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Objective: To verify whether icariin has drug toxicity to osteoblasts and its pre protective effect on inflammatory osteoblasts induced by lipopolysaccharide. Methods: (1) The osteoblasts of newborn SD rats were extracted, cultured and passaged. By observing the morphology of osteoblasts and ALP staining, the activity and proliferation of osteoblasts were determined. (2) CCK-8 method was used to observe the effect of Icariin on osteoblast activity. (3) Different concentrations of lipopolysaccharide (LPS) were used to induce inflammatory osteoblasts in fetal rats. CCK-8 method was used to select the best concentration for induction.(4) This experiment was divided into control group, low concentration group,middle concentration group and high concentration group. CCK-8 method was used to observe whether icariin could protect osteoblasts from inflammatory reaction. Results: (1) The number of osteoblasts in the third generation increased, the shape of osteoblasts overlapped like tiles, most of osteoblasts grew in the center, the center was dense and the specific shape was difficult to see. After ALP staining, the positive cells showed gray black granules in cytoplasm and irregular cell body shape under inverted microscope; (2) DWhen the concentration of icariin was lower than 1 μ g / ml, it had no significant effect on osteoblasts (P < 0.05); when it was higher than 10 μ g / ml, icariin had no significant effect on osteoblasts (P < 0.05); (3) When the concentration of lipopolysaccharide was higher than 80 μ g / ml, there was a significant trend of inflammatory damage to osteoblasts, which was statistically significant (P < 0.01). Therefore, 80 μ g / ml was selected as the best injury concentration in this experiment;(4) When the concentration of icariin was lower than 1 μ g / ml, there was no significant pre protective effect on the inflammatory response of osteoblasts (P < 0.05); when it was higher than 10 μ g / ml, there was significant pre protective effect on the inflammatory response of osteoblasts (P < 0.05). Conclusion: When the concentration of icariin reaches a certain level, it can promote the proliferation of osteoblasts and has a certain pre protective effect on inflammatory osteoblasts.

Much recent progress in monaural speech separation (MSS) has been achieved through a series of deep learning architectures based on autoencoders, which use an encoder to condense the input signal into compressed features and then feed these features into a decoder to construct a specific audio source of interest. However, these approaches can neither learn generative factors of the original input for MSS nor construct each audio source in mixed speech. In this study, we propose a novel weighted-factor autoencoder (WFAE) model for MSS, which introduces a regularization loss in the objective function to isolate one source without containing other sources. By incorporating a latent attention mechanism and a supervised source constructor in the separation layer, WFAE can learn source-specific generative factors and a set of discriminative features for each source, leading to MSS performance improvement. Experiments on benchmark datasets show that our approach outperforms the existing methods. In terms of three important metrics, WFAE has great success on a relatively challenging MSS case, i.e., speaker-independent MSS.

Xinjiang Uyghur Autonomous Region in China embraces a unique geographical and ecological environment, and the macrofungi represent a rich resource. However, few studies on the genus

Content authentication and tampering detection of multimedia is a vital application by using digital watermarking. In this paper, we propose a novel fraGile wateRmArking of speeCh based on Endpoint Detection (namely GRACED) to verify the integrity of speech. Firstly, speech signal is framed word by word and each speech frame includes one intact nonsilence word. Subsequently, feature fusion is adopted to generate the fragile watermark which will be embedded into the coefficients of hybrid domain of discrete wavelet transform (DWT) and singular value decomposition (SVD). Finally, the tampering detection is accomplished without using any synchronous code to detect kinds of attacks. Several experiments are executed in order to quantify the performance of the proposed method. Experimental evaluation and comparisons with other schemes demonstrate that the signal-to-noise ratio of the proposed method is high with a favorable imperceptibility. Additionally, the tampering localization of various malicious attacks can be achieved without using synchronous code and the proposed scheme even can determine the attack types.

Serum uric acid (UA) is a traditional biomarker in the clinical diagnosis of gout and hyperuricemia. However, serum treatment and storage are cumbersome, and wounds are susceptible to infection. Therefore, in this study, a simple and noninvasive method was developed to detect the UA in human saliva to monitor the gout. An Inertsil ODS-3 column was used for the analysis under the condition of isocratic elution with the mixed solution phosphate buffer (74 mM, pH=2.2): Methanol=98:2 (v:v) and the UV detection at 284 nm. Using salivary UA data from healthy volunteers (HVs) (n=68) and gout patients (GPs) (n=14), we examined the salivary UA difference in their content. The intra-and inter-day accuracy and precision (RSD %) were less than 2.56%, the limit of detection (LOD) of UA was 5.0 ng/mL, the mean recoveries of the corresponding compounds were 102.48%. Saliva levels of UA in HVs and GPs were 35.26±14.06 µg/mL and 91.96±23.90 µg/mL, respectively. The concentrations of salivary UA in GPs were significantly higher than those in HVs ( p < 0.001). This method was also expected to monitor the hyperuricemia and other metabolic disorders in the future.

To understand the oscillatory behavior exhibited in the timelike electromagnetic form factors of nucleons, we propose a toy model based on the Jost function of the $N\bar N$ pair into the timelike form factors with the help of the distorted-wave Born approximation. By constructing a simple square-well potential reflecting the final-state interaction of $N\bar N$, we naturally represent the damped oscillatory phenomenon in the timelike electromagnetic form factors of nucleons. Especially, our study reveals that the ``period" of the oscillation is approximately determined by the Yukawa interaction range $1/m_\pi$. Other possible potentials are also discussed. The threshold enhancements of the cross sections for $e^+e^-\to n\bar n$, $\Lambda\bar\Lambda$, and $\Lambda_c\bar\Lambda_c$ can also be understand within this scenario., Comment: 7 pages, 3 figures. We provide supplemental materials to show that the new data from the BESIII collaboration (arXiv:2303.07629) are consistent with our earlier description

Owing to the complexity of the electroforming mechanism, the structure of electroformed deposits is affected by many process parameters, and defects such as pinholes and nodules in electroformed deposits must be solved. In this study, the mechanism by which hard particles inhibit the formation of the above defects in the electroforming process of Ni-Co alloys was analyzed. Through the friction-assisted electroforming Ni-Co alloy tests, the effects of friction and current density on the hardness, texture and microstructure of the Ni-Co electroformed deposits were studied. The results show that the microhardness of the Ni-Co coatings obtained is between 651 HV and 669 HV with the increase of the cathode speed from 8 rpm to 512 rpm. When the cathode speed is 16rpm, the grain sizes of Ni-Co coatings increase with the increase of cathode current density from 2 A dm−2 to 8 A dm−2, and the microhardness of the coatings is between 672 HV and 590 HV.

In this work, we investigate the open-charm decay process $\ensuremath{\psi}\ensuremath{\rightarrow}{\mathrm{\ensuremath{\Lambda}}}_{c}{\overline{\mathrm{\ensuremath{\Lambda}}}}_{c}$ via the hadronic loop mechanism for vector charmonia above ${\mathrm{\ensuremath{\Lambda}}}_{c}{\overline{\mathrm{\ensuremath{\Lambda}}}}_{c}$ threshold. The branching ratios of these vector charmonium states to ${\mathrm{\ensuremath{\Lambda}}}_{c}{\overline{\mathrm{\ensuremath{\Lambda}}}}_{c}$ are estimated. The charmonium explanation of the $Y(4630)$ observed in ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{\mathrm{\ensuremath{\Lambda}}}_{c}{\overline{\mathrm{\ensuremath{\Lambda}}}}_{c}$ is tested. Furthermore, for the predicted higher vector charmonia above 4.7 GeV, the branching ratios $\mathcal{B}[\ensuremath{\psi}(nS)\ensuremath{\rightarrow}{\mathrm{\ensuremath{\Lambda}}}_{c}{\overline{\mathrm{\ensuremath{\Lambda}}}}_{c}]$ with $n=7$, 8, 9 are found to be of the order of magnitude of ${10}^{\ensuremath{-}4}\ensuremath{-}{10}^{\ensuremath{-}3}$ while $\mathcal{B}[\ensuremath{\psi}(mD)\ensuremath{\rightarrow}{\mathrm{\ensuremath{\Lambda}}}_{c}{\overline{\mathrm{\ensuremath{\Lambda}}}}_{c}]$ with $m=6$, 7, 8 are of the order of magnitude of ${10}^{\ensuremath{-}3}\ensuremath{-}{10}^{\ensuremath{-}2}$. The experimental signals of these missing charmonium states are discussed. The search for them may be an interesting topic in the future BESIII and Belle II experiments.

Vestibular organs have unique planar cell polarity (Figure 1A), and their normal development and function are dependent on the regular polarity of cilia (Figure 1B) requires. Rab11a is a small G protein that participates in the transportation of intracellular and extracellular materials required for polarity formation; however, our understanding of the mechanisms of the actions of Rab11a in vestibular organs is limited. Here, we showed that the general shape of the utricle was abnormal in Rab11aCKO/CKO mice. These mice also showed abnormal morphology of the stereocilia bundles, which were reduced in both length and number, as well as disturbed tissue-level polarity. Rab11a affected the distribution of polarity proteins in the vestibular organs, indicating that the normal development of cilia requires Rab11a and intraflagellar transportation. Furthermore, small G protein migration works together with intraflagellar transportation in the normal development of cilia. FIGURE 1Morphological changes of stereocilia in the extrastriolar hair cells from Rab11a single or Rab11a/IFT88 double-mutant utricles. (A) Medial view of a mouse left inner ear with its five vestibular sensory organs (gray). Enlarged are the utricle showing their subdivisions, LPR (yellow line), and striola (blue). LES, lateral extrastriola; MES, medial extrastriola; LPR, line of polarity reversal. (B) Schematic view of vestibular hair cell. Kinocilium is marked with ace-tubulin. Basal body is marked with γ-tubulin. (C,C1,D,D1) Normal appearance of the stereocilia of extrastriolar hair cells of wild-type controls. (E,E1,F,F1) Altered morphology in Rab11aCKO/CKO animals. (G,G1,H,H1) The changes in the stereocilia morphology were more severe in Rab11aCKO/CKO/IFT 88CKO/+ mice. (I–L) Higher magnification of confocal images of hair cells. (M–P) Scanning electron microscopy images of hair cells from wild-type controls and Rab11a mutants. (I,M) Morphology of normal. hair cells of wild-type controls. (J,N) The number of stereocilia on a single hair cell was deceased in the Rab11a mutant. (K,O) Stereocilia were shorter in mutants compared to the wild-type controls. (L,P) The staircase-like hair bundle architecture of hair cells was lost in Rab11a mutant mice. (Q) The percentage of hair cells with abnormal development of static cilia bundles in the extrastriola region was counted as a percentage of the total (n = 5). The percentage of abnormal hair cells was higher in Rab11aCKO/CKO, IFT88CKO/+ mice compared to Rab11aCKO/CKO. The abnormal ratios of single and double knockout hair cells were 42.1 ± 5.7 and 71.5 ± 10.4, respectively. In (A–J), for all primary panels, hair cell stereociliary bundles were marked with phalloidin (green), the actin-rich cuticular plate of hair cells was labeled with β-spectrin (red), while the basal body of the hair cell was labeled with γ-tubulin (blue). Scale bars: 10 μm (C–H1), 5 μm (J–N). *P < 0.05.

To compare the effect of electroacupuncture (EA), metformin and EA plus metformin on the cognitive ability and senile plaques (SPs) in cerebral cortex and hippocampus of Alzheimer's disease (AD) mice, so as to explore a better treatment method for AD.Twenty-four male APP/PS1 mice were randomly divided into model, metformin (medication), EA and EA+medication groups, with 6 mice in each group. Other 6 male wild C57 mice were used as the control group. EA (2 Hz, 1.0 mA) was applied to "Baihui" (GV20) and "Shenshu" (BL23) for 15 min, once a day, for 4 weeks, with 1 day's off every week. The mice of the medication group received gavage of metformin (300 mg·kgCompared with the control group, the escape latency, number of SPs and the expression of βACE1 in the cortex and hippocampus were ob-viously increased (EA, metformin and EA plus metformin can improve cognitive ability and relieve SP formation in cerebral cortex and hippocampus in AD mice, which may be associated with their functions in down-regulating the expression of βACE1 and up-regulating the expression of IDE. The therapeutic effects of EA plus metformin are apparently better than those of simple EA and simple metformin.

Rheumatoid arthritis (RA) is a chronic, progressive and systemic autoimmune disease mainly characterized by symmetric multijoint synovitis. Quercetin has anti-inflammatory, anti-oxidation and immune regulation activities, and therefore shows high medicinal value. The present study aimed to observe the effect of quercetin on fibroblast-like synoviocytes (FLSs) in RA. Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) were pretreated with 50 nmol/l quercetin for 2 h and were then stimulated using TNF-α for 24 h for subsequent experiments. RAFLSs were transfected with short interfering (si)-X-inactive specific transcript (XIST), microRNA (miR)-485 mimic, miR-485 inhibitor or si-PSMB8 or combination. ELISA, PCR and western blotting was used to evaluate the effect of quercetin on RAFLSs treated with TNF-α. It was revealed that quercetin inhibited the production of inflammatory cytokines and the expression of XIST in RAFLSs induced by TNF-α. Bioinformatics analysis indicated that XIST acted as a sponge for miR-485 and that proteasome subunit β type-8 (PSMB8) was a direct target of miR-485. Moreover, PSMB8 functioned as a suppressor in inflammatory cytokine production of RAFLSs induced by TNF-α. Overall, quercetin was observed to inhibit the production of inflammatory cytokines and the expression of XIST in RAFLSs induced by TNF-α. Moreover, XIST-silencing could suppress the inflammatory reaction by sponging miR-485 in cells treated with TNF-α. Altogether, quercetin could suppress the development of RA in vitro.

To analyze the potential genetic cause of thrombocytopenia-absent radius (TAR) syndrome in a family and provide prenatal diagnosis for them.Genetic mutation analysis of the sporadic family with TAR syndrome was performed with chromosome microarray analysis (CMA), quantitative polymerase chain reaction (qPCR) and Sanger sequencing. DNA samples were collected from 4 members of the family, including the proband, her parents and her sister. CMA, qPCR and Sanger sequencing were performed to determine the pathogenic mutation and prenatal diagnosis of the fetus was made accordingly.The proband had a 378 kb genomic heterozygous deletion in 1q21.1, which containedThe heterozygous deletion in 1q21.1 and

Background To robustly identify synergistic combinations of drugs, high-throughput screenings are desirable. It will be of great help to automatically identify the relations in the published papers with machine learning based tools. To support the chemical disease semantic relation extraction especially for chronic diseases, a chronic disease specific corpus for combination therapy discovery in Chinese (RCorp) is manually annotated. Methods In this study, we extracted abstracts from a Chinese medical literature server and followed the annotation framework of the BioCreative CDR corpus, with the guidelines modified to make the combination therapy related relations available. An annotation tool was incorporated to the standard annotation process. Results The resulting RCorp consists of 339 Chinese biomedical articles with 2367 annotated chemicals, 2113 diseases, 237 symptoms, 164 chemical-induce-disease relations, 163 chemical-induce-symptom relations, and 805 chemical-treat-disease relations. Each annotation includes both the mention text spans and normalized concept identifiers. The corpus gets an inter-annotator agreement score of 0.883 for chemical entities, 0.791 for disease entities which are measured by F score. And the F score for chemical-treat-disease relations gets 0.788 after unifying the entity mentions. Conclusions We extracted and manually annotated a chronic disease specific corpus for combination therapy discovery in Chinese. The result analysis of the corpus proves its quality for the combination therapy related knowledge discovery task. Our annotated corpus would be a useful resource for the modelling of entity recognition and relation extraction tools. In the future, an evaluation based on the corpus will be held.

A novel chiral derivatization reagent, the N-[1-oxo-5-(triphenylphosphonium)pentyl]- (R)-1,3-thiazolidinyl-4-N-hydroxysuccinimide ester bromide salt (OTPTHE), was developed for the separation and selective detection of chiral DL-amino acids by RP-HPLC analysis. The OTPTHE reacted with DL-amino acids at 60°C maintained for 30 minutes in the presence of 100 mM borate buffer (pH 9.5). The separability of the diastereomeric derivatives was evaluated in terms of the resolution value (Rs) using 13 kinds of DL-amino acids, which were completely separated by reversed-phase chromatography using C18 column at 254 nm. The Rs of the DL-amino acids varied from 1.62 to 2.51. As for the application of the DL-amino acids, the determination of DL-Ser in the human plasma of healthy volunteers was performed based on our developed method. It was shown that linear calibrations were available with high coefficients of correlation (r2 > 0.9997). The limit of detection (S/N = 3) of the DL-Ser enantiomers was 5.0 pmol; the relative standard deviations of the intraday and interday variations were below 4.56%; the accuracy ranged between 95.40%-110.06% and 95.45%-109.80%, respectively; the mean recoveries (%) of the DL-Ser spiked in the human plasma were 99.49%-103.74%. The amounts of DL-Ser in the human plasma of healthy volunteers were determined.

A few small retrospective studies recently found that endoscopic retrograde cholangiopancreatography (ERCP) in asymptomatic compared with symptomatic common bile duct stones (CBDSs) patients appeared to increase the risk of post-ERCP pancreatitis (PEP). This study aimed to determine the risk of ERCP in asymptomatic CBDS patients.A total of 327 consecutive patients with native papilla were invited to participate into the study and divided into two groups: 53 in the asymptomatic group and 274 in the symptomatic group, who underwent CBDS removal by ERCP. Patient's characteristics and outcomes were analyzed.A total of 46 (14.1%) patients had ERCP-related complications, including PEP, cholangitis, perforation, and bleeding. The overall complication rate in the asymptomatic group was higher than in the control group (26.4% vs 11.7%, P0.01). PEP was the most common complication (30/327, 9.2%). Of the 30 cases of PEP, 25 (83.3%) were mild, and the severity in both groups was similar (9/1/1 vs 16/2/1, P0.05). The incidence rate of PEP in the asymptomatic group was higher than in the symptomatic group (20.8% vs 6.9%, P0.01). Multivariate regression analysis identified asymptomatic CBDSs (odds ratio = 0.241, 95% confidence interval: 0.092-0.628) as being independently associated with PEP occurrence.Asymptomatic CBDSs were associated with increased incidence of PEP compared with symptomatic CBDSs.

Mesenchymal stem cells (MSCs) secrete various cytokines with angiogenic and neuroprotective effects. This study aimed to assess the effects of human umbilical cord Wharton's jelly-derived MSCs (hWJ-MSCs) on diabetes-related intracavernosal pressure (ICP) impairment in rats. hWJ-MSCs were isolated from human umbilical cord Wharton's jelly and transplanted into the corpus cavernosum of streptozotocin (STZ)-induced diabetic rats by unilateral injection. The erectile function was evaluated at 4 weeks, as well as the expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endothelial nitric oxide synthase (eNOS), and insulin-like growth factor 1 (IGF1). STZ-induced diabetic rats showed impaired ICP, which was significantly improved by hWJ-MSC treatment. VEGF, eNOS, IGF1, and bFGF expression levels were higher in hWJ-MSC injection sites than those in control ones in STZ-induced diabetic rats. These results suggest that hWJ-MSC transplantation might improve diabetic erectile dysfunction through increased production of paracrine growth factors, highlighting a novel potential therapeutic option for erectile dysfunction.

The gene editing technology CRISPR/Cas9 is presently applied in several fields. Here, we routinely infected A172 and U251 cells with lentiviral vectors in which aquaporin-8 (AQP8) was knocked down using CRISPR/Cas9. Cryopreservation did not significantly alter the viral infection efficiency, but it affected the expression of AQP8 protein and its mRNA in infected cells compared with non-cryopreserved samples. The expression of AQP8 and its mRNA in cryopreserved infected cells that were recovered did not significantly differ from that in the blank and negative controls. This finding indicated that the lentiviral vector lost viability due to cryopreservation at low temperatures and failed to release the AQP8 gene-targeting guide RNA in the infected cells, or the guide RNA was released, but underwent changes that caused it to malfunction in CRISPR/Cas9-mediated AQP8 gene knockdown. This finding might provide a new direction for the prevention and treatment of viral infections.

BACKGROUND In 2020, the discoverers of CRISPR/Cas9 technology, Jennifer A. Doudna and Emmanuelle Charpentier, were awarded the Nobel Prize in Chemistry. This technology has revolutionized the field of biomedical science since its birth and contributed to the treatment of a variety of complex diseases. Scholars have carried out many studies on the development trend of CRISPR technology, bibliometrics, visualization and other aspects. However, there are few studies on the hot spot analysis and topic changes in the biomedical field, which is not conducive to scholars' thinking. OBJECTIVE This study aimed to:(1) mining and analyzing the research hotspots of CRISPR/Cas9 system in each stage; (2) sorting out and visualizing the evolution direction of the hot research topics of CRISPR/Cas9 gene editing technology in the past decade; (3) exploring the hidden research hotspots of CRISPR/Cas9 gene editing technology, so as to provide reference for further research METHODS In this study, research papers related to CRISPR/Cas9 gene editing technology in biomedical field published on the Web of Science core datasets from 2010 to 2020 were used; literature research method, analysis method and expert consultation method and other methods were comprehensively utilized; CiteSpace software and VOS viewer software were selected as visualization tools to analyze hot topics and topic evolution in research. RESULTS The generated co-occurrence map and cluster map were analyzed by keyword analysis strategy to determine the hot topics in each development stage. The topic evolution types and evolution paths are studied based on the categories and keywords of hot topics in each stage and the characteristics of their advancement along the time axis, and the topic evolution diagram and evolution path diagram were presented respectively. CONCLUSIONS Based on the above research results, firstly, in recent years, scholars have attached great importance to the research on this technology in the field of biomedical science, and the research topics have been deepened and enriched. Secondly, the development of CRISPR/Cas9 system shows different hot research directions in different periods, which is in line with the development of The Times. Finally, the theme evolution of CRISPR/Cas9 in the field of biomedicine generally shows a trend from single to multiple, and from theory to practice. Hidden research hotspots focus on the detection and treatment of infectious diseases, aging mitigation, drug resistance and other common diseases.

Software-defined networking for IoT (SDN-IoT) has become popular owing to its utility in smart applications. However, IoT devices are limited in computing resources, which makes them vulnerable to Low-rate Distributed Denial of Service (LDDoS). It is worth noting that LDDoS attacks are extremely stealthy and can evade the monitoring of traditional detection methods. Therefore, how to choose the optimal features to improve the detection performance of LDDoS attack detection methods is a key problem. In this paper, we propose DIAMOND, a structured coevolution feature optimization method for LDDoS detection in SDN-IoT. DIAMOND is consisted of a reachable count sorting clustering algorithm, a group structuring method, a comutation strategy, and a cocrossover strategy. By analysing the information of SDN-IoT network features in the solution space, the relationship between different SDN-IoT network features and the optimal solution is explored in DIAMOND. Then, the individuals with associated SDN-IoT network features are divided into different subpopulations, and a structural tree is generated. Further, multiple structural trees evolve in concert with each other. The evaluation results show that DIAMOND can effectively select optimal low-dimension feature sets and improve the performance of the LDDoS detection method, in terms of detection precision and response time.

A 47-year-old man with idiopathic mesenteric phlebosclerosis presented to our hospital because of a 2-month history of diarrhea and edema of both lower limbs. Contrastenhanced abdominal computed tomography (CT) showed a 2-cm mass of mixed density in the ascending colon. On coloscopy, a solid, ulcerated, semi-pedunculated, lobulated protruding mass of 3.5×3.5×1.5 cm was observed and removed with hot snare polypectomy. Histologic examination demonstrated a hamartomatous polyp with normal epithelium and an inflammatory infiltrate with dilated, mucus-filled cystic glands in the lamina propria, indicating a juvenile polyp.

As an emerging architecture, Software-Defined Networking (SDN) is suffering from a lot of security issues. Network anomaly detection technology plays a crucial role in addressing SDN security issues. In SDN, the network status can be denoted by the packets or flow entries. Hence, the existing network anomaly detection methods are commonly designed based on inspecting packets or flow entries. Subsequently, these anomaly detection methods have to collect packets or flow entries from the underlying switches. More seriously, some anomaly detection methods even need to add extra modules to the switches. Unlike these existing network anomaly detection methods, this work proposes a lightweight network anomaly detection method. The main design principle of the proposed method is mining the inherent OpenFlow messages in SDN to represent the network status and further detect the network anomaly. The proposed method does not need to collect any additional messages from the underlying switches or add any additional modules to the underlying switches. The evaluation results demonstrate that the proposed network anomaly detection method can afford high detection accuracy and reduce the overhead of SDN controller.

In recent years, the dominant speech separation methods model the sequence gradually to encompass global information with the time steps accumulated. However, due to the limited memory capacity of the model, the sequence information in the later position occupies a large proportion, making it impossible to form good interactions between sequences that are farther away. In this paper, we propose a modeling approach Dual-Path Recurrent Neural Network with Transformer (DPRNN-Transformer), which is based on the fusion of local and global information. Through this method, the interrelationships between sequences can be directly established. And the proposed model can effectively merge local and global information in the high-dimensional space by combining both sequence masking and non-masking, thus solving problems such as sequence information forgetting in speech separation area. In addition, in order for the model to extract as much speaker-related feature information as possible, we add the auxiliary task of speaker recognition after speech separation. By co-training with speaker recognition, the speech separation module will be constrained by the additional Triplet loss, thus incorporating speaker information to facilitate separation. Experimental results on WSJ0-2mix dataset show that our proposed method greatly improves the performance of speech separation.

Diabetes mellitus (DM) has a high prevalence in patients with pancreatic cancer (PaC), but the prognostic value of DM in PaC remains controversial. Alterations of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) contribute to multidrug resistance and intestinal metabolism in a variety of cancer types, which may be implicated in DM development. This study aimed to explore the potential prognostic value of P-gp and CYP3A4 in PaC patients in the context of DM through long-term follow-up. We retrospectively reviewed the medical records of patients with PaC admitted at The First People's Hospital of Changzhou, Jiangsu, China, from January 2011 to November 2019 and identified two cohorts of adult patients with PaC, including 24 with DM and 24 without DM (non-DM). The baseline clinical characteristics and outcomes were compared. Immunohistochemistry showed that protein expression of P-gp, but not CYP3A, in duodenum tissues was significantly upregulated in PaC patients with DM compared with those without DM. Kaplan-Meier analysis and log-rank test showed that the survival of patients with PaC and DM/high expression of P-gp was not significantly reduced compared with that of patients without DM/low expression of P-gp. These findings suggested that P-gp expression levels were different in the DM and non-DM groups of patients with PaC, but DM and duodenal P-gp levels were not associated with the long-term survival of patients with PaC. It appears that the presence of DM or P-gp expression levels may not serve as effective prognostic markers for PaC.

Background With the increasing incidences and mortality of digestive system tumor diseases in China, ways to use clinical experience data in Chinese electronic medical records (CEMRs) to determine potentially effective relationships between diagnosis and treatment have become a priority. As an important part of artificial intelligence, a knowledge graph is a powerful tool for information processing and knowledge organization that provides an ideal means to solve this problem. Objective This study aimed to construct a semantic-driven digestive system tumor knowledge graph (DSTKG) to represent the knowledge in CEMRs with fine granularity and semantics. Methods This paper focuses on the knowledge graph schema and semantic relationships that were the main challenges for constructing a Chinese tumor knowledge graph. The DSTKG was developed through a multistep procedure. As an initial step, a complete DSTKG construction framework based on CEMRs was proposed. Then, this research built a knowledge graph schema containing 7 classes and 16 kinds of semantic relationships and accomplished the DSTKG by knowledge extraction, named entity linking, and drawing the knowledge graph. Finally, the quality of the DSTKG was evaluated from 3 aspects: data layer, schema layer, and application layer. Results Experts agreed that the DSTKG was good overall (mean score 4.20). Especially for the aspects of “rationality of schema structure,” “scalability,” and “readability of results,” the DSTKG performed well, with scores of 4.72, 4.67, and 4.69, respectively, which were much higher than the average. However, the small amount of data in the DSTKG negatively affected its “practicability” score. Compared with other Chinese tumor knowledge graphs, the DSTKG can represent more granular entities, properties, and semantic relationships. In addition, the DSTKG was flexible, allowing personalized customization to meet the designer's focus on specific interests in the digestive system tumor. Conclusions We constructed a granular semantic DSTKG. It could provide guidance for the construction of a tumor knowledge graph and provide a preliminary step for the intelligent application of knowledge graphs based on CEMRs. Additional data sources and stronger research on assertion classification are needed to gain insight into the DSTKG’s potential.

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and chronic airway inflammation, caused by a combination of environmental and genetic factors. It is the third leading cause of death worldwide. In recent years, researchers have applied the genome-wide association study (GWAS) and identified a large number of genetic variants associated with lung functions and potential drug targets for treating COPD. In this review, we summarize the results of GWAS studies and perform a review of the literature since 2007 to highlight the progress of GWAS on COPD. We discuss the challenges, the underlying mechanisms, and the possible drug targets, thereby providing insights on the pathogenesis and potential treatment strategies for COPD.慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)是一种以不完全可逆的气流受限为主要特征的慢性气道炎症,是一种由遗传因素和环境因素共同作用的复杂疾病,也是世界主要致死疾病之一。近年来,随着全基因组关联研究(genome-wide association study, GWAS)的不断深入,研究者们发现了大量与肺功能或COPD相关的遗传变异或基因位点、药物靶点等。本文综述了2007年以来世界范围内针对肺功能或COPD的GWAS方面的研究工作及其进展综述,分析了可能存在的药物靶点,并探讨了COPD在全基因组关联研究中面临的挑战和困难,为深入研究COPD发病机制提供新思路。.

BACKGROUND The rapid spread of the COVID-19 pandemic in the United States has made people uncertain about their perceptions of the threat of COVID-19 and COVID-19 response measures. To mount an effective response to this epidemic, it is necessary to understand the public's perceptions, behaviors, and attitudes. OBJECTIVE We aimed to test the hypothesis that people’s perceptions of the threat of COVID-19 influence their attitudes and behaviors. METHODS This study used an open dataset of web-based questionnaires about COVID-19. The questionnaires were provided by Nexoid United Kingdom. We selected the results of a questionnaire on COVID-19–related behaviors, attitudes, and perceptions among the US public. The questionnaire was conducted from March 29 to April 20, 2020. A total of 24,547 people who lived in the United States took part in the survey. RESULTS In this study, the average self-assessed probability of contracting COVID-19 was 33.2%, and 49.9% (12,244/24,547) of the respondents thought that their chances of contracting COVID-19 were less than 30%. The self-assessed probability of contracting COVID-19 among women was 1.35 times that of males. A 5% increase in perceived infection risk was significantly associated with being 1.02 times (OR 1.02, 95% CI 1.02-1.02; P10 people, and being 1.01 times (OR 1.01, 95% CI 1.01-1.01; PP=.85). Generally, participants who lived in states with 1001-10,000 COVID-19 cases, were aged 20-40 years, were obese, smoked, drank alcohol, never used drugs, and had no underlying medical conditions were more likely to be in close contact with >10 people. Most participants (21,017/24,547, 85.6%) agreed with washing their hands and maintaining social distancing, but only 20.2% (4958/24,547) of participants often wore masks. Additionally, male participants and participants aged CONCLUSIONS This survey is the first attempt to describe the determinants of the US public’s perception of the threat of COVID-19 on a large scale. The self-assessed probability of contracting COVID-19 differed significantly based on the respondents’ genders, states of residence, ages, body mass indices, smoking habits, alcohol consumption habits, drug use habits, underlying medical conditions, environments, and behaviors. These findings can be used as references by public health policy makers and health care workers who want to identify populations that need to be educated on COVID-19 prevention and health.

Background The rapid spread of the COVID-19 pandemic in the United States has made people uncertain about their perceptions of the threat of COVID-19 and COVID-19 response measures. To mount an effective response to this epidemic, it is necessary to understand the public's perceptions, behaviors, and attitudes. Objective We aimed to test the hypothesis that people’s perceptions of the threat of COVID-19 influence their attitudes and behaviors. Methods This study used an open dataset of web-based questionnaires about COVID-19. The questionnaires were provided by Nexoid United Kingdom. We selected the results of a questionnaire on COVID-19–related behaviors, attitudes, and perceptions among the US public. The questionnaire was conducted from March 29 to April 20, 2020. A total of 24,547 people who lived in the United States took part in the survey. Results In this study, the average self-assessed probability of contracting COVID-19 was 33.2%, and 49.9% (12,244/24,547) of the respondents thought that their chances of contracting COVID-19 were less than 30%. The self-assessed probability of contracting COVID-19 among women was 1.35 times that of males. A 5% increase in perceived infection risk was significantly associated with being 1.02 times (OR 1.02, 95% CI 1.02-1.02; P10 people, and being 1.01 times (OR 1.01, 95% CI 1.01-1.01; P10 people. Most participants (21,017/24,547, 85.6%) agreed with washing their hands and maintaining social distancing, but only 20.2% (4958/24,547) of participants often wore masks. Additionally, male participants and participants aged Conclusions This survey is the first attempt to describe the determinants of the US public’s perception of the threat of COVID-19 on a large scale. The self-assessed probability of contracting COVID-19 differed significantly based on the respondents’ genders, states of residence, ages, body mass indices, smoking habits, alcohol consumption habits, drug use habits, underlying medical conditions, environments, and behaviors. These findings can be used as references by public health policy makers and health care workers who want to identify populations that need to be educated on COVID-19 prevention and health.

TcpC is a multifunctional virulence factor of uropathogenic E. coli (UPEC). Neutrophil extracellular trap formation (NETosis) is a crucial anti-infection mechanism of neutrophils. Here we show the influence of TcpC on NETosis and related mechanisms. We show NETosis in the context of a pyelonephritis mouse model induced by TcpC-secreting wild-type E. coli CFT073 (CFT073wt) and LPS-induced in vitro NETosis with CFT073wt or recombinant TcpC (rTcpC)-treated neutrophils are inhibited. rTcpC enters neutrophils through caveolin-mediated endocytosis and inhibits LPS-induced production of ROS, proinflammatory cytokines and protein but not mRNA levels of peptidylarginine deiminase 4 (PAD4). rTcpC treatment enhances PAD4 ubiquitination and accumulation in proteasomes. Moreover, in vitro ubiquitination kit analyses show that TcpC is a PAD4-targetd E3 ubiquitin-ligase. These data suggest that TcpC inhibits NETosis primarily by serving as an E3 ligase that promotes degradation of PAD4. Our findings provide a novel mechanism underlying TcpC-mediated innate immune evasion., TcpC is a well characterised multifunctional virulence factor expressed by uropathogenic Eschericia coli. Here the authors show that TcpC also targets neutrophil NETosis via its E3 ligase functionality promoting the degradation of PAD4, and represents an additional immune evasion function of this bacterially derived virulence factor.

As a repository that holds computing facilities, storage facilities, network facilities and other facilities, the Software Defined Data Center (SDDC) can provide computing and storage resources for users. For a SDDC, it is important to provide continuous services for users. Hence, in order to achieve high reliability in Software Defined Data Center Networks (SDDCNs), a network failure recovery method for software defined data center networks (REVERT) is proposed to recover failures in SDDCNs. In REVERT, the network failures that occurred in SDDCNs are classified into three types, which are switch failure, failure of links among switches and failure of links between switches and servers. Specially, except recovering the switch failure and failure of links between switches, REVERT can also recover the failures of links between the switches and servers. To achieve that, a failure preprocessing method used to classify the network failures, a data structure for storing and finding the affected flows, a server cluster agent for communicating with the server clustering algorithm and a routing path calculation method are designed in REVERT. Meanwhile, REVERT has been implemented and evaluated on RYU controller and Mininet using three routing algorithms. Compared with the link usage before recovering the network failures, when there are more than 200 flows in the network, the mean link usages only slightly increase at about 1.83 percent. More importantly, the evaluation results also demonstrate that except recovering switch failures, intra-topo link failures, REVERT has the ability of recovering failures of links between servers and edge switches successfully.

BACKGROUND Ethnic background may affect the prevalence of nasal bone absence and the length of the nasal bone. This study aimed to elucidate the significance of absent or hypoplastic fetal nasal bone in the Chinese Han population and to formulate an optimal management plan for patients age 35 or older in cases of isolated abnormal fetal nasal bone. MATERIAL AND METHODS We prospectively assigned pregnant women whose fetuses had nasal bone absence or hypoplasia to separate groups according to their choice for noninvasive prenatal screening (NIPS) between January 1, 2013, and December 31, 2018. Demographic data, ultrasound findings, results of conventional maternal serum screening and NIPS, fetal karyotype, pregnancy outcomes, and expenses associated with prenatal testing were recorded. The incidence and odds ratio of nasal bone abnormality and the sensitivity and specificity of different prenatal genetic screening tests were calculated. RESULTS A total of 1946 cases with fetal nasal bone absence or hypoplasia were included. Cases of isolated nasal bone abnormality (1736 cases) were divided into the NIPS group (Gr 1, n=429) and the non-NIPS group (Gr 2, n=1307). Sixty-four cases involved chromosomal abnormality. The sensitivity, specificity, and positive and negative predictive values of NIPS in Gr 1 were 100%, 100%, 100%, and 100%, respectively. The odds ratio of fetal chromosomal abnormalities for isolated fetal nasal bone abnormalities when maternal age was ≥35 was 4.615 (95% CI: 1.592-13.381). The cost-effectiveness ratio of contingent screening (NIPS first) was significantly lower than amniocentesis directly. CONCLUSIONS The nasal bone provides an important marker for chromosome abnormalities in some populations, but to a lesser extent in the Chinese Han population. NIPS is an excellent first option for follow-up among pregnant women age ≥35 in cases of absent or hypoplastic fetal nasal bone in the first trimester ultrasound scan.

Background The coronavirus disease (COVID-19), a pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown its destructiveness with more than one million confirmed cases and dozens of thousands of death, which is highly contagious and still spreading globally. World-wide studies have been conducted aiming to understand the COVID-19 mechanism, transmission, clinical features, etc. A cross-language terminology of COVID-19 is essential for improving knowledge sharing and scientific discovery dissemination. Methods We developed a bilingual terminology of COVID-19 named COVID Term with mapping Chinese and English terms. The terminology was constructed as follows: (1) Classification schema design; (2) Concept representation model building; (3) Term source selection and term extraction; (4) Hierarchical structure construction; (5) Quality control (6) Web service. We built open access for the terminology, providing search, browse, and download services. Results The proposed COVID Term include 10 categories: disease, anatomic site, clinical manifestation, demographic and socioeconomic characteristics, living organism, qualifiers, psychological assistance, medical equipment, instruments and materials, epidemic prevention and control, diagnosis and treatment technique respectively. In total, COVID Terms covered 464 concepts with 724 Chinese terms and 887 English terms. All terms are openly available online (COVID Term URL: http://covidterm.imicams.ac.cn). Conclusions COVID Term is a bilingual terminology focused on COVID-19, the epidemic pneumonia with a high risk of infection around the world. It will provide updated bilingual terms of the disease to help health providers and medical professionals retrieve and exchange information and knowledge in multiple languages. COVID Term was released in machine-readable formats (e.g., XML and JSON), which would contribute to the information retrieval, machine translation and advanced intelligent techniques application.

To observe the effect of electroacupuncture (EA) on the expression of insulin phosphatidylinositol-3 kinase/glycogen synthetase kinase-3α (PI3K/GSK3α) signal pathway related proteins in the hippocampus in mice with Alzheimer's disease (AD), and to explore the regulatory mechanism of EA on improving the pathological characteristics of AD.Twelve male APP/PS1 double transgenic mice were randomly divided a model group and a treatment group, 6 mice in each group; another 6 wild-type male mice were taken as the control group. The mice in the treatment group were treated with EA (continuous wave, 2 Hz of frequency) at "Baihui" (GV 20) and bilateral "Shenshu" (BL 23), once a day; 7-day treatment was taken as a course of treatment, and 2 courses of treatment were given. The immunohistochemistry method and Western blot method were used to detect the distribution and expression level of hippocampal PI3K/GSK3α signal pathway related proteins P85α, P110α, GSK3α and pSThe proteins of P85α, P110α, GSK3α and pSEA could effectively regulate the expression of PI3K/GSK3α signal pathway related proteins in the hippocampus in mice with AD, so as to reduce the formation and deposition of SP.

Distributed Denial of Service (DDoS) is quite a serious security issue existing in Software-Defined Networking (SDN). In order to mitigate DDoS attack, we present MIND, a message classification based controller scheduling method, where how to store and process messages is designed based on analyzing and classifying the OpenFlow messages received by SDN controller. The experiment results validate that the proposed controller scheduling method can significantly improve the availability of SDN controller under DDoS attack.

This study proposes an image segmentation method based on bottleneck detection and watershed algorithm to solve the problem of overlapping cervical cell image. First, we use polygon approximation to get all feature points on the cell contour and then use bottleneck detection and ellipse fitting to obtain the correct split point pairs. Therefore, the approximate range of the overlapping region was determined. The watershed algorithm was used to obtain the internal boundary information for the gradient image of the region. Finally, the segmentation results of the overlapped cells were obtained by superimposing with the outer contour. The experimental results show that this algorithm can segment the contour of a single cell from the overlapping cervical cell images with good accuracy and integrity. The segmentation result is close to that of doctors' manual marking, and the segmentation result is better than other existing algorithms.

Background Magnetoencephalography (MEG) has high temporal and spatial resolution and good spatial accuracy in determining the locations of source activity among most non-invasive imaging. The recently developed technology of optically-pumped magnetometer (OPM) has sensitivity comparable to that of the superconducting quantum interference device (SQUID) used in commercial MEG system. New method Double-channel OPM-MEG system detects human photic blocking of alpha rhythm at the occipital region of skull in the magnetically shielded environment via a wearable whole-cortex 3D-printed helmet. Results The alpha rhythm can be detected by the OPM-MEG system, the MEG signals are undoubtedly caused by photic blocking and similar with the results measured by SQUID magnetometer. Comparison with existing methods Due to the dependency of current commercial whole-cortex SQUID-MEG system on the liquid helium, the separation from the liquid helium space to the human head is usually at least a few centimeters. The wearable OPM-MEG system, however, can significantly improve the detection efficiency since its sensors can be mounted close to scalp, normally less than 1 cm. Conclusions OPM-MEG system successfully detects alpha rhythm blocked by light stimulation and works well in the home-made magnetically shielded environment. OPM-MEG system shows a substitute for the traditional MEG system.

In order to expand the application in the medical field and enhance pharmacological effects, casein-myricetin nanomicelles were prepared by the self-assembly method and characterised by ultraviolet-visible spectroscopy and Fourier transform infrared spectroscopy. The parameters in self-assembly were optimised according to the factors of particle size, encapsulation yield, and drug loading. The result showed a pH of 5.5, a casein concentration of 2 mg/ml, a mass ratio of casein to myricetin of 8:1, ultrasonic power of 300 W, ultrasonic time of 5 min and ethanol volume of 7 ml were the optimal conditions. The situ cycle intestinal perfusion methods indicated that casein-myricetin nanomicelles can be more easily absorbed by small intestine than myricetin standard sample. Therefore, casein micelles are effective for improving the water solubility of myricetin.

As the development of information and communication technology (ICT) and the affirmation of the importance of healthcare, using wireless sensor networks (WSNs) is a promising approach to assist modern medical practices. The transmission optimization of HWSNs is an issue worth studying deeply, which is facing challenges such as data diversity, real-time requirement, reliable transmission, dynamic environment and so on. This paper considers four kinds of transmission cost comprehensively, and adopts the stochastic differential game theory to discuss this issue. With the objective of minimizing the transmission cost, three kinds of game models are constructed, i.e., cooperative model, partial cooperative model and non-cooperative model. The optimal transmission strategies under different game modes are obtained for HWSNs. The numerical simulation compares three strategies and verifies the validity of the method present in this paper.

BACKGROUND With the increasing incidences and mortality of digestive system tumor diseases in China, ways to use clinical experience data in Chinese electronic medical records (CEMRs) to determine potentially effective relationships between diagnosis and treatment have become a priority. As an important part of artificial intelligence, a knowledge graph is a powerful tool for information processing and knowledge organization that provides an ideal means to solve this problem. OBJECTIVE This study aimed to construct a semantic-driven digestive system tumor knowledge graph (DSTKG) to represent the knowledge in CEMRs with fine granularity and semantics. METHODS This paper focuses on the knowledge graph schema and semantic relationships that were the main challenges for constructing a Chinese tumor knowledge graph. The DSTKG was developed through a multistep procedure. As an initial step, a complete DSTKG construction framework based on CEMRs was proposed. Then, this research built a knowledge graph schema containing 7 classes and 16 kinds of semantic relationships and accomplished the DSTKG by knowledge extraction, named entity linking, and drawing the knowledge graph. Finally, the quality of the DSTKG was evaluated from 3 aspects: data layer, schema layer, and application layer. RESULTS Experts agreed that the DSTKG was good overall (mean score 4.20). Especially for the aspects of “rationality of schema structure,” “scalability,” and “readability of results,” the DSTKG performed well, with scores of 4.72, 4.67, and 4.69, respectively, which were much higher than the average. However, the small amount of data in the DSTKG negatively affected its “practicability” score. Compared with other Chinese tumor knowledge graphs, the DSTKG can represent more granular entities, properties, and semantic relationships. In addition, the DSTKG was flexible, allowing personalized customization to meet the designer's focus on specific interests in the digestive system tumor. CONCLUSIONS We constructed a granular semantic DSTKG. It could provide guidance for the construction of a tumor knowledge graph and provide a preliminary step for the intelligent application of knowledge graphs based on CEMRs. Additional data sources and stronger research on assertion classification are needed to gain insight into the DSTKG’s potential.