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Simultaneously producing acetone-butanol-ethanol (ABE) and decolorizing Methyl orange (MO) by fermentation with solid food waste (SFW) was studied. During the batch fermentation with MO concentration from 100 mgL−1 to 1000 mgL−1, carbon source utilization efficiency was above 93% with yields of acetone, butanol and ethanol being 0.13 gg-1, 0.23 gg-1 and 0.04 gg-1, respectively. During the repeated fermentation with the bagasse as the cell immobilization material, carbon source utilization efficiencies were all above 90% in the first 5 cycles fermentation. The maximum butanol and ABE concentration were 12.8 gL-1 and 22.1 gL-1, respectively. The solvent yield of acetone, butanol and ethanol were around 0.13 gg-1, 0.25 gg-1 and 0.06 gg-1, respectively. The MO decolorization had no negative effect on the ABE production and the decolorization efficiencies were all above 99% during batch fermentation or repeated fermentation with electrons transferred from intracellular to extracellular by mediator with the help of azo reductase to decolorize MO. [Display omitted] • ABE fermentation and wastewater treatment containing MO were combined. • Solid food waste was used to simultaneously produce ABE and decolorize MO. • MO decolorization efficiencies are above 99% in the range of 100–1000 mgL-1. • Maximum butanol and total ABE concentration were 12.8 gL-1 and 22.1 gL-1 respectively. • Cells can be used for 7 cycles with stable decolorization-fermentation performance. [ABSTRACT FROM AUTHOR]

Chemical accidents occur frequently in China owing to inadequate process safety risk management and control in warehouses. Real-time dynamic risk assessment can identify stored process risks and reduce the accident probability. The support vector machine (SVM) is an effective dynamic risk assessment method. To improve the dynamic risk assessment performance of the SVM model, the electrostatic discharge method (ESDA), which has a strong optimization ability, was used to optimize the model parameters. An improved mixed kernel (NP mixed kernel) that was a linear combination of the novel radial basis function and polynomial kernel was constructed, and an intelligent assessment model of the warehouse fire dynamic risk based on the ESDA and improved SVM (ESDA-NPSVM) was proposed. The experimental results indicated that the proposed model had excellent performance for the dynamic risk assessment of fire accidents in Class A hazardous chemical warehouses, suggesting that it is useful for practical applications. [ABSTRACT FROM AUTHOR]

• Stacked mesh electrodes with the regular porous structure have been presented. • Smaller bubble sizes and faster bubble transport can be achieved. • Overpotentials of 247 mV and 350 mV can be achieved for HER and OER at 1000 mA cm−2. • Microporous structure flowing integrated with catalysis has been carried out. • Energy consumption of 4 kWh Nm−3 can be achieved for hydrogen production. In order to promote gas bubble transport during water splitting for hydrogen production, stacked mesh electrodes integrated microporous structure flowing and electrolytic water splitting have been fabricated by electrodepositing CoFe alloy. The average size of the bubble on the mesh electrode surface is 40 μm and the release time of trapped bubbles in the pores of the electrode is 2.11 s during the process of water splitting at 50 mA cm−2 and 1 M KOH. The electrodes show excellent performance in both hydrogen evolution reaction (HER, 247 mV at 1000 mA cm−2) and oxygen evolution reaction (OER, 350 mV at 1000 mA cm−2). The required cell voltage at 1000 mA cm−2 for flow-through electrolyzer assembled with the stacked mesh electrodes is only 2 V under the condition of 6 M KOH, and 343 K. The voltage caused by the bubble in the flow-through electrolyzer assembled with stacked mesh electrodes is just about 50 mV at the current density of 1000 mA cm−2. The energy required for hydrogen production is only 4.04 kWh Nm−3 and 4.78 kWh Nm−3 under the current density of 200 mA cm−2 and 1000 mA cm−2, respectively. Besides, the flow-through electrolyzer assembled with the stacked mesh electrodes shows excellent stability with only a 60 mV increase in cell voltage after continuing electrolytic water splitting for 100 h at 1000 mA cm−2. [ABSTRACT FROM AUTHOR]

We report on the magic wavelength measurement of our optical lattice clock based on fermion strontium atoms at the National Institute of Metrology (NIM). A Ti:sapphire solid state laser locked to a reference cavity inside a temperature-stabilized vacuum chamber is employed to generate the optical lattice. The laser frequency is measured by an erbium fiber frequency comb. The trap depth is modulated by varying the lattice laser power via an acousto-optic modulator. We obtain the frequency shift coefficient at this lattice wavelength by measuring the differential frequency shift of the clock transition of the strontium atoms at different trap depths, and the frequency shift coefficient at this lattice wavelength is obtained. We measure the frequency shift coefficients at different lattice frequencies around the magic wavelength and linearly fit the measurement data, and the magic wavelength is calculated to be 368554672(44) MHz. [ABSTRACT FROM AUTHOR]

BACKGROUND: The emergency rescue ability of firefighters is particularly important in the event of major disasters or accidents. Therefore, an assessment of the firefighter-training effectiveness is necessary. OBJECTIVE: This paper aims to achieve a scientific and effective assessment of the firefighter-training effectiveness in China. An assessment method based on human factor parameters and machine learning was proposed. METHOD: The model is constructed by collecting the corresponding human factor parameters such as electrocardiographic signals, electroencephalographic signals, surface electromyographic signals, and photoplethysmographic signals through wireless sensors and using them as constraint indicators. For the problems of weak human factor parameters and high noise proportion, an improved flexible analytic wavelet transform algorithm is used to denoise and extract the corresponding feature values. To overcome the limitations of traditional assessment methods, improved machine learning algorithms are used to comprehensively assess the training effectiveness of firefighters and provide targeted training suggestions. RESULTS: The effectiveness of this study's evaluation method is verified by comparing it with the expert scoring method and considering firefighters from a special fire station in Xhongmen, Daxing District, Beijing, as an example. CONCLUSION: This study can effectively guide the scientific training of firefighters and the method is more objective and accurate than the traditional method. [ABSTRACT FROM AUTHOR]

We report our observation of the spin polarized 1S0 → 3P0 clock transition spectrum in an optical lattice clock based on fermionic 87Sr. The atoms are trapped and pre-cooled to about 2 μK with two stages of laser cooling at 461 nm and 689 nm, respectively. Then the atoms are loaded into an optical lattice formed by the interference of counter-propagating laser beams at 813 nm. An external cavity diode laser at 698 nm, which is stabilized to a high finesse cavity with a linewidth of about 5 Hz and a drift rate of less than 0.2 Hz/s, is used to excite the atoms to the 3P0 state. The π-polarized clock transition spectrum of resolvable mF states is obtained by applying a small bias magnetic field along the polarization axis of the probe beam. A spin polarized clock transition spectrum as narrow as 10 Hz with an 80 ms probe pulse is obtained. [ABSTRACT FROM AUTHOR]

Bubble evolution induced overpotential for hydrogen production by water electrolysis is an important issue and the internal/external surface of the electrode can be covered by the generated bubbles. Herein, flow-through electrodes with in-situ restructured Co-based nanosheets loaded in Ni foam pores are presented. The adhesion between H 2 bubbles and the superaerophobic catalyst layer is reduced from 14.2 μN to about zero and H 2 bubbles size is reduced from 41.76 μm to 23.17 μm. Under the condition of flow-through mode, the catalysts can be adequately exposed because the generated bubbles can be timely removed from the catalyst surface. The overpotential can be reduced by about 100 mV for hydrogen evolution reaction (HER) and 57 mV for oxygen evolution reaction (OER) under the condition of 300 mA cm−2 and electrolyte flux of 339 m3 m−2 h−1. A novel electrolyzer assembled with flow-through electrode for hydrogen production by alkaline water electrolysis is conducted. The cell voltage can be decreased by 50 mV at 200 mA cm−2 at 6 M KOH, 338 K, and 1 atm, with the energy of 4.42 kW h Nm−3 required. The results provide insights into the design of various electrodes for electrolyzer setups that can be used for gas-involving reactions. [Display omitted] • A flow-through electrode for efficient water splitting was fabricated. • Bubble adhesive force can be attenuated because of superaerophobicity. • Bubble detachment can be accelerated under flow-through mode. • Rapid bubble detachment enhanced the contact between electrolytes and catalysts. • An electrolyzer assembled with flow-through electrode was fabricated. [ABSTRACT FROM AUTHOR]

Site-specific recombination systems are widely used as bioengineering tools. However, the traditional site-specific recombination system requires a consensus sequence for the specific site. Such sequence-level constraints limit effective recombination between sites. Therefore, in order to develop an efficient site-specific recombination system, we investigated the attC site of the bacterial integration subsystem and built a predictive model to infer the important features that contribute to recombination. Here, we design an attC site prediction algorithm based on a combination optimisation strategy. Based on the structural features of attC sites, the prediction algorithm realises the high-precision prediction of the recombination frequencies between sites and the screening of the top 20 important features that play a role in recombination, which are effective for improving the design method of attC sites. The algorithm has better portability and higher prediction accuracy compared with the existing advanced algorithms, among which the Pearson correlation coefficient is 0.87, explained variance score is 0.73, root mean square error is 0.006 and mean absolute error is 0.041. This can not only provide ideas for the research of efficient recombination systems but also provide a theoretical basis for developing genetic engineering further. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cu/ZIF-8/Ag@Ti binder-free electrochemical sensing membrane is prepared. • Flow-through detection mode increases mass transfer. • High sensitivity and low detection limit can be achieved. • Electrochemical sensing membrane has excellent compatibility. To increase the sensitivity and decrease the detection limit, electrochemical sensing membrane under the flow-through detection mode with enhanced mass transfer during the electrochemical detecting process is developed in this study. The Cu/ZIF-8/Ag@Ti electrochemical sensing membrane with Cu/ZIF-8/Ag immobilized in Ti membrane pores has been fabricated and then as a novel sensor for sensing under the flow-through detection mode. Electrochemical impedance spectroscopy (EIS) indicates that the electron transport resistance can be reduced by 50 % with the flow rate of 1 mL min−1, compared with that of 0 mL min−1 (under conventional static mode). The limiting current analysis shows that the mass transfer coefficient of glucose increased by 18 % and the boundary layer thickness decreased by 15 %. The detection of glucose shows that the sensitivity increased from 3453 to 20,665 μA mM−1 cm−2, and the detection limit decreased from 0.26 to 0.04 μM. The Cu/ZIF-8/Ag@Ti sensing membrane under the flow-through mode has a well reliability of 88.6–110.9 % in real blood samples. In addition, the sensing membrane of MnO 2 @Ti for uric acid and Au/Ag@Ti for H 2 O 2 detection also shows high sensitivity and low detection limit under the flow-through detection mode. [ABSTRACT FROM AUTHOR]

Saccharide mapping was a promising scheme to unveil the mystery of polysaccharide structure by analysis of the fragments generated from polysaccharide decomposition process. However, saccharide mapping was not widely applied in the polysaccharide analysis for lacking of systematic introduction. In this review, a detailed description of the establishment process of saccharide mapping, the pros and cons of downstream technologies, an overview of the application of saccharide mapping, and practical strategies were summarized. With the updating of the available downstream technologies, saccharide mapping had been expanding its scope of application to various kinds of polysaccharides. The process of saccharide mapping analysis included polysaccharides degradation and hydrolysates analysis, and the degradation process was no longer limited to acid hydrolysis. Some downstream technologies were convenient for rapid qualitative analysis, while others could achieve quantitative analysis. For the more detailed structure information could be provided by saccharide mapping, it was possible to improve the quality control of polysaccharides during preparation and application. This review filled the blank of basic information about saccharide mapping and was helpful for the establishment of a professional workflow for the saccharide mapping application to promote the deep study of polysaccharide structure. [Display omitted] • The detailed structure information was crucial for the deep study and application of polysaccharides. • Saccharide mapping provided a professional workflow for the characterization and identification of polysaccharides. • The methods of obtaining oligosaccharides and several excellent downstream technologies were assessed. • Application scenarios and strategies for saccharide mapping were provided. [ABSTRACT FROM AUTHOR]

Background: Determining T cell responses to naturally processed and presented antigens is a critical immune correlate to determine efficacy of an investigational immunotherapeutic in clinical trials. In most cases, minimal epitopes and HLA restriction elements are unknown. Results: Here, we detail the experimental use of ex vivo expanded autologous B cells as antigen presenting cells to overcome the limitation of unknown HLA restriction, and the use of electroporated full length mRNA encoding full length parental proteins to ensure that any observed T cell responses are specific for antigens that are naturally processed and presented. Conclusions: This technique can serve as useful experimental approach to determine the induction or enhancement of specific responses to naturally processed and presented antigens on HLA class I molecules in peripheral blood or tumor infiltrating T cells. [ABSTRACT FROM AUTHOR]

• A CMR was developed for hydrogen production from methanol steam reforming. • Cu/ZnO/Al 2 O 3 catalyst in-situ immobilized in Ti membrane pores by flowing synthesis. • Enhanced mass transfer can be achieved due to the reaction being confined in pores. • Hydrogen yield of 500 mmol h−1 g-1 cat. and selectivity of 100% can be achieved. • Methanol conversion rate of over 95% can be expected if 5 CMR is assembled in series. A flow-through catalytic membrane micro-reactor (CMR) with Cu/ZnO/Al 2 O 3 nanoparticles immobilized in porous membrane pores has been developed for hydrogen production by methanol steam reforming (MSR). The characteristics for CMR demonstrated Cu/ZnO/Al 2 O 3 nanoparticles with almost 200 nm were successfully in situ immobilized in membrane pores. During MSR for hydrogen production in CMR by flow-through mode, hydrogen yield of 500 mmol h−1 g−1 and selectivity of 100% can be achieved under the condition of temperature being 360℃, molar ratio of water to methanol of 8.8 and weight hourly space velocity (WHSV) of 9.28 h−1. Compared with the commercial fixed bed reactor, the hydrogen productivity in CMR is one order of magnitude higher, owing to MSR confined in the space of membrane pore with micro-scale. The methanol conversion rate of over 95% can be expected, if five sheets of CMR with thickness of 5 mm were assembled in series. [ABSTRACT FROM AUTHOR]

Neoadjuvant immunotherapies (NITs) have led to clinical benefits in several cancers. Characterization of the molecular mechanisms underlying responses to NIT may lead to improved treatment strategies. Here we show that exhausted, tumor-infiltrating CD8+ T (Tex) cells display local and systemic responses to concurrent neoadjuvant TGF-β and PD-L1 blockade. NIT induces a significant and selective increase in circulating Tex cells associated with reduced intratumoral expression of the tissue-retention marker CD103. TGF-β-driven CD103 expression on CD8+ T cells is reversed following TGF-β neutralization in vitro , implicating TGF-β in T cell tissue retention and impaired systemic immunity. Transcriptional changes implicate T cell receptor signaling and glutamine metabolism as important determinants of enhanced or reduced Tex treatment response, respectively. Our analysis illustrates physiological and metabolic changes underlying T cell responses to NIT, highlighting the interplay between immunosuppression, tissue retention, and systemic anti-tumor immunity and suggest antagonism of T cell tissue retention as a promising neoadjuvant treatment strategy. [Display omitted] • Neoadjuvant immunotherapy (NIT) predominantly activates exhausted tumor CD8+ T cells • Activated CD8+ T cells have increased T cell receptor activity and altered metabolism • PD-L1/TGF-β NIT polarizes regulatory CD4+ T cells toward an effector phenotype • Results implicate TGF-β as a driver of CD103 expression and tissue retention of T cells Sievers et al. evaluate dynamic T cell compartment changes in tumor and peripheral blood following neoadjuvant PD-L1 blockade and TGF-β neutralization in newly diagnosed head and neck cancers unrelated to HPV and provide evidence that reversing tissue retention of tumor-specific T cells may enhance systemic anti-tumor immunity. [ABSTRACT FROM AUTHOR]

An Ag@PAN catalytic nanofiber composite membrane has been fabricated by combining electrospinning PAN nanofiber seeding with 2-MI and flowing synthesis. ZIF-8 can be immobilized on the surface of the nanofibers with Zn(NO 3) 2 solution flowing through the 2-MI/PAN nanofiber membrane and Ag nanoparticles can be immobilized on the nanofibers with Zn2+ in ZIF-8 exchanged by Ag+ followed with reduction reaction. The characteristics of XRD, XPS, FTIR, TGA, HRTEM, and BET proved the successful immobilization of Ag nanoparticles derived from ZIF-8 on PAN nanofiber. The permeance of the Ag@PAN catalytic nanofiber composite membrane can reach 19,227 L m−2 h−1 bar−1 with Ag nanoparticles immobilization amount of 49.64%. The p -NP conversion reaction is addressed for the catalytic performance of the Ag@PAN catalytic nanofiber composite membrane. The conversion rate of 99% can be achieved under the condition of p -NP concentration of 0.025 mM and membrane flux of 300 L m−2 h−1. The apparent reaction rate constant of 236.63 min−1 can be achieved by flowing through mode, which is 4-5 orders of magnitude higher than that in a stirred tank reactor with Ag powders as the catalyst. The catalytic performance of the composite membranes has not declined significantly after ten cycles of the catalysis experiment, implied the good repeatability of the Ag@PAN catalytic nanofiber composite membranes. [Display omitted] • Combining electrospinning PAN nanofiber seeding with 2-MI and flowing synthesis. • Ag Nanoparticles are uniformly dispersed on membrane nanofibers. • High amount of Ag nanoparticles immobilization on nanofibers achieved. • High permeance of the catalytic nanofiber composite membranes achieved. • Flowing through synergism enhances mass transfer and improves catalytic reaction rate. [ABSTRACT FROM AUTHOR]

A catalytic membrane nano reactor (CMNR) with deep-permeation nanocomposite structure (DPNS) has been fabricated by flowing synthesis for methanol dehydrogenation to formaldehyde. In this structure, Cu/ZnO nanoparticles are in situ immobilized in the pores of Ti membrane substrate with thickness 1 mm, pore size 10 μm and porosity 45%. The characterization by XRD, TGA, XPS, SEM and TEM indicates that the Cu/ZnO nanoparticles with mean size of 82 nm was successfully embedded into the membrane pores, and well distributed along the thickness direction of the membrane. The ICP measurement results demonstrate that the immobilization amount of 20 mg of Cu/ZnO nanoparticles per gram of Ti membrane substrate can be obtained. The prepared Cu/ZnO/Ti CMNR was built in the technological apparatus for catalytic dehydrogenation of methanol. For one sheet of membrane setting up, the conversion efficiency of methanol 7.5%, the mass specific activity 183 mmol MeOH ·h-1·g cat -1, the pressure drop 2.7 kPa with gas permeating the membrane have been measured, under mass ratio of Cu to ZnO 0.05 in the membrane, reaction temperature 360 °C, the gas flux 8 m3·m-2·h-1 through the membrane. The selectivity of formaldehyde is up to 98% and increases with increasing reaction temperature, the highest mass specific activity of 318 mmol MeOH ·h-1·g cat -1 can be achieved with mass ratio of Cu to ZnO 0.12 at 360 °C. For three sheets of CMNRs setting up in serials, over 18% of conversion efficiency has been achieved with gas pressure drop 6.8 kPa. If 70 sheets of CMNRs are packed in serials to build a reactor with 70 mm thickness, which will produce the gas pressure drop 162 kPa, the conversion efficiency of 99% would be expected according to a simple simulation based on the experimental measurement. [Display omitted] • Catalytic membrane nano reactor (CMNR) was fabricated by flowing synthesis. • Cu/ZnO nanoparticles in situ immobilized in membrane pores uniformly. • Excellent performance of methanol dehydrogenation to formaldehyde in CMNR. • Methanol conversion efficiency over 99% can be obtained by set up CMNRs in serials. [ABSTRACT FROM AUTHOR]

An electrocatalytic composite membrane with deep-permeation nano structure (DPNS) has been fabricated by flowing synthesis. The nano electrocatalyst MnO 2 is in situ successfully assembled in membrane pores and uniformly immobilized in membrane pores along the direction of membrane thickness. The size of MnO 2 nanoparticles immobilized in membrane pores is in the range of 33–35 nm, which is one-tenth of that immobilized on the membrane surface. The increased current density and the lower charge transfer resistance of the electrocatalytic composite membrane implied that a fast electron transfer can be achieved. As a concept-of-proof, the removal of phenol was applied to test the catalytic performance of the electrocatalytic composite membrane under the flow-through reaction mode, and the removal rate of phenol of being over 97% can be achieved under the condition of membrane flux of being 13.5 L m−2 h−1. The apparent reaction rate constant could be increased by 2–3 orders of magnitude, owing to the enhanced contact by uniform distribution of membrane pores, as well as the confined space effect of membrane pores and the flow-through synergism enhancing mass transfer. The species of free radical can be determined as ·OH via ESR measurements for phenol oxidation. This electrocatalytic composite membrane (ECCM) with DPNS has good reusability and can provide a promising prospect for industrial application. [Display omitted] • Electrocatalytic composite membrane with DPNS fabricated by flowing synthesis. • Faster electron transfer can be achieved. • Enhanced contact can be achieved by uniform distribution of membrane pores. • Confined space effect and flow-through synergism can enhance mass transfer. [ABSTRACT FROM AUTHOR]

Digital-to-analog converter (DAC) with a high sampling-rate has been extensively applied in optical discrete multi-tone (DMT) system for high data-rate signal generation. However, there exist various imperfections during the manufacturing of DAC when its sampling rate is tens of giga-samples per second and beyond. Clock tone leakage (CTL) is a kind of interference in high-speed DACs. One or more data subcarriers of the generated DMT signal may suffer from additional clock tones, which may degrade the overall bit error rate (BER) performance of the optical DMT system. In the literature, several schemes have been proposed to compensate CTL for short-reach applications. Nevertheless, these compensation schemes may not work effectively in the asynchronous DMT system in the presence of sampling clock frequency offset (SFO) between DAC and analog-to-digital converter. In this paper, an effective CTL compensation (CLC) with the digital interpolation scheme is proposed and experimentally investigated in a short-reach 100G DMT transmission system with direct detection. The results indicate that the proposed CLC with a fourth-order interpolation (FOI) scheme can effectively compensate the CTL in the presence of an SFO up to ± 1000 parts per million (ppm). What is more, we discuss the impact of SFO estimation error on the BER performance of the 64-ary quadrature amplitude modulation-encoded DMT system. It shows that the BER performance penalty can be ignored by shortening the DMT frame even though the estimation error is up to 2 ppm. • An effective CLC with FOI is proposed and investigated in a short-reach DMT system. • The proposed scheme can compensate CTL in the presence of an SFO up to ± 1000 ppm. • The BER performance penalty is ignored when the SFO estimation error is up to 2 ppm. [ABSTRACT FROM AUTHOR]

Vehicle-to-vehicle (for short, V2V) communication technology is regarded as a promising technology to improve traffic efficiency and safety. In this paper, an extended car-following model is proposed to simulate traffic flow by considering multi-anticipative average velocity effect (including the average velocity and the mean expected velocity field effect of preceding vehicles group) under V2V environment. The stability condition of this model is obtained by applying the linear stability theory. The phase diagram comparison and analysis shows that the multi-anticipative average velocity effect can effectively enhance the stabilization of traffic system. In particular, the average velocity effect plays a more important role than that of the mean expected velocity field effect in improving the stability of traffic flow. The mKdV equation is derived to describe the evolution characteristics of traffic density waves by using the reductive perturbation method. Furthermore, the numerical simulation is carried out to validate the theoretical results, and indicates that the traffic jam can be suppressed efficiently via taking into account multi-anticipative average velocity effect. • A new car-following model considering multi-anticipative average velocity effect is presented. • Linear analysis is carried out to study the stability of traffic flow. • The mKdV equation is derived from nonlinear analysis to describe the density wave of traffic jam. • The effect of multi-anticipative average velocity can effectively improve the stability of traffic flow. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the distribution of immune cell subsets within laryngeal papillomas and to study the function of potentially immunosuppressive neutrophilic and regulatory T cells (Tregs)., Methods: Fresh clinical papilloma specimens were collected at the time of surgery and studied with multiparameter flow cytometry. Papilloma infiltrating neutrophilic cells and Tregs were sorted and studied functionally with ex vivo T cell suppression assays., Results: Flow cytometric analysis of fresh laryngeal papillomas samples from 18 adult patients with recurrent respiratory papillomatosis revealed patterns in immune constituency between patients. Clearly divergent phenotypes based primarily on the degree of neutrophilic and T cell infiltration were identified. Relative neutrophilic cell enrichment and T cell depletion were observed in 50% of samples and neutrophilic cell depletion and T cell enrichment were observed in the others. Greater papilloma neutrophilic cell enrichment was positively associated with the number of clinically indicated interventions required in the 12 months prior to sample collection, linking papilloma neutrophil inflammation to disease severity. Functional assays revealed the ability of both papilloma infiltrating neutrophilic and Tregs to suppress T cell function at roughly equal magnitudes, but substantially increased infiltration of neutrophilic cells compared to Tregs across samples., Conclusion: Neutrophilic cells are an important contributor to immunosuppression within the respiratory papilloma microenvironment. Given these data and the association between greater neutrophilic cell infiltration and lack of clinical response to therapeutic vaccination, additional study of strategies aimed at limiting neutrophilic cell infiltration or function within papillomas is warranted., Level of Evidence: 4 Laryngoscope, 134:3238-3244, 2024., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Preoperative knowledge of mutational status of gastrointestinal stromal tumors (GISTs) is essential to guide the individualized precision therapy., Aim: To develop a combined model that integrates clinical and contrast-enhanced computed tomography (CE-CT) features to predict gastric GISTs with specific genetic mutations, namely KIT exon 11 mutations or KIT exon 11 codons 557-558 deletions., Methods: A total of 231 GIST patients with definitive genetic phenotypes were divided into a training dataset and a validation dataset in a 7:3 ratio. The models were constructed using selected clinical features, conventional CT features, and radiomics features extracted from abdominal CE-CT images. Three models were developed: Model CT sign , model CT sign + rad , and model CT sign + rad + clinic . The diagnostic performance of these models was evaluated using receiver operating characteristic (ROC) curve analysis and the Delong test., Results: The ROC analyses revealed that in the training cohort, the area under the curve (AUC) values for model CT sign , model CT sign + rad , and model CT sign + rad + clinic for predicting KIT exon 11 mutation were 0.743, 0.818, and 0.915, respectively. In the validation cohort, the AUC values for the same models were 0.670, 0.781, and 0.811, respectively. For predicting KIT exon 11 codons 557-558 deletions, the AUC values in the training cohort were 0.667, 0.842, and 0.720 for model CT sign , model CT sign + rad , and model CT sign + rad + clinic , respectively. In the validation cohort, the AUC values for the same models were 0.610, 0.782, and 0.795, respectively. Based on the decision curve analysis, it was determined that the model CT sign + rad + clinic had clinical significance and utility., Conclusion: Our findings demonstrate that the combined model CT sign + rad + clinic effectively distinguishes GISTs with KIT exon 11 mutation and KIT exon 11 codons 557-558 deletions. This combined model has the potential to be valuable in assessing the genotype of GISTs., Competing Interests: Conflict-of-interest statement: The authors have declared that no competing interests exist., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Missense mutations affect the function of human proteins and are closely associated with multiple acute and chronic diseases. The identification of disease-associated missense mutations and their classification for pathogenicity can provide insights into the genetic basis of disease and protein function. This paper proposes MLAE (Method based on LSTM-Ladder AutoEncoder), a deep learning classification model for identifying disease-associated missense mutations and classifying their pathogenicity based on the Variational AutoEncoder (VAE) framework. MLAE overcomes the limitations of the VAE framework by introducing the Ladder structure, combined with LSTM networks. This reduces the loss of original information during the transmission process, thereby making the model more effective in learning. In the experiment, MLAE classified all 27572 possible missense variants of the three input proteins with an average classification AUC of 0.941. This result provides evidence that MLAE is effective in predicting pathogenicity. Additionally, MLAE provides results for multi-label classification, with an average Hamming loss of 0.196, supporting the classification of complex variants. The proposed MLAE method provides an insightful approach to effectively capture amino acid sequence information and accurately predict the pathogenicity of mutations, thereby providing an analytical basis for the study and prevention of related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A cortical plasticity after long-duration single side deafness (SSD) is advocated with neuroimaging evidence while little is known about the short-duration SSDs. In this case-cohort study, we recruited unilateral sudden sensorineural hearing loss (SSNHL) patients and age-, gender-matched health controls (HC), followed by comprehensive neuroimaging analyses. The primary outcome measures were temporal alterations of varied dynamic functional network connectivity (dFNC) states, neurovascular coupling (NVC) and brain region volume at different stages of SSNHL. The secondary outcome measures were pure-tone audiograms of SSNHL patients before and after treatment. A total of 38 SSNHL patients (21 [55%] male; mean [standard deviation] age, 45.05 [15.83] years) and 44 HC (28 [64%] male; mean [standard deviation] age, 43.55 [12.80] years) were enrolled. SSNHL patients were categorized into subgroups based on the time from disease onset to the initial magnetic resonance imaging scan: early- (n = 16; 1-6 days), intermediate- (n = 9; 7-13 days), and late- stage (n = 13; 14-30 days) groups. We first identified slow state transitions between varied dFNC states at early-stage SSNHL, then revealed the decreased NVC restricted to the auditory cortex at the intermediate- and late-stage SSNHL. Finally, a significantly decreased volume of the left medial superior frontal gyrus (SFGmed) was observed only in the late-stage SSNHL cohort. Furthermore, the volume of the left SFGmed is robustly correlated with both disease duration and patient prognosis. Our study offered neuroimaging evidence for the evolvement from functional to structural brain alterations of SSNHL patients with disease duration less than 1 month, which may explain, from a neuroimaging perspective, why early-stage SSNHL patients have better therapeutic responses and hearing recovery., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Recurrent respiratory papillomatosis (RRP) is a rare, debilitating neoplastic disorder caused by chronic infection with human papillomavirus (HPV) type 6 or 11 and characterized by growth of papillomas in the upper aerodigestive tract. There is no approved medical therapy, and patients require repeated debulking procedures to maintain voice and airway function. PRGN-2012 is a gorilla adenovirus immune-therapeutic capable of enhancing HPV 6/11-specific T cell immunity. This first-in-human, phase 1 study (NCT04724980) of adjuvant PRGN-2012 treatment in adult patients with severe, aggressive RRP demonstrates the overall safety and clinically meaningful benefit observed with PRGN-2012, with a 50% complete response rate in patients treated at the highest dose. Responders demonstrate greater expansion of peripheral HPV-specific T cells compared with nonresponders. Additional correlative studies identify an association between reduced baseline papilloma HPV gene expression, greater interferon responses and expression of CXCL9 and CXCL10 , and greater papilloma T cell infiltration in responders. Conversely, nonresponders were characterized by greater HPV and CXCL8 gene expression, increased neutrophilic cell infiltration, and reduced T cell papilloma infiltration. These results suggest that papilloma HPV gene expression may regulate interferon signaling and chemokine expression profiles within the tumor microenvironment that cooperate to govern clinical response to therapeutic HPV vaccination in patients with respiratory papillomatosis.

Background: Regional citrate anticoagulation (RCA) is being used more commonly in children for continuous renal replacement therapy. Few reports describe the application of membrane-based therapeutic plasma exchange (mTPE) with RCA in children with liver failure (LF)., Aims: To explore the application of RCA-mTPE in children with LF., Methods: We retrospectively analyzed data from children with LF who underwent RCA-mTPE in the Children's Hospital of Chongqing Medical University's pediatric intensive care unit. We used the total to ionized calcium ratio (T/iCa) > 2.5 as the diagnostic criteria for citrate accumulation (CA). The patients were divided into two groups according to the occureence of CA at the end of RCA-mTPE (CA group: T/iCa > 2.5; NCA group: T/iCa ≤ 2.5). To evaluate the clinical safety and efficacy of RCA-mTPE, the following data from medical records were assessed and compared between groups: clinical characteristics, reasons for LF, RCA-mTPE parameters and duration, laboratory findings, and complications., Results: In total, 92 RCA-mTPE treatments were administered to 21 children with LF over 3.8 ± 0.9 h. The following mean values were determined: blood flow rate (QB) = 2.8 ml/kg/min, 4% sodium citrate dose/blood flow rate ratio (QCi/QB) = 1.1(QCi,ml/kg/h); plasma dose/body weight ratio(QP/BW) = 18.5 (QP, ml/kg/h); 10% calcium gluconate dose/blood flow rate ratio (QCa/QB) = 0.2(QCa, ml/kg/h). The mean concentration of iCa in vitro was 0.38 ± 0.07 mmol/L. Citrate accumulation was recorded after 34 (37%) treatments. Hypocalcemia occurred in 11 (12%) and 7 (7.6%) treatments, during and after mTPE, respectively. Three hypotensive and one convulsive events, related to hypocalcemia, and two clotting events occurred during RCA-mTPE. After RCA-mTPE, the patients' pH, HCO 3 - and Na + levels, and T/iCa were significantly increased and the total bilirubin (TB), conjugated bilirubin (DB), prothrombin time (PT), activated partial thromboplastin time (APTT), alanine aminotransferase (ALT), aspartate aminotransferase (AST),and ammonia levels were significantly decreased. The TB, DB, and lactic acid levels, before RCA-mTPE, were significantly higher in the CA group than in the NCA group, but there were no significance between the two groups in QB/BW, QCi/QB, and QP/BW, mTPE duration, and estimated amount of citrate metabolized., Conclusions: Children with LF undergoing RCA-mTPE are at risk of hypocalcemia. With proper protocol adjustment, however, RCA-mTPE can be used safely and effectively in these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Hu, Wang, Bai and Liu.)

Zero-shot image recognition aims to classify data from unseen classes, by exploring the association between visual features and the semantic representations of each class. Most existing approaches focus on learning a shared single-scale embedding space (often at the output layer of the network) for both visual and semantic features, ignoring a fact that different-scale visual features exhibit different semantics. In this article, we propose a multi-scale visual-attribute co-attention (mVACA) model, considering both visual-semantic alignment and visual discrimination at multiple scales. At each scale, a hybrid visual attention is realized by attribute-related attention and visual self-attention. The attribute-related attention is guided by a pseudo attribute vector inferred via a mutual information regularization (MIR). The visual self-attentive features further influence the attribute attention to emphasize visual-associated attributes. Leveraging multiscale visual discrimination, mVACA unifies standard zero-shot learning (ZSL) and generalized ZSL tasks in one framework, achieving state-of-the-art or competitive performance on several commonly used benchmarks of both setups. To better understand the interaction between images and attributes in mVACA, we also provide visualized analysis.

Objective: Introduce a novel protocol to prevent clotting and citrate accumulation (CA) from blood product transfusion (BPT) during continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in children., Methods: We prospectively compared fresh frozen plasma (FFP) and platelet transfusions between the two BPT protocols, direct transfusion protocol (DTP) and partial replacement of citrate transfusion protocol (PRCTP), in terms of the risks of clotting, citric accumulation (CA), and hypocalcemia. For DTP, blood products were directly transfused without any adjustment to the original RCA-CRRT regimen. For PRCTP, the blood products were infused into the CRRT circulation near the sodium citrate infusion point, and the dosage of 4% sodium citrate was reduced depending on the dosage of sodium citrate in the blood products. Basic information and clinical data were recorded for all children. Heart rate, blood pressure, ionized calcium (iCa) and various pressure parameters were recorded before, during and after BPT, as well as coagulation indicators, electrolytes, and blood cell counts before and after BPT., Results: Twenty-six children received 44 PRCTPs and 15 children received 20 DTPs. The two groups had similar in vitro ionized calcium (iCa) concentrations (PRCTP: 0.33 ± 0.06 mmol/L, DTP: 0.31 ± 0.04 mmol/L), total filter lifespan (PRCTP: 49.33 ± 18.58, DTP: 50.65 ± 13.57 h), and filter lifespan after BPT (PRCTP: 25.31 ± 13.87, DTP: 23.39 ± 11.34 h). There was no visible filter clotting during BPT in any of the two groups. The two groups had no significant differences in arterial pressure, venous pressure, and transmembrane pressure before, during, or after BPT. Neither treatment led to significant decreases in WBC, RBC, or hemoglobin. The platelet transfusion group and the FFP group each had no significant decrease in platelets, and no significant increases in PT, APTT, and D-dimer. The most clinically significant changes were in the DTP group, in which the ratio of total calcium to ionized calcium (T/iCa) increased from 2.06 ± 0.19 to 2.52 ± 0.35, the percentage of patients with T/iCa above 2.5 increased from 5.0% to 45%, and the level of in vivo iCa increased from 1.02 ± 0.11 to 1.06 ± 0.09 mmol/L (all p  < 0.05). Changes in these three indicators were not significant in the PRCTP group., Conclusion: Neither protocol was associated with filter clotting during RCA-CRRT. However, PRCTP was superior to DTP because it did not increase the risk of CA and hypocalcemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Sun, Li, Bai, Xu, Liu and Dang.)

Background: Regional citrate anticoagulant (RCA) is recommended as the preferred anticoagulant regimen for continuous renal replacement therapy (CRRT) in adults; however, it is rarely reported in neonates due to concerns associated with their immature liver. Few studies have reported on the use of RCA to evaluate the safety and efficacy of RCA-CRRT in neonates., Method: In this retrospective observational study, we reviewed the clinical records of neonates who underwent RCA-CRRT at our pediatric intensive care unit between September 2015 to January 2021., Results: A total of 23 neonates underwent 57 sessions of RCA-CRRT. Their mean age was 10.1 ± 6.9 days and mean weight was 3.0 ± 0.7 kg (range, 0.95-4 kg). The mean filter life was 31.54 ± 19.58 h (range, 3.3-72.5 h). Compared to pretreatment values, the total-to-ionized calcium ratio (T/iCa) on RCA-CRRT increased (2.00 ± 34 0.36 vs. 2.19 ± 0.40, P  = 0.056) as did the incidence of T/iCa levels >2.5 (11.4 vs. 14.3, P  = 0.477), albeit not significantly. Using a post-treatment T/iCa threshold of 2.5, we divided all the cases into citrate accumulation (CA) and non-CA (NCA) groups. Compared with the NCA group, the CA group had significantly higher body weight (3.64 ± 0.32 kg vs. 2.95 ± 0.41 kg, P  = 0.033) and significantly lower blood flow rate per body weight ml/kg/min (3.08 ± 0.08 vs. 4.07 ± 0.71, P  = 0.027); however, there was no significant difference between the two groups in terms of age, corrected gestational age, the PRISM-III score, and biochemical tests., Conclusion: RCA-CRRT is safe and effective for neonates. After appropriate adjustments of the RCA-CRRT parameters, the incidence of CA was not higher in neonates than in children or adults, and CA was not found to be significantly correlated with age or corrected gestational age., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Huang, Deng, Bai, Liu, Xu and Dang.)

The climbing microrobots have attracted growing attention due to their promising applications in exploration and monitoring of complex, unstructured environments. Soft climbing microrobots based on muscle-like actuators could offer excellent flexibility, adaptability, and mechanical robustness. Despite the remarkable progress in this area, the development of soft microrobots capable of climbing on flat/curved surfaces and transitioning between two different surfaces remains elusive, especially in open spaces. In this study, we address these challenges by developing voltage-driven soft small-scale actuators with customized 3D configurations and active stiffness adjusting. Combination of programmed strain distributions in liquid crystal elastomers (LCEs) and buckling-driven 3D assembly, guided by mechanics modeling, allows for voltage-driven, complex 3D-to-3D shape morphing (bending angle > 200°) at millimeter scales (from 1 to 10 mm), which is unachievable previously. These soft actuators enable development of morphable electroadhesive footpads that can conform to different curved surfaces and stiffness-variable smart joints that allow different locomotion gaits in a single microrobot. By integrating such morphable footpads and smart joints with a deformable body, we report a multigait, soft microrobot (length from 6 to 90 mm, and mass from 0.2 to 3 g) capable of climbing on surfaces with diverse shapes (e.g., flat plane, cylinder, wavy surface, wedge-shaped groove, and sphere) and transitioning between two distinct surfaces. We demonstrate that the microrobot could navigate from one surface to another, recording two corresponding ceilings when carrying an integrated microcamera. The developed soft microrobot can also flip over a barrier, survive extreme compression, and climb bamboo and leaf.

Background: Regional citrate anticoagulation (RCA) is increasingly used for continuous renal replacement therapy (CRRT) in children, but it is rarely used in children with liver injury, especially liver failure (LF). We analyze this issue through the following research., Methods: We retrospectively analyzed 75 children with liver injury who underwent RCA-CRRT in the Pediatric Intensive Care Unit (PICU) of Children's Hospital of Chongqing Medical University. The patients were divided into the LF group and liver dysfunction (LD) group. The two groups were compared to evaluate the clinical safety and efficacy of RCA-CRRT in children with liver injury and to explore RCA-CRRT management strategies, in terms of the following indicators: the incidence of bleeding, clotting, citrate accumulation (CA), acid-base imbalance, and electrolyte disturbance, as well as filter lifespans, changes in biochemical indicators, and CRRT parameters adjustment., Results: The total incidence of CA (TCA) and persistent CA (PCA) in the LF group were significantly higher than those in the LD group (38.6 vs. 16.2%, p < 0.001; 8.4 vs. 1.5%, p < 0.001); and the CA incidence was significantly reduced after adjustment both in the LF (38.6 vs. 8.4%, p < 0.001) and LD groups (16.2 vs. 1.5%, p < 0.001). The incidence of hypocalcemia was significantly higher in the LF group than in the LD group either before (34.9 vs. 8.8%, p < 0.001) or after treatment (12.0 vs. 0%, p < 0.001). The speed of the blood and citrate pumps after adjustment was lower than the initial setting values in both the LF and LD groups. The dialysis speed plus replacement speed were higher than the initial settings parameters., Conclusion: For children undergoing RCA-CRRT, the risks of CA and hypocalcemia are significantly higher in children with liver failure than those with liver dysfunction, but through the proper adjustment of the protocol, RCA-CRRT can still be safely and effectively approached for children with LD and even LF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Sun, Bai and Liu.)

Electronic devices with engineered three-dimensional (3D) architectures are indispensable for frictional-force sensing, wide-field optical imaging, and flow velocity measurement. Recent advances in mechanically guided assembly established deterministic routes to 3D structures in high-performance materials, through controlled rolling/folding/buckling deformations. The resulting 3D structures are, however, mostly formed on planar substrates and cannot be transferred directly onto another curved substrate. Here, we introduce an ordered assembly strategy to allow transformation of 2D thin films into sophisticated 3D structures on diverse curved surfaces. The strategy leverages predefined mechanical loadings that deform curved elastomer substrates into flat/cylindrical configurations, followed by an additional uniaxial/biaxial prestretch to drive buckling-guided assembly. Release of predefined loadings results in an ordered assembly that can be accurately captured by mechanics modeling, as illustrated by dozens of complex 3D structures assembled on curved substrates. Demonstrated applications include tunable dipole antennas, flow sensors inside a tube, and integrated electronic systems capable of conformal integration with the heart.

Objective: To explore the efficacy and safety of vancomycin as measured by pharmacokinetic/pharmacodynamic parameters in children with severe infection in the Pediatric Intensive Care Unit (PICU) and to determine the appropriate threshold for avoiding nephrotoxicity., Methods: The medical records of hospitalized children with severe infection treated with vancomycin in the PICU of a tertiary pediatric hospital from September 2018 to January 2021 were retrospectively collected. Univariate analysis was used to assess the correlation between vancomycin pharmacokinetic/pharmacodynamic parameters and therapeutic efficacy or vancomycin-related nephrotoxicity. Binary logistic regression was used to analyze the risk factors for vancomycin-related nephrotoxicity. The vancomycin area under the concentration-time curve over 24 h (AUC 0-24 ) threshold was determined by receiver operating characteristic (ROC) curve analysis., Results: One hundred and 10 patients were included in this study. Seventy-six patients (69.1%) exhibited clinically effective response, while the rest exhibited clinically ineffective response. There were no significant differences in APACHE II score, steady-state trough concentration, peak concentration or AUC 0-24 of vancomycin between the effective and ineffective groups. Among the 110 patients, vancomycin-related nephrotoxicity occurred in 15 patients (13.6%). Multivariate analysis showed that vancomycin treatment duration, trough concentration, and AUC 0-24 were risk factors for vancomycin-related nephrotoxicity. The ROC curve indicated that AUC 0-24 < 537.18 mg.h/L was a suitable cutoff point for predicting vancomycin-related nephrotoxicity., Conclusion: No significant correlations were found between the trough concentration or AUC 0-24 of vancomycin and therapeutic efficacy when the daily dose of vancomycin was approximately 40 mg/kg d, while the trough concentration and AUC 0-24 were both closely related to vancomycin-related nephrotoxicity. The combination of AUC 0-24 and trough concentration for therapeutic drug monitoring may reduce the risk of nephrotoxicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Xiong, Bai, Dang, Li, Xu, Fu and Liu.)

Elastic stretchability and function density represent two key figures of merits for stretchable inorganic electronics. Various design strategies have been reported to provide both high levels of stretchability and function density, but the function densities are mostly below 80%. While the stacked device layout can overcome this limitation, the soft elastomers used in previous studies could highly restrict the deformation of stretchable interconnects. Here, we introduce stacked multilayer network materials as a general platform to incorporate individual components and stretchable interconnects, without posing any essential constraint to their deformations. Quantitative analyses show a substantial enhancement (e.g., by ~7.5 times) of elastic stretchability of serpentine interconnects as compared to that based on stacked soft elastomers. The proposed strategy allows demonstration of a miniaturized electronic system (11 mm by 10 mm), with a moderate elastic stretchability (~20%) and an unprecedented areal coverage (~110%), which can serve as compass display, somatosensory mouse, and physiological-signal monitor.

Activation of antigen-specific T-lymphocyte responses may be needed to cure disorders caused by chronic infection with low-risk human papillomavirus (lrHPV). Safe and effective adjuvant therapies for such disorders are needed. The safety and efficacy of a novel gorilla adenovirus vaccine expressing a protein designed to elicit immune responses directed against HPV6 and HPV11, PRGN-2012, was studied using in vitro stimulation of T lymphocytes from patients with recurrent respiratory papillomatosis, in vivo vaccination studies, and therapeutic studies in mice bearing tumors expressing lrHPV antigen. PRGN-2012 treatment induces lrHPV antigen-specific responses in patient T lymphocytes. Vaccination of wild-type mice induces E6-specific T-lymphocyte responses without toxicity. In vivo therapeutic vaccination of mice bearing established HPV6 E6 expressing tumors results in HPV6 E6-specific CD8+ T-lymphocyte immunity of sufficient magnitude to induce tumor growth delay. The clinical study of PRGN-2012 in patients with disorders caused by chronic infection with lrHPV is warranted.

Structures that significantly and rapidly change their shapes and sizes upon external stimuli have widespread applications in a diversity of areas. The ability to miniaturize these deployable and morphable structures is essential for applications in fields that require high-spatial resolution or minimal invasiveness, such as biomechanics sensing, surgery, and biopsy. Despite intensive studies on the actuation mechanisms and material/structure strategies, it remains challenging to realize deployable and morphable structures in high-performance inorganic materials at small scales (e.g., several millimeters, comparable to the feature size of many biological tissues). The difficulty in integrating actuation materials increases as the size scales down, and many types of actuation forces become too small compared to the structure rigidity at millimeter scales. Here, we present schemes of electromagnetic actuation and design strategies to overcome this challenge, by exploiting the mechanics-guided three-dimensional (3D) assembly to enable integration of current-carrying metallic or magnetic films into millimeter-scale structures that generate controlled Lorentz forces or magnetic forces under an external magnetic field. Tailored designs guided by quantitative modeling and developed scaling laws allow formation of low-rigidity 3D architectures that deform significantly, reversibly, and rapidly by remotely controlled electromagnetic actuation. Reconfigurable mesostructures with multiple stable states can be also achieved, in which distinct 3D configurations are maintained after removal of the magnetic field. Demonstration of a functional device that combines the deep and shallow sensing for simultaneous measurements of thermal conductivities in bilayer films suggests the promising potential of the proposed strategy toward multimodal sensing of biomedical signals., Competing Interests: The authors declare no competing interest.

Microelectronic devices with reconfigurable three-dimensional (3D) microarchitecture that can be repetitively switched among different geometrical and/or working states have promising applications in widespread areas. Traditional approaches usually rely on stimulated deformations of active materials under external electric/magnetic fields, which could potentially introduce parasitic side effects and lower device performances. Development of a rational strategy that allows access to high-performance 3D microdevices with multiple stable geometric configurations remains challenging. We introduce a mechanically guided scheme to build geometrically reconfigurable 3D mesostructures through a bottom-up design strategy based on a class of elementary reconfigurable structures with the simplest ribbon geometries. Quantitative mechanics modeling of the structural reconfigurability allows for the development of phase diagrams and design maps. Demonstrations of ~30 reconfigurable mesostructures with diverse geometric topologies and characteristic dimensions illustrate the versatile applicability. The multimode nature enables customized distinct beamforming and discrete beam scanning using a single antenna capable of on-demand reconfiguration., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background: To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing., Methods: All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiologic history of these patients were retrospectively collected and analyzed., Results: The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 × 10/L and 2 cases (8%) less than 4 × 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 ± 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital., Conclusions: The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.

Regional citrate anticoagulation (RCA) was recommended as the first treatment option for adults by the Kidney Disease Improving Global Outcomes Kidney Foundation in 2012, for the characteristic of sufficient anticoagulation in vitro, but almost no anticoagulation in vivo. Traditionally, the substitute for RCA is calcium-free. This study investigated a simplified protocol of RCA for continuous hemofiltration (CHF) in children using a commercially available substitute containing calcium.An analytical, observational, retrospective study assessed 59 pediatric patients with 106 sessions and 3580 hours of CHF. Values before and after treatment were compared, including Na, ionic calcium (iCa) and HCO3 concentrations, pH, and the ratio of total calcium to iCa (T/iCa). In addition, in vivo and in vitro iCa, treatment time, sessions with continuous transmembrane pressure >200 mm Hg, and sessions with clotting and bleeding were recorded.The average treatment time was 33.8 ± 10.1 hours. In vitro, 88.5% of iCa achieved the target (0.25-0.35 mmol/L), and in vivo, 95.4% of iCa achieved the target (1.0-1.35 mmol/L). There were 8 sessions with a transmembrane pressure >200 mm Hg and 3 sessions with filters clotted. After treatment, there were 2, 1, and 2 sessions with T/iCa > 2.5 (implying citrate accumulation), iCa < 0.9 mmol/L, and iCa > 1.35 mmol/L. No sodium disorders were recorded. There were fewer cases of acidemia and more cases of alkalemia after treatment compared to before.RCA-CHF with a substitute containing calcium and close monitoring could be a safe and effective treatment for children. In addition, the calcium test site in vitro and the adjustment of citrate should be given strict attention.

The T cell antigen receptor (TCR) expressed on thymocytes interacts with self-peptide major histocompatibility complex (pMHC) ligands to signal apoptosis or survival. Here, we found that negative-selection ligands induced thymocytes to exert forces on the TCR and the co-receptor CD8 and formed cooperative TCR-pMHC-CD8 trimolecular 'catch bonds', whereas positive-selection ligands induced less sustained thymocyte forces on TCR and CD8 and formed shorter-lived, independent TCR-pMHC and pMHC-CD8 bimolecular 'slip bonds'. Catch bonds were not intrinsic to either the TCR-pMHC or the pMHC-CD8 arm of the trans (cross-junctional) heterodimer but resulted from coupling of the extracellular pMHC-CD8 interaction to the intracellular interaction of CD8 with TCR-CD3 via associated kinases to form a cis (lateral) heterodimer capable of inside-out signaling. We suggest that the coupled trans-cis heterodimeric interactions form a mechanotransduction loop that reinforces negative-selection signaling that is distinct from positive-selection signaling in the thymus.

Cordyceps militaris is a dietary therapeutic fungus that is an important model species in Cordyceps research. In this study, we purified a novel protein from the fruit bodies of C. militaris and designated it as Cordyceps militaris protein (CMP). CMP has a molecular mass of 18.0 kDa and is not glycosylated. Interestingly, CMP inhibited cell viability in murine primary cells and other cell lines in a time- and dose-dependent manner. Using trypan blue staining and a lactate dehydrogenase release assay, we showed that CMP caused cell death in the murine hepatoma cell line BNL 1MEA.7R.1. Furthermore, the frequency of BNL 1MEA.7R.1 cells at the sub-G1 stage was increased by CMP. Apoptosis, as determined by Annexin V and propidium iodide analysis, indicated that CMP could mediate BNL 1MEA.7R.1 apoptosis, but not necrosis. After coincubation with CMP, a decrease in mitochondria potential was detected using 3,3'-dihexyloxacarbocyanine iodide. These results suggest that CMP is a harmful protein that induces apoptosis through a mitochondrion-dependent pathway. Stability experiments demonstrated that heat treatment and alkalization degraded CMP and further destroyed its cell-death-inducing ability, implying that cooking is necessary for food containing C. militaris., (Copyright © 2017. Published by Elsevier B.V.)

Aim: To evaluate the diagnostic value of different sonographic methods in hemorrhoids., Methods: Forty-two healthy volunteers and sixty-two patients with grades I-IV hemorrhoids received two different sonographic examinations from January 2013 to January 2016 at the First and Second Hospitals of Xinjiang Medical University in a prospective way. We analyzed the ultrasonographic findings of these participants and evaluated the outcomes. Resected grades III and IV hemorrhoid tissues were pathologically examined. The concordance of ultrasonographic results with pathology results was assessed with the Cohen's kappa coefficient., Results: All healthy volunteers and all patients had no particular complications related to sonography. There were no statistically significant differences between the participants regarding age ( P = 0.5919), gender ( P = 0.4183), and persistent symptoms ( P > 0.8692). All healthy control participants had no special findings. However, 30 patients with hemorrhoids showed blood signals around the dentate line on ultrasonography. When grades I and II hemorrhoids were analyzed, there were no significant differences between transrectal ultrasound (TRUS), transperianal ultrasound (TPUS), and transvaginal ultrasound (TVUS) ( P > 0.05). Grades III and IV hemorrhoids revealed blood flow with different directions which could be observed as a "mosaic pattern". In patients with grades III and IV hemorrhoids, the number of patients with "mosaic pattern" as revealed by TRUS, TPUS and TVUS was 22, 12, and 4, respectively. Patients with grades III and IV disease presented with a pathologically abnormal cushion which usually appeared as a "mosaic pattern" in TPUS and an arteriovenous fistula in pathology. Subepithelial vessels of resected grades III and IV hemorrhoid tissues were manifested by obvious structural impairment and retrograde and ruptured changes of internal elastic lamina. Some parts of the Trietz's muscle showed hypertrophy and distortion. Arteriovenous fistulas and venous dilatation were obvious in the anal cushion of hemorhoidal tissues. After pathological results with arteriovenous fistulas were taken as the standard reference, we evaluated the compatibility between the two methods according to the Cohen's kappa co-efficiency calculation. The compatibility (Cohein kappa co-efficiency value) between "mosaic pattern" in the TPUS and arteriovenous fistula in pathology was very good (ĸ = 0.8939). When compared between different groups, TRUS presented the advantage that the mosaic pattern could be confirmed in more patients, especially for group A. There was a statistical difference when comparing group A with group B or C ( P < 0.05 for both). There were obvious statistical differences between group A and group B with regard to the vessel diameter and blood flow velocity measured by TRUS ( P < 0.05)., Conclusion: Patients with grades III and IV hemorrhoids present with a pathologically abnormal cushion which usually appears as a "mosaic pattern" in sonography, which is in accord with an arteriovenous fistula in pathology. There are clearly different hemorrhoid structures shown by sonography. "Mosaic pattern" may be a parameter for surgical indication of grades III and IV hemorrhoids., Competing Interests: Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists. All the authors have no commercial associations or other interest in connection. Cai Yan has received fees for serving as an advisory board manager for the First Affiliated Hospital of Xinjiang Medical University. Cai Yan has received research funding from the National Natural Science Foundation of China. De Lixiati is an employee of the Research Center of Xinjiang Medical University.

Pristine graphene is strongly diamagnetic. However, graphene with single carbon atom defects could exhibit paramagnetism. Theoretically, the π magnetism induced by the monovacancy in graphene is characteristic of two spin-split density-of-states (DOS) peaks close to the Dirac point. Since its prediction, many experiments have attempted to study this π magnetism in graphene, whereas only a notable resonance peak has been observed around the atomic defects, leaving the π magnetism experimentally elusive. Here, we report direct experimental evidence of π magnetism by using a scanning tunneling microscope. We demonstrate that the localized state of the atomic defects is split into two DOS peaks with energy separations of several tens of meV. Strong magnetic fields further increase the energy separations of the two spin-polarized peaks and lead to a Zeeman-like splitting. Unexpectedly, the effective g factor around the atomic defect is measured to be about 40, which is about 20 times larger than the g factor for electron spins.

Adaptive cellular immunity requires accurate self- vs. nonself-discrimination to protect against infections and tumorous transformations while at the same time excluding autoimmunity. This vital capability is programmed in the thymus through selection of αβT-cell receptors (αβTCRs) recognizing peptides bound to MHC molecules (pMHC). Here, we show that the pre-TCR (preTCR), a pTα-β heterodimer appearing before αβTCR expression, directs a previously unappreciated initial phase of repertoire selection. Contrasting with the ligand-independent model of preTCR function, we reveal through NMR and bioforce-probe analyses that the β-subunit binds pMHC using Vβ complementarity-determining regions as well as an exposed hydrophobic Vβ patch characteristic of the preTCR. Force-regulated single bonds akin to those of αβTCRs but with more promiscuous ligand specificity trigger calcium flux. Thus, thymic development involves sequential β- and then, αβ-repertoire tuning, whereby preTCR interactions with self pMHC modulate early thymocyte expansion, with implications for β-selection, immunodominant peptide recognition, and germ line-encoded MHC interaction.

Aim: To compare biofeedback-guided pelvic floor exercise therapy (BFT) with the use of oral polyethylene glycol (PEG) for the treatment of obstructive defecation., Methods: A total of 88 subjects were assigned to treatment with either BFT (n = 44) or oral PEG (n = 44). Constipation symptoms (including difficult evacuation, hard stool, digitation necessity, incomplete emptying sensation, laxative dependence, perianal pain at defecation, and constipation satisfaction), Wexner Scores, and quality of life scores were assessed after 1, 3, and 6 mo., Results: At the 6 mo follow-up, the symptoms of the BFT group patients showed significantly greater improvements compared with the PEG group regarding difficult evacuation, hard stools, digitation necessity, laxative dependence, perianal pain at defecation, constipation satisfaction, Wexner Constipation Score, and quality of life score (P < 0.05). The quality of life score of the BFT group at the final follow-up time (6 mo) was 80 ± 2.2. After a complete course of training, improvements in the clinical symptoms of the BFT group were markedly improved (P < 0.05), and the Wexner Constipation Scores were greatly decreased compared with the oral PEG group (P < 0.05)., Conclusion: We concluded that manometric biofeedback-guided pelvic floor exercise training is superior to oral polyethylene glycol therapy for obstructive defecation.

Aim: To discuss the impact of Lycium Barbarum Polysaccharide (LBP) and Danshensu purified from Traditional Chinese Medicine (TCM) on vascular endothelial growth factor (VEGF) of rabbits with retinal neovascularization., Methods: Forty rabbits were divided into normal control group, model control group, LBP group and Danshensu group. Animals in the normal control group were fed in the normal oxygen environment. Animals in the other three groups were put into the environment with 70% oxygen for 5 days in order to build the model of oxygen-induced vascular proliferation retinopathy. And then different TCM extract was injected into the abdominal cavities of these annimals. After 7 days, the VEGF content of in the serum of rabbit was measured by double antibody sandwich method., Results: DATA ANALYSIS INDICATED THAT VEGF CONTENT WAS AS FOLLOWS: Danshensu group was lower than model control group (12.92±3.84ng/L vs 19.32±4.15ng/L, P<0.05); LBP group and normal control group were lower than model control group (12.92±3.84ng/L, 9.26±1.61ng/L vs 19.32±4.15ng/L, P<0.01); total blood viscosity, plasma viscosity, cholesterol content, fibrinogen content and triacylglycerol content after peritoneal injection of LBP and Danshensu were obviously lower than before injection., Conclusion: TCM extract-LBP and Danshensu can prominently reduce the content of VEGF in the process of vascular proliferative retinopathy of rabbit; can prevent the occurrence of retinal microvascular disease by improving partial oxygen-deficient environment or affecting all kinds of new growth factor.

Objective: To explore the relationships of serum vascular endothelial growth factor (VEGF) and endometrial cancer of Uighur Women in Xinjiang., Methods: The serum of 50 endometrial cancer patient's and 70 healthy women' s were collected. VEGF expressions were tested by ELISA method and the correlations of endometrial cancer with VEGF were analysed. The variety of serum VEGF in different clinical stages of endometrial cancer was analyzed., Results: Serum VEGF expressions on endometrial cancer were significantly higher than normal ones (P < 0.01); The serum VEGF level in late stage was significantly higher than early stage (P < 0.01). The serum VEGF level significantly increased from well differentiated to the poorly differentiated cases (P < 0.05)., Conclusion: high level expressions of VEGF are related to the endometrial cancer. Uighur Women in Xinjiang, particularly high expressed in advanced and poorly differentiated endometrial cancer.

Objective: To evaluate the efficacy and safety of percutaneous balloon kyphoplasty as a new therapy for patients with painful osteoporotic vertebral compressive fractures of the lumbar and thoracic spine., Methods: A retrospective analysis was conducted in 38 consecutive patients (28 females, 10 males), whose ages ranged from 56 to 82 years (mean age 72 years). The symptom- and sign-positive spinal segment was identified by MRI. The time between onset of symptoms and surgical intervention ranged from 2 days to 1 year. 62 segments (36 thoracic, 26 lumbar) were treated in this cohort. The pain score estimated by Visual Analog Scale and activity degree were assessed immediately after operation and at 1-, 6-, and 12-month postoperative follow-up. Preoperative and postoperative anterior, midline vertebral heights in fractured vertebrae were measured on lateral radiographs to evaluate the effect of the procedure., Results: The method achieved a swift pain relief associated with an evidently increased weight-bearing ability. The pain score was reduced from 8.2 to 2.4 points. The anterior and midline vertebral heights in 62 fractured vertebral bodies increased up to 82.76%+/-26.84%, 88.82%+/-21.75% and the wedge decreased from 15 to 8 degrees. This effect persisted at least over a period of two years. The procedure did not induce narrowing of the spinal canal and no severe complications occurred., Conclusions: Balloon kyphoplasty can result in immediate clinical improvement of mobility and pain relief, increase vertebral body height, and quickly return patient's activity. The short-term results are approved excellent, and the long-term results need further judgment.

Objectives: To discuss and evaluate the selection of surgical procedure for the treatment of idiopathic scoliosis according to the location and degree of the deformity., Methods: 175 patients with idiopathic scoliosis underwent surgical treatment with correction and fusion. The patients were divided into four groups according to the location and degree of the deformity and four different procedures were used for each group. For each group, the blood loss, surgery time, correction rate, loss of correction at final follow up and complications were compared and analyzed., Results: All patients underwent surgery safely and no neurological complication occurred. The correction rate was 81% for Group I, 86% for Group II, 68% for Group III and 72% for Group IV. All patients were followed up at least 2 years and the average time was 38 months (24 approximately 52)., Conclusion: Proper selection of surgical procedure according to the location and degree of the scoliotic deformity, satisfactory results can be achieved in the treatment of idiopathic scoliosis.