UCHL3 promotes cervical cancer development and metastasis by stabilizing NRF2 via deubiquitination.

Cervical cancer is one of the most lethal gynaecological malignancies in females. The deubiquitylase UCHL3 has been studied as an oncogenic factor in multiple cancers. However, the expression pattern and function profile of UCHL3 in cervical cancer hasn't been fully characterized. Here, we revealed that UCHL3 was highly expressed in cervical cancer and overexpressed UCHL3 predicted a poor survival probability in cervical cancer patients. Our findings showed that knockdown of UCHL3 inhibited cell growth, migration and invasion in cervical cancer cells while UCHL3 knockdown inhibited cervical cancer development and metastasis in vivo in mouse models. Mechanistically, co-immunoprecipitation assay showed that UCHL3 directly interacted with NRF2. Knockdown of UCHL3 decreased NRF2 expression while overexpression of UCHL3 stabilized NRF2 via deubiquitination. In addition, overexpression of UCHL3 with C92A mutation didn't affect NRF2 stability. Moreover, we revealed that overexpression of NRF2 could antagonize the function of UCHL3 knockdown in cervical cancer cells. Collectively, our findings suggest that UCHL3 promotes cervical cancer development and metastasis by stabilizing NRF2 via deubiquitination. Thus, UCHL3/NRF2 axis could be utilized to develop efficient treatments for cervical cancer patients.

LncRNA AL592284.1 facilitates proliferation and metastasis of cervical cancer cells via miR-30a-5p/Vimentin/EMT axis.

OBJECTIVE: Long non-coding RNAs (lncRNAs) are implicated in cancer-related cellular behaviors. Our research aimed to explore the biological functions of lncRNA AL592284.1 (AL592284.1) in cervical cancer (CC). METHODS: qRT-PCR was performed to examine AL592284.1 expressions in cell lines and tumor specimens. To study the roles of AL592284.1 on malignant behaviors in both in vitro and in vivo, Loss-of-function assays were carried out. Besides, bioinformatics prediction and dual-luciferase reporter assays were performed to reveal the interaction among AL592284.1 and its target genes. The functions of the AL592284.1/miR-30a-5p/Vimentin axis in CC cells was clarified by rescue assays. RESULTS: We observed that the levels of AL592284.1 in CC were distinctly increased. Functional assays revealed that knockdown of AL592284.1 suppressed the proliferation, migration, invasion and EMT progress of CC cells. Luciferase reporter assay confirmed that miR-30a-5p/Vimentin regulatory axis is the direct downstream of AL592284.1. Rescue experiments indicated that AL592284.1 induced overexpression of Vimentin via sponging miR-30a-5p, resulting in the promotion of CC progression. CONCLUSION: The present study proves that AL592284.1 plays an tumor-promotive role in CC via regulating the miR-30a-5p/Vimentin axis, and inhibition of AL592284.1 may pave the way for CC treatment.

Synthesis, insecticidal evaluation and mode of action of novel anthranilic diamide derivatives containing sulfur moiety as potential ryanodine receptor activators.

Anthranilic diamide insecticide could control lepidopteran pests by selectively binding and activating insect ryanodine receptors (RyRs), and the unique mode of action is different from other conventional insecticides. In order to discover new anthranilic diamide insecticide as ryanodine receptors activators, a series of 11 novel anthranilic diamides derivatives (Ia-k) were synthesized and confirmed by melting point, 1H NMR, 13C NMR and elemental analyses. The preliminary bioactivity revealed that most title compounds showed moderate to remarkable activities against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella). Especially, compounds Ia and If, which exhibited 100% larvicidal activity against oriental armyworm at 1.0 mg L-1, and comparable to that of chlorantraniliprole (100% at 1 mg L-1). If displayed 60% insecticidal activity against diamondback moth at 0.01 mg L-1, better than chlorantraniliprole (45% at 0.01 mg L-1). The preliminary structure activity relationships were discussed. In addition, the calcium imaging experiment indicated that the insect ryanodine receptor is the potential target of If.

(R)-2-Phenyl-4,5-Dihydrothiazole-4-Carboxamide Derivatives Containing a Diacylhydrazine Group: Synthesis, Biological Evaluation, and SARs.

A series of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a diacylhydrazine moiety were designed and synthesized. Their structures were confirmed by melting points, 1H NMR, 13C NMR, and elemental analysis (EA). Their antifungal and insecticidal activities were evaluated. The antifungal activity result indicated that most title compounds against Cercospora arachidicola, Alternaria solani, Phytophthora capsici, and Physalospora piricola exhibited apparent antifungal activities at 50 mg/L, and better than chlorothalonil or carbendazim. The EC50 values of (R)-N'-benzoyl-2-(4-chlorophenyl)-4,5-dihydrothiazole-4-carbohydrazide (I-5) against six tested phytopathogenic fungi were comparable to those of chlorothalonil. The CoMSIA model showed that a proper hydrophilic group in the R1 position, as well as a proper hydrophilic and electron-donating group in the R2 position, could improve the antifungal activity against Physalospora piricola, which contributed to the further optimization of the structures. Meanwhile, most title compounds displayed good insecticidal activities, especially compound (R)-N'-(4-nitrobenzoyl)-2-(4-nitrophenyl)-4,5-dihydrothiazole-4-carbohydrazide (III-3). The insecticidal mechanism results indicated that compound III-3 can serve as effective insect Ca2+ level modulators by disrupting the cellular calcium homeostasis in Mythimna separata.

Anthranilic diamides derivatives as potential ryanodine receptor modulators: Synthesis, biological evaluation and structure activity relationship.

A series of novel anthranilic diamides derivatives (7a-s) containing halogen, trifluoromethyl group and cyano group were designed, synthesized, and characterized by melting point, 1H NMR, 13C NMR and elemental analyses. The bioactivity revealed that most of them showed moderate to excellent activities against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella). Above all, the larvicidal activity of 7o against oriental armyworm was 100% and 40% at 0.25 and 0.1 mg L-1, comparable to that of the standard chlorantraniliprole (100%, 0.25 mg L-1 and 20%, 0.1 mg L-1). What is more, 7o against diamondback moth displayed 90% insecticidal activity at 0.01 mg L-1, superior to chlorantraniliprole (45%, 0.01 mg L-1). The experiments 7o on the American cockroach (Periplaneta Americana) heart beating rates (Dorsal vessel) and contractile force were compared with chlorantraniliprole. In addition, 7o could affect the calcium homeostasis in the central neurons of the third larvae of oriental armyworm, which revealed that the ryanodine receptor is the potential target of 7o. The density functional theory (DFT) calculation results revealed the amide bridge, the benzene ring of anthraniloyl moiety and pyrazole ring might play an important role in the insecticidal activity through hydrophobic interactions and π-π conjugations.

Dichapetalin-type triterpenoids from Dichapetalum longipetalum and their anti-inflammatory activity.

A phytochemical research on the twigs of Dichapetalum longipetalum (Turcz.) Engl. Resulted in five undescribed dichapetalin-type triterpenoids 1-5. Their chemical structures were determined by spectroscopic analysis of HR-ESIMS and NMR spectra and the absolute configuration of compound 1 was completely elucidated by single crystal X-ray crystallography. Through preliminary anti-inflammatory activity assessment, compound 1 exhibited inhibitory effect on LPS-induced NO production in RAW264.7 murine macrophages with an IC50 value of 2.09 µM.

Molecular epidemiological survey of hemoglobinopathies in the Wuxi region of Jiangsu Province, eastern China.

In order to determine the prevalence and molecular characterization of hemoglobinopathies in the Wuxi region of Jiangsu Province in the People's Republic of China (PRC), a total of 10,297 healthy people selected from a regional hospital were screened. Hemoglobin (Hb) electrophoresis, complete blood cell (CBC) count, polymerase chain reaction (PCR), DNA sequencing, reverse dot-blot and multiplex ligation-dependent probe amplification (MLPA) were used to detect Hb variants, thalassemias and hereditary persistence of fetal Hb (HPFH). Two thousand and twenty-one adult subjects were screened for thalassemia, five cases were identified as α-thalassemia (α-thal) carriers including three cases of the -α(3.7) (rightward) deletion, one case of the - -(SEA) deletion and one case of ß-thal [IVS-II-654 (C>T), (HBB: c.316-197C>T)]. The incidence of Hb variants, thalassemia and HPFH/δß-thal were 0.136% (14/10,297), 0.25% (5/2021) and 0.0001% (1/10,297), respectively. Eight genotypes of Hb variants were found, including Hb E [ß26(B8)Glu→Lys, GAG>AAG; HBB: c.79G>A], Hb J-Bangkok [ß56(D7)Gly→Asp (GGC>GAC); HBB; c.170G>A], Hb G-Coushatta [ß22(4)Glu→Ala (GAA>GCA); HBB: c.68A>C], Hb Queens [α34(B15)Leu→Arg (CTG>CGG) (α2 or α1); HBA2: c.104T>G (or HBA1)], Hb I [α16(A14)Lys→Glu, AAG>GAG (α1); HBA1: c.49A>G], Hb Beijing [α16(A14)Lys→Asn (AAG>AAC or AAT) (α2 or α1); HBA2: c.51G>C (or HBA1) or 51G>T (or HBA1)], Hb Ube-2 [α68(E17)Asn→Asp (AAC>GAC) (α2 or α1); HBA2: c.205A>G (or HBA1)] and Hb G-Taipei [ß22(B4)Glu→Gly (GAA>GGA); HBB: c.68A>G]. A Sicilian δß(0)-thal, identified for the first time in Asia, was also found in this survey.

Optimisation of antioxidant peptide preparation from corn gluten meal.

BACKGROUND: Corn gluten meal, containing approximately 600 g kg(-1) protein, is a main by-product of corn wet milling. The annual output of corn gluten meal in China is over 840 000 tons. However, it is difficult to utilise corn gluten meal in the food industry because of its low water solubility and amino acid imbalance. In the present study, corn gluten meal was hydrolysed by different proteases to produce hydrolysates with antioxidant activity in order to increase its value. The hydrolysis conditions were optimised by multiple linear regression and response surface methodology. Furthermore, the amino acid sequence of one corn peptide was determined. RESULTS: The optimal conditions for alkaline protease hydrolysis were a pH of 9.5, an enzyme/substrate (E/S) ratio of 8 g per 100 g, a liquid/solid ratio of 25 mL g(-1) and a time of 75 min, while the optimal conditions for flavourzyme hydrolysis were a pH of 7, an E/S ratio of 4.2 g per 100 g and a time of 66 min. After gel filtration chromatography, fraction F2 exhibited the highest antioxidant activities. The amino acid sequence of a purified peptide in fraction F2 was determined as Gly-His-Lys-Pro-Ser (507.2 Da). CONCLUSION: The results indicate that corn gluten meal hydrolysates and/or its isolated peptides are potent antioxidants.

[A study of in vitro activity of daptomycin against 2679 Gram-positive cocci].

OBJECTIVE: To evaluate the in vitro activity of daptomycin against 2679 Gram-positive cocci. METHODS: A total of 2679 non-duplicate Gram-positive cocci isolates were collected from 17 teaching hospitals during January, 2010 and December, 2011. The minimal inhibitory concentrations (MICs) of daptomycin and other anti-microbial agents against 4 Gram-positive cocci were determined by micro-broth dilution method and agar dilution respectively. The data of drug susceptibility were analyzed by WHONET5.6 software. RESULTS: Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococci (MRSCoN) detection rates were 45.8% and 84.2%, respectively. The susceptibility rates of sulfamethoxazole, chloramphenicol, erythromycin, tetracycline, clindamycin and rifampicin against MRSA were 93.1%, 85.5%, 13.8%, 26.6%, 63.2% and 50.0%, respectively. The susceptibility rates of daptomycin, vancomycin and linezolid against MRSA and MRSCoN were all 100.0%. The daptomycin MIC50 and MIC90 of MRSCoN and MRSA were 0.5 mg/L. The high level gentamicin resistance rate of 513 Enterococci isolates was 56.9%. The susceptibility rates of chloramphenicol and tetracycline were 76.0% and 44.1%, respectively. The susceptibility rates of tigecycline and daptomycin reached 100.0%. The MIC50 and MIC90 of daptomycin against 17 vancomycin-resistant Enterococci (VRE) were both 2 mg/L. The susceptibility rates of daptomycin against Streptococcus pneumoniae and ß-hemolytic Streptococcus were 100.0%. The prevalence of penicillin-nonsusceptible Streptococcus pneumoniae (PNSSP) was 63.1%. The MIC50 and MIC90 of daptomycin against PNSSP were 0.125 mg/L and 0.25 mg/L, respectively according to the breakpoint of oral penicillin. The MIC50 and MIC90 daptomycin against ß-hemolytic Streptococci were 0.008 mg/L and 0.032 mg/L. CONCLUSIONS: Daptomycin have excellent in vitro activity against common Gram-positive cocci, including multi-drug resistant bacteria. It may be a good choice for clinicians to treat drug-resistant Gram-positive cocci.

Unusual presentation of systemic lupus erythematosus as hemophagocytic lymphohistiocytosis in a female patient: A case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disorder, often resulting in the immune-mediated injury of multiple organ systems, including primary HLH and secondary HLH (sHLH). Among them, sHLH results from infections, malignant, or autoimmune conditions, which have quite poor outcomes even with aggressive management and are more common in adults. CASE SUMMARY: We report a rare case of a 36-year-old female manifested with sHLH on background with systemic lupus erythematosus (SLE). During hospitalization, the patient was characterized by recurrent high-grade fever, petechiae and ecchymoses of abdominal skin, and pulmonary infection. Whole exon gene sequencing revealed decreased activity of natural killer cells. She received systematic treatment with Methylprednisolone, Etoposide, and anti-infective drugs. Intravenous immunoglobulin and plasmapheresis were applied when the condition was extremely acute and progressive. The patient recovered and did not present any relapse of the HLH for one year of follow-up. CONCLUSION: The case showed sHLH, thrombotic microvascular, and infection in the whole course of the disease, which was rarely reported by now. The treatment of the patient emphasizes that early recognition and treatment of sHLH in SLE patients was of utmost importance to improve the prognosis and survival rate of patients.

Trehalose prevents glyphosate-induced testicular damage in roosters via its antioxidative properties.

Glyphosate (GLY), an active ingredient of the most commonly used herbicide, when in crops and feed, is deleterious to male reproductive health. Trehalose (Tre), a naturally non-reducing disaccharide, is shown to counteract the adverse stresses due to its antioxidation effect. Thus, this study was designed to investigate whether Tre can improve GLY-induced testicular damage via suppressing oxidative stress. 60 healthy Hy-Line Brown breeder roosters were utilized to assess the protective effects of Tre supplementation against testicular oxidative damage caused by GLY. Data showed that Tre administration significantly alleviated GLY- induced reduction in testis weight, decreased GLY level in the testis tissues, and alleviated GLY-caused testicular pathological damage. Concurrently, GLY treatment significantly elevated serum malondialdehyde (MDA) and testicular reactive oxygen species (ROS) levels, decreased serum total anti-oxidation capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, which were all notably reversed by Tre administration. Moreover, GLY- inhibited nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in rooster testis, a master regulator of oxidative stress, was markedly recovered by Tre administration. In summary, these findings demonstrated that Tre can prevent GLY-induced testicular damage in roosters by ameliorating oxidative stress.

Glyphosate damages blood-testis barrier via NOX1-triggered oxidative stress in rats: Long-term exposure as a potential risk for male reproductive health.

Blood-testis barrier (BTB) creates a privileged niche indispensable for spermatogenesis. Glyphosate (GLY), the most commonly used herbicide worldwide, has been reported to decrease sperm quality. However, whether and how GLY destroys the BTB to affect sperm quality remains to be elucidated. Herein, this study was designed to investigate the influence of GLY on the BTB in vivo and in vitro experiments. The results showed that male rats exposed to GLY for 4 months exhibited a decrease in sperm quality and quantity, accompanied by BTB integrity disruption and testicular oxidative stress. Additionally, GLY-induced reactive oxygen species (ROS) contributed to the downregulation of BTB-related proteins in primary Sertoli cells (SCs). Intriguingly, we identified a marked upregulation of oxidative stress-related gene NOX1 in GLY-exposed testis based on transcriptome analysis. NOX1 knockdown blocked the GLY-induced oxidative stress, as well as prevented BTB-related protein decrease in SCs. Furthermore, the estrogen receptor (ER)-α was significantly upregulated in vivo and in vitro models. An ER-α inhibitor decreased the expression levels of both ER-α and NOX1. Mechanistically, GLY directly interacted with ER-α at the site of Pro39 and Lys401 to promote ER-α activation, which boosted NOX1 expression to trigger ROS accumulation. Collectively, these results demonstrate that long-term GLY exposure adversely affects BTB integrity, which disrupts spermatogenesis via activation of ER-α/NOX1 axis. This study presents a better understanding of the risk of long-term GLY exposure to male fertility.

Glyphosate-induced mitochondrial reactive oxygen species overproduction activates parkin-dependent mitophagy to inhibit testosterone synthesis in mouse leydig cells.

Glyphosate (GLY), one of the most extensively used herbicides in the world, has been shown to inhibit testosterone synthesis in male animals. Mitochondria are crucial organelles for testosterone synthesis and its dysfunction has been demonstrated to induce the inhibition of testosterone biosynthesis. However, whether low-dose GLY exposure targets mitochondria to inhibit testosterone synthesis and its underlying mechanism remains unclear. Here, an in vitro model of 10 µM GLY-exposed mouse Leydig (TM3) cells was established to elucidate this issue. Data firstly showed that mitochondrial malfunction, mainly manifested by ultrastructure damage, disturbance of mitochondrial dynamics and mitochondrial reactive oxygen species (mtROS) overproduction, was responsible for GLY-decreased protein levels of steroidogenic enzymes, which leads to the inhibition of testosterone synthesis. Enhancement of autophagic flux and activation of mitophagy were shown in GLY-treated TM3 cells, and further studies have revealed that GLY-activated mitophagy is parkin-dependent. Notably, GLY-inhibited testosterone production was significantly improved by parkin knockdown. Finally, data showed that treatment with mitochondria-targeted antioxidant Mito-TEMPO (M-T) markedly reversed GLY-induced mitochondrial network fragmentation, activation of parkin-dependent mitophagy and consultant testosterone reduction. Overall, these findings demonstrate that GLY induces mtROS overproduction to activate parkin-dependent mitophagy, which contributes to the inhibition of testosterone synthesis. This study provides a potential mechanistic explanation for how GLY inhibits testosterone synthesis in mouse Leydig cells.

Glyphosate-induced gut microbiota dysbiosis facilitates male reproductive toxicity in rats.

Glyphosate (GLY), a ubiquitous environmental pollutant, can result in gut microbiota dysbiosis intimately involving various diseases. The latest research has shown an association between gut microbiota alteration and defective spermatogenesis. Here, we aimed to investigate whether GLY-induced gut microbiota dysbiosis contributed to male reproductive toxicity. Data showed that GLY-exposed rats exhibited male reproductive dysfunction, evidenced by impaired testis architectural structure, reduced sperm motility, together with increased sperm malformation ratio. 16S rDNA sequencing analysis indicated that GLY exposure altered the composition of gut commensal microbiota, of which the relative abundance of Bacteroidetes and Firmicutes phyla was significantly changed. Unexpectedly, the increased abundance of Prevotella_1 and Bacteroides genera was negatively correlated with sperm quality. Mechanistically, the pathological changes in GLY-exposed testis were accompanied by the increased interleukin (IL)-17A production, probably due to gut microbes-derived Th17 cell migration. Furthermore, activation of IL-17A signaling triggered testicular oxidative damage. Taken together, these findings uncover an underlying mechanistic scenario that gut microbiota dysbiosis-driven local IL-17A production is one reason responsible for male reproductive toxicity induced by GLY, which provides new insights into the male reproductive toxicity of GLY in mammals.

Global Research Trends in Dental Stem Cells: A Bibliometric and Visualized Study.

Dental stem cells (DSCs) are mesenchymal stem cell-like populations with self-renewal and multidifferentiation potential. These cells have been studied in regenerative medicine and tissue engineering. Despite rapid progress in the past two decades, there has been no bibliometric analysis of DSC research. Here, we performed a comparative study using bibliometric methods for DSCs. A total of 5498 articles were included. Our results showed that the United States was the leader in international cooperation and numbers of citations and was the largest contributor. The Journal of Endodontics published the largest number of articles. The author with the greatest contribution was Songtao Shi. The keywords were mainly related to the fields of tissue engineering and regenerative medicine. Relative research interest and the number of publications increased yearly worldwide. The hotspots of DSC research were transiting from basic research to clinical regenerative medicine. Impact statement Dental stem cells (DSCs) are stem cells with self-renewal and multidirectional differentiation potential. Research in this field is attracting increasing attention. This study aimed to understand the current research status of DSCs and to predict promising keywords and trends. We found the global trend of DSCs and their application in the field of regenerative medicine and tissue engineering. Our study makes a significant contribution to the literature because it will help researchers to understand the research trends and directions in this field.

Plasma metabolites associated with physiological and biochemical indexes indicate the effect of caging stress on mallard ducks (Anas platyrhynchos).

OBJECTIVE: Cage rearing has critical implications for the laying duck industry because it is convenient for feeding and management. However, caging stress is a type of chronic stress that induces maladaptation. Environmental stress responses have been extensively studied, but no detailed information is available about the comprehensive changes in plasma metabolites at different stages of caging stress in ducks. We designed this experiment to analyze the effects of caging stress on performance parameters and oxidative stress indexes in ducks. METHODS: Liquid chromatography tandem mass spectrometry (LC/MS-MS) was used to determine the changes in metabolites in duck plasma at 5 (CR5), 10 (CR10), and 15 (CR15) days after cage rearing and traditional breeding (TB). The associated pathways of differentially altered metabolites were analyzed using Kyoto encyclopedia of genes and genomes (KEGG) database. RESULTS: The results of this study indicate that caging stress decreased performance parameters, and the plasma total superoxide dismutase levels were increased in the CR10 group compared with the other groups. In addition, 1,431 metabolites were detected. Compared with the TB group, 134, 381, and 190 differentially produced metabolites were identified in the CR5, CR10, and CR15 groups, respectively. The results of principal component analysis (PCA) show that the selected components sufficiently distinguish the TB group and CR10 group. KEGG analysis results revealed that the differentially altered metabolites in duck plasma from the CR5 and TB groups were mainly associated with ovarian steroidogenesis, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism. CONCLUSION: In this study, the production performance, blood indexes, number of metabolites and PCA were compared to determine effect of the caging stress stage on ducks. We inferred from the experimental results that caging-stressed ducks were in the sensitive phase in the first 5 days after caging, caging for approximately 10 days was an important transition phase, and then the duck continually adapted.

Effect of maternal folic acid supplementation on hepatic one-carbon unit associated gene expressions in newborn piglets.

Intrauterine growth retardation (IUGR) induces alterations to hepatic gene expressions which might program poor postnatal growth and health status. Maternal folic acid supplementation was administered in gilt diets to test whether hepatic mRNA expressions of some important genes induced by IUGR could be rescued by folic acid supplementation. Thirty-two Yorkshire gilts were allotted to two treatment groups of control (C folic acid 1.3 mg/kg) or folic acid supplementation (FS folic acid 30 mg/kg) after mating, to study the effects of maternal folic acid supplementation on the mRNA expression of methionine adenosyltransferase (MAT), cystathionine-ß-synthase (CBS), methylenetetrahydrofolate reductase (MTHFR), DNA methyltransferase1 (DNMT1), peroxisomal proliferator-activated receptor (PPARγ), glucocorticoid receptor (GR), obesity receptor (ob-R) and Acyl-CoA oxidase (AOX) in the liver of IUGR and NBW piglets. Blood and liver samples were collected for determinations of serum folic acid and gene expressions. The total number of born piglets, number of piglets born alive, average birth weight and 21 days average weight were not affected by dietary treatment (P>0.05), and serum folic acid concentration of piglets was greater in FS than C groups (P<0.05). Real-time PCR indicated that gene expression of MAT1A, MAT2A and DNMT1 were lower in IUGR piglets but could be elevated by maternal folic acid supplementation. Transcript expression levels of PPARγ, GR and AOX were higher in IUGR piglets, but were decreased to the level of normal piglets by maternal folic acid supplementation. Our results suggested that maternal folic acid supplementation be an effective way to rescue the gene expressions negatively induced by IUGR.

Global transcriptome profiling reveals antagonizing response of head kidney of juvenile common carp exposed to glyphosate.

Glyphosate (GLY) frequently detected in various water bodies has imposed a serious risk on fish. Head kidney of fish is an important defense organ, playing a vital part in antagonizing exogenous hazardous matter. The objective of this study was to characterize toxic mechanisms of GLY in head kidney of common carp based on transcriptome profiling. After 45-days exposure of GLY at environmentally relevant concentrations, juvenile common carp were used as experimental subjects to analyze how the head kidney responded to GLY. The transcriptome profiling identified 1381 different expressed genes (DEGs) between the control and exposure groups (5 and 50 mg/L). Functional analysis of DEGs substantiated over-representative pathways mainly involving cellular stress responses, cell proliferation and turnover, apoptosis, lipid metabolism, and innate immune processes in both treated groups compared with the control group. Predicted network of gene regulation indicated that GLY-induced tp53 played a vital role in linking a battery of signals. Furthermore, the expression of 10 candidate genes by qRT-PCR aligned with transcriptional profiling. In addition, western blotting analysis confirmed that GLY-induced apoptosis and cellular proliferation were closely involved in activating MAKP signaling pathway and lipid metabolism pathway in both treated groups. Collectively, these data demonstrate that head kidney of juvenile common carp mainly leverages upregulation of genes related to cell proliferation and turnover, apoptosis, and lipid metabolism to combat sub-chronic exposure of GLY. This study casts new understanding into the risk of GLY in aquatic animals.

Role and molecular mechanism of stem cells in colorectal cancer initiation.

In recent years, the rate of colorectal cancer has sharply increased, especially in China, where it ranks second for the number of cancer fatalities. Currently, the treatment of colorectal cancer patients involves the combination of resection surgery and treatment with postoperative anticancer drugs such as 5-FU and oxaliplatin. However, recurrence and metastasis after treatment are still the dominant reasons for the low survival rate. Colorectal cancer stem cells (CSCs) are regarded as the key contributors to tumour recurrence and metastasis due to their resistance to chemotherapy drugs and their extremely high tumourigenicity. Once CSCs overcome chemotherapy treatment, they continue to survive and reinitiate proliferation to form tumours, leading to recurrence. The dominant reason for CSC resistance is that most anticancer drugs are aimed at inhibiting proliferative pathways in cancer cells that differ from those in CSCs. Therefore, studies on the characteristics of CSCs and their intracellular molecular pathways are essential for the exploration of CSC-targeted drugs. In this report, we review recent advances in the research of CSCs and, in particular, review the important intracellular molecular pathways, such as HOXA5-catenin, STRAP-NOTCH and YAP/TAZ, related to the maintenance and differentiation of stem cells to generate a theoretical basis for the exploration of CSC-targeted drugs.

Multifunctional Quaternary Phosphorus/Bromoargentate Hybrids: The Achievement of Greenish Blue Luminescence, Repeatable Photocurrent Responses and Durable Antimicrobial Activities with Enhanced Water Stability.

BACKGROUND: The realization of multifunction in one bulk material is fascinating for developing a new generation of devices. Quaternary phosphorus salts were seldom utilized as templates in haloargentate systems, and the hybridization of alkyl(triphenyl)phosphonium with halometallate will be a good strategy for the development of multifunctional material, especially for biological material. METHODS: Under the template of (triphenyl)phosphonium-based quaternary phosphorus salts with different spacer lengths (n=2, 3, 4), three bromoargentate hybrids were constructed via the solution method, ie, (1,2-DBTPP)(Ag2Br4) (1), {(1,3-DBTPP)2(Ag7Br11)]∙CH3CN∙H2O} n (2), and {[(1,4-DBTPP)(Ag5Br7)](CH3CN)2∙H2O} n (3) (1,2-DBTPP2+=ethane-1,2-diylbis (triphenyl)phosphonium, 1,3-DBTPP2+=propane-1,3-diylbis (triphenyl)phosphonium, 1,4-DBTPP2+=butane-1,4-diylbis (triphenyl)phosphonium)). RESULTS: The (Ag7Br11) n 4n- chain in 2 is a new type of 1-D bromoargentate chain constructed from cubane-like Ag4Br4 nodes, AgBr4 tetrahedrons and AgBr3 triangles. Interestingly, by elongating spacer n from 2 to 4, argentophilicity interactions are weakened, and the hydrogen bonds are strengthened. Consequently, their water stabilities and photocurrents are improved, in which the Ag-4d/Br-4p to π* anti-bonding orbital of the quaternary phosphorus transfer is facilitated. Furthermore, the greenish blue emissions can be detected. Finally, high inhabitation rates against Streptococcus mutans and Candida albicans can be observed in 2 and 3. CONCLUSION: In all experiments, by elongating the spacer lengths of quaternary phosphorus salts, multifunctions were integrated in the quaternary phosphorus/bromoargentate hybrids, including greenish blue luminescence, repeatable photocurrent responses and durable antimicrobial activities with enhanced water stability. This work could provide a theoretical guide for the design of new biologically multifunctional materials.