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Load-bearing soft tissues normally show J-shaped stress–strain behaviors with high compliance at low strains yet high strength at high strains. They have high water content but are still tough and durable. By contrast, naturally derived hydrogels are weak and brittle. Although hydrogels prepared from synthetic polymers can be strong and tough, they do not have the desired bioactivity for emerging biomedical applications. Here, we present a thermomechanical approach to replicate the combinational properties of soft tissues in protein-based photocrosslinkable hydrogels. As a demonstration, we create a gelatin methacryloyl fiber hydrogel with soft tissue-like mechanical properties, such as low Young’s modulus (0.1 to 0.3 MPa), high strength (1.1 ± 0.2 MPa), high toughness (9,100 ± 2,200 J/m 3 ), and high fatigue resistance (2,300 ± 500 J/m 2 ). This hydrogel also resembles the biochemical and architectural properties of native extracellular matrix, which enables a fast formation of 3D interconnected cell meshwork inside hydrogels. The fiber architecture also regulates cellular mechanoresponse and supports cell remodeling inside hydrogels. The integration of tissue-like mechanical properties and bioactivity is highly desirable for the next-generation biomaterials and could advance emerging fields such as tissue engineering and regenerative medicine.

Clinically serious congenital heart valve defects arise from improper growth and remodeling of endocardial cushions into leaflets. Genetic mutations have been extensively studied but explain less than 20% of cases. Mechanical forces generated by beating hearts drive valve development, but how these forces collectively determine valve growth and remodeling remains incompletely understood. Here we decouple the influence of those forces on valve size and shape, and study the role of YAP pathway in determining the size and shape. The low oscillatory shear stress promotes YAP nuclear translocation in valvular endothelial cells (VEC), while the high unidirectional shear stress restricts YAP in cytoplasm. The hydrostatic compressive stress activated YAP in valvular interstitial cells (VIC), whereas the tensile stress deactivated YAP. YAP activation by small molecules promoted VIC proliferation and increased valve size. YAP inhibition suppressed the VIC proliferation and reduced valve size, but enhanced cell-cell adhesions between VEC thus maintaining an elongated shape. Finally, left atrial ligation was performed in chick embryonic hearts to manipulate the shear and hydrostatic stress in-vivo. The restricted flow in the left ventricle induced a globular and hypoplastic left atrioventricular (AV) valves with an inhibited YAP expression. By contrast, the right AV valves with sustained YAP expression grew and elongated normally. This study establishes a simple yet elegant mechanobiological system by which transduction of local stresses regulates valve growth and remodeling. This system guides leaflets to grow into proper sizes and shapes with the ventricular development, without the need of a genetically prescribed timing mechanism.Abstract Figure

Background Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors. The prognosis of patients with advanced NSCLC is poor due to metastasis. In recent years, the role of long non-coding RNAs (lncRNAs), a class of non-coding RNA molecules, in NSCLC has become an increasingly popular focus of studies. This study aimed to investigate the effects of ZNF674-AS1 and microRNA (miR)-23a on the migration and invasion abilities of NSCLC cells in vitro and explore the underpinning molecular mechanisms. Methods The expression levels of ZNF674-AS1 and miR-23a in NSCLC tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Scratch test and transwell test were used to detect the effects of ZNF674-AS1 and miR-23a on the migration and invasion of NSCLC cells. The luciferase reporter gene experiment was used to verify miRNA targets. Western blot experiments were used to analyze protein expression. Results ZNF674-AS1 was downregulated in NSCLC tissues and cells, and inhibited the migration and invasion of NSCLC cells in vitro. In contrast, the expression of miR-23a, a downstream target of ZNF674-AS1, was increased in NSCLC tissues and cells. We found that miR-23a could antagonize the role of ZNF674-AS1 in NSCLC. E-cadherin was identified as a downstream target gene of miR-23a, and miR-23a could directly inhibit its expression. Conclusions ZNF674-AS1 inhibits the migration and invasion of NSCLC cells by regulating a miR-23a/E-cadherin axis. ZNF674-AS1 and miR-23a could become potential therapeutic targets for NSCLC.

The taxonomy of trilobites Abadiella Hupé, 1953 and Parabadiella Zhang, 1966 from the lower Cambrian of Gondwana has long been a controversy. Based on newly-collected and formerly-reported materials, 94 trilobite cranidia within 21 species are selected for morphometric analyses: principal components analysis (PCA) and canonical variates analysis (CVA). The integrated morphological characters are successfully accounted for by two principal components in PCA. The further validations for the presupposed qualitative groupings are indispensable to detect and calibrate the ultimate taxonomic results in CVA. By this way, all specimens distributed in a consistent morphospace in PCA and the short distances between them demonstrate their close morphological affinity, supporting their congeneric status within Abadiella. Additionally, three morphotypes were recognized from all selected specimens and they were eventually revised and incorporated into A. bourgini Hupé, 1953, A. huoi Zhang, 1966, and A. yunnanensis Luo, 1981, through stepwise test-calibration to get a high correct rate as far as possible in CVA. From this, it is certain that A. huoi is conspecific in South Australia and South China. Its occurrence allows to correlate the Australian A. huoi Range Zone to the identical zone in South China (in platform), having an approximately consistent stratigraphic range in the two regions. In comparison with A. huoi, A. bourgini was reported from fewer localities in South China. Nevertheless, its presence in the Daguinaspis Zone of Issendalenian Stage in Morocco permits a correlation with Chinese and Australian A. huoi Zone. As an auxiliary marker for A. huoi, the occurrence of A. bourgini in Morocco, South Australia and South China reinforce the correlation potential and resolution in species-level for the Cambrian Stage 3 in Gondwana region.

To obtain the dynamic characteristics of reactor secondary circuit under transient conditions, the system analysis program was developed in this study, where dynamic models of secondary circuit were established. The heat transfer process and the mechanical energy transfer process are modularized. Models of main equipment were built, including main turbine, condenser, steam pipe and feedwater system. The established models were verified by design value. The simulation of the secondary circuit system was conducted based on the verified models. The system response and characteristics were investigated based on the parameter transients under emergency shutdown and overload. Various operating conditions like turbine emergency shutdown and overspeed, condenser high water level, ejector failures were studied. The secondary circuit system ensures sufficient design margin to withstand the pressure and flow fluctuations. The adjustment of exhaust valve group could maintain the system pressure within a safe range, at the expense of steam quality. The condenser could rapidly take out most heat to avoid overpressure.

Wood is a renewable material that has been widely utilized as indoor and outdoor construction and decoration material in our daily life. Although wood has many advantages (i.e., light weight, high strength, low price and easy machinability), it has some drawbacks that influence dimensional stability, cracking and decay resistance in real practical applications. To mitigate these issues, superhydrophobic surfaces have been introduced to wood substrates, creating superhydrophobic wood surfaces (SHWSs) that can improve stability, water resistance, ultraviolet radiation resistance and flame retardancy. Herein, the recent developments and future perspectives of SHWSs are reviewed. Firstly, the preparation methods of SHWSs are summarized and discussed in terms of immersion, spray-coating, hydrothermal synthesis, dip-coating, deposition, sol-gel process and other methods, respectively. Due to the characteristics of the above preparation methods and the special properties of wood substrates, multiple methods are suggested to be combined to prepare SHWSs rather than each individual method. Secondly, the versatile practical applications of SHWSs are introduced, including anti-fungi/anti-bacteria, oil/water separation, fire-resistance, anti-ultraviolet irradiation, electromagnetic interference shielding, photocatalytic performance, and anti-icing. When discussing these practical applications, the advantages of SHWSs and the reason why SHWSs can be used in such applications are also mentioned. Finally, we provide with perspectives and outlooks for the future developments and applications of SHWSs, expecting to extend the utilization of SHWSs in our daily life and industry.

Percolating composites with negative permittivity can be promising candidates for metamaterials. Herein, novel all-organic composite films containing of random coil polypyrrole (PPy) and poly(vinylidene fluoride) (PVDF) are fabricated via a solution casting method. The random coil PPy is prepared by oxidative template assembly approach for the first time. The experimental result indicates that the negative permittivity is easily adjusted through controlling the random coil PPy contents. Especially, the random coil PPy contents exceeded 7 wt% the negative permittivity appear attributed to the formation of 3D interconnected PPy network. This facile approach not only opens a new way to preparing negative permittivity of all-organic composite films, but also points out a route to facilitate the practical applications of metamaterials. Keywords: Polypyrrole, Composite films, Random coil, Negative permittivity

Background The capacity of general internal medicine (GIM) clinical teaching units has been strained by decreasing resident supply and increasing patient demand. The objective of our study was to compare the number of residents (supply) with the volume and duration of patient care activities (demand) to identify inefficiency. Methods Using the most recently available data from an academic teaching hospital in Toronto, Ontario, we identified each occurrence of a set of patient care activities that took place on the clinical teaching unit from 2015 to 2019. We completed a descriptive analysis of the frequencies of these activities and how the frequencies varied by hour, day, week, month and year. Patient care activities included admissions, rounds, responding to pages, meeting with patients and their families, patient transfers, discharges and responding to cardiac arrests. The estimated time to complete each task was based on the available data in our electronic medical record system and interviews with GIM physicians and trainees. To calculate resident utilization, the person-hours of patient care tasks was divided by the person-hours of resident supply. Resident utilization was computed for 3 scenarios corresponding to varying levels of resident absenteeism. Results During the study period, there were 14 581 consultations to GIM from the emergency department. Patient volumes tended to be highest during January and lowest during May and June, and highest on Monday morning and lowest on Friday night. Daily admissions to hospital from the emergency department were higher on weekdays than on weekends, and hourly admissions peaked at 8 am and between 3 pm and 1 am. Weekday resident utilization was generally highest between 8 am and 2 pm, and lowest between 1 am and 8 am. In a scenario in which all residents were present apart from those who were post-call, resident utilization generally never exceeded 100%; in scenarios in which at least 1 resident was absent owing to illness or vacation, it was common for resident utilization to approach or exceed 100%, particularly during daytime working hours. Interpretation Analyzing supply and demand on a GIM ward has allowed us to identify periods when supply and demand are not aligned and to demonstrate empirically the vulnerability of current staffing models. These data have the potential to inform and optimize scheduling on an internal medicine ward.

During valvulogenesis, cytoskeletal, secretory and transcriptional events drive endocardial cushion growth and remodeling into thin fibrous leaflets. Genetic disorders play an important role in understanding valve malformations but only account for a minority of clinical cases. Mechanical forces are ever present, but how they coordinate molecular and cellular decisions remains unclear. In this study, we used osmotic pressure to interrogate how compressive and tensile stresses influence valve growth and shape maturation. We found that compressive stress drives a growth phenotype, whereas tensile stress increases compaction. We identified a mechanically activated switch between valve growth and maturation, by which compression induces cushion growth via BMP-pSMAD1/5, while tension induces maturation via pSer-19-mediated MLC2 contractility. The compressive stress acts through BMP signaling to increase cell proliferation and decrease cell contractility, and MEK-ERK is essential for both compressive stress and BMP mediation of compaction. We further showed that the effects of osmotic stress are conserved through the condensation and elongation stages of development. Together, our results demonstrate that compressive/tensile stress regulation of BMP-pSMAD1/5 and MLC2 contractility orchestrates valve growth and remodeling.

BackgroundThe capacity of the general internal medicine clinical teaching units has been strained by decreasing resident supply and increasing patient demand. The objective of our study was to quantitatively compare the number of residents (supply) with the volume and duration of patient care activities (demand) to identify inefficiency.MethodsUsing the most recently available data from an academic teaching hospital, we identified each occurrence of a set of patient care activities that took place on the clinical teaching unit. We completed a descriptive analysis of the frequencies of these activities and how the frequencies varied by hour, day, week, month, and year. Patient care activities included admissions, rounds, responding to pages, meeting with patients and their families, patient transfers, discharges, and responding to cardiac arrests. The estimated time to complete each task was based on the available data in our electronic healthcare system and interviews with general internal medicine physicians or trainees. To calculate resident utilization, the person-hours of patient care tasks was divided by the person-hours of resident supply. Resident utilization was computed for three scenarios corresponding to varying levels of resident absenteeism.ResultsBetween 2015 and 2019 there were 14,581 consultations to general internal medicine from the emergency department. Patient volumes tended to be highest during January and lowest during May and June; and highest on Monday morning and lowest on Friday night. Daily admissions into hospital from the emergency department were higher on weekdays than on weekends, and hourly admissions peaked at 8:00 AM and between 3:00 PM and 1:00 AM. Weekday resident utilization was generally highest between 8:00 AM and 2:00 PM and lowest between 1:00 AM and 8:00 AM. In a scenario where all residents were present apart from those who were post-call, resident utilization generally never exceeded 100%; in scenarios where at least one resident was absent due to illness and/or vacation, it was common for resident utilization to approach or exceed 100%, particularly during daytime working hours.InterpretationAnalyzing supply and demand on a general internal medicine ward has allowed us to identify periods where supply and demand are not aligned and to empirically demonstrate the vulnerability of current staffing models. These data have the potential to inform and optimize scheduling on an internal medicine ward.

The SmCo alloys are widely used in the field of precision instruments and high temperatures due to their excellent temperature stability. At present, the effect of high temperature on the domain structure of SmCo alloy lacks sufficient study. In this paper, the effect of temperature on the magnetic domain of type 2:17 SmCo alloy was investigated by domain structure observation and micromagnetic simulation. After heating at 240 ℃ and 300 ℃, the reverse domains could be observed on the surface of the magnet, and the domains nucleated at the center region of the grains and then expanded into maze domains. The in-situ heating test using Lorentz electron microscope confirms, from a microscopic point of view that thermal activation causes irreversible movement of the walls of the domains. It was found by the comparison between batch heating tests and continuous heating tests that part of the inverted domains are unstable during the cooling from high temperature down to room temperature, and the micromagnetic simulation results verified that without the temperature field and magnetic field, the unstable inverted domains would disappear under the influence of the interaction, and the domains pinned by the phase boundary will be stably retained. The micromagnetic simulation results reveal that the nucleation sites of the reverse domains in the SmCo alloy are at the intersection of the 2:17 R phase and Zr-rich phase, which is due to the lower pinning field of the Zr-rich phase.

Application of a continuum damage mechanics formulation rests on the ease with which the material constants involved in the formulation can be determined. For an initially linear elastic material, the changes in elastic constants induced by damage depend on certain damage related material constants that are commonly determined by experiments in addition to those required to determine the initial properties. This additional experimental task can render the continuum damage mechanics theory less attractive. The present paper will only deal with those associated with damage representation. We propose here a procedure for analytically determining seven out of eight damage related material constants for unidirectional composites assumed initially transversely isotropic and containing a parallel array of matrix cracks along fibres. The remaining constant can be determined experimentally or by a numerical experiment proposed here for the purpose. The analytical expressions derived are in terms of initial elasticity constants of a unidirectional composite and are verified for their accuracy by numerical experiments. Since a unidirectional composite forms a building block in composite laminates, the results obtained here can be naturally used for damage in laminates.

Graphene quantum dots (GQDs) are a new type of carbon material that have received widespread attention in recent years. However, due to their complex structure, it is difficult to explore their fluorescence emission mechanism and application mechanism. In this work, GQDs with simple structure were prepared using citric acid as a single precursor. The fluorescence properties and structure of GQDs were characterized, and the results confirmed that their luminescence originated from the n → π* electronic transition produced by the oxygen-containing functional groups in the edge state. Significantly, GQDs can be used as excellent probes to detect Hg2+ and ClO− in aqueous solution. Hg2+ combines with the carboxyl groups of the edge states of GQDs to form a complex, and then reduces the fluorescence emission through non-radiative electron transfer. ClO− can oxidize the hydroxyl groups in the edge states of GQDs to make them positively charged, which prevents electron transfer related to the luminescent center and reduces fluorescence emission.

Pt3Ni alloy supported by carbon nanofibers (CNs) composites (Pt3Ni/CNs) synthesized by a simple solvothermal process was introduced into dye-sensitized solar cells (DSCs) as counter electrode (CE) for the first time, and the DSCs based on Pt3Ni/CNs CE obtained a power conversion efficiency (PCE) of 8.34%. To enhance the catalytic activity of Pt3Ni/CNs composites, transition metal chrome (Cr) was doped in Pt3Ni/CNs to synthesize the composites of Cr-Pt3Ni/CNs using the same method. Due to the high electro-catalytic activity and rapid charge transfer ability, the PCE of the DSCs employing Cr-Pt3Ni/CNs as CE increased to 8.76%, which was much higher than that of Pt CE (7.04%) measured in the same condition. The impressive results along with low cost and simple synthesis process demonstrated transition metal doping was a promising method to produce substitutes for Pt to reduce the cost and increase the PCE of DSCs. (C) 2016 Published by Elsevier B.V.

Incorporation of nanophase ceria into the cathode catalyst Pt/C was used as alternative cathode catalysts for the oxygen reduction reaction in an air-cathode single-chamber microbial fuel cell (SCMFC) for the first time. Electrochemical results reveal that the ceria doped Pt/C catalysts exhibited a higher catalytic performance than the pure Pt/C catalyst. The highest voltage of 580 mV and the maximum power density of 840 ± 24 mW m−2 were achieved from the 3 wt% CeO2 doped Pt/C cathode, which was larger than that of the pure Pt/C cathode.

This study presents the characteristics and treatment of small cell lung cancer (SCLC) and an analysis of the factors that impact survival in northeastern Chinese populations, among both smokers and non-smokers.A retrospective review was performed using 485 Chinese patients diagnosed with pathologically confirmed SCLC diagnoses between January 2001 and December 2007. Data on patient characteristics, treatment patterns, and outcome information was collected systematically. Univariate analysis and the Cox multivariate regression model were used to evaluate prognostic factors.Median survival time was 16 months in all patients, 31 months in limited stage (LS) patients, and 10 months in extensive-stage (ES) patients. Never-smoking patients (P= 0.0368) with good performance status (PS) (P= 0.0044) or with normal lactate dehydrogenase (LDH) levels (P0.0001), demonstrated superior survival rates. Multivariate analysis identified that cycles of chemotherapy, PS, LDH levels, recurrence or progression, and clinical stage were each independent prognostic factors applicable to all patients. In LS-SCLC, cycles of chemotherapy were the only prognostic indicator; however, cycles of chemotherapy, LDH levels, and recurrence or progression, were all significant factors in ES-SCLC.Cycles of chemotherapy, PS, LDH levels, recurrence or progression, and clinical stage were proved to be independent prognostic factors for SCLC with variant value based on the SCLC tumor stage.

A novel combined cycle system comprising of a supercritical CO2 (sCO2) cycle and a Kalina cycle is proposed in this paper. Exergoeconomic comparison between the combined sCO2/Kalina cycle a...

Background: This study presents the characteristics and treatment of small cell lung cancer (SCLC) and an analysis of the factors that impact survival in northeastern Chinese populations, among both smokers and non-smokers. Methods: A retrospective review was performed using 485 Chinese patients diagnosed with pathologically confirmed SCLC diagnoses between January 2001 and December 2007. Data on patient characteristics, treatment patterns, and outcome information was collected systematically. Univariate analysis and the Cox multivariate regression model were used to evaluate prognostic factors. Results: Median survival time was 16 months in all patients, 31 months in limited stage (LS) patients, and 10 months in extensive-stage (ES) patients. Never-smoking patients (P= 0.0368) with good performance status (PS) (P= 0.0044) or with normal lactate dehydrogenase (LDH) levels (P < 0.0001), demonstrated superior survival rates. Multivariate analysis identified that cycles of chemotherapy, PS, LDH levels, recurrence or progression, and clinical stage were each independent prognostic factors applicable to all patients. In LS-SCLC, cycles of chemotherapy were the only prognostic indicator; however, cycles of chemotherapy, LDH levels, and recurrence or progression, were all significant factors in ES-SCLC. Conclusion: Cycles of chemotherapy, PS, LDH levels, recurrence or progression, and clinical stage were proved to be independent prognostic factors for SCLC with variant value based on the SCLC tumor stage.

Studies using xenograft mouse models have shown that plasma applied to the skin overlying tumors results in tumor shrinkage. Plasma is considered a nonpenetrating treatment; however, these studies demonstrate plasma effects that occur beyond the postulated depth of physical penetration of plasma components. The present study examines the propagation of plasma effects through a tissue model using three-dimensional, cell-laden extracellular matrices (ECMs). These ECMs are used as barriers against direct plasma penetration. By placing them onto a monolayer of target cancer cells to create an in-vitro analog to in-vivo studies, we distinguished between cellular effects from direct plasma exposure and cellular effects due to cell-to-cell signaling stimulated by plasma. We show that nanosecond-pulsed dielectric barrier discharge plasma treatment applied atop an acellular barrier impedes the externalization of calreticulin (CRT) in the target cells. In contrast, when a barrier is populated with cells, CRT externalization is restored. Thus, we demonstrate that plasma components stimulate signaling among cells embedded in the barrier to transfer plasma effects to the target cells.

BACKGROUND AND OBJECTIVE Concurrent chemoradiotherapy for cervical carcinoma develops rapidly and has become a common and standard therapy in recent years. Both the local control rate and survival rate of patients were increased and the risk of death fell by 30%-50%. This study aimed to explore the efficacy of concurrent chemoradiotherapy plus adjuvant chemotherapy on and the treatment compliance of the patients with advanced cervical squamous cell carcinoma. METHODS A total of 156 patients with stage IIa-IIIb cervical squamous cell carcinoma were randomly divided into the concurrent chemoradiotherapy group (experimental group) and radiotherapy group (control group). Intracavity and external beam radiation therapy were administered. At point A, 40-48 Gy were given by 10-12 fractions; at point B, 46-50 Gy were given by 23-25 fractions. In the same time, experimental group was treated by cisplatin (DDP, 40 mg) on day 1, repeated every week. Ten days after radiation therapy, TP regimen was administered as adjuvant chemotherapy. RESULTS For the experimental and control groups, the objective response rates were 88.61% and 75.32%, 1-year survival rates were 88.57% and 70.77%, 1-year local control rates were 81.43% and 64.62%, 3-year survival rates were 82.14% and 57.69%, and 3-year local control rates were 75.00% and 46.15%, with significant differences (P