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Identifying factors associated with transitioning from mild cognitive impairment (MCI) to dementia due to Alzheimer’s disease (AD dementia) or dementia due to any cause (all-cause dementia) may inform economic assessments of disease and early care planning. A multivariate logistic regression approach identified potential predictors of progression to AD dementia or all-cause dementia in individuals with MCI or cognitive impairment (CI). Eligible patients and variables of interest were identified using claims data from the Medicare Advantage Patient Database, by Optum. Predictors of an AD dementia diagnosis included age (odds ratio [OR], 1.71) and use of antipsychotics (OR, 2.50) and hypertension medication (OR, 1.25). Medication use for comorbid conditions was a better indicator of risk than comorbidity coding. Diagnosis of CI by a neurologist increased the odds of an AD dementia diagnosis. Possible protective factors for progression included the use of anxiolytics (OR, 0.76), inpatient status at time of diagnosis (OR, 0.49), and a history of stroke (OR, 0.87). None of these factors differentiated AD dementia from all-cause dementia. Identifying patients at risk for AD dementia allows for improved system-level planning to guide policy and optimize economic and clinical outcomes for patients, caregivers, and society.

The experience of developed countries shows that the development of the road network and transport infrastructure determines the intensity of economic ties and is one of the most important conditions for the development of the state’s economy. Optimization of the composition and production technology of asphalt concrete mixture – the basis of paved roads, is of great importance, both from an economic and environmental point of view. The production of asphalt concrete mixture directly (during the production process at asphalt concrete plants) and indirectly (during delivery from the plant to the place of installation) determines the energy costs for the production of asphalt concrete. At asphalt-concrete plants the specific energy consumption per ton of hot asphalt concrete mixture varies from 0.3 to 0.7 GJ. The range in energy costs is large. This situation indicates the presence of a significant energy-saving potential of asphalt concrete mixture thermal technology. The exergy analysis of technical systems proposed in this paper, which are operated in the asphalt concrete mixture production processes, makes it possible to judge the efficiency of energy use in their thermal units. This approach is expedient not only in the primary production of asphalt concrete mixture, but also for more environmentally friendly, energy- and resource-saving production processes for the operation of equipment during the regeneration of road asphalt concrete.

Supplemental Digital Content is available in the text, Background: Clinical outcomes of undifferentiated arthritis (UA) are diverse, and only 40% of patients with UA develop rheumatoid arthritis (RA) after 3 years. Discovering predictive markers at disease onset for further intervention is critical. Therefore, our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development. Methods: We performed a prospective, multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals. Clinical and serological parameters were obtained at recruitment. Follow-up was undertaken in all patients every 12 weeks for 2 years. Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression. Results: A total of 234 patients were recruited in this study, and 17 (7.3%) patients failed to follow up during the study. Among the 217 patients who completed the study, 83 (38.2%) patients went into remission. UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs. 16.8%, χ2 = 8.228, P = 0.008), anti-cyclic citrullinated peptide (CCP) antibody-positivity (66.7% vs. 10.7%, χ2 = 43.897, P

Melatonin (MEL) has been demonstrated to exert a protective effect against subarachnoid hemorrhage (SAH), and nitric oxide (NO) has been shown to play an important role in the pathogenesis of vasospasm. This study aims to explore the underlying molecular mechanisms of MEL in the control of vasospasm following SAH. MEL administration attenuates SAH-induced vasospasm and neurobehavioral deficits. Expressions of H19, eNOS, and miR-675 are low in the SAH group, while expressions of miR-138 and HIF1α are high in the SAH group. Also, MEL treatment upon SAH rats completely restores the dysregulation of H19, eNOS, miR-675, miR-138, and HIF1α to their normal levels. Moreover, MEL dose dependently increases the luciferase activity of H19 promoter and hence the expression of H19. Additionally, H19 directly targets miR-675 and miR-138 to increase miR-675 expression and inhibit miR-138 expression. As virtual target genes of miR-675 and miR-138, respectively, HIF1α and eNOS are also regulated by the treatment with MEL. In particular, MEL treatment increases the expression of miR-675 and eNOS level while decreasing the expression of miR-138 and HIF1α in a dose dependent manner. Our study found that MEL ameliorates post-SAH vasospasm by regulating the expression of eNOS and HIF1α via the H19/miR-138/eNOS/NO and H19/miR-675/HIF1α signaling pathways.

Food logo detection plays an important role in the multimedia for its wide real-world applications, such as food recommendation of the self-service shop and infringement detection on e-commerce platforms. A large-scale food logo dataset is urgently needed for developing advanced food logo detection algorithms. However, there are no available food logo datasets with food brand information. To support efforts towards food logo detection, we introduce the dataset FoodLogoDet-1500, a new large-scale publicly available food logo dataset, which has 1,500 categories, about 100,000 images and about 150,000 manually annotated food logo objects. We describe the collection and annotation process of FoodLogoDet-1500, analyze its scale and diversity, and compare it with other logo datasets. To the best of our knowledge, FoodLogoDet-1500 is the first largest publicly available high-quality dataset for food logo detection. The challenge of food logo detection lies in the large-scale categories and similarities between food logo categories. For that, we propose a novel food logo detection method Multi-scale Feature Decoupling Network (MFDNet), which decouples classification and regression into two branches and focuses on the classification branch to solve the problem of distinguishing multiple food logo categories. Specifically, we introduce the feature offset module, which utilizes the deformation-learning for optimal classification offset and can effectively obtain the most representative features of classification in detection. In addition, we adopt a balanced feature pyramid in MFDNet, which pays attention to global information, balances the multi-scale feature maps, and enhances feature extraction capability. Comprehensive experiments on FoodLogoDet-1500 and other two benchmark logo datasets demonstrate the effectiveness of the proposed method. The FoodLogoDet-1500 can be found at this https URL., This paper has been accepted to ACM MM 2021. The FoodLogoDet-1500, see https://github.com/hq03/FoodLogoDet-1500-Dataset

Lung cancer remains the leading cause of cancer mortality because of its metastatic potential and high malignancy. The discovery of new applications for old drugs is a shortcut for cancer therapy. We recently investigated the antitumor effect of digoxin, a well-established drug for treating heart failure, against nonsmall cell lung cancer A549 and H1299 cells. Digoxin inhibited the proliferation and colony-forming ability of the two cell lines and arrested the cell cycle at the G0/G1 phase in A549 cells and the G2/M phase in H1299 cells. Mitochondria-mediated apoptosis was induced in A549 cells but not in H1299 cells after treatment with digoxin. Moreover, digoxin inhibited the migration, invasion, adhesion and epithelial–mesenchymal transition of A549 and H1299 cells. Autophagy was induced in both cell lines after treatment with digoxin, with an increase in autophagosome foci. In addition, digoxin inhibited the phosphorylation of Akt, mTOR and p70S6K, signaling molecules of the PI3K/Akt pathway that are known to be involved in tumor cell survival, proliferation, metastasis and autophagy. Our findings suggest that digoxin has the potential to be used for therapy for human nonsmall cell lung cancer, but further evidence is required.

Shaobin Dong,1 Nicole Tsao,2 Qiang Hou,1 Duygu Bozkaya,1 Bart P Leroy3– 5 1Value and Access, Biogen, Cambridge, MA, USA; 2Medical Health Outcomes and Research, Biogen, Cambridge, MA, USA; 3Department of Ophthalmology & Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium; 4Department of Head & Skin, Ghent University, Ghent, Belgium; 5Division of Ophthalmology & Center for Cellular & Molecular Therapeutics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USACorrespondence: Shaobin DongValue and Access, Biogen, 225 Binney Street, Cambridge, MA, 02142, USATel +1-857-331-5246Email shaobin.dong@biogen.comPurpose: Choroideremia is a progressive, inherited retinal dystrophy that leads to blindness. This study of choroideremia addresses health resource utilization (HRU) and costs from a US payor perspective using insurance claims data. The retrospective analysis used data between January 2013 and December 2018 from the IBM MarketScan Commercial, Medicare Supplemental, and Multi-State Medicaid Databases.Patients and Methods: Patients having ≥ 1 claim with an International Classification of Diseases, Ninth or Tenth Edition, diagnostic code for choroideremia (363.55/H31.21) were included; a control group was matched 3:1 to the choroideremia group. Patients were followed for ≥ 6 months. All-cause HRU and costs were compared between cohorts using generalized linear models adjusted for Charlson Comorbidity Index.Results: There were 199 and 597 patients in the choroideremia and control groups, respectively; the choroideremia group had a higher mean baseline Charlson Comorbidity Index (0.47 vs 0.26). The choroideremia group had a significantly greater mean number of hospital admissions (0.09 vs 0.06), outpatient visits (22.33 vs 11.22), and emergency department visits (0.41 vs 0.26) per patient per year than the control group. The choroideremia cohort had higher all-cause total annualized costs than the control cohort ($15,372 vs $9285), primarily driven by outpatient visits ($8306 vs $4702). This trend was observed across age categories, particularly among patients aged 20 to 44 years (choroideremia, $14,544 vs control, $5953).Conclusion: The choroideremia group had higher all-cause HRU and total costs versus the control group. These findings provide economic context around HRU associated with choroideremia and help assess the potential impact of novel treatments.Keywords: vision loss, inherited retinal dystrophy, claims data, health economics

A highly efficient cinchona alkaloid-derived squaramide catalysed asymmetric Michael/cyclization cascade reaction of 4-arylmethylidene-2,3-dioxopyrrolidines with 2-isothiocyanato-1-indanones was successfully developed. This protocol provides an efficient and mild access to indanone-derived spiropyrrolidone scaffolds containing three contiguous stereocenters with two spiroquaternary stereocenters in excellent yields (up to 99%) with high enantio- and diastereoselectivities (up to 99% ee and up to >20 : 1 dr). This method provides an economical and practical approach for the asymmetric synthesis of medicinally relevant molecules.

Chemical modification of a specific amino acid residue on peptides represents an efficient strategy to improve their pharmacokinetics and facilitates the potential to achieve post-synthetic diversification of peptides. Herein, we reported the first Pd-catalyzed late-stage ortho-olefination of Tyr residues on peptides with high chemo- and site-selectivity, by employing the easily attached and removable silanol as a bifunctional protecting group and directing group. Up to hexapeptides with variation on amino acid sequences or locations of the Tyr residue and different olefins were compatible with this protocol, which enriched the chemical toolbox for late-stage modification via C(sp2)–H functionalization. Furthermore, the orthogonal protection strategies of Tyr were also developed and could be applied to SPPS., Efficient Pd-catalyzed ortho-olefination of Tyr residues by employing silanol as a directing group with high chemo- and site-selectivity was developed. Orthogonal protection strategies were also successfully applied to SPPS.

Nickel–cobalt oxide has been given more attention to being used as the supercapacitor's electrode materials due to its two-dimensional layered structure, good electron conductivity, and excellent stability. In this work, NiCo2O4 nanosheets were successfully prepared by the simple solvothermal reaction and the thermal treatment process. Under the three-electrode system, it exhibits a maximum specific capacitance of 978 F/g at 1.5 A/g and good cycle stability. Meanwhile, a freestanding of partially reduced graphene oxides/carbon nanotubes (PRGO/CNTs) film was obtained by the vacuum filter and solvothermal methods, which can provide a wide potential window of − 1 ~ 0 V and a maximum specific capacitance of 236 F/g at 0.5 A/g. Finally, an asymmetric supercapacitor of PRGO/CNTs//NiCo2O4 was assembled, which exhibits good electrochemical performance, such as specific capacitance of 82 F/g at 0.5 A/g, energy density of 18.8 Wh/kg at 0.32 kW/kg, and 99.5% of capacitance retention after 5000 cycles at 5 A/g. This test results reveal that PRGO/CNTs//NiCo2O4 ASC has great potential for practical application in energy storage systems.

Nowadays, the members in a supply chain are seen as an integrity. In order to maximize the supply chain profit, the authors consider a contract of buyback. In this article, they focus on a single manufacturer and a single retailer in the supply chain. In order to match the market demand, a new perspective is introduced into the buyback contract model. By comparing the predicted demand of the manufacturer and the retailer with the real demand, they will obtain four quadrants about the difference of the market demand forecasts. By combining the profit models with different market demand forecasts in the four quadrants, the closed-form optimal market model is created. The solutions of the optimal price and the optimal quantity under the centralized mode, non-contract decentralized mode and buyback contract mode are compared. The authors find that the non-contract decentralized mode model cannot successfully coordinate the supply chain, while the buyback contract mode allows for the coordination of the supply chain and the generation of more profit from the supply chain. From this new perspective of the supply chain contract, a reasonable result can be obtained. Numerical examples are provided to illustrate the results, with analysis conducted on the model.

Purpose The authors consider a dynamic emission-reduction technology investment decision-making problem for an emission-dependent dyadic supply chain consists of a manufacturer and a retailer under subsidy policy for carbon emission reduction. The consumers are assumed to prefer to low-carbon products and formulate a supply chain optimal control problem. Design/methodology/approach The authors adopt differential game to analyze investment strategies of cost subsidy coefficient with respect to vertical incentive of a manufacturer and a retailer. A comparison analysis under four different decision-making situations, including decentralized decision-making, centralized decision-making, maximizing social welfare, is obtained. Findings The results show that the economic benefit and environmental pressure have a win–win performance in centralized decision-making. In four different game models, equilibrium strategies, profits and social welfare show changing diversity and have a consistent development trend as time goes on. Research limitations/implications The authors estimate the demand function is a linear function in this paper. According to the consumers’ preference to low-carbon products, consumer’s awareness meets the law of diminishing marginal utility like advertising goodwill accumulation. The carbon-sensitive coefficient might be a quadratic expression, which will complicate the problem and be consistent with reality. Practical implications It captures that there is a necessity to strengthen cooperation and exchange of carbon emission technology among the enterprises by simulation of different decision-makings when government granted cost subsidy. Social implications The results provide significant guidelines for the supply chain to make decision-makings of emission-reduction technology investment and relevant government departments to determine emission subsidies costs. Originality/value An endogenous subsidies coefficient is produced by the social welfare function. Distinguished from previous study, it also considered the influences of carbon emission trade policy and consumer preference.

Bulk samples of K doping K2xFeTe1-xSx with x = 0.07, 0.1, 0.2, 0.3 are successfully prepared by using easy-to-use stable compound K2S as the reactant. The lattice constant calculated from X-ray diffraction patterns indicate that K ions enter the Fe-Te-S layers. K doping is beneficial enhance the superconductivity transition temperature from the R-T curves. The apparent diamagnetic signal is observed in M-T curves when the content of K is smaller than 0.1. However, differential curves (dM/dT) in K-rich samples appear sharp slope mutations, which means that the Meissner effect signal is covered by the increased excess ferromagnetic ions. The number of excess Fe magnetic ions is proportional to K content, which may play an important role in determining the superconductivity.

To improve the ineluctable agglomeration and weak inherent conductivity of MgAl2O4 electrode materials, MgAl2O4/rGO composite is synthesized by a facile method and it shows large specific surface area and enhanced conductivity. Its particular framework can availably hold back the aggregation of MgAl2O4 and restacking of rGO, and accelerate reversible redox reactions. The MgAl2O4/rGO composite shows a specific capacity of 536.6 F/g at 1 A/g (257.3 F/g at 40 A/g) and retains 96.9% after 10,000 cycles at 5 A/g. An asymmetric supercapacitor is developed with MgAl2O4/rGO composite and activated carbon. An energy density of 16.2 Wh/kg is obtained at a power density of 400 kW/kg. Additionally, this device has successfully lighted up a LED, demonstrating its promising application in energy storage.

Polycrystalline samples of Sn/FeTe0.8S0.2 with weight ratio x (Sn: FeTe0.8S0.2) = 0%, 3%, 5%, and 7% were successfully synthesized. Morphological characterizations of the samples indicate that introducing Sn is beneficial for grain growth, thus contributing to enhancement of superconductivity. In particular, the x = 3% sample exhibits a sharp superconducting transition and $$ T_{\text{c}}^{\text{zero}} $$ is increased by about 3 K based on R–T curves. The low-melting-point material, Sn, is proposed to have two roles. One role is acting as the adhesive to combine the adjacent particles at the melting temperature of Sn, which is of benefit for improving the $$ T_{\text{c}}^{\text{zero}} $$ of the superconductivity. The other role is acting as the dopant in the tetragonal phase, which is of benefit for improving the $$ T_{\text{c}}^{\text{onset}} $$ of the superconductivity. This proposal may provide a new strategy for improving the superconductivity in other superconductors.

Comparative analyses are adopted to examine the influences of Cl− on the degradation of the film on Alloy 690TT in high-temperature water. According to the results of surface analyses and TEM, the composition and structure of the oxide film formed in a chloride solution are determined. Unlike the duplex layer oxide film formed on the sample in pure water, a thinner and monolayer Cr-rich oxide scale with several little corrosion pits on the surface is formed, which is closely related to the adsorption of Cl− ions due to their affinity to material surface and the selective dissolution of Ni-rich oxides.

The molecular of scaffold of thiazole orange has a number of merits for being as a fluorescent dye with tailor-made structure advancement for many useful applications. Structural modification based on 1-methylquinolinium moiety of thiazole orange is able to induce critical effects on fluorescent signal discrimination ability towards certain secondary or tertiary DNA structures. The electronic effect of the substituent on both molecular signaling and binding preference were investigated in the present study. We systematically compared the structural influence on the fluorescence signaling and binding preference towards nucleic acids in vitro through the addition of a number of substituent groups including p-methylstrylyl, p-hydroxylstyryl, p-chlorostyryl, p-bromostyryl, p-fluorostyryl, and (p-fluorobenzyl)-1,3-butadien-1-yl. The dyes synthesized were investigated with 19 nucleic acids for their interaction kinetics and fluorescent signal response with fluorescence titration experiments. The experimental results indicate that both the electronic effect and the molecular size of the dyes show significant influence on achieving higher binding affinity and fluorescent signal discrimination for G-quadruplex DNA. In addition, the dye with the introduction of a p-fluorostyryl substituent exhibits excellent linear relationship of the enhanced signal with respect to the concentration of telo21 DNA in vitro. The limit of detection (LOD) obtained was found to be 9 nM, which is much better than other analogues under the same conditions.

In this paper, artificial Intelligence (AI) algorithm is used in the Rietveld refinement process instead of the human decision. The program, PowderBot, is developed based on Fullprof engine, which proves the effectiveness of AI in Rietveld refinement. In this program, the decision making in refinement process is modelled as a Markov decision process (MDP), and solved by a reinforcement learning algorithm. PowderBot is designed to be a self-learning system capable of conducting structure refinement without human intervention. The program has already been successfully applied to Rietveld refinements. We hope this paper will encourage more Rietveld programs become more intelligent by the help of AI algorithm.

Single-cell RNA sequencing and transcriptome analysis enable novel discovery and precise characterization of new cell types and states, which improves the understanding of the cellular context of tumorigenesis. Herein, we applied this powerful approach to analyze 368 single cells from three esophageal squamous cell carcinoma (ESCC) and two esophageal adenocarcinoma (EAC) tumors. Using inferred copy number variation analysis, we successfully distinguished carcinoma cells from heterogeneous cellular populations, identifying gene signatures and crucial cancer-related signaling pathways related to ESCC and EAC. In particular, we found that NOTCH signaling was exclusively activated in ESCC, but not in EAC. ESCC tumors with higher NOTCH activity were associated with significantly worse survival rates than those with lower NOTCH activity. Collectively, this study revealed that ESCC and EAC are distinct in terms of cellular transcriptome profiles, which leads to a wide range of intratumoral cellular heterogeneity. The findings suggest that different therapeutic strategies that target the differences between two types of esophageal cancers are required, guiding cancer-specific future drug development.

New fluorescent dyes derivatized on a classical thiazole orange framework are able to show unexpectedly strong interaction signal and unusual binding selectivity with different structures of nucleic acid, particularly when bound with double-stranded DNA or G-quadruplex DNA. The present study reveals that these small binding ligands simply bearing an additional amino side group on its parent molecule of thiazole orange have almost no background fluorescence in solution. Conversely, they are able to produce an extremely strong yellow emission signal upon interaction with targeting nucleic acids in live cells. The induced fluorescence intensity was approximately 10–15 times stronger than that of thiazole orange. The dyes are therefore excellent fluorescent stains for bio-sensing and bio-imaging applications. It is particularly suitable for fluorescence microscopy experiments requiring very low working concentration (0.25 μM or less) targeting nucleic acids. This was demonstrated using pu27 G-quadruplex DNA, which has a low limit of detection (LOD = 3–4 nM) while thiazole orange was much higher (LOD = 48.7 nM) under the same conditions. In addition, it was found that structural modification on the quinolinium scaffold of thiazole orange was less effective than modification on the benzothiazole moiety. The findings of the present study provide important information for structural advancement of small molecules based on the widely used thiazole orange skeleton, resulting in analogues that are able to achieve higher sensitivity and selectivity for targeting at a specific class of nucleic acids. Computational docking studies were also conducted to illustrate the interaction behaviors of the dyes with different DNA structures.

For some infectious diseases, such as herpes and tuberculosis, there is incomplete recovery and relapse. These phenomena make them difficult to control. In consequence of this status, an SEIRS epidemic model with incomplete recovery and relapse on networks is established and the global dynamics is studied. The results show that when the basic reproduction number R 0 1, the endemic equilibrium is globally asymptotically stable. In addition, in consideration of vaccination control strategy, an SVEIRS model is introduced and the optimal control is solved. At last, the theoretical results are illustrated with numerical simulations.

Word embedding representation has been a research hot spot in the field of computer vision and natural language processing. The semantic quality of representation severely affects the effects of machine translation and image caption. The key factors affecting the quality of word embedding representation are capture of contextual semantics and solution of the problem of polysemy. In this paper, the principles of the current mainstream word embedding representation methods were explored, such as sparse representation (One-Hot), static representation (Word2Vec, GloVe), dynamic representation (ELMo, BERT) representation and based on position information (NN.Embedding-Position Embedding). The impact of those word embedding representations on image caption task was researched attentively. And those representations methods were compared experimentally using the MSCOCO data based on the same image caption model. The pros and cons of these methods were judged according to the accuracy and richness of the extracted label data. Experimental results show that the BERT model representation with dynamic bidirectional semantics has the best performance in image caption tasks, but it requires longer training time. The NN.Embedding representation has the second best image semantic description effect, and its training speed is the fastest.

Introduction: Severe cerebral edema further compromises survival and functional outcomes in patients suffering from large hemispheric infarction (LHI). This study aims to compare the healthcare resource use and costs during the acute hospitalization and post-discharge, in a cohort of US patients with possible LHI with and without cerebral edema (CED). Methods: Using IBM MarketScan Commercial, Medicaid, and Medicare databases (2016Q1-2018Q4), a cohort of patients aged 18-85 were identified using ICD10 codes for hospitalization due to occlusion of the carotid or middle cerebral arteries, which are most closely associated with LHI. We classified patients with ICD10 codes G93.5 (compression of brain), G93.6 (cerebral edema), or a craniectomy procedure as having had CED. In addition to the inpatient resource use and outcomes, annualized frequency of resource utilization and costs during the follow-up period were reported in those who survived and continued to be enrolled in their health plan post-index hospitalization. Logistic regression was used to estimate the odds ratio of mortality, generalized linear models for mean in healthcare utilization and costs between those with and without CED, adjusting for age, sex, and comorbidity. Results: Of the 7,336 commercial, 1,946 Medicaid, and 5,015 Medicare patients with possible LHI, we found 7.8%, 6.9%, and 4.3% had CED, respectively. Those with CED had higher length of stay, mortality, and costs during the index hospitalization across the populations examined (Table). CED was also consistently associated with higher post-discharge resource utilization and costs in the commercially-insured population (Table). Conclusions: This real-world evidence from private and public health plans highlights the substantial clinical and economic burden during the index hospitalization and post-discharge in patients who develop cerebral edema after LHI.

Qiang Hou,1,2,* Zhenzhen Jiang,2,* Ziwei Li,2 Mingfeng Jiang1,2 1Department of Clinical Laboratory, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, 320000, People’s Republic of China; 2Cancer Research Institute, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, 320000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingfeng JiangDepartment of Clinical Laboratory, Hangzhou Cancer Hospital, 34# Yan-Guan Street, Shang-Cheng District, Hangzhou, Zhejiang, 320000, People’s Republic of ChinaEmail wounding110@126.comIntroduction: Esophageal squamous cell carcinoma (ESCC) is often resistant to radiotherapy, likely due to sub-clones that survive and repopulate in the tumor. The analysis of genomic sequencing data related to radiotherapy will provide a better understanding of the intratumoral heterogeneity and genetic evolution of ESCC during radiotherapy.Methods: We analyzed whole-exome sequencing data from pre- and post-irradiation ESCC patients at single-cell and bulk levels in public datasets. We investigated the gene functions involving radioresistance in ESCC cell lines. Furthermore, we established gene knockdown cell lines and explored the transcriptional alterations induced by RNA interference (RNAi) of these genes in KYSE-150 ESCC cell line.Results: We identified three candidate genes related to radioresistance: AHNAK2, EVPL and LAMA5. Knockdown of AHNAK2 and EVPL genes led to increased radioresistance in ESCC cell lines, but not LAMA5. The transcriptome analysis indicated that these genes may regulate the expression of interleukins, interleukin receptors and chemokines by inhibiting the NF-κB and TNF signaling pathways in radioresistant ESCC cells, thereby suppressing their immune response.Conclusion: These data may provide new therapeutic strategies by targeting general ESCC radioresistance-related genes, which may eventually help the development of targeted therapies.Keywords: esophageal squamous cell carcinoma, radiotherapy, TNF signaling, NF-κB signaling

Highlights • In this work a non-autonomous SIS network model is developed and analyzed. • The transmission rate is periodic to study impacts of the heterogeneity networks and seasonal diseases. • There exists a unique periodic solution which is globally asymptotically stable. • The heterogeneity is important in accelerating disease spreading and increasing the amplitude of solution., Seasonal forcing and contact patterns are two key features of many disease dynamics that generate periodic patterns. Both features have not been ascertained deeply in the previous works. In this work, we develop and analyze a non-autonomous degree-based mean field network model within a Susceptible-Infected-Susceptible (SIS) framework. We assume that the disease transmission rate being periodic to study synergistic impacts of the periodic transmission and the heterogeneity of the contact network on the infection threshold and dynamics for seasonal diseases. We demonstrate both analytically and numerically that (1) the disease free equilibrium point is globally asymptotically stable if the basic reproduction number is less than one; and (2) there exists a unique global periodic solution that both susceptible and infected individuals coexist if the basic reproduction number is larger than one. We apply our framework to Scale-free contact networks for the simulation. Our results show that heterogeneity in the contact networks plays an important role in accelerating disease spreading and increasing the amplitude of the periodic steady state solution. These results confirm the need to address factors that create periodic patterns and contact patterns in seasonal disease when making policies to control an outbreak.

Summary: Anterior segment dysgenesis is often associated with cornea diseases, cataracts, and glaucoma. In the anterior segment, the ciliary body (CB) containing inner and outer ciliary epithelia (ICE and OCE) secretes aqueous humor that maintains intraocular pressure (IOP). However, CB development and function remain poorly understood. Here, this study shows that NOTCH signaling in the CB maintains the vitreous, IOP, and eye structures by regulating CB morphogenesis, aqueous humor secretion, and vitreous protein expression. Notch2 and Notch3 function via RBPJ in the CB to control ICE-OCE adhesion, CB morphogenesis, aqueous humor secretion, and protein expression, thus maintaining IOP and eye structures. Mechanistically, NOTCH signaling transcriptionally controls Nectin1 expression in the OCE to promote cell adhesion for driving CB morphogenesis and to directly stabilize Cx43 for controlling aqueous humor secretion. Finally, NOTCH signaling directly controls vitreous protein secretion in the ICE. Therefore, this study provides important insight into CB functions and involvement in eye diseases.

Computerized systems and software, which allow optimizing and planning the processes of production, storage, transportation, sale, and distribution of goods, have emerged in the industry. Scheduling systems, in particular, are designed to control and optimize the manufacturing process. This tool can have a significant effect on the productivity of the industry because it reduces the time and cost through well-defined optimization algorithms. Recently, the applicability of blockchain technology has been demonstrated in scheduling systems to add decentralization, traceability, au-ditability, and verifiability of the immutable information that this technology provides. This is a novel contribution that provides scheduling systems with an additional layer of security. With the latest version of Hyperledger Fabric, the appropriate levels of permission and policies for access to information can be established with significant levels of privacy and security, which prevent malicious actors from trying to cheat or abuse the system. Different alternatives exist to manage all processes associated with the operation of a blockchain network, and among them, providers of blockchain as a service have emerged. Chainstack stands out for its simplicity and scalability features to deploy and operate a blockchain network. Our goal in this work is to create a solution for secure storage of and access to task-scheduling scheme on the consortium blockchain and inter-planetary file system as a proof of concept to demonstrate its potential and usability.

The catalytic asymmetric Mannich-type reaction of 3-hydroxy/3-aminooxindoles with 2-aminoacrylates to afford oxindole-derived acyclic amino acid derivatives bearing vicinal tetrasubstituted stereocenters is reported. (DHQ)

Climate change and greenhouse gas emission reduction have become common concerns. Carbon trading systems and low-carbon cost subsidies are important emission reduction measures. Impacts of a combination of the two policies on micro-supply chain emission-reduction technology investment have become a focal research area. This paper: (1) constructs an investment game model based on cost-sharing coordination under a cost subsidy between manufacturers and retailers, (2) examines the equilibrium strategy and optimal results according to the interests and game relationships of each stakeholder, and (3) explores the effectiveness of supply chain enterprise behavior based on cost-sharing coordination under the cost subsidy. This paper uses a numerical simulation method to compare the path evolution under different scenarios and to analyze the sensitivity of parameters, identifying the influence of various parameters on the general structure and pathways. The study finds that the cost subsidy policy has a regulatory effect on enterprise emission reduction investment and enterprise profit under a carbon trading system, and the difference caused by the regulation effect is enhanced over time. The study also shows that the dynamic path of each parameter strengthens over time.

We report the first highly enantio- and diastereoselective three-component Povarov reaction between anilines and aldehydes catalyzed by a chiral amine catalyst. A wide variety of substituted tetrahydroquinolines were obtained with moderate to good yields and excellent enantioselectivity and diastereoselectivity (up to 99% ee and >95:5 dr) under the reaction conditions. Furthermore, the reaction intermediates could be efficiently converted to other valuable building blocks.

One-dimensional Si

The relationship between grain boundaries (GBs), carbides and stress corrosion cracking (SCC) of Alloy 690TT is investigated by immersion experiments using reverse U-bent specimens in a high temperature alkaline solution containing lead. The microstructures of blank samples and reverse U-bents are analyzed by scanning electron microscope with electron back scattering diffraction and transmission electron microscope. Detailed analyses indicate that Σ3 coherent twin boundaries are less susceptible to SCC than random high angle grain boundaries (RHGBs) due to the combined effect of carbides and GBs. A clear correlation and mechanism understanding relating GB character, carbide and susceptibility to SCC is established.

Purpose The majority (70%) of the esophageal squamous cell carcinoma (ESCC) cases in the world occur in China, where radiation therapy is the most common treatment. Yet the majority of ESCC patients still relapse. Methods and Materials To better understand the genetic basis of radiation therapy resistance for ESCC, we performed longitudinal, whole-exome sequencing throughout radiation therapy on 42 patient tumor samples, including single-cell whole-exome sequencing for 147 cells for 2 patients. Results Significant allelic changes were observed during clinical irradiation, with 42 recurrent radioresponsive genes (sensitive and resistant) identified in multiple patients, including NOTCH1, MAML3, CDKN2A, NFE2L2, GAS2L2, OBSCN and TP53, with the last 3 genes implicated as radioresponsive in both bulk and single-cell whole-exome sequencing. Most (37/42) radioresponsive genes showed regional variegation in both radioresistant and radiosensitive mutations, with a paucity of resistant-only mutations (2.5%). A subset of sensitive mutations in 10 genes and resistant mutations in 18 genes defined a significantly improved prognosis and the shortest time for locoregional recurrence, respectively, indicating possible clinical utility. We also confirmed these significant mutational signatures in orthogonal Cancer Genome Atlas ESCC cohorts. Conclusions Overall, our results quantify the allelic shifts underlying radioresponse in bulk and single-cell ESCC exomes for the first time, provide a temporal resolution to such mutational dynamics, and offer new therapeutic target genes and loci for esophageal and potentially other cancers.

In this work, the hybrid nanostructures composed of Ni-Co hydroxide, reduced graphene oxide (rGO) and carbon nanotubes (CNTs) are successfully synthesized and used as a self-supported electrode for supercapacitors. It is found that the hybrid shows a big capacity of 1093 F g−1, excellent rate capability, and superior cycle life (100% capacity maintain after 5000 cycles). One asymmetric supercapacitor (ASC) is developed using Ni-Co hydroxide/rGO/CNTs as positive material and active carbon as negative material. This ASC displays a maximum energy density of 34.7 Wh kg−1 at a high power density of 1.55 kW kg−1 and still keeps 20.7 Wh kg−1 at 15.5 kW kg−1. Moreover, it displays remarkable cycle life with 112.8% capacity retention after 10000 cycles. Such asymmetric supercapacitor demonstrates great potential for practical application in energy storage devices.

Vanadium oxides (V2O5) have been intensely investigated for advanced supercapacitors due to its extensive multifunctional properties of typical layered structure and multiple stable oxide states of vanadium in its oxides. In this study, V2O5 nanosheets are synthesized via V2O5 xerogel solvothermal reaction in ethanol solvent at 200 °C for 12 h. The V2O5 nanosheets facilitate the easy accessibility of ions and can provide more area available for electrochemical reactions. We have achieved the highest specific capacitance of 298 F/g and good rate discharge for V2O5 electrodes. Notably, the capacitance still retains a high retention rate of 85% after 10,000 cycles at 200 mV/s. Furthermore, asymmetric supercapacitors is assembled based on V2O5 nanosheets and active carbon electrode, and a specific capacitance of 13.2 F/g is obtained at 1 A/g, with a energy density of 4.7 Wh/kg at a power density of 0.798 kW/kg and remains 2.28 Wh/kg at 7.992 kW/kg. Based on these results, the asymmetric supercapacitor exhibits a good cycle life with 77.3% capacitance retention after 3000 cycles. It suggests that the V2O5 nanosheets are promising electrode material for electrochemical supercapacitors.

Purpose To investigate the effect of body position on intraocular pressure (IOP) in silicone oil tamponade eyes. Methods This prospective study included 18 eyes from 18 silicone oil tamponade patients and 24 eyes from 24 healthy subjects. Intraocular pressures were measured by Accupen Applanation Tonometer sitting with face forward, sitting with face down, supine, nondependent lateral decubitus, dependent lateral decubitus, and prone positions. The IOPs in each position and the magnitudes of IOP change were compared between the silicone oil and normal groups. Results In both groups, the IOPs in sitting positions were significantly lower than that of each recumbent position. The IOPs were highest in prone among all positions. No significant difference was found between IOPs of each group in each position. Between both groups, the IOP elevations in each position had no statistical difference compared with sitting with face forward. Conclusion The IOP is lowest in the sitting position and highest in the prone position in both silicone oil and normal groups. Between both groups, the amount of IOP elevations is equivalent in each position compared with sitting with face forward. Ophthalmologists should be aware that IOP is higher in the prone position and that it should be monitored accordingly.

Paclitaxel is widely used in the combination chemotherapy for many cancers including esophageal squamous cell carcinoma (ESCC). However, the paclitaxel resistance occurs frequently in treating ESCC and the mechanism is not fully understood yet. The heterogeneity of gene expression within the drug-resistant cancer cells may be one of the major factors contributing to its resistance. In the present study, we successfully induced paclitaxel resistance in ESCC cell line KYSE-30 through low dose and long-term treatment of paclitaxel. Gene expression profiles were measured utilizing population RNA-seq and single-cell RNA-seq (scRNA-seq). 37 single cells from KYSE-30 cells and 73 single cells from paclitaxel resistant KYSE-30 cells (Taxol-R) were subjected to scRNA-seq. Weighted gene co-expression network analysis (WGCNA) of scRNA-seq data revealed two major subpopulations in both KYSE-30 and Taxol-R cancer cells. Two subpopulations based on the KRT19 expression levels in KYSE-30 cells exhibited different paclitaxel sensitivity, suggesting the existence of an intrinsic paclitaxel resistance in KYSE-30 cells. In addition, the Taxol-R cells that acquired the resistance to paclitaxel through induction were characterized with higher expressions of proteasomes but a lower expression of HIF-1 signaling genes. Furthermore, we showed that carfilzomib (CFZ), a proteasome inhibitor, could attenuate the paclitaxel resistance in Taxol-R cancer cells through activating the HIF-1 signaling. Our new finding may pave a way leading to an improvement in the treatment on cancers including ESCC by combining CFZ with paclitaxel as a novel approach for cancer therapy.

Uniform MoS2 nanosheets assembling three-dimensional nanospheres are prepared by using a facile hydrothermal procedure with SiO2 nanospheres as the template. The morphologies and structure of MoS2 nanospheres are thorough characterized and evaluated as electrode material for supercapacitors. Galvanostatic charge/discharge measurements reveal that MoS2 nanospheres deliver a specific capacity of 683 F/g at 1 A/g, and the specific capacity retains about 85.1% after 10000 cycles. An aqueous asymmetric supercapacitor is fabricated by employing MoS2 nanospheres and activated carbon as the positive and negative electrodes, respectively. The specific capacitance is 65.33 F/g at a current density of 1 A/g. An energy density of 20.42 Wh/kg is obtained at power density of 750.31 kW/kg. The results show an attractive performance to take advantage of MoS2 nanosheets assembling three-dimensional nanospheres as electrode material for supercapacitors. Two cells in series can easily light the light-emitting diode lamp brightly, further demonstrates the high energy storage capability of the prepared MoS2 material.

The open reading frame 2 (ORF2) of Porcine circovirus type 2 (PCV2) encodes the major Capsid (Cap) protein, which self-assembles into virus-like particle (VLP) of similar morphology to the PCV2 virion and accumulates in the nucleus through the N-terminal arginine-rich nuclear localization signal (NLS). In this study, PCV2 Cap protein and its derivates were expressed via the baculovirus expression system, and the cellular localization of the recombinant proteins were investigated using anti-Cap mAb by imaging flow cytometry. Analysis of subcellular localization of Cap protein and its variants demonstrated that NLS mediated Cap protein nuclear export as well as nuclear import, and a phosphorylation site (S17) was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the NLS domain to regulate Cap protein nuclear export. Phosphorylation of NLS regulating the PCV2 Cap protein nuclear export was also demonstrated in PK15 cells by fluorescence microscopy. Moreover, the influence of Rep and Rep' protein on Cap protein subcellular localization was investigated in PK15 cells. Phosphorylation of NLS regulating Cap protein nuclear export provides more detailed knowledge of the PCV2 viral life cycle.

A new model is introduced in the process of evaluating efficiency value of decision making units (DMUs) through data envelopment analysis (DEA) method. Two virtual DMUs called ideal point DMU and anti-ideal point DMU are combined to form a comprehensive model based on the DEA method. The ideal point DMU is taking self-assessment system according to efficiency concept. The anti-ideal point DMU is taking other-assessment system according to fairness concept. The two distinctive ideal point models are introduced to the DEA method and combined through using variance ration. From the new model, a reasonable result can be obtained. Numerical examples are provided to illustrate the new constructed model and certify the rationality of the constructed model through relevant analysis with the traditional DEA model.