Refugial isolation and range expansions drive the genetic structure of \u3cem\u3eOxyria sinensis\u3c/em\u3e (Polygonaceae) in the Himalaya-Hengduan Mountains

The formation of the Mekong-Salween Divide and climatic oscillations in Pleistocene were the main drivers for the contemporary diversity and genetic structure of plants in the Himalaya-Hengduan Mountains (HHM). To identify the relative roles of the two historical events in shaping population history of plants in HHM, we investigated the phylogeographic pattern of Oxyria sinensis, a perennial plant endemic to the HHM. Sixteen chloroplast haplotypes were identified and were clustered into three phylogenetic clades. The age of the major clades was estimated to be in the Pleistocene, falling into several Pleistocene glacial stages and postdating the formation of the Mekong-Salween Divide. Range expansions occurred at least twice in the early and middle Pleistocene, but the spatial genetic distribution rarely changed since the Last Glacial Maximum. Our results suggest that temporary mountain glaciers may act as barriers in promoting the lineage divergence in O. sinensis and that subsequential range expansions and secondary contacts might reshape the genetic distribution in geography and blur the boundary of population differentiation created in the earlier glacial stages. This study demonstrates that Pleistocene climatic change and mountain glaciers, rather than the Mekong-Salween Divide, play the primary role in shaping the spatial genetic structure of O. sinensis

Acupuncture therapies for cancer-related fatigue: A Bayesian network meta-analysis and systematic review

BackgroundCancer-related fatigue (CRF) is one of the most commonly reported symptoms impacting cancer survivors. This study evaluated and compared the effectiveness and safety of acupuncture treatments for CRF.MethodsWe searched PubMed, Embase, Web of Science, Cochrane Library, China Biology Medicine China National Knowledge Infrastructure, China Science and Technology Journal Database, and WanFang Database from inception to November 2022 to identify eligible randomized controlled trials (RCTs) comparing acupuncture treatments with sham interventions, waitlist (WL), or usual care (UC) for CRF treatment. The outcomes included the Cancer Fatigue Scale (CFS) and Pittsburgh Sleep Quality Index (PSQI), and pair-wise and Bayesian network meta-analyses were performed using STATA v17.0.ResultsIn total, 34 randomized controlled trials featuring 2632 participants were included. In the network meta-analysis, the primary analysis using CFS illustrated that point application (PA) + UC (standardized mean difference [SMD] = −1.33, 95% CI = −2.02, −0.63) had the highest probability of improving CFS, followed by manual acupuncture (MA) + PA (SMD = −1.21, 95% CI = −2.05, −0.38) and MA + UC (SMD = −0.80, 95% CI = −1.50, −0.09). Moreover, the adverse events of these interventions were acceptable.ConclusionThis study demonstrated that acupuncture was effective and safe on CRF treatment. However, further studies are still warranted by incorporating more large-scale and high-quality RCTs.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42022339769

Mutation spectrum of PTS gene in patients with tetrahydrobiopterin deficiency from jiangxi province

Background: Hyperphenylalaninemia (HPA) is the most common inborn error in amino acid metabolism. It can be primarily classified into phenylalanine hydroxylase (PAH) deficiency and tetrahydrobiopterin (BH4) deficiency. BH4 deficiency (BH4D) is caused by genetic defects in enzymes involved in the biosynthesis and regeneration of BH4. 6-pyruvoyl-tetrahydropterin synthase (PTPS/PTS), which is encoded by the PTS gene, participates in the biosynthesis of BH4. PTPS deficiency (PTPSD) is the major cause of BH4D. In this study, we investigated that the prevalence of BH4D in Jiangxi province was approximately 12.5 per 1,000,000 live births (69/5,541,627). Furthermore, the frequency of BH4D was estimated to be 28.8% (69/240) in the HPA population of Jiangxi. In this study, we aimed to characterize the mutational spectrum of the PTS gene in patients with PTPSD from Jiangxi province.Method: Newborn screening data of Jiangxi province from 1997 to 2021 were analyzed and 53 families with PTPSD were enrolled for the analysis of the PTS gene variants by Sanger sequencing.Results: 106 variants were identified in 106 alleles of 53 patients with PTPSD, including 13 types of variants reported previously, and two novel variants (c.164-36A>G and c.146_147insTG). The predominant variant was c.259C>T (47.2%), followed by c.84-291A>G (19.8%), c.155A>G (8.5%), c.286G>A (6.6%) and c.379C>T (4.7%).Conclusion: The results of this study can not only provide guidance for the molecular diagnosis and genetic counseling in cases of PTPS deficiency but also enrich the PTS mutation database

CIP2A Causes Tau/APP Phosphorylation, Synaptopathy, and Memory Deficits in Alzheimer's Disease

Protein phosphatase 2A (PP2A) inhibition causes hyperphosphorylation of tau and APP in Alzheimer's disease (AD). However, the mechanisms underlying the downregulation of PP2A activity in AD brain remain unclear. We demonstrate that Cancerous Inhibitor of PP2A (CIP2A), an endogenous PP2A inhibitor, is overexpressed in AD brain. CIP2A-mediated PP2A inhibition drives tau/APP hyperphosphorylation and increases APP beta-cleavage and A beta production. Increase in CIP2A expression also leads to tau mislocalization to dendrites and spines and synaptic degeneration. In mice, injection of AAV-CIP2A to hippocampus induced AD-like cognitive deficits and impairments in long-term potentiation (LTP) and exacerbated AD pathologies in neurons. Indicative of disease exacerbating the feedback loop, we found that increased CIP2A expression and PP2A inhibition in AD brains result from increased A beta production. In summary, we show that CIP2A overexpression causes PP2A inhibition and AD-related cellular pathology and cognitive deficits, pointing to CIP2A as a potential target for AD therapy

Antagonism of miR-21 Reverses Epithelial-Mesenchymal Transition and Cancer Stem Cell Phenotype through AKT/ERK1/2 Inactivation by Targeting PTEN

BACKGROUND: Accumulating evidence suggested that epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) characteristics, both of which contribute to tumor invasion and metastasis, are interrelated with miR-21. MiR-21 is one of the important microRNAs associated with tumor progression and metastasis, but the molecular mechanisms underlying EMT and CSC phenotype during miR-21 contributes to migration and invasion of breast cancer cells remain to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study, MDA-MB-231/anti-miR-21 cells were established by transfected hsa-miR-21 antagomir into breast cancer MDA-MB-231 cells. EMT was evaluated by the changes of mesenchymal cell markers (N-cadherin, Vimentin, and alpha-SMA), epithelial cell marker (E-cadherin), as well as capacities of cell migration and invasion; CSC phenotype was measured using the changes of CSC surface markers (ALDH1 and CD44), and the capacity of sphereforming (mammospheres). We found that antagonism of miR-21 reversed EMT and CSC phenotype, accompanied with PTEN up-regulation and AKT/ERK1/2 inactivation. Interestingly, down-regulation of PTEN by siPTEN suppressed the effects of miR-21 antagomir on EMT and CSC phenotype, confirming that PTEN is a target of miR-21 in reversing EMT and CSC phenotype. The inhibitors of PI3K-AKT and ERK1/2 pathways, LY294002 and U0126, both significantly suppressed EMT and CSC phenotype, indicating that AKT and ERK1/2 pathways are required for miR-21 mediating EMT and CSC phenotype. CONCLUSIONS/SIGNIFICANCE: In conclusion, our results demonstrated that antagonism of miR-21 reverses EMT and CSC phenotype through targeting PTEN, via inactivation of AKT and ERK1/2 pathways, and showed a novel mechanism of which might relieve the malignant biological behaviors of breast cancer

Multiple-Face Tracking System For General Region-Of-Interest Video Coding

An algorithm has been developed which locates and tracks faces in color video sequences for use in region-of-interest video compression. Our face-tracking algorithm detects faces in the huesaturation -value (HSV) color space, and reduces false alarms based on various cues, including size, shape, position, and aspect ratio. The algorithm also performs temporal filtering to enforce consistency from frame to frame. The face tracker is integrated in the rate control of a video encoder, which allows more bits to be committed to the face regions at the cost of reduced bits in the non-face regions. Thus, image quality can be greatly improved in face regions at the cost of reduced quality in background regions, resulting in better overall subjective quality for many sequences. 1. INTRODUCTION There exist many different face-tracking algorithms in the research literature [2--3], with applications ranging from human-computer interaction interface to video conferencing. One common technique used..

Molecular characteristics of clinical IMP-producing Klebsiella pneumoniae isolates: novel IMP-90 and integron In2147

Abstract Background Since the first report of carbapenem-resistant Klebsiella pneumoniae isolates in China in 2007, the prevalence of CRKP and CRE has increased significantly. However, the molecular characteristics of IMP-producing Klebsiella pneumoniae (IMPKp) are rarely reported. Methods A total of 29 IMPKp isolates were collected from a Chinese tertiary hospital from 2011 to 2017. Clinical IMPKp were identified by VITEK®MS, and further analyzed by whole-genome DNA sequencing with HiSeq and PacBio RSII sequencer. Sequencing data were analyzed using CSI Phylogeny 1.4, Resfinder, PlasmidFinder and the MLST tool provided by the Centre for Genomic Epidemiology. The analysis results were visualized using iTOL editor v1_1. The open reading frames and pseudogenes were predicted using RAST 2.0 combined with BLASTP/BLASTN searches against the RefSeq database. The databases CARD, ResFinder, ISfinder, and INTEGRALL were performed for annotation of the resistance genes, mobile elements, and other features. The types of bla IMP in clinical isolates were determined by BIGSdb-Pasteur. Integrons were drawn by Snapgene, and the gene organization diagrams were drawn by Inkscape 0.48.1. Results Four novel ST type, including ST5422, ST5423, ST5426 and ST5427 were identified. The IMP-4 and IMP-1 were the dominant IMP type. The majority of bla IMP-carrying plasmids belonged to IncN and IncHI5. Two novel bla IMP-carrying integrons (In2146 and In2147) were uncovered. A novel variant bla IMP-90 presented in novel integron In2147 has been identified. Conclusions IMPKp showed low prevalence in China. Novel molecular characteristics of IMPKp have been identified. Continuous monitoring of IMPKp shall also be carried out in the future