Intestinal dysbiosis mediates cognitive impairment via the intestine and brain NLRP3 inflammasome activation in chronic sleep deprivation.

Growing evidence suggests the involvement of the microbiota-gut-brain axis in cognitive impairment induced by sleep deprivation (SD), however how the microbiota-gut-brain axis work remains elusive. Here, we discovered that chronic SD induced intestinal dysbiosis, activated NLRP3 inflammasome in the colon and brain, destructed intestinal/blood-brain barrier, and impaired cognitive function in mice. Transplantation of "SD microbiota" could almost mimic the pathological and behavioral changes caused by chronic SD. Furthermore, all the behavioral and pathological abnormalities were practically reversed in chronic sleep-deprived NLRP3-/- mice. Regional knockdown NLRP3 expression in the gut and hippocampus, respectively. We observed that down-regulation of NLRP3 in the hippocampus inhibited neuroinflammation, and ameliorated synaptic dysfunction and cognitive impairment induced by chronic SD. More intriguingly, the down-regulation of NLRP3 in the gut protected the intestinal barrier, attenuated the levels of peripheral inflammatory factors, down-regulated the expression of NLRP3 in the brain, and improved cognitive function in chronic SD mice. Our results identified gut microbiota as a driver in chronic SD and highlighted the NLRP3 inflammasome as a key regulator within the microbiota-gut-brain axis.

Liver X receptor agonists exert antitumor effects against hepatocellular carcinoma via inducing REPS2 expression.

Recent studies show that liver X receptor (LXR) agonists exert significant antitumor effects in a variety of tumor cell lines including hepatocellular carcinoma (HCC). But the molecular mechanisms underlying LXR antitumor activity are not fully understood. In this study we investigated the effect of LXR agonist T0901317 (T317) on HCC development and its relationship with RalA binding protein 1 (RALBP1)-associated EPS domain containing 2 (REPS2)/epidermal growth factor receptor (EGFR) signaling axis. We showed that T317 (0.1-0.5 µM) dose-dependently increased REPS2 expression in normal hepatocytes (BNLCL.2 and LO2) and HCC cells (HepG2 and Huh-7). Using promoter activity assay and chromatin immunoprecipitation (CHIP) assay we demonstrated that T317 enhanced REPS2 expression at the transcriptional level via promoting the binding of LXR protein to the LXR-response element (LXRE) in the REPS2 promoter region. We showed that the inhibitory effect of T317 on the proliferation and migration of HCC cells was closely related to REPS2. Moreover, we revealed that T317 (400 nM) increased expression of REPS2 in HepG2 cells, thus inhibiting epidermal growth factor (EGF)-mediated endocytosis of EGFR as well as the downstream activation of AKT/NF-κB, p38MAPK, and ERK1/2 signaling pathways. Clinical data analysis revealed that REPS2 expression levels were inversely correlated with the development of HCC and reduced REPS2 expression associated with poor prognosis, suggesting that REPS2 might be involved in the development of HCC. In conclusion, this study provides new insights into the potential mechanisms of LXR agonist-inhibited HCC.

Transcription factor 21 accelerates vascular calcification in mice by activating the IL-6/STAT3 signaling pathway and the interplay between VSMCs and ECs.

Vascular calcification is caused by the deposition of calcium salts in the intimal or tunica media layer of the aorta, which increases the risk of cardiovascular events and all-cause mortality. However, the mechanisms underlying vascular calcification are not fully clarified. Recently it has been shown that transcription factor 21 (TCF21) is highly expressed in human and mouse atherosclerotic plaques. In this study we investigated the role of TCF21 in vascular calcification and the underlying mechanisms. In carotid artery atherosclerotic plaques collected from 6 patients, we found that TCF21 expression was upregulated in calcific areas. We further demonstrated TCF21 expression was increased in an in vitro vascular smooth muscle cell (VSMC) osteogenesis model. TCF21 overexpression promoted osteogenic differentiation of VSMC, whereas TCF21 knockdown in VSMC attenuated the calcification. Similar results were observed in ex vivo mouse thoracic aorta rings. Previous reports showed that TCF21 bound to myocardin (MYOCD) to inhibit the transcriptional activity of serum response factor (SRF)-MYOCD complex. We found that SRF overexpression significantly attenuated TCF21-induced VSMC and aortic ring calcification. Overexpression of SRF, but not MYOCD, reversed TCF21-inhibited expression of contractile genes SMA and SM22. More importantly, under high inorganic phosphate (3 mM) condition, SRF overexpression reduced TCF21-induced expression of calcification-related genes (BMP2 and RUNX2) as well as vascular calcification. Moreover, TCF21 overexpression enhanced IL-6 expression and downstream STAT3 activation to facilitate vascular calcification. Both LPS and STAT3 could induce TCF21 expression, suggesting that the inflammation and TCF21 might form a positive feedback loop to amplify the activation of IL-6/STAT3 signaling pathway. On the other hand, TCF21 induced production of inflammatory cytokines IL-1ß and IL-6 in endothelial cells (ECs) to promote VSMC osteogenesis. In EC-specific TCF21 knockout (TCF21ECKO) mice, VD3 and nicotine-induced vascular calcification was significantly reduced. Our results suggest that TCF21 aggravates vascular calcification by activating IL-6/STAT3 signaling and interplay between VSMC and EC, which provides new insights into the pathogenesis of vascular calcification. TCF21 enhances vascular calcification by activating the IL-6-STAT3 signaling pathway. TCF21 inhibition may be a new potential therapeutic strategy for the prevention and treatment of vascular calcification.

MARIS plays important roles in Arabidopsis pollen tube and root hair growth.

In flowering plants, male gametes are delivered to female gametes for double fertilization through pollen tubes. Therefore, pollen tube growth is crucial for double fertilization. Despite its importance to sexual reproduction, genetic mechanisms of pollen tube growth remain poorly understood. In this study, we characterized the receptor-like cytoplasmic protein kinase (RLCK) gene, MARIS (MRI) that plays critical roles in pollen tube growth. MRI is preferentially expressed in pollen grains, pollen tubes and roots. Mutation in MRI by a Ds insertion led to a burst of pollen tubes after pollen germination. Pollen-rescue assay by pollen and pollen tube-specific expression of MRI in the mri-4 mutant showed that loss of MRI function also severely affected root hair elongation. MRI protein interacted with the protein kinase OXIDATIVE SIGNAL INDUCIBLE1 (OXI1) in the in vitro and in vivo assays, which functions in plant defence and root hair development, and was phosphorylated by OXI1 in vitro. Our results suggest that MRI plays important roles in pollen tube growth and may function in root hair elongation through interaction with OXI1.

[Bonding strength of resin and tooth enamel after teeth bleaching with cold plasma].

OBJECTIVE: To investigate the immediate bond strength and surface structure of resin and the tooth enamel which treated by cold plasma. METHODS: In the study, 40 bovine incisors were divided into two equal parts. In this sense, all enamel adhesive samples were prepared and then randomly divided into 4 groups (n =20). group 1: acid + single bond 2+resin composite (control group); group 2:beyond bleaching+ acid+single bond 2+resin composite; group 3: treated by cold plasma for 5 minutes+ acid+single bond 2+resin composite; group 4: treated by cold plasma for 5 minutes+single bond 2+resin composite. Single bond 2 bonding system and Filtek Z250 resin were used in this experiment. The shear bond strength was tested by universal testing machine. The surface of the enamel in different processes was observed by scanning electron microscope (SEM). Statistical analyses by the single factor analysis of variance and multiple pairwise comparisons were performed with SPSS 17.0 . RESULTS: The shear bond strength of group 4 (8.60 MPa) was significantly lower than that of the other three groups (P<0.05). The shear bond strength of group 2 (17.89 MPa) was higher than that of group 4, but lower than group 1 and group 3 (P<0.05).There was no significant difference between group 1 (34.82 MPa) and group 3 (34.69 MPa). Scanning electron microscope indicated that the enamel treated by cold plasma had slight molten form, which was different from etched enamel surface.The fractured surface of group 3 was mix fracture, which was similar to the control group (group 1). CONCLUSION: Compared with the conventional clinic bleaching, immediate bond strength of resin-enamel that treated by cold plasma has not been affected.

Evaluation of Sealer Remnants Using a Bioceramic Sealer Single-cone Technique after Post Space Preparation and its Influence on the Adhesion of Fibre Posts in vitro.

OBJECTIVE: To compare calcium silicate-based endodontic sealer and epoxy resin-based sealer remnants on root canal walls after post space preparation and their influence on the bond strength of fibre posts fixed with a dual-cured resin cement. METHODS: Thirty-six extracted single-root mandibular premolars were instrumented and divided randomly into two equal groups with different endodontic sealers. iRoot SP (Innovative BioCeramix, Vancouver, Canada) was employed in the experimental group and AH Plus (Dentsply Sirona, Charlotte, NC, USA) was used in the control group. Sealer remnants were observed under an endodontic microscope after root canal therapy and post space preparation. Fibre posts were fixed with dual-cured resin cement. Specimens were taken at each third of the post space. The push-out bond strength was measured using a universal testing machine and fracture modes were assessed. Statistical analysis was performed using an independent samples t test and one-way analysis of variance. RESULTS: There was no statistically significant difference in bond strength of fibre posts between the control and experimental group (P > 0.05); however, sealer remnants were observed in 38.9% of the samples treated with iRoot SP and none of the samples treated with AH Plus. The major fracture mode in samples treated with iRoot SP was adhesive failure between the resin cement and the post, and no adhesive failure between the resin cement and dentine occurred at the site of the sealer remnant. The presence of iRoot SP remnants on the root canal walls after post space preparation did not interfere with bonding. CONCLUSION: iRoot SP is a viable option for root canal obturation before fibre post cementation.

Diagnostic value of the cerebrospinal fluid lipoarabinomannan assay for tuberculous meningitis: a systematic review and meta-analysis.

Objective: This systematic review aims to evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) lipoarabinomannan (LAM) assays in detecting tuberculous meningitis (TBM). Methods: A systematic review search was conducted in PubMed and five other databases up to April 2023. Studies that evaluated the diagnostic accuracy of CSF LAM assays were included with either definitive or composite reference standard used as the preferred reference standard. The quality of the included studies was assessed using the QUADAS-2 tool. We performed a bivariate random-effects meta-analysis and calculated the summary diagnostic statistics. Results: A total of six studies, including a sample size of 999, were included in the final analysis. The pooled sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of CSF LAM for diagnosing TBM were determined to be 0.44 (95% CI: 0.31-0.58), 0.89 (95% CI: 0.81-0.93), and 0.76 (95% CI: 0.73-0.80), respectively. Significant heterogeneity was observed in both sensitivity (Q = 73.82, p < 0.01; I2 = 86.45, 95%CI: 79.64-93.27) and specificity (Q = 95.34, p < 0.01; I2 = 89.51, 95% CI: 84.61-94.42). Regression analysis indicated that the study design (retrospective vs. prospective) was associated with the heterogeneity of pooled sensitivity and specificity (all p < 0.05). Conclusion: Although more prospective studies are required to validate the role of the CSF LAM assay, current evidence supports that the performance of the CSF LAM assay is unsatisfactory for the TBM diagnosis. Additionally, the optimization of the CSF LAM assay (e.g., improvements in CSF collection and preparation methods) should be considered to improve its performance.

The incremental value of CCTA-derived myocardial radiomics signature for ischemia diagnosis with reference to CT myocardial perfusion imaging.

OBJECTIVES: To explore the incremental value of myocardial radiomics signature derived from static coronary computed tomography angiography (CCTA) for identifying myocardial ischemia based on stress dynamic CT myocardial perfusion imaging (CT-MPI). METHODS: Patients who underwent CT-MPI and CCTA were retrospectively enrolled from two independent institutions, one used as training and the other as testing. Based on CT-MPI, coronary artery supplying area with relative myocardial blood flow (rMBF) value <0.8 was considered ischemia. Conventional imaging features of target plaques which caused the most severe narrowing of the vessel included area stenosis, lesion length (LL), total plaque burden, calcification burden, non-calcification burden, high-risk plaque (HRP) score, and CT fractional flow reserve (CT-FFR). Myocardial radiomics features were extracted at three vascular supply areas from CCTA images. The optimized radiomics signature was added to the conventional CCTA features to build the combined model (radiomics + conventional). RESULTS: There were 168 vessels from 56 patients enrolled in the training set, and the testing set consisted of 135 vessels from 45 patients. From either cohort, HRP score, LL, stenosis ≥50% and CT-FFR ≤0.80 were associated with ischemia. The optimal myocardial radiomics signature consisted of nine features. The detection of ischemia using the combined model was significantly improved compared with conventional model in both training and testing set (AUC 0.789 vs 0.608, p < 0.001; 0.726 vs 0.637, p = 0.045). CONCLUSIONS: Myocardial radiomics signature extracted from static CCTA combining with conventional features could provide incremental value to diagnose specific ischemia. ADVANCES IN KNOWLEDGE: Myocardial radiomics signature extracted from CCTA may capture myocardial characteristics and provide incremental value to detect specific ischemia when combined with conventional features.

DI-3-n-butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of NLRP3-Mediated neuroinflammation.

Our previous study has demonstrated that chronic stress could cause cognitive deficits and tau pathology. However, the underlying mechanism and whether/how DI-3-n-Butylphthalide (NBP) ameliorates these effects are still unclear. Here, Wild-type mice were subjected to chronic unpredictable and mild stress (CUMS) for 8 weeks. Following the initial 4 weeks, the stressed animals were separated into susceptible (depressive) and unsusceptible (resilient) groups based on behavioral tests. Then, NBP (30 mg/kg i.g) was administered for 4 weeks. Morris water maze (MWM), Western-blot, Golgi staining, immunofluorescence staining and ELISA were used to examine behavioral, biochemical, and pathological changes. The results showed that both depressive and resilient mice displayed spatial memory deficits and an accumulation of tau in the hippocampus. Activated microglia and NLRP3 inflammasome were found after 8-week chronic stress. We also found a decreased level of postsynaptic density (PSD) related proteins (PSD93 and PSD95) and decreased the number of dendritic spines in the hippocampus. Interestingly, almost all the pathological changes in depressive and resilient mice previously mentioned could be reversed by NBP treatment. To further investigate the role of NLRP3 inflammasome in chronic stress-induced cognitive deficits, NLRP3 KO mice were also exposed to chronic stress. And these changes induced by chronic stress could not be found in NLRP3 KO mice. These results show an important role for the NLRP3/caspase-1/IL-1ß axis in chronic stress-induced cognitive deficits and NBP meliorates cognitive impairments and selectively attenuates phosphorylated tau accumulation in stressed mice through regulation of NLRP3 inflammatory signaling pathway.

[Spatial structure and distribution simulation of Aphis gossipii Glover population based on GIS].

Based on geographic information system (GIS) and geostatistical analysis, this paper studied the spatial structure of Aphis gossipii Glover population in Xiangshan District of Zhongwei City, Ningxia Province, with the spatial distribution of the population simulated by ordinary Kriging interpretation. The spatial structure of A. gossipii population varied with its occurrence stage (initial, blossom, and final stage). The semivariograms of A. gossipii could be described by exponential or Gaussian model, indicating that A. gossipii had an aggregated spatial arrangement. The aggregation degrees at different occurrence stages were all beyond 45%, and the spatial correlation ranged from 10.37 km to 29.11 km. The spatial variance was greatly affected by spatial autocorrelation. The population dynamics of A. gossipii at its different occurrence stages could be easily analyzed and intuitively simulated from the two aspects of time and space by spatial distribution simulation, and thus, the occurrence position and degree of A. gossipii could be easily determined.

[Suitable habitat of Therioaphis trifolii population on arable lands of southern Ningxia based on GIS].

Based on GIS techniques, the interpolation maps of Therioaphis trifolii population on the arable lands in Yuanzhou District of Guyuan City in different periods were overlapped with the ecological regionalization map and digital altitude map, aimed to analyze the relations of T. trifolii population density with its ecological environment and geographical distribution. In the study area, the occurrence and distribution of T. trifolii had close relations with climate, geomorphology, and altitude. The suitable habitat of T. trifolii in the District was located in the semi-arid plain area and semi-arid holly area at the altitude 1440-2000 m, while the most possible occurrence area was the semi-arid plain at the altitude 1600-1800 m. By combining the suitable habitat with the interpolation maps of T. trifolii population in different periods, the spatial dynamics of T. trifolii population in variety of ecological areas could be analyzed quantitatively.

[Spatial structure analysis and distribution simulation of Therioaphis trifolii population based on geostatistics and GIS].

Based on geographic information system and geostatistics, the spatial structure of Therioaphis trifolii population of different periods in Yuanzhou district of Guyuan City, the southern Ningxia Province, was analyzed. The spatial distribution of Therioaphis trifolii population was also simulated by ordinary Kriging interpretation. The results showed that Therioaphis trifolii population of different periods was correlated spatially in the study area. The semivariograms of Therioaphis trifolii could be described by exponential model, indicating an aggregated spatial arrangement. The spatial variance varied from 34.13%-48.77%, and the range varied from 8.751-12.049 km. The degree and direction of aggregation showed that the trend was increased gradually from southwest to northeast. The dynamic change of Therioaphis trifolii population in different periods could be analyzed intuitively on the simulated maps of the spatial distribution from the two aspects of time and space, The occurrence position and degree of Therioaphis trifolii to a state of certain time could be determined easily.