Biology subjects

Yang, Y.

Publications and source records attributed to Yang, Y..

At least 1,351 records · Page 75Linked to original sources

bioRxiv2019

Impact of Prior Cancer on Outcomes in Nasopharyngeal Carcinoma

BackgroundPrior cancer is a common exclusion criterion in nasopharyngeal carcinoma (NPC) trials. However, whether a prior cancer diagnosis affects trial outcomes is still unknown. We aimed to determine the impact of prior cancer on survival in NPC. MethodsWe identified patients diagnosed with NPC between 2004 and 2009 in the Surveillance, Epidemiology, and End Results (SEER) database. Variables were compared by chi-squared test and t-test as appropriate. Propensity score-adjusted Kaplan-Meier methods and Cox proportional hazard models were used to evaluate the impact of prior cancer on overall survival (OS). ResultsAmong 3,131 eligible NPC patients, 349 (11.15%) patients had a history of prior cancer. The Kaplan-Meier curves did not show a statistically significantly different OS (p=0.19). Subgroup analyses stratified by timing of prior cancer and AJCC TNM stage of index cancer displayed the same tendency, prior cancer didnt adversely affect OS compared with patients without prior cancer (p>0.05). Furthermore, in propensity score-adjusted COX models analysis, patients with prior cancer had the same/non-inferior OS (hazard ratio [HR] = 1.12, 95% confidence interval= 0.88 to 1.42). ConclusionsAmong patients with nasopharyngeal carcinoma, prior cancer does not convey an adverse effect on clinical outcomes, regardless of the timing of prior cancer and AJCC TNM stage of index cancer. Broader inclusion trial criteria could be adopted in nasopharyngeal carcinoma patients with a history of prior cancer. However, further studies are still needed to confirm.

epidemiology↗

bioRxiv2019

Association between ApoE polymorphism and type 2 diabetes: A meta-analysis of 59 studies

(1) AimsDue to the ever increasing incidence of T2DM, it is estimated that only half of the 79 million adults with type 2 diabetes (T2DM) will have adequate access to insulin by 2030 if the current levels of access is not improved. It is urgent to identify the important risk factors for T2DM and develop effective strategies to address the problem of T2DM. Our study aimed to evaluate the association between apolipoprotein E (ApoE) genetic polymorphism and type 2 diabetes, and to provide clues for the etiology of T2DM and even molecular marker of targeted therapy for the treatment of T2DM. (2) MethodsCase-control studies of ApoE polymorphism and T2DM, which were included in PubMed, Web of Science, Medline, WanFang, VIP, and CNKI databases, were selected and evaluated according to criteria of inclusion and exclusion. Eligible data were extracted and pooled, and were analyzed and assessed using R soft-ware (version 3.4.3). Random-effect models were used when heterogeneity existed in between-study, and fixed-effect models were applied otherwise. (3) ResultsA total of 59 studies that consisted of 6,872 cases with T2DM and 8,250 controls were selected. Alleles and genotypes of ApoE between cases and controls were compared. For ApoE alleles, we observed the contrast of {varepsilon}4 versus {varepsilon}3 allele yielding a pooled OR of 1.18 (95% CI: 1.09-1.28; P<0.001). For ApoE genotypes, compared with {varepsilon}3/{varepsilon}3 genotype, {varepsilon}2/{varepsilon}2 genotype showed a possible association with T2DM (OR=1.46; 95% CI: 1.11-1.93; P=0.007), {varepsilon}3/{varepsilon}4 genotype had a 1.11-fold risk of developing T2DM (OR=1.11; 95% CI: 1.01-1.22; P=0.039), and {varepsilon}4/{varepsilon}4 genotype had a 1.71-fold risk of developing T2DM (OR=1.71; 95% CI: 1.33-2.19; P<0.001). (4) ConclusionsThere is an association between ApoE polymorphism and T2DM: allele {varepsilon}4 and genotypes ({varepsilon}2/{varepsilon}2, {varepsilon}3/{varepsilon}4, and {varepsilon}4/{varepsilon}4) are associated with the increased risk for the development of T2DM, and they may be risk factors for T2DM.

genetics↗

bioRxiv2019

Earliest-known intentionally deformed human cranial fossil from Asia and the initiation of hereditary hierarchy in the early Holocene

Hereditary hierarchy is one of the major features of complex societies. Without a written record, prehistoric evidence for hereditary hierarchy is rare. Intentional cranial deformation (ICD) is a cross-generational cultural practice that embodies social identity and culture beliefs in adults through the behavior of altering infant head shape. Therefore, ICD is usually regarded as an archeological clue for the occurrence of hereditary hierarchy. With a calibrated radiocarbon age of 11245-11200 years BP, a fossil skull of an adult male displaying ICD discovered in Northeastern China is among the oldest-known ICD practices in the world. Along with the other earliest global occurrences of ICD, this discovery points to the early initiation of complex societies among the non-agricultural local societies in Northeastern Asia in the early Holocene. A population increase among previously more isolated terminal Pleistocene/early Holocene hunter-gatherer groups likely increased their interactions, possibly fueling the formation of the first complex societies.View Full Text

paleontology↗

bioRxiv2019

Intraoperative contrast-enhanced ultrasound for cerebral glioma resection and the relationship with microvessel density

PurposeWe studied the value of intraoperative contrast-enhanced ultrasound (iCEUS) for real-time monitoring of resection of cerebral gliomas, and analyzed the relationship between CEUS parameters and microvessel density (MVD) of different pathologic grades of cerebral gliomas. Materials and MethodsICEUS was performed in 49 patients with cerebral gliomas. The enhancement characteristics of cerebral gliomas were observed before and after tumor resection. The number of microvessels was counted by immunostaining with anti-CD34. Differences in these quantitative parameters in cerebral gliomas were compared and subjected to a correlation analysis with MVD. ResultsThe color Doppler flow classification within lesions were significantly different before and after iCEUS (p<0.05). The assessment of iCEUS parameters and tumor MVD showed that cerebral gliomas of different pathological grades had different characteristics. The time-to-peak (Tmax) was significantly shorter, the peak intensity (PI) and MVD were significantly higher in high-grade cerebral gliomas than in low-grade cerebral gliomas (p<0.05). According to the immunostaining, PI was positively (r=0.637) correlated with MVD and Tmax was negatively (r=-0.845) correlated with MVD. ConclusionICEUS may determine the borders of lesions more clearly, indicate the microvascular perfusion in real time, and be helpful in understanding the cerebral gliomas grade.

neuroscience↗

bioRxiv2019

Genetic diversity analysis of an isolate of microsporidia infesting Athetis lepigone

In this study, PCR amplification, cloning and sequencing analysis were adopted to explore genetic diversity of microsporidia (LEP9557) infecting Athetis lepigone. The small subunit ribosomal DNA (SSU rDNA), internal transcribed spacer (ITS) and intergenic spacers (IGS) of ribosomal RNA (rRNA) were cloned from the strain and sequenced. By means of multiple sequence alignment, we found that the three gene regions had different levels of polymorphism. There was greater polymorphism in ITS (74 variable sites) and IGS (55.59%) regions than in the SSU rDNA (17 variable sites). Phylogenetic analysis was performed using Kimura 2-parameter with neighbor joining and the results showed that LEP9557 had a close relationship with Nosema bombycis. Sequences of each clone were submitted to Genbank (Accession number: MF150254-MF150258). All of the results indicated the presence of genetic diversity in LEP9557, which established the foundation for identifying the phylogeny and relationships with other microsporidian strains, and had significant biological meaning for maintaining the survival and population continuity of the strain.

microbiology↗

bioRxiv2019

O-GlcNAc transferase suppresses necroptosis and liver fibrosis

Over a billion people suffer from chronic liver diseases worldwide, which often leads to fibrosis and then cirrhosis. Treatments for fibrosis remain experimental, in part because no unifying mechanism has been identified that initiates liver fibrosis. Here we report that O-linked {beta}-N-acetylglucosamine (O-GlcNAc) modification protects against hepatocyte necroptosis and initiation of liver fibrosis. Decreased O-GlcNAc levels were seen in patients with liver cirrhosis and in mice with ethanol-induced liver injury. Liver-specific O-GlcNAc transferase (OGT) knockout (OGT-LKO) mice exhibited ballooning degeneration and elevated circulating alanine aminotransferase (ALT) levels at an early age and progressed to liver fibrosis and portal inflammation by 10 weeks of age. OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis. Furthermore, glycosylation of RIPK3 by OGT reduced RIPK3 protein stability. Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.

physiology↗

bioRxiv2019

DYRK1A-related intellectual disability: a syndrome associated with congenital anomalies of the kidney and urinary tract

PurposeHaploinsufficiency of DYRK1A causes a recognizable clinical syndrome. The goal of this paper is to investigate congenital anomalies of the kidney and urinary tract (CAKUT) and genital defects (GD) in patients with DYRK1A mutations.\n\nMethodsA large database of clinical exome sequencing (ES) was queried for de novo DYRK1A mutations and CAKUT/GD phenotypes were characterized. Xenopus laevis (frog) was chosen as a model organism to assess Dyrk1as role in renal development.\n\nResultsPhenotypic details and mutations of 19 patients were compiled after an initial observation that one patient with a de novo pathogenic mutation in DYRK1A had GD. CAKUT/GD data were available from 15 patients, 11 of whom present with CAKUT/GD. Studies in Xenopus embryos demonstrate that knockdown of Dyrk1a disrupts the development of segments of developing embryonic nephrons, which ultimately give rise to the entire genitourinary (GU) tract. These defects could be rescued by co-injecting wildtype human DYRK1A RNA, but not with truncated DYRK1AR205* RNA.\n\nConclusionEvidence supports routine GU screening of all individuals with de novo DYRK1A pathogenic variants to ensure optimized clinical management. Collectively, the reported clinical data and loss of function studies in Xenopus substantiate a novel role for DYRK1A in GU development.

genetics↗

bioRxiv2019

Efficacy and Safety of Immunosuppressive Treatment in IgA Nephropathy: A Meta-analysis of Randomized Controlled Trials

BackgroundThere is some controversy regarding the efficacy and safety of immunosuppressive agents for the treatment of kidney diseases. The recent STOP-IgAN and TESTING studies have focused attention on the application of immunosuppressive agents in IgA nephropathy (IgAN). This study investigated the benefits and risks of immunosuppressive agents in IgAN.\n\nMethodsMEDLINE, EMBASE, the Cochrane Library, and article reference lists were searched for randomized controlled trials (RCTs) comparing immunosuppressive agents with any other non-immunosuppressive agents for treating IgAN. A meta-analysis was performed on the outcomes of proteinuria, creatinine (Cr), estimated glomerular filtration rate (eGFR), and adverse events in patients with IgAN, and trial sequential analyses were also performed for outcomes.\n\nResultsTwenty-nine RCTs (1957 patients) that met our inclusion criteria were identified. Steroids (weighted mean difference [WMD] -0.70, 95% confidence interval [CI] -1.2 to -0.20), non-steroidal immunosuppressive agents (NSI) (WMD -0. 43, 95% CI -0.55 to -0.31), and combined steroidal and non-steroidal immunosuppressive agents (S&NSI) (WMD -1.46, 95% CI -2.13 to -0.79) therapy significantly reduced proteinuria levels in patients with IgAN. Steroid treatment significantly reduced the risk for end-stage renal disease (ESRD) (relative risk [RR] 0.39, CI 0.19 to 0.79). The immunosuppressive therapy group showed significant increases in gastrointestinal, hematological, dermatological, and genitourinary side effects, as well as impaired glucose tolerance or diabetes. Hyperkalemia was more common in the control group.\n\nConclusionImmunosuppressive therapy can significantly reduce proteinuria and ESRD risk in patients with IgAN, but with a concomitant increase in adverse reactions. Therefore, care is required in the application of immunosuppressive agents in IgAN.

immunology↗

bioRxiv2018

Loud music and the specific sound stress open the blood-brain barrier: new fundamental, biomedical, and social aspects

The blood-brain barrier (BBB) poses a significant challenge for drug brain delivery. The limitation of our knowledge about the nature of BBB explains the slow progress in the therapy of brain diseases and absence of methods for drug brain delivery in the clinical practice.\n\nHere we show that BBB opens for low/high weight molecules and nanocarriers after exposure of loud music/sound of 90 dB and 100 dB (regardless its frequency) as being easily produced by MP3/MP4 players, kitchen appliances, loudspeakers at concerts. The role of sound, sound-induced stress and molecular mechanisms behind is discussed in the framework of BBB opening as an informative platform for a novel fundamental knowledge about the nature of BBB and for the development of a non-invasive brain drug delivery technology.\n\nSocial aspects of music/sound-induced opening of BBB provide completely new information about noise and healthy life conditions that will stimulate new research in this field.

neuroscience↗

bioRxiv2018

Optical imaging of single protein size, charge, mobility, binding and conformational change

Protein analysis has relied on electrophoresis, mass spectroscopy and immunoassay, which separate, detect and identify proteins based on the size, charge, mobility and binding to antibodies. However, measuring these quantities at the single molecule level has not been possible. We tether a protein to a surface with a flexible polymer, drive the protein into mechanical oscillation with an alternating electric field, and image the protein oscillation with a near field imaging method, from which we determine the size, charge, mobility of the protein. We also measure binding of antibodies to single proteins and ligand binding-induced conformational changes in single proteins. This work provides new capabilities for protein analysis and disease biomarker detection at the single molecule level.

biophysics↗

bioRxiv2018

Whole-tree heartwood inducing technique for Dalbergia odorifera

The dried heartwood of Dalbergia odorifera is a very important traditional Chinese medicine. In nature, D. odorifera heartwood forms slowly over several decades, and excessive harvesting has caused large-scale reductions of its wild populations. To date, there have been no studies on artificial methods to induce heartwood formation in trees that have not already begun producing heartwood. We have published a patent for a whole-tree heartwood inducing technique for D. odorifera (the \"Dodor-Wit\" method); here, we describe and analyze its efficacy. Trees in four plantations in China were treated using this method. After two years, in 2016 and 2017, they were harvested and analyzed. Average heartwood yield per tree was 3,161.95 g. Heartwood induction rate (dry heartwood weight to total dry trunk weight after peeling) was 21.60%. Average volatile oil content per tree was 1.42%. Alcohol-soluble extract of the induced heartwood was 15.77%, exceeding the Chinese Pharmacopoeia standard. This is the first report on the Dodor-Wit method and heartwood induction in D. odorifera trees aged 5-8 years. The heartwood induced by Dodor-Wit satisfies the requirements of the Chinese Pharmacopoeia. The Dodor-Wit method has an important role in solving the extreme scarcity of Chinese medicinal herbs.

plant biology↗

bioRxiv2018

Nationwide population genetic screening improves outcomes of newborn screening for hearing loss in China

PurposeConcurrent newborn hearing and genetic screening has been reported, but its benefits have not been statistically proven due to limited sample sizes and outcome data. To fill this gap, we analyzed outcomes of a large number of newborns with genetic screening results.\n\nMethodsNewborns in China were screened for 20 hearing-loss-related genetic variants from 2012-2017. Genetic results were categorized as positive, at-risk, inconclusive, or negative. Hearing screening results, risk factors, and up-to-date hearing status were followed-up via phone interviews.\n\nResultsWe completed genetic screening on one million newborns and followed up 12,778. We found that a positive genetic result significantly indicated a higher positive predictive value of the initial hearing screening (60% vs. 5.0%, P<0.001) and a lower rate of loss-to-follow-up (5% vs. 22%, P<0.001) than an inconclusive one. Importantly, 42% of subjects in the positive group with reported or presymptomatic hearing loss were \"missed\" by conventional hearing screening. Furthermore, genetic screening identified 0.23% of subjects predisposed to preventable ototoxicity.\n\nConclusionOur results demonstrate that limited genetic screening identified additional cases, reduced loss-to-follow-up, and informed families of ototoxicity risks, providing convincing evidence to support integrating genetic screening into universal newborn hearing screening programs.

genetics↗

bioRxiv2018

Predicting circRNA-RBP interaction sites using a codon-based encoding and hybrid deep neural networks

Circular RNAs (circRNAs), with their crucial roles in gene regulation and disease development, have become a rising star in the RNA world. A lot of previous wet-lab studies focused on the interaction mechanisms between circRNAs and RNA-binding proteins (RBPs), as the knowledge of circRNA-RBP association is very important for understanding functions of circRNAs. Recently, the abundant CLIP-Seq experimental data has made the large-scale identification and analysis of circRNA-RBP interactions possible, while no computational tool based on machine learning has been developed yet.\n\nWe present a new deep learning-based method, CRIP (CircRNAs Interact with Proteins), for the prediction of RBP binding sites on circRNAs, using only the RNA sequences. In order to fully exploit the sequence information, we propose a stacked codon-based encoding scheme and a hybrid deep learning architecture, in which a convolutional neural network (CNN) learns high-level abstract features and a recurrent neural network (RNN) learns long dependency in the sequences. We construct 37 datasets including sequence fragments of binding sites on circRNAs, and each set corresponds to one RBP. The experimental results show that the new encoding scheme is superior to the existing feature representation methods for RNA sequences, and the hybrid network outperforms conventional classifiers by a large margin, where both the CNN and RNN components contribute to the performance improvement. To the best of our knowledge, CRIP is the first machine learning-based tool specialized in the prediction of circRNA-RBP interactions, which is expected to play an important role for large-scale function analysis of circRNAs.

bioinformatics↗

bioRxiv2018

Galectin-3, A Novel Endogenous Trem2 Ligand, Regulates Inflammatory Response and Aβ Fibrilation in Alzheimer’s Disease

Alzheimers disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (A{beta}) peptide, intraneuronal tau neurofibrillary tangles and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brains of AD patients and 5xFAD (familial Alzheimers disease) mice, and found specifically expressed in microglia associated with A{beta} plaques. Single nucleotide polymorphisms in the LGALS3 gene, which encodes gal3, were associated to an increased risk of AD. Gal3 deletion in 5xFAD mice attenuated microglia-associated immune responses, particularly those associated with TLR and TREM2/DAP12 signaling. In vitro data demonstrated the requirement of gal3 to fully activate microglia in response to fibrillar A{beta}. Gal3 deletion decreased the A{beta} burden in 5xFAD mice and improved cognitive behavior. Electron microscopy of gal3 in AD mice demonstrated i) a preferential expression of gal3 by plaque-associated microglia, ii) its presence in the extracellular space and iii) its association to A{beta} plaques. Low concentrations (1 nM) of pure gal3 promoted cross-seeding fibrilization of pure A{beta}. Importantly, a single intrahippocampal injection of gal3 along with A{beta} monomers in WT mice was sufficient to induce the formation of insoluble A{beta} aggregates that were absent when gal3 was lacking. High-resolution microscopy (STORM) demonstrated close co-localization of gal3 and TREM2 in microglial processes, and a direct interaction was shown by a fluorescence anisotropy assay involving the gal3 CRD domain. Furthermore, gal3 stimulated the TREM2-DAP12 signaling pathway. In conclusion, we provide evidence that gal3 is a central regulator of microglial immune response in AD. It drives proinflammatory activation and A{beta} aggregation, as well as acting as an endogenous ligand to TREM2, a key receptor driving microglial response under disease conditions. Gal3 inhibition may, hence, be a potential pharmacological approach to counteract AD.

neuroscience↗

bioRxiv2018

Time-resolved digital immunoassay for rapid and sensitive quantitation of procalcitonin with plasmonic imaging

Timely diagnosis of acute diseases improves treatment outcomes and saves lives, but it requires fast and precision quantification of biomarkers. Here we report a time-resolved digital immunoassay based on plasmonic imaging of binding of single nanoparticles to biomarkers captured on a sensor surface. The real-time and high contrast of plasmonic imaging lead to fast and precise counting of the individual biomarkers over a wide dynamic range. We demonstrated the detection principle, evaluated the performance of the method using procalcitonin (PCT) as an example, and achieved a limit of detection of ~ 3 pg/mL, dynamic range of 4-12500 pg/mL, for a total detection time of ~ 25 mins.

bioengineering↗

bioRxiv2018

Pervasive translation of circular RNAs driven by short IRES-like elements

Although some circular RNAs (circRNAs) were found to be translated through IRES-driven mechanism, the scope and functions of circRNA translation are unclear because endogenous IRESs are rare. To determine the prevalence and mechanism of circRNA translation, we developed a cell-based system to screen random sequences and identified 97 overrepresented hexamers that drive cap-independent circRNA translation. These IRES-like short elements are significantly enriched in endogenous circRNAs and sufficient to drive circRNA translation. We further identified multiple trans-acting factors that bind these IRES-like elements to initiate translation. Using mass-spectrometry data, hundreds of circRNA-coded peptides were identified, most of which have low abundance due to rapid degradation. As judged by mass-spectrometry, 50% of translatable endogenous circRNAs undergo rolling circle translation, several of which were experimentally validated. Consistently, mutations of the IRES-like element in one circRNA reduced its translation. Collectively, our findings suggest a pervasive translation of circRNAs, providing profound implications in translation control.

molecular biology↗

bioRxiv2018

Model-Aware Deep Learning Based Strategies for Clutter Suppression in Contrast Enhanced Ultrasound

Contrast enhanced ultrasound is a radiation-free imaging modality which uses encapsulated gas microbubbles for improved visualization of the vascular bed deep within the tissue. It has recently been used to enable imaging with unprecedented subwavelength spatial resolution by relying on super-resolution techniques. A typical preprocessing step in super-resolution ultrasound is to separate the microbubble signal from the cluttering tissue signal. This step has a crucial impact on the final image quality. Here, we propose a new approach to clutter removal based on robust principle component analysis (PCA) and deep learning. We begin by modeling the acquired contrast enhanced ultrasound signal as a combination of a low rank and sparse components. This model is used in robust PCA and was previously suggested in the context of ultrasound Doppler processing and dynamic magnetic resonance imaging. We then illustrate that an iterative algorithm based on this model exhibits improved separation of microbubble signal from the tissue signal over commonly practiced methods. Next, we apply the concept of deep unfolding to suggest a deep network architecture tailored to our clutter filtering problem which exhibits improved convergence speed and accuracy with respect to its iterative counterpart. We compare the performance of the suggested deep network on both simulations and in-vivo rat brain scans, with a commonly practiced deep-network architecture and the fast iterative shrinkage algorithm, and show that our architecture exhibits better image quality and contrast.

bioengineering↗

bioRxiv2018

Spatiotemporal expression of FRIGIDA modulate flowering time in Arabidopsis thaliana

FRIGIDA (FRI) as the major regulator of flowering time in Arabidopsis accessions can activate its target FLOWERING LOCUS C (FLC) to delay flowering before vernalization. Besides FLC, other FRI targets also exist in Arabidopsis. Although leaves sense environmental cues to modulate flowering time, it is not known if roots also regulate the floral transition. In this study, we investigated the spatiotemporal effect of FRI on flowering time. Local expression of FRI in the phloem and leaves activated FLC to delay flowering. Furthermore, we found that local expression of FRI in the roots also delayed flowering by activating other targets MADS AFFECTING FLOWERING4 (MAF4) and MAF5 in the roots. Graft and genetic experiments revealed that the spatial expression of FRI in the root might generate a mobile signal, which is transmitted from roots to shoot and antagonizes the FT signal to delay flowering. Specifically expressing FRI in the embryo efficiently delayed flowering, even expressing FRI as early as pro-embryo stage is enough to upregulate FLC expression to delay flowering. Together, our findings confirm the spatiotemporal effect of FRI on delaying flowering, and propose that root tissue also perceives the flowering signal to fine-tune the flowering time through MAF4/5 as novel targets of FRI.\n\nHighlightRoot FRIDIGA activated the novel targets MAF4/5 to delay flowering; Temporal expressing FRIGIDA at as early as pro-embryo stage is efficient to delay flowering.

plant biology↗