Mesoporous TiO2 Single-Crystal Particles from Controlled Crystallization-Driven Mono-Micelle Assembly as an Efficient Photocatalyst.

Mesoporous materials with crystalline frameworks have been widely explored in many fields due to their unique structure and crystalline feature, but accurate manipulations over crystalline scaffolds, mainly composed of uncontrolled polymorphs, are still lacking. Herein, we explored a controlled crystallization-driven monomicelle assembly approach to construct a type of uniform mesoporous TiO2 particles with atomically aligned single-crystal frameworks. The resultant mesoporous TiO2 single-crystal particles possess an angular shape ∼80 nm in diameter, good mesoporosity (a high surface area of 112 m2 g-1 and a mean pore size at 8.3 nm), and highly oriented anatase frameworks. By adjusting the evaporation rate during assembly, such a facile solution-processed strategy further enables the regulation of the particle size and mesopore size without the destruction of the oriented crystallites. Such a combination of ordered mesoporosity and crystalline orientation provides both effective mass and charge transportation, leading to a significant increase in the hydrogen generation rate. A maximum hydrogen evolution rate of 12.5 mmol g-1 h-1 can be realized, along with great stability under solar light. Our study is envisaged to extend the possibility of mesoporous single crystal growth to a range of functional ceramics and semiconductors toward advanced applications.

The anti-atherosclerotic effect of Paeonol against the lipid accumulation in macrophage-derived foam cells by inhibiting ferroptosis via the SIRT1/NRF2/GPX4 signaling pathway.

Atherosclerosis (AS) is the underlying cause of many severe vascular diseases and is primarily characterized by abnormal lipid metabolism. Paeonol (Pae), a bioactive compound derived from Paeonia Suffruticosa Andr., is recognized for its significant role in reducing lipid accumulation. Our research objective is to explore the link between lipid buildup in foam cells originating from macrophages and the process of ferroptosis, and explore the effect and mechanism of Pae on inhibiting AS by regulating ferroptosis. In our animal model, ApoE-deficient mice, which were provided with a high-fat regimen to provoke atherosclerosis, were administered Pae. The treatment was benchmarked against simvastatin and ferrostatin-1. The results showed that Pae significantly reduced aortic ferroptosis and lipid accumulation in the mice. In vitro experiments further demonstrated that Pae could decrease lipid accumulation in foam cells induced by oxidized low-density lipoprotein (LDL) and challenged with the ferroptosis inducer erastin. Crucially, the protective effect of Pae against lipid accumulation was dependent on the SIRT1/NRF2/GPX4 pathway, as SIRT1 knockdown abolished this effect. Our findings suggest that Pae may offer a novel therapeutic approach for AS by inhibiting lipid accumulation through the suppression of ferroptosis, mediated by the SIRT1/NRF2/GPX4 pathway. Such knowledge has the potential to inform the creation of novel therapeutic strategies aimed at regulating ferroptosis within the context of atherosclerosis.

Paeonol Attenuates Atherosclerosis by Inhibiting Vascular Smooth Muscle Cells Senescence via SIRT1/P53/TRF2 Signaling Pathway.

Atherosclerosis is a chronic inflammatory disease leading to various vascular diseases. Vascular smooth muscle cell (VSMC) senescence promotes atherosclerotic inflammation and the formation of plaque necrosis core, in part through telomere damage mediated by a high-fat diet. Our previous research found that paeonol, a potential anti-inflammatory agent extracted from Cortex Moutan, could significantly improve VSMCs dysfunction. However, the impact of paeonol on the senescence of VSMCs remains unexplored. This study presents the protective effects of paeonol on VSMCs senescence, and its potential activity in inhibiting the progression of atherosclerosis in vivo and in vitro. Sirtuin 1 (SIRT1) is a nuclear deacetylase involved in cell proliferation, senescence, telomere damage, and inflammation. Here, SIRT1 was identified as a potential target of paeonol having anti-senescence and anti-atherosclerosis activity. Mechanistic studies revealed that paeonol binds directly to SIRT1 and then activates the SIRT1/P53/TRF2 pathway to inhibit VSMCs senescence. Our results suggested that SIRT1-mediated VSMCs senescence is a promising druggable target for atherosclerosis, and that pharmacological modulation of the SIRT1/P53/TRF2 signaling pathway by paeonol is of potential benefit for patients with atherosclerosis.

[Mechanism of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" in treating cardiovascular diseases with syndrome of combined phlegm and stasis based on serum metabolomics].

This study aimed at investigating the mechanism of Trichosanthis Fructus-Allii Macrostemonis Bulbus(GX) in treating cardiovascular diseases in rats with the syndrome of combined phlegm and stasis. The rat model was established by a high-fat diet, ice-water bath combined with subcutaneous injection of adrenalin hydrochloride, and the syndrome score was determined. The serum samples of rats in the control, model, and GX groups were collected. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to analyze the metabolic profiles of the serum samples. The differential metabolites were screened and identified by partial least squares-discriminant analysis(PLS-DA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). The intervention targets of GX-regulated metabolites and their metabolic pathways were searched against MetaboAnalyst. Gene Ontology enrichment was carried out to predict the biological pathways associated with the intervention targets of metabolic pathways. A total of 129 potential biomarkers were detected in the rat model with the syndrome of combined phlegm and stasis via metabolomics, and GX regulated 54 metabolites in several metabolic pathways such as linoleic acid metabolism, sphingolipid metabolism, and tricarboxylic acid cycle. The further screening against MetaboAnalyst showed that GX recovered the levels of nine metabolites associated with cardiovascular diseases with the syndrome of combined phlegm and stasis, which involved 69 targets in the pathways regarding cholesterol metabolism, fatty acid metabolism, inflammatory response, and glucose homeostasis and metabolism. The above-mentioned results suggested that GX can alleviate the symptoms of the rat model of cardiovascular diseases with the syndrome of combined phlegm and stasis by regulating the metabolism of linoleic acid, sphingosine, docosahexaenoic acid, rosemary acid, succinic acid, adenine, L-phenylalanine, L-valine and modulating the biological pathways such as cholesterol metabolism, fatty acid metabolism, inflammatory response, and glucose homeostasis and metabolism.

CircHIPK3 relieves vascular calcification via mediating SIRT1/PGC-1α/MFN2 pathway by interacting with FUS.

BACKGROUND: Circular RNAs (circRNAs) have been reported to regulate the biological processes of human diseases. CircHIPK3 has been implicated in vascular calcification, but the downstream regulatory mechanisms remain unclear. Our study aimed to understand the regulatory function of circHIPK3 in vascular calcification. METHODS: CircHIPK3 expression in atherosclerosis (AS) serum samples and vascular smooth muscle cells (VSMCs) calcification model was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The binding relationships between fused in sarcoma (FUS) and circHIPK3 or sirtuin 1 (SIRT1) were verified by RNA immunoprecipitation (RIP) assay and RNA pull-down assays. Alkaline phosphatase (ALP) activity and alizarin red staining assays were performed to evaluate the biological effect of ß-glycerophosphate (ß-GP) and circHIPK3 on calcium deposition. qRT-PCR and western blot assays were used to examine the effect of ß-GP, circHIPK3, SIRT1, mitofusin 2 (MFN2), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) on VSMCs calcification and the expression of calcification-related proteins. RESULTS: In AS serum samples and VSMCs calcification model, the expression of circHIPK3 was significantly reduced. CircHIPK3 overexpression inhibited ALP activity and calcium deposition in ß-GP-induced VSMCs. Moreover, circHIPK3 could recruit FUS to further stabilize SIRT1 mRNA. CircHIPK3 promoted MFN2 expression to alleviate VSMCs calcification via activating SIRT1/PGC-1α signaling. CONCLUSION: The positive regulation of circHIPK3/FUS/SIRT1/PGC-1α/MFN2 signaling pathway contributed to the alleviate VSMCs calcification, revealing a novel regulatory axis for vascular calcification.

Chronic ß-adrenergic stress contributes to cardiomyopathy in rodents with collagen-induced arthritis.

Patients with rheumatoid arthritis (RA) have a much higher incidence of cardiac dysfunction, which contributes to the high mortality rate of RA despite anti-arthritic drug therapy. In this study, we investigated dynamic changes in cardiac function in classic animal models of RA and examined the potential effectors of RA-induced heart failure (HF). Collagen-induced arthritis (CIA) models were established in rats and mice. The cardiac function of CIA animals was dynamically monitored using echocardiography and haemodynamics. We showed that cardiac diastolic and systolic dysfunction occurred in CIA animals and persisted after joint inflammation and that serum proinflammatory cytokine (IL-1ß, TNF-α) levels were decreased. We did not find evidence of atherosclerosis (AS) in arthritic animals even though cardiomyopathy was significant. We observed that an impaired cardiac ß1AR-excitation contraction coupling signal was accompanied by sustained increases in blood epinephrine levels in CIA rats. Furthermore, serum epinephrine concentrations were positively correlated with the heart failure biomarker NT-proBNP in RA patients (r2 = +0.53, P < 0.0001). In CIA mice, treatment with the nonselective ßAR blocker carvedilol (2.5 mg·kg-1·d-1, for 4 weeks) or the specific GRK2 inhibitor paroxetine (2.5 mg·kg-1·d-1, for 4 weeks) effectively rescued heart function. We conclude that chronic and persistent ß-adrenergic stress in CIA animals is a significant contributor to cardiomyopathy, which may be a potential target for protecting RA patients against HF.

Improving machine learning force fields for molecular dynamics simulations with fine-grained force metrics.

Machine learning force fields (MLFFs) have gained popularity in recent years as they provide a cost-effective alternative to ab initio molecular dynamics (MD) simulations. Despite a small error on the test set, MLFFs inherently suffer from generalization and robustness issues during MD simulations. To alleviate these issues, we propose global force metrics and fine-grained metrics from element and conformation aspects to systematically measure MLFFs for every atom and every conformation of molecules. We selected three state-of-the-art MLFFs (ET, NequIP, and ViSNet) and comprehensively evaluated on aspirin, Ac-Ala3-NHMe, and Chignolin MD datasets with the number of atoms ranging from 21 to 166. Driven by the trained MLFFs on these molecules, we performed MD simulations from different initial conformations, analyzed the relationship between the force metrics and the stability of simulation trajectories, and investigated the reason for collapsed simulations. Finally, the performance of MLFFs and the stability of MD simulations can be further improved guided by the proposed force metrics for model training, specifically training MLFF models with these force metrics as loss functions, fine-tuning by reweighting samples in the original dataset, and continued training by recruiting additional unexplored data.

Identification and quantitative analysis of the chemical constituents of Gandouling tablets using ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

Gandouling tablets are used in a clinical agent for the treatment of hepatocellular degeneration; however, their chemical constituents have not been elucidated. Here, we screened and identified the chemical constituents of Gandouling tablets using ultra-high-performance liquid chromatography (UHPLC)-quadrupole time of flight/mass spectrometry. A method for the quality evaluation of Gandouling tablets was developed by combining the UHPLC fingerprints and the simultaneous quantitative analysis of multiple active ingredients. For fingerprint analysis, 20 shared peaks were identified to assess the similarities among the 10 batches of Gandouling tablets and the similarity was >0.9. The levels of nine representative active ingredients were simultaneously determined to ensure consistency in quality. A total of 99 chemical components were identified, including 18 alkaloids, 20 anthraquinones, 13 flavonoids, 11 phenolic acids, 9 polyphenols, 7 phenanthrenes, 5 sesquiterpenes, 3 curcuminoids, 2 lignans, 2 isoflavones, 2 dianthranones, and 7 other components. The retention times, molecular formulae, and secondary fragmentation information of these compounds were analyzed, and the cleavage pathways and characteristic fragments of some of the representative compounds were elucidated. This systematic analysis used to identify the chemical components of Gandouling tablets lays the foundation for its further quality control and research on their pharmacodynamic substances.

The susceptibility of Hyphantria cunea larvae to microbial pesticides Bacillus thuringiensis and Mamestra brassicae nuclear polyhedrosis virus under Cd stress.

Heavy metal pollution is an abiotic factor that can affect the efficiency of pest control. In this study, two microbial pesticides, Bacillus thuringiensis and Mamestra brassicae nuclear polyhedrosis virus (MbNPV), were used to treat Hyphantria cunea larvae with Cd pre-exposure, and the humoral and cellular immunity of H. cunea larvae with Cd exposure were evaluated. The results showed that Cd exposure increased the susceptibility of H. cunea larvae to microbial pesticides B. thuringiensis and MbNPV, and the lethal effect of Cd exposure and microbial pesticides on H. cunea larvae was synergistic. Cd exposure significantly decreased the expression of pathogen recognition genes (GNBP1 and GNBP3), signal transduction genes (Relish, Myd88, Tube, and Imd), and antimicrobial peptide gene (Lebocin) in the humoral immunity of H. cunea larvae compared with the untreated larvae. Parameters of cellular immunity, including the number of hemocytes, phagocytic activity, melanization activity, encapsulation activity, and the expression of three phagocytic regulatory genes (HEM1, GALE1, GALE2), were also found to decrease significantly in Cd-treated larvae. TOPSIS analysis showed that humoral immunity, cellular immunity, and total immunity levels of H. cunea larvae with Cd exposure were weaker than those in untreated larvae. Correlation analysis showed that the mortality of two microbial pesticides investigated in H. cunea larvae was negatively correlated with the humoral and cellular immunity of larvae. Taken togther, Cd exposure results in immunotoxic effects on H. cunea larvae and the use of microbial pesticides are an effective strategy for pest control in heavy metal-polluted areas.

GC-MS Fingerprinting Combined with Chemical Pattern-Recognition Analysis Reveals Novel Chemical Markers of the Medicinal Seahorse.

Seahorse is a valuable marine-animal drug widely used in traditional Chinese medicine (TCM), and which was first documented in the "Ben Cao Jing Ji Zhu" during the Liang Dynasty. Hippocampus kelloggi (HK) is the most common seahorse species in the medicinal material market and is one of the genuine sources of medicinal seahorse documented in the Chinese pharmacopeia. It is mainly cultivated in the Shandong, Fujian, and Guangxi Provinces in China. However, pseudo-HK, represented by Hippocampus ingens (HI) due to its similar appearance and traits, is often found in the market, compromising the safety and efficacy of clinical use. Currently, there is a lack of reliable methods for identifying these species based on their chemical composition. In this study, we employed, for the first time, a strategy combining gas chromatography-mass spectrometry (GC-MS) fingerprints and chemical patterns in order to identify HK and HI; it is also the first metabolomic study to date of HI as to chemical components. The obtained results revealed remarkable similarities in the chemical fingerprints, while significant differences were also observed. By employing hierarchical cluster analysis (HCA) and principal component analysis (PCA), based on the relative contents of their characteristic peaks, all 34 samples were successfully differentiated according to their species of origin, with samples from the same species forming distinct clusters. Moreover, nonadecanoic acid and behenic acid were exclusively detected in HK samples, further distinguishing them from HI samples. Additionally, the relative contents of lauric acid, tetradecanoic acid, pentadecanoic acid, n-hexadecanoic acid, palmitoleic acid, margaric acid, oleic acid, fenozan acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) exhibited significant differences between HK and HI (p < 0.0001), as determined by an unpaired t-test. Orthogonal partial least squares discriminant analysis (OPLS-DA) identified seven components (DHA, EPA, n-hexadecanoic acid, tetradecanoic acid, palmitoleic acid, octadecanoic acid, and margaric acid) with high discriminatory value (VIP value > 1). Thus, nonadecanoic acid, behenic acid, and these seven compounds can be utilized as chemical markers for distinguishing HK from HI. In conclusion, our study successfully developed a combined strategy of GC-MS fingerprinting and chemical pattern recognition for the identification of HK and HI, and we also discovered chemical markers that can directly differentiate between the two species. This study can provide a foundation for the authentication of Hippocampus and holds significant importance for the conservation of wild seahorse resources.

Geographic Differentiation of Essential Oil from Rhizome of Cultivated Atractylodes lancea by Using GC-MS and Chemical Pattern Recognition Analysis.

The rhizome of Atractylodes lancea (RAL) is a well-known Chinese herbal medicine (CHM) that has been applied in clinical settings for thousands of years. In the past two decades, cultivated RAL has gradually replaced wild RAL and become mainstream in clinical practice. The quality of CHM is significantly influenced by its geographical origin. To date, limited studies have compared the composition of cultivated RAL from different geographical origins. As essential oil is the primary active component of RAL, a strategy combining gas chromatography-mass spectrometry (GC-MS) and chemical pattern recognition was first applied to compare the essential oil of RAL (RALO) from different regions in China. Total ion chromatography (TIC) revealed that RALO from different origins had a similar composition; however, the relative content of the main compounds varied significantly. In addition, 26 samples obtained from various regions were divided into three categories by hierarchical cluster analysis (HCA) and principal component analysis (PCA). Combined with the geographical location and chemical composition analysis, the producing regions of RAL were classified into three areas. The main compounds of RALO vary depending on the production areas. Furthermore, a one-way analysis of variance (ANOVA) revealed that there were significant differences in six compounds, including modephene, caryophyllene, γ-elemene, atractylon, hinesol, and atractylodin, between the three areas. Hinesol, atractylon, and ß-eudesmol were selected as the potential markers for distinguishing different areas by orthogonal partial least squares discriminant analysis (OPLS-DA). In conclusion, by combining GC-MS with chemical pattern recognition analysis, this research has identified the chemical variations across various producing areas and developed an effective method for geographic origin tracking of cultivated RAL based on essential oils.

["Trichosanthis Fructus-Allii Macrostemonis Bulbus" combination inhibits NLRP3 inflammasome activation and reduces inflammatory response in RAW264.7 macrophage by inducing autophagy].

This study aims to explore the effect of "Trichosanthis Fructus-Allii Macrostemonis" combination(GX) on the activation of NOD-, LRR-, and pyrin domain-containing protein 3(NLRP3) inflammasome, the release of inflammatory cytokines, and the level of autophagy in RAW264.7 macrophage damaged by lipopolysaccharide(LPS), and the mechanism of GX against inflammatory response in macrophages. To be specific, LPS was used to induce the injury of RAW264.7 cells. Cell Counting Kit-8(CCK-8) assay was employed to measure the survival rate of cells, and Western blot to detect the protein expression of NLRP3, apoptosis-associated speck-like protein(ASC), cysteine-aspartic acid protease(caspase)-1, interleukin(IL)-18, IL-1ß, microtubule-associated protein light chain 3(LC3)-Ⅱ, and selective autophagy junction protein p62/sequestosome 1 in RAW264.7 macrophages. ELISA was used to measure the levels of IL-18 and IL-1ß in RAW264.7 cells. Transmission electron microscopy was applied to observe the number of autophagosomes in RAW264.7 cells. Immunofulourescence staining was used to detect the expression of LC3-Ⅱ and p62 in RAW264.7 cells. The result showed that GX significantly reduced the protein expression of NLRP3, ASC, and caspase-1 in RAW264.7 cells, significantly increased the protein expression of LC3Ⅱ, decreased the expression of p62, significantly inhibited the secretion of IL-18 and IL-1ß, significantly increased the number of autophagosomes, significantly enhanced the immunofluorescence of LC3Ⅱ, and reduced the immunofluorescence of p62. Furthermore, 3-methyladenine(3-MA) could reverse the inhibitory effect of GX on NLRP3, ASC, and caspase-1 and reduce the release of IL-18 and IL-1ß. In summary, GX can increase of the autophagy activity of RAW264.7 and inhibit the activation of NLRP3 inflammasome, thereby reducing the release of inflammatory cytokines and suppressing inflammatory response in macrophages.

Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia.

Myeloid-derived suppressor cells (MDSC) are a group of heterogeneous immature myeloid cells and display immunosuppressive function. In this study, MDSC populations were evaluated in acquired aplastic anemia (AA) (n=65) in which aberrant immune mechanisms contributed to bone marrow destruction. Our data demonstrate that both the proportion and immunosuppressive function of MDSC are impaired in AA patients. Decreased percentage of MDSC, especially monocytic MDSC, in the blood of AA patients (n=15) is positively correlated with the frequency of T-regulatory cells, bone marrow level of WT1 and decreased plasma level of arginase-1. RNA sequencing analyses reveal that multiple pathways including DNA damage, interleukin 4, apoptosis, and Jak kinase singnal transducer and activator of transcription are upregulated, whereas transcription, IL-6, IL-18, glycolysis, transforming growth factor and reactive oxygen species are downregulated in MDSC of AA (n=4), compared with that of healthy donors (n=3). These data suggest that AA MDSC are defective. Administration of rapamycin significantly increases the absolute number of MDSC and levels of intracellular enzymes, including arginase-1 and inducible nitric-oxide synthase. Moreover, rapamycin inhibits MDSC from differentiating into mature myeloid cells. These findings reveal that impaired MDSC are involved in the immunopathogenesis of AA. Pharmacologically targeting of MDSC by rapamycin might provide a promising therapeutic strategy for AA.

Cd exposure-triggered metabolic disruption increases the susceptibility of Lymantria dispar (Lepidoptera: Erebidae) larvae to Mamestra brassicae nuclear polyhedrosis virus: A multi-omics study.

Biological control is an environmentally friendly and effective pest control strategy, but it is often affected by a variety of abiotic factors in the pest control area. Here, the susceptibility of gypsy moth larvae to Mamestra brassicae nuclear polyhedrosis virus (MbNPV) under Cd treatment at the low and high dosages was investigated, and the mechanism of Cd stress affecting virus susceptibility of gypsy moth larvae was analyzed from a metabolic perspective by combining transcriptome and metabolome of the larval fat body. Our results showed that the mortality of MBNPV infection on gypsy moth larvae pre-exposed to Cd was significantly higher than that of larvae without Cd pre-exposure, and the joint effects of Cd exposure and virus infection on larval mortality were demonstrated to be synergistic. Transcriptome analysis revealed that amino acid and carbohydrate transport and metabolism accounted for most of the differently expressed genes in the low Cd and high Cd treatment groups. Consistent with the transcriptome results, metabolome analysis also showed that most metabolites affected by Cd exposure were involved in amino acid and carbohydrate metabolism. Function analysis showed that the contents of several amino acids (e.g. tryptophan and tyrosine) with antioxidant properties were significantly increased in Cd-treated gypsy moth larvae. Taken together, Cd exposure as an environmental factor, promotes the susceptibility of gypsy moth larvae to MbNPV, and metabolic disruption, especially amino acids and carbohydrates-related metabolism, is responsible for the increased susceptibility of gypsy moth larvae to virus under Cd stress.

The immunotoxicity of Cd exposure to gypsy moth larvae: An integrated analysis of cellular immunity and humoral immunity.

Heavy metal exposure-triggered growth retardation and physiology disorder in phytophagous insects have been widely understood, but only a few studies have investigated its immunomodulatory effects on herbivorous insects. Here, the innate immunity of gypsy moth (Lymantria dispar) larvae under Cd stress was evaluated by integrating cellular and humoral immunity, and the immunomodulation mechanism of Cd stress was further understood by the proteomics analysis of larval hemolymph. Our results showed that the total hemocyte count, as well as phagocytic, encapsulation and bacteriostatic activity, of hemolymph in gypsy moth larvae exposed to Cd stress was significantly lower than that in un-treated larvae. Further proteomic analysis revealed that Cd exposure may reduce the total hemocyte count in larval hemolymph by inducing endoplasmic reticulum pathway-mediated hemocyte apoptosis, thereby causing the collapse of cellular immunity in gypsy moth larvae. In addition, the transcriptional level of signal transduction genes (IMD, Toll, Relish, JAK and STAT) and antimicrobial peptide genes (cecropin and lebocin), as well as the protein abundance of pattern recognition receptors (PGRP and GNBP3) in the Toll, IMD and JAK/STAT signaling pathways was significantly decreased in Cd-treated larvae, clearly implying an immunosuppresive effect of Cd stress on pathogen recognition, signal transduction and effector synthesis of humoral immunity in gypsy moth larvae. Taken together, these results suggest that Cd exposure decreases both cellular immunity and humoral immunity of gypsy moth larvae, and provides a new entry point for systematically and comprehensively unraveling the heavy metal pollutants-caused immunotoxicity.

Cd exposure-triggered susceptibility to Bacillus thuringiensis in Lymantria dispar involves in gut microbiota dysbiosis and hemolymph metabolic disorder.

The immunotoxicity induced by heavy metals on herbivorous insects reflect the alterations of the susceptibility to entomopathogenic agents in herbivorous insects exposed to heavy metal. In the present study, the susceptibility of gypsy moth larvae to Bacillus thuringiensis under Cd treatment at low and high dosages was investigated, and the gut microbiome-hemolymph metabolome responses that affected larval disease susceptibility caused by Cd exposure were examined. Our results showed that mortality of gypsy moth larvae caused by B. thuringiensis was significantly higher in larvae pre-exposed to Cd stress, and there was a synergistic effect between Cd pre-exposure and bacterial infection. Exposure to Cd significantly decreased the abundance of several probiotics (e.g., Serratia for the low Cd dosage and Weissella, Aeroonas, and Serratia for the high Cd dosage) and increased the abundances of several pathogenic bacteria (e.g., Stenotrophomonas, Gardnerella, and Cutibacterium for the low Cd dosage and Pluralibacter and Tsukamurella for the high Cd dosage) compared to the controls. Moreover, metabolomics analysis indicated that amino acid biosynthesis and metabolism were significantly perturbed in larval hemolymph under Cd exposure at both the low and high dosages. Correlation analysis demonstrated that several altered metabolites in larval hemolymph were significantly correlated with changes in the gut microbial community. The results demonstrate that prior exposure to Cd increases the susceptibility of gypsy moth larvae to B. thuringiensis in a synergistic fashion due to gut microbiota dysbiosis and hemolymph metabolic disorder, and thus microbial-based biological control may be the best pest control strategy in heavy metal-polluted areas.

Design, Synthesis and Fungicidal Activity of N-(thiophen-2-yl) Nicotinamide Derivatives.

Based on the modification of natural products and the active substructure splicing method, a series of new N-(thiophen-2-yl) nicotinamide derivatives were designed and synthesized by splicing the nitrogen-containing heterocycle natural molecule nicotinic acid and the sulfur-containing heterocycle thiophene. The structures of the target compounds were identified through 1H NMR, 13C NMR and HRMS spectra. The in vivo bioassay results of all the compounds against cucumber downy mildew (CDM, Pseudoperonospora cubensis (Berk.et Curt.) Rostov.) in a greenhouse indicated that compounds 4a (EC50 = 4.69 mg/L) and 4f (EC50 = 1.96 mg/L) exhibited excellent fungicidal activities which were higher than both diflumetorim (EC50 = 21.44 mg/L) and flumorph (EC50 = 7.55 mg/L). The bioassay results of the field trial against CDM demonstrated that the 10% EC formulation of compound 4f displayed excellent efficacies (70% and 79% control efficacies, respectively, each at 100 mg/L and 200 mg/L) which were superior to those of the two commercial fungicides flumorph (56% control efficacy at 200 mg/L) and mancozeb (76% control efficacy at 1000 mg/L). N-(thiophen-2-yl) nicotinamide derivatives are significant lead compounds that can be used for further structural optimization, and compound 4f is also a promising fungicide candidate against CDM that can be used for further development.

[Ectopic opening of the ejaculatory duct into the urethra: A case report and literature review].

OBJECTIVE: To explore the diagnosis and treatment of ectopic seminal duct opening into the urethra. METHODS: We reviewed the literature and retrospectively analyzed the clinical data on a case of sex development abnormality. The patient was a 16-year-old gender female seeking medical improvement of female signs, admitted to hospital with "clitoris hypertrophy, no menstruation and chromosome karyotype 46XY", treated by bilateral orchiectomy, and simultaneously examined by seminal vesiculography and cystoscopy. RESULTS: Seminal vesiculography showed the ectopic opening of the right ejaculatory duct into the urethra accompanied by dysplasia of the seminal vesicle. Cystoscopy exhibited a fissrure-like opening in the right wall of the urethra but no verumontanum. Postoperative pathology revealed bilateral undeveloped testes and epididymides. CONCLUSION: Ectopic opening of the seminal duct into the urethra is extremely rare and often complicated by many malformations, for the diagnosis of which the most reliable options are seminal vesiculography and retrograde radiography through the ectopic orifice under the cystoscope. The treatment of the disease should follow the principles of timeliness, individualization and consideration of associated malformations.

[Compatibility mechanism of Trichosanthis Fructus-Allii Macrostemonis Bulbus combination against atherosclerosis: based on metabolomics and network pharmacology].

This study aims to investigate the compatibility mechanism of Trichosanthis Fructus-Allii Macrostemonis Bulbus combination against atherosclerosis(AS) in apolipoprotein E-deficient(ApoE~(-/-)) mice. To be specific, high-fat diet was used to induce AS in mice. The pathological morphology of mice aorta was evaluated based on hematoxylin-eosin(HE) staining and Masson staining. The metabolic profiling of mouse serum samples was performed with ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Multiple statistical analysis methods including partial least squares-discriminant analysis and orthogonal partial least squares-discriminant analysis were employed to screen potential biomarkers in mice. With the techniques in network pharmacology, the metabolites related to AS and the targets in the metabolic pathways were screened out. The results showed that Trichosanthis Fructus alone and the pair all reduced the plaque area of aortic sinus(P<0.05) and collagen area(P<0.05). Compared with the Trichosanthis Fructus alone and Allii Macrostemonis Bulbus alone, the combination significantly decreased the plaque area of aortic sinus(P<0.05) and collagen area(P<0.05). Metabolomics revealed 16 biomarkers in mice. Trichosanthis Fructus re-gulated the abnormal levels of 4 metabolites in glycerophosphatide metabolic pathway. Allii Macrostemonis Bulbus modulated the abnormal levels of 2 metabolites in arachidonic acid metabolic pathway and the combination recovered the levels of 8 metabolites in glycerophosphatide, linoleic acid, arachidonic acid, and pyrimidine metabolic pathways. Network pharmacology suggested that Trichosanthis Fructus regulated 24 targets which related to 2 AS-associated metabolites and involved glycerophosphatide metabolic pathway. Allii Macroste-monis Bulbus modulated 40 targets which related to 2 AS-associated metabolites and involved the arachidonic acid metabolic pathway. The combination regulated 57 targets which related to 6 AS-metabolites and involved linoleic acid metabolic pathway, glycerophosphatide metabolic pathway, and arachidonic acid metabolic pathway. These results indicate that the Trichosanthis Fructus-Allii Macrostemonis Bulbus combination enhances the regulation of linoleic acid metabolism, glycerophosphatide metabolism, and arachido-nic acid metabolism, thereby synergistically alleviating lipid disorder and inflammatory response in AS mice.

Detection for ship by dual-polarization imaging radiometer.

Passive millimeter wave (PMMW) imagers are increasingly becoming practical sensor candidates for target detection tasks. This paper is devoted to the ship detection by land-based W band passive polarized imager. The radiation characteristics of sky, sea surface and the atmospheric absorption characteristics of sea area near Qingdao are calculated based on sounding data. And the W band radiation characteristic of painted metal is measured. Then, the experiments of detection for sea surface ship are carried out in different ranges including 2,5, and 15 kilometers. The results show that land-based PMMW imager can detect and locate ship target from sea surface more than tens of kilometers away in thick fog, and polarization selection has influence on detection performance.