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This study examined the longitudinal associations between parental feeding practices and child weight status, and their potential modification effects by child sex, age, and maternal and paternal educations among children. Data were collected from 2015 to 2017 of 2139 children aged 6–17 years and their parents in five Chinese mega-cities. Parental feeding practices were assessed using 11-items from Child Feeding Questionnaire. Waist-to-height ratio (WHtR), body mass index (BMI), and general and central obesity were measured and analyzed using a mixed-effects model. Three parental feeding patterns were identified by factor analysis including “concern”, “pressure to eat”, and “control”. Concern was associated with higher BMI z-score, WHtR (βs ranged from 0.01 to 0.16), and general obesity (ORs ranged from 1.29 to 6.41) among children aged ≤12 years and >12 years, regardless of child sex and parental educations. Pressure to eat was associated with lower BMI z-score (β = −0.08, p < 0.001), WHtR (β = −0.004, p < 0.01), and general (OR = 0.53, 95%CI = 0.42, 0.66) and central obesity (OR = 0.72, 95%CI = 0.58, 0.90) among children aged ≤12 years. Further analyses showed that significant associations were found for children with maternal or paternal education of college and above. Control was associated with increased risk of general and central obesity among children with maternal education of college and above, regardless of age. Our study indicates that higher concern and lower pressure to eat were associated with increased risk of obesity among children. Control was associated with increased risk of obesity among children with maternal education of college and above. Future childhood obesity preventions may optimize parental feeding practices.

Harsh local microenvironment, such as hypoxia and lack of instructive clues for transplanted stem cells, presents the serious obstacle for stem cell therapies’ efficacy. Therefore, continued efforts have been taken to improve stem cells’ viability and plasticity. Hepatocyte growth factor (HGF) have previously been reported to mitigate complications of various human diseases in animal model studies and in some clinical trials. Besides, human stem cells from root apical papilla (SCAP) are deemed a better resource of mesenchymal stem cells due to derived stem cells holding greater amplification ability in vitro compared with those from other dental resources. To move forward, evaluating effects and understanding underlying molecular mechanisms of HGF on SCAP for periodontal regeneration are needed. In this study, HGF was transgenic expressed in SCAP, and it was found that HGF enhanced osteo/dentinogenic differentiation capacity of SCAP compared with those non-treated control in an ectopic mineralization model. Moreover, HGF reduced apoptosis of SCAP under both normoxia and hypoxia condition, whereas combination of HGF and hypoxia exposure had inhibitory effects on cell proliferation during an eight-day in vitro culture period. Transcriptome analysis further revealed that suppressed cell cycle progression and activated BMP/ TGFβ, Hedgehog, WNT, FGF, HOX and other morphogen family members upon HGF overexpression, which may render SCAP recapitulate part of neural crest stem cells characteristics. Moreover, strengthened stress-response modulation such as unfolded protein response, macroautophagy and anti-apoptotic molecules might explain increased viability of SCAP. In all, our results imply that these potential mechanisms underlying HGF promoting SCAP differentiation could be further elucidated and harnessed to improve dental tissue regeneration.

The resilience of the fiscal system has a driving effect on environmental governance, and it is always a challenge to solve the problem of matching fiscal power with administrative power. Based on the panel data of 193 cities in China from 2013 to 2018, the data envelopment analysis method was used to evaluate the comprehensive indicators of urban environmental efficiency. The impact of fiscal stress on environmental efficiency is examined from the perspective of urban horizontal imbalance. We find that the smaller the fiscal stress, the higher urban environmental efficiency. The endogeneity is mitigated by using instrumental variables and the generalized method of moments, and the results are still robust after considering the interference of sample selection bias and variable estimation bias. At the same time, the impact of fiscal stress on environmental efficiency varies with spatial location, ecological strategic planning, economic development, and other factors, especially in southern cities, cities in the Yangtze River Basin, and cities in urban agglomerations, where reducing fiscal stress promotes environmental efficiency. In addition, green production and public environmental services are important channels for its role, and the rational allocation of self-raised funds can effectively moderate the improvement of environmental efficiency.

An ultra-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) method for the simultaneous determination of Crocin-I and its primary metabolites Crocetin was established, and a comparison of metabolic characteristics in vivo is made to Crocin-I and Crocetin in normoxic and hypoxic rats after intragastric administration. The acute hypoxic rat model was established by simulating high altitude environment in a hypobaric hypoxia animal experimental chamber. After intragastric administration of 400 mg•kg

To alleviate the negative impact of noise on wireless federated learning (FL), we propose a channel-weighted aggregation scheme of FL (CWA-FL), in which the parameter server (PS) makes aggregation of the gradients according to the channel conditions of devices.} \textcolor{blue}{In the proposed scheme}, the gradients are transmitted to the PS in an uncoded way through an orthogonal multiple access (OMA) channel\textcolor{blue}{, which can avoid the synchronization issue among devices faced by over-the-air FL.} The convergence analysis of CWA-FL is conducted and the theoretical results show that the scheme can converge with the rate of O(1/T). Simulation results show that the proposed scheme performs better than the equal-weighted aggregation scheme of FL (EWA-FL) and is more robust to noise.

BackgroundCOVID-19 has caused more than 2.6 billion infections and several million deaths since its outbreak 2 years ago. We know very little about the long-term cellular immune responses and the kinetics of neutralizing antibodies (NAbs) to SARS-CoV-2 because it has emerged only recently in the human population.MethodsWe collected blood samples from individuals who were from the first wave of the COVID-19 epidemic in Wuhan between December 30, 2019, and February 24, 2020. We analyzed NAbs to SARS-CoV-2 using pseudoviruses and IgG antibodies to SARS-CoV-2 spike (S) and nucleocapsid (N) protein using enzyme-linked immunosorbent assay in patients’ sera and determined SARS-CoV-2-specific T-cell responses of patients with ELISpot assays.ResultsWe found that 91.9% (57/62) and 88.9% (40/45) of COVID-19 patients had NAbs against SARS-CoV-2 in a year (10–11 months) and one and a half years (17–18 months), respectively, after the onset of illness, indicating that NAbs against SARS-CoV-2 waned slowly and possibly persisted over a long period time. Over 80% of patients had IgG antibodies to SARS-CoV-2 S and N protein one and a half years after illness onset. Most patients also had robust memory T-cell responses against SARS-CoV-2 one and a half years after the illness. Among the patients, 95.6% (43/45) had an IFN-γ-secreting T-cell response and 93.8% (15/16) had an IL-2-secreting T-cell response. The T-cell responses to SARS-CoV-2 were positively correlated with antibodies (including neutralizing antibodies and IgG antibodies to S and N protein) in COVID-19 patients. Eighty percent (4/5) of neutralizing antibody-negative patients also had SARS-CoV-2-specific T-cell response. After long-term infection, protective immunity was independent of disease severity, sex, and age.ConclusionsWe concluded that SARS-CoV-2 infection elicited a robust and persistent neutralizing antibody and memory T-cell response in COVID-19 patients, indicating that these sustained immune responses, among most SARS-CoV-2-infected people, may play a crucial role in protection against reinfection.

Background: Breast cancer is a complex disease with high prevalence in women, the molecular mechanisms of which are still unclear at present. Most transcriptomic studies on breast cancer focus on differential expression of each gene between tumor and the adjacent normal tissues, while the other perturbations induced by breast cancer including the gene regulation variations, the changes of gene modules and the pathways, which might be critical to the diagnosis, treatment and prognosis of breast cancer are more or less ignored. Objective: We presented a complete process to study breast cancer from multiple perspectives, including differential expression analysis, constructing gene co-expression networks, modular differential connectivity analysis, differential gene connectivity analysis, gene function enrichment analysis key driver analysis. In addition, we prioritized the related anti-cancer drugs based on enrichment analysis between differential expression genes and drug perturbation signatures. Methods: The RNA expression profiles of 1109 breast cancer tissue and 113 non-tumor tissues were downloaded from The Cancer Genome Atlas (TCGA) database. Differential expression of RNAs was identified using the “DESeq2” bioconductor package in R, and gene co-expression networks were constructed using the weighted gene co-expression network analysis (WGCNA). To compare the module changes and gene co-expression variations between tumor and the adjacent normal tissues, modular differential connectivity (MDC) analysis and differential gene connectivity analysis (DGCA) were performed. Results: Top differential genes like MMP11 and COL10A1 were known to be associated with breast cancer. And we found 23 modules in the tumor network had significantly different co-expression patterns. The top differential modules were enriched in Goterms related to breast cancer like MHC protein complex, leukocyte activation, regulation of defense response and so on. In addition, key genes like UBE2T driving the top differential modules were significantly correlated with the patients’ survival. Finally, we predicted some potential breast cancer drugs, such as Eribulin, Taxane, Cisplatin and Oxaliplatin. Conclusion: As an indication, this framework might be useful in understanding the molecular pathogenesis of diseases like breast cancer and inferring useful drugs for personalized medication.

This article presents a switched-transformer-based polar Doherty digital power amplifier (DPA) for deep back-off efficiency enhancement. A single-transformer-footprint parallel-combining transformer (PCT) power combiner is introduced for 1.3–3.5-GHz wide frequency coverage, dynamic load modulation at 0-/6-/12-/18-dB power back-off (PBO) levels, and an ultra-compact die size. Implemented in 40-nm CMOS, the DPA is powered by a 1.1-V supply and only occupies 0.7 $\times $ 1.15 mm2 chip area. It achieves 21.4-dBm peak power with the power added efficiencies (PAEs) of 31.3%, 27.7%, 16.6%, and 7.7% for 0-/6-/12-/18-dB PBOs at 1.5 GHz. With 20-MHz 64QAM long term evolution (LTE) signal, the DPA achieves ${P}_{{\text {avg}}}$ of 15.2 dBm and the average PAE of 25.3% with −32.5-dB error vector magnitude (EVM) at 1.5 GHz. Moreover, for 20-MHz 64 QAM WLAN signal, ${P}_{{\text {avg}}}$ of 14.7 dBm with the average PAE of 20.1% is obtained with − 25-dB EVM at 2.4 GHz.

Recently recommender systems become more and more significant in the daily life. Although the recommender systems based on the generative adversarial network (GAN) are competent, the user trust information is seldom taken into consideration. In this paper, we propose a Trust-Aware Generative adversarial network with recurrent neural network for RECommender systems named TagRec, which makes use of the user trust information for top-N recommendation. In the framework, the discriminative model is a multi-layer perceptron to distinguish whether a sample is from the real data or fake data. The discriminator helps to guide the training of the generative model to make it fit the data distribution of the user trust information. The generative model is a recurrent neural network (RNN) with long short-term memory (LSTM) cells, aiming to confuse the discriminative model by generating samples as similar as possible to the real data. Through the adversarial training between the discriminative and generative models, the user trust information can be fully used to improve the recommendation performance. We conduct extensive experiments on real-word datasets to validate the effectiveness of the TagRec.

Reactive Black 5 (RB5) is a typical refractory azo dye. Widespread utilization of RB5 has caused a variety of environmental and health problems. The enzymatic degradation of RB5 can be a promising solution due to its superiority as an eco-friendly and cost-competitive process. Bacterial CotA-laccase shows great application prospect to eliminate hazardous dyes from wastewater. However, efficient decolorization of RB5 CotA-laccase generally requires the participation of costly, toxic mediators. In the present study, we modified the amino acids Thr415 and Thr418 near the type 1 copper site and the amino acid Gln442 at the entrance of the substrate-binding pocket of Bacillus pumilus W3 CotA-laccase to boost its RB5 decolorization activity based on molecular docking analysis and site-saturation mutagenesis. Through the strategies, two double site mutants T415D/Q442A and T418K/Q442A obtained demonstrated 43.94 and 52.64% RB5 decolorization rates in the absence of a mediator at pH 10.0, respectively, which were about 3.70- and 4.43-fold higher compared with the wild-type CotA-laccase. Unexpectedly, the catalytic efficiency of the T418K/Q442A to ABTS was enhanced by 5.33-fold compared with the wild-type CotA-laccase. The mechanisms of conferring enhanced activity to the mutants were proposed by structural analysis. In summary, the mutants T415D/Q442A and T418K/Q442A have good application potentials for the biodegradation of RB5. KEY POINTS: • Three amino acids of CotA-laccase were manipulated by site-saturation mutagenesis. • Decolorization rate of two mutants to RB5 was enhanced 3.70- and 4.43-fold, respectively. • The mechanisms of awarding enhanced activity to the mutants were supposed.

This letter presents a fractional-N frequency synthesizer with an ultrawideband continuously tuning range of 32.4% centered at 26.85- and 8.7-GHz chirp for frequency-modulated continuous-wave (FMCW) radars. The synthesizer uses a fractional-N 9-GHz charge-pump phase-locked loop (CPPLL) cascaded by an injection-locked frequency tripler (ILFT). A voltage-controlled oscillator (VCO) with transformer (TFM) coupling for an enhanced linear control voltage range, a better quality factor and good isolation from the load seen by the resonator, and a wide output voltage range charge-pump (CP) are used to achieve the ultrawideband CPPLL. The ILFT is implemented using a weakly coupled TFM for broadband locking range and 3-dB output power. The synthesizer is fabricated in the 40-nm CMOS technology and consumes 28.5 mW. The phase noise (PN) of the synthesizer at 27 GHz is -97.87 dBc/Hz at 1 MHz and the prototype is capable of generating a triangle or sawtooth chirp of 8.7-GHz modulation bandwidth with an rms FM error of 0.04% of BWchirp.

Fiber-shaped supercapacitors (FSCs) are promising energy storage devices that meet the growing demands for the miniaturization, flexibility and compatibility of wearable electronics. However, when compared with batteries, the low energy density remains the main limitation to practical applications. Conjugated microporous polymer (CMP) network synthesized using Buchwald-Hartwig cross-coupling reactions, featured tailorable porous structures, reversible redox chemistry and demonstrated highly efficient capacitive performance. Herein CMP network grafted on carbon nanotube fibers (CNF@CMP) with high areal specific capacitance (671.9 mF cm-2 at a current density of 1 mA cm-2) were successfully achieved for polytriphenylamine (PTPA)-based network. All-solid-state symmetrical twisted CNF@PTPA FSCs fabricated with PVA/H3PO4 as gel electrolyte exhibited a high specific areal capacitance of 398 mF cm-2 (0.28 mA cm-2), a maximal operating voltage of 1.4 V, and an energy density of 18.33 μWh cm-2. Moreover, they showed excellent flexibility and mechanical stability retaining 84.5% of the initial capacitance after 10000 bending cycles. These materials provide a new route to high-performance wearable supercapacitors (HPWS), with wide potential applications in wearable electronics, as shown by the examples provided.

To investigate the transport characteristics of chloride ions in cement-based materials, the Mori-Tanaka (M-T) prediction scheme of the effective diffusion coefficient in composites containing single-phase and multi-phase inclusions is systematically deduced based on the theory of composite mechanics and porous medium. The volume fraction, morphology and distribution of aggregates, as well as the interfacial transition zone (ITZ) are fully taken into consideration in this proposed model. The results show that the algorithm of M-T prediction scheme with high accuracy is relatively simple.

Previously, we reported that the longest variant of the GABA A receptor γ2 subunit (GABRG2) was associated with suicidal behavior. The present study therefore aimed to determine whether polymorphisms near the alternatively spliced exon of GABRG2 are associated with suicide attempt (SA) and its related traits, and how these variants might interact with reported childhood trauma (CT) in their association with suicidal behavior.We examined 5 single nucleotide polymorphisms (SNPs) of GABRG2. Subjects were suicide Attempters (N = 94), non-suicide attempters (N = 168) with MDD or Bipolar depression, and healthy volunteers (N = 100). Data on demographics, depression severity and suicide attempts were collected. Participants also completed a set of instruments assessing CT, and lifetime aggression and impulsivity.. GABRG2 polymorphisms were genotyped using Sanger sequencing.Allele A of rs211034 was a protective factor for SA (OR = 0.50 (0.32, 0.80), p = 0.003), and had an interaction effect with emotional neglect (OR = 0.89 (0.82, 0.97), p = 0.006) on depression. One haploblock (consisting of rs211035 and rs211034) was identified within these SNPs, and subjects with haplotype GA (frequency = 7.3%), had lower rate of SA (OR=0.26(0.10, 0.67), p = 0.006). Cognitive impulsivity (OR=1.38)1.24,1.55), p 0.001), non-planning impulsivity (OR = 1.18 (1.10,1.25), p 0.001), anger (OR = 1.13 (1.07,1.19), p 0.001), impulsivity total score (OR = 1.10(1.06,1.15), p 0.001), hostility (OR = 1.10 (1.04, 1.15), p 0.001), aggression total score (OR = 1.05 (1.03,1.07), p 0.001) were associated with depression, meanwhile, hopelessness (OR = 2.18 (1.56, 3.04), p 0.001) and impulsivity total score (OR = 1.05 (1.02,1.08), p 0.001) were associated with the risk of SA, adjusted by age and gender. There was no mediation effect in the relationship among CT, gene polymorphisms and SA or depression through increased impulsivity or aggression.The main limitation of this study is its modest sample size. More genetic variants as well as epigenetic markers should be examined in future studies.These findings add to evidence for the involvement of GABRG2 and impulsivity and hopelessness in SA independent from their association with depression. More research is needed on possible mediators of the relationship between GABA-related gene and SA.

To enhance dibenzothiophene (DBT) capture performance, we innovatively synthesized a series of novel multimetal–organic frameworks (MMOFs) by the incorporation of Ag+, Cu2+, Zn2+, and Ni2+ within one structure. Those novel desulfurizers have been fully characterized and their structural changes further compared in terms of nitrogen adsorption–desorption, powder X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, inductively coupled plasma, X-ray photoelectron spectroscopy, and so forth. The DBT capture properties with as-synthesized MMOFs in different simulated fuels were evaluated through a series of batch tests. All further investigations demonstrated that the Ag/Zn/Ni/Cu-BTC exhibited a remarkably high sulfur capacity attributed to the associative effects of π-complexation and acid–base interaction. Additionally, based on sieving and inertia mechanisms, this adsorbent possessed an extremely high affinity for DBT capture in the presence of benzene and octane. Especially, the Ag/Zn/Ni/Cu-BTC could sustain an outstanding desulfurization property after the fifth cycle. Our study opens up a new perspective for the design of desirable MMOF materials, promoting their potential development in the aspects of adsorption desulfurization.

In the corrosive environment of chloride, the drying–wetting alternating zones are most seriously eroded by harmful media. Firstly, based on the new porosity and tortuosity model, considering the i...

Many metal–organic frameworks (MOFs) suffer from hydrothermal instability issues, which definitely restricted their practical applications, such as deep desulfurization. In the present contribution...

Glycyrrhiza uralensis Fisch., known as licorice, is one of the most famous traditional Chinese medicines. In this study, we perform a metabolome analysis using liquid chromatography-tandem mass spectrometry to assign bioactive components in different parts of licorice from different geographical origins in Gansu province of China. Sixteen potential biomarkers of taproots from different geographical origins were annotated, such as glycycoumarin, gancaonin Z, licoricone, and dihydroxy kanzonol H mainly exist in the sample of Jiuquan; neoliquiritin, 6'-acetylliquiritin, licochalcone B, isolicoflavonol, glycyrol, and methylated uralenin mainly exist in Glycyrrhiza uralensis from Lanzhou; gancaonin L, uralenin, and glycybridin I mainly exist in licorice from Wuwei for the first time.

Gesture air-writing is an advanced nontouching interaction method that replaces traditional typewriter keyboards, touch screens and other input devices. Due to its low power consumption, noncontact detection and independence from light conditions, millimeter wave radar has become a valuable gesture air-writing solution. In this paper, we proposed a prototype of a gesture air-writing tracking system that is based on the 24-GHz frequency-modulated continuous-wave (FMCW) radar system-on-chip (SoC). The transmitted chirp signal of this radar chip covers up to a 4-GHz bandwidth, which provides sufficient range resolution to track hand gestures. With the development of single input, multiple output (SIMO) antennas, the air-writing symbols can be reconstructed in an observation plane. A system design and signal processing algorithm for gesture air-writing applications is proposed for the prototype system in this paper. To test the performance of the proposed method, experiments with cases of five simple gestures, air-writing numbers and letter tracking are carried out. The experimental results verify the efficiency and accuracy of the proposed method.

Aim: Insulin antibodies (IAs) affects blood glucose control in patients using insulin therapy. We aim to investigate the association between different glucose-lowering treatments and IAs in patients with type 2 diabetic mellitus (T2DM).Methods: In this cross-sectional, retrospective study, patients with T2DM who were using exogenous insulin therapy were included. All the patients had stable antidiabetic therapy in the last 3 months and measured IA levels using the iodine-125 array. Results: A total of 1863 patients were enrolled. There were 902 (48.4%) patients with positive IAs (IA level >5%), and the mean IA level was 11.06 (10.39, 11.72) %. IA level was positively correlated with fasting blood glucose (OR=1.069, p p The IA levels in patients using sulfonylureas/glinides (8.3 %), metformin (9.6 %), and DPP-4 inhibitors (8.2 %) were all lower than in patients without these drugs (p all Conclusions: IA levels should be measured in patients with long-term insulin therapy. Insulin glargine and the combination of oral glucose-lowering drugs should be considered in IA positive patients.

The TEMPO/NaBr/NaClO system was used to modify konjac glucomannan and prepare β-1,4-linked D-mannuronic/glucuronic acid oligosaccharides. The impact of oxidant amount on the degree of oxidation, molecular weight, terminal structure and the ratio of sugar units were systematically investigated. Mannoses were transformed to mannuronic acids quantitatively, while some glucose were transformed to glucuronic acids, some degraded. The unspecific oxidation causes strong degradation of konjac glucomannan sugar chains. Multiple terminal structures were observed in the oxidized KGM products. According to those observations, the oxidation pattern of konjac glucomannan with the TEMPO/NaBr/NaClO system was speculated. It is suggested that the axial hydroxyl group at position 2 in mannose might form a hydrogen bond with the oxygen on the sugar ring. It would against the unspecific oxidation. While, both specific and unspecific oxidations were observed at glucose units with an equatorial hydroxyl group at position 2, and the degradation occurs mostly on glucose during the oxidation.

Background and AimsTo compare the effects of real-time and retrospective flash glucose monitoring (FGM) on daily glycemic control and lifestyle in patients with type 2 diabetes on premix insulin therapy.Methods and ResultsA total of 172 patients using premix insulin, with HbA1c ≥ 7.0% (56 mmol/mol), or the time below the target (TBR) ≥ 4%, or the coefficient of variation (CV) ≥36% during the screening period, were randomly assigned to retrospective FGM (n = 89) or real-time FGM group (n = 83). Another two retrospective or real-time 14-day FGMs were performed respectively, 1 month apart. Both groups received educations and medication adjustment after each FGM. Time in range (3.9~10.0 mmol/l, TIR) increased significantly after 3 months in the real-time FGM group (6.5%) compared with the retrospective FGM group (-1.1%) (p = 0.014). HbA1c decreased in both groups (both p < 0.01). Real-time FGMs increased daily exercise time compared with the retrospective group (p = 0.002).ConclusionsReal-time FGM with visible blood glucose improves daily glycemic control and diabetes self-care behaviors better than retrospective FGM in patients with type 2 diabetes on premix insulin therapy.Clinical Trial Registrationhttps://clinicaltrials.gov/NCT04847219.

Thyroid cancer was the most common cancer in the endocrine system with relatively slow progression and high survival rate. BRAF mutations were the common diagnostic biomarker. There have several methods used to detect BRAF mutations, including next-generation sequencing (NGS). However, NGS was an expensive detection that was not suitable for initial screening of all clinical patients. In this study, mass spectroscopy (MS) method, as a more sensitive, low price and accurate detection method, was applied for the detection of BRAF V600E mutation from Fine-needle aspiration (FNA) samples of thyroid carcinoma patients, and compare its sensitivity with that of NGS. For the 93 FNA samples that had previously undergone NGS detecting, the MS method was used to detect BRAF mutation in DNA samples and then compared using the BRAF mutation status in NGS detection as a standard.

The purpose of this study was to investigate the relationship between molecular variation and clinicopathological features in GIST patients by targeted next-generation sequencing (NGS), in order to deepen the understanding of GIST individualized treatment.

With the rapid development of Artificial Intelligence (AI) and Internet of Things (IoTs), an increasing number of computation intensive or delay sensitive biomedical data processing and analysis tasks are produced in vehicles, bringing more and more challenges to the biometric monitoring of drivers. Edge computing is a new paradigm to solve these challenges by offloading tasks from the resource-limited vehicles to Edge Servers (ESs) in Road Side Units (RSUs). However, most of the traditional offloading schedules for vehicular networks concentrate on the edge, while some tasks may be too complex for ESs to process. To this end, we consider a collaborative vehicular network in which the cloud, edge and terminal can cooperate with each other to accomplish the tasks. The vehicles can offload the computation intensive tasks to the cloud to save the resource of edge. We further construct the virtual resource pool which can integrate the resource of multiple ESs since some regions may be covered by multiple RSUs. In this paper, we propose a Multi-Scenario offloading schedule for biomedical data processing and analysis in Cloud-Edge-Terminal collaborative vehicular networks called MSCET. The parameters of the proposed MSCET are optimized to maximize the system utility. We also conduct extensive simulations to evaluate the proposed MSCET and the results illustrate that MSCET outperforms other existing schedules.

Phenolipids are characteristic phytochemicals of Syzygium genus. However, the antidiabetic potential and underlying molecular mechanism of these components are not fully elucidated. Herein, we studied the anti-diabetic effects of jambone E (JE), a phenolipid from S. cumini, with in vitro and in vivo models. Data from current study showed that JE enhanced glucose consumption and uptake, promoted glycogen synthesis, and suppressed gluconeogenesis in insulin resistant (IR)-HepG2 cells and primary mouse hepatocytes. JE also attenuated streptozotocin-induced hyperglycemia and hyperlipidemia in type 1 diabetic (T1D) mice. Eleven metabolites (e.g. trimethylamine n-oxide, 4-pyridoxic acid, phosphatidylinositol 39:4, phenaceturic acid, and hippuric acid) were identified as potential serum biomarkers for JE's antidiabetic effects by an untargeted metabolomics approach. The further molecular mechanistic study revealed that JE up-regulated phosphorylation levels of protein kinase B (AKT), glycogen synthase kinase 3 beta, and forkhead box O1 (FoxO1), promoted nuclear exclusion of FoxO1 whilst decreased gene expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha, phosphoenolpyruvate carboxykinase and glucose 6-phosphatase in IR-HepG2 cells and T1D mice. Our data suggested that JE might be a potent activator for AKT-mediated insulin signaling pathway, which was confirmed by the usage of AKT inhibitor and AKT-target siRNA interference, as well as the cellular thermal shift assay. Findings from the current study shed light on the anti-diabetic effects of phenolipids in the Syzygium species, which supports the use of medicinal plants in the Syzygium genus for potential pharmaceutical applications.

Tanshinone IIA (TAN) is widely employed for handling cardiovascular disorders. The current study explored the potential role of miRs in the antifibrotic effect of TAN on heart. Fibrotic features were induced in cardiac fibroblasts (CFs) and in rat hearts, and then handled with TAN. MicroRNAs (miRs) responding to TAN were determined using a microarray assay. The selected miR was modulated to verify its role in antifibrotic effects of TAN. TAN suppressed the viability and the production of α-SMA in CFs, which was associated with 101 miR being upregulated and 223 miR being downregulated. MiR-618 was selected as the potential target of TAN. Ang II inhibited miR-618 level and resulted in the upregulation of pro-fibrosis factors, which was reversed by TAN. The antifibrotic effect of TAN was weakened by miR-618 inhibition. TAN inhibits hypertrophy and collagen deposition in heart tissues, which is associated with the increased level of miR-618. PRACTICAL APPLICATIONS: The findings outlined in the current study show that the antifibrotic function of TAN is closely related to the function of miRs: the induction of miR-618 is indispensable for the function of TAN against the fibrotic process after heart injury, which will promote the application of TAN as an adjuvant therapy for improving heart function.

The emerging coronavirus diseases such as COVID-19, MERS, and SARS indicated that animal coronaviruses (CoVs) spillover to humans are a huge threat to public health. Therefore, we needed to understand the CoVs carried by various animals. Wild hedgehogs were collected from rural areas in Wuhan and Xianning cities in Hubei Province for analysis of CoVs. PCR results showed that 5 out of 51 (9.8%) hedgehogs (Erinaceus amurensis) were positive to CoVs in Hubei Province with 3 samples from Wuhan City and 2 samples from Xianning City. Phylogenetic analysis based on the partial sequence of RNA-dependent RNA polymerase showed that the CoVs from hedgehogs are classified into Merbecovirus of the genus Betacoronavirus; the hedgehog CoVs formed a phylogenetic sister cluster with human MERS-CoVs and bat MERS-related CoVs. Among the 12 most critical residues of receptor binding domain in MERS-CoV for binding human Dipeptidyl peptidase 4, 3 residuals were conserved between the hedgehog MERS-related CoV obtained in this study and the human MERS-CoV. We concluded that hedgehogs from Hubei Province carried MERS-related CoVs, indicating that hedgehogs might be important in the evolution and transmission of MERS-CoVs, and continuous surveillance of CoVs in hedgehogs was important.

Sinomenine (SIN) is an effective anti-inflammatory agent, but its therapeutic efficacy is limited by its short half-life and the high dosage required. Tissue-specific strategies have the potential to overcome these limitations. The synovial homing peptide (CKSTHDRLC) was identified to have high synovial endothelium targeting affinity. In this work, two peptide-drug conjugates (PDCs), conjugate (L) and conjugate (C), were synthesized, in which SIN was covalently connected to the linear and cyclic synovial homing peptide, respectively, via a 6-aminocaproic acid linker. An evaluation of biostability showed that conjugate (C) was more stable in mouse serum and inflammatory joint homogenate than conjugate (L). The two conjugates gradually released free SIN. Interestingly, conjugate (L) self-cyclized via a disulfide bridge in a biological environment, which significantly impacted its biostability. It had an almost equipotent half-life in serum but faster degradation in the inflammatory joint than conjugate (C). Therefore, conjugate (C) exhibited better therapeutic efficacy and tissue targeting. All the results indicated that PDCs particularly in its cyclic form might be more efficient for targeted deliver and represent a potential strategy for the treatment of rheumatoid arthritis.

PEGylation is one of the most successful technologies for reducing immunogenicity, improving the stability and circulation time of nanocarriers, and has been applied in the clinic for over three decades. However, linear PEG-modified nanocarriers have been found to induce anti-PEG IgM at the first injection, which triggers the accelerated blood clearance (ABC) phenomenon upon repeated injections. Furthermore, clinical and research evidence has revealed that anti-PEG antibodies also cause serious complement activation-related pseudoallergies (CARPA), which greatly reduce the safety of linear PEGylated nanocarriers. In this study, as an alternative to linear PEG, branched PEG was selected owing to its low antigenicity. We pioneer the use of branched PEG lipid derivatives [DSPE-mPEG

Background Various randomized trials have demonstrated that postmastectomy radiotherapy (RT) to the chest wall and comprehensive regional nodal areas improves survival in patients with axillary node-positive breast cancer. Controversy exists as to whether the internal mammary node (IMN) region is an essential component of regional nodal irradiation. Available data on the survival benefit of IMN irradiation (IMNI) are conflicting. The patient populations enrolled in previous studies were heterogeneous and most studies were conducted before modern systemic treatment and three-dimensional (3D) radiotherapy (RT) techniques were introduced. This study aims to assess the efficacy and safety of IMNI in the context of modern systemic treatment and computed tomography (CT)-based RT planning techniques. Methods POTENTIAL is a prospective, multicenter, open-label, parallel, phase III, randomized controlled trial investigating whether IMNI improves disease-free survival (DFS) in high-risk breast cancer with positive axillary nodes (pN+) after mastectomy. A total of 1800 patients will be randomly assigned in a 1:1 ratio to receive IMNI or not. All patients are required to receive ≥ six cycles of anthracycline and/or taxane-based chemotherapy. Randomization will be stratified by institution, tumor location (medial/central vs. other quadrants), the number of positive axillary nodes (1–3 vs. 4–9 vs. ≥10), and neoadjuvant chemotherapy (yes vs. no). Treatment will be delivered with CT-based 3D RT techniques, including 3D conformal RT, intensity-modulated RT, or volumetric modulated arc therapy. The prescribed dose is 50 Gy in 25 fractions or 43.5 Gy in 15 fractions. Tiered RT quality assurance is required. After RT, patients will be followed up at regular intervals. Oncological and toxilogical outcomes, especially cardiac toxicities, will be assessed. Discussion This trial design is intended to overcome the limitations of previous prospective studies by recruiting patients with pN+ breast cancer, using DFS as the primary endpoint, and prospectively assessing cardiac toxicities and requiring RT quality assurance. The results of this study will provide high-level evidence for elective IMNI in patients with breast cancer after mastectomy. Trial registration ClinicalTrails.gov, NCT04320979. Registered 25 Match 2020, https://clinicaltrials.gov/ct2/show/NCT04320979

PEGylation increases the circulation time of the nanocarrier, but also triggers accelerated blood clearance (ABC) phenomenon. It is well-known that the ABC phenomenon results in shortened blood circulation and aberrant increase in liver and spleen accumulation, which greatly limits the application of PEGylated nano-preparations. For many years, researchers have been working hard to find ways to reduce or eliminate the ABC phenomenon. Previous studies have focused on PEG molecular weight and PEG alternative materials, but there has never been any research on the effect of different PEG chain types on the ABC phenomenon. Therefore, 40 kDa molecular weight of linear PEG lipid derivatives (DSPE-mPEG

The biological effect of engineered carbon nanotubes (CNTs) as beneficial biomaterials on the intestine, especially on its development, remains unclear. Here, we investigated the profitable effect of CNTs with a different graphene layer and surface modification on the 3D model of intestinal organoids and demonstrated that CNTs (50 μg/mL) promoted the development of intestinal organoids over time (0-5 days). The mechanisms involve the modulation of extracellular matrix (ECM) viscoelasticity and intracellular energy metabolism. In particular, CNTs reduced the hardness of the extracellular matrix through decreasing the elasticity and increasing the viscosity as a result of elevated metalloproteinase and binding to a protein scaffold, which activated the mechanical membrane sensors of cells, Piezo, and downstream P-p38-yes-associated protein (YAP) pathway. Moreover, CNTs altered the metabolic profile of intestinal organoids and induced increased mitochondria activity, respiration, and nutrient absorption. These mechanisms cooperated with each other to promote the proliferation and differentiation of intestinal organoids. In addition, the promoted effect of CNTs is highly dependent on the number of graphene layers, manifested as multiwalled CNTs > single-walled CNTs. Our findings highlight the CNT-intestine interaction and imply the potential of CNTs as biomaterials for intestine-associated tissue engineering.