more effectively to overcome their limitations, including high toxicity, strong immunogenicity, long development time, and poor pharmacokinetics. This review aims to summarize the composition and function of ISACs, incorporating current design considerations and ongoing clinical trials. Additionally, the review delves into the current issues with ISACs and potential solutions, such as adjusting the drug-antibody ratio (DAR) to improve the bioavailability of ISACs. By leveraging the affinity and bioavailability-enhancing properties of bispecific antibodies, the utility between antibodies and immunostimulatory agents can be balanced. Commonly used immunostimulatory agents may induce systemic immune reactions, and BTK (Bruton's tyrosine kinase) inhibitors can regulate immunogenicity. Finally, the concept of grafting ADC's therapeutic principles is simple, but the combination of payload, linker, and targeted functional molecules is not a simple permutation and combination problem. The development of conjugate drugs faces more complex pharmacological and toxicological issues. Standing on the shoulders of ADC, the development and application scenarios of ISAC are endowed with broader space.

The Relationship Between Congenital Heart Disease in Newborns and Maternal Prenatal Folic Acid Supplementation, and Analysis of Other High-Risk Factors.

Objective: To analyze the relationship between congenital heart disease (CHD) in newborns and maternal prenatal folic acid supplementation, as well as other high-risk factors. Method: A retrospective analysis was conducted on clinical data of 114 pregnant women diagnosed with congenital heart disease (CHD) in the prenatal stage at our hospital between January 2021 and January 2023. These pregnant women were included in the case group. Additionally, an equal number of pregnant women with normal examination results during the same period were selected as the control group at a 1:1 ratio. Basic information about the families of pregnant women and information about relevant exposure factors during the periconception period were analyzed based on survey forms previously completed by pregnant women during their prenatal check-ups at the hospital. Possible influencing factors were analyzed through multifactor logistic regression. Results: High-risk factors during the perinatal period for new CHD in newborns include maternal age at this pregnancy >35 years (OR=1.907), the presence of adverse pregnancy history (OR=2.213), a family history of CHD (OR=3.049), exposure to secondhand smoke during the perinatal period (OR=2.934), the use of cold medications (OR=1.719), fever (OR=2.034), exposure to noisy environments (OR=1.981), prolonged use of electronic devices (OR=1.827), consumption of pickled foods (OR=1.892). Prenatal folic acid supplementation is a protective factor for new CHD in newborns (OR=0.342). Conclusion: Pregnant women should choose an appropriate gestational age for conception. During the perinatal period, pregnant women should avoid exposure to the aforementioned high-risk factors as much as possible and supplement folic acid appropriately. It is essential to cultivate good dietary and lifestyle habits, as this has significant implications for preventing and reducing the occurrence of CHD in newborns. Healthcare professionals should prioritize educating pregnant women about the risks associated with the identified high-risk factors and emphasize the importance of early prenatal care. Furthermore, promoting appropriate folic acid supplementation during the periconception period should be an integral part of prenatal care protocols. By implementing these recommendations, healthcare providers can contribute to reducing the occurrence of CHD in newborns and improving maternal and infant health outcomes.

Directing Highly Ordered and Dense Li Deposition to Achieve Stable Li Metal Batteries.

Li metal anode is promising to achieve high-energy-density battery. However, it has rapid capacity fading due to the generation of inactive Li (dead Li), especially at high current density. This study reveals that the random distribution of Li nuclei leads to large uncertainty for the further growth behavior on Cu foil. Here, periodical regulation of Li nucleation sites on Cu foil by ordered lithiophilic micro-grooves is proposed to precisely manipulate the Li deposition morphology. The management of Li deposits in the lithiophilic grooves can induce high pressure on the Li particles, leading to the formation of dense Li structure and smooth surface without dendrite growth. Li deposits comprising tightly packed large Li particles largely reduce the side reaction and the generation of isolated metallic Li at high current density. Less dead Li accumulating on the substrate significantly prolongs the cycling life of full cells with limited Li inventory. The precise manipulation of the Li deposition on Cu is promising for high-energy and stable Li metal batteries.

bHLH transcription factor EcdR controls conidia production, pigmentation and virulence in Aspergillus fumigatus.

Invasive Aspergillus fumigatus infection is a disease with high morbidity and mortality rates. Abnormalities in sporulation and pigmentation can significantly alter the pathogenicity of A. fumigatus, thus the mechanisms of conidiation and pigment biosynthesis have gained increasing attention. In Aspergillus oryzae, a novel predicted bHLH protein-encoding gene, ecdR, plays a role in asexual development, and its ortholog has also been characterized in A. nidulans. Herein, we determined its role in A. fumigatus by testing whether ecdR deletion affects asexual development, melanin synthesis, and regulation of virulence in this fungus. Our study shows that EcdR controls conidia and melanin production in A. fumigatus. In addition, we found that virulence in the ΔecdR strain was significantly reduced in the infection model of immunodeficiency mice.

Pan-cancer analysis of NLRP3 inflammasome with potential implications in prognosis and immunotherapy in human cancer.

NLRP3 inflammasome was introduced as a double-edged sword in tumorigenesis and influenced immunotherapy response by modulating host immunity. However, a systematic assessment of the NLRP3-inflammasome-related genes across human cancers is lacking, and the predictive role of NLRP3 inflammasome in cancer immunotherapy (CIT) response remains unexplored. Thus, in this study, we performed a pan-cancer analysis of NLRP3-inflammasome-related genes across 24 human cancers. Out of these 24 cancers, 15 cancers had significantly different expression of NLRP3-inflammasome-related genes between normal and tumor samples. Meanwhile, Cox regression analysis showed that the NLRP3 inflammasome score could be served as an independent prognostic factor in skin cutaneous melanoma. Further analysis indicated that NLRP3 inflammasome may influence tumor immunity mainly by mediating tumor-infiltrating lymphocytes and macrophages, and the effect of NLRP3 inflammasome on immunity is diverse across tumor types in tumor microenvironment. We also found that the NLRP3 inflammasome score could be a stronger predictor for immune signatures compared with tumor mutation burden (TMB) and glycolytic activity, which have been reported as immune predictors. Furthermore, analysis of the association between NLRP3 inflammasome and CIT response using six CIT response datasets revealed the predictive value of NLRP3 inflammasome for immunotherapy response of patients in diverse cancers. Our study illustrates the characterization of NLRP3 inflammasome in multiple cancer types and highlights its potential value as a predictive biomarker of CIT response, which can pave the way for further investigation of the prognostic and therapeutic potentials of NLRP3 inflammasome.

Omnidirectional defect mode in one-dimensional photonic crystal with a (chiral) hyperbolic metamaterial defect.

The wavelength of defect mode in all-dielectric photonic crystals (PCs) with a dielectric defect are blue-shifted as incident angle increases for both transverse electric and transverse magnetic (TM) polarized waves. The blue-shifted property of defect mode limits the design of some optical devices including omnidirectional optical filters and wide-angle polarization selectors. Here we introduce a hyperbolic metamaterial (HMM) layer as a defect into dielectric one-dimensional photonic crystals (1DPCs) to obtain an omnidirectional defect mode for TM polarized waves at near-infrared regimes. Since only one HMM layer is introduced, omnidirectional defect mode with transmittance as high as 71% can be realized. Because of the unusual angle-dependence of propagating phase in the HMM defect, the total phase for satisfying the resonance condition of defect mode can be unchanged in a wide-angle range at a fixed wavelength, which leads to the omnidirectional defect mode. Moreover, the manipulation of propagating phase can be generalized to the case of circularly polarized waves, and we obtain an omnidirectional defect mode for left-handed circularly polarized waves in 1DPCs with a chiral hyperbolic metamaterial defect. Nevertheless, the defect mode for right-handed circularly polarized waves is still blue-shifted. Such spin-selective omnidirectional defect mode can be utilized to greatly enhance circular dichroism in a wide-angle range up to 64.1°. Our structure facilitates the design of omnidirectional optical filters with a high transmittance and circular polarization selectors working in a wide-angle range.

Clinical usefulness of the lymphocyte-to-monocyte ratio and aggregate index of systemic inflammation in patients with esophageal cancer: a retrospective cohort study.

BACKGROUND: Multiple perioperative inflammatory markers are considered important factors affecting the long-term survival of esophageal cancer (EC) patients. Hematological parameters, whether single or combined, have high predictive value. AIM: To investigate the inflammatory status of patients with preoperative EC using blood inflammatory markers, and to establish and validate competing risk nomogram prediction models for overall survival (OS) and progression-free survival (PFS) in EC patients. METHODS: A total of 508 EC patients who received radical surgery (RS) treatment in The First Affiliated Hospital of Zhengzhou University from August 5, 2013, to May 1, 2019, were enrolled and randomly divided into a training cohort (356 cases) and a validation cohort (152 cases). We performed least absolute shrinkage and selection operator (LASSO)-univariate Cox- multivariate Cox regression analyses to establish nomogram models. The index of concordance (C-index), time-dependent receiver operating characteristic (ROC) curves, time-dependent area under curve (AUC) and calibration curves were used to evaluate the discrimination and calibration of the nomograms, and decision curve analysis (DCA) was used to evaluate the net benefit of the nomograms. The relative integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to evaluate the improvement in predictive accuracy of our new model compared with the AJCC staging system and another traditional model. Finally, the relationship between systemic inflammatory response markers and prognostic survival was explored according to risk plot, time-dependent AUC, Kaplan-Meier and restricted cubic spline (RCS). RESULTS: Based on the multivariate analysis for overall survival (OS) in the training cohort, nomograms with 10 variables, including the aggregate index of systemic inflammation (AISI) and lymphocyte-to-monocyte ratio (LMR), were established. Time-dependent ROC, time-dependent AUC, calibration curves, and DCA showed that the 1-, 3-, and 5 year OS and PFS probabilities predicted by the nomograms were consistent with the actual observations. The C-index, NRI, and IDI of the nomograms showed better performance than the AJCC staging system and another prediction model. Moreover, risk plot, time-dependent AUC, and Kaplan-Meier showed that higher AISI scores and lower LMR were associated with poorer prognosis, and there was a nonlinear relationship between them and survival risk. CONCLUSION: AISI and LMR are easy to obtain, reproducible and minimally invasive prognostic tools that can be used as markers to guide the clinical treatment and prognosis of patients with EC.

Plasma Meets MOFs: Synthesis, Modifications, and Functionalities.

As a porous and network materials consisting of metals and organic ligands, metal-organic frameworks (MOFs) have become one of excellent crystalline porous materials and play an important role in the era about materials science. Plasma, as a useful tool for stimulating efficient reactions under many conditions, and the plasma-assisted technology gets more attractions and endows MOFs more properties. Based on its feature, the research about the modifications and functionalities of MOFs have been developing a certain extent. This review contains a description of the methods for plasma-assisted modification and synthesis of MOFs, with specifically focusing on the plasma-assisted potential for modifications and functionalities of MOFs. The different applications of plasma-assisted MOFs were also presented.

Association between alcohol consumption and incidence of type 2 diabetes mellitus in Japanese men: a secondary analysis of a Retrospective Cohort Study.

BACKGROUND: Alcohol consumption is known to be associated with an increased risk of type 2 diabetes (T2DM). However, the effect of alcohol intake on the incidence of T2DM remains controversial due to inconsistent results across studies. This study aimed to bridge the gap among available literature in order to better define the association between alcohol consumption and incidence of T2DM. METHODS: We performed a secondary analysis using open-access data from a retrospective Japanese cohort of 15,464 participants who underwent regular medical examinations at Murakami Memorial Hospital. All participants underwent an initial exam including a questionnaire survey, physical examination, and blood biochemical testing to establish a at baseline. The primary outcome was new-onset T2DM during the follow-up exam. Statistical analysis was conducted using Cox regression and Kaplan-Meier methods to assess the risk of alcohol consumption on T2DM. RESULTS: During a median follow-up time of 5.39 years, 373 new-onset T2DM events were observed. The cumulative risk of T2DM incidence was higher in the heavy alcohol consumption group vs. the other three groups: none/minimal, light, and moderate consumption (log-rank test, P = 0.0002). Multivariate Cox regression analysis indicated incidental T2DM was independently associated with alcohol consumption. The adjusted hazard ratio relative to the none/minimal consumption group was as follows: 1.02 (95% confidence interval: 0.71, 1.48) for light consumption, 1.06 (0.71, 1.57) for moderate consumption, and 2.06 (1.30, 3.24) for heavy consumption (P value = 0.024). Subsequent subgroup analysis confirmed the association between alcohol consumption and T2DM incidence in men, but not in women. CONCLUSION: Heavy alcohol consumption was independently associated with an increased risk of new-onset T2DM in Japanese men.

Role of genetics in amyotrophic lateral sclerosis: a large cohort study in Chinese mainland population.

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

The evolution of mechanism of accommodation and a novel hypothesis.

Myopia and presbyopia are two major optometry problems facing the whole society. The mechanism of accommodation is strongly related to the treatments of myopia and presbyopia. However, the key mechanism of accommodation has puzzled us for over 400 years and is still not clear at present, leading to the stagnation of prevention and treatment of myopia and presbyopia. With the continued development of experimental technologies and equipment, the approaches to elucidate accommodation's intricacies have become more methodological and sophisticated. Fortunately, some significant progress has been made. This article is to review the evolution of the mechanism of accommodation. Helmholtz proposed a classical theory of "zonules relax during accommodation." In contrast, Schachar put forward a theory of "zonules taut during accommodation." Those hypotheses are relatively complete, but either do not fully explain everything about the accommodation mechanism or lack sufficient experimental and clinical evidence to support them. Then, some contentious issues are discussed in detail to find the truth. Finally, we proposed our hypothesis about accommodation based on the anatomy of the accommodative apparatus.

Immunoregulatory signal networks and tumor immune evasion mechanisms: insights into therapeutic targets and agents in clinical development.

Through activation of immune cells, the immune system is responsible for identifying and destroying infected or otherwise damaged cells including tumorigenic cells that can be recognized as foreign, thus maintaining homeostasis. However, tumor cells have evolved several mechanisms to avoid immune cell detection and killing, resulting in tumor growth and progression. In the tumor microenvironment, tumor infiltrating immune cells are inactivated by soluble factors or tumor promoting conditions and lose their effects on tumor cells. Analysis of signaling and crosstalk between immune cells and tumor cells have helped us to understand in more detail the mechanisms of tumor immune evasion and this forms basis for drug development strategies in the area of cancer immunotherapy. In this review, we will summarize the dominant signaling networks involved in immune escape and describe the status of development of therapeutic strategies to target tumor immune evasion mechanisms with focus on how the tumor microenvironment interacts with T cells.

Inulin-type oligosaccharides of Morinda officinalis exerted antidepressant effects by reducing hippocampal inflammation.

Neuroinflammation contributes to the pathogenesis of depression. Inulin-type oligosaccharides of Morinda officinalis (IOMO) exert antidepressant-like effects in rodents and patients with depression, while the underlying mechanisms remain unclear. This study used chronic restraint stress (CRS) and lipopolysaccharide (LPS) to induce depression-like behaviors in mice. Western blotting and ELISA analysis were used to investigate the effects of IOMO on inflammatory cytokine levels. Immunofluorescence analysis was used to investigate the effects of IOMO on hippocampal NLRP3 inflammasome and microglial cells. The results suggested that 6 weeks of CRS induced significant depression-like behaviors based on the sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST), which were accompanied by increases in the expression of IL-6 and the activation of hippocampal microglial cells. Chronic treatment with IOMO (25 mg/kg, i.g.) for 28 days significantly reversed these depression-like behaviors and inhibited the activation of microglial cells. Furthermore, LPS (0.5 mg/kg, i.p.) also significantly induced depression-like behaviors in the TST, FST, and novelty-suppressed feeding test (NSFT), as well as increased the expression of IL-1ß and caspase-1, and activated the microglial cells and the NLRP3 inflammasome in the hippocampus. Treatment with IOMO for 9 days significantly reversed these depression-like behaviors and normalized the LPS-induced activation of the microglial cells and NLRP3 inflammasome. Taken together, these results suggested that IOMO exerted antidepressant-like effects via hippocampal microglial NLRP3 inflammasome mediation followed by caspase-1 inhibition and the production of IL-1ß. These findings provide a basis for developing new antidepressants targeting the microglial NLRP3 inflammasome.

[Effects of Pearl Hydrolysate on Hepatic Sinusoidal Endothelial Cell Viability and Capillarization in Liver Fibrosis].

Objective To study the effect and mechanism of pearl hydrolysate on hepatic sinusoidal capillarization in liver fibrosis. Methods Hepatic sinusoidal endothelial cells (HSEC) and hepatic stellate cells (HSC-LX2) were incubated with Hepu pearl hydrolysate.The proliferation of HSEC and HSC-LX2 was examined by MTT colorimetry.The cell cycle and apoptosis of HSC-LX2 were measured by flow cytometry.The changes of the microstructures such as fenestra and basement membrane of HSEC were observed by transmission electron microscopy. Results The intervention with leptin increased the viability of HSC-LX2 (P=0.041),decreased the viability of HSEC (P=0.004),and caused capillarization signs such as decreased number and diameter of fenestrae and formation of continuous basement membrane.The treatment with pearl hydrolysate at different doses increased and expanded the fenestrae of HSEC (low dose:P=0.020;medium dose:P=0.028;high dose:P=0.032),disintegrated the extracellular basement membrane of HSEC (low dose:P=0.020;medium dose:P=0.028;high dose:P=0.032),decreased the viability of HSC-LX2 (low dose:P=0.018;medium dose:P=0.013;high dose:P=0.009),and induced the apoptosis of HSC-LX2 (low dose:P=0.012;medium dose:P=0.006;high dose:P=0.005).Pearl hydrolysate exerted therapeutic effect on capillarization in a dose-dependent manner (low dose:P=0.020;medium dose:P=0.028;high dose:P=0.032).Moreover,high-dose pearl hydrolysate showed stronger effect on capillarization of hepatic sinuses than colchicine (P=0.034) and salvianolic acid B (P=0.038). Conclusion Hepu pearl hydrolysate can increase the viability of HSEC,restore the area of fenestrae,disintegrate the basement membrane,and decrease the viability and induce the apoptosis of HSC-LX2,demonstrating significant pharmacological effects on the capillarization of HSEC and HSC-LX2.