Targeted inhibition of the HNF1A/SHH axis by triptolide overcomes paclitaxel resistance in non-small cell lung cancer.

Paclitaxel resistance is associated with a poor prognosis in non-small cell lung cancer (NSCLC) patients, and currently, there is no promising drug for paclitaxel resistance. In this study, we investigated the molecular mechanisms underlying the chemoresistance in human NSCLC-derived cell lines. We constructed paclitaxel-resistant NSCLC cell lines (A549/PR and H460/PR) by long-term exposure to paclitaxel. We found that triptolide, a diterpenoid epoxide isolated from the Chinese medicinal herb Tripterygium wilfordii Hook F, effectively enhanced the sensitivity of paclitaxel-resistant cells to paclitaxel by reducing ABCB1 expression in vivo and in vitro. Through high-throughput sequencing, we identified the SHH-initiated Hedgehog signaling pathway playing an important role in this process. We demonstrated that triptolide directly bound to HNF1A, one of the transcription factors of SHH, and inhibited HNF1A/SHH expression, ensuing in attenuation of Hedgehog signaling. In NSCLC tumor tissue microarrays and cancer network databases, we found a positive correlation between HNF1A and SHH expression. Our results illuminate a novel molecular mechanism through which triptolide targets and inhibits HNF1A, thereby impeding the activation of the Hedgehog signaling pathway and reducing the expression of ABCB1. This study suggests the potential clinical application of triptolide and provides promising prospects in targeting the HNF1A/SHH pathway as a therapeutic strategy for NSCLC patients with paclitaxel resistance. Schematic diagram showing that triptolide overcomes paclitaxel resistance by mediating inhibition of the HNF1A/SHH/ABCB1 axis.

CXCR4 and TYROBP mediate the development of atrial fibrillation via inflammation.

Atrial fibrillation (AF) is a rapid supraventricular arrhythmia. However, the pathogenesis of atrial fibrillation remains controversial. We obtained transcriptome expression profiles GSE41177, GSE115574 and GSE79768 from GEO database. WGCNA was performed, DEGs were screened, PPI network was constructed using STRING database. CTD database was used to identify the reference score of hub genes associated with cardiovascular diseases. Prediction of miRNAs of hub genes was performed by TargetScan. DIANA-miRPath v3.0 was applied to make functional annotation of miRNA. The animal model of atrial fibrillation was constructed, RT-PCR was used to verify the expression of hub genes. Immunofluorescence assay for THBS2 and VCAN was made to identify molecular. Design of BP neural network was made to explore the prediction relationship of CXCR4 and TYROBP on AF. The merged datasets contained 104 up-regulated and 34 down-regulated genes. GO and KEGG enrichment analysis results of DEGs showed they were mainly enriched in 'regulation of release of sequestered calcium ion into cytosol', 'actin cytoskeleton organization' and 'focal adhesion'. The hub genes were CXCR4, SNAI2, S100A4, IGFBP3, CSNK2A1, CHGB, VCAN, APOE, C1QC and TYROBP, which were up-regulated expression in the AF compared with control tissues. There was strong correlation among the CXCR4, TYROBP and AF based on the BP neural network. Through training, best training performance is 9.6474e-05 at epoch 14, and the relativity was 0.99998. CXCR4 and TYROBP might be involved in the development of atrial fibrillation by affecting inflammation-related signalling pathways and may serve as targets for early diagnosis and preventive treatment.

A possible new activator of PI3K-Huayu Qutan Recipe alleviates mitochondrial apoptosis in obesity rats with acute myocardial infarction.

Obesity, which has unknown pathogenesis, can increase the frequency and seriousness of acute myocardial infarction (AMI). This study evaluated effect of Huayu Qutan Recipe (HQR) pretreatment on myocardial apoptosis induced by AMI by regulating mitochondrial function via PI3K/Akt/Bad pathway in rats with obesity. For in vivo experiments, 60 male rats were randomly divided into 6 groups: sham group, AMI group, AMI (obese) group, 4.5, 9.0 and 18.0 g/kg/d HQR groups. The models fed on HQR with different concentrations for 2 weeks before AMI. For in vitro experiments, the cardiomyocytes line (H9c2) was used. Cells were pretreated with palmitic acid (PA) for 24 h, then to build hypoxia model followed by HQR-containing serum for 24 h. Related indicators were also detected. In vivo, HQR can lessen pathohistological damage and apoptosis after AMI. In addition, HQR improves blood fat levels, cardiac function, inflammatory factor, the balance of oxidation and antioxidation, as well as lessen infarction in rats with obesity after AMI. Meanwhile, HQR can diminish myocardial cell death by improving mitochondrial function via PI3K/Akt/Bad pathway activation. In vitro, HQR inhibited H9c2 cells apoptosis, improved mitochondrial function and activated the PI3K/Akt/Bad pathway, but effects can be peripeteiad by LY294002. Myocardial mitochondrial dysfunction occurs following AMI and can lead to myocardial apoptosis, which can be aggravated by obesity. HQR can relieve myocardial apoptosis by improving mitochondrial function via the PI3K/Akt/Bad pathway in rats with obesity.

Flexible MXene-Based Composite Films: Synthesis, Modification, and Applications as Electrodes of Supercapacitors.

MXenes, as a 2D planar structure nanomaterial, were first reported in 2011. Due to their large specific surface area, high ductility, high electrical conductivity, strong hydrophilic surface, and high mechanical flexibility, MXenes have been extensively explored in the development of various functional materials with desired performances. This review is aimed to summarize the current progress in synthesis, modification, and applications of MXene-based composite films as electrode materials of flexible energy storage devices. In the synthesis of MXenes, the evolution and exploration of etchants are emphasized. Furthermore, in order to develop MXene-based composite films, the components used to modify the MXene nanoflakes, including 0D, 1D, and 2D nanomaterials, are summarized, and the perspectives and research direction of such materials are also discussed.

Bioinformatics analysis of gene and microRNA targets for fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is the most common chronic pain disease in middle-aged women. Patients may also complain of migraine, irritable bowel syndrome and depression, which seriously affect their work and life, causing huge economic losses to society. However, the pathogenesis of FM is still controversial and the effect of the current treatment is far from satisfactory. METHODS: Differentially expressed genes (DEGs) and miRNAs (DEMs) were found between FM and normal blood samples. The pathway and process enrichment analysis of the genes were performed. Protein-protein interaction network were constructed. Hub genes were found and analysed in The Comparative Toxicogenomics Database. RESULTS: A total of 102 genes were up-regulated and 46 down-regulated, 206 miRNAs down-regulated, and 15 up-regulated in FM. CD38, GATM, HDC, FOS were found as canditate genes. These genes were significantly associated with musculoskeletal disease, mental disorder, immune system disease. There was partial overlap between metformin therapy-related genes and FM-related genes. CONCLUSIONS: We found DEGs and DEMs in FM patients through bioinformatics analysis, which may be involved in the occurrence and development of FM and serve as potential targets for diagnosis and treatment.

Identification of biomarkers in macrophages of atherosclerosis by microarray analysis.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) refers to a series of diseases caused by atherosclerosis (AS). It is one of the most important causes of death worldwide. According to the inflammatory response theory, macrophages play a critical role in AS. However, the potential targets associated with macrophages in the development of AS are still obscure. This study aimed to use bioinformatics tools for screening and identifying molecular targets in AS macrophages. METHODS: Two expression profiling datasets (GSE7074 and GSE9874) were obtained from the Gene Expression Omnibus dataset, and differentially expressed genes (DEGs) between non-AS macrophages and AS macrophages were identified. Functional annotation of the DEGs was performed by analyzing the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. STRING and Cytoscape were employed for constructing a protein-protein interaction network and analyzing hub genes. RESULTS: A total of 98 DEGs were distinguished between non-AS macrophages and AS macrophages. The functional variations in DEGs were mainly enriched in response to hypoxia, respiratory gaseous exchange, protein binding, and intracellular, ciliary tip, early endosome membrane, and Lys63-specific deubiquitinase activities. Three genes were identified as hub genes, including KDELR3, CD55, and DYNC2H1. CONCLUSION: Hub genes and DEGs identified by using microarray techniques can be used as diagnostic and therapeutic biomarkers for AS.

Phase Transformation of GeO2 Glass to Nanocrystals under Ambient Conditions.

Theoretically, the accomplishment of phase transformation requires sufficient energy to overcome the barriers of structure rearrangements. The transition of an amorphous structure to a crystalline structure is implemented traditionally by heating at high temperatures. However, phase transformation under ambient condition without involving external energy has not been reported. Here, we demonstrate that the phase transformation of GeO2 glass to nanocrystals can be triggered at ambient conditions when subjected to aqueous environments. In this case, continuous chemical reactions between amorphous GeO2 and water are responsible for the amorphous-to-crystalline transition. The dynamic evolution process is monitored by using in situ liquid-cell transmission electron microscopy, clearly revealing this phase transformation. It is the hydrolysis of amorphous GeO2 that leads to the formation of clusters with a size of ∼0.4 nm, followed by the development of dense liquid clusters, which subsequently aggregate to facilitate the nucleation and growth of GeO2 nanocrystals. Our finding breaks the traditional understanding of phase transformation and will bring about a significant revolution and contribution to the classical glass-crystallization theories.

The more critical murderer of atherosclerosis than lipid metabolism: chronic stress.

BACKGROUND: The mortality of atherosclerotic cerebrovascular disease is on the rise, and changes in intimal and media thickness are a leading cause of cerebral ischemia-related death. Levels of low density lipoprotein cholesterol (LDLC), total cholesterol (TC), and chronic stress (CS) are all recognized risk factors for atherosclerosis (AS). However, the leading independent risk factor is indistinct. This study explored the effects of chronic stress, LDLC, and TC on AS and intimal and media thickness, preliminarily explored the main risk factor of AS, and analyzed the related histocyte mechanisms for macrophages and endothelial cells. METHODS: Conditions include normal, high-fat diet (HF), and HF plus CS. The correlations between intimal and media thickness and general risk factors were analyzed using χ2, Spearman's rho test, and multiple linear regression. Univariate Cox regression was used to identify potential factors that affect the non-depression time (NDT). We performed a ROC curve to determine the ability of this condition to predict the thickness. Immunohistochemistry was implemented to detect macrophagocytes and endotheliocytes. RESULTS: Based on χ2 and Spearman's rho test, LDLC, TC, and CS are all related with intimal and media thickness (P < 0.05). However, in multiple linear regression, CS is still a risk factor of thickness (P < 0.05) but LDLC and TC are not. High levels of LDLC, TC, and CS were correlated with poor NDT (P < 0.05). This condition can predict the thickness sensitively. The endarterium is richest in macrophagocytes, and the arrangement of endotheliocytes is disordered and cracked under CS. CONCLUSION: CS is the main independent risk factor for AS and intimal (and media) thickness, rather than LDLC or TC.

Tlr22 structure and expression characteristic of barbel chub, Squaliobarbus curriculus provides insights into antiviral immunity against infection with grass carp reovirus.

Grass carp reovirus (GCRV) is the most virulent agent to Grass carp, Ctenopharyngodon idella, and causes a severe infectious disease called hemorrhagic disease of grass carp. Generally, barbel chub, Squaliobarbus curriculus, a genetically closely related species to grass carp, exhibits significant resistance against GCRV infection compared to grass carp. To investigate whether the Toll-like receptor 22 (tlr22) has got a vital role against the GCRV infection, the full cDNA sequence of tlr22 from barbel chub (Sctlr22) was cloned by RACE-PCR, and the structure and expression feature were studied. The complete cDNA sequence of Sctlr22 has a size of 3504 bp, encoding for 960 amino acid residues. Sctlr22 possesses typical structural features of the tlrs family, including 19 leucine rich repeats (LRRs), a transmembrane (TM) and a Toll/interleukin-1 receptor (TIR) domain. Phylogenetic analysis revealed that barbel chub Tlr22 was clustered together with the Tlr22 of grass carp (Citlr22). Structurally, barbel chub Tlr22 have two different structure in LRRs domain and TIR domain with grass carp (Susceptible to GCRV), but was similar to that of Danio rerio and Cyprinus carpio (Resistance to GCRV). Quantitative RT-PCR analysis has shown that Sctlr22 is prominently expressed in immune relevant tissues such as head kidney and spleen. After GCRV infection, Sctlr22 expression level was up-regulated in four tested tissues and the highest expression of Sctlr22 appeared fast and higher than Citlr22. The interferon-ß (ifn-ß) expression level in CIK cells over-expressing fused cDNA encoding the LRR domain of Sctlr22 to the transmembrane and TIR domain of Citlr22 was significantly higher than that cells overexpressing Citlr22 after GCRV infection. The virus titer was significantly reduced compared to Citlr22 over-expressing cells. These results suggested that Sctlr22 seems to play a vital role in the immune response against GCRV.

Multiplicative interaction between mean corpuscular volume and red cell distribution width with target organ damage in hypertensive patients.

BACKGROUND: Accumulating evidence suggests that increased red cell distribution width (RDW) and mean corpuscular volume (MCV) were both poor prognostic factors for patients with cardiovascular diseases. Recently, the multiplicative interaction between RDW and MCV has been observed for predicting mortality in elderly patients without anemia; however, the relationship between the product of RDW-MCV and hypertension-induced target organ damage (TOD) has not been evaluated. METHODS: We performed a cross-sectional study in 1115 hypertensive patients. RDW and MCV were determined using automated hematology analyzers. Prevalence of TOD was evaluated by estimated glomerular filtration rate, carotid intima-media thickness, and left ventricular mass index. RESULTS: The prevalence of TOD was observed to be increased with the RDW or product of RDW-MCV quartiles. Moreover, RDW, MCV and product of RDW-MCV were significantly higher in patients with TOD compared to those without TOD. According to two logistic regression models, the associations of RDW and MCV with TOD were lost after adjustment for other factors. However, product of RDW-MCV remains an independent predictor of TOD, with per 0.4 fL increase in the product of RDW-MCV associated with a 16% increased risk of TOD (P=.012). CONCLUSIONS: The inclusion of MCV by calculating the product of RDW-MCV appears to enhance the association of RDW with TOD.

De novo annotation of the immune-enriched transcriptome provides insights into immune system genes of Chinese sturgeon (Acipenser sinensis).

Chinese sturgeon (Acipenser sinensis), one of the oldest extant actinopterygian fishes with very high evolutionary, economical and conservation interest, is considered to be one of the critically endangered aquatic animals in China. Up to date, the immune system of this species remains largely undetermined with little sequence information publicly available. Herein, the first comprehensive transcriptome of immune tissues for Chinese sturgeon was characterized using Illumina deep sequencing. Over 67 million high-quality reads were generated and de novo assembled into the final set of 91,739 unique sequences. The annotation pipeline revealed that 25,871 unigenes were successfully annotated in the public databases, of which only 2002 had significant match to the existing sequences for the genus Acipenser. Overall 22,827 unigenes were categorized into 52 GO terms, 12,742 were classified into 26 KOG categories, and 4968 were assigned to 339 KEGG pathways. A more detailed annotation search showed the presence of a notable representation of immune-related genes, which suggests that this non-teleost actinopterygian fish harbors the same intermediates as in the well known immune pathways from mammals and teleosts, such as pattern recognition receptor (PRR) signaling pathway, JAK-STAT signaling pathway, complement and coagulation pathway, T-cell receptor (TCR) and B-cell receptor (BCR) signaling pathways. Additional genetic marker discovery led to the retrieval of 20,056 simple sequence repeats (SSRs) and 327,140 single nucleotide polymorphisms (SNPs). This immune-enriched transcriptome of Chinese sturgeon represents a rich resource that adds to the currently nascent field of chondrostean fish immunogenetics and furthers the conservation and management of this valuable fish.

Incidence and molecular basis of CD36 deficiency in Shanghai population.

BACKGROUND: CD36 is a multifunctional membrane receptor and is expressed in several cell lines. Individuals who lack platelet (PLT) CD36 are at risk for immunization against this antigen, leading to several clinical syndromes. This study aimed to investigate the frequency and molecular basis of CD36 deficiency in Shanghai. STUDY DESIGN AND METHODS: Whole blood samples were collected from healthy blood donors, and the PLTs and monocytes were analyzed using flow cytometry to determine CD36 deficiency type. After genomic DNA was extracted, Exons 3 to 14 of CD36 gene including a part of relevant flanking introns were amplified. Direct nucleotide sequencing and sequence alignment were performed. The samples that showed mutations were confirmed by clonal sequencing. RESULTS: Of the 1022 healthy blood donors analyzed, 22 individuals failed to express CD36 on PLTs; two of them expressed no CD36 on their monocytes either. These results demonstrated that the frequencies of Type I (lacking CD36 expression on PLTs and monocytes) and Type II (lacking CD36 expression on PLTs only) CD36 deficiency among the study population were 0.2 and 2.0%, respectively. Nucleotide sequencing analysis revealed nine different mutations including six mutations that were not yet reported. The most frequent mutations among the study population were 329-330delAC and 1228-1239delATTGTGCCTATT. CONCLUSION: The study findings have confirmed the fact that the frequency of CD36 deficiency in the Chinese population is slightly lower than that in other Asian countries. The identification of several new mutation types indicated the polymorphism of CD36 gene in the Shanghai population.

The cytotoxicology of momordicins I and II on Spodoptera litura cultured cell line SL-1.

Momordicin I and II are secondary metabolites from bitter melon (Momordica charantia L.) that are toxic to the Spodoptera litura ovary cell line (SL-1 cell). Both momordicin I and II significantly inhibited SL-1 cells proliferation. IC50 values after 24 h were 8.35 and 82.31 µg/mL, 6.11 and 77.49 µg/mL for 36 h, 4.93 and 49.42 µg/mL for 48 h for cells treated by momordicin I and II, respectively. IC50 values of the azadirachtin A control were 149.63, 54.54 and 23.66 µg/mL at 24, 36 and 48 h respectively, indicating that the cytotoxicity of momordicin I was significantly higher than that of momordicin II and azadirachtin A. Using inverted phase contrast microscopy we found that after 24 h exposure to momordicin I and II, cell shapes changed to circular, swelling increased, adherence ability declined and the cellular membrane bubbled. After 48 h exposure to momordicin I, most cells were suspended and dead; vacuole deformation and cytoplasm leakage indicated that momordicin I was more toxic to the cytoskeleton than momordicin II. Cells treated with momordicin I and II inhibited glucose absorption by 23.04 and 13.38% after 48 h and 47.60 and 20.92% after 60 h. Flow cytometry analysis suggested that SL-1 cells treated with momordicin I and II dramatically accumulated during the G2/M phase of the cell cycle, and total cell protein content increased by 56.93 and 35.81% respectively after 48 h treatment. Following treatment with momordicin I and II the karyotheca dissolved, the chromatin condensed abnormally and the nucleoli were damaged, migrated, or disappeared. The PI fluorescent value by FCM showed that the relative fluorescent intensity of SL-1 cells induced by momordicin I and II increased to 521.45 and 370.17, higher than 135.04 induced by control group treatment for 48 h. This indicated significant damage to the cytomembrane. Overall, the results demonstrate that suppression of cytoskeletal function, interference of mitotic figures and destruction of nuclear structure are effects of momordicin I and II exposure. These effects play major roles in momordicin I and II inhibition of SL-1 cells growth. The mode of action by which momordicins inhibit insect cell growth and development may be useful in the development of novel pest control formulations containing cucurbitane-type triterpene glycosides.

Alleviating pain hypersensitivity through activation of type 4 metabotropic glutamate receptor.

Hyperactivity of the glutamatergic system is involved in the development of central sensitization in the pain neuraxis, associated with allodynia and hyperalgesia observed in patients with chronic pain. Herein we study the ability of type 4 metabotropic glutamate receptors (mGlu4) to regulate spinal glutamate signaling and alleviate chronic pain. We show that mGlu4 are located both on unmyelinated C-fibers and spinal neurons terminals in the inner lamina II of the spinal cord where they inhibit glutamatergic transmission through coupling to Cav2.2 channels. Genetic deletion of mGlu4 in mice alters sensitivity to strong noxious mechanical compression and accelerates the onset of the nociceptive behavior in the inflammatory phase of the formalin test. However, responses to punctate mechanical stimulation and nocifensive responses to thermal noxious stimuli are not modified. Accordingly, pharmacological activation of mGlu4 inhibits mechanical hypersensitivity in animal models of inflammatory or neuropathic pain while leaving acute mechanical perception unchanged in naive animals. Together, these results reveal that mGlu4 is a promising new target for the treatment of chronic pain.

Caucasian origin of disease associated HLA haplotypes in chinese blood donors with IgA deficiency.

PURPOSE: Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Caucasians with a prevalence of 1:600. However, the prevalence of IgAD is markedly lower in East Asian countries but no genetic studies have been performed on IgAD individuals in the Mongoloid population. METHODS: We investigated the prevalence of IgAD in a large number of Chinese blood donors (n = 39,015) in Shanghai, China. We measured immunoglobulin class, IgG subclass and anti-IgA serum levels among the IgAD donors. These donors were subsequently tissue typed and the allele frequency was compared with the Shanghai bone marrow donor HLA registry. RESULTS: Seventeen IgAD Chinese blood donors were identified, giving a prevalence of 1: 2,295. Two previously identified IgAD blood donor samples were added in the subsequent tests. Most IgAD donors had serum IgG levels above the normal range with no major IgG subclass deficiency and one donor was weakly positive for anti-IgA. Two-thirds of the Chinese IgAD donors carried Caucasian IgAD associated risk haplotypes, including DRB1*0301-DQB1*0201, DRB1*0701-DQB1*0202 and DRB1*0102-DQB1*0501, giving a significantly higher frequency of these haplotypes as compared to the Shanghai bone marrow donor HLA registry. CONCLUSIONS: The prevalence of IgAD in Chinese in this study is markedly lower than in Caucasians. This is the first study to investigate the genetics of IgAD in the Mongoloid population and two-thirds of the Chinese IgAD donors showed a mixture of Caucasian IgAD risk haplotypes. The low prevalence of IgAD could potentially be due to the low frequency of the disease associated risk haplotypes in China.

Assessment of thermal sensitivity in rats using the thermal place preference test: description and application in the study of oxaliplatin-induced acute thermal hypersensitivity and inflammatory pain models.

Thermal sensitivity is an essential characteristic of some painful states, including oxaliplatin-induced neuropathy. The thermal place preference test (TPPT) was designed to finely assess thermal sensitivity in rodents. The TPPT monitors the time spent by unrestrained rodents on a test plate at fixed temperatures (5-50°C) compared with an adjacent reference plate at a neutral temperature (25°C). Here, we report the results of a study designed (i) to validate the optimal methodological parameters for measuring thermal sensitivity in rats, (ii) to assess the thermal sensitivity of healthy rats and animal models of pain and (iii) to explore the pharmacological effects of analgesic drugs. The most reproducible conditions occurred when the TPPT was performed in the morning and in the dark for 3 min with the reference plate set to 25°C. The temperature preferences of healthy rats were more than 17°C and less than 40°C. When compared with control animals, oxaliplatin-treated rats showed thermal hypersensitivity at 12, 20 and 35°C, and carrageenan-treated rats showed thermal hypersensitivity at 15 and 45°C. Duloxetine (2.5 mg/kg, intraperitoneal) reversed oxaliplatin-induced cold hypersensitivity (20°C) and morphine (1 mg/kg, intravenous) reversed carrageenan-induced heat hypersensitivity (45°C). We conclude that the TPPT enables a fine-grained assessment of thermal sensitivity that is relevant to the pathophysiological exploration of animal pain models and to the pharmacological assessment of analgesic drugs.

Pathological and microbiological findings from mortality of the Chinese giant salamander (Andrias davidianus).

The Chinese giant salamander, Andrias davidianus, is a nationally protected and cultured species in China. Recently, a severe epizootic occurred in cultured Chinese giant salamanders in Hubei, Hunan, Sichuan, Shaanxi, and Zhejiang provinces of China, causing substantial economic losses. The typical clinical signs of diseased larval animals were jaw and abdominal swelling and subcutaneous hemorrhaging. Diseased adult animals exhibited skin hemorrhages, ulceration of the hind limbs, and multiple hemorrhagic spots in the visceral organs. Histopathological observation indicated tissue necrosis and cytoplasmic inclusions in the spleen, liver and kidney, suggestive of viral disease. A viral agent was isolated from affected tissues in cell culture. The virus was determined to be pathogenic after experimental infection. Electron microscopy revealed iridovirus-like virions with a size of 140-180 nm in diameter inside the kidney of naturally infected animals and in cell culture. The major capsid protein (MCP) of the virus exhibited 98-99 % sequence identity to ranaviruses. Additionally, phylogenetic analysis indicated that the virus belonged to the genus Ranavirus. Comparative analysis of the MCP gene sequence with those of other viruses previously isolated from Chinese giant salamanders revealed that these isolates were highly similar, although a few variations were observed. The virus was preliminarily named Chinese giant salamander iridovirus (GSIV).

Pluronic-poly (acrylic acid)-cysteine/Pluronic L121 mixed micelles improve the oral bioavailability of paclitaxel.

The aim of the study is to synthesize a thiolated Pluronic copolymer, Pluronic-poly (acrylic acid)-cysteine copolymer, to construct a mixed micelle system with the Pluronic-poly (acrylic acid)-cysteine copolymer and Pluronic L121 (PL121) and to evaluate the potential of these mixed micelles as an oral drug delivery system for paclitaxel. Compared with Pluronic-poly (acrylic acid)-cysteine micelles, drug-loading capacity of Pluronic-poly (acrylic acid)-cysteine/PL121 mixed micelles was increased from 0.4 to 2.87%. In vitro release test indicated that Pluronic-poly (acrylic acid)-cysteine/PL121 mixed micelles exhibited a pH sensitivity. The permeability of drug-loaded micelles in the intestinal tract was studied with an in situ perfusion method in rats. The presence of verapamil and Pluronic both improved the intestinal permeability of paclitaxel, which further certified the inhibition effect of thiolated Pluronic on P-gp. In pharmacokinetic study, the area under the plasma concentration-time curve (AUC0→∞) of paclitaxel-loaded mixed micelles was four times greater than that of the paclitaxel solution (p < 0.05). In general, Pluronic-poly (acrylic acid)-cysteine/PL121 micelles were proven to be a potential oral drug delivery system for paclitaxel.

Cucurbitane-type triterpenoids from the leaves of Momordica charantia.

Phytochemical investigation of the ethanol extract from the leaves of Momordica charantia L. led to the isolation of two new (1, 2) and four known (3-6) cucurbitane-type triterpenoids. Their structures were elucidated on the basis of extensive analyses of spectroscopic data including IR, UV, MS, 1D, and 2D NMR. Also the absolute configurations of momordicines I (3) and II (4) were determined for the first time by application of the modified Mosher's method, acid hydrolysis, and GC analysis.

Bmo-miR-3351 modulates glutathione content and inhibits BmNPV proliferation by targeting BmGSTe6 in Bombyx mori.

MicroRNAs (miRNAs) are small non-coding RNAs that play pivotal roles in the host response to invading pathogens. Among these pathogens, Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the main causes of substantial economic losses in sericulture, and there are relatively few studies on the specific functions of miRNAs in the B. mori-BmNPV interaction. Therefore, we conducted transcriptome sequencing to identify differentially expressed (DE) messenger RNAs (mRNAs) and miRNAs in the midgut of 2 B. mori strains (BmNPV-susceptible strain P50 and BmNPV-resistant strain A35) after BmNPV infection. Through correlation analysis of the miRNA and mRNA data, we identified a comprehensive set of 21 miRNAs and 37 predicted target mRNAs. Notably, miR-3351, which has high expression in A35, exhibited remarkable efficacy in suppressing BmNPV proliferation. Additionally, we confirmed that miR-3351 binds to the 3' untranslated region (3' UTR) of B. mori glutathione S-transferase epsilon 6 (BmGSTe6), resulting in its downregulation. Conversely, BmGSTe6 displayed an opposite expression pattern to miR-3351, effectively promoting BmNPV proliferation. Notably, BmGSTe6 levels were positively correlated with glutathione S-transferase activity, consequently influencing intracellular glutathione content in the infected samples. Furthermore, our investigation revealed the protective role of glutathione against BmNPV infection in BmN cells. In summary, miR-3351 modulates glutathione content by downregulating BmGSTe6 to inhibit BmNPV proliferation in B. mori. Our findings enriched the research on the role of B. mori miRNAs in the defense against BmNPV infection, and suggests that the antiviral molecule, glutathione, offers a novel perspective on preventing viral infection in sericulture.