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Background: This study aimed to clarify the relationship between the gut microbiota and osteoporosis combining Mendelian randomization (MR) analysis with animal experiments. Methods: We conducted an analysis on the relationship between differential bacteria and osteoporosis using open-access genome-wide association study (GWAS) data on gut microbe and osteoporosis obtained from public databases. The analysis was performed using two-sample MR analysis, and the causal relationship was examined through inverse variance weighting (IVW), MR Egger, weighted median, and weighted mode methods. Bilateral oophorectomy was employed to replicate the mouse osteoporosis model, which was assessed by micro computed tomography (CT), pathological tests, and bone transformation indexes. Additionally, 16S rDNA sequencing was conducted on fecal samples, while SIgA and indexes of IL-6, IL-1β, and TNF-α inflammatory factors were examined in colon samples. Through immunofluorescence and histopathology, expression levels of tight junction proteins, such as claudin-1, ZO-1, and occludin, were assessed, and conduct correlation analysis on differential bacteria and related environmental factors were performed. Results: A positive correlation was observed between g_Ruminococcus1 and the risk of osteoporosis, while O_Burkholderiales showed a negative correlation with the risk of osteoporosis. Furthermore, there was no evidence of heterogeneity or pleiotropy. The successful replication of the mouse osteoporosis model was assessed, and it was found that the abundance of the O_Burkholderiales was significantly reduced, while the abundance of g_Ruminococcus was significantly increased in the ovariectomized (OVX)-mice. The intestinal SIgA level of OVX mice decreased, the expression level of inflammatory factors increased, barrier damage occurred, and the content of LPS in the colon and serum significantly increased. The abundance level of O_Burkholderiales is strongly positively correlated with bone formation factors, gut barrier indicators, bone density, bone volume fraction, and trabecular bone quantity, whereas it was strongly negatively correlated with bone resorption factors and intestinal inflammatory factors, The abundance level of g_Ruminococcus shows a strong negative correlation with bone formation factors, gut barrier indicators, and bone volume fraction, and a strong positive correlation with bone resorption factors and intestinal inflammatory factors. Conclusion: O_Burkholderiales and g_Ruminococcus may regulate the development of osteoporosis through the microbiota-gut-bone axis. [ABSTRACT FROM AUTHOR]

Background As is known, CD4 cell count is a significant parameter predicting HIV progression, opportunistic infections and death in HIV-infected individuals, as well was an important indicator for initiating antiretroviral therapy (ART). In China’s National Free Antiretroviral Treatment Program, people with HIV (PWH) on ART can receive a CD4 count test at least once every six months. Importantly, the baseline CD4 count (before ART initiation) is significantly correlated with ART and even prognosis, but the influence of the peak CD4 cell count on ART and/or clinical outcomes is still unknown. Methods A retrospective study was conducted among 7965 PWH who received ART from October 2003 to September 2022 at Yunnan Infectious Disease Hospital. Clinical features and laboratory data were collected and analyzed by Chi-square test, univariate and multivariate Cox regression analysis. After elimination of confounding variables, multivariate Cox regression analysis was performed to identify survival-related factors. Results Of a total of 7965 PWH in the ART treatment cohort who met the inclusion and exclusion criteria, 7939 were finally included in the subsequent analyses. First, it was found that the proportion of clinical variables, including sex, age distribution, interval from diagnosis to ART initiation, marital status, and others, was significantly different between the living and dead groups (P<0.05). Impressively, significantly more PWH had the higher level of baseline, peak and recent CD4 cell counts in the living group compared to those in the dead group. Due to multicollinearity effect, after excluding confounders, the following factors were found to be significantly associated with mortality by multivariate Cox regression analysis: (1) male sex (hazard ratio (HR)=1.268 [1.032, 1.559]; P=0.024); (2) time from HIV confirmation to ART initiation≥6 months (HR=1.962 [1.631, 2.360]; P<0.001); (3) peak CD4 cell count: Peak CD4<100cells/µL group (HR=16.093 [12.041, 21.508]; P<0.001), 100cells/µL≤x<200cells/µL group (HR=7.904 [6.148, 10.160]; P<0.001), 200cells/µL≤x<350cells/µL group (HR=3.166 [2.519, 3.980]; P<0.001), 350cells/µL≤x<500cells/µL group (HR=1.668 [1.291, 2.155]; P<0.001). Conclusion Interestingly, patients in male, time from HIV confirmation to ART initiation≥6 months, or peak CD4 count<500 cells/µl had inferior clinical outcomes, in other word, a lower peak CD4 cell count significantly increased the risk of death, and peak CD4 cell was independent in predicting the overall survival of PWH. It is important to promote “early diagnosis and treatment of HIV” and regularly monitor CD4 levels in HIV/AIDS to evaluate the efficacy of ART and immune reconstitution, and optimize the ART regimen in time to further reduce the mortality of PWH. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease of the gastrointestinal tract. This study aimed to determine the effect of cathelicidinrelated antimicrobial peptide (Cramp) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice and to investigate the underlying mechanisms. Acute UC was induced in C57BL/6 mice with 3% DSS for 7 days, 4 mg/kg b.w. synthetic Cramp peptide was administrated once daily starting on day 4 of the experimental period. Mice were evaluated for body weight, colon length, colon histopathology, and inflammatory cytokines in colon tissue. Using 16 s rRNA sequencing, the composition structure of gut microbiota was characterized. Metabolomic profiling of the serum was performed. The results showed that DSS treatment significantly induced intestinal damage as reflected by disease activity index, histopathological features, and colon length, while Cramp treatment significantly prevented these trends. Meanwhile, Cramp treatment decreased the levels of inflammatory cytokines in both serum and colonic tissue on DSS-induced colitis. It was also observed that DSS damaged the integrity of the intestinal epithelial barrier, whereas Cramp also played a protective role by attenuating these deteriorated effects. Furthermore, Cramp treatment reversed the oxidative stress by increasing the antioxidant enzymes of GSH-PX and decreasing the oxidant content of MDA. Notably, compared to the DSS group, Cramp treatment significantly elevated the abundance of Verrucomicrobiota at the phylum level. Furthermore, at the genus level, Parasutterella and Mucispirllum abundance was increased significantly in response to Cramp treatment, although Roseburia and Enterorhabdus reduced remarkably. Metabolic pathway analysis of serum metabolomics showed that Cramp intervention can regulate various metabolic pathways such as α-linolenic acid, taurine and hypotaurine, sphingolipid, and arachidonic acid metabolism. The study concluded that Cramp significantly ameliorated DSS-induced colonic injury, colonic inflammation, and intestinal barrier dysfunction in mice. The underlying mechanism is closely related to the metabolic alterations derived from gut microbiota. [ABSTRACT FROM AUTHOR]

Homalotylus tianjinensis Zu, sp. nov., H. bicolor Zu, sp. nov. and H. guangxiensis Zu, sp. nov. are described as new to science; H. agarwali Anis & Hayat, 1998, H. hemipterinus (De Stefani, 1898) and H. varicolorus Krishnachaitanya & Manickavasagam, 2016 are newly recorded from China. A key to Chinese species based on females is also presented. [ABSTRACT FROM AUTHOR]

The polymorphism of the simple sequence repeat (SSR) in the 5′ untranslated coding region (5′-UTR) of the antiviral gene IRF (LvIRF) has been shown to be implicated in the resistance to viral pathogens in shrimp Litopenaeus vannamei (L. vannamei). In this study, we explored the potential of this (CT)n-SSR marker in disease resistance breeding and the hereditary property of disease resistance traits in offspring. From 2018 to 2021, eight populations were generated through crossbreeding by selecting individuals according to microsatellite genotyping. Our results demonstrated that shrimp with the shorter (CT)n repeat exhibited higher resistance to white spot syndrome virus (WSSV) or Decapod iridescent virus 1 (DIV1); meanwhile, these resistance traits could be inherited in offspring. Interestingly, we observed that the longer (CT)n repeats were associated with bacterial resistance traits. Accordingly, shrimp with longer (CT)n repeats exhibited higher tolerance to Vibrio parahaemolyticus infection. Taken together, these results indicate that the single (CT)n-SSR marker could be used to selective breeding for both resistance to virus and bacteria in shrimps. [ABSTRACT FROM AUTHOR]

Introduction: Recent studies have indicated that the dosage of LMWH in patients with specific weights may be controversial. Therefore, we conducted a meta-analysis to explore an appropriate dosage of LMWH for the prevention and treatment of venous thromboembolism (VTE) in patients with obesity. Materials and methods: We searched the PubMed, EMBASE, and Cochrane Library databases up to July 23, 2022. Study selection, bias analysis, and information extraction were performed by three independent reviewers. The occurrence or recurrence of VTE and bleeding events were the primary outcomes we assessed. Results: Eleven studies (a total of 6266 patients) were included in the prevention group, and 6 studies (a total of 3225 patients) were included in the treatment group. For VTE prophylaxis, compared with the standard-dosage group, the high-dosage group had a lower incidence of VTE (OR: 0.47, 95% CI: 0.27-0.82, P=0.007) and a similar incidence of bleeding events (OR: 0.86, 95% CI: 0.69-1.08, P=0.020). For VTE therapy, compared to the standard-dosage group, the reduced-dosage group had a similar incidence of VTE recurrence (OR: 0.86, 95% CI: 0.11-6.84, P=0.89) but a lower incidence of bleeding events (OR: 0.30, 95% CI: 0.10-0.89, P=0.03). Conclusion: In patients with obesity, increasing the dosage of LMWH is a more appropriate option for the prevention of VTE. Due to the limited evidence, reducing the therapeutic dosage of LMWH requires careful consideration. Larger-scale, well-designed randomized controlled trials are necessary. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier ID=CRD42022298128. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate the target dose discrepancy caused by intrafraction variation during stereotactic body radiotherapy (SBRT) for lung cancer. Methods: Intensity-modulated radiation therapy (IMRT) plans were designed based on average computed tomography (AVG CT) utilizing the planning target volume (PTV) surrounding the 65% and 85% prescription isodoses in both phantom and patient cases. Variation was simulated by shifting the nominal plan isocenter along six directions from 0.5 mm to 4.5 mm with a 1-mm step size to produce a series of perturbed plans. The dose discrepancy between the initial plan and the perturbed plans was calculated as the percentage of the initial plan. Dose indices, including ΔD99 for internal target volume (ITV) and gross tumor volume (GTV), were adopted as endpoint samples. The mean dose discrepancy was calculated under the 3-dimensional space distribution. Results: We found that motion can lead to serious dose degradation of the target and ITV in lung SBRT, especially during SBRT with PTV surrounding the lower isodose line. Lower isodose line may lead to larger dose discrepancy, while make steeper dose fall-off gradient. This phenomenon was compromised when 3-dimensional space distribution was considered. Discussion: This result may provide a prospective reference for target dose degradation due to motion during lung SBRT treatment. [ABSTRACT FROM AUTHOR]

The oral epithelium's normal morphological structure and function play an important role in maintaining oral homeostasis, among which microbiota and chronic stress are key contributing factors. However, the effects of microbiota and chronic stress on the morphological structures and molecular function of oral homeostasis remain unclear. In this study, morphological staining was used to compare the tongue structure of specific pathogen-free and germfree mice, and an integrated multi-omics analysis based on transcriptomics, proteomics, and metabolomics was performed to investigate the regulatory mechanisms of microbiota and chronic stress on oral homeostasis. We found that the morphological structure of the tongue in germ-free mice was disordered compared with in specific pathogen-free mice, especially in the epithelium. Multi-omics analysis indicated that differentially expressed molecules of the tongue between germ-free and specific pathogen-free mice were significantly enriched in the mitochondrial metabolic process and immune response. Interestingly, microbiota also significantly influenced the permeability of the oral epithelial barrier, represented by the differential expression of keratinization, and cell adhesion molecules. It was worth noting that the above changes in the tongue between specific pathogen-free and germ-free mice were more significant after chronic stress. Collectively, this is the first study to reveal that the microbiota might maintain oral homeostasis by reshaping the structure of the oral epithelial barrier and changing the function of molecular biology, a process that may be driven by the immune response and mitochondrial metabolic process of oral tissue. Furthermore, chronic stress can enhance the regulatory effects of microbiota on oral homeostasis. [ABSTRACT FROM AUTHOR]

Chronic neuropathic pain is commonly accompanied by cognitive impairment. However, the underlying mechanism in the occurrence of cognitive deficits under constant nociceptive irritation remains elusive. Herein, we established a chronic neuropathic pain model by chronic constriction injury (CCI) of the unilateral sciatic nerve in rats. Behavioral tests indicated that CCI rats with long-term nociceptive threshold decline developed significant dysfunction of working memory and recognitive memory starting at 14 days and lasting for at least 21 days. Afterward, circRNA expression profiles in the hippocampus of CCI and sham rats were analyzed via high-throughput sequencing to explore the potential key factors associated with cognitive impairment induced by ongoing nociception, which showed 76 differentially expressed circRNAs, 39 upregulated and 37 downregulated, in the CCI group. These differentially expressed circRNA host genes were validated to be primarily associated with inflammation and apoptotic signaling pathways according to GO/KEGG analysis and the circRNA-miRNA-mRNA network, which was also confirmed through the analysis of neuroinflammation and neuronal apoptosis. Consequently, we assumed that enhanced neuroinflammation and neuronal apoptosis might act as potential regulators of cognitive impairment induced by chronic neuropathic pain. The identification of the regulatory mechanism would provide promising clinical biomarkers or therapeutic targets in the diagnostic prediction and intervention treatment of memory deficits under neuropathic pain conditions. [ABSTRACT FROM AUTHOR]

A highly sensitive electrochemical sensor based on both potential and current dual signals was constructed via polypyrrole-coated chiral carbon nanotubes (L/DCNT@ PPy) loaded with Pt nanoparticles (Pt NPs) and β-cyclodextrin (β-CD) hybrid. Using L/D-CNT and β-CD as chiral selectors, PPy and Pt NPs enhanced the conductivity and the sensors showed excellent performance for chiral recognition of tyrosine (Tyr) and tryptophan (Trp). The linear ranges of the D-CNT@PPy@Pt NPs@β-CD sensor were 3-30 µM (Tyr) and 19.6-196 µM (Trp), respectively, the detection limits were 0.107 nM (Tyr) and 0.133 nM (Trp), respectively, and the recoveries for L-Tyr were 96.56%-106.32%. This electrochemical sensor based on a dual-signal strategy of potential and current was expected to be used in the field of point of care testing (POCT). [ABSTRACT FROM AUTHOR]

Background/Aims Some inflammatory bowel disease (IBD) patients in remission suffer from irritable bowel syndrome (IBS)-like symptoms (IBD-IBS). The pathogenesis has not yet been elucidated. The study aim is to evaluate relationships among quality of life (QOL), psychological status, and visceral sensitivity, and explore the formation mechanism of IBD-IBS. Methods Forty-seven patients with Crohn's disease in remission, 24 ulcerative colitis in remission, 26 IBS, and 20 healthy controls were included in the study. The abdominal pain, QOL, anxiety, and depression were evaluated through questionnaires. Visceral sensitivity was measured by rectal balloon distension. The serum levels of 5-hydroxytryptamine (5-HT) and nerve growth factor (NGF) were measured by enzyme-linked immunosorbent assay. The expressions of tryptase, 5-HT, NGF, and related receptors in colonic tissues were detected by immunohistochemistry and western blot. Results Prevalence of IBS-like symptoms in Crohn's disease and ulcerative colitis patients in clinical remission was 29.8% and 50.0%, respectively. The QOL was lower, the anxiety/depression scores were higher in IBD-IBS patients than those without IBS-like symptoms. Additionally, patients with IBD-IBS existed visceral hypersensitivity. Besides, abdominal pain was associated with poor QOL, visceral hypersensitivity, anxiety, and depression in IBD-IBS patients. The number of mast cells (MCs) and expressions of 5-HT, NGF, and related receptors were higher in IBD-IBS patients than those with no such symptoms. The serum levels of 5-HT and NGF positively correlated with abdominal pain and visceral hypersensitivity. Conclusion IBD-IBS patients may have low QOL and psychological abnormalities, as wells as visceral hypersensitivity which may be related to increased 5-HT and NGF levels released from activated mast cells. [ABSTRACT FROM AUTHOR]

The research on laser drilling of amorphous foils can promote the application of amorphous alloy in micro-machining. In this article, the effects of current, pulse width and defocusing amount on the quality of machined hole on Fe78Si9B13 amorphous alloy foils were analyzed by controlling the laser parameters. The experimental results showed that the hole diameter, remelting area (RMA) thickness and heat affected zone (HAZ) thickness increased obviously with the increase of current and pulse width. But high current caused serious erosion near the entrance of the hole and the taper of the machined holes increased with increasing pulse width. When the defocusing amount was 0, the hole diameter was the smallest and the forming quality of the machined hole was the best. Every parameter needs to be adjusted and coordinated to improve the quality of laser drilling. [ABSTRACT FROM AUTHOR]

An efficient and easy template-free method for the preparation of hierarchical porous carbons (HPCs) has been developed using low-priced coal tar pitch (CP) as the starting material. Application of the diketone (-COCO-) radical provides a carbonyl methylene group for polycyclic aromatic hydrocarbons by condensation and produces an effective micro-mesoporous network with a high specific surface area. With the help of controlled Friedel-Crafts reaction and oxidation, carboxyl-functionalized CP is obtained as the stratified porous CP precursor, and the high-temperature decarboxylation (>230°C) helped in generating well-developed micro-mesoporous carbon. The total pore volume of porous carbon of 1277.3 and 1.45 cm³g-1 the maximum BET surface area suggests that the rapid electrolyte ion exchange and charge transportability would be better for the electrochemical capacitor. [ABSTRACT FROM AUTHOR]

Brown planthopper (BPH) is one of the most destructive insects affecting rice (Oryza sativa L.) production. Phenylalanine ammonialyase (PAL) is a key enzyme involved in plant defense against pathogens, but the role of PAL in insect resistance is still poorly understood. Here we show that expression of the majority of PALs in rice is significantly induced by BPH feeding. Knockdown of OsPALs significantly reduces BPH resistance, whereas overexpression of OsPAL8 in a susceptible rice cultivar significantly enhances its BPH resistance. We found that OsPALs mediate resistance to BPH by regulating the biosynthesis and accumulation of salicylic acid and lignin. Furthermore, we show that expression of OsPAL6 and OsPAL8 in response to BPH attack is directly up-regulated by OsMYB30, an R2R3 MYB transcription factor. Taken together, our results demonstrate that the phenylpropanoid pathway plays an important role in BPH resistance response, and provide valuable targets for genetic improvement of BPH resistance in rice. [ABSTRACT FROM AUTHOR]

Developing high activity, strong durability, and cost-efficient electrocatalysts for the hydrogen evolution reaction (HER) is critical for the sustainable production of hydrogen energy. Herein, we have rationally designed three-dimensional (3D) heterogeneous catalyst of hollow nickel phosphide spheres coupled with molybdenum sulfide nanosheets (Ni2P@MoS2). Benefiting from the hollow spherical structure and the coupling effects between MoS2 and Ni2P, Ni2P@MoS2 shows superior activity for hydrogen generation over a wide pH range. It displays overpotentials of 181, 269 and 535 mV in 1.0 M KOH, 0.5 M H2SO4 and 1.0 M PBS, respectively, at a current density of 10 mAcm-2. A series of characterization techniques demonstrate that the strong coupling interaction between Ni2P and MoS2 effectively optimizes the electronic structure of the Ni2PMoS2 3D/2D interfaces, beneficial for regulating H* adsorption energy. This work offers a novel strategy for enhancing the HER performance of metal phosphide/sulfide catalysts by constructing heterostructured materials with abundant 3D/2D interfaces. [ABSTRACT FROM AUTHOR]

Glioma is one of the most common types of primary brain tumors. Ivermectin (IVM), a broad-spectrum antiparasitic drug, has been identified as a novel anticancer agent due to its inhibitory effects on the proliferation of glioma cells in vitro and in vivo. However, the ability of IVM to induce autophagy and its role in glioma cell death remains unclear. The main objective of the present study was to explore autophagy induced by IVM in glioma U251 and C6 cells, and the deep underlying molecular mechanisms. In addition, we examined the effects of autophagy on apoptosis in glioma cells. In the present study, transmission electronmicroscopy (TEM), immunofluorescence, Western blot and immunohistochemistry were used to evaluate autophagy activated by IVM. Cell viability was measured by 3-(4,5-dimethylthiazol2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and colony formation assay. The apoptosis rate was detected by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Meanwhile, autophagy inhibition was achieved by using chloroquine (CQ). U251-derived xenografts were established for examination of IVM-induced autophagy on glioma in vivo. Taken together, the results of the present study showed that autophagy induced by IVM has a protective effect on cell apoptosis in vitro and in vivo. Mechanistically, IVM induced autophagy through AKT/mTOR signaling and induced energy impairment. Our findings show that IVM is a promising anticancer agent and may be a potential effective treatment for glioma cancers. [ABSTRACT FROM AUTHOR]

TiO2 was loaded on SBA-15 mesoporous molecular sieves using the sol-gel method, and TiO2-SBA-15 was doped with Ce via Ce (NO3)3 ion exchange. The two aspects of TiO2 modification mentioned above were effectively combined. First, the TiO2catalyst was supported on the mesoporous molecular sieve SBA-15 using a sol-gel method, and then TiO2-SAB-15 was doped with Ce via ion exchange. The Ce-TiO2-SBA-15 catalyst was characterized using XRD, FT-IR, and N2 adsorption-desorption. The results showed that SBA-15 loaded with TiO2 still had a highly ordered two-dimensional hexagonal structure, and the specific surface area was slightly reduced, which showed that the porous structure of SBA-15 was beneficial for the dispersion of TiO2. The specific surface area of TiO2-SBA-15 increased without any change in structure after doping with Ce. The photo catalytic effects of different catalysts were investigated using the photo catalytic degradation of rhodamine B as a probe reaction. The degradation rate of rhodamine B (98.4 %.) was highest with an illumination time of 120 min. The results showed that the rare earth Ce-TiO2-SBA-15 catalyst can effectively reduce the photosynthesis of aquatic organisms after water pollution. The photo catalytic reaction was subject to first order reaction kinetics. [ABSTRACT FROM AUTHOR]

Deoxycytidine monophosphate deaminase (dCMP deaminase, DCD) is crucial to the production of dTTP needed for DNA replication and damage repair. However, the effect of DCD deficiency and its molecular mechanism are poorly understood in plants. Here, we isolated and characterized a rice albinic leaf and growth retardation (alr) mutant that is manifested by albinic leaves, dwarf stature and necrotic lesions. Map-based cloning and complementation revealed that ALR encodes a DCD protein. OsDCD was expressed ubiquitously in all tissues. Enzyme activity assays showed that OsDCD catalyses conversion of dCMP to dUMP, and the ΔDCD protein in the alr mutant is a loss-of-function protein that lacks binding ability. We report that alr plants have typical DCD-mediated imbalanced dNTP pools with decreased dTTP; exogenous dTTP recovers the wild-type phenotype. A comet assay and Trypan Blue staining showed that OsDCD deficiency causes accumulation of DNA damage in the alr mutant, sometimes leading to cell apoptosis. Moreover, OsDCD deficiency triggered cell cycle checkpoints and arrested cell progression at the G1/S-phase. The expression of nuclear and plastid genome replication genes was down-regulated under decreased dTTP, and together with decreased cell proliferation and defective chloroplast development in the alr mutant this demonstrated the molecular and physiological roles of DCD-mediated dNTP pool balance in plant development. [ABSTRACT FROM AUTHOR]

Intestinal microbes are an important system in the human body, with significant effects on behavior. An increasing body of research indicates that intestinal microbes affect brain function and neurogenesis, including sensitivity to stress. To investigate the effects of microbial colonization on behavior, we examined behavioral changes associated with hormones and hormone receptors in the hypothalamic-pituitary-adrenal (HPA) axis under stress. We tested germ-free (GF) mice and specific pathogen-free (SPF) mice, divided into four groups. A chronic restraint stress (CRS) protocol was utilized to induce external pressure in two stress groups by restraining mice in a conical centrifuge tube for 4 h per day for 21 days. After CRS, Initially, GF restraint-stressed mice explored more time than SPF restraint-stressed mice in the center and total distance of the OFT. Moreover, the CRH, ACTH, CORT, and ALD levels in HPA axis of GF restraint-stressed mice exhibited a significantly greater increase than those of SPF restraint-stressed mice. Finally, the Crhr1 mRNA levels of GF CRS mice were increased compared with SPF CRS mice. However, the Nr3c2 mRNA levels of GF CRS mice were decreased compared with SPF CRS mice. All results revealed that SPF mice exhibited more anxiety-like behavior than GF mice under the same external stress. Moreover, we also found that GF mice exhibited significant differences in, hormones, and hormone receptors compared with SPF mice. In conclusion, Imbalances of the HPA axis caused by intestinal microbes could affect the neuroendocrine system in the brain, resulting in an anxiety-like behavioral phenotype. This study suggested that intervention into intestinal microflora may provide a new approach for treating stress-related diseases. [ABSTRACT FROM AUTHOR]

Pyroptosis is a type of proinflammatory programmed cell death mediated by caspase 1 activity and occurs in several types of eukaryotic tumor cells, including gliomas. MicroRNAs (miRNAs), small endogenous noncoding RNAs, have been demonstrated to be advantageous in glioma therapy. However, the question of whether miRNAs regulate pyroptosis in glioma remains unknown. The current study found that caspase 1 expression was substantially increased in both glioma tissues and glioma cell lines, U87 and T98G, while miR-214 expression was significantly downregulated. Luciferase reporter assay recognized caspase 1 as a target gene of miR-214. These findings demonstrate that miR-214 could inhibit cell proliferation and migration through the regulation of pyroptosis intermediated by caspase 1 in glioma U87 and T98G cells and may suggest a novel therapeutic for the intervention of glioma. [ABSTRACT FROM AUTHOR]

In somatic cells spindle microtubules are nucleated from centrosomes that act as major microtubule organizing centers (MTOCs), whereas oocytes form meiotic spindles by assembling multiple acentriolar MTOCs without canonical centrosomes. Aurora A and Plk1 are required for these events, but the underlying mechanisms remain largely unknown. Here we show that CIP2A regulates MTOC organization by recruiting aurora A and Plk1 at spindle poles during meiotic maturation. CIP2A colocalized with pericentrin at spindle poles with a few distinct cytoplasmic foci. Although CIP2A has been identified as an endogenous inhibitor of protein phosphatase 2A (PP2A), overexpression of CIP2A had no effect on meiotic maturation. Depletion of CIP2A perturbed normal spindle organization and chromosome alignment by impairing MTOC organization. Importantly, CIP2A was reciprocally associated with CEP192, promoting recruitment of aurora A and Plk1 at MTOCs. CIP2A was phosphorylated by Plk1 at S904, which targets CIP2A to MTOCs and facilitates MTOC organization with CEP192. Our results suggest that CIP2A acts as a scaffold for CEP192-mediated MTOC assembly by recruiting Plk1 and aurora A during meiotic maturation in mouse oocytes. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM), one of the most aggressive human malignant brain tumors, is induced by multiple complex pathological mechanisms. The main cause of mortality in patients with GBM is the invasion-metastasis cascade of tumor cells. The dysfunction of Parkinson protein 2 E3 ubiquitin protein ligase (PARK2) is closely linked with the development of certain human cancers. However, whether PARK2 is associated with metastasis in GBM remains unknown. The present study demonstrated that the metastasis and invasion of U87 cells were significantly repressed by PARK2 overexpression. Conversely, knockdown of PARK2 facilitated the metastasis and invasion of A172 cells. Furthermore, PARK2 downregulated zinc finger E-box-binding homeobox 1 (ZEB1) expression and mitigated epithelial-mesenchymal transition (EMT). Promoter effects of PARK2 knockdown on cell metastasis and EMT were antagonized by silencing ZEB1 expression. These results indicated that PARK2 participated in regulating the invasion-metastasis cascade of cancer cells by depressing ZEB1 expression and acting as a metastasis suppressor in GBM progression, providing a potential therapeutic approach for GBM treatment. [ABSTRACT FROM AUTHOR]

Plants have evolved a repertoire of strategies collectively termed the shade-avoidance syndrome to avoid shade from canopy and compete for light with their neighbors. However, the signaling mechanism governing the adaptive changes of adult plant architecture to shade is not well understood. Here, we show that in Arabidopsis, compared with the wild type, several PHYTOCHROME-INTERACTING FACTORS (PIFS) overexpressors all display constitutive shade-avoidance syndrome under normal high red to far-red light ratio conditions but are less sensitive to the simulated shade, whereas the MIR156 overexpressors exhibit an opposite phenotype. The simulated shade induces rapid accumulation of PIF proteins, reduced expression of multiple MIR156 genes, and concomitant elevated expression of the SQUAMOSA- PROMOTER BINDING PROTEIN-LIKE (SPL) family genes. Moreover, in vivo and in vitro assays indicate that PIFs bind to the promoters of several MIR156 genes directly and repress their expression. Our results establish a direct functional link between the phytochrome-PIFs and miR156-SPL regulatory modules in mediating shade-avoidance syndrome. [ABSTRACT FROM AUTHOR]

Hsp70 regulates α-Synuclein (α-Syn) degeneration in Parkinson's disease (PD), indicating that Hsp70 promotion may be able to prevent or reverse α-Syn-induced toxicity in PD. Additionally, it has been demonstrated that glutamine (Gln) enhances Hsp70 expression. In the present study, Gln-induced Hsp70 promotion in pheochromocytoma was investigated with reverse transcription-quantitative polymerase chain reaction and western blotting methods. Then it was observed whether heat shock factor (HSF)-1 was required for this phenomenon with an RNA interference strategy. The regulatory role of Gln on α-Syn degeneration was also determined in the α-Syn-overexpressed PC12 [PC12 (α-Syn+)] cells, which were treated with or without the proteasomal inhibitor lactacystin (Lac). The results demonstrated that treatment with =10 mM Gln significantly increased Hsp70 mRNA and protein levels (P<0.05) and that this promotion was HSF-1-dependent, as HSF-1 knockout with HSF-1-specific small interfering RNA abrogated Hsp70 promotion in PC12 (α-Syn+) cells. Furthermore, Gln treatment markedly upregulated α-Syn degeneration in PC12 (α-Syn+) cells, which was significantly reduced (P<0.05) in the presence of Lac. Therefore, the present study suggests that Gln is able to induce the promotion of Hsp70 expression in PC12 cells in an HSF-1-dependent manner and that Gln-mediated Hsp70 promotion may increase α-Syn degradation even in the presence of proteasomal inhibitor. Thus, glutamine may be a potential therapeutic agent to prevent α-Syn aggregation in PD. [ABSTRACT FROM AUTHOR]