Mechanism of Dendrobium Nobile Polysaccharide Inhibition of Ferroptosis in Rats with Spinal Cord Injury.

BACKGROUND: It has been reported that ferroptosis participates in the pathophysiological mechanism of spinal cord injury (SCI). Our preliminary experiments verified that dendrobium nobile polysaccharide (DNP) improved the behavioral function of SCI rats. Therefore, the purpose of this study was to examine the role of DNP on ferroptosis and its neuroprotective mechanism in SCI rats. METHODS: Adult female sprague dawley (SD) rats were exposed to SCI by Allen's method, followed by an intragastric injection of 100 mg/kg DNP per day for 2 weeks. Behavioral features were verified by the Basso-Beattie-Bresnahan (BBB) scale and footprint evaluation. Iron content and glutathione (GSH) were assessed spectrophotometrically. Mitochondrial morphology was examined by transmission electron microscopy. The expression of ferroptosis-related genes, including System Xc- light chain (xCT), G-rich RNA sequence binding Factor 1 (GRSF1) and glutathione peroxidase 4 (Gpx4), was examined by real-time polymerase chain reaction (PCR) and western blot. The spinal cavity was defined using hematoxylin-eosin (HE) staining, and neuronal modifications were detected by immunofluorescence. RESULTS: Compared with the SCI group, the BBB score of rats in the DNP group increased at 7 d, 14 d, 21 d, and 28 d. The differences between the two groups were statistically significant. At 12 h post-injury the iron content began to decrease. At 24 h post-injury the iron content decreased significantly in the DNP group. The morphological changes of the mitochondrial crest and membrane in the DNP group were ameliorated within 24 h. Compared with the sham group, the expression of xCT, GSH, Gpx4, and GRSF1 were significantly reduced after SCI. After DNP treatment, the expression of xCT, Gpx4, and GSH were higher. The tissue cavity area was significantly reduced and the amount of NeuN+ cells was increased in the DNP group at 14 d and 28 d after SCI. CONCLUSIONS: DNP facilitated the post-injury recovery in SCI rats via the inhibition of ferroptosis.

Ultra-processed food consumption and the risk of incident chronic kidney disease: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Recent individual studies have indicated that ultra-processed food (UPF) consumption may be associated with the incidence of chronic kidney disease (CKD). We conducted a systematic review and meta-analysis based on those longitudinal studies evaluating the relationship between UPF consumption and the risk of incident CKD, and synthesizing the results. METHOD: PubMed, Embase, The Cochrane Library, Web of Science, and Scopus were searched from inception through 22 March 2023. Any longitudinal studies evaluating the relationship between UPF consumption and the risk of incident CKD were included. Two researchers independently conducted the literature screening and data extraction. RR and its 95% CI were regarded as the effect size. The Newcastle-Ottawa Scale (NOS) was applied to assess the quality of the studies included, and the effect of UPF consumption on the risk of incident CKD was analyzed with STATA version 15.1. This study's protocol was registered in PROSPERO (CRD42023411951). RESULTS: Four cohort studies with a total of 219,132 participants were included after screening. The results of the meta-analysis suggested that the highest UPF intake was associated with an increased risk of incident CKD (RR = 1.25; 95% CI: 1.18-1.33). CONCLUSIONS: High-dose UPF intake was associated with an increased risk of incident CKD. However, the underlying mechanisms remain unknown. Thus, more standardized clinical studies and further exploration of the mechanisms are needed in the future.

The PLATZ Transcription Factor GL6 Affects Grain Length and Number in Rice.

Grain size is one of the key determinants of grain yield. Although a number of genes that control grain size in rice (Oryza sativa) have been identified, the overall regulatory networks behind this process remain poorly understood. Here, we report the map-based cloning and functional characterization of the quantitative trait locus GL6, which encodes a plant-specific plant AT-rich sequence- and zinc-binding transcription factor that regulates rice grain length and spikelet number. GL6 positively controls grain length by promoting cell proliferation in young panicles and grains. The null gl6 mutant possesses short grains, whereas overexpression of GL6 results in large grains and decreased grain number per panicle. We demonstrate that GL6 participates in RNA polymerase III transcription machinery by interacting with RNA polymerase III subunit C53 and transcription factor class C1 to regulate the expression of genes involved in rice grain development. Our findings reveal a further player involved in the regulation of rice grain size that may be exploited in future rice breeding.

Transcriptome-wide investigation of circular RNAs in rice.

Various stable circular RNAs (circRNAs) are newly identified to be the abundance of noncoding RNAs in Archaea, Caenorhabditis elegans, mice, and humans through high-throughput deep sequencing coupled with analysis of massive transcriptional data. CircRNAs play important roles in miRNA function and transcriptional controlling by acting as competing endogenous RNAs or positive regulators on their parent coding genes. However, little is known regarding circRNAs in plants. Here, we report 2354 rice circRNAs that were identified through deep sequencing and computational analysis of ssRNA-seq data. Among them, 1356 are exonic circRNAs. Some circRNAs exhibit tissue-specific expression. Rice circRNAs have a considerable number of isoforms, including alternative backsplicing and alternative splicing circularization patterns. Parental genes with multiple exons are preferentially circularized. Only 484 circRNAs have backsplices derived from known splice sites. In addition, only 92 circRNAs were found to be enriched for miniature inverted-repeat transposable elements (MITEs) in flanking sequences or to be complementary to at least 18-bp flanking intronic sequences, indicating that there are some other production mechanisms in addition to direct backsplicing in rice. Rice circRNAs have no significant enrichment for miRNA target sites. A transgenic study showed that overexpression of a circRNA construct could reduce the expression level of its parental gene in transgenic plants compared with empty-vector control plants. This suggested that circRNA and its linear form might act as a negative regulator of its parental gene. Overall, these analyses reveal the prevalence of circRNAs in rice and provide new biological insights into rice circRNAs.

An-1 encodes a basic helix-loop-helix protein that regulates awn development, grain size, and grain number in rice.

Long awns are important for seed dispersal in wild rice (Oryza rufipogon), but are absent in cultivated rice (Oryza sativa). The genetic mechanism involved in loss-of-awn in cultivated rice remains unknown. We report here the molecular cloning of a major quantitative trait locus, An-1, which regulates long awn formation in O. rufipogon. An-1 encodes a basic helix-loop-helix protein, which regulates cell division. The nearly-isogenic line (NIL-An-1) carrying a wild allele An-1 in the genetic background of the awnless indica Guangluai4 produces long awns and longer grains, but significantly fewer grains per panicle compared with Guangluai4. Transgenic studies confirmed that An-1 positively regulates awn elongation, but negatively regulates grain number per panicle. Genetic variations in the An-1 locus were found to be associated with awn loss in cultivated rice. Population genetic analysis of wild and cultivated rice showed a significant reduction in nucleotide diversity of the An-1 locus in rice cultivars, suggesting that the An-1 locus was a major target for artificial selection. Thus, we propose that awn loss was favored and strongly selected by humans, as genetic variations at the An-1 locus that cause awn loss would increase grain numbers and subsequently improve grain yield in cultivated rice.

Regional thermochemotherapy versus hepatic arterial infusion chemotherapy for palliative treatment of advanced hilar cholangiocarcinoma: a retrospective controlled study.

OBJECTIVES: To retrospectively assess the efficacy of regional thermochemotherapy (TCT) compared with hepatic arterial infusion chemotherapy (HAIC)-alone for palliative treatment of advanced hilar cholangiocarcinoma (HC) and to determine the prognostic factors associated with survival. METHODS: Forty-three consecutive patients with advanced HC underwent regional TCT (TCT group) and HAIC (HAIC group). We analyzed baseline characteristics, overall survival (OS), progression-free survival (PFS), stent patency time (SPT), adverse events (AEs), and prognostic factors for OS between the two groups. RESULTS: OS of patients treated with regional TCT was significantly longer compared to that of patients treated with HAIC (median OS: 20.3 vs. 13.2 months, P = 0.004), and SPT and PFS were significantly increased in the TCT group compared with the HAIC group (median SPT: 26.5 vs. 10.5 months, P < 0.001; median PFS: 16.5 vs. 10.2 months, P = 0.001). TCT and metal stent insertion were two independent prognostic factors associated with survival. The treatment-related AEs were tolerable and similar in the two groups, except for hilar pain (34.6 %) and skin rashes (24.6 %) in the TCT group. CONCLUSIONS: Our results show that regional TCT is safe and more effective than HAIC-alone and may be a promising option for palliative treatment of advanced HC. Metal stenting before TCT appears to improve patients' OS. KEY POINTS: • Regional TCT is a novel combination for palliative treatment of advanced HC • Our data showed significantly promising outcomes in the TCT group • HC patients with metal stenting appeared to derive greater benefit from TCT.

Genetic control of seed shattering in rice by the APETALA2 transcription factor shattering abortion1.

Seed shattering is an important agricultural trait in crop domestication. SH4 (for grain shattering quantitative trait locus on chromosome 4) and qSH1 (for quantitative trait locus of seed shattering on chromosome 1) genes have been identified as required for reduced seed shattering during rice (Oryza sativa) domestication. However, the regulatory pathways of seed shattering in rice remain unknown. Here, we identified a seed shattering abortion1 (shat1) mutant in a wild rice introgression line. The SHAT1 gene, which encodes an APETALA2 transcription factor, is required for seed shattering through specifying abscission zone (AZ) development in rice. Genetic analyses revealed that the expression of SHAT1 in AZ was positively regulated by the trihelix transcription factor SH4. We also identified a frameshift mutant of SH4 that completely eliminated AZs and showed nonshattering. Our results suggest a genetic model in which the persistent and concentrated expression of active SHAT1 and SH4 in the AZ during early spikelet developmental stages is required for conferring AZ identification. qSH1 functioned downstream of SHAT1 and SH4, through maintaining SHAT1 and SH4 expression in AZ, thus promoting AZ differentiation.

Large primary hepatocellular carcinoma: transarterial chemoembolization monotherapy versus combined transarterial chemoembolization-percutaneous microwave coagulation therapy.

BACKGROUND AND AIM: To evaluate the clinical benefits of transarterial chemoembolization (TACE) monotherapy or TACE combined with percutaneous microwave coagulation therapy (PMCT) and the long-term survival rate of patients with large primary hepatocellular carcinoma (HCC) treated with these techniques. METHODS: This is a retrospective study involving 136 patients with unresectable large HCC (189 tumor nodules, ≥ 5.0 cm in diameter) admitted to Sun Yat-Sen University Memorial Hospital (Guangzhou, China) between January 2004 and December 2011. The median follow-up time was 41 months (range, 6-96 months). Of these patients, 80 patients received TACE monotherapy and 56 patients received TACE combined with PMCT. The median interval between treatments and overall survival (OS) were hierarchically analyzed using log-rank tests. RESULTS: All patients successfully underwent TACE alone or TACE with PMCT with no serious complications. The median survival time was 13 months (range, 3-84 months) for the TACE group and 25 months (range, 7-96 months) for the TACE-PMCT group. The 1-year, 3-year, and 5-year OS rates were 62.5%, 17.5%, and 5.0% in the TACE group, respectively. In contrast, in the TACE-PMCT group, the 1-year, 3-year, and 5-year OS rates were 87.5%, 50.0%, and 10.0%, respectively. This difference was statistically significant between the groups (P < 0.001). CONCLUSIONS: TACE combined with PMCT had advantages in prolonging OS with satisfying time to progression and improving liver function in patients with large unresectable HCC. The results suggest that further prospective studies are required to confirm the findings of this study.

Predictive value of C-reactive protein for disease severity and survival in COVID-19 patients: a systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19) is an infectious disease that can develop multiple complications and even be life-threatening. The aim of this study is to summarize current evidence of C-reactive protein's (CRP) predictive value for disease severity and survival of COVID-19 patients, focusing on curing patients and reducing the risk of death. We systematically searched related studies from four large databases: Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang Database, all published between December 2019 and June 2021. Then, we implemented meta-analysis using random-effects models through STATA 15.1 and Review Manager 5.3. We also implemented sensitivity analysis and used funnel plots to check publication bias. From the systematic search of the four databases, we were able to identify 18 studies containing a total of 3052 patients. Meta-analysis results showed that 1) CRP levels were lower in non-severe patients than in severe patients (Standardized Mean Difference (SMD) = - 0.87 mg/L, 95% Confidence Interval (CI) = [ - 1.27, - 0.47], p < 0.001); 2) CRP levels were lower in non-intensive care unit (ICU) patients than in ICU patients (SMD = - 1.39 mg/L, 95% CI = [- 1.68, - 1.11], p < 0.001), and 3) CRP levels were lower in survivors than in non-survivors (SMD =- 1.32 mg/L, 95% CI = [- 1.95, - 0.69], p < 0.001). Sensitivity analysis showed these results were stable. Funnel plots indicated no publication bias. The CRP level may timely reflect disease severity and predict survival of COVID-19 patients and may be worthy of further popularization and application in clinic practice.

Negative Life Events, Negative Copying Style, and Internet Addiction in Middle School Students: A Large Two-year Follow-up Study.

Through a two-year follow-up study among 2,845 middle school students, we examined the impact of baseline negative life events (NLE) on follow-up negative copying style (NCS) and Internet addiction (IA), and the mediation of NCS between NLE and IA. We found that all NLE, NCS, and IA were correlated, and that both NLE and NCS were risk factors for IA. Structural equation modeling (SEM) results showed that NLE were associated with increased NCS (ß = 0.17, p < 0.01) and IA (ß = 0.16, p < 0.01), that NCS was associated IA ( ß = 0.33, p < 0 0.01), and that NCS partially mediated the effect of NLE on IA ( ß = 0.17, p < 0.01). This large longitudinal study provided solid empirical evidence that NLE and NCS played important roles in IA among middle school students. Educators and policy makers may adopt corresponding approaches to address IA among this population.

Untargeted serum and liver metabolomics analyses reveal the gastroprotective effect of polysaccharide from Evodiae fructus on ethanol-induced gastric ulcer in mice.

This study aimed at investigating the gastroprotective effect of Evodiae fructus polysaccharide (EFP) against ethanol-induced gastric ulcer in mice. Biochemical indexes along with untargeted serum and liver metabolomics were determined. Results showed that pre-treatment of EFP alleviated ethanol-induced gastric ulcer in mice. EFP lessened oxidative stress and inflammation levels of stomachs, showing as increments of SOD and GSH-Px activities, GSH content and IL-10 level, and reductions of MDA and IL-6 levels. Meanwhile, EFP activated the Keap1/Nrf2/HO-1 signaling pathway through increasing Nrf2 and HO-1 protein expressions, and decreasing Keap1 protein expression. Serum and liver metabolomics analyses indicated that 10 metabolic potential biomarkers were identified among normal control, ulcer control and 200 mg/kg·bw of EFP groups, which were related to 5 enriched metabolic pathways including vitamin B6 metabolism, nicotinate and nicotinamide metabolism, pentose phosphate pathway, bile secretion and ascorbate and aldarate metabolism. Further pearson's correlation analysis indicated that there were some positive and negative correlations between the biomarkers and the biochemical indexes. It could be concluded that the gastroprotection of EFP might be related to anti-oxidative stress, anti-inflammation, activation of Keap1/Nrf2/HO-1 signaling pathway and alteration of metabolic pathways. This study supports the potential application of EFP in preventing ethanol-induced gastric ulcer.

Advances in health-promoting effects of natural polysaccharides: Regulation on Nrf2 antioxidant pathway.

Natural polysaccharides (NPs) possess numerous health-promoting effects, such as liver protection, kidney protection, lung protection, neuroprotection, cardioprotection, gastrointestinal protection, anti-oxidation, anti-diabetic, and anti-aging. Nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway is an important endogenous antioxidant pathway, which plays crucial roles in maintaining human health as its protection against oxidative stress. Accumulating evidence suggested that Nrf2 antioxidant pathway might be one of key regulatory targets for the health-promoting effects of NPs. However, the information concerning regulation of NPs on Nrf2 antioxidant pathway is scattered, and NPs show different regulatory behaviors in their different health-promoting processes. Therefore, in this article, structural features of NPs having regulation on Nrf2 antioxidant pathway are overviewed. Moreover, regulatory effects of NPs on this pathway for health-promoting effects are summarized. Furthermore, structure-activity relationship of NPs for health-promoting effects by regulating the pathway is preliminarily discussed. Otherwise, the prospects on future work for regulation of NPs on this pathway are proposed. This review is beneficial to well-understanding of underlying mechanisms for health-promoting effects of NPs from the view angle of Nrf2 antioxidant pathway, and provides a theoretical basis for the development and utilization of NPs in promoting human health.

Time-restricted feeding's effect on overweight and obese patients with chronic kidney disease stages 3-4: A prospective non-randomized control pilot study.

Background: Time-restricted feeding (TRF) has become a popular weight loss method in recent years. It is widely used in the nutritional treatment of normal obese people and obese people with chronic diseases such as diabetes mellitus and hypertension, and has shown many benefits. However, most TRF studies have excluded chronic kidney disease (CKD) patients, resulting in a lack of sufficient evidence-based practice for the efficacy and safety of TRF therapy for CKD. Therefore, we explore the efficacy and safety of TRF in overweight and obese patients with moderate-to-severe stage CKD through this pilot study, and observe patient compliance to assess the feasibility of the therapy. Methods: This is a prospective, non-randomized controlled short-term clinical trial. We recruited overweight and obese patients with CKD stages 3-4 from an outpatient clinic and assigned them to either a TRF group or a control diet (CD) group according to their preferences. Changes in renal function, other biochemical data, anthropometric parameters, gut microbiota, and adverse events were measured before the intervention and after 12 weeks. Results: The change in estimated glomerular filtration rate (eGFR) before and after intervention in the TRF group (Δ = 3.1 ± 5.3 ml/min/1.73m2) showed significant improvement compared with the CD group (Δ = -0.8 ± 4.4 ml/min/1.73m2). Furthermore, the TRF group had a significant decrease in uric acid (Δ = -70.8 ± 124.2 µmol/L), but an increase in total protein (Δ = 1.7 ± 2.5 g/L), while the changes were inconsistent for inflammatory factors. In addition, the TRF group showed a significant decrease in body weight (Δ = -2.8 ± 2.9 kg) compared to the CD group, and body composition indicated the same decrease in body fat mass, fat free mass and body water. Additionally, TRF shifted the gut microbiota in a positive direction. Conclusion: Preliminary studies suggest that overweight and obese patients with moderate-to-severe CKD with weight loss needs, and who were under strict medical supervision by healthcare professionals, performed TRF with good compliance. They did so without apparent adverse events, and showed efficacy in protecting renal function. These results may be due to changes in body composition and alterations in gut microbiota.

Combining effect of camellia oil and squalene on hyperlipidemia-induced reproductive damage in male rats.

Introduction: Camellia oil (CO), a common edible oil in China, contains a variety of active ingredients. In this study, we explored the combining effect and optimal feeding time of CO and squalene on hyperlipemia-induced reproductive damage rats and probably provided supportive data for use of CO for health benefits. Methods: We established the hyperlipidaemia-induced reproductive damage model, and then the successfully modeled rats were randomly classified into four groups including a model control (MC) group, a camellia oil (CO) group, a camellia oil + squalene (COS) group, and a sildenafil (SN) group, which were feeding with different subjects during days 30 and 60. The normal (NC) group was fed under the same conditions. Results: Our results showed that compared with the MC group, the CO, COS, and SN groups could significantly decline the serum TG, TC and LDL-C levels, increase the serum testosterone levels, the sperm counts in epididymidis and organ coefficients of penises, and no pathological change in penis and testis at days 30 and 60. Compared with the pure CO, the mixture of CO and squalene could significantly enhance the effect of decreasing the concentrations of TG, TC, and LDL-C and increasing the serum testosterone level and sperm count of epididymal tail, and the results of day 30 were better than those of day 60. Discussion: CO and squalene have a combining effect on lowering blood lipid, improving the level of testosterone and the number of epididymal tail sperm, and promoting the recovery of erectile and sexual function on hyperlipidemia-induced reproductive damage rats on day 30.

Safety and efficacy of aspiration thrombectomy versus stent retriever thrombectomy for acute ischaemic stroke: a systematic review and meta-analysis.

Introduction: Although aspiration thrombectomy has shown comparable safety and efficacy to stent retriever thrombectomy for acute ischaemic stroke (AIS), the use of aspiration thrombectomy as first-line endovascular treatment for AIS remains controversial. Aim: To perform a systematic evaluation of the safety and efficacy of aspiration thrombectomy versus stent retriever thrombectomy in the treatment of AIS. Material and methods: We searched the online databases PubMed, Embase, Cochrane Library, and SinoMed to collect randomized controlled trials and retrospective studies concerning the treatment of AIS with aspiration thrombectomy and stent retriever thrombectomy. Primary outcomes included 90-day all-cause mortality, a 90-day mRS scores of 0-2, intracranial haemorrhage, and successful recanalization rate. The Jadad scale and the MINORS evaluation items were used to evaluate study quality, and RevMan 5.2 was used to conduct a meta-analysis. Any differential effects in rates between the two strategies were assessed using a random effect model. Results: A total of 15 articles were found, including 2 randomized controlled trials and 13 retrospective studies. It showed that aspiration thrombectomy and stent retriever thrombectomy had similar results in terms of 90-day all-cause mortality (p = 0.88), 90-day mRS scores 0-2 (p = 0.29), and intracranial haemorrhage (p = 0.47). And in terms of successful recanalization rates, the aspiration thrombectomy group had better outcomes than the stent retriever thrombectomy group (p = 0.0003). The heterogeneity of 90-day all-cause mortality (I2 = 0%), 90-day mRS scores of 0-2 (I2 = 6%), intracranial haemorrhage (I2 = 21%), and successful recanalization rate (I2 = 0%) were less than 30%. Conclusions: Both aspiration thrombectomy and stent thrombectomy can be used as the first line of intravascular treatment for AIS.

The REDUCED LEAFLET genes encode key components of the trans-acting small interfering RNA pathway and regulate compound leaf and flower development in Lotus japonicus.

The endogenous trans-acting small interfering RNA (ta-siRNA) pathway plays a conserved role in adaxial-abaxial patterning of lateral organs in simple-leafed plant species. However, its function in compound-leafed species is largely unknown. Using the compound-leafed species Lotus japonicus, we identified and characterized two independent mutants, reduced leaflet1 (rel1) and rel3, whose most conspicuous defects in compound leaves are abaxialized leaflets and reduction in leaflet number. Concurrent mutations in REL genes also compromise flower development and result in radial symmetric floral organs. Positional cloning revealed that REL1 and REL3 encode the homologs of Arabidopsis (Arabidopsis thaliana) SUPPRESSOR OF GENE SILENCING3 and ARGONAUTE7/ZIPPY, respectively, which are key components of the ta-siRNA pathway. These observations, together with the expression and functional data, demonstrated that the ta-siRNA pathway plays conserved yet distinct roles in the control of compound leaf and flower development in L. japonicus. Moreover, the phenotypic alterations of lateral organs in ta-siRNA-deficient mutants and the regulation of downstream targets by the ta-siRNA pathway in L. japonicus were similar to those in the monocots but different from Arabidopsis, indicating many parallels between L. japonicus and the monocots in the control of lateral organ development by the ta-siRNA pathway.

Effects of imperatorin on apoptosis and synaptic plasticity in vascular dementia rats.

In view of the complicated pathophysiological process of vascular dementia (VD), drugs for the clinical treatment of VD mainly target related risk factors, while drugs with excellent efficacy in cognitive function are still relatively lacking. Imperatorin (IMP), an active constituent extracted from angelica dahuricae and notopterygium Notopterygii, which has anti-inflammatory, vasodilator, anticoagulant, block calcium channel, anticonvulsant, and anti oxygen free radical injury properties. Therefore,the present study examined its effects on VD rats and the underlying molecular mechanisms, in order to provide promising therapeutic methods. VD was established by modified ligation of perpetual two-vessel occlusion (2VO). After 2VO surgery, IMP (2.5, 5, and 10 mg/kg) was administered by intraperitoneal injection for 12 consecutive weeks to evaluate therapeutic effects. Cognitive function was verified by the Morris water maze. The neuronal morphological changes were examined via Hematoxylin-Eosin staining. Real-Time PCR and Western blot were used for detecting pro- and antiapoptotic biomarkers, and the hippocampus synaptic damage was examined by Transmission electron microscope. We revealed that 2VO-induced cognitive impairment, hippocampus CA1 neuron damage, apoptosis and synaptic damage. IMP-treatment significantly improved 2VO-induced cognitive deficits and hippocampus neuron damage. Molecular analysis revealed that IMP inhibited apoptosis through the down regulation of Bax, Caspase-3 and upregulation of Bcl-2. Meanwhile, IMP-treatment markedly improved synaptic ultrastructure morphology, increased the SAZ length, PSD thickness and up-regulated PSD-95 expression. Collectively, our findings demonstrated that IMP was effective in the treatment of 2VO-induced VD via inhibiting apoptosis of hippocampus neurons and reducing the synaptic plasticity destroy.

Expression of circular RNAs in the vascular dementia rats.

PURPOSE: Circular RNAs (circRNAs) are a class of endogenous noncoding RNA molecules that lack free 5' and a 3' end poly(A) tail. CircRNAs are enriched in neural tissues, and have been found to be associated with various diseases of the central nervous system. This study aimed to examine key circRNAs involved in vascular dementia(VD) model rats. METHODS: Total RNA-seq profiles of hippocampus samples from normal and vascular dementia rats were extracted and high throughput sequencing was performed. Quantitative real-time polymerase chain reaction (qPCR) was used to confirm the circRNA expression profiles. Differential expression of circRNA has been used for analysis via the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The circRNA-miRNA-mRNA network was then constructed. RESULTS: The data of high-throughput sequencing showed that there were 425 circRNAs differentially expressed between VD and normal rats (fold change (FC)≥2.0 and p-value< 0.05). In the VD group, a total of 237 were significantly upwardly revised, while the other 188 were downwardly revised. Eleven of these expressed more than 10 times in the VD model rats. The Expression levels of 10 circRNAs (circ_Map2k5, circ_Ulk2, circ_Plekha5, circ_Plcl1, circ_Sntg1, circ_Morc3, circ_Rims1, circ_ Stxbp5l, circ_ Agtpbp1, circ_Lrrc28) were verified by qPCR, which were persistent with RNA-seq data(P < 0.05). GO analysis indicated that majority of predicted target genes were involved in biological processes, such as cellular processes, nervous system development, etc. Cellular component, such as cellular parts, intracellular parts, cytoplasm and molecular function, such as binding, catalytic activity, etc. Moreover, KEGG analysis showed that many genes were enriched in cholinergic synapses, the MAPK signaling pathways, GABAergic synapses, metabolic pathways, the mTOR signaling pathways, and so on. CONCLUSIONS: Our results suggest the involvement of different ncRNA expression patterns in the pathogenesis (are associated with the pathogenesis of VD. Our findings provide a novel perspective for further research into potential mechanisms of VD and might facilitate the development of novel therapeutics targeting ncRNAs.

Stable ZnO-doped hydroxyapatite nanocoating for anti-infection and osteogenic on titanium.

Titanium and titanium alloys have been widely used in orthopedics and related fields. However, their clinical applications are limited due to the lack of anti-infection, osteoinductivity and angiogenic ability. In the present study, we utilized pulse electrochemical deposition method to prepare polypyrrole (PPy) by the in-situ oxidative polymerization of pyrrole (Py), and through the coordination and doping of ions, the function of PPy as a dual regulator of hydroxyapatite nanoparticles (HA-NPs) and zinc oxide nanoparticles (ZnO-NPs) was achieved. Bioactivity test showed that the composite coating could induce the formation of apatite, and the apatite was in a neat arrangement preferentially grew along the (002) crystal plane, indicating good bioactivity. The release test showed that the dual regulation effect of PPy coordination and doping reduced the release rate of Ca2+ and Zn2+ from the composite coating. Antibacterial tests showed that the composite coating against Escherichia coli and Staphylococcus aureus. Besides, bone marrow-derived mesenchymal stem cells (BMSCs) exhibited good adhesion, proliferation and differentiation on the composite coating, and fluorescence staining experiments demonstrated good osteoinductivity of the composite coating. In this study, a multifunctional composite coating with anti-infection, angiogenic and osteoinductivity was successfully constructed on the titanium surface via pulse electrochemical deposition method.

Transarterial Chemoembolization and Sorafenib Combined with Microwave Ablation for Advanced Primary Hepatocellular Carcinoma: A Preliminary Investigation of Safety and Efficacy.

PURPOSE: The aim of this study was to investigate the safety and efficacy of transarterial chemoembolization and sorafenib (TACE-S) combined with microwave ablation (TACE-S-MWA) for the treatment of patients with advanced primary hepatocellular carcinoma (HCC). METHODS: Between January 2015 and December 2018, 152 consecutive advanced HCC patients, who underwent TACE-S-MWA (MWA group, n=77) or TACE-S (Non-MWA group, n=75), were investigated. Overall survival (OS), time to progression (TTP) and safety were compared between the two groups. Prognostic factors were analyzed using the Cox proportional hazard regression model. RESULTS: Baseline patient characteristics were balanced between the two groups. MWA group was associated with a higher OS (median, 19.0 vs 13.0 months; P<0.001) and a longer TTP (median, 6.0 vs 3.0 months; P<0.001) compared with non-MWA group. Multivariate analyses showed that portal vein tumor thrombosis (PVTT) (P=0.002), duration of sorafenib (P<0.001), and MWA treatment (P=0.011) were independently associated with OS. MWA treatment strategy (P<0.001) was a significant predictor of TTP. There were no treatment-related mortalities in either group. The rates of minor complications (42.9% vs 38.7%, P=0.599) and major complications (1.29% vs 1.33%, P=0.985) in the MWA group were similar to those in the non-MWA group. CONCLUSION: TACE-S-MWA was safe and effective for advanced primary HCC. TACE-S-MWA resulted in better OS and TTP than did TACE-S for treatment of patients with advanced primary HCC.