A rapid VEGF-gene-sequence photoluminescence detector for osteoarthritis

Osteoarthritis (OA) has become a serious problem to the human society for years due to its high economic burden, disability, pain, and severe impact on the patient’s lifestyle. The importance of current clinical imaging modalities in the assessment of the onset and progression of OA is well recognized by clinicians, but these modalities can only detect OA in the II stage with significant structural deterioration and clinical symptoms. Blood vessel formation induced by vascular endothelial growth factor (VEGF) occurs in the early stage and throughout the entire course of OA, enables VEGF relating gene sequence to act as a biomarker in the field of early diagnosis and monitoring of the disease. Here in, a facile rapid detection of VEGF relating ssDNA sequence was developed, in which manganese-based zeolitic imidazolate framework nanoparticles (Mn-ZIF-NPs) were synthesized by a simple coprecipitation strategy, followed by the introduction and surficial absorption of probe ssDNAs and the CRISPR/Cas12a system components. Furthermore, fluorescence experiments demonstrated that the biosensor displayed a low detection limit of 2.49 nM, a good linear response to the target ssDNA ranging from 10 nM to 500 nM, and the ability of distinguishing single nucleotide polymorphism. This finding opens a new window for the feasible and rapid detection of ssDNA molecules for the early diagnose of OA

Novel genetic variants of PIP5K1C and MVB12B of the endosome-related pathway predict cutaneous melanoma-specific survival

Endosomes regulate cell polarity, adhesion, signaling, immunity, and tumor progression, which may influence cancer outcomes. Here we evaluated associations between 36,068 genetic variants of 228 endosome-related pathway genes and cutaneous melanoma disease-specific survival (CMSS) using genotyping data from two previously published genome-wide association studies. The discovery dataset included 858 CM patients with 95 deaths from The University of Texas MD Anderson Cancer Center, and the replication dataset included 409 CM patients with 48 deaths from the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). In multivariate Cox proportional hazards regression analysis, we found that two novel SNPs (PIP5K1C rs11666894 A>C and MVB12B rs12376285 C>T) predicted CMSS, with adjusted hazards ratios of 1.47 (95% confidence interval = 1.15-1.89 and P = 0.002) and 1.73 (1.30-2.31 and 0.0002), respectively. Combined analysis of risk genotypes of these two SNPs revealed a dose-dependent decrease in CMSS associated with an increased number of risk genotypes (P trend = 0.0002). Subsequent expression quantitative trait loci (eQTL) analysis revealed that PIP5K1C rs11666894 was associated with mRNA expression levels in lymphoblastoid cell lines from 373 European descendants (P<0.0001) and that MVB12B rs12376285 was associated with mRNA expression levels in cultured fibroblasts from 605 European-Americans (P<0.0001). Our findings suggest that novel genetic variants of PIP5K1C and MVB12B in the endosome-related pathway genes may be promising prognostic biomarkers for CMSS, but these results need to be validated in future larger studies

Patterns and rates of exonic de novo mutations in autism spectrum disorders

Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified1,2. To identify further genetic risk factors, we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n= 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant and the overall rate of mutation is only modestly higher than the expected rate. In contrast, there is significantly enriched connectivity among the proteins encoded by genes harboring de novo missense or nonsense mutations, and excess connectivity to prior ASD genes of major effect, suggesting a subset of observed events are relevant to ASD risk. The small increase in rate of de novo events, when taken together with the connections among the proteins themselves and to ASD, are consistent with an important but limited role for de novo point mutations, similar to that documented for de novo copy number variants. Genetic models incorporating these data suggest that the majority of observed de novo events are unconnected to ASD, those that do confer risk are distributed across many genes and are incompletely penetrant (i.e., not necessarily causal). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5 to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favor of CHD8 and KATNAL2 as genuine autism risk factors

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Efficacy and safety of oral compared with intravenous tranexamic acid in reducing blood loss after primary total knee and hip arthroplasty: a meta-analysis

Abstract Background Tranexamic acid (TXA) is an anti-fibrinolytic agent successfully preventing blood loss when using intravenously (IV) in total hip arthroplasty (THA) and total knee arthroplasty (TKA). An oral administration, which is available on blood sparing, has been reported exhibit profound cost-saving benefits. The aim of this meta-analysis is to investigate whether the administration of oral and intravenous tranexamic acid postoperatively has equivalent blood-sparing properties in these patients. Methods The online electronic databases were searched for eligible literatures updated on September 2018. Studies assessing the effect between oral TXA and intravenous TXA (IV-TXA) in those undergoing TKA or THA were included. All the data were pooled with the corresponding 95% confidence interval (CI) using RevMan software. Based on the heterogeneity, we performed a systematic analysis to explore the overall results across the included studies. Results Nine studies met our inclusion criteria. No significant differences were identified with regard to the Hb drop (SMD = − 0.03,95%CI = − 0.18–0.12, P = 0.67), total Hb loss (SMD = 0.10,95%CI = − 0.06–0.26, P = 0.24), total blood loss (SMD = − 0.00,95%CI = − 0.20–0.20, P = 1.00), transfusion rate (OR = 0.77,95%CI = 0.54–1.10, P = 0.14), DVT rate (OR = 0.58,95%CI = 0.19–1.75, P = 0.33), and length of hospital stay (SMD = − 0.05,95%CI = − 0.28–0.17, P = 0.63) between the oral groups and intravenous group. Conclusion The blood-sparing efficacy of oral TXA is similar to that of the intravenous forms in the setting of THA and TKA. Considering the cost-benefit superiority and ease of administration of oral TXA, further studies and clinical trials are required to further identify the optimal administration for THA and TKA

An Indoor Ultrasonic Positioning System Based on TOA for Internet of Things

With the development of Internet of Things, the position information of indoor objects becomes more important for most application scenarios. This paper presents an ultrasonic indoor positioning system, which can achieve centimeter-level precise positioning of objects moving indoors. Transmitting nodes, receiving nodes, and display control terminal are needed to constitute the entire system. The system is based on long-baseline positioning technology that uses code division multiplexing access mechanism. There is no limit to the number of receiving nodes as the system works in the up-transmit-down-receive mode. Positioning of a receiving node is found based on ultrasonic Time of Arrival ranging technology. To accurately determine the positioning, there must be at least four or five transmitting nodes. The working radius will not be less than 5 meters when the height is larger than 3 meters. The system uses wideband pseudorandom noise signal called Gold sequences for multiuser identification and slant range measurement. The paper first gives a brief introduction of popular indoor ultrasonic positioning methods and then describes the theory of proposed algorithm and provides the simulation results. To examine the correctness of the approach and its practicality, the practical implementation and experimental results are provided also in the paper

Quorum Sensing Activity and Hyphal Growth by External Stimuli in the Entomopathogenic Fungus Ophiocordyceps sinensis

The entomopathogenic fungus Ophiocordyceps sinensis is one of the best known and most precious medicines and health food in China. The blastospores-hyphae (dimorphism) transition of this fungus in host hemolymph is critical for the virulence and the mummification of host larvae. To regulate this transition, the effects of inoculum density and fifteen chemicals including fungal nutrients, fungal metabolites, quorum-sensing molecules (QSMs) and insect hormones on the dimorphism in O. sinensis were investigated in vitro. The blastospores tended to exhibit budding growth when inoculated at 107 blastospores per mL, and hyphal growth at concentrations lower than 106 blastospores per mL. At 105 blastospores per mL, the percentage of hyphal formation decreased with the addition of filtered spent medium containing 107 blastospores per mL, indicating the quorum-sensing effect. Blastospores-hyphae transition in this fungus by fifteen chemicals was varied from no response to dimorphic reversion. The addition of N-acetylglucosamine at three concentrations significantly stimulated hyphal formation while inhibiting budding growth. For the first time, insect hormone 20-hydroxyecdysone was found to be involved in the hyphal formation in fungi. These results open new possibilities to regulate the dimorphism, which would be beneficial for the cultivation of the Chinese cordyceps

Preliminary Evaluation of FY-3E Microwave Temperature Sounder Performance Based on Observation Minus Simulation

The FY-3E satellite was successfully launched on 5 July 2021 and carries on board the Microwave Temperature Sounder-III (MWTS-III). In this study, the biases of MWTS-III data with respect to simulations are analyzed according to the instrument field of view and location latitude over the Pacific region. The cloud liquid water path (CLWP) over oceans is retrieved from two new window channels at 23.8 and 31.4 GHz and is used for detecting the clouds-affected microwave sounding data. The absolute bias between the observed and simulated brightness temperature (O–B) under the clear sky point is, in general, less than 2.0 K, depending on the MWTS-III channel. The standard deviations of O-B in most channels are less 1.0 K, but they are 1–1.5 K in channels 1–4 and 17. The average and the standard deviation of O−B from the channels 1–10 shows an obvious symmetrical variation with FOV. The evaluation results all indicate good prospects for the assimilation application of FY-3E microwave sounding data

Design of Animal Myocardial Contractile Force Detection System Based on Tissue Engineering

International audienceThis paper uses the sensor convert animal myocardial contractile force into a voltage signal, which is collect by a MCU acquisition, transferred to the computer, using the PC visualization language VB compiled a data acquisition and processing platform, collected data can be stored into a computer, and real-time curve of the data changes is plotted at any time. Through testing the tissue engineered cardiac tissue strips micro contractility, it was proved that the platform operation is of stable performance, accurate data acquisition, processing method effective, the system can also be applied in other similar signal detection and acquisition and other fields