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Tracing the sources of cyber-attacks in Power Industrial Control Systems (PICS) can help the defense systems to block the attacks, and support the decision of the grid control policies. However, there has been no work on the cyber-attack source traceback for PICS, and the methods for the Internet are not suitable for PICS in terms of fineness, real-time performance, and supporting communication protocols. Therefore, a method for tracing cyber-attacks in PICS is proposed. First, the communication network architecture of PICS and the cyber security threats to PICS are analyzed. Then, an extended hybrid tracing method (ExtHT) based on packet marking and packet logging is proposed. This method involves all the devices working at the data link layer and upper layers to achieve more fine-grained attack tracing. At the same time, taking the costs of attack tracing into consideration, a coarse-grained tracing mode is presented to improve the tracing speed. In addition, a log database optimization scheme is provided to reduce storage costs. To facilitate the application of this method in practice, a cyber-attack source tracing system and its deployment architecture are designed for PICS. Further, the applicability and limitations of ExtHT are analyzed, theory ratiocinations are given to justify our ExtHT, and the performance of our ExtHT is compared with that of existing mainstream methods. Finally, two cyber-attack scenarios against PICS are constructed and the feasibility of ExtHT is verified on them.

To translate the English version Child Food Neophobia Scale (CFNS) into the Chinese version and test its reliability and validity in preschool children.To create the Chinese version of the CFNS, it was translated, back-translated, and cross-culturally adapted. The use of the Chinese version of CFNS by 575 parents of preschool children in two kindergartens in Yangzhou City was investigated using cluster sampling to assess the reliability and validity of the scale.The Chinese version of CFNS has nine items in total. The scale-level average content validity index (S-CVI/Ave) is 0.983. Exploratory factor analysis (EFA) extracted 2 common factors, and the cumulative variance contribution rate was 49.437%. Confirmatory factor analysis (CFA) showed that the 2-factor model was well fitted. The Cronbach'α coefficient of the scale was 0.759, the Cronbach'α coefficients of the two factors were 0.735 and 0.713, the split-half reliability was 0.788, and the test-retest reliability was 0.756.The Chinese version of the Child Food Neophobia Scale has good reliability and validity in preschool children and can be used as an assessment tool for food neophobia in preschool children in China.This study has gone through a rigorous translation process, and the CFNS may support future exploration of food neophobia in preschool children. Food allergy factors in the results may be the next step in the research, and several studies are still needed to understand the relationship between food allergy and food neophobia.

Osteochondral injury is a common and frequent orthopedic disease that can lead to more serious degenerative joint disease. Tissue engineering is a promising modality for osteochondral repair, but the implanted scaffolds are often immunogenic and can induce unwanted foreign body reaction (FBR). Here, we prepare a polypept(o)ide-based PAA-RGD hydrogel using a novel thiol/thioester dual-functionalized hyperbranched polypeptide P(EG

Chronic inflammation of adipose tissue may be one of the key factors contributing to the development of insulin resistance in T2DM adipose tissue. Transient receptor potential vanilloid type 4 (TRPV4) can be involved in a variety of cellular inflammatory responses. In this study, we evaluated the role of TRPV4 channelin in the T2DM adipose tissue inflammatory pathway.Based on the gene expression profiling data of the public database, bioinformatics methods were used to screen the target gene population of the TRPV4 channel protein involved in the regulation of T2DM fat cells. A mature adipocyte model was constructed to verify the expression level of target genes and to evaluate the regulatory effect of TRPV4 channel inhibition on target genes of inflammation-related pathways.In shTRPV4 adipocytes, 144 genes with downregulation expression were screened, a PPI network was constructed and a core module containing 15 genes was screened out, and the core genes were mainly enriched in the Toll-like receptor signaling pathway through enrichment analysis. Constructing a mature adipocyte model found that the TRPV4 inhibitor HC067047 inhibited the effect of upregulation of the expression level of the relevant gene in the signaling pathway.Our findings suggest that the expression of highly expressed pro-inflammatory cytokines and chemokines in T2DM adipose tissue decreases after inhibiting the expression of TRPV4 in adipocytes, suggesting that TRPV4 may become a potential drug target for the treatment of T2DM.

Amyloid-β oligomers (AβOs) was the core-biomarker of Alzheimer's disease (AD), and the detection of AβOs is very important for the early diagnosis of AD. However, existing tests for AβOs are majorly suffering from complex process and poor sensitivity. Thus, an adjustable AβOs electrochemiluminescence (ECL) aptasensor based on the synergistic effect of self-enhanced metal-organic gel (AgCNS) and triple-helix DNA system (THS) was successfully constructed. AgCNS was prepared by an extremely simple one-pot method and was an innovative luminophore with excellent ECL performance. The AgCNS-labeled complementary sequence (AgCNS@CP) was interlaced with the unlabeled aptamer (Apt) carrying two short-arms fixed on the gold electrode (GE) to form the THS. Along with the specific-binding of AβOs and Apt, the THS was disrupted and adjusted flexibly between "on" and "off", resulting in significant changes in the ECL signals. Thus, ECL detection of AβOs was sensitively achieved with a detection limit as low as 0.23 fM and the different forms of Aβ can be specifically distinguished. The aptasensor also exhibited satisfactory selectivity, stability and reproducibility. Moreover, when proposed method and ELISA-kit were simultaneously applied to artificial cerebrospinal fluid (A-CSF) samples, the obtained results were completely consistent, reflecting the potential clinical application value of this work.

Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused an extensive burden to the world. Consequently, a large number of clinical trials have examined the efficacy of traditional Chinese medicine (TCM) for treating and preventing COVID-19, with coinciding proliferation of reviews summarizing these studies.This study aimed to evaluate the methodological quality and evidence quality of systematic reviews and meta-analyses on the efficacy of TCM.Seven electronic databases, including PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chongqing VIP, Wanfang Data and SinoMed, were searched for systematic reviews and meta-analyses in October 2021. Search terms such as "Chinese medicine," "Lianhua Qingwen" and "COVID-19" were used.Systematic reviews and meta-analyses of randomized controlled trials that evaluated the efficacy of TCM treatment of COVID-19 were included.A Measurement Tool to Assess Systematic Reviews Version 2.0 (AMSTAR 2) was used to evaluate the methodological quality. The quality of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Data extraction and analysis were performed by two reviewers independently.There were 17 meta-analyses included in our overview. The intervention group was defined as TCM combined with Western medicine, while the control group was Western medicine alone. The methodological quality of all the included studies was moderate to poor. A total of 89 outcome indicators were evaluated, of which, 8 were rated as moderate quality, 39 as low quality, and 41 as very low quality. Only one outcome measure was graded as being of high quality. The moderate quality of evidence indicated that, for the treatment of COVID-19, the clinical efficacy of TCM in combination with Western medicine was better, in terms of lung recovery, rate of conversion to severe/critical cases, symptom scores, duration of symptoms, mortality, and length of hospital stay.Evidence from the included studies shows that, compared with conventional Western medical therapy alone, the addition of TCM to COVID-19 treatment may improve clinical outcomes. Overall, the quality of evidence of TCM for COVID-19 was moderate to poor. Meta-analyses of the use of TCM in the treatment of COVID-19 can be used for clinical decision making by accounting for the experiences of clinical experts, medical policies, and other factors.

Klebsiella pneumoniae is one of the major pathogens causing global multidrug-resistant infections. Therefore, strategies for preventing and controlling the infections are urgently needed. Phage depolymerase, often found in the tail fiber protein or the tail spike protein, is reported to have antibiofilm activity. In this study, phage P560 isolated from sewage showed specific for capsule locus type KL47 K. pneumoniae, and the enlarged haloes around plaques indicated that P560 encoded a depolymerase. The capsule depolymerase, ORF43, named P560dep, derived from phage P560 was expressed, purified, characterized and evaluated for enzymatic activity as well as specificity. We reported that the capsule depolymerase P560dep, can digest the capsule polysaccharides on the surface of KL47 type K. pneumoniae, and the depolymerization spectrum of P560dep matched to the host range of phage P560, KL47 K. pneumoniae. Crystal violet staining assay showed that P560dep was able to significantly inhibit biofilm formation. Further, a single dose (50 μg/mouse) of depolymerase intraperitoneal injection protected 90%-100% of mice from lethal challenge before or after infection by KL47 carbapenem-resistant K. pneumoniae. And pathological changes were alleviated in lung and liver of mice infected by KL47 type K. pneumoniae. It is demonstrated that depolymerase P560dep as an attractive antivirulence agent represents a promising tool for antimicrobial therapy.

The aim of the study was to comprehensively understand the combined hepatocellular and cholangiocarcinoma (CHC) and develop a nomogram for prognostic prediction of CHC.Data were collected from the Surveillance, Epidemiology and End Results (SEER) database (year 2004-2014). Propensity-score matching (PSM) was used to match the demographic characteristic of the CHC versus hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). A nomogram model was established to predict the prognosis in terms of cancer specific survival (CSS). The established nomogram was externally validated by a multicenter cohort.A total of 71,756 patients enrolled in our study including 62,877 HCC patients, 566 CHC patients, and 8303 ICC patients. The CHC, HCC, and ICC are not exactly similar in clinical characteristic. After PSM, the CSS of CHC was better than HCC but comparable to ICC. Tumor size, M stage, surgery, chemotherapy, and surgery were independently prognostic factors of CHC and were included in the establishment of novel nomogram. The c-index of the novel nomogram in SEER training set and multicenter validation was 0.779 and 0.780, respectively, which indicated that the model was with better discrimination power. In addition, decision curve analyses proved the favorable potential clinical effect of the predictive model. Lastly, a risk classification based on nomogram also verified the reliability of the model.CHC had better survival than HCC but was comparable to ICC. The nomogram was established based on tumor size, M stage, chemotherapy, surgery, and radiotherapy and well validated by external multicenter cohort.

Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

To facilitate the identification of related genes and candidate biomarkers for disorders of sex development (DSD), we present disorders of sex development atlas (http://dsd.geneworks.cn). Disorders of sex development are a spectrum of endocrine diseases with distinct mutations of genes or chromosomes, but several issues regarding their pathogenesis remain elusive. High-throughput methods have allowed genomic and transcriptomic analyses of DSD; however, these data are deposited in various repositories owing to a lack of integrated online resources.A descriptive study of a specialized gene discovery platform designed for DSD.Publicly available DSD omics datasets and self-produced datasets.None.None.The gene ranking result, with detailed information based on DSD terms in a gene-disease association knowledge base, and results of differential gene expression and mutation analyses from omics datasets.The disorders of sex development atlas maintains both a knowledgebase for ranking DSD candidate genes and a database for DSD-related omics data analysis and visualization. We included 4 dominant classes of DSD in the knowledgebase: 15 subclasses and 44 specific disease names. Construction of the knowledgebase was centered upon Phenolyzer, with add-on seed gene databases customized by DSD-related genes collected from MalaCards, GeneCards, and DisGeNET. For the database, 25 experimental datasets related to DSD were integrated, including 24 public datasets from Gene Expression Omnibus and Sequence Read Archive and 1 self-generated dataset. A total of 474 samples from 240 DSD samples were collected for the database.This platform provides a friendly interface that integrates flexible and comprehensive analysis tools for differential expression and gene mutations between the DSD groups and controls.

This paper addresses an uncertain nonlinear control system problem with complex state constraints and mismatched uncertainties. A novel Gaussian Mixture Model (GMM) based adaptive PID-Nonsingular Terminal Sliding Mode Control (NTSMC) (GMM-adaptive-PID-NTSMC) method is proposed. It is achieved by combining a GMM based adaptive potential function with a novel switching surface of PID-NTSMC. Next, the stability of the closed-loop system is proved. The main contribution of this paper is that the GMM method is applied to obtain the analytic description of the complex bounded state constraints, ensuring that the states’ constraints are not violated with GMM-based adaptive potential function. The developed potential function can consider the influence of uncertainties. More importantly, the GMM-adaptive-PID-NTSMC can be generalized to control a more representative class of uncertain nonlinear systems with constrained states and mismatched uncertainties. In addition, the proposed controller enhances the robustness, and requires less control cost and reduces the steady state error with respect to the Artificial Potential Function based Nonsingular Terminal Sliding Mode Control (APF-NTSMC), GMM-NTSMC and GMM-adaptive-NTSMC. At last, numerical simulation is performed to validate the superior performance of the proposed controller.

Parkinson's disease (PD) is a threatening neurodegenerative disorder that seriously affects patients' life quality. Substantial evidence links the overexpression and abnormal aggregation of alpha-synuclein (α-Syn) to PD. α-Syn has been identified as a characteristic biomarker of PD, which indicates its great value of diagnosis and designing effective therapeutic strategy. This article systematically summarizes the pathogenic process of α-Syn based on recent researches, outlines and compares commonly used analysis and detection technologies of α-Syn. Specifically, the detection of α-Syn by new electrochemical, photochemical, and crystal biosensors is mainly examined. Furthermore, the speculation of future study orientation is discussed, which provides reference for the further research and application of α-Syn as biomarker.

Obstructive sleep apnea syndrome (OSAS) has mostly been examined using in-laboratory polysomnography (Lab-PSG), which may overestimate severity. This study compared sleep parameters in different environments and investigated the association between the plasma levels of neurochemical biomarkers and sleep parameters.Thirty Taiwanese participants underwent Lab-PSG while wearing a single-lead electrocardiogram patch. Participants' blood samples were obtained in the morning immediately after the recording. Participants wore the patch for the subsequent three nights at home. Sleep disorder indices were calculated, including the apnea-hypopnea index (AHI), chest effort index, and cyclic variation of heart rate index (CVHRI). The 23 eligible participants' derived data were divided into the normal-to-moderate (N-M) group and the severe group according to American Association of Sleep Medicine (AASM) guidelines (Lab-PSG) and the recommendations of a previous study (Rooti Rx). Spearman's correlation was used to examine the correlations between sleep parameters and neurochemical biomarker levels.The mean T-Tau protein level was positively correlated with the home-based CVHRI (r = 0.53, p 0.05), whereas no significant correlation was noted between hospital-based CVHRI and the mean T-tau protein level (r = 0.25, p = 0.25). The home-based data revealed that the mean T-Tau protein level in the severe group was significantly higher than that in the N-M group (severe group: 24.75 ± 6.16 pg/mL, N-M group: 19.65 ± 3.90 pg/mL; p 0.05). Furthermore, the mean in-hospital CVHRI was higher than the mean at-home values (12.16 ± 13.66 events/h).Severe OSAS patients classified by home-based CVHRI demonstrated the higher T-Tau protein level, and CVHRI varied in different sleep environments.