Accumulation of extracellular elastin-derived peptides disturbed neuronal morphology and neuron-microglia crosstalk in aged brain.

Extracellular elastin-derived peptides (EDPs) accumulate in the aging brain and have been associated with vascular dementia and Alzheimer's disease (AD). The activation of inflammatory processes in glial cells with EDP treatment has received attention, but not in neurons. To properly understand EDPs' pathogenic significance, the impact on neuronal function and neuron-microglia crosstalk was explored further. Among the EDP molecules, Val-Gly-Val-Ala-Pro-Gly (VGVAPG) is a typical repeating hexapeptide. Here, we observed that EDPs-VGVAPG influenced neuronal survival and morphology in a dose-dependent manner. High concentrations of VGVAPG induced synapse loss and microglia hyperactivation in vivo and in vitro. Following EDP incubation, galectin 3 (Gal-3) released by neurons served as a chemokine, attracting microglial engulfment. Blocking Gal-3 and EDP binding remedied synapse loss in neurons and phagocytosis in microglia. In response to the accumulation of EDPs, proteomics in matrix remodeling and cytoskeleton dynamics, such as a disintegrin and metalloproteinase (ADAM) family, were engaged. These findings in extracellular EDPs provided more evidence for the relationship between aging and neuron dysfunction, increasing the insight of neuroinflammatory responses and the development of new specialized extracellular matrix remolding-targeted therapy options for dementia or other neurodegenerative disease.

Efficacy and safety of botulinum neurotoxin in the treatment of hemifacial spasms: a systematic review and meta-analysis.

BACKGROUND: Hemifacial spasm (HFS) is a neuromuscular disorder characterized by unilateral facial muscle spasms, negatively impacts quality of life due to social embarrassment. Botulinum Neurotoxin (BoNT) injections have emerged as a viable therapeutic approach. This systematic review evaluated the efficacy and safety of BoNT injections for HFS management, along with effects on patients' quality of life and mental health. MATERIALS AND METHODS: A systematic search for studies on BoNT treatment for HFS published between January 1, 2000, and May 1, 2024, was performed across major databases. Study quality was evaluated using Cochrane and Joanna Briggs Institute (JBI) tools, with data management handled by EndNote X9 and statistical analyses conducted via Review Manager (RevMan 5.4) and STATA 14.0. RESULTS: Thirty-five studies met the inclusion criteria: 2 RCTs comprising 83 HFS patients compared the efficacy of perioral injections of botulinum toxin and placebo, while 33 single-arm studies reported outcomes for 2786 patients post-BoNT injection. The selection of 17 single-arm studies focused on the effectiveness rate as the key outcome metric. Pooled estimate signified a remarkably high effectiveness (ES: 0.882, 95% CI: 0.830, 0.926, P < 0.001). Analysis of depression scale (SMD: -0.85, 95% CI: -1.34, -0.35, P < 0.001), anxiety scale (SMD: -1.50, 95% CI: -2.19, -0.80, P < 0.001) and total scale of quality of life (SMD: -0.64, 95% CI: -0.87, -0.41, P = 0.766) showed that BoNT therapy worked well especially in improving mental state and quality of life. Ptosis was considered as the most common adverse reaction during BoNT injections (OR: 0.30, 95% CI: 0.11, 0.81, P = 0.843). CONCLUSION: BoNT injection showed validity and clinical safety in the treatment of HFS, particular for depression relief. Injections around the mouth were only effective for HFS cases with severe symptoms. A standardized strategy for BoNT injections in managing HFS, detailing parameters such as injection sites, doses, and frequencies, remained elusive. Additional RCTs are necessary to further elucidate the interplay between efficacy and these components.

Association between occupational burnout and psychological symptoms among Chinese medical staff: moderating role of social support.

This study aimed to examine the association between occupational burnout and psychological symptoms among Chinese medical staff, assuming social support to play a moderating role in the aforementioned relationship. The survey was conducted online from May 1 to June 28, 2022, and the questionnaires were distributed and retrieved through a web-based platform. The final sample was comprised of 1461 Chinese medical staff in this cross-sectional study. Several multiple linear regressions were performed to analyze the data. After controlling for potential confounding factors, all three dimensions of occupational burnout were associated with poorer psychological symptoms. Emotional exhaustion (ß = 0.33; 95% confidence interval [CI], 1.018, 1.479) had the strongest association with psychological symptoms, followed by depersonalization and diminished personal accomplishment. Moreover, medical staff with higher levels of friend support (ß = -0.11; 95% CI, -4.063, -0.573) and significant other support (ß = -0.10; 95% CI, -3.965, -0.168) were less likely to suffer from psychological symptoms when faced with occupational burnout. The results suggested that interventions aimed at lessening occupational burnout and boosting social support can be an effective way to promote the psychological health of medical staff.

Tunable Van Hove Singularity without Structural Instability in Kagome Metal CsTi_{3}Bi_{5}.

In kagome metal CsV_{3}Sb_{5}, multiple intertwined orders are accompanied by both electronic and structural instabilities. These exotic orders have attracted much recent attention, but their origins remain elusive. The newly discovered CsTi_{3}Bi_{5} is a Ti-based kagome metal to parallel CsV_{3}Sb_{5}. Here, we report angle-resolved photoemission experiments and first-principles calculations on pristine and Cs-doped CsTi_{3}Bi_{5} samples. Our results reveal that the van Hove singularity (vHS) in CsTi_{3}Bi_{5} can be tuned in a large energy range without structural instability, different from that in CsV_{3}Sb_{5}. As such, CsTi_{3}Bi_{5} provides a complementary platform to disentangle and investigate the electronic instability with a tunable vHS in kagome metals.

ZIF-8 induced hydroxyapatite-like crystals enabled superior osteogenic ability of MEW printing PCL scaffolds.

ZIF-8 may experience ion-responsive degradation in ionic solutions, which will change its initial architecture and restrict its direct biological use. Herein, we report an abnormal phenomenon in which ZIF-8 induces large hydroxyapatite-like crystals when soaked directly in simulated body fluid. These crystals grew rapidly continuously for two weeks, with the volume increasing by over 10 folds. According to Zn2+ release and novel XRD diffraction peak presence, ZIF-8 particles can probably show gradual collapse and became congregate through re-nucleation and competitive coordination. The phenomenon could be found on ZIF-8/PCL composite surface and printed ZIF-8/PCL scaffold surface. ZIF-8 enhanced PCL roughness through changing the surface topography, while obviously improving the in-vivo and in-vitro osteoinductivity and biocompatibility. The pro-biomineralization property can make ZIF-8 also applicable in polylactic acid-based biomaterials. In summary, this study demonstrates that ZIF-8 may play the role of a bioactive additive enabling the surface modification of synthetic polymers, indicating that it can be applied in in-situ bone regeneration.

Single and joint toxic effects of waterborne exposure to copper and cadmium on Coregonus ussuriensis Berg.

Heavy metal contamination severely affects the aquatic environment and organisms. Copper (Cu) and cadmium (Cd) are two of the most common heavy metal contaminants that impair the survival, development, and reproduction of aquatic organisms. With the growth of agriculture and industry, there is a possibility of heavy metal pollution in Coregonus ussuriensis Berg's water source. However, there are no published studies on the toxicity to C. ussuriensis. Acute toxicity experiments in C. ussuriensis revealed the 96-h median lethal concentrations of copper and cadmium to be 0.492 mg·L-1 (95% confidence interval: 0.452-0.529) and 1.548 mg·L-1 (95% confidence interval: 1.434-1.657), respectively, and safe concentrations of 4.92 µg·L-1 and 15.48 µg·L-1, respectively. C. ussuriensis was then treated for 96 h with Cu (20% of 96 h LC50), Cd (20% of 96 h LC50), and a combination of Cu and Cd (20% of Cu 96 h LC50 + 20% of Cd 96 h LC50). The histological damage caused by the three different exposure modes to the liver and gills of C. ussuriensis was verified using hematoxylin and eosin staining. All three exposure modes caused different degrees of vacuolization, nuclear consolidation, and necrosis in the liver tissue of C. ussuriensis and edema, hyperplasia, laminar fusion, and epithelial elevation in the gill tissue compared with the reference group. The severity of the damage increased with increasing exposure time. Anti-oxidant activity in the gill and liver tissues were measured using enzyme activity assay kits to reflect oxidative stress induced by copper and cadmium exposure alone and in combination. The enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH) were substantially higher than those in the reference groups. However, the activities of the enzymes decreased with increasing exposure time. Malondialdehyde (MDA) activity significantly increased during exposure in relation to that in the reference group. Analysis of immune gene expression in C. ussuriensis gill and liver tissues was executed using real-time inverse transcript polymerase chain response (RT-PCR). The expression levels of the pro-inflammatory cytokines interleukin one beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) were positively correlated with exposure time and were significantly upregulated with increasing exposure time. Metallothionein (MT) gene expression levels were significantly upregulated in the short term after exposure compared to the reference group but decreased with increasing exposure time. Our results indicate that exposure to aqueous copper and cadmium solutions, either alone or in combination, causes histopathological damage, oxidative stress, and immunotoxicity in C. ussuriensis gill and liver tissue. This study investigated the toxic effects of copper and cadmium on C. ussuriensis to facilitate the monitoring of heavy metals in water sources for healthy aquaculture.

Association between bisphenol A exposure and thyroid dysfunction in adults: a systematic review and meta-analysis.

The occurrence of thyroid dysfunction is affected by environmental factors, and BPA is a ubiquitous environmental pollutant with the potential to cause thyroid dysfunction. However, the limited epidemiological evidence shows an inconsistent association between BPA exposure and thyroid dysfunction. Therefore, the literature on the impact of BPA on thyroid was sorted and analyzed to study the relationship between BPA and adult thyroid function. The studies published on or before 23rd May 2022 from PubMed, Web of Science, and Scopus were collected analyzing the association between BPA exposure and the levels of thyroid hormones. The methodological quality of each study was assessed, the sensitivity analysis and subgroup analysis based on study population and gender were also performed, and publication bias was evaluated. A total of 2969 literature studies were retrieved. Based on inclusion and exclusion criteria, eleven studies were included. Our results showed that BPA concentration was negatively correlated with FT4 and TSH in males. Pooled correlation coefficients between BPA and FT4/TSH were -0.027 (95%CI = -0.030∼-0.024) and -0.058 (95%CI = -0.111∼-0.004). BPA concentration was positively correlated with FT4 in females, and the pooled correlation coefficient was 0.006 (95%CI = 0.003-0.008). The effects of BPA on thyroid hormone levels were significantly different between males and females. BPA may significantly decrease the levels of FT4 and TSH in males but increase the levels of FT4 in females. Considering the high heterogeneity among studies and the limited investigations into subgroups, the relationship between BPA exposure and thyroid dysfunction needs to be further investigated.

High Performance Bifunctional Electrocatalysts Designed Based on Transition-Metal Sulfides for Rechargeable Zn-Air Batteries.

Due to the energy crisis by the excessive consumption of fossil fuels, Zinc-air batteries (ZABs) with high theoretical energy density have attracted people's attention. The overall performance of ZABs is largely determined by the air cathode catalyst. Therefore, it is necessary to develop high-efficiency and low-cost bifunctional catalysts to replace noble metal catalysts to promote the development of ZABs. Among a variety of cathode catalysts, TMS has become a research hotspot in recent years because of its better electrical conductivity than metal phosphides and metal oxides. In this work, we focus on the means of improving the electrocatalytic performance of transition-metal sulfides (TMS) providing ideas for us to rationally design high-performance catalysts. Furthermore, the performance improvement law between catalyst performance and ZABs is also discussed in this work. Finally, some challenges and opportunities faced in the research of TMS electrocatalysis are briefly proposed, and strategies for improving the performance of ZABs are prospected.

Hollow Capsule NiCo2 NS Prepared by Self-Sacrificing Template Method for High-Efficiency Bifunctional Catalyst and Its Application in Zn-Air Battery.

Exploring the application of high-efficiency bifunctional oxygen catalysts to rechargeable zinc-air batteries has been a research hotspot in recent years. We succeeded in obtaining NiCo2 NS with a hollow capsule structure through the self-sacrificing template method, which has a larger specific surface area and can provide more active sites for electrocatalysis relative to his solid. The introduction of S can change the valence distribution of N and the electronic structure of the M-N bond, so that NiCo2 NS exhibits excellent performance in the overpotential and stability of the oxygen reduction and oxygen evolution reactions. It shows an overpotential of 154 mV at 10 mA cm-2 and a half-wave potential of 0.76 V. When used as a bi-functional catalyst in zinc-air batteries, it exhibits good stability within 400 h. The flexible battery assembled by NiCo2 NS also shows excellent performance, and can be cycled stably for 20 h. The current maintains good stability when it is bent at different angles during the cycle.

Gabapentin Alleviates Brain Injury in Intracerebral Hemorrhage Through Suppressing Neuroinflammation and Apoptosis.

Neuroinflammation plays an important role in brain tissue injury during intracerebral hemorrhage. Gabapentin can reduce inflammation and oxidative stress through inhibiting nuclear factor κB (NFκB) signals. Here, we showed that gabapentin reduced brain tissue injury in ICH through suppressing NFκB-mediated neuroinflammation. ICH was induced by injecting collagenase IV into the right striatum of Sprague-Dawley rats. PC12 and BV2 cells injury induced by Hemin were used to simulate ICH in vitro. Inflammation and apoptosis were assessed in rat brain tissue and in vitro cells. The neurobehavioral scores were significantly decreased in ICH rats compared with sham rats. Phosphorylated IκB-α and cleaved caspase3, and apoptosis rate were significantly higher in tissue surrounding the hematoma than in brain tissues from rats subjected to sham surgery. Furthermore, serum IL-6 levels in ICH rats were higher than in sham rats. Gabapentin treatment significantly improved the behavioral scores, decreased levels of phosphorylated IκB-α and cleaved caspase3, apoptosis rate, and serum IL-6 level in ICH rats. Hemin-treated BV2 cells displayed higher levels of phosphorylated IκB-α, cleaved caspase3, and IL-6 in the supernatant compared with vehicle-treated cells. Hemin treatment induced a significantly lower level of peroxisome proliferator-activated receptor γ (PPARγ) in BV2 cells. BV2-PC12 co-culture cells treated by hemin displayed higher levels of cleaved caspase3 in PC12 cells. Furthermore, gabapentin treatment could reduce these effects induced by hemin and the protective effects of gabapentin were significantly attenuated by PPARγ inhibitor. Therefore, gabapentin may reduce inflammation and apoptosis induced by the ICH through PPARγ-NFκB pathway.

Molecular characterization and antibacterial immunity functional analysis of the antimicrobial peptide hepcidin from Coregonus ussuriensis berg.

Antimicrobial peptides are immune system molecules existing in different organisms including mollusks, crustaceans and vertebrates. Hepcidins are a group of cysteine rich antimicrobial peptides, which plays an important role in fish response to a variety of pathogens. In this study, we cloned and identified Hepcidin from the Coregonus ussuriensis Berg, and its functions in vivo and in vitro was investigated. Our results showed that, CuHepc contains a 267 bp coding sequence (CDS) region that encodes 88 putative amino acids with a molecular weight of 9.77 kD. Hepcidin transcripts were most abundant in the liver of healthy C. ussuriensis Berg. The synthesized Hepcidin peptide exhibited a wide range of antibacterial activity against Gram-positive and Gram-negative bacteria in vitro, and the results of in vivo bacterial attack assays showed that the CuHepc gene was differentially up-regulated in the six tissues investigated after infection with Aeromonas hydrophila. To analyze the changes in protein levels in C. ussuriensis, we generated Hepc polyclonal antibodies in rabbits and verified that the protein expression was increased after bacterial infection with Western blot assay. MIC assay results showed a geometric mean value of 5.513 µM for CuHepc peptide. In the in vivo experiment, immune-related genes IL-10, NF-κB, TLR3 were up-regulated post-infection CuHepc peptide in liver and intestine. Finally, CuHepc peptide reduced the tissues microbial load compared to infection with Aeromonas hydrophila. The above results indicate that Hepc plays a role in the immune response of C. ussuriensis to exogenous disturbances, indicate that CuHepc might act a candidate for modulation of the innate immune system in C. ussuriensis.

Physiological responses to heat stress in the liver of rainbow trout (Oncorhynchus mykiss) revealed by UPLC-QTOF-MS metabolomics and biochemical assays.

Rainbow trout (Oncorhynchus mykiss) is one of the world's most widely farmed cold-water fish. However, the rise in water temperature caused by global warming has seriously restricted the development of rainbow trout aquaculture. In this study, we investigated the physiological responses in the liver of rainbow trout exposed to 20 â„ƒ and 24 â„ƒ and returning to the initial temperature (14 â„ƒ) by combining biochemical analyses and UPLC-QTOF-MS metabolomics. The results of the biochemical analysis showed that serum aminotransferase, lysozyme, total bilirubin, alkaline phosphatase and liver superoxide dismutase, glutathione peroxidase, and malondialdehyde in rainbow trout under heat stress changed significantly. Even after the temperature recovery, some of the above indicators were still affected. Compared to the control group, 115, 130, and 121 differentially expressed metabolites were identified in the 20 â„ƒ, 24 â„ƒ, and recovery groups, respectively. Further pathway enrichment of these metabolites revealed that heat stress mainly affected the linoleic acid metabolism, α-linolenic acid metabolism, glycerophospholipid metabolism, and sphingolipid metabolism in the liver of rainbow trout, and continuously affected these metabolic pathways during the recovery period. Notably, the enrichment of glutathione metabolic pathways was consistent with the changes in glutathione peroxidase in the biochemical results. The results above suggest that heat stress can induce immune responses and oxidative stress inside the rainbow trout. After temperature recovery, some of the hepatic functions of fish return to normal gradually. The biochemical analysis and UPLC-QTOF-MS metabolomics tools provide insight into the physiological regulation of rainbow trout in response to heat stress.

miR-301b-5p and its target gene nfatc2ip regulate inflammatory responses in the liver of rainbow trout (Oncorhynchus mykiss) under high temperature stress.

Rainbow trout (Oncorhynchus mykiss) is a typical cold-water aquaculture fish and a high-end aquatic product. When water temperature exceeds its optimal range of 12-18 °C, the immune system of rainbow trout becomes weakened and unbalanced. High temperature in summer and global warming severely impact rainbow trout industry. The focus of this study was to explore the mechanisms regulating the immune response of rainbow trout under high temperature stress and identify molecular elements that account for resistance to high temperature. In this study, individual fish were screened in a high temperature stress experiment and divided into resistant (R) and sensitive (S) groups. The hepatic transcriptome sequencing and analysis of mRNAs and microRNAs of the R, S, and control groups showed that the number of the differentially expressed genes (DEGs) in the S group (9259) was higher than that in the R group (5313). Furthermore, the 1233 genes differentially expressed between S and R groups were mainly enriched in immune-related pathways, including cytokine-cytokine receptor interaction, TNF signaling and IL-17 signaling. Among these DEGs were miR-301b-5p and its target gene that encodes nuclear factor of activated T cells two interacting protein (nfatc2ip). The dual-luciferase reporter system and immunofluorescence experiments verified the relationship between miR-301b-5p and nfatc2ip. We also showed that expression levels of miR-301b-5p and nfatc2ip significantly negatively correlated in the liver of rainbow trout under high temperature stress. By performing functional experiments, we showed that activation of miR-301b-5p expression or inhibition of nfatc2ip expression stimulated the phosphorylation of p65, p38, and JNK in the classical nuclear factor kappa-B and mitogen-activated protein kinase pathways under high temperature stress. These manipulations initially promoted the secretion of the pro-inflammatory factor IL-1ß and then increased the levels of IL-6, IL-12, and TNF-α. In addition, activation of miR-301b-5p expression or inhibition of nfatc2ip expression stimulated the repair of the hepatic ultrastructural damage caused by high temperature stress by activating the inflammatory response in rainbow trout liver.

Comprehensive analysis of miRNA-mRNA/lncRNA during gonadal development of triploid female rainbow trout (Oncorhynchus mykiss).

Chromosomal ploidy manipulation is one of the means to create excellent germplasm. Triploid fish could provide an ideal sterile model for searching of a underlying mechanism of abnormality in meiosis. The complete understanding of the coding and noncoding RNAs regulating sterility caused by meiosis abnormality is still not well understood. By high-throughput sequencing, we compared the expression profiles of gonadal mRNA, long non-coding RNA (lncRNA), and microRNA (miRNA) at three different developmental stages between the diploid (XX) and triploid (XXX) female rainbow trout. These stages were gonads before differentiation (65 days post fertilisation, dpf), at the beginning of morphological differences (180 dpf) and showing clear difference between diploids and triploids (600 dpf), respectively. A majority of differentially expressed (DE) RNAs were identified, and 22 DE mRNAs related to oocyte meiosis and homologous recombination were characterized. The predicted miRNA-mRNA/lncRNA networks of 3 developmental stages were constructed based on the target pairs of DE lncRNA-miRNA and DE mRNA-miRNA. According to the networks, meiosis-related gene of ccne1 was targeted by dre-miR-15a-5p_R + 1, and 6 targeted DE lncRNAs were identified. Also, qRT-PCR was performed to validate the credibility of the network. Overall, this study explored the potential interplay between coding and noncoding RNAs during the gonadal development of polyploid fish. The mRNA, lncRNA and miRNA screened in this study may be helpful to identify the functional elements regulating fertility of rainbow trout, which may provide reference for character improvement in aquaculture.

First-Principles-Based Optimized Design of Fluoride Electrolytes for Sodium-Ion Batteries.

Because of the abundance and low cost of sodium, sodium-ion batteries (SIBs) are next-generation energy storage mediums. Furthermore, SIBs have become an alternative option for large-scale energy storage systems. Because the electrolyte is a critical component of SIBs, fluorination is performed to improve the cycling performance of electrolytes. Based on the first-principles study, we investigated the effects of the type, quantity, and relative position relationships of three fluorinated units, namely -CF1, -CF2, and -CF3, on the cyclic ester molecule ethylene carbonate (EC) and the linear ether molecule 1,2-dimethoxylethane (DME). The optimal fluorination was proposed for EC and DME by studying the bond length, highest occupied molecular orbital, lowest unoccupied lowest orbital, and other relevant parameters. The results revealed that for EC, the optimal fluorination is 4 F fluorination based on four -CF1 units; for DME, CF3CF1CF1-, CF3CF2CF2-, CF3CF1CF2CF3, and CF3CF2CF2CF3, four combinations of three -CF1, -CF2, and -CF3 units are optimal. The designed fluorinated EC and DME exhibited a wide electrochemical stability window and high ionic solvation ability, which overcomes the drawback of conventional solvents and can improve SIB cycling performance.

Realizing Kagome Band Structure in Two-Dimensional Kagome Surface States of RV_{6}Sn_{6} (R=Gd, Ho).

We report angle resolved photoemission experiments on a newly discovered family of kagome metals RV_{6}Sn_{6} (R=Gd, Ho). Intrinsic bulk states and surface states of the vanadium kagome layer are differentiated from those of other atomic sublattices by the real-space resolution of the measurements with a small beam spot. Characteristic Dirac cone, saddle point, and flat bands of the kagome lattice are observed. Our results establish the two-dimensional (2D) kagome surface states as a new platform to investigate the intrinsic kagome physics.

Effects of exposure to urban particulate matter SRM 1648a during pregnancy on the neurobehavioral development of offspring mice.

The development of the nervous system is crucial to a child's health. However, the nervous system is also susceptible to a variety of factors during development. To date, epidemiological studies have reported controversial results on the relationship between prenatal exposure to particulate matter (PM) and neurobehavioral development. Thus, we investigated the effect of PM exposure during pregnancy on the neurobehavioral development of offsprings. Adult C57BL/6 mice were exposed to PM from gestation day (GD) 0.5-21 by the intratracheal instillation. The daily exposure doses were 250 µg/kg.b.w and 2500 µg/kg.b.w respectively. The offspring mice began behavioral tests at the 5th week. We assessed neurobehavioral development, and the gene expression level changes in the mouse hippocampus using RNA-seq. In the open field test, the movement distance in the central area was significantly decreased in the high-dose group. Serum free triiodothyronine (FT3) levels were significantly increased in male offspring mice with prenatal high-dose PM exposure. The RNA-seq results suggested that the Prkca, Med12l, Ep300, and Slc16a10 in the thyroid hormone signaling pathway were significantly decreased in offspring mice in the high-dose group. Our data showed that prenatal PM exposure caused the offspring mice's anxiety-like behaviors and increased serum FT3 levels. The changes in thyroid hormone pathway-related genes might be the causes of the above series of changes.

The activated ATM/p53 pathway promotes autophagy in response to oxidative stress-mediated DNA damage induced by Microcystin-LR in male germ cells.

Microcystin-LR (MC-LR) is an intracellular toxin with multi-organ toxicity and the testis is one of its important target organs. Although there is increasing research on MC-LR in male reproductive toxicity, the association between DNA damage and autophagy induced by MC-LR in male germ cells are still unclear. Therefore, it is important to explore the mechanism of MC-LR-induced DNA damage and the role of the activated ATM/p53 signaling pathway in testicular toxicity. The present study showed that MC-LR exposure significantly reduced gonadal index and induced pathological damage of the testes in mice. In addition, MC-LR increased the oxidative stress-related indicator hydroxyl radical, accompanied by increased levels of DNA damage-related indicators gamma-H2AX, 8-hydroxy-2'-deoxyguanosine, the olive tail moment (OTM) and DNA content of comet tail (TailDNA%) in trailing cells. Moreover, MC-LR activated the ATM/p53 pathway by enhancing the phosphorylation levels of ATM, CHK2 and p53 proteins, and then led to cell autophagy, ultimately triggering disrupted testicular cell arrangement, reduced sperm count and spermatogenic cell shedding. Importantly, after pretreatment with the antioxidant NAC, the expression levels of DNA damage-related indicators and the extent of damage in male germ cells were significantly reduced. Furthermore, pretreatment with the ATM inhibitor KU55933 could reduce the occurrence of autophagy and mitigate testicular toxicity of MC-LR through inhibiting the activation of the ATM/p53 pathway. These results indicate that MC-LR-induced oxidative stress can activate the DNA damage-mediated ATM/p53 signalling pathway to induce autophagy in male germ cells. This study provides a novel insight to further clarify the reproductive toxicity caused by MC-LR and to protect male reproductive health.

miR-152-5p suppresses glioma progression and tumorigenesis and potentiates temozolomide sensitivity by targeting FBXL7.

A generally used chemotherapeutic drug for glioma, a frequently diagnosed brain tumour, is temozolomide (TMZ). Our study investigated the activity of FBXL7 and miR-152-5p in glioma. Levels of microRNA-152-5p (miR-152-5p) and the transcript and protein of FBXL7 were assessed by real-time PCR and Western blotting, respectively. The migratory and invasive properties of cells were measured by Transwell migration and invasion assay and their viability were examined using CCK-8 assay. Further, the putative interaction between FBXL7 and miR-152-5p were analysed bioinformatically and by luciferase assay. The activities of FBXL7, TMZ and miR-152-5p were analysed in vivo singly or in combination, on mouse xenografts, in glioma tumorigenesis. The expression of FBXL7 in glioma tissue is significantly up-regulated, which is related to the poor prognosis and the grade of glioma. TMZ-induced cytotoxicity, proliferation, migration and invasion in glioma cells were impeded by the knock-down of FBXL7 or overexpressed miR-152-5p. Furthermore, the expression of miR-152-5p reduced remarkably in glioma cells and it exerted its activity through targeted FBXL7. Overexpression of miR-152-5p and knock-down of FBXL7 in glioma xenograft models enhanced TMZ-mediated anti-tumour effect and impeded tumour growth. Thus, the miR-152-5p suppressed the progression of glioma and associated tumorigenesis, targeted FBXL7 and increased the effect of TMZ-induced cytotoxicity in glioma cells, further enhancing our knowledge of FBXL7 activity in glioma.

Receptor kinase FERONIA regulates flowering time in Arabidopsis.

BACKGROUND: The receptor-like kinase FEROINA (FER) plays a crucial role in controlling plant vegetative growth partially by sensing the rapid alkalinization factor (RALF) peptide. However, the role of RALF1-FER in the vegetative-reproductive growth transition remains unknown. Here, we analyze the mechanism through which FER affects the flowering time in Arabidopsis. RESULTS: We found that the FER mRNA levels exhibit an oscillating pattern with a diurnal rhythm and that the clock oscillator CIRCADIAN CLOCK-ASSOCIATED1 (CCA1) up-regulates the expression of FER by associating with its chromatin. In addition, FER expression is regulated by clock genes, and FER also modulates the expression patterns of clock genes. Consistent with its gene expression pattern, FER positively regulates flowering by modulating the transcript accumulation and mRNA alternative splicing of certain flowering-related genes, including FLOWERING LOCUS C (FLC) and its homolog MADS AFFECTING FLOWERING (MAF). However, the RALF1 ligand negatively regulates flowering compared with FER. CONCLUSIONS: We found that FER, which is up-regulated by CCA1, controls the flowering time by regulating the transcript accumulation and mRNA alternative splicing (AS) of some important flowering genes, and these findings link FER to the floral transition.