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The research and development (R&D) of industrial generic technologies (IGTs) is a collaborative innovation involving many stakeholders. The key to ensure the R&D success of IGT is how to effectively mobilize various stakeholders to take a more active approach to increase the degree of joint efforts and cooperation. Considering that the degree of effort and cooperation among the stakeholders, and the commonality of IGT and the difficulty of subsequent commercialization have an important impact on its success, in this article, we exploit the thought and methods of gray-target decision model, group negotiations, and game theory to design a government-subsidies incentive mechanism. Besides, considering the government's special role in the R&D, we introduce the stakeholders’ risk preferences of IGTs and discuss the decision-making behaviors of different stakeholders under the circumstances of either cooperation or noncooperation. At the end, we confirm the rationality and validity of our model by using a real case.

BACKGROUND: The Ling sound test cannot provide the test of Chinese tone for preschool children with hearing aid and cochlear implants. OBJECTIVE: The paper tries to design a new tone test method composed of the Ling sound test and four Chinese tones to evaluate the hearing level of Chinese hearing-impaired children. METHODS: The tone identification rates of 20 cochlear implant children were statistically analyzed to verify the validity of the Ling sound test in the Chinese tone version. In addition, this paper analyzed the pronunciation characteristics of the Ling sound test in the Chongqing-accented Mandarin version of 20 subjects. RESULTS: The identification rate of Ling six sounds was more than 97.0%, the identification rate of tone was more than 81.0%, and the identification rate of vowels was 83.1%, which was higher than that of consonants 79.0%. The Ling sound test n the Chongqing-accented Mandarin version has a narrower frequency range. CONCLUSION: The results verify the effectiveness and feasibility of the Ling sound test in the Chinese tone version in the assessment of frequency range and tone identification for cochlear implant users.

In this work, we propose the stabilization of soft sea sand by an epoxy composite solidifier, which can be extremely beneficial in the fields of national defense, rescue engineering, and traffic emergency support under complex conditions. The effects of material ratio, curing time, curing temperature, and moisture content on the mechanical performance (compressive strength, bending strength, and splitting tensile strength) of solidified sea sand are investigated by indoor tests. The results indicate that the epoxy composite solidifier can rapidly enhance the mechanical performance of sea sand, thereby improving the beach trafficability and facilitating traffic emergency support. The strength of solidified sandy soil increases with the increase in curing time and temperature or with the decrease in moisture content. Furthermore, the epoxy composite solidifier exhibits good solidification capability under low temperatures and saturated moisture content. Keywords: epoxy resin; solidifier; sea sand; mechanical test

Therapeutic effects and potential mechanism of action of homogeneous polysaccharide SCP2 on AD rats.

This study evaluated the learning effects and examined the participants' perceptions of an interprofessional shared decision-making (IP-SDM) training program.This mixed-method study used a quasi-experimental pretest-posttest design in the quantitative phase and semi-structured interviews in the qualitative phase. The 6-week curriculum design, based on Kolb's experiential learning cycle, consisted of two simulated objective structured clinical examinations with standardized patients and blended teaching methods through various course modules.A total of 39 multidisciplinary healthcare personnel completed the 6-week training program, and 32 of them participated in qualitative interviews. The IP-SDM training program effectively improved the SDM process competency of the participants from the perspectives of the participants, standardized patients, and clinical teachers. The interviews illustrated how the curriculum design enhanced learning; the effectiveness results indicated improvements in learners' attitude, knowledge, skills, and teamwork.This IP-SDM training program improved multidisciplinary healthcare personnel's competency, self-efficacy, and intention to engage in IP-SDM.Applying Kolb's experiential learning cycle and blended teaching methods to develop and implement the IP-SDM training program can improve multidisciplinary healthcare personnel's knowledge, attitude, skills, and teamwork in IP-SDM.

Taking the military industry listed companies from 2010 to 2019 as a research sample, comprehensively use high-level team theory, investment decision theory, human capital theory and other related theories to deeply explore the influence mechanism of political connections on military industry enterprise innovation performance. The research results show that: for military enterprises, the politically connected characteristics of senior managers will promote the innovation performance of enterprises. Managers’ overconfidence plays a part of the mediating effect in the influence of political connections on enterprise innovation performance. At the same time, the inflow of R & D personnel has produced a negative moderating effect in the relationship between political connections and corporate innovation performance. Further research shows that, from the perspective of the level of political relevance, politically connected managers at the central level have a negative impact on corporate innovation performance. The negative moderating effect of the inflow of R & D personnel in the political connection and enterprise innovation performance is related to the political connection at the central level.

As a basic course of management disciplines, management science is the theoretical basis of various other management classification disciplines. It scientifically explains the operation rules and management methods of various organizations, and provides methodological guidance for other disciplines. In the process of management teaching, and dilute the present situation of the value guide, this paper puts forward the ideological elements into the teaching process of management teaching, through ideological elements to deepen the understanding of professional knowledge, at the same time in the process of professional knowledge of students’ ideological and moral construction, cultivate college students who have both ability and political integrity.

The line widths of broad line regions (BLRs) of AGNs are key parameters for understanding the central super massive black holes (SMBHs). However, due to obscuration from dusty torus, optical recombination lines from BLRs in type II AGNs can not be directly detected. Radio recombination lines (RRLs), with low extinction, can be ideal tracers to probe emission from BLRs in type II AGNs. We performed RRL observations for H35$\alpha$ and H36$\alpha$ toward the center of Circinus galaxy with ALMA. Narrow components of H35$\alpha$ and H36$\alpha$, which are thought to be mainly from star forming regions around the nuclear region, are detected. However, only upper limits are obtained for broad H35$\alpha$ and H36$\alpha$. Since Circinus galaxy is one of the nearest AGN, non-detection of broad RRLs in Circinus galaxy at this band tells us that it is hopeless to detect broad RRL emission in local AGNs with current facilities. Submillimetre RRLs, with flux densities that are dozens of times higher than those at the millimetre level, could be the tools to directly detect BLRs in type II AGNs with ALMA, once its backend frequency coverage has been upgraded to several times better than its current capabilities., Comment: 5 pages, 2 Figures, published in MNRAS Letters

Innovation-driven development strategy as China's national strategy, it is of strategic significance for China to form a new international competitive advantage and enhance the long-term driving force for development. This paper constructs an index system the for the evaluation of regional defense technology collaborative innovation , with eight innovation reform experimental area and cities and states as a research object, using big data technology and methods to collect index data online, and at the same time based on AHP level comprehensive evaluation and the "normalization" processing methods of network search heat value, to conduct an in-depth analysis of the development trend of national defense and national defense science and technology collaborative innovation in the region, and form a visual image display. Research results show that: in the process of coordinated development of regional defense science and technology, the pilot zone for innovation and reform in urban areas, including Beijing-Tianjin-Hebei, ChengDeMian and other aeras, are enjoying good momentum of collaborative innovation in defense science and technology. Chengdu, Mianyang and other urban defense science and technology collaborative innovation development trend is good, which provides data support for the regional defense science and technology collaborative innovation research and promote the in-depth development of defense science and technology collaborative innovation.

Bacteriocins are bacterial-derived peptides that exhibit antimicrobial activity and can be used as food preservatives. Here, using the indicator strain

Qishen granules (QSG), a Chinese herbal formula, has been widely used in the treatment of myocardial ischemic chronic heart failure (CHF) for many years, but its mechanism of action is still unclear. In this study, comprehensive metabolomics was used to investigate the underlying protective mechanisms of QSG in an isoproterenol-induced CHF rat model. A total of 14 biomarkers were identified in serum and 34 biomarkers in urine, which were mainly related to fatty acid metabolism, bile acid metabolism, amino acid metabolism, purine metabolism, vitamin metabolism, and inflammation. Finally, 22 markers were selected for quantitative analysis of serum, urine, and fecal samples to verify the reliability of the results of untargeted metabolomics, and the results were similar to those of untargeted metabolomics. The correlation analysis showed that the targeted quantitative endogenous metabolites and CHF-related indexes were closely related. QSG might alleviate myocardial inflammatory response, oxidative stress, and amino acid metabolism disorder in CHF by regulating the level of endogenous metabolites. This study revealed QSG could regulate potential biomarkers and correlated metabolic pathway, which provided support for the further application of QSG.

As a well-known traditional Chinese medicine formula, the chemical constituents of Shengxian Decoction still remain unclear due to its complexity. In this study, a multidimensional strategy based on ultra-performance liquid chromatography coupled with ion mobility spectrometry quadrupole time-of-flight mass spectrometry and informatics UNIFI platform was applied to achieve rapid and comprehensive identification of the complex composition of Shengxian Decoction. Data-independent acquisition, fast data-directed analysis, and high-definition MS

Driver status monitoring systems are a vital component of smart cars in the future, especially in the era when an increasing amount of time is spent in the vehicle. The heart rate (HR) is one of the most important physiological signals of driver status. To infer HR of drivers, the mainstream of the existing research focused on capturing subtle heartbeat-induced vibration of the torso or leveraged photoplethysmography (PPG) that detects cardiac cycle-related blood volume changes in the microvascular. However, existing approaches rely on dedicated sensors that are expensive and cumbersome to be integrated or are vulnerable to ambient noise. Moreover, their performance on the detection of HR does not guarantee a reliable computation of the HR variability (HRV) measure, which is a more applicable metric for inferring mental and physiological status. The accurate computation HRV measure is based on the precise measurement of the beat-to-beat interval, which can only be accomplished by medical-grade devices that attach electrodes to the body. Considering these existing challenges, we proposed a facial expression-based HRV estimation solution. The rationale is to establish a link between facial expression and heartbeat since both are controlled by the autonomic nervous system. To solve this problem, we developed a tree-based probabilistic fusion neural network approach, which significantly improved HRV estimation performance compared to conventional random forest or neural network methods and the measurements from smartwatches. The proposed solution relies only on commodity camera with a lightweighted algorithm, facilitating its ubiquitous deployment in current and future vehicles. Our experiments are based on 3400 km of driving data from nine drivers collected in a naturalistic field study.

Excessive apoptosis of placental trophoblast cells is considered a major cause of pre-eclampsia (PE) pathogenesis. Phosphorylation of the widely expressed cAMP response element binding protein (CREB) regulates apoptosis and may be involved in PE incidence. Low-dose aspirin (LDA) is an effective approach for preventing PE with unclear mechanisms. Thus we examined whether LDA protects against PE by inhibiting trophoblast cell apoptosis through CREB. The effects of LDA on human PE placenta, PE model rat placenta, and hydrogen peroxide (H(2)O(2))-induced HTR-8/SVneo cell apoptosis were analyzed. TUNEL assay, immunohistochemistry, Cell Counting Assay Kit-8 (CCK-8) assay, western blot, and flow cytometry assay were performed. In the placenta of human PE and rat PE models, the TUNEL index increased and was partially corrected with LDA pre-treatment. Meanwhile, decreased Bcl-2 and increased Bax expression were significantly reversed by LDA pre-treatment. In HTR-8/SVneo cells, H(2)O(2) decreased cell viability, promoted apoptosis, reduced the Bcl-2/Bax ratio, aggravated loss of mitochondrial membrane potential (MMP), increased cytoplasmic cytochrome c release, and simultaneously activated caspase-9 and caspase-3. These effects were effectively restored by LDA pre-treatment in the cells. Moreover, LDA promoted CREB phosphorylation in trophoblast cells. CREB interference further promoted apoptosis, reduced the Bcl-2/Bax ratio, and increased MMP loss. CREB interference also reversed the inhibitory effect of LDA on H(2)O(2)-induced apoptosis in HTR-8/SVneo cells. Thus, LDA was shown to inhibit trophoblast cell mitochondrial apoptosis by activating the CREB/Bcl-2 pathway, providing novel evidence for the protective mechanism of LDA in PE. Abbreviations; PE: Pre-eclampsia; LDA: low-dose aspirin; CREB: cAMP response element binding protein; ROS: reactive oxygen species; H(2)O(2): hydrogen peroxide; PBS: Phosphate-buffered saline; Bcl-2: B-cell lymphoma-2; MMP: Mitochondrial membrane potential; Cyt-c: CytochromeC.

Aim: The aim of the study was to characterize and investigate the mechanism of action of anti-hyperglycemic and anti-hyperlipidemic constitutents of Allophylus africanus. Background: Allophylus africanus P. Beauv is a medicinal plant commonly used in sub-Sahara Africa for the treatment of metabolic disorders and infectious diseases. Objectives: The objective of the study was to isolate and characterize anti-hyperglycemic and antihyperlipidemic chemical constituents from Allophylus africanus, and to investigate the mechanism of their enzymatic inhibitions. Methods: The chemical constituents were isolated using various column chromatographic techniques. The anti-hyperlipidemic and anti-hyperglycemic properties of the chemical constituents were investigated by measuring their inhibitory effects on porcine pancreatic lipase and α- glucosidase enzymes. Fluorescence quenching constants obtained from Stern−Volmer plots were used to determine the mechanisms of inhibitory action. Results: Twelve compounds, of which three were new peptide alkaloids, ethylamino asperphenamate (10), allophylane (11) and allophyline (12), were isolated. The new peptide alkaloids and asperphenamate (9) inhibited porcine pancreatic lipase in a dose-dependent manner with IC50 < 90 μM. Also, 9, 12, stigmasta-5, 22-dien-3-O-β-D-glucoside (3) and eudesmenol (5) inhibited α- glucosidase enzymes with IC50 < 165 μM, which was lower than that of standard drug, acarbose (432.16 ± 6.52 μM). From the Stern-Volmer plots, 9 and 10 indicated a static quenching, while 11 and 12 suggested the occurrence of both static and dynamic quenching mechanisms on porcine pancreatic lipase. On α-glucosidase, only 12 exhibited a concurrent static and dynamic quenching mechanism. Conclusion: The anti-diabesity compounds obtained from A. africanus established its potential for the treatment of metabolic disorders. Among the isolated compounds, three have been reported for the first time in nature while others have been reported for the first time in the plant.

Breast cancer (BC) is one of the major public health challenges worldwide. Studies that address the new evidence on trends of BC are of great importance for preventing and controlling the occurrence and development of diseases and improving health. The aim of this study was to analyze the outcomes for the global burden of disease (GBD), incidence, deaths, and risk factors for BC from 1990 to 2019, and predict the GBD of BC until 2050 to inform global BC control planning efforts. In this study, the results show that the regions with low levels of socio-demographic index (SDI) will have the largest disease burden of BC in the future. The leading global risk factor for death attributable to BC in 2019 was metabolic risks, followed by behavioral risks. This study supports the worldwide urgent need for comprehensive cancer prevention and control strategies to reduce exposure, early screening, and improve treatment to effectively reduce the GBD of BC.

With the gradual increase of international willingness to reach the carbon peak and carbon neutrality, this paper decomposes the influencing factors of China’s carbon emission changes from 2008 to 2019 using the Logarithmic Mean Divisia Index model (LMDI), and analyzes the contribution amount and rate of each influencing factor. The results found that: for the whole country, the cumulative growth of carbon emissions during the study period is about 416,484.47 (104 tons), among which the economic growth effect plays a major role in promoting, with a cumulative contribution rate of 284.16%; The increase in regulation intensity and the optimization of industrial structure, however, suppress carbon emissions well, with a cumulative contribution rate of about – 199.21% and − 64.75%, respectively, during the study period. For economic regions, the cumulative influence direction of each driver is the same as that of the whole country, while the population size effect in the northeast economic region and the regulation input effect in the eastern coastal economic region act in the opposite direction from other economic regions, and the carbon emission reduction direction of the energy intensity effect varies from one economic region to another. Accordingly, this paper proposes policy recommendations to enhance regulatory intensity, optimize industrial and energy consumption structure, implement localized emission reduction strategies, and promote synergistic emission reduction in economic zones.

Climate change has significant implications for macro-economic growth. The impacts of greenhouse gases and anthropogenic aerosols on economies via altered annual mean temperature (AMT) have been studied. However, the economic impact of land-use and land-cover change (LULCC) is still unknown because it has both biogeochemical and biogeophysical impacts on temperature and the latter differs in latitudes and disturbed land surface types. In this work, based on multi-model simulations from the Coupled Model Intercomparison Project Phase 6, contrasting influences of biogeochemical and biogeophysical impacts of historical (1850–2014) LULCC on economies are found. Their combined effects on AMT result in warming in most countries, which harms developing economies in warm climates but benefits developed economies in cold climates. Thus, global economic inequality is increased. Besides the increased AMT by the combined effects, day-to-day temperature variability is enhanced in developing economies but reduced in developed economies, which further deteriorates global economic inequality.

Background: Autoimmune glial fibrillary acidic protein astrocytic lesion （GFAP-A）is a new central nervous system autoimmune disease first described in humans at the Mayo Clinic in 2016. The diagnosis mainly depends on the IgG antibody of GFAP in cerebrospinal fluid (CSF). Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a kind of inflammatory demyelinating disease of the central nervous system in which MOG antibodies are found in serology or cerebrospinal fluid. Today, clinicians also have a certain understanding of demyelinating diseases, but the mechanism of these diseases is still not very clear, so clinical cases are still worthy of attention and summary. Case presentation: We report a case of GFAP-A and a case of Overlapping syndrome of MOG‑IgG‑associated disease and autoimmune GFAP astrocytopathy. Our cases show that the severity of GFAP-A is no less severe than that of Overlapping syndrome of MOG‑IgG‑associated disease and autoimmune GFAP astrocytopathy, but this is only a case-based guess. Conclusions: Reading the literature, we found great heterogeneity in patients with these inflammatory demyelinating central nervous system diseases, which also brings difficulties to clinical diagnosis. Therefore, we believe that when clinically suspected demyelinating diseases of the central nervous system, APQ4, MOG, GFAP, MBP, and other related antibodies should be detected at the same time to avoid missed diagnosis.

Purpose: Although gefitinib prolonged the progression-free survival (PFS) of patients with non–small cell lung cancer (NSCLC), unpredictable resistance limited its clinical efficacy. Novel predictive biomarkers with explicit mechanisms are urgently needed. Experimental Design: A total of 282 patients with NSCLC with gefitinib treatment were randomly assigned in a 7:3 ratio to exploratory (n = 192) and validation (n = 90) cohorts. The candidate polymorphisms were selected with Haploview4.2 in Hapmap and genotyped by a MassARRAY system, and the feature variables were identified through Randomforest Survival analysis. Tanswell and clonogenic assays, base editing and cell-derived tumor xenograft model were performed to uncover the underlying mechanism. Results: We found that the germline missense polymorphism rs3742076 (A>G, S628P), located in transactivation domain of FOXM1, was associated with PFS in exploratory (median PFS: GG vs. GA&AA, 9.20 vs. 13.37 months, P = 0.00039, HR = 2.399) and validation (median PFS: GG vs. GA&AA, 8.13 vs. 13.80 months, P = 0.048, HR = 2.628) cohorts. We elucidated that rs3742076_G conferred resistance to gefitinib by increasing protein stability of FOXM1 and facilitating an aggressive phenotype in vitro and in vivo through activating wnt/β-catenin signaling pathway. Meanwhile, FOXM1 level was highly associated with prognosis in patients with EGFR-mutant NSCLC. Mechanistically, FOXM1 rs3742076_G upregulated wnt/β-catenin activity by directly binding to β-catenin in cytoplasm and promoting transcription of β-catenin in nucleus. Remarkably, inhibition of β-catenin markedly reversed rs3742076_G-induced gefitinib resistance and aggressive phenotypes. Conclusions: These findings characterized rs3742076_G as a gain-of-function polymorphism in mediating gefitinib resistance and tumor aggressiveness, and highlighted the variant as a predictive biomarker in guiding gefitinib treatment.

In this paper, we develop and analyze numerical methods for high dimensional Fokker-Planck equations by leveraging generative models from deep learning. Our starting point is a formulation of the Fokker-Planck equation as a system of ordinary differential equations (ODEs) on finite-dimensional parameter space with the parameters inherited from generative models such as normalizing flows. We call such ODEs neural parametric Fokker-Planck equations. The fact that the Fokker-Planck equation can be viewed as the $L^2$-Wasserstein gradient flow of Kullback-Leibler (KL) divergence allows us to derive the ODEs as the constrained $L^2$-Wasserstein gradient flow of KL divergence on the set of probability densities generated by neural networks. For numerical computation, we design a variational semi-implicit scheme for the time discretization of the proposed ODE. Such an algorithm is sampling-based, which can readily handle the Fokker-Planck equations in higher dimensional spaces. Moreover, we also establish bounds for the asymptotic convergence analysis of the neural parametric Fokker-Planck equation as well as the error analysis for both the continuous and discrete versions. Several numerical examples are provided to illustrate the performance of the proposed algorithms and analysis.

Aromatic carboxylic acids (ACAs) may be as transformed key metabolites via gut microbiome for playing better pharmacological effects. However, it's rare to achieve high-specificity, high-sensitivity, and high-throughput detection simultaneously, especially, for tracing trace ACAs in gut microbiome. In this work, firstly, a novel dual-template and double-shelled molecularly imprinted 96-well microplates (DDMIPs) was designed and amplified signal for p-hydroxybenzoic acid (PBA) and 3,4,5-trimethoxycinnamic acid (TMA). Additionally, the DDMIPs and a stable isotope labeling derivatization (SILD) method combined with the ultra-high performance liquid chromatography triple quadrupole tandem mass spectrometry (UHPLC-TQ MS) was firstly stepwise integrated, achieving high-effective, high-sensitive, and high-throughput study of gut microbiome metabolism. The whole strategy showed lower limits of detections (LODs) up to 1000 folds than the traditional method, and revealed a more real metabolism-time profile of PBA and TMA by 3-step signal amplification. The platform also laid the foundation for fast, simple, high-selective, high-effective, and high-throughput metabolism and pharmacological research.

Chrysanthemum is a kind of herb that can be used for both medicine and food. Although it has been shown to affect the redox damage of the lens, but the mechanism of action has not been systematically studied. This study identified the chemical profile of Fubai Chrysanthemum. Meanwhile, network pharmacology and the enrichment of the Kyoto Encyclopedia of Genes and Genomes pathway were combined to investigate the substance basis of Fubai Chrysanthemum for preventing cataract. The aqueous extracts of Fubaiju mainly contained 39 compounds. Compared with Gongju, Jinsiju, and wild chrysanthemum, Fubai Chrysanthemum showed a higher scavenging rate of 1,1-diphenyl-2-picrylhydrazyl free radicals and a higher content of total flavonoid. Fourteen chemical differences in four kinds of chrysanthemum were found based on principal component difference analysis. Pathway enrichment analysis showed that the main mechanisms of Fubai Chrysanthemum for preventing cataract were affecting the oxidative stress process and regulating cell growth and metabolism. Eventually, 11 key targets of Fubai Chrysanthemum for cataract prevention were identified. The strategy provided a better understanding of the chemical profile of Fubai Chrysanthemum and elucidated that its higher flavonoid content plays an important role in preventing cataract through antioxidant action and regulating cell growth.