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Abstract The increasing incidence of hepatocellular carcinoma (HCC) is of great concern globally, but the molecular pathogenesis of these tumors remains unclear. Sorafenib is a first-line drug for the treatment of advanced HCC. However, the efficacy of sorafenib in improving patient survival is limited, and most patients inevitably develop resistance to this drug. Recent studies have demonstrated that the activation of the IRE1α–XBP1s pathway might play a protective role in the response to sorafenib and contribute to malignancy in HCC. Here, we found that RCN1, an endoplasmic reticulum resident protein, is significantly upregulated in sorafenib-resistant HCC cells and promotes tumor progression. Our analysis showed that RCN1 may be an independent predictor of tumor recurrence and overall survival. Mechanistically, RCN1 promotes the dissociation of GRP78 from IRE1α in sorafenib-resistant cells by interacting with GRP78 through its EFh1/2 domain. Subsequently, the IRE1α–XBP1s pathway, a branch of the unfolded protein response, is sustainably activated. Interestingly, IRE1α–XBP1s pathway activity is required for c-MYC signaling, one of the most highly activated oncogenic pathways in HCC. These results suggest that RCN1-targeted therapy might be a feasible strategy for the treatment of HCC.

Time synchronization is the basis and prerequisite for precise information perception in intelligent mines. Many characteristics of underground space in coal mines, such as narrow and long terrain and uneven surface of the roadway, can cause large cumulative effect of synchronization error and poor reliability of signal transmission, which brings great challenges to the research of time synchronization technology among wireless nodes. Two basic time synchronization methods, hierarchical time synchronization and distributed time synchronization method, are introduced in this paper. The special requirements of time synchronization methods for underground coal mine IoTs are analyzed. In addition to the convergence and synchronization precision, the energy efficiency, the topology robustness and the scalability of the synchronization algorithm need to be considered as well. The method should have less communication volume, longer synchronization period and certain topology robustness. Moreover, the method should be able to reduce the cumulative effect of synchronization error caused by large network diameter, and adapt to impact of network scale changes. The current research status of time synchronization of underground coal mine IoTs perception layer is analyzed, and it is concluded that the current research results mainly focus on network structure, synchronization precision and synchronization energy consumption. The research direction of time synchronization technology for underground coal mine IOTs perception layer is prospected, and it is pointed out that the focuses of future research is to design a time synchronization method with certain robustness to topology and time delay in the context of the particularity of underground communication environment and space environment in coal mine: ① It is suggested to improve the robustness of time synchronization method to topology from the perspective of topology dynamic maintenance. ② It is advised to improve the convergence speed of consistent time synchronization method from the perspective of communication topology virtual construction. ③ It is proposed to improve the robustness of time synchronization method to transmission delay from the perspective of timestamp processing and matrix completion.

Abstract This study investigates the protective effect of Erigeron breviscapus injection, a classic traditional Chinese medicine most typically used by Chinese minority to treat stroke, on cerebral ischemia–reperfusion injury and the related signaling pathways. Use network pharmacology methods to study the relationship between E. breviscapus (Vant.) Hand-Mazz. and ischemic stroke, predict the mechanism and active ingredients of E. breviscapus (Vant.) Hand-Mazz. in improving ischemic stroke disease. We study the protective effect of E. breviscapus injection on blood–brain barrier (BBB) injuries induced by cerebral ischemia in rats by regulating the ROS/RNS-MMPs-TJs signaling pathway. The rat model of focal cerebral ischemia–reperfusion injury has been prepared using the wire-suppository method. Firstly, the efficacy of E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid in protecting BBB injury caused by cerebral ischemia has been evaluated. Secondly, the following two methods have been used to study the mechanism of E. breviscapus injection in regulating the ROS/RNS-MMPS-TJS signaling pathway: real-time PCR and western blot for the determination of iNOS, MMP-9, claudin-5, occludin, ZO-1 mRNA and protein expression in brain tissue. We find that PI3K-Akt signaling pathway predicted by network pharmaology affects the blood–brain barrier function, so we chose the blood–brain barrier-related MMP-9, claudin-5, iNOS, occludin and ZO-1 proteins are used for research. The results of our research show that 3 drugs can reduce the rate of cerebral infarction in rats, relieve the abnormal neuroethology of rats, reduce the degree of brain tissue lesion, increase the number of the Nissl corpuscle cells and repair the neuron ultrastructure in injured rats. At the same time, it can obviously reduce the ultrastructure damage of the BBB in rats. All three drugs significantly reduced the content of Evans blue in the ischemic brain tissue caused by cerebral ischemia in rats with BBB injury. In addition, E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid can decrease the protein expression of iNOS and MMP-9 in rat ischemic brain tissue. In addition, 3,5-dicaffeoylquinic acid can increase the protein expression of claudin-5. We conclude that E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid have obvious therapeutic effects on BBB and neuron injury induced by cerebral ischemia in rats. Our results from studying the mechanism of action show that E. breviscapus injection and Scutellarin inhibited the activation of MMP-9 by inhibiting the synthesis of iNOS, 3,5-dicaffeoylquinic acid inhibits the expression and activation of MMP-9 by inhibiting the activation of iNOS and reducing the generation of free radicals, thus reducing the degradation of important cytoskeleton connexin claudin-5 in the tight junction (TJ) structure by inhibiting the expression and activation of MMP-9. Finally BBB structure integrity was protected.

Background & Aims: XBP1 modulates the macrophage proinflammatory response, but its function in macrophage stimulator of interferon genes (STING) activation and liver fibrosis is unknown. X-box binding protein 1 (XBP1) has been shown to promote macrophage nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) activation in steatohepatitis. Herein, we aimed to explore the underlying mechanism of XBP1 in the regulation of STING signalling and the subsequent NLRP3 activation during liver fibrosis. Methods: XBP1 expression was measured in the human fibrotic liver tissue samples. Liver fibrosis was induced in myeloid-specific Xbp1-, STING-, and Nlrp3-deficient mice by carbon tetrachloride injection, bile duct ligation, or a methionine/choline-deficient diet. Results: Although increased XBP1 expression was observed in the fibrotic liver macrophages of mice and clinical patients, myeloid-specific Xbp1 deficiency or pharmacological inhibition of XBP1 protected the liver against fibrosis. Furthermore, it inhibited macrophage NLPR3 activation in a STING/IRF3-dependent manner. Oxidative mitochondrial injury facilitated cytosolic leakage of macrophage self-mtDNA and cGAS/STING/NLRP3 signalling activation to promote liver fibrosis. Mechanistically, RNA sequencing analysis indicated a decreased mtDNA expression and an increased BCL2/adenovirus E1B interacting protein 3 (BNIP3)-mediated mitophagy activation in Xbp1-deficient macrophages. Chromatin immunoprecipitation (ChIP) assays further suggested that spliced XBP1 bound directly to the Bnip3 promoter and inhibited the transcription of Bnip3 in macrophages. Xbp1 deficiency decreased the mtDNA cytosolic release and STING/NLRP3 activation by promoting BNIP3-mediated mitophagy activation in macrophages, which was abrogated by Bnip3 knockdown. Moreover, macrophage XBP1/STING signalling contributed to the activation of hepatic stellate cells. Conclusions: Our findings demonstrate that XBP1 controls macrophage cGAS/STING/NLRP3 activation by regulating macrophage self-mtDNA cytosolic leakage via BNIP3-mediated mitophagy modulation, thus providing a novel target against liver fibrosis. Lay summary: Liver fibrosis is a typical progressive process of chronic liver disease, driven by inflammatory and immune responses, and is characterised by an excess of extracellular matrix in the liver. Currently, there is no effective therapeutic strategy for the treatment of liver fibrosis, resulting in high mortality worldwide. In this study, we found that myeloid-specific Xbp1 deficiency protected the liver against fibrosis in mice, while XBP1 inhibition ameliorated liver fibrosis in mice. This study concluded that targeting XBP1 signalling in macrophages may provide a novel strategy for protecting the liver against fibrosis.

Summary: Background: Low vaccine uptake has the potential to seriously undermine COVID-19 vaccination programs, as very high coverage levels are likely to be needed for virus suppression to return life to normal. We aimed to determine the influence of vaccine attributes (including access costs) on COVID-19 vaccination preferences among the Malaysian public to improve national uptake. Methods: An online Discrete Choice Experiment (DCE) was conducted on a representative sample of 2028 Malaysians. Respondents were asked to make vaccination decisions in a series of hypothetical scenarios. A nested, mixed logit model was used to estimate the preferences for vaccination over vaccine refusal and for how those preferences varied between different sub-populations. The attributes were the risk of developing severe side effects of the vaccine, vaccine effectiveness, vaccine content, vaccination schedule, and distance from home to vaccination centre. Findings: Reported public uptake of COVID-19 vaccination was primarily influenced by the risk of developing severe side effects (b = −1·747, 95% CI = −2·269, -1·225), vaccine effectiveness (b = 3·061, 95% CI = 2·628, 3·494) and its Halal status (b = 3·722, 95% CI = 3·152, 4·292). Other factors such as appointment timing and travel distance to the vaccination centre also had an effect on vaccine uptake. There was substantial heterogeneity in preferences between different populations, particularly for age groups, ethnicity, regions, and underlying health conditions. Interpretation: Perceived effectiveness and side effects are likely to affect COVID-19 vaccine uptake in Malaysia. Halal content is critical to Malays’ vaccination choices. Reducing the physical distance to vaccination centres, particularly in rural areas where uptake is lower, is likely to improve uptake. Funding: Ministry of Health Research Grant from the Malaysian government [NIH/800-3/2/1 Jld.7(46), grant reference no: 57377 and warrant no: 91000776].

Gear honing is a cost-efficient method for the finishing of hardened gears in which material removal is realized through honing wheel and workpiece gear interactions. There are a number of indicators used for evaluating the degrees of these interactions, among which specific energy is a more appropriate one than the others since it is capable of quantifying the amount of energy consumption during the material removal process. Nevertheless, models for the prediction of specific energy in gear honing have not been thoroughly investigated. This work presents a theoretical model of specific energy to quantitatively evaluate the material removal efficiency in the external gear honing process. To develop the model, an analytical material removal rate and a honing force model are proposed, and the feasibility of the proposed model is validated against external gear honing experiments. The correlations of specific energy with processing parameters are investigated and the material removal efficiency scores of external gear honing and grinding are compared and discussed. The present approach enables an in-depth understanding of the abrasive–material interactions in the gear honing process and the effects of processing parameters on material removal efficiency.

In the containment control problem of multi-agent systems (MASs), the convergence of followers is always a potential threat to the security of system operations. From the perspective of system topology, the inherently non-linear properties of the algebraic connectivity of the follower2follower (F2F) network, combined with the influence of the leader2follower (L2F) topology on the system, make it difficult to design the convergence positions of the followers through mere mathematical analysis. Therefore, in the background of temporary networking tasks for large-scale systems, to achieve the goal of forecasting the performance of the whole system when networking is only completed with local information, this paper investigates the application and effectiveness of recurrent neural networks (RNNs) in the containment control system performance identification, thus improving the efficiency of system networking while ensuring system security. Two types of identification models based on two types of neural networks (NNs), MLP and standard RNN are developed, according to the range of information required for performance identification. Evaluation of the models is carried out by means of the coefficient of determination (R2) as well as the root-mean-square error (RMSE). The results show that each model may produce a better forecasting accuracy than the other models in specific cases, with models based on the standard RNN possessing smaller errors. With the proposed method, model identification can be achieved, but in-depth development of the model in further studies is still necessary to the extent the accuracy of the model.

Research suggests that unpleasant emotions induced by feedback may reduce its efficiency in enhancing students’ performance, which is a crucial issue to address in education. In the context of Chinese language instruction in higher education, this study sought to investigate how students regulate their emotions as a result of feedback through the lens of individuals’ feedback orientation. In light of the feedback orientation lens and its conceptual framework, we applied in-depth qualitative interviews to explore how students experienced feedback, the negative emotions they experienced, and the emotion regulation strategies they used. Eleven undergraduates across years one to five joined our in-depth interviews. Students reported negative emotions when they received feedback that did not live up to their expectations or was unrealistic for them to accept. However, students’ feedback orientation supported their emotion regulation techniques, which in turn supported students’ adaptive feedback processing to interpret and take action to use feedback for academic performance improvement. Students also actively sought further teacher feedback or peer support to deal with a wide range of negative emotions. These findings imply the significance of fostering in students a high level of feedback orientation and the necessity of additional empirical investigation into the relationships between feedback orientation and emotional well-being in higher education. By shedding light on how students regulate the emotions that external feedback causes in them, the study adds valuable qualitative findings to the existing literature on positive psychology research in terms of emotions and emotion regulation. It also emphasizes how crucial students’ personal feedback orientation is for improving emotional well-being in the context of feedback.

Abstract Routine dental visit is the most common approach to detect the gingivitis. However, such diagnosis can sometimes be unavailable due to the limited medical resources in certain areas and costly for low-income populations. This study proposes to screen the existence of gingivitis and its irritants, i.e., dental calculus and soft deposits, from oral photos with a novel Multi-Task Learning convolutional neural network (CNN) model. The study can be meaningful for promoting the public dental health, since it sheds light on a cost-effective and ubiquitous solution for the early detection of dental issues. With 625 patients included in this study, the classification Area Under the Curve (AUC) for detecting gingivitis, dental calculus and soft deposits were 87.11%, 80.11%, and 78.57%, respectively; Meanwhile, according to our experiments, the model can also localize the three types of findings on oral photos with moderate accuracy, which enables the model to explain the screen results. By comparing to general-purpose CNNs, we showed our model significantly outperformed on both classification and localization tasks, which indicates the effectiveness of Multi-Task Learning on dental disease detection. In all, the study shows the potential of deep learning for enabling the screening of dental diseases among large populations.

The adoption of bus rapid transit (BRT) systems has gained worldwide popularity over the past several decades. China is no exception as it has long been aiming at promoting public transportation. Prior studies have provided extensive evidence that BRT has substantial effects on house prices with traditional econometric techniques, such as hedonic pricing models. However, few of those investigations have discussed the non-linear relationship between BRT and house prices. Using the Xiamen data, this study employs a machine learning technique, namely the gradient boosting decision tree (GBDT), to scrutinize the non-linear relationship between BRT and house prices. This study documents a positive association between accessibility to BRT stations and house prices and a negative association between proximity to the BRT corridor and house prices. Moreover, it suggests a non-linear relationship between BRT and house prices and indicates that GBDT has more substantial predictive power than hedonic pricing models.

Abstract Epidermal growth factor receptor (EGFR) is among the first discovered transmembrane receptor tyrosine kinases. Ligand binding to the extracellular domain of EGFR results in the formation of homo‐dimeric or hetero‐dimeric complexes, activation, and auto‐phosphorylation in the intracellular tyrosine kinase domain, then regulates the cell's proliferation, differentiation, migration, and invasion. It has been reported that EGFR is overexpressed, amplified, or mutated in several epithelial tumors. EGFR tyrosine kinase inhibitors (EGFR‐TKIs) specifically bind to the tyrosine kinase domain of EGFR. Homogeneous time‐resolved fluorescence (HTRF) assay is successfully used in kinase assays and is a crucial tool in the drug discovery of various kinases. Moreover, the HTRF assay has been determined to exhibit many advantages, such as being easy to miniaturize, simple to read, and excellent to repeat. In these guidelines, the theory, materials, and reagent preparation of HTRF kinase assay are described and emphasized. Furthermore, the protocol and optimization of the assay are determined to establish an HTRF screening platform, then an optimized HTRF kinase assay is performed to test the compounds for screening potential EGFR‐TKIs. In addition, these guidelines can contribute to verifying the high‐throughput screening results of HTRF and help to reveal the underlying mechanism of the EGFR kinase and tested compounds.

ObjectiveRoux-en-Y gastric bypass is an effective intervention for metabolic disorder. We aim to elucidate whether ghrelin contributes to weight reduction, and glycemic and lipid control after Roux-en-Y gastric bypass (RYGB).DesignFour-week-old WT and Ghrl-TSC1-/- mice were fed high fat diet for 12 weeks before surgery, and continued to be on the same diet for 3 weeks after surgery. Body weight, food intake, glycemic and lipid metabolism were analyzed before and after surgery.ResultsGastric and circulating ghrelin was significantly increased in mice with RYGB surgery. Hypoghrelinemia elicited by deletion of TSC1 to activate mTOR signaling in gastric X/A like cells demonstrated no effect on weight reduction, glycemic and lipid control induced by Roux-en-Y gastric bypass surgery.ConclusionLower ghrelin levels does not impact the metabolic benefit induced by Roux-en-Y gastric bypass.

ABSTRACT Phylogenetic evidence from the recent resurgence of high-pathogenicity avian influenza (HPAI) virus subtype H5N1, clade 2.3.4.4b, observed in European wild birds and poultry since October 2021, suggests at least two different and distinct reservoirs. We propose contrasting hypotheses for this emergence: (i) resident viruses have been maintained, presumably in wild birds, in northern Europe throughout the summer of 2021 to cause some of the outbreaks that are part of the most recent autumn/winter 2021 epizootic, or (ii) further virus variants were reintroduced by migratory birds, and these two sources of reintroduction have driven the HPAI resurgence. Viruses from these two principal sources can be distinguished by their hemagglutinin genes, which segregate into two distinct sublineages (termed B1 and B2) within clade 2.3.4.4b, as well as their different internal gene compositions. The evidence of enzootic HPAI virus circulation during the summer of 2021 indicates a possible paradigm shift in the epidemiology of HPAI in Europe.

At the current stage of a global energy shortage, the optimization of marine energy consumption has received attention. In order to save marine energy consumption and reduce pollution, research on low-energy-consumption Unmanned Surface Vessels (USVs) and their green and low-carbon cooperative operation methods needs to be paid attention to. Due to the ever-changing environment of USVs in actual sea conditions and the increasingly complex tasks, the cooperation of a single swarm of USVs is incompetent. First, in order to cope with larger-scale and complex tasks, we construct the multilateral cooperative control system for USVs with topology scalability under a polymorphic network and propose the multilateral distributed control protocol. Second, in order to reduce the energy consumption of the cooperative operation of USVs, the low-energy-consumption and low-carbon USVs are selected with the lowest EEOI index as the optimization goal, and based on ad hoc on-demand distance vector routing (AODV), the optimal path between USVs is obtained. Then, the swarms are grouped by External Equitable Partition (EEP), and the green autonomous cooperative formation strategy is proposed. Finally, the simulation examples are used to verify the effectiveness of the method proposed in this article.

Introduction Vaccine safety is a primary concern among vaccine-hesitant individuals. We examined how seven persuasive messages with different frames, all focusing on vaccine safety, influenced Malaysians to accept the COVID-19 vaccine, and recommend it to individuals with different health and age profiles; that is, healthy adults, the elderly, and people with pre-existing health conditions.Methods A randomised controlled experiment was conducted from 29 April to 7 June 2021, which coincided with the early phases of the national vaccination programme when vaccine uptake data were largely unavailable. 5784 Malaysians were randomly allocated into 14 experimental arms and exposed to one or two messages that promoted COVID-19 vaccination. Interventional messages were applied alone or in combination and compared against a control message. Outcome measures were assessed as intent to both take the vaccine and recommend it to healthy adults, the elderly, and people with pre-existing health conditions, before and after message exposure. Changes in intent were modelled and we estimated the average marginal effects based on changes in the predicted probability of responding with a positive intent for each of the four outcomes.Results We found that persuasive communication via several of the experimented messages improved recommendation intentions to people with pre-existing health conditions, with improvements ranging from 4 to 8 percentage points. In contrast, none of the messages neither significantly improved vaccination intentions, nor recommendations to healthy adults and the elderly. Instead, we found evidence suggestive of backfiring among certain outcomes with messages using negative attribute frames, risky choice frames, and priming descriptive norms.Conclusion Message frames that briefly communicate verbatim facts and stimulate rational thinking regarding vaccine safety may be ineffective at positively influencing vaccine-hesitant individuals. Messages intended to promote recommendations of novel health interventions to people with pre-existing health conditions should incorporate safety dimensions.Trial registration number NCT05244356.

Abstract Background Poor mental health status and associated risk factors of public health workers have been overlooked during the COVID-19 pandemic. This study used the effort–reward imbalance model to investigate the association between work-stress characteristics (effort, over-commitment, reward) and mental health problems (anxiety and depression) among front-line public health workers during the COVID-19 pandemic in China. Methods A total of 4850 valid online questionnaires were collected through a self- constructed sociodemographic questionnaire, the adapted ERI questionnaire, the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item General Anxiety Disorder Scale (GAD-7). Hierarchical logistic regression analysis was conducted to investigate the association between ERI factors and mental health problems (i.e., depression and anxiety), with reward treated as a potential moderator in such associations. Results The data showed that effort and over-commitment were positively associated with depression and anxiety, while reward was negatively associated with depression and anxiety. Development and job acceptance were the two dimensions of reward buffered the harmful effect of effort/over-commitment on depression and anxiety, whereas esteem was non-significant. Conclusions This study confirmed the harmful effects of effort and over-commitment on mental health among public health workers during the COVID-19 pandemic in China. Such effects could be alleviated through an appropriate reward system, especially the development and job acceptance dimensions of such a system. These findings highlight the importance of establishing an emergency reward system, comprising reasonable work-allocation mechanism, bonuses and honorary titles, a continuous education system and better career-development opportunities.

Abstract Background COVID-19 has resulted in high mortality worldwide. Information regarding cardiac markers for precise risk-stratification is limited. We aim to discover sensitive and reliable early-warning biomarkers for optimizing management and improving the prognosis of COVID-19 patients. Methods A total of 2954 consecutive COVID-19 patients who were receiving treatment from the Wuhan Huoshenshan Hospital in China from February 4 to April 10 were included in this retrospective cohort. Serum levels of cardiac markers were collected after admission. Coronary artery disease diagnosis and survival status were recorded. Single-cell RNA-sequencing and bulk RNA-sequencing from different cohorts of non-COVID-19 were performed to analyze SARS-CoV-2 receptor expression. Results Among 2954 COVID-19 patients in the analysis, the median age was 60 years (50–68 years), 1461 (49.5%) were female, and 1515 (51.3%) were severe/critical. Compared to mild/moderate (1439, 48.7%) patients, severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. In severe/critical COVID-19 patients, those with abnormal serum levels of BNP (42 [24.6%] vs 7 [1.1%]), hs-TNI (38 [48.1%] vs 6 [1.0%]), α- HBDH (55 [10.4%] vs 2 [0.2%]), CK-MB (45 [36.3%] vs 12 [0.9%]), and LDH (56 [12.5%] vs 1 [0.1%]) had a significantly higher mortality rate compared to patients with normal levels. The same trend was observed in the ICU admission rate. Severe/critical COVID-19 patients with pre-existing coronary artery disease (165/1,155 [10.9%]) had more cases of BNP (52 [46.5%] vs 119 [16.5%]), hs-TNI (24 [26.7%] vs 9.6 [%], α- HBDH (86 [55.5%] vs 443 [34.4%]), CK-MB (27 [17.4%] vs 97 [7.5%]), and LDH (65 [41.9%] vs 382 [29.7%]), when compared with those without coronary artery disease. There was enhanced SARS-CoV-2 receptor expression in coronary artery disease compared with healthy controls. From regression analysis, patients with five elevated cardiac markers were at a higher risk of death (hazards ratio 3.4 [95% CI 2.4–4.8]). Conclusions COVID-19 patients with pre-existing coronary artery disease represented a higher abnormal percentage of cardiac markers, accompanied by high mortality and ICU admission rate. BNP together with hs-TNI, α- HBDH, CK-MB and LDH act as a prognostic biomarker in COVID-19 patients with or without pre-existing coronary artery disease.

This paper proposes a distributed energy management strategy, based on dual decomposition mixed integer linear programming for port integrated energy systems (PIESs), to improve the utilization of renewable energy, and to foster green ports. Firstly, due to the distributed characteristics presented by various heterogeneous devices, a polymorphic network-based PIES was established, instead of the traditional single IP protocol, incorporating electricity replacement and energy conversion devices. Secondly, taking into account the coupling of various energy flows, an energy management model was constructed, to ensure reliable operation for the PIES. Thirdly, an energy management strategy based on distributed dual decomposition mixed integer linear programming for the PIES was proposed, which took into account the distributed characteristic of the PIES. Finally, the effectiveness of the proposed strategy was demonstrated, by simulation cases in different scenarios for the PIES. The obtained energy management results were similar to the centralized algorithm.

Electronic and magnetic properties of Ga14N16−nGd2Cn monolayers are investigated by means of the first principle calculation. The generalized gradient approximation (GGA) of the density functional theory with the on-site Coulomb energy U was considered (GGA + U). It is found that the total magnetic moment of a Ga14N16Gd2 monolayer is 14 μB with an antiferromagnetic (AFM) phase. C atom substitutional impurity can effectively change the magnetic state of Ga14N16−nGd2Cn monolayers to ferromagnetic phases (FM), and the magnetic moment increases by 1μB/1C. The stable FM phase is due to the p-d coupling orbitals between the C-2p and Gd-5d states. Moreover, Curie temperature (TC) close to room temperature (TR, 300 K) is observed in the Ga14N16Gd2C2 monolayer, and the highest value can reach 261.46 K. In addition, the strain effect has a significant positive effect on the TC of the Ga14N16−nGd2Cn monolayer, which is much higher than the TR, and the highest value is 525.50 K. This provides an opportunity to further explore the application of two-dimensional magnetic materials in spintronic devices.

Risk identification, monitoring and early warning of typical coal mine dynamic disasters such as rock burst, coal and gas outburst is the focus and difficulty of coal mine safety production. During the 13th Five-Year Plan period. In order to solve this problem, we carried out the research on the development of key technologies and equipment for risk identification, monitoring and early warning of typical power disasters in coal mines, a new theory of breeding and evolution mechanism and occurrence and development of coal mine dynamic disaster under the effect of mining disturbance and multi-field coupling superposition was established, the intelligent identification theory and early warning method of multi parameter precursory information of typical dynamic disasters in coal mines were put forward; the precursory information acquisition and sensing technology and equipment with fault self-diagnosis, high sensitivity and long calibration period were developed. Through the research of heterogeneous data fusion, ad hoc network, anti-interference and other technologies, the comprehensive collection of man-machine environment parameters and multi information in key areas of coal mines are proposed The new method of common network transmission provides technical support for the safe and trouble free operation of coal mine typical power disaster monitoring and early warning system. An automatic, informatized and intelligent early warning platform is constructed, which realizes the functions of fault self diagnosis, high sensitivity, short response time, long calibration period, anti-interference, etc., and the early warning accuracy is improved to more than 90 %. Through the organic integration of early warning basic research, key technology development and application demonstration has realized online monitoring, intelligent identification and real-time accurate early warning of hidden major disasters in coal mine have been realized.

ABSTRACT Background Public health workers at the Chinese Centre for Disease Control and Prevention (China CDC) and primary health care institutes (PHIs) were among the main workers who implemented prevention, control, and containment measures. However, their efforts and health status have not been well documented. We aimed to investigate the working conditions and health status of front line public health workers in China during the COVID-19 epidemic. Methods Between 18 February and 1 March 2020, we conducted an online cross-sectional survey of 2,313 CDC workers and 4,004 PHI workers in five provinces across China experiencing different scales of COVID-19 epidemic. We surveyed all participants about their work conditions, roles, burdens, perceptions, mental health, and self-rated health using a self-constructed questionnaire and standardised measurements (i.e., Patient Health Questionnaire and General Anxiety Disorder scale). To examine the independent associations between working conditions and health outcomes, we used multivariate regression models controlling for potential confounders. Results The prevalence of depression, anxiety, and poor self-rated health was 21.3, 19.0, and 9.8%, respectively, among public health workers (27.1, 20.6, and 15.0% among CDC workers and 17.5, 17.9, and 6.8% among PHI workers). The majority (71.6%) made immense efforts in both field and non-field work. Nearly 20.0% have worked all night for more than 3 days, and 45.3% had worked throughout the Chinese New Year holiday. Three risk factors and two protective factors were found to be independently associated with all three health outcomes in our final multivariate models: working all night for >3 days (multivariate odds ratio [ORm]=1.67~1.75, p 1 month at the current work intensity (ORm=0.44~0.55, p

When communicating in aeronautical wireless channels, the difficulty of radio modulation recognition increases due to the loss of information caused by noise; particularly in circumstances with low signal-to-noise ratios (SNRs), it is difficult to achieve recognition rates exceeding 90.0%. To improve the radio modulation recognition performances of networks at low SNRs in complex electromagnetic environments, a modulation recognition method based on multidimensional feature analysis is proposed in this paper. It is realized through a cascaded structure including a Deep Cross Network (DCN) and an improved Visual Geometry Group Network 16 (VGG16). Our network framework is divided into two modules. In the one-dimensional data analysis module, we take the high-order cumulant of a transmitted signal as the one-dimensional feature input of the DCN. In the two-dimensional data analysis module, the color constellation density of the signal is extracted as the feature map input of the improved VGG16. Finally, we build a cascaded neural network with hybrid feature inputs for modulation recognition. Experimental results show that the recognition rate of our method is higher than 90.0% at an SNR of −4 dB. Compared with other methods, the proposed method has better recognition performance at low SNRs in aeronautical wireless channels.

This paper presents a supply-insensitive low-power quadrature local oscillation (LO) generator based on the current-reused voltage-controlled oscillator (VCO) and divide-by-two frequency divider (FD). By utilizing the mutual power-supply rejection (M-PSR) technique, a voltage regulator is embedded into the FD to provide a supply-insensitive voltage for VCO. Meanwhile, the feedback loop provides a supply-insensitive current and time constant compensation for FD. The M-PSR technique does not require extra voltage headroom, thus the proposed quadrature LO generator can work under the supply of 0.9 V. A prototype of the proposed quadrature LO generator is implemented in a 28-nm CMOS process. Measurement results indicate that the LO generator achieves a phase noise of −110.5 dBc/Hz@1MHz at the carrier of 5.9 GHz and the power consumption is 1.8 mW. This work has a competitive figure of merit in supply sensitivity or in area (FOMss or FOMa respectively) among the state-of-the-art works.

Abstract Background The minimum clinical important differences (MCIDs) of resilience instruments in patients with cancer have not been comprehensively described. This study was designed to evaluate MCIDs of 10-item and 25-item resilience scales specific to cancer (RS-SC-10 and RS-SC-25). Methods From June 2015 to December 2018, RS-SCs were longitudinally measured in 765 patients with different cancer diagnoses at baseline (T0) and 3 months later (T1). The EORTC QLQ-C30, Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Allostatic Load Index were measured concurrently as anchors. Anchor-based methods (linear regression, within-group), distribution-based methods(within-group), and receiver operating characteristic curves (ROCs, within-subject) were performed to evaluate the MCIDs. Results 623 of 765 (84.1%) patients had paired RS-SCs scores. Moderate correlations were identified between the change in RS-SCs and change in anchors (r = 0.38–0.44, all p

Accurate detection and location of tumor lesions are essential for improving the diagnosis and personalized cancer therapy. However, the diagnosis of lesions with fuzzy histology is mainly dependent on experiences and with low accuracy and efficiency. Here, we developed a logistic regression model based on mutational signatures (MS) for each cancer type to trace the tumor origin. We observed MS could distinguish cancer from inflammation and healthy individuals. By collecting extensive datasets of samples from ten tumor types in the training cohort (5,001 samples) and independent testing cohort (2,580 samples), cancer-type-specific MS patterns (CTS-MS) were identified and had a robust performance in distinguishing different types of primary and metastatic solid tumors (AUC:0.76 ∼ 0.93). Moreover, we validated our model in an Asian population and found that the AUC of our model in predicting the tumor origin of the Asian population was higher than 0.7. The metastatic tumor lesions inherited the MS pattern of the primary tumor, suggesting the capability of MS in identifying the tissue-of-origin for metastatic cancers. Furthermore, we distinguished breast cancer and prostate cancer with 90% accuracy by combining somatic mutations and CTS-MS from cfDNA, indicating that the CTS-MS could improve the accuracy of cancer-type prediction by cfDNA. In summary, our study demonstrated that MS was a novel reliable biomarker for diagnosing solid tumors and provided new insights into predicting tissue-of-origin.

Abstract Background Tendon adhesion is one of the most common clinical problems, which poses a considerable challenge to orthopedics doctors. Quercetin (QUE) as a popular drug at present, it has various biological functions, including anti-inflammatory, anti-ischemic, anti-peroxidation, and antioxidant. The purpose of this study was to investigate the effect of quercetin on tendon adhesion and whether quercetin can inhibit oxidative stress. Method Thirty-six rats were randomly divided into three groups, including control group, low QUE (50 mg/kg/day) group, and high QUE (100 mg/kg/day) group. After 1 week, the levels of SOD, MDA and GPx were measured. The degree of tendon adhesion was assessed by macroscopic evaluation and histological evaluation. After 4 weeks. Besides, the pharmacological toxicity of quercetin to main organs were evaluated by histological analysis. Results The extent of superoxide dismutase (SOD) and glutathione peroxidase (GPx) of tendon tissue in high QUE group was significantly higher than those of low QUE group and control group. And the extent of malondialdehyde (MDA) of tendon tissue in high QUE group was significantly lower than that of low QUE group and control group. By macroscopic evaluation and histological analysis, the extent of tendon adhesion in high QUE group was lower than low QUE group and control group. However, there were no significant changes of the major organs through histological analysis. Conclusions Quercetin may be a good and safe strategy in preventing tendon adhesion. But further clinical research is needed before its recommendation in the prevention and treatment of tendon adhesion.

Lignin, as a major by-product of pulp and paper industry, has attracted extensive interest for the preparation of high value-added products, due to the merits of abundant, sustainable, inexpensive, and unique functional groups. This review focuses on the strategies to develop high performance polyurethane (PU) materials from lignin on the basis of main reports, in which lignin was used not only as macromonomer to substitute petroleum-based polyols, but also as blending filler for PU industry. Pre-treatment approaches, especially lignin fractions extracted with various solvents and chemical modifications, e.g., depolymerization, hydroxyalkylation, dealkylation, and esterication, were widely explored to enable lignin more reactive and available to synthesize PU products. In addition, lignin/PU blends were also prepared to fulfill industrial demand. With adjustment of lignin structure, the PU formulation, and synthesis procedures, various lignin-based PU products with advanced properties and a higher bio-substitution ratio have been developed, demonstrating the potential industrial application of lignin for high value-added sustainable materials.

Agrocybe cylindracea, an edible mushroom, is widely cultivated for its abundance of nutrients and flavor, and many of its metabolites are reported to have beneficial roles, such as medicinal effects on tumors and chronical illnesses. However, the lack of genomic information has hindered further molecular studies on this fungus. Here, we present a genome assembly of A. cylindracea together with comparative genomics and pathway analyses of Agaricales species. The draft, generated from both next-generation sequencing (NGS) and single-molecule real-time (SMRT) sequencing platforms to overcome high genetic heterozygosity, is composed of a 56.5 Mb sequence and 15,384 predicted genes. This mushroom possesses a complex reproductive system, including tetrapolar heterothallic and secondary homothallic mechanisms, and harbors several hydrolases and peptidases for gradual and effective degradation of various carbon sources. Our pathway analysis reveals complex processes involved in the biosynthesis of polysaccharides and other active substances, including B vitamins, unsaturated fatty acids, and N-acetylglucosamine. RNA-seq data show that A. cylindracea stipes tend to synthesize carbohydrate for carbon sequestration and energy storage, whereas pilei are more active in carbon utilization and unsaturated fatty acid biosynthesis. These results reflect diverse functions of the two anatomical structures of the fruiting body. Our comprehensive genomic and transcriptomic data, as well as preliminary comparative analyses, provide insights into the molecular details of the medicinal effects in terms of active compounds and nutrient components.

Abstract Background The rapid identification of pathogenic bacteria is important for determining an appropriate antimicrobial therapy for pneumonia, but traditional bacterial culture is time-consuming and labourious. The aim of this study was to develop and evaluate a DNA microarray assay for the simultaneous detection of fifteen bacterial species directly from respiratory tract specimens in patients with pneumonia. These species included Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Mycoplasma pneumoniae, Enterococcus faecalis, Enterococcus faecium, Enterobacter cloacae, Stenotrophomonas maltophilia, Burkholderia cepacia, Legionella pneumophila and Chlamydia pneumoniae. The 16S rDNA genes and other specific genes of each pathogen were chosen as the amplification targets, amplified via multiplex polymerase chain reaction (PCR), and hybridized to oligonucleotide probes in a microarray. Results The DNA microarray detection limit was 103 copies/μL. Nineteen standard strains and 119 clinical isolates were correctly detected with our microarray, and 3 nontarget species from 4 clinical isolates were not detected. Additionally, bacterial pathogens were accurately identified when two or three bacterial targets were mixed together. Furthermore, the results for 99.4% (156/157) of clinical specimens were the same as those from a conventional assay. Conclusions We developed a DNA microarray that could simultaneously detect various bacterial pathogens in pneumonia. The method described here has the potential to provide considerable labour and time savings due to its ability to screen for 15 bacterial pathogens simultaneously.

Abstract Introduction Patient education is crucial for improving disease outcomes in atopic dermatitis (AD). This review aims to summarize evidence about the effectiveness of educational programs for parents of pediatric AD patients. Methods PubMed and Embase (inception to Feb 2020) were searched and randomized controlled trials (RCTs) in English were included. Risk of bias was assessed using Cochrane risk of bias tools and quality of evidence was assessed by Grading of Recommendations Assessment, Development and Evaluation (GRADE). Pooled standardized mean difference (SMD) and 95% confidence intervals (CIs) were calculated for the disease severity instrument (Scoring of Atopic Dermatitis, SCORAD) and quality of life (QoL) instruments using the random-effects model. Results A total of 13 RCTs were included in the systematic review. The meta-analysis of SCORAD contained seven studies with a total of 1853 patients. The reduction in disease severity (SCORAD) was larger in the treatment group (SMD = − 8.22, 95% CI = − 11.29, − 5.15; P

Abstract Background Horseshoe crabs are ancient marine arthropods with a long evolutionary history extending back approximately 450 million years, which may benefit from their innate immune systems. However, the genetic mechanisms underlying their abilities of distinguishing and defending against invading microbes are still unclear. Results Here, we describe the 2.06 Gbp genome assembly of Tachypleus tridentatus with 24,222 predicted protein-coding genes. Comparative genomics shows that T. tridentatus and the Atlantic horseshoe crab Limulus polyphemus have the most orthologues shared among two species, including genes involved in the immune-related JAK-STAT signalling pathway. Divergence time dating results show that the last common ancestor of Asian horseshoe crabs (including T. tridentatus and C. rotundicauda) and L. polyphemus appeared approximately 130 Mya (121–141), and the split of the two Asian horseshoe crabs was dated to approximately 63 Mya (57–69). Hox gene analysis suggests two clusters in both horseshoe crab assemblies. Surprisingly, selective analysis of immune-related gene families revealed the high expansion of conserved pattern recognition receptors. Genes involved in the IMD and JAK-STAT signal transduction pathways also exhibited a certain degree of expansion in both genomes. Intact coagulation cascade-related genes were present in the T. tridentatus genome with a higher number of coagulation factor genes. Moreover, most reported antibacterial peptides have been identified in T. tridentatus with their potentially effective antimicrobial sites. Conclusions The draft genome of T. tridentatus would provide important evidence for further clarifying the taxonomy and evolutionary relationship of Chelicerata. The expansion of conserved immune signalling pathway genes, coagulation factors and intact antimicrobial peptides in T. tridentatus constitutes its robust and effective innate immunity for self-defence in marine environments with an enormous number of invading pathogens and may affect the quality of the adaptive properties with regard to complicated marine environments.

Abstract Background Mesenchymal stem cells (MSCs) are pluripotent mesenchymal cells present in various adult tissues. MSCs secrete exosomes as regulators of the tumor niche, with involvement in tumorigenesis and metastasis. The regulatory role of microRNAs (miRs or miRNAs) in MSCs via targeting cyclin E1 (CCNE1) or cyclin E2 (CCNE2) has been extensively reported. Since exosomes are considered as protective and enriched sources of shuttle miRNAs, we hypothesized that exosomal transfer of miR-144 from bone marrow-derived MSCs (BMMSCs) would affect the development of non-small cell lung cancer (NSCLC) cells by targeting CCNE1 and CCNE2. Methods We first quantified the levels of miR-144, CCNE1, and CCNE2 in NSCLC tissues and cell lines and then undertook gain- and loss-of-function studies of miR-144, CCNE1, and CCNE2 to investigate their roles in the biological characteristics of NSCLC in vitro. NSCLC cells (A549) were exposed to exosomes derived from MSCs, and cell proliferation and colony formation rate were determined using in vitro assays. Finally, effects of BMMSC-derived exosomal miR-144 on tumor development were studied in vivo. Results In NSCLC tissues and cell lines, miR-144 was expressed poorly and CCNE1 and CCNE2 were expressed highly. Artificially elevating miR-144 inhibited cell proliferation, colony formation, and the number of S phase-arrested cells in NSCLC by downregulating CCNE1 and CCNE2. Additionally, BMMSC-derived exosomal miR-144 led to restrained NSCLC cell proliferation and colony formation. These inhibitory effects of BMMSC-derived exosomes carrying miR-144 on NSCLC were confirmed by experiments in vivo. Conclusion Collectively, these findings revealed inhibitory effects of BMMSC-derived exosomal miR-144 on NSCLC progression, which were mediated by downregulation of CCNE1 and CCNE2.

In the current study, the orthographic knowledge required for writing Chinese characters was assessed among participants with L1 Vietnamese background who learn Chinese as a foreign language. A total of 42 undergraduates were recruited. They were invited to participate in a delayed Chinese character copying task consisting of 32 characters. Their Chinese character reading abilities were also obtained using a character naming task. All the tests were conducted online during the pandemic in 2021. Results indicated that the participants’ accuracy in the copying task was affected by the familiarity of the characters and the number of strokes of the characters. These effects minimized as reading performance increased. In the inter-stroke interval (ISI) analysis, results indicated a significant boundary effect where ISIs between orthographic units were longer than ISIs within orthographic units, showing the participants’ tendency to chunk Chinese characters into functional units when they write. Only high achievers in the reading task demonstrated the use of both large and small grain-size units in writing (i.e., radical-boundary ISI > logographeme-boundary ISI > non-boundary ISI), while the low achievers only used small grain-size units in their writing. We suggest that the delayed copying task incorporated with handwriting measures is an effective method to assess orthographic knowledge of L2 Chinese learners.

ABSTRACT Bacterial small RNAs (sRNAs) function as vital regulators in response to various environmental stresses by base pairing with target mRNAs. The sRNA DsrA, an important posttranscriptional regulator, has been reported to play a crucial role in defense against oxidative stress in Salmonella enterica serovar Typhimurium, but its regulatory mechanism remains unclear. The transcriptome sequencing (RNA-seq) results in this study showed that the genes involved in glycolysis, pyruvate metabolism, the tricarboxylic acid (TCA) cycle, and NADH-dependent respiration exhibited significantly different expression patterns between S. Typhimurium wild type (WT) and the dsrA deletion mutant (ΔdsrA strain) before and after H2O2 treatment. This indicated the importance of DsrA in regulating central carbon metabolism (CCM) and NAD(H) homeostasis of S. Typhimurium. To reveal the direct target of DsrA action, fusion proteins of six candidate genes (acnA, srlE, tdcB, nuoH, katG, and pflB) with green fluorescent protein (GFP) were constructed, and the fluorescence analysis showed that the expression of pflB encoding pyruvate-formate lyase was repressed by DsrA. Furthermore, site-directed mutagenesis and RNase E-dependent experiments showed that the direct base pairing of DsrA with pflB mRNA could recruit RNase E to degrade pflB mRNA and reduce the stability of pflB mRNA. In addition, the NAD+/NADH ratio in WT-ppflB-pdsrA was significantly lower than that in WT-ppflB, suggesting that the repression of pflB by DsrA could contribute greatly to the redox balance in S. Typhimurium. Taken together, a novel target of DsrA was identified, and its regulatory role was clarified, which demonstrated that DsrA could modulate CCM and redox balance by directly repressing pflB expression in S. Typhimurium. IMPORTANCE Small RNA DsrA plays an important role in defending against oxidative stress in bacteria. In this study, we identified a novel target (pflB, encoding pyruvate-formate lyase) of DsrA and demonstrated its potential regulatory mechanism in S. Typhimurium by transcriptome analysis. In silico prediction revealed a direct base pairing between DsrA and pflB mRNA, which was confirmed in site-directed mutagenesis experiments. The interaction of DsrA-pflB mRNA could greatly contribute to the regulation of central carbon metabolism and intracellular redox balance in S. Typhimurium. These findings provided a better understanding of the critical roles of small RNA in central metabolism and stress responses in foodborne pathogens.

This study aims to investigate the association of organizational and patient behaviors (reflecting the internal and external environment of hospital, respectively) with physician well-being. A national cross-sectional survey was conducted in 77 hospitals across seven provinces in China between July 2014 and April 2015. Physician well-being was assessed with job satisfaction, career regret and happiness. Organizational behaviors were assessed with organizational fairness, leadership attention and team interaction; patient behaviors were assessed with patient trust and unreasonable requests from patients. Of a study sample of 3,159 physicians, 1,788 were men (56.6%) and 1,371 were women (43.4%). Overall, positive organizational and patient behaviors reported by physicians were relatively low. Negative organizational behaviors and patient behaviors including lower organizational fairness, lower leadership attention, lower team interaction and lower patient trust were associated with lower job satisfaction and lower life satisfaction, and higher career regret. The association between organizational behaviors and physician well-being exhibited some gender differences, while no clear gender difference was found for the relationship between patient behaviors and physician well-being. Given the importance of physician well-being for the healthcare system, interventions for improving internal and external hospital environments (e.g., organizational fairness, leadership attention, team interaction and patient trust) may benefit physician well-being.

We present a modified Picard-like method to solve absolute value equations by equivalently expressing the implicit fixed-point equation form of the absolute value equations as a two-by-two block nonlinear equation. This unifies some existing matrix splitting algorithms and improves the efficiency of the algorithm by introducing the parameter ω. For the choice of ω in the new method, we give a way to determine the quasi-optimal values. Numerical examples are given to show the feasibility of the proposed method. It is also shown that the new method is better than those proposed by Ke and Ma in 2017 and Dehghan and Shirilord in 2020.

Although robotic spatial printing (RSP) has demonstrated a new way of fabricating building components with a good stiffness-to-weight ratio, the complexity of the applied geometries is still limited. Among them are branching geometries, which refer to the bio-inspired branching structures (BIBSs) in the building industry. This paper presents a cutting-edge approach to tackle this bottleneck problem, in which we propose an automated printing path generation (APPG) approach for the RSP of branching geometries, including an original hierarchical framework of printing node permutations and a linear workflow that incorporates five core algorithms: the heat method, graph generation, graph traversal, curve adjustment, and lattice generation. Through the execution of this workflow, a lattice structure and its corresponding printing path can be generated. This work is validated by the simulation of three prototypes: two-branch geometry, multi-branch geometry, and multi-level-branch geometry. Printing expenses are compared with each of the related algorithms to validate the efficiency of this proposed approach. Along with the appropriate APPG solutions, an analytical tool for topological type is also presented in this paper.

It is important to explore efficient materials to alleviate the negative effect of atrazine in soils or water. In this paper, four Fe/Mn-modified biochars were prepared to enhance atrazine removal. The batch adsorption experiment was conducted to explore the adsorption ability of biochar(DBC) and modified biochars (F3M1DBC, F1M3DBC, MnDBC, and FeDBC) on atrazine, and the adsorption mechanism was conducted by XRD, XPS, and FTIR. The modified biochar showed larger specific surface areas and zero-point charge than those of the original biochar. The increased oxygen functional groups (OH, C=C, and C=O) and the formation of Fe3O4, Mn3O4, and FeMnO3 on modified biochar improved atrazine removal. The maximum atrazine adsorption by F3M1DBC was 4.3 times higher than that of DBC. The atrazine adsorption by modified biochar was not pH-dependent, and their removal of atrazine was dominated by adsorption rather than degradation. The desorption rate was 8.61% for F3M1DBC, 15.95% for F1M3DBC, 26.19% for MnDBC, and 29.83% for FeDBC, which were 29.1–79.5% lower than that of DBC, accordingly decreased the environmental risk. XPS and FTIR analysis proved that the adsorption mechanisms of Fe/Mn-modified biochars were mainly attributed to their strong π–π interactions between atrazine and oxygen functional groups, graphitic carbon, and Fe/Mn-oxides on the surface of biochar. In addition, the larger surface area and pore structure of modified biochar contributed to the adsorption and pore filling of atrazine on biochar. In general, the Fe/Mn-modified biochars can be used as effective adsorbents to remove atrazine from soils and waters.

Abstract This study evaluates the precipitation over East Asia simulated by the variable resolution CAM‐MPAS featuring the Model for Prediction Across Scales (MPAS) atmospheric dynamical core coupled with the physics parameterizations of the Community Atmosphere Model (CAM) version 5.4. Two CAM‐MPAS experiments, one with a global quasi‐uniform resolution mesh of 120 km (MPAS‐UR) and the other with a variable resolution mesh of 30–120 km refined over East Asia (MPAS‐VR), are conducted from 1989 to 2005 following the Atmospheric Model Intercomparison Project protocol. Two regional climate model simulations at ∼25 km resolution from the Coordinated Regional Downscaling Experiment East Asia second plan are also analyzed for comparison. Results show that CAM‐MPAS performs better than the selected regional models in simulating the precipitation climatology over East Asia. Compared with MPAS‐UR, MPAS‐VR with refinement over East Asia better simulates the precipitation over and around the Tibetan Plateau (TP), the upper‐level circulation, the precipitation frequency and intensity in various regions of China, and the interannual precipitation pattern associated with the East Asian summer monsoon. Both decreased grid spacing and the use of finer‐scale terrain information contribute to the improvements in MPAS‐VR relative to MPAS‐UR. However, decreased grid spacing is more essential for simulating the precipitation magnitude over TP and the location of peak precipitation south of TP, likely due to the better resolved physical and dynamical processes associated with orographic precipitation. The 30–120 km CAM‐MPAS model is shown to be a promising tool for precipitation simulation over East Asia.

In this review, motivated by the recent interest in high-temperature materials, we review our recent progress in theories of lattice dynamics in and out of equilibrium. To investigate thermodynamic properties of anharmonic crystals, the self-consistent phonon theory was developed, mainly in the 1960s, for rare gas atoms and quantum crystals. We have extended this theory to investigate the properties of the equilibrium state of a crystal, including its unit cell shape and size, atomic positions and lattice dynamical properties. Using the equation-of-motion method combined with the fluctuation–dissipation theorem and the Donsker–Furutsu–Novikov (DFN) theorem, this approach was also extended to investigate the non-equilibrium case where there is heat flow across a junction or an interface. The formalism is a classical one and therefore valid at high temperatures.

The deoxyribonucleotide (DNA) molecule is a stable carrier for large amounts of genetic information and provides an ideal storage medium for next-generation information processing technologies. Technologies that process DNA information, representing a cross-disciplinary integration of biology and computer techniques, have become attractive substitutes for technologies that process electronic information alone. The detailed applications of DNA technologies can be divided into three components: storage, computing, and self-assembly. The quality of DNA information processing relies on the accuracy of DNA reading. Nanopore detection allows researchers to accurately sequence nucleotides and is thus widely used to read DNA. In this paper, we introduce the principles and development history of nanopore detection and conduct a systematic review of recent developments and specific applications in DNA information processing involving nanopore detection and nanopore-based storage. We also discuss the potential of artificial intelligence in nanopore detection and DNA information processing. This work not only provides new avenues for future nanopore detection development, but also offers a foundation for the construction of more advanced DNA information processing technologies.

Tumor staging of upper tract urothelial carcinomas (UTUCs) is relatively difficult to assert accurately before surgery. Here, we used copy number (CN) signatures as a tool to explore their clinical significance of molecular stratification in UTUC. CN signatures were extracted by non-negative matrix factorization from the whole-genome sequencing (WGS) data of 90 Chinese UTUC primary tumor samples. A validation UTUC cohort (n = 56) and a cohort from urinary cell-free DNA (cfDNA) of urothelial cancer patients (n = 94) and matched primary tumors were also examined. Survival analyses were measured using the Kaplan–Meier, and Cox regression was used for multivariate analysis. Here, we identified six CN signatures (Sig1–6). Patients with a high contribution of Sig6 (Sig6high) were associated with higher microsatellite instability level and papillary architecture and had a favorable outcome. Patients with a low weighted genome integrity index were associated with positive lymph node and showed the worst outcome. Sig6high was identified to be an independently prognostic factor. The predictive significance of CN signature was identified by a validation UTUC cohort. CN signatures retained great concordance between primary tumor and urinary cfDNA. In conclusion, our results reveal that CN signature assessment for risk stratification is feasible and provides a basis for clinical studies that evaluate therapeutic interventions and prognosis.

The identification of asymptomatic, non-severe presymptomatic, and severe presymptomatic coronavirus disease 2019 (COVID-19) in patients may help optimize risk-stratified clinical management and improve prognosis. This single-center case series from Wuhan Huoshenshan Hospital, China, included 2,980 patients with COVID-19 who were hospitalized between February 4, 2020 and April 10, 2020. Patients were diagnosed as asymptomatic (n = 39), presymptomatic (n = 34), and symptomatic (n = 2,907) upon admission. This study provided an overview of asymptomatic, presymptomatic, and symptomatic COVID-19 patients, including detection, demographics, clinical characteristics, and outcomes. Upon admission, there was no significant difference in clinical symptoms and CT image between asymptomatic and presymptomatic patients for diagnosis reference. The mean area under the receiver operating characteristic curve (AUC) of the differential diagnosis model to discriminate presymptomatic patients from asymptomatic patients was 0.89 (95% CI, 0.81-0.98). Importantly, the severe and non-severe presymptomatic patients can be further stratified (AUC = 0.82). In conclusion, the two-step risk-stratification model based on 10 laboratory indicators can distinguish among asymptomatic, severe presymptomatic, and non-severe presymptomatic COVID-19 patients on admission. Moreover, single-cell data analyses revealed that the CD8+T cell exhaustion correlated to the progression of COVID-19.

PurposeImmunotherapy is regarded as the most promising treatment for cancer. However, immune checkpoint inhibitors (ICIs) are not effective for all patients. Herein, we conducted a systematic review and meta-analysis to explore whether tumor mutational burden (TMB) can be used as a potential prognostic biomarker for cancer patients treated with ICIs.MethodsWe systematically retrieved relevant literature published in the PubMed, Embase, Web of Science, and Cochrane databases up to December 28, 2020. All cohort studies and clinical trials that reported hazard ratios (HRs) for overall (OS) and progression-free survival (PFS), as well as the corresponding 95% confidence intervals (CIs) of high and low TMB patients, were included. All statistical analyses were performed using the R software.ResultsPooled results from a total of 32 studies with 6,131 participants showed significantly increased OS (HR: 0.61, 95% CI: 0.53–0.71; P

Abstract Background The genome topology network (GTN) is a new approach for studying the phylogenetics of bacterial genomes by analysing their gene order. The previous GTN tool gives a phylogenetic tree and calculate the different degrees (DD) of various adjacent gene families with complete genome data, but it is limited to the gene family level. Result In this study, we collected 51 published complete and draft group B Streptococcus (GBS) genomes from the NCBI database as the case study data. The phylogenetic tree obtained from the GTN method assigned the genomes into six main clades. Compared with single nucleotide polymorphism (SNP)-based method, the GTN method exhibited a higher resolution in two clades. The gene families located at unique node connections in these clades were associated with the clusters of orthologous groups (COG) functional categories of “[G] Carbohydrate transport and metabolism,”, “[L] Replication, recombination, and repair” and “[J] translation, ribosomal structure and biogenesis”. Thus, these genes were the major factors affecting the differentiation of these six clades in the phylogenetic tree obtained from the GTN. Conclusion The modified GTN analyzes draft genomic data and exhibits greater functionality than the previous version. The gene family clustering algorithm embedded in the GTN tool is optimized by introducing the Markov cluster algorithm (MCL) tool to assign genes to functional gene families. A bootstrap test is performed to verify the credibility of the clades when allowing users to adjust the relationships of the clades accordingly. The GTN tool gives additional evolutionary information that is a useful complement to the SNP-based method. Information on the differences in the connections between a gene and its adjacent genes in species or clades is easily obtained. The modified GTN tool can be downloaded from https://github.com/0232/Genome_topology_network

Objective To investigate the clinical efficacy and safety of percutaneous local injection of 0.1% pingyangmycin for treatment of oral vascular malformation in children. Methods This retrospective study was conducted among 56 children with oral vascular malformation with complete clinical and follow-up data, who received treatment by percutaneous injection of 0.1% pingyangmycin between January, 2009 and December, 2015. In all the cases the dose of pingyangmycin was determined based on the size, depth and location of the tumors. The patients received the injections at the interval of 2-4 weeks, and in each case the number of the injections ranged from 1 to 16. The patients were followed up for 2 years after the last treatment to evaluate the therapeutic effects and adverse events related to the treatment. Results All the 56 children completed the whole treatment course. Forty-eight of the patients showed favorable response to the treatment, and 45 were basically cured; 7 patients failed to respond to the treatment. During the treatment, 4 patients experienced local ulcer and pigmentation; none of the patients showed severe adverse events related to the injections. The basic cure rate in these children was higher than the average rate reported in previous studies. Conclusion Percutaneous local injection of 0.1% pingyangmycin is a safe, effective and convenient treatment for oral vascular malformation in children.