MicroRNA miR-103a-3p targets NPAS3 to regulate progression of Alzheimer’s disease

Purpose: This study aimed at investigating miR-103a-3p expression, functional roles and underlying mechanism in regulating Alzheimer’s progression.Methods: RT-qPCR was used to assessed miR-103a-3p and NPAS3 expression in human neuroblastoma cells. Cell transfection of overexpressed or knocked down genes and CCK-8 assay measured cell viability while RT-qPCR was used to detect proliferation and apoptosis in biomarkers, Ki87 and PCNA, caspase-8 and caspase-3, respectively. Furthermore, luciferase assay was used to evaluate the luciferase activity while western blotting  analysis was applied to determine protein biomarkers regarding proliferation and apoptosis.Results: Expression of miR-103a-3p decreased but NPAS3 increased in AD cell lines. Overexpressed miR-103a-3p attenuated cell viability and NPAS3 bound miR-103a-3p to regulate AD progression. The inhibitory effect of miRNA on cell viability in AD was reversed by NPAS3.Conclusion: miR-103a-3p/NPAS3 might help to enrich knowledge on treatment of AD. Keywords: Alzheimer’s development, cell growth, cell proliferatio

Comprehensive analysis of clinical significance of stem-cell related factors in renal cell cancer

<p>Abstract</p> <p>Background</p> <p>C-MYC, LIN28, OCT4, KLF4, NANOG and SOX2 are stem cell related factors. We detected whether these factors express in renal cell carcinoma (RCC) tissues to study their correlations with the clinical and pathological characteristics.</p> <p>Methods</p> <p>The expressions of c-MYC, LIN28, SOX2, KLF4, OCT4 and NANOG in 30 RCC patients and 5 non-RCC patients were detected with quantitative real-time reverse transcription-PCR (qRT-PCR). The data were analyzed with Wilcoxon signed rank sum test and x²test.</p> <p>Results</p> <p>In RCC group, c-MYC expression was significantly higher in RCC tissues compared with normal tissues (P < 0.05). The expression levels of OCT4, KLF4, NANOG and SOX2 were significantly lower in RCC tissues compared with normal tissues (P < 0.05). LIN28 expression level was not significant. No difference was observed when it comes to clinical and pathological characteristics such as gender, age, tumor size, cTNM classification and differentiation status (P > 0.05). Also the expression levels of all above factors were not significantly changed in non-RCC group (P > 0.05).</p> <p>Conclusions</p> <p>The present analysis strongly suggests that altered expression of several stem cell related factors may play different roles in RCC. C-MYC may function as an oncogene and OCT4, KLF4, NANOG and SOX2 as tumor suppressors.</p

High-speed rail and tourism expansion in China: a spatial spillover effect perspective

Tourism exerts a great effect on the modern economy and relies largely on the flow of people facilitated by high-quality transportation infrastructure. Applying a spatial econometric method, this paper investigates the effect of high-speed rail (HSR) on tourism expansion in China from the view of the spatial spillover effect. Based on a 276 Chinese cities’ panel dataset over 2005–2019, a positive role of HSR in tourism expansion is observed. Compared with cities unconnected to the HSR network, cities accessible by HSR experienced a 22% increase in tourism revenue and a 38% rise in tourist arrivals. In addition, the connection of a city to the HSR network also exerts a great spatial spillover role in the increase of tourism revenue and arrivals in peripheral cities which are not directly connected by HSR. The research findings offer important insights on the relationship between transportation infrastructure and tourism with significant policy implications regarding tourism development. First published online 6 November 202

Visualization of multifractal superconductivity in a two-dimensional transition metal dichalcogenide in the weak-disorder regime

Eigenstate multifractality is a distinctive feature of non-interacting disordered metals close to a metal-insulator transition, whose properties are expected to extend to superconductivity. While multifractality in three dimensions (3D) only develops near the critical point for specific strong-disorder strengths, multifractality in 2D systems is expected to be observable even for weak disorder. Here we provide evidence for multifractal features in the superconducting state of an intrinsic weakly disordered single-layer NbSe$_2$ by means of low-temperature scanning tunneling microscopy/spectroscopy. The superconducting gap, characterized by its width, depth and coherence peaks' amplitude, shows a characteristic spatial modulation coincident with the periodicity of the quasiparticle interference pattern. Spatial inhomogeneity of the superconducting gap width, proportional to the local order parameter in the weak-disorder regime, follows a log-normal statistical distribution as well as a power-law decay of the two-point correlation function, in agreement with our theoretical model. Furthermore, the experimental singularity spectrum f($\alpha$) shows anomalous scaling behavior typical from 2D weakly disordered systems

Gate-Tunable Critical Current of the Three-Dimensional Niobium Nano-Bridge Josephson Junction

Recent studies have shown that the critical currents of several metallic superconducting nanowires and Dayem bridges can be locally tuned using a gate voltage {V_g}. Here, we report a gate-tunable Josephson junction structure constructed from a three-dimensional (3D) niobium nano-bridge junction (NBJ) with a voltage gate on top. Measurements up to 6 K showed that the critical current of this structure can be tuned to zero by increasing {V_g}. The critical gate voltage Vgc was reduced to 16 V and may possibly be reduced further by reducing the thickness of the insulation layer between the gate and the NBJ. Furthermore, the flux modulation generated by Josephson interference of two parallel 3D NBJs can also be tuned using {V_g} in a similar manner. Therefore, we believe that this gate-tunable Josephson junction structure is promising for superconducting circuit fabrication at high integration levels.Comment: 15 pages, 5 figure

Expression and clinical value of CXCR4 in high grade gastroenteropancreatic neuroendocrine neoplasms

BackgroundCXC chemokine receptor 4 (CXCR4) is associated with the progression and metastasis of numerous malignant tumors. However, its relationship with Gastroenteropancreatic Neuroendocrine Neoplasms Grade 3 (GEP-NENs G3) is unclear. The aim of this study was to characterize the expression of CXCR4 in GEP-NENS and to explore the clinical and prognostic value of CXCR4.MethodsThis study retrospectively collected clinical and pathological data from patients with GEP-NENs who receiving surgery in Qilu Hospital of Shandong University from January 2013 to April 2021, and obtained the overall survival of the patients based on follow-up. Immunohistochemistry (IHC) was performed on pathological paraffin sections to observe CXCR4 staining. Groups were made according to pathological findings. Kaplan-Meier (K-M) curve was used to evaluate prognosis. SPSS 26.0 was used for statistical analysis.Results100 GEP-NENs G3 patients were enrolled in this study. There was a significant difference in primary sites (P=0.002), Ki-67 index (P&lt;0.001), and Carcinoembryonic Antigen (CEA) elevation (P=0.008) between neuroendocrine tumor (NET) G3 and neuroendocrine carcinoma (NEC). CXCR4 was highly expressed only in tumors, low or no expressed in adjacent tissues (P&lt;0.001). The expression level of CXCR4 in NEC was significantly higher than that in NET G3 (P=0.038). The K-M curves showed that there was no significant difference in overall survival between patients with high CXCR4 expression and patients with low CXCR4 expression, either in GEP-NEN G3 or NEC (P=0.920, P=0.842. respectively).ConclusionDifferential expression of CXCR4 was found between tumor and adjacent tissues and between NET G3 and NEC. Our results demonstrated that CXCR4 can be served as a new IHC diagnostic indicator in the diagnosis and differential diagnosis of GEP-NENs G3. Further studies with multi-center, large sample size and longer follow-up are needed to confirm the correlation between CXCR4 expression level and prognosis

High drug-loaded microspheres enabled by controlled in-droplet precipitation promote functional recovery after spinal cord injury

High drug loading improves therapeutic efficacy and reduces side effects in drug delivery. Here, the authors use controlled diffusion of solvents to precipitate drug nanoparticles in polymer particles while the polymer is solidifying and demonstrate the particles for drug delivery in a spinal cord injury model. Drug delivery systems with high content of drug can minimize excipients administration, reduce side effects, improve therapeutic efficacy and/or promote patient compliance. However, engineering such systems is extremely challenging, as their loading capacity is inherently limited by the compatibility between drug molecules and carrier materials. To mitigate the drug-carrier compatibility limitation towards therapeutics encapsulation, we developed a sequential solidification strategy. In this strategy, the precisely controlled diffusion of solvents from droplets ensures the fast in-droplet precipitation of drug molecules prior to the solidification of polymer materials. After polymer solidification, a mass of drug nanoparticles is embedded in the polymer matrix, forming a nano-in-micro structured microsphere. All the obtained microspheres exhibit long-term storage stability, controlled release of drug molecules, and most importantly, high mass fraction of therapeutics (21.8-63.1 wt%). Benefiting from their high drug loading degree, the nano-in-micro structured acetalated dextran microspheres deliver a high dose of methylprednisolone (400 mu g) within the limited administration volume (10 mu L) by one single intrathecal injection. The amount of acetalated dextran used was 1/433 of that of low drug-loaded microspheres. Moreover, the controlled release of methylprednisolone from high drug-loaded microspheres contributes to improved therapeutic efficacy and reduced side effects than low drug-loaded microspheres and free drug in spinal cord injury therapy.Peer reviewe

Elevated CO2 reduces copper accumulation and toxicity in the diatom Thalassiosira pseudonana

The projected ocean acidification (OA) associated with increasing atmospheric CO2 alters seawater chemistry and hence the bio-toxicity of metal ions. However, it is still unclear how OA might affect the long-term resilience of globally important marine microalgae to anthropogenic metal stress. To explore the effect of increasing pCO2 on copper metabolism in the diatom Thalassiosira pseudonana (CCMP 1335), we employed an integrated eco-physiological, analytical chemistry, and transcriptomic approach to clarify the effect of increasing pCO2 on copper metabolism of Thalassiosira pseudonana across different temporal (short-term vs. long-term) and spatial (indoor laboratory experiments vs. outdoor mesocosms experiments) scales. We found that increasing pCO2 (1,000 and 2,000 μatm) promoted growth and photosynthesis, but decreased copper accumulation and alleviated its bio-toxicity to T. pseudonana. Transcriptomics results indicated that T. pseudonana altered the copper detoxification strategy under OA by decreasing copper uptake and enhancing copper-thiol complexation and copper efflux. Biochemical analysis further showed that the activities of the antioxidant enzymes glutathione peroxidase (GPX), catalase (CAT), and phytochelatin synthetase (PCS) were enhanced to mitigate oxidative damage of copper stress under elevated CO2. Our results provide a basis for a better understanding of the bioremediation capacity of marine primary producers, which may have profound effect on the security of seafood quality and marine ecosystem sustainability under further climate change

Mutation screening of the SLC26A4 gene in a cohort of 192 Chinese patients with congenital hypothyroidism

ABSTRACT Objective: Pendred syndrome (PS) is an autosomal recessive disorder characterised by sensorineural hearing loss and thyroid dyshormonogenesis. It is caused by biallelic mutations in the SLC26A4 gene encoding for pendrin. Hypothyroidism in PS can be present from birth and therefore diagnosed by neonatal screening. The aim of this study was to examine the SLC26A4 mutation spectrum and prevalence among congenital hypothyroidism (CH) patients in the Guangxi Zhuang Autonomous Region of China and to establish how frequently PS causes hearing impairment in our patients with CH. Subjects and methods: Blood samples were collected from 192 CH patients in Guangxi Zhuang Autonomous Region, China, and genomic DNA was extracted from peripheral blood leukocytes. All exons of the SLC26A4 gene together with their exon-intron boundaries were screened by nextgeneration sequencing. Patients with SLC26A4 mutations underwent a complete audiological evaluation including otoscopic examination, audiometry and morphological evaluation of the inner ear. Results: Next generation sequencing analysis of SLC26A4 in 192 CH patients revealed five different heterozygous variations in eight individuals (8/192, 4%). The prevalence of SLC26A4 mutations was 4% among studied Chinese CH. Three of the eight were diagnosed as enlargement of the vestibular aqueduct (EVA), no PS were found in our 192 CH patients. The mutations included one novel missense variant p.P469S, as well as four known missense variants, namely p.V233L, p.M147I, p.V609G and p.D661E. Of the eight patients identified with SLC26A4 variations in our study, seven patients showed normal size/location of thyroid gland, and one patients showed a decreased size one. Conclusions: The prevalence of SLC26A4 pathogenic variants was 4% among studied Chinese patients with CH. Our study expanded the SLC26A4 mutation spectrum, provided the best estimation of SLC26A4 mutation rate for Chinese CH patients and indicated the rarity of PS as a cause of CH. Arch Endocrinol Metab. 2016;60(4):323-

Mutation screening of the SLC26A4 gene in a cohort of 192 Chinese patients with congenital hypothyroidism

ABSTRACT Objective: Pendred syndrome (PS) is an autosomal recessive disorder characterised by sensorineural hearing loss and thyroid dyshormonogenesis. It is caused by biallelic mutations in the SLC26A4 gene encoding for pendrin. Hypothyroidism in PS can be present from birth and therefore diagnosed by neonatal screening. The aim of this study was to examine the SLC26A4 mutation spectrum and prevalence among congenital hypothyroidism (CH) patients in the Guangxi Zhuang Autonomous Region of China and to establish how frequently PS causes hearing impairment in our patients with CH. Subjects and methods: Blood samples were collected from 192 CH patients in Guangxi Zhuang Autonomous Region, China, and genomic DNA was extracted from peripheral blood leukocytes. All exons of the SLC26A4 gene together with their exon-intron boundaries were screened by next-generation sequencing. Patients with SLC26A4 mutations underwent a complete audiological evaluation including otoscopic examination, audiometry and morphological evaluation of the inner ear. Results: Next generation sequencing analysis of SLC26A4 in 192 CH patients revealed five different heterozygous variations in eight individuals (8/192, 4%). The prevalence of SLC26A4 mutations was 4% among studied Chinese CH. Three of the eight were diagnosed as enlargement of the vestibular aqueduct (EVA), no PS were found in our 192 CH patients. The mutations included one novel missense variant p.P469S, as well as four known missense variants, namely p.V233L, p.M147I, p.V609G and p.D661E. Of the eight patients identified with SLC26A4 variations in our study, seven patients showed normal size/location of thyroid gland, and one patients showed a decreased size one. Conclusions: The prevalence of SLC26A4 pathogenic variants was 4% among studied Chinese patients with CH. Our study expanded the SLC26A4 mutation spectrum, provided the best estimation of SLC26A4 mutation rate for Chinese CH patients and indicated the rarity of PS as a cause of CH