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Children/adolescents with type 1 diabetes (T1D) require holistic approach and continuous care. However, the coronavirus disease 2019 (COVID-19) pandemic has made challenges for the T1D children and their caregivers, professionals, and the healthcare system. This minireview aims to consolidate and discuss the difficulties and solutions of children with type 1 diabetes in the COVID-19 pandemic. T1D has been the most common type of diabetes in children and adolescents and the last decades has seen a rapid increase in the prevalence of T1D in youths worldwide, which deserves a public concern particularly in the COVID-19 pandemic. As reported in previous studies, T1D is a risk factor related to severe cases, while the virus may induce new-onset diabetes and serious complications. Moreover, restriction strategies influence medical availability and lifestyle, impact glycemic control and compilation management, and thus pose stress on families and health providers of youths with T1D, especially on those with certain fragile conditions. Therefore, special treatment plans are required for children provided by caregivers and the local health system. Latest health tools such as improved medical devices and telemedicine service, as well as a combined support may benefit in this period. This minireview emphasises that continued medical access and support are required to prevent deteriorated condition of children and adolescents with diabetes throughout this pandemic. Therefore, strategies are supposed to be formulated to mitigate the difficulties and stress among this group, particularly in the most at-risk population. Proposed solutions in this minireview may help individuals and the health system to overcome these problems and help youths with T1D in better diabetes management during such emergency situations. Published version

Hepatocellular carcinoma (HCC) has a high degree of malignancy and poor prognosis. Treatment options for patients with advanced HCC are limited. There is currently no evidence to approve the accumulation of targeted therapies for HCC to support the inhibition of the PI3K/Akt/mTOR signaling pathway as an effective therapeutic strategy. We report on a patient with advanced HCC carrying the TSC1 gene mutation who responded well to the mammalian target of rapamycin inhibitor everolimus. Computed tomography revealed tumor shrinkage and maintenance of partial remission after everolimus treatment for >12.3 months. To the best of our knowledge, this is the first clinical case report showing benefit from everolimus treatment in HCC patients with TSC1 gene mutations. Therefore, everolimus may be used as a potential targeted therapy for HCC with TSC1 gene mutation.

Aims To evaluate the effectiveness and safety of cryoballoon ablation (CBA) compared with radiofrequency ablation (RFA) for symptomatic paroxysmal or drug-refractory persistent atrial fibrillation (AF). Methods and results Prospective cluster cohort study in experienced CBA and RFA centres. Primary endpoint was ‘atrial arrhythmia recurrence’, secondary endpoints were as follows: procedural results, safety, and clinical course. A total of 4189 patients were included: CBA 2329 (55.6%) and RFA 1860 (44.4%). Cryoballoon ablation population was younger, with fewer comorbidities. Procedure time was longer in the RFA group (P = 0.01). Radiation exposure was 2487 (CBA) and 1792 cGycm2 (RFA) (P Conclusions The primary endpoint did not differ between CBA and RFA. Cryoballoon ablation was completed rapidly; the radiation exposure was greater. Rehospitalization due to re-ablations and adverse events during follow-up were observed significantly less frequently after CBA than after RFA. Subgroup analysis suggested a lower risk of recurrence after CBA in paroxysmal AF. Trial Registration ClinicalTrials.gov (NCT01360008), https://clinicaltrials.gov/ct2/show/NCT01360008.

Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation, but the underlying ionic mechanism for this association remains unclear. We recently reported that expression of the small-conductance calcium-activated potassium channel 2 (SK2, encoded by KCCN2) in atria from diabetic mice is significantly down-regulated, resulting in reduced SK currents in atrial myocytes from these mice. We also reported that the level of SK2 mRNA expression is not reduced in DM atria but that the ubiquitin-proteasome system (UPS), a major mechanism of intracellular protein degradation, is activated in vascular smooth muscle cells in DM. This suggests a possible role of the UPS in reduced SK currents. To test this possibility, we examined the role of the UPS in atrial SK2 down-regulation in DM. We found that a muscle-specific E3 ligase, F-box protein 32 (FBXO-32, also called atrogin-1), was significantly up-regulated in diabetic mouse atria. Enhanced FBXO-32 expression in atrial cells significantly reduced SK2 protein expression, and siRNA-mediated FBXO-32 knockdown increased SK2 protein expression. Furthermore, co-transfection of SK2 with FBXO-32 complementary DNA in HEK293 cells significantly reduced SK2 expression, whereas co-transfection with atrogin-1ΔF complementary DNA (a nonfunctional FBXO-32 variant in which the F-box domain is deleted) did not have any effects on SK2. These results indicate that FBXO-32 contributes to SK2 down-regulation and that the F-box domain is essential for FBXO-32 function. In conclusion, DM-induced SK2 channel down-regulation appears to be due to an FBXO-32-dependent increase in UPS-mediated SK2 protein degradation.

To analyze the rules of acupoint selection in the acupuncture treatment of cervical spondylotic radiculopathy by data mining.The randomized controlled trials (RCTs) regarding acupuncture for cervical spondylotic radiculopathy published from July 15 of 2009 to July 15 of 2019 were retrieved from databases of CNKI, VIP, Wanfang, SinoMed, PubMed and EMbase. A database was established with Microsoft Excel 2016. The frequency and total effective rate of high-frequency acupoints, meridians and acupoint combinations were analyzed, and the association rules of acupoints and meridians were analyzed by Apriori algorithm.A total of 87 RCTs were included, involving 104 acupoints with a total frequency of 921. Among them, the high-frequency acupoints were cervical Jiaji (EX-B 2, 87 times), Fengchi (GB 20, 70 times), Houxi (SI 3, 54 times), etc. The frequently-used acupoints were mainly distributed in the handIt is feasible to explore the acupoint selection and compatibility rules of acupuncture for cervical spondylotic radiculopathy by data mining. This study could provide corresponding reference for clinical treatment.

Objective To systematically evaluate the clinical efficacy and safety of acupuncture in the treatment of Tic Disorders (TD) in children, and to clarify the current evidence regarding the clinical application of acupuncture in the treatment of TD. Methods Randomized controlled trials (RCTs) comparing acupuncture treatment with pharmaceutical treatment for TD were included in this review. A comprehensive search of 6 electronic literature databases was conducted, and the retrieval date was from the establishment of the database to April 2020. The Cochrane Collaboration’s bias risk assessment tool was used to evaluate the bias risk of the included literature, and adopted the Review Manager 5.3 was used for statistical analysis of the data in the included literature. Results A total of 22 RCTs (1668 participants) were included in this review. Meta-analysis indicated that acupuncture showed superior effects in the following aspects, including higher overall effective rate [RR = 1.20,95 % CI(1.09,1.20),P＜0.00001], significant reduction in Yale Global Tic Severity Scale (YGTSS) scores [MD=-2.79,95 %CI(-4.75,-0.82),P = 0.005], lower incidence of adverse effects [RR = 0.26,95 %CI(0.17,0.41),P＜0.00001], and reduced recurrence rate [RR = 0.28,95 %CI(0.17,0.46),P＜0.00001]. Conclusion Acupuncture treatment alone is more effective in the treatment of TD than pharmaceutical treatment, as seen in the reduction of YGTSS scores, fewer adverse effects and lower recurrence rates.

Objectives We assessed the effectiveness and safety of cryoballoon ablation (CBA) in the Chinese population with paroxysmal atrial fibrillation (AF) with a 1-year follow-up and determined the association of early recurrence of atrial tachyarrhythmias (ERAT) with late recurrence (LR). Methods A total of 114 patients (age 61 ± 10 years, 78 males) with paroxysmal AF who underwent CBA were consecutively enrolled. After procedures, patients were observed for 3 days with continuous electrocardiogram monitoring in the hospital with routine follow-up visits at 3 months, 6 months, and 1 year. Documented atrial tachyarrhythmia >30 seconds was defined as recurrence. ERAT was defined as any recurrence during the first 3 months, and LR was recurrence between 3 and 12 months. Results With the first 3 months as blanking period, 76% of patients were free of LR at 12 months. Five patients (4%) experienced complications, including phrenic nerve palsy, stroke, and groin complications. Forty-five percent of patients had ERAT in the first 3 months and 31% of patients had ERAT in the first 3 days. Patients with ERAT had higher LR rate (LRR) than those without ERAT (43% vs 8%, P

This paper presents a three-dimensional dynamic model of laser controlled dynamic self-assembly of nanostructure. A phase field model is employed to study the surface fabrication of silicon which is induced by the laser. The mechanism of the surface fabrication is that the heating effect enhances surface diffusion mobility results in atoms outward flow. The computational model systematically integrate for high reliability of the whole analysis, the experimental and simulated measurements have been quantitatively investigated. A semi-implicit Fourier spectral scheme is applied for high efficiency and numerical stability. The performed simulations suggest a substantial potential of the presented model, which provides a reliable technology of nanostructure fabrications on the surface of silicon.

The L-type calcium channel (LTCC) is one of the major ion channels that are known to be associated with the electrical remodeling of atrial fibrillation (AF). In AF, there is significant downregulation of the LTCC, but the underlying mechanism for such downregulation is not clear. We have previously reported that microRNA-499 (miR-499) is significantly upregulated in patients with permanent AF and that KCNN3, the gene that encodes the small-conductance calcium-activated potassium channel 3 (SK3), is a target of miR-499. We found that CACNB2, an important subunit of the LTCC, is also a target of miR-499. We hypothesize that miR-499 plays an important role in AF electrical remodeling by regulating the expression of CACNB2 and the LTCC. In atrial tissue from patients with permanent AF, CACNB2 was significantly downregulated by 67% (n = 4, p, Highlights • LTCC is downregulated with electrical remodeling of atrial fibrillation. • MiR-499 is increased and CACNB2 is reduced in atria from patients with atrial fibrillation. • MiR-499 binds to the 3′UTR of CACNB2 and inhibits its protein expression. • Downregulation of CACNB2 results in the downregulation of LTCC pore-forming subunit. • MiR-499 contributes to the electrical remodeling of AF through regulation of CACNB2.

This study evaluated 24-hour ambulatory blood pressure (ABP) monitoring in patients with chronic kidney disease (CKD) who had a normal casual blood pressure (CBP) of less than 140/90 mmHg. A total of 350 patients with CKD (Stages 1-5) and a normal CBP were included, and 24-hour ABPs were monitored. Of these patients, 147 patients (42.0%) exhibited increased mean ABP; 69 patients (19.7%) exhibited masked hypertension; 199 patients (56.9%) exhibited an abnormal BP mode (circadian rhythm disappearing); and 204 patients (58.3%) exhibited increased BP load. The 24-hour ABP and mean day and night BPs in patients with higher CBP were significantly higher than those in patients with normal CBP and healthy controls (P0.01). Results indicate that abnormal BPs exist in patients with CKD who exhibit normal CBPs.

An increasing amount of evidence shows that childhood leukemia is initiated in utero. Birth characteristics initiated in utero, such as gestational age, may play a role in leukemogenesis. The purpose of our meta-analysis is to explore the association between gestational age and childhood leukemia.Relevant studies up to 21 April 2017 were collected by searching PubMed and EMBASE databases. Subgroup analysis, sensitivity analysis and publication bias assessment were conducted.A total of 13 studies were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for preterm birth and postterm birth were 1.06 (0.98, 1.13) and 1.01 (0.90, 1.13) for childhood leukemia, 1.04 (0.97, 1.11) and 1.03 (0.95, 1.12) for acute lymphocytic leukemia (ALL), 1.20 (1.00, 1.44) and 1.20 (1.00, 1.43) for acute myeloid leukemia (AML), compared with full-term birth. Study type and study region were the reasons behind the heterogeneity. In subgroup analyses, the summary ORs with 95% CI for childhood leukemia and ALL were 1.23 (1.07, 1.41) and 1.21 (1.06, 1.39) for postterm birth in cohort studies. No significant changes in sensitivity analyses and no publication bias were observed in our analysis.Our results suggest that both preterm and postterm infants have an elevated risk of developing AML. In addition, postterm birth increased the risk of childhood leukemia and ALL in cohort studies. However, more studies are warranted to validate these results and explore the biologic mechanisms underlying these relationships.

In microfluidic chips, most micro-channel cross-section shapes are rectangular or triangular in existing chip fabricating technologies, including hot embossing, lithography, etching, injection molding, etc. However, compared with the above micro-channel shapes, a circular shape has advantages in aspects of fluid flow, droplet generation, heat transfer and blood vessel replication. This paper presents a sandwich-like microfluidic chip with circular cross-section micro-channels. The sandwich-like structure includes three layers. The top and bottom layers are PDMS material while the middle layer is composed of micron glass capillaries (used as micro-channels) with circular cross-sections. The glass capillaries are made of borosilicate tube by a glass heating process. Sphere shaped paraffin wax is used as a sacrificial material to form micro-channel junctions. To test the functions of the fabricated micro sandwich-like microfluidic chip, a droplet generating experiment was conducted in the T-junction chip. The droplet size can be controlled in the range of 20–400 [Formula: see text]m by varying the water and oil flow rates. This proposed microfluidic chip structure has the advantages of short processing cycle, low cost and small flow resistance.

The concentration of fourteen environmentally important trace elements (Be, V, Cr, Co, Ni, Cu, Zn, Mo, Sn, Ba, Tl, Pb, Th and U) was studied in thirteen coal samples from Xinan coalfield, Henan province. In addition, virtrinite reflectance analysis, proximate analysis and elemental analysis were also conducted on these samples. The vitrinite reflectance values (Ro) ranges from 2% to 2.35%, revealing that these samples are lean coal. The coals have low moisture content, with Madvalue ranging from 0.57 to 0.95%. The ash and volatile matter content vary between 8.11-22.61% and 10.36-14.64%, respectively. Carbon, hydrogen, sulphur and nitrogen content vary between 71.51-83.54%, 3.068-3.879%, 0.494-2.326% and 0.953-1.38%, respectively. In comparison with the crustal average (Clarke value), some potentially hazardous elements are moderately enriched in the coals from Xinan coalfield, such as Pb, Th, U, Sn and Mo. The average concentration of most of the elements in Xinan coalfield coals is in the range of Chinese coals and world coals. No elements with the abnormally high concentrations analyzed are found.

As a renewable, clear and inexhaustible energy, solar energy receives much more attention and has partly substituted traditional energies in many fields. Multi-crystalline silicon plays an important role for its low cost, abundant reserves and excellent photoelectric conversion in solar cells. Mixed acid etching is an effectively method to texture the morphology on the surface of mc-Si, While stochastic etching between silicon and acids results in irregular texturing and high reflectivity. In this paper, ultrasonic standing wave is introduced into acid solution, which aid wet etching to texture on the surface of mc-Si by controlling distribution of atoms of acids. Scanning electron microscope experiment shows that the morphology on the surface of mc-Si textured by this method is similar to that of mono-crystalline silicon. And the average reflectivity is 8%, much lower than mixed acid etching.

W/C ratio and the quantity of fly ash added have obvious influence on creep of high performance concrete. Effect of different quantities of fly ash on creep of high performance concrete of different W/C ratios used in bridge is studied in this research whose results reflect that creep value reduces along with reduction of W/C ratio at a certain quantity of fly ash added. Adding fly ash restrains creep on the whole, however, the degree depends on the quantity of fly ash added. Creep value of high performance concrete mixed with class-I fly ash at blend ratio of 12~40% is lower than that of standard concrete and fly ash at blend ratio of 18% has the best effect. Creep value in 365d is 51% of that of standard concrete at fly ash blend ratio of 18%, while at fly ash blend ratio of 40%, creep value in 365d is lower than that of standard concrete but higher than that of concrete at other blend ratios. It is generally considered that inhibition of creep of high performance concrete begins to fall beyond blend ratio of 30%.

The renin-angiotensin-aldosterone system (RAAS) plays a key role in atrial structural and electrical remodeling. The aim of this study was to investigate the potential associations of angiotensin-converting enzyme (ACE) gene insertion/ deletion (I/D) and aldosterone synthase (CYP11B2) gene −344T/C polymorphisms with the risk and recurrence of lone atrial fibrillation (AF). One hundred and ninety-three patients who underwent successful catheter ablation for lone AF were recruited. Two hundred and ninety-seven sinus rhythm subjects without a history of arrhythmia served as controls. The subjects were genotyped for ACE gene I/D and CYP11B2 gene −344T/C polymorphisms. Results showed that the ACE gene DD genotype and D allele were associated with a greater prevalence of lone AF (both P

Background The objective of the study was to explore the clinical expression, radiological and pathological features, differential diagnosis, and biological behavior of a clear cell myomelanocytic tumor. In a case involving a clear cell myomelanocytic tumor located in the hepatic falciform ligament, we evaluated clinical expression, radiological characteristics, histopathology, immunohistochemistry, and biological behavior; we also reviewed the relevant literature. Case presentation Clear cell myomelanocytic tumor is a benign soft-tissue neoplasm that often occurs in women, and is expressed as a painless mass. The falciform ligament is its most frequent site of occurrence. The imaging characteristics of this lesion were uneven enhancement in the arterial phase, continuing to strengthen in the venous phase, and equal density in the balance phase. Histological and immunohistochemical analysis revealed the main transparent epithelioid cells and smooth muscle spindle cells to be HMB-45(+), smooth muscle actin(+), and melan-A (+). Conclusion Hepatic vascular epithelioid cell tumors are very rare mesenchymal neoplasms. Few studies have investigated this tumor in the hepatic falciform ligament; consequently, its diagnosis and the selection of an appropriate treatment and follow-up protocol are challenging. Treatment outcome remains unpredictable. Therefore, clear cell myomelanocytic tumor should be viewed as a tumor with uncertain malignant potential requiring long-term follow-up.

Surface texturing of silicon can reduce the reflectance of incident light and increase the conversion efficiency of solar cells. Many approaches have been present in texturing silicon solar cell. In this paper, ultrasound is introduced into acid solution to texture the surface of multicrystalline silicon (mc-Si) solar cell. The morphology images are obtained by scanning electron microscope (SEM), more holes and regular distributed morphology for the presented method can be observed. Antireflectance of the mc-Si surface is measured by spectrophotometer, and the reflectance of 10.2% is obtained for the presented method, which is much less than that of acid etching.

Nowadays solar energy receives more and more attention for its clear, non-pollutant and renewable characteristics. Although the production cost of electricity by solar cell is much higher than those by fossil fuels currently, solar cell has partly substituted traditional energy and be used in some fields. Silicon wafer surface texture act an important role in solar cell, which can trap the incident lights and influence the photoelectric conversion. In this paper, a new method using ultrasonic standing wave is present based on the previous researches. The acid molecules are droved to distribute regularly in terms of the standing wave. Then regular morphology can be textured on the surface of mc-Si by the acid molecules etching with silicon. SEM experiment illustrate the present method can texture regular morphology on the surface of multi-crystalline silicon (mc-Si) , also the antireflection of 9.4% is much lower than that of traditional acid etching.

The numerical simulation analysis, by using senior nonlinear finite element analysis software MSC.Marc, was achieved in this paper for the tie-replacing procedures of a steel tube tied-arch filled with concrete. Through this analysis, the control parameters were accurately determined for the installing of new ties and the removing of old ties. Results of numerical analysis ensured the bridge structure stable during the replacement, made the construction of safe and convenient, and played a guiding role in the maintenance and reinforcement. The successful experience could be referenced by other similar projects.

Roughness parameters such as the root-mean-square (RMS) roughness in super smooth surfaces are heavily influenced by evaluation ways and measuring method. With the help of CCI6000, relationships were investigated respectively between the RMS roughness with the instrument parameter set and cutoff wavelength. The study revealed that there was an optimal set of measurement parameters and a dynamic cutoff wavelength that would identify different wavelength regimes when measuring super smooth surfaces. It was found that the proposed scheme greatly reduced the influences of CCI instrument parameters and cutoff length on RMS roughness in the measurement of hard disk surfaces. RMS roughness exhibited a steady-state trend and the processed surface morphology conformed to the arrangement of atoms and the polishing feature of CMP technique.

With the development of economy and society, more and more energy is needed to meet the requirement of industries and social life. It is necessary to find new types of energy that is clear, high effective and non-polluted. Although wet etching is widely used in industries to prepare the silicon surface texture, the etching process is stochastic and the influence light trapping. Many efforts have been made such as adjusting the proportion of different acids, to improve the quality of silicon surface by wet etching, the result does not meet the ideal requirement by now. In this paper, a new approach is presented to prepare the surface texturing. By combining wet etching and ultrasonic vibration, the sodium or acid molecular motion can be controlled, and the pyramid structure in silicon surface can be made regular.

Surface texturing of silicon can reduce the reflectance of incident light and hence increase the conversion efficiency of solar cells. Many approaches have been present in texturing silicon solar cell. As a practical method, chemical wet etching has been widely used in monocrystalline silicon and multicrystalline silicon (mc-Si), but the cost and high reflectance hamper its widely used. In this paper, a new approach is present by using ionized bubble to texture multicrystalline solar cell. The electric field and ultrasonic wave is introduced into traditional chemical wet etching. After mixed solution ionized by electrolysis and gasified by the ultrasonic wave, the ionized bubble is formed. The movement of ionized bubble is observed to study the impact on the surface of mc-Si solar cell. At last, a spectrophotometer was used to measure mc-Si surface reflectance to test the efficiency of two methods. The result express that the reflectance of mc-Si surface textured by ionized bubble is much low than that of chemical mixed acid etching.

Tolerance information plays a critical role in many steps of the product life cycle. It is especially important due to the advances in Internet technologies and increasing integration requirements from industry. In this paper, geometric tolerances information in manufacturing process (IMP) is studied, and the layered conformance level of geometric tolerances is established according to ASME Y14.5-1994, STEP and DMIS. An EXPRESS-G data model of geometric tolerance information in IMP is established. The XML language is used to represent and program the geometric tolerances information in IMP.

Traffic incident influences the security of people in the popularity of navigation. It is urgently necessary to develop intelligent vehicles by using new technologies and advanced methodologies. In this paper, a new approach based on holonic conception is presented to study the intelligent control in vehicle tool. The control structure in car is divided into three levels and is defined three holonary, the function of every holon level is discussed, then a distributed multilevel intelligent control architecture in car based on holon is developed. The cooperation relation is analyzed between different levels; the cooperative model is established to study cooperation mechanisms among different holon level, which will help to improve the intelligent control and vehicle security for car.

With the development of economy and society, more and more energy is needed to meet the requirement of industries and social life. It is necessary to find new types of energy that is clear, high effective and non-polluted. Although wet etching is widely used in industries to prepare the silicon surface texture, the etching process is stochastic and the influence light is trapping. Many efforts have been made, such as adjusting the proportion of different acids, to improve the quality of silicon surface by wet etching, the effectiveness is still limited. In this paper, a new approach is presented to prepare the surface texturing. By combining wet etching and ultrasonic vibration, the sodium or acid molecular motion can be controlled, and the pyramid structure in silicon surface can be made regular.

With the rapid development of information technology, ontology is gradually used for knowledge engineering and information science sphere. Agricultural Ontology mainly is composed of the concept and relationship between concepts in agricultural knowledge, as well as the computer can identify the composition of the formal description language. The goal of build the agricultural ontology is to form a common understanding of the agricultural information organizational structure, to known and analysis of knowledge in the field of agriculture so as to further establish the foundation for the agriculture semantic web. In this paper, we present a design principles and implementation process in vegetable products domain ontology. Through the collection and analysis of the field of vegetable products information as well as the use of inference engine, used to build vegetable domain ontology with OWL. In the information extraction prototype system, we achieved a semi-automatic filled with examples of vegetable products domain ontology. Through compared to the results before and after the use of inference engine, it show that vegetables and semi-automatic domain ontology building methods is feasible.

The potential of an in situ gel-forming adhesive was examined as a hemostatic surgical sealant. The gel-forming mechanism for this adhesive mimics the last stages of blood coagulation but uses nonblood proteins. Specifically, gelatin is used as the structural protein and a calcium-independent microbial transglutaminase (mTG) is used as the crosslinking enzyme. In vitro burst pressure tests with porcine skin demonstrate that the gelatin-mTG adhesive forms a gel within 30 min under moist conditions and this gel can restrain pressures of 200 mmHg. In vivo tests with a rat liver wound model showed that the gelatin-mTG adhesive achieves complete hemostasis in 2.5 min and the gel (i.e., the biomimetic clot) offers substantial adhesive and cohesive strength. Complete hemostasis was also observed in 2.5 min after the gelatin-mTG adhesive was applied to a briskly bleeding rat femoral artery wound. In a large animal porcine model, a femoral artery wound that resulted in extensive bleeding was sealed in 4 min by (i) clamping the artery for temporary hemostasis, (ii) removing excess blood, and (iii) applying the gelatin-mTG adhesive. Thus, the biomimetic gelatin-mTG adhesive may provide a simple, safe, and cost-effective surgical sealant.

Gelatin is one of the most commonly used biomaterials for creating cellular scaffolds due to its innocuous nature. In order to create stable gelatin hydrogels at physiological temperatures (37 degrees C), chemical crosslinking agents such as glutaraldehyde are typically used. To circumvent potential problems with residual amounts of these crosslinkers in vivo and create scaffolds that are both physiologically robust and biocompatible, a microbial transglutaminase (mTG) was used in this study to enzymatically crosslink gelatin solutions. HEK293 cells encapsulated in mTG-crosslinked gelatin proliferated at a rate of 0.03 day(-1). When released via proteolytic degradation with trypsin, the cells were able to recolonize tissue culture flasks, suggesting that cells for therapeutic purposes could be delivered in vivo using an mTG-crosslinked gelatin construct. Upon submersion in a saline solution at 37 degrees C, the mTG-crosslinked gelatin exhibited no mass loss, within experimental error, indicating that the material is thermally stable. The proteolytic degradation rate of mTG-crosslinked gelatin at RT was slightly faster than that of thermally-cooled (physically-crosslinked) gelatin. Thermally-cooled gelatin that was subsequently crosslinked with mTG resulted in hydrogels that were more resistant to proteolysis. Degradation rates were found to be tunable with gelatin content, an attribute that may be useful for either long-time cell encapsulation or time-released regenerative cell delivery. Further investigation showed that proteolytic degradation was controlled by surface erosion.

Background Cancer-testis antigen (CTA) is a family of the most noticeable tumor antigens which could be potential tumor markers for cancer diagnosis.In this research we aimed to investigate the expression of SSX-1 and NY-ESO-1 mRNA,two members of the CTA family,in tissue and peripheral blood of patients with hepatocellular carcinoma (HCC) to assess their feasibility for the immunotherapy and diagnosis of HCC and the association of their expression levels with diverse clinical indicators. Methods Thirty-six north Chinese patients with HCC and 30 normal controls were enrolled in this study.Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of SSX-1 and NY-ESO-1 mRNA in tumor tissues and corresponding levels in peripheral blood of patients. Results The positive rates of SSX-1 and NY-ESO-1 mRNA expression were 61.1% (22/36) and 11.1% (4/36), respectively,in cancer tissues;38.9% (14/36) and 5.6% (2/36),respectively,in the corresponding peripheral blood samples.No positive expression of either SSX-1 or NY-ESO-1 mRNA was detected in the samples of cancer-adjacent tissues,cirrhotic tissues,normal liver tissue or the peripheral blood of control patients.No significant relationship was found between the expression of these two genes and clinical indicators such as age,gender,tumor size,extent of differentiation,serum a-fetoprotein (AFP) level or infection with hepatitis B virus (P0.05).The short term recurrence rate was 46.2% (6/13) in patients whose peripheral blood expressed SSX-1 mRNA,while the recurrence rate in patients with negative SSX-1 mRNA was 28.6% (4/14). Conclusions SSX-1 and NY-ESO-1 antigens might be new potentially promising targets for antigen-specific immunotherapy for HCC.High specific expression of SSX-1 and NY-ESO-1 mRNA suggested that we could apply them as tumor markers.The short term recurrence rate was significantly higher in patients whose peripheral blood expressed SSX-1 mRNA,suggesting that SSX-1 mRNA could be used as indicator for recurrence,metastasis and prognosis of HCC. Chin Med J 2007;120(12):1042-1046

Phenol reaction cascades are commonly used in nature to create crosslinked materials that perform mechanical functions. These processes are mimicked by electrochemically initiating a reaction cascade to examine if the mechanical properties of a biopolymer film can be predictably altered. Specifically, thin films (≈ 30–45 μm) of the polysaccharide chitosan are cast onto gold-coated silicon wafers, the chitosan-coated wafers are immersed in catechol-containing solutions, and the phenol is anodically oxidized. The product of this oxidation is highly reactive and undergoes reaction with chitosan chains adjacent to the anode. After reaction, the flexible chitosan film can be peeled from the wafer. Chemical and physical evidence support the conclusion that electrochemically initiated reactions crosslink chitosan. When gold is patterned onto the wafer, the electrochemical crosslinking reactions are spatially localized and impart anisotropic mechanical properties to the chitosan film. Further, deswelling of chitosan films can reversibly transduce environmental stimuli into contractile forces. Films patterned to have spatial variations in crosslinking respond to such environmental stimuli by undergoing reversible changes in shape. These results suggest the potential to enlist electrochemically initiated reaction cascades to engineer chitosan films for actuator functions.

The signal-guided and sequential assembly of biomolecules onto patterned surfaces is demonstrated. Readily transmittable electric signals are used to guide spatially selective deposition of the pH-responsive polysaccharide, chitosan, and functionalized chitosan conjugates, by generating localized pH gradients. The nucleophilic primary amine groups of chitosan enable facile conjugation of proteins and nucleic acids by two approaches, one an enzymatic approach and the other a standard chemical modification, thus providing flexibility when sequentially assembling biomolecules in a spatially selective manner. Moreover, we developed an agarose gel "biomask" for the sequential assembly of single-stranded DNA and confirmed its functionality through nucleic acid hybridization assays.

Biological systems routinely use phenols to construct complex materials with diverse functions. Typically, these phenolic materials are generated using oxidative enzymes to initiate a cascade of uncatalyzed reactions. We mimic these processes to micro-pattern films of the aminopolysaccharide chitosan. Specifically, we microfabricate silicon wafers to have gold patterns, cast a chitosan film onto the patterned wafers, and commence pattern transfer by polarizing the underlying gold surfaces to electrochemically initiate the phenol reaction cascade. The electrochemically initiated reactions lead to modification of the chitosan film's chemistry, structure, and fluorescence. Further, electrochemically initiated modification of the chitosan film is localized to the interfacial region between the film and the anode, with resolution in the lateral direction of at least 20 μm. These results demonstrate that electrochemical pattern transfer provides a promising new method for micropatterning flexible films.

Emerging opportunities are placing greater demands on device fabrication: next-generation microelectronics will need minimum features of less than 100 nm, high-throughput drug screening will require facile methods to incorporate sensitive biological components into microelectromechanical systems (MEMS), and implantable devices will need to be built from biocompatible materials. Increasingly, these emerging demands are being addressed by combining traditional microfabrication methods with 'biofabrication': namely, the use of biologically derived materials and biocatalysts. Recent fabrication techniques are using biological construction materials as process aids or structural components, and enzymes are being considered for their potential to fabricate devices with high selectivity under mild conditions. If incompatibilities between biology and microfabrication can be eliminated, then biofabrication will be poised to emerge as the standard for nanoscale construction.

A protein's functional properties can be adjusted by conjugating it to other polymers. We used a nature-inspired route to create a protein−polysaccharide conjugate and examined the properties of this conjugate. Specifically, the enzyme tyrosinase was used to oxidize accessible tyrosine residues of the model protein green fluorescent protein (GFP). Oxidation yields quinone residues that are “activated” for the covalent conjugation of GFP to nucleophilic groups of the aminopolysaccharide chitosan. Conjugation to chitosan conferred distinct properties to GFP. The GFP−chitosan conjugate was observed to have pH-responsive, “smart” properties, and GFP could be conjugated onto a gel matrix. Additionally, the GFP−chitosan conjugate can be selectively deposited onto a micropatterned surface in response to an applied voltage. This nature-inspired method provides a simple and safe method to conjugate proteins to chitosan, and these conjugates can be readily assembled onto patterned surfaces.

Chitosan, a naturally occurring biopolymer, was used as a scaffold for the covalent binding of single-stranded DNA oligonucleotide probes in a fluorescence-based nucleic acid hybridization assay. Chitosan's pH dependent chemical and electrostatic properties enable its deposition on electrodes and metal surfaces, as well as on the bottom of microtiter plates. A combinatorial 96-well microtiter plate format was used to optimize chemistries and reaction conditions leading to hybridization experiments. We found the coupling of oligonucleotides using relatively common glutaraldehyde chemistry was quite robust. Our hybridization results for complementary ssDNA oligonucleotides (E. coli dnaK sequences) demonstrated linear fluorescence intensity with concentration of E. coli dnaK-specific oligonucleotide from 0.73 μM to 6.6 μM. Moreover, hybridization assays were specific as there was minimal fluorescence associated with noncomplementary groEL oligonucleotide. Finally, these results demonstrate the portability of a DNA hybridization assay based on covalent coupling to chitosan, which, in turn, can be deposited onto various surfaces. More arduous surface preparation techniques involving silanizing agents and hazardous washing reagents are eliminated using this technique. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 646–652, 2003.

Hydrogels are increasingly considered for creating three-dimensional structures in miniaturized devices, yet few techniques exist for creating such hydrogel structures. We report a new approach for creating hydrogels using the amine-containing polysaccharide chitosan. Specifically, electrodes are immersed into a slightly acidic chitosan solution and a voltage is applied to promote the proton-consuming hydrogen evolution reaction at the cathode surface. This reaction leads to a high localized pH in the vicinity of the cathode surface, and if this localized pH exceeds about 6.3, then chitosan becomes insoluble and deposits at the cathode surface. As the current density is increased, the region of high pH is expected to extend further from the cathode surface into the bulk solution. Using moderately high current densities (50 A/m2), we observed that chitosan deposited as a thick hydrogel. Measurements of the water content confirmed that the deposited chitosan was a hydrogel. To suggest the potential utility,...

The amine-containing polysaccharide chitosan was selectively deposited onto patterned gold surfaces in response to an applied voltage. Standard microfabrication techniques were used to pattern gold onto silicon wafers, and these gold patterns served as templates for the electric field directed deposition of chitosan. Experiments conducted with a fluorescently labeled chitosan derivative demonstrated the spatially selective deposition of chitosan onto gold surfaces that were polarized to serve as negative electrodes. Studies with unlabeled chitosan demonstrated that a “templated” chitosan, deposited by voltage programming of electrodes, can subsequently react with standard amine-selective functional groups. This indicates that common coupling chemistries can be exploited to assemble a variety of compounds onto the deposited chitosan pattern. Thus, chitosan appears to be a unique interface material that can be “templated” onto patterned inorganic surfaces and is reactive for the subsequent assembly of organ...

We examined the assembly of the amine-rich polysaccharide chitosan from solution onto electrode surfaces as a result of voltage bias on the electrode. Chitosan is positively charged and water soluble under mildly acidic conditions and is uncharged and insoluble under basic conditions. We observed that chitosan is deposited from acidic solution onto the surface of a negative electrode and the thickness of the deposited layer is on the order of a micron. The thickness of the deposited layer was observed to be dependent upon the deposition time, the applied voltage, and the chitosan concentration. No deposition was observed on the positive electrode or on an “electrode” that had no applied voltage. Once deposited and neutralized, the chitosan layer can be retained on the electrode surface without the need for an applied voltage. Infrared (FT-IR) and electrospray mass spectrometry confirmed that the deposited material was chitosan. These results demonstrate that chitosan can be deposited and retained on elect...

Eph receptor (Eph)‐ephrin signaling plays an important role in organ development and tissue regeneration. Bidirectional signaling of EphB4–ephrinB2 regulates cardiovascular development. To assess the role of EphB4–ephrinB2 signaling in cardiac lineage development, we utilized two GFP reporter systems in embryonic stem (ES) cells, in which the GFP transgenes were expressed in Nkx2.5+ cardiac progenitor cells and in α‐MHC+ cardiomyocytes, respectively. We found that both EphB4 and ephrinB2 were expressed in Nkx2.5‐GFP+ cardiac progenitor cells, but not in α‐MHC‐GFP+ cardiomyocytes during cardiac lineage differentiation of ES cells. An antagonist of EphB4, TNYL‐RAW peptides, that block the binding of EphB4 and ephrinB2, impaired cardiac lineage development in ES cells. Inhibition of EphB4–ephrinB2 signaling at different time points during ES cell differentiation demonstrated that the interaction of EphB4 and ephrinB2 was required for the early stage of cardiac lineage development. Forced expression of human full‐length EphB4 or intracellular domain‐truncated EphB4 in EphB4‐null ES cells was established to investigate the role of EphB4‐forward signaling in ES cells. Interestingly, while full‐length EphB4 was able to restore the cardiac lineage development in EphB4‐null ES cells, the truncated EphB4 that lacks the intracellular domain of tyrosine kinase and PDZ motif failed to rescue the defect of cardiomyocyte development, suggesting that EphB4 intracellular domain is essential for the development of cardiomyocytes. Our study provides evidence that receptor‐kinase‐dependent EphB4‐forward signaling plays a crucial role in the development of cardiac progenitor cells. J. Cell. Biochem. 116: 467–475, 2015. © 2014 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals, Inc.

To investigate the impact of serum α-fetoprotein (AFP) level on survival and short-term recurrence after R0 resection in primary hepatocellular carcinoma (HCC).The clinical data of 582 cases of primary HCC underwent R0 resection from January 1997 to December 2009 was analyzed retrospectively. There were 488 male and 94 female patients whose average age was 51 years (ranging from 31 to 73 years). The survival rate of 1-, 3- and 5-year and clinopathological factors between the AFP-negative group and AFP-positive group were compared. The risk factors of short-term recurrence after R0 resection of HCC patients in AFP-positive group were further analyzed.The age and histological differentiation in AFP-positive group were significantly lower than the AFP-negative group (χ(2) = 11.004, 32.293; P = 0.000). Otherwise the serum γ-glutamyl transferase level, diameter of tumor, TNM stage and short-term recurrence were higher than the AFP-negative group (χ(2) = 9.814 to 14.009, P0.05) , and solitary HCC in AFP-positive group was less than AFP-negative group (χ(2) = 8.509, P = 0.004). Survival analysis showed that overall survival rate of 1-, 3- and 5- year were 80.5%, 53.9%, 40.2% and 89.2%, 69.8%, 50.3% in the AFP-positive group and AFP-negative group, respectively (χ(2) = 11.884, P = 0.001), and the disease-free survival rate of 1-, 3- and 5- year were 65.6%, 38.4%, 29.6% and 81.7%, 51.0%, 42.1% (χ(2) = 15.574, P = 0.000). The median overall survival time of short-term recurrence and not short-term recurrence were 10 months and 62 months, respectively (χ(2) = 45.013, P = 0.000). The median survival time from recurrence to death were 6 months and 14 months, respectively (χ(2) = 40.581, P = 0.000). Multiple-factor analysis suggested that non-solitary HCC and histological low differentiation are independent risk factors which influence short-term recurrence of HCC patients.The increase of preoperative serum AFP level suggests the potency of HCC short-term recurrency.

An ultrathin palladium film on a porous TiO2 ceramic membrane was successfully synthesized by a novel photocatalytic deposition (PCD) method. The mechanism was interpreted by the photocatalytic reaction between the surface of the TiO2 semiconductor and the Pd(II) solution. Energy dispersive (EDS) analysis and argon permeability of the membrane were used to characterize the deposited Pd. During the PCD process, photoreaction took place with higher efficiency when the pH value of the solution was controlled at the 3—3.5 range. A short irradiation time of 18 min was enough for PCD at a normal reaction temperature. A methanol additive in the solution of about 40 vol. % was optimum for the deposition of Pd. XRD and SEM results on the Pd-based membrane prepared by PCD indicated that the metal existed in the form of a pure palladium element, with a layer thickness of about 0.1 μm. The gas permeation experiment was conducted in a high-temperature permeator from 623 to 723 K. The results indicated that there were contributions to the hydrogen flux attributable to both dense and microholes parts of the resulting Pd/TiO2 membrane.

An ultrathin palladium membrane was prepared by an improved electroless plating technique on the surface of a porous titania ceramic substrate. A simple yet new and valuable activation technique named photocatalytic deposition (PCD) has been presented. The thickness of the resulting palladium membrane was about 0.3−0.4 μm. Hydrogen permeation through the composite membrane was proportional to the hydrogen partial pressure difference. The hydrogen permeability and H2:N2 selectivity through the palladium composite membrane are 6.3 × 10-6 mol m-2 s-1 Pa-1 and 1140 at 773 K, respectively. The activation energy for hydrogen permeation is 21.27 kJ/mol at the temperature range of 673−773 K. Long-term hydrogen permeation operation at 673 K indicated that the flux through the resulting membrane under hydrogen/nitrogen gradients requires 80 h to reach a steady state. The steady-state hydrogen flux showed no observable changes during the thermal cycles between 673 and 773 K.

Background We studied the relationships among Cx43, CD105, and VEGF in specimens of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different serum AFP levels with respect to recurrence and metastasis. Methods Expressions of Cx43, CD105, and VEGF in 234 HCC tissue specimens were examined using tissue microarray and immunohistochemistry. Cx43 mRNA expression was examined in 38 frozen HCC specimens using RT-PCR. Correlations between these expressions and tumor recurrence, metastasis, and prognosis were analyzed using Kaplan–Meier and Cox regression analyses. Results Cx43 expression correlated with early tumor recurrence (P = 0.001), disease-free survival (P = 0.026), and overall survival (P = 0.000) in patients with serum AFP P = 0.018 and 0.023, respectively), histological differentiation (P = 0.002), vessel tumor embolism (P = 0.029), and focal number (P = 0.017). Immunohistochemistry showed that Cx43 expression in patients with low AFP was lower in patients with distant metastases than in those with no metastasis or those with liver metastasis. Patients with early recurrence expressed less Cx43 mRNA than did those with no recurrence (χ2 = 9.827, P = 0.002). Conclusions Cx43 expression can delay early HCC recurrence, metastasis, and poor prognosis after radical hepatectomy in patients with HBV-related HCC and low AFP.

To investigate the expression of CK19 in HBV-related hepatocellular carcinoma (HCC) tissues in patients with low serum AFP concentration and the relationship between them and the recurrence and prognosis of HCC after R0 radical hepatectomy.The expressions of CK19 and Ki67 in HCC tissues of 235 cases were examined using tissue microarray and two-step methods of PV-6000 immunohistochemistry. The expression of CK19 mRNA in 20 frozen HCC specimens was examined by RT-PCR. The correlation between gene expressions and tumor recurrence and prognosis was analyzed.Among the 235 HBV-related HCC patients after R0 radical hepatectomy, the median disease-free survival (DFS) was 31.2 months in the patients with serum AFP400 µg/L and 13.8 months in the patients with serum AFP ≥ 400 µg/L (P = 0.041), the overall survival (OS) was 84.0 and 58.6 months in the two subgroups (P = 0.125), and the tumor recurrence within one year was in 43 cases (27%) and 37 cases (49.3%), respectively, (P = 0.001). The DFS was 11.6 months in the CK19-positive cases and 27.0 months in the CK19-negative cases (P0.05). The OS was significantly lower in the CK19-positive cases than that in the CK19-negative cases (P = 0.023). Both DFS and OS in the CK19-positive cases with AFP400 µg/L were significantly lower than those in the CK19-negative cases with AFP400 µg/L (both P0.05). The CK19 expression was significantly correlated with histological differentiation (P = 0.023), number of tumor foci (P = 0.044), vascular tumor embolism (P = 0.005), regional lymph node metastasis (P = 0.023), and 1-year recurrence (P = 0.006). Among the patients with AFP400 µg/L, the 1-year recurrence was 53% in the CK19-positive cases and 23% in the CK19-negative cases (P0.001), the median DFS was 11.3 months in CK19-positive cases and 34.0 months in CK19-negative cases (P = 0.010), and the median OS was 19.5 months in the CK19-positive cases, significantly lower than 84.0 months in the CK19-negative cases (P = 0.001). Cox regression analysis showed that CK19-positive expression was an independent factor affecting early HCC recurrence and prognosis.In HBV-related HCC patients after radical hepatectomy with AFP400 µg/L, positive expression of CK19 indicates a higher proliferation and invasiveness of HCC, and is an important factor of early recurrence and poor prognosis.