A drug-loaded flexible substrate improves the performance of conformal cortical electrodes

Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial infection and inflammatory reaction risks associated with foreign body exposure.Moreover,inflammation of the wound area can dramatically worsen in response to bacterial infection.These consequences can not only lead to the failure of cortical electrode implantation but also threaten the lives of patients.Herein,we prepared a hydrogel made of bacterial cellulose(BC),a flexible substrate for cortical electrodes,and further loaded antibiotic tetracycline(TC)and the anti-inflammatory drug dexamethasone(DEX)onto it.The encapsulated drugs can be released from the BC hydrogel and effectively inhibit the growth of Gram-negative and Gram-positive bacteria.Next,therapeutic cortical electrodes were developed by integrating the drug-loaded BC hydrogel and nine-channel serpentine arrays;these were used to record electrocorticography(ECoG)signals in a rat model.Due to the controlled release of TC and DEX from the BC hydrogel substrate,therapeutic cortical electrodes can alleviate or prevent symptoms associated with the bacterial infection and inflammation of brain tissue.This approach facilitates the development of drug delivery electrodes for resolving complications caused by implantable electrodes.

Unveiling the secrets of gastrointestinal mucous adenocarcinoma survival after surgery with artificial intelligence:A population-based study

BACKGROUND Research on gastrointestinal mucosal adenocarcinoma(GMA)is limited and controversial,and there is no reference tool for predicting postoperative survival.AIM To investigate the prognosis of GMA and develop predictive model.METHODS From the Surveillance,Epidemiology,and End Results database,we collected clinical information on patients with GMA.After random sampling,the patients were divided into the discovery(70%of the total,for model training),validation(20%,for model evaluation),and completely blind test cohorts(10%,for further model evaluation).The main assessment metric was the area under the receiver operating characteristic curve(AUC).All collected clinical features were used for Cox proportional hazard regression analysis to determine factors influencing GMA’s prognosis.RESULTS This model had an AUC of 0.7433[95% confidence intervals(95%CI):0.7424-0.7442]in the discovery cohort,0.7244(GMA:0.7234-0.7254)in the validation cohort,and 0.7388(95%CI:0.7378-0.7398)in the test cohort.We packaged it into Windows software for doctors’use and uploaded it.Mucinous gastric adenocarcinoma had the worst prognosis,and these were protective factors of GMA:Regional nodes examined[hazard ratio(HR):0.98,95%CI:0.97-0.98,P<0.001]and chemotherapy(HR:0.62,95%CI:0.58-0.66,P<0.001).CONCLUSION The deep learning-based tool developed can accurately predict the overall survival of patients with GMA postoperatively.Combining surgery,chemotherapy,and adequate lymph node dissection during surgery can improve patient outcomes.

Progress in Mechanical Modeling of Implantable Flexible Neural Probes

Implanted neural probes can detect weak discharges of neurons in the brain by piercing soft brain tissue,thus as important tools for brain science research,as well as diagnosis and treatment of brain diseases.However,the rigid neural probes,such as Utah arrays,Michigan probes,and metal microfilament electrodes,are mechanically unmatched with brain tissue and are prone to rejection and glial scarring after implantation,which leads to a significant degradation in the signal quality with the implantation time.In recent years,flexible neural electrodes are rapidly developed with less damage to biological tissues,excellent biocompatibility,and mechanical compliance to alleviate scarring.Among them,the mechanical modeling is important for the optimization of the structure and the implantation process.In this review,the theoretical calculation of the flexible neural probes is firstly summarized with the processes of buckling,insertion,and relative interaction with soft brain tissue for flexible probes from outside to inside.Then,the corresponding mechanical simulation methods are organized considering multiple impact factors to realize minimally invasive implantation.Finally,the technical difficulties and future trends of mechanical modeling are discussed for the next-generation flexible neural probes,which is critical to realize low-invasiveness and long-term coexistence in vivo.

Design of AI-Enhanced and Hardware-Supported Multimodal E-Skin for Environmental Object Recognition and Wireless Toxic Gas Alarm

Post-earthquake rescue missions are full of challenges due to the unstable structure of ruins and successive aftershocks.Most of the current rescue robots lack the ability to interact with environments,leading to low rescue efficiency.The multimodal electronic skin(e-skin)proposed not only reproduces the pressure,temperature,and humidity sensing capabilities of natural skin but also develops sensing functions beyond it—perceiving object proximity and NO2 gas.Its multilayer stacked structure based on Ecoflex and organohydrogel endows the e-skin with mechanical properties similar to natural skin.Rescue robots integrated with multimodal e-skin and artificial intelligence(AI)algorithms show strong environmental perception capabilities and can accurately distinguish objects and identify human limbs through grasping,laying the foundation for automated post-earthquake rescue.Besides,the combination of e-skin and NO2 wireless alarm circuits allows robots to sense toxic gases in the environment in real time,thereby adopting appropriate measures to protect trapped people from the toxic environment.Multimodal e-skin powered by AI algorithms and hardware circuits exhibits powerful environmental perception and information processing capabilities,which,as an interface for interaction with the physical world,dramatically expands intelligent robots’application scenarios.

多项式族的分离及其在单点边界上的计算

研究了多项式族的分离表示形式及其在单点边界上的计算问题 .对结构型不确定性多项式族进行了分类 ,在此基础上建立了多项式族在单点边界上的计算规则 ,从而为直接使用计算机研究系统的鲁棒稳定性提供了必要的数值计算基础 .

Lead helix winding tricuspid chordae tendineae: A case report

BACKGROUND As left bundle branch pacing(LBBP)is more like physiological pacing,LBBP has emerged as a novel pacing strategy that uses the native conduction system to improve ventricular synchronization with stable pacing parameters.LBBP has been revealed associated with a significantly reduced risk of new-onset atrial fibrillation and heart failure compared with conventional permanent pacemaker implantation.CASE SUMMARY A 64-year-old man was admitted with a 24-h history of chest distress and shortness of breath,which continued unabated.The patient had no symptoms of chest pain,dizziness,syncope,nausea nor vomiting.There were no abnormalities found in routine examinations after admission.Twelve-lead electrocardiogram presented a result of 2:1 atrioventricular block.Coronary angiography was performed the next day and no abnormality was found.Finally,the patient agreed to received LBBP and signed the informed consent.During the process of withdrawing the Medtronic Model 3830 lead into sheath,we found the lead helix was wrapped around the chordae tendineae of the septal valve of tricuspid.Attempts to rotate the 3830 lead failed to release the lead helix from the chordae tendineae,and ultimately we used radiofrequency ablation to ablate the wrapped chordae tendineae.CONCLUSION Radiofrequency ablation effectively solved this problem without complications.It is an effective and reliable method to resolve lead winding chordae.

Galactose Supramolecular Docking Orchestrates Macrophage Phenotype

目的探究半乳糖超分子结合细胞膜受体,调控巨噬细胞极化和肿瘤杀伤的行为。方法通过半乳糖分子与探针分子共价结合,构建半乳糖超分子探针,选用SEM和化学组成分析等技术对探针分子进行表征。随后,将半乳糖探针与巨噬细胞孵育,明确二者在细胞膜表面发生相互作用。选用荧光染色技术探究巨噬细胞和半乳糖探针之间结合的敏感性和特异性。

The Influence of Glucose on Numerical Simulation of a Vascular Solid Tumor Growth

Glucose is the mainly nutrient substances in tumor growth,which played an important role in tumor cells' growth,proliferation and immigration.Numerical simulation will help a good understanding for the influence of glucose which affected on a vascular solid tumor growth.We present a hybrid on-Lattice Model to simulate the influence of glucose on a-vascular tumor growth.The hybrid model we developed focuses on five key variables implicated in the invasion process:tumor cells,extracellular matrix,matrix-degradative enzymes,oxygen and glucose.And about the discrete model,we consider cell evolution dynamics on cell level.Results indicate that the number of proliferation and quiescent cells is decreasing by decreasing the initial glucose concentration,consequently increase necrotic area relatively.Thus there is inhabitation effect on tumor growth by decreasing initial glucose concentration.

Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Ferroptosis,a unique modality of cell death with mechanistic and morphological differences from other cell death modes,plays a pivotal role in regulating tumorigenesis and offers a new opportunity for modulating anticancer drug resistance.Aberrant epigenetic modifications and posttranslational modifications(PTMs)promote anticancer drug resistance,cancer progression,and metastasis.Accumulating studies indicate that epigenetic modifications can transcriptionally and translationally determine cancer cell vulnerability to ferroptosis and that ferroptosis functions as a driver in nervous system diseases(NSDs),cardiovascular diseases(CVDs),liver diseases,lung diseases,and kidney diseases.In this review,we first summarize the core molecular mechanisms of ferroptosis.Then,the roles of epigenetic processes,including histone PTMs,DNA methylation,and noncoding RNA regulation and PTMs,such as phosphorylation,ubiquitination,SUMOylation,acetylation,methylation,and ADP-ribosylation,are concisely discussed.The roles of epigenetic modifications and PTMs in ferroptosis regulation in the genesis of diseases,including cancers,NSD,CVDs,liver diseases,lung diseases,and kidney diseases,as well as the application of epigenetic and PTM modulators in the therapy of these diseases,are then discussed in detail.Elucidating the mechanisms of ferroptosis regulation mediated by epigenetic modifications and PTMs in cancer and other diseases will facilitate the development of promising combination therapeutic regimens containing epigenetic or PTM-targeting agents and ferroptosis inducers that can be used to overcome chemotherapeutic resistance in cancer and could be used to prevent other diseases.In addition,these mechanisms highlight potential therapeutic approaches to overcome chemoresistance in cancer or halt the genesis of other diseases.

A toroidal SAW gyroscope with focused IDTs for sensitivity enhancement

A surface acoustic wave(SAW)gyroscope measures the rate of rotational angular velocity by exploiting a phenomenon known as the SAW gyroscope effect.Such a gyroscope is a great candidate for application in harsh environments because of the simplification of the suspension vibration mechanism necessary for traditional microelectromechanical system(MEMS)gyroscopes.Here,for the first time,we propose a novel toroidal standing-wave-mode SAW gyroscope using focused interdigitated transducers(FIDTs).Unlike traditional SAW gyroscopes that use linear IDTs to generate surface acoustic waves,which cause beam deflection and result in energy dissipation,this study uses FIDTs to concentrate the SAW energy based on structural features,resulting in better focusing performance and increased SAW amplitude.The experimental results reveal that the sensitivity of the structure is 1.51µV/(°/s),and the bias instability is 0.77°/s,which are improved by an order of magnitude compared to those of a traditional SAW gyroscope.Thus,the FIDT component can enhance the performance of the SAW gyroscope,demonstrating its superiority for angular velocity measurements.This work provides new insights into improving the sensitivity and performance of SAW gyroscopes.

Optimization of ferroelectricity and endurance of hafnium zirconium oxide thin films by controlling element inhomogeneity

Ferroelectric thin films based on HfO_(2) have garnered increasing attention worldwide,primarily due to their remarkable compatibility with silicon and scalability,in contrast to traditional perovskite-structured ferroelectric materials.Nonetheless,significant challenges remain in their widespread commercial utilization,particularly concerning their notable wake-up effect and limited endurance.To address these challenges,we propose a novel strategy involving the inhomogeneous distribution of Hf/Zr elements within thin films and explore its effects on the ferroelectricity and endurance of Hf_(0.5)Zr_(0.5)O_(2) thin films.Through techniques such as grazing incidence X-ray diffraction,transmission electron microscopy,and piezoresponse force microscopy,we investigated the structural characteristics and domain switching behaviors of these materials.The experimental results indicate that the inhomogeneous distribution of Hf/Zr contributes to improving the frequency stability and endurance while maintaining a large remnant polarization in Hf_(0.5)Zr_(0.5)O_(2) ferroelectric thin films.By adjusting the distribution of Zr/Hf within the Hf_(0.5)Zr_(0.5)O_(2) thin films,significant enhancements in the remnant polarization(2P_(r)>35μC/cm2)and endurance(>109)along with a reduced coercive voltage can be achieved.Additionally,the fabricated ferroelectric thin films also exhibit high dielectric tunability(≥26%)under a low operating voltage of 2.5 V,whether in the wake-up state or not.This study offers a promising approach to optimize both the ferroelectricity and endurance of HfO_(2)-based thin films.

Association between coronary artery stenosis and myocardial injury in patients with acute pulmonary embolism:A case-control study

Background:The potential impact of pre-existing coronary artery stenosis(CAS)on acute pulmonary embolism(PE)episodes remains underexplored.This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I(hs-cTnI)levels in patients with PE.Methods:In this multicenter,prospective case-control study,88 cases and 163 controls matched for age,sex,and study center were enrolled.Cases were patients with PE with elevated hs-cTnI.Controls were patients with PE with normal hs-cTnI.Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography.CAS was defined as≥50%stenosis of the lumen diameter in any coronary vessel>2.0 mm in diameter.Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results:The percentage of CAS was higher in the case group compared to the control group(44.3%[39/88]vs.30.1%[49/163];P=0.024).In multivariable conditional logistic regression model 1,CAS(adjusted odds ratio[OR],2.680;95%confidence interval[CI],1.243-5.779),heart rate>75 beats/min(OR,2.306;95%CI,1.056-5.036)and N-terminal pro-B type natriuretic peptide(NT-proBNP)>420 pg/mL(OR,12.169;95%CI,4.792-30.900)were independently associated with elevated hs-cTnI.In model 2,right CAS(OR,3.615;95%CI,1.467-8.909)and NT-proBNP>420 pg/mL(OR,13.890;95%CI,5.288-36.484)were independently associated with elevated hs-cTnI.Conclusions:CAS was independently associated with myocardial injury in patients with PE.Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

SPEED:an integrated,smartphone-operated,handheld digital PCR Device for point-of-care testing

This study elaborates on the design,fabrication,and data analysis details of SPEED,a recently proposed smartphonebased digital polymerase chain reaction(dPCR)device.The dPCR chips incorporate partition diameters ranging from 50μm to 5μm,and these partitions are organized into six distinct blocks to facilitate image processing.Due to the superior thermal conductivity of Si and its potential for mass production,the dPCR chips were fabricated on a Si substrate.A temperature control system based on a high-power density Peltier element and a preheating/cooling PCR protocol user interface shortening the thermal cycle time.The optical design employs four 470 nm light-emitting diodes as light sources,with filters and mirrors effectively managing the light emitted during PCR.An algorithm is utilized for image processing and illumination nonuniformity correction including conversion to a monochromatic format,partition identification,skew correction,and the generation of an image correction mask.We validated the device using a range of deoxyribonucleic acid targets,demonstrating its potential applicability across multiple fields.Therefore,we provide guidance and verification of the design and testing of the recently proposed SPEED device.

An integrated microfluidic platform for nucleic acid testing

This study presents a rapid and versatile low-cost sample-to-answer system for SARS-CoV-2 diagnostics.The system integrates the extraction and purification of nucleic acids,followed by amplification via either reverse transcriptionquantitative polymerase chain reaction(RT–qPCR)or reverse transcription loop-mediated isothermal amplification(RT–LAMP).By meeting diverse diagnostic and reagent needs,the platform yields testing results that closely align with those of commercial RT-LAMP and RT‒qPCR systems.Notable advantages of our system include its speed and costeffectiveness.The assay is completed within 28 min,including sample loading(5 min),ribonucleic acid(RNA)extraction(3 min),and RT-LAMP(20 min).The cost of each assay is≈$9.5,and this pricing is competitive against that of Food and Drug Administration(FDA)-approved commercial alternatives.Although some RNA loss during on-chip extraction is observed,the platform maintains a potential limit of detection lower than 297 copies.Portability makes the system particularly useful in environments where centralized laboratories are either unavailable or inconveniently located.Another key feature is the platform’s versatility,allowing users to choose between RT‒qPCR or RT‒LAMP tests based on specific requirements.

Characterization of forced localization of disordered weakly coupled micromechanical resonators

The mode localization phenomenon of disordered weakly coupled resonators(WCRs)is being used as a novel transduction scheme to further enhance the sensitivity of micromechanical resonant sensors.In this paper,two novel characteristics of mode localization are described.First,we found that the anti-resonance loci behave as a linear function of the stiffness perturbation.The antiresonance behavior can be regarded as a new manifestation of mode localization in the frequency domain,and mode localization occurs at a deeper level as the anti-resonance approaches closer to the resonance.The anti-resonance loci can be used to identify the symmetry of the WCRs and the locations of the perturbation.Second,by comparing the forced localization responses of the WCRs under both the single-resonator-driven(SRD)scheme and the double-resonator-driven(DRD)scheme,we demonstrated that the DRD scheme extends the linear measurement scale while sacrificing a certain amount of sensitivity.We also demonstrated experimentally that the amplitude ratio-based sensitivity under the DRD scheme is approximately an order of magnitude lower than that under the SRD scheme,that is,the amplitude ratio-based sensitivity is−70.44%(Nm^(−1))^(−1) under the DRD scheme,while it is−785.6%(Nm^(−)1)^(−1) under the SRD scheme.These characteristics of mode localization are valuable for the design and control of WCR-based sensors.

Observer-based control for the platform of a tethered space robot

This paper addresses the attitude control problem of a space tethered robot platform in the presence of unknown external disturbance caused by a connecting elastic tether. The tethergenerated unknown disturbance leads to tremendous challenges for attitude control of the platform.In this work, the perturbed attitude dynamics of the platform are derived with a consideration of the libration of the elastic tether, and then with the purpose of compensating the unknown disturbance, major attention is dedicated to develop a nonlinear disturbance observer based on gyros measurements, after which, an adaptive attitude scheme is proposed by combining the disturbance observer with a sliding mode controller. Finally, benefits from the observer based on an adaptive controller are validated by series of numerical simulations.

Chip-based ion chromatography (chip-IC) with a sensitive five-electrode conductivity detector for the simultaneous detection of multiple ions in drinking water

The emerging need for accurate,efficient,inexpensive,and multiparameter monitoring of water quality has led to interest in the miniaturization of benchtop chromatography systems.This paper reports a chip-based ion chromatography(chip-IC)system in which the microvalves,sample channel,packed column,and conductivity detector are all integrated on a polymethylmethacrylate(PMMA)chip.A laser-based bonding technique was developed to guarantee simultaneous robust sealing between the homogeneous and heterogeneous interfaces.A five-electrode-based conductivity detector was presented to improve the sensitivity for nonsuppressed anion detection.Common anions(F^(−),Cl^(−),NO_(3)^(−),and SO _(4)^(2−))were separated in less than 8 min,and a detection limit(LOD)of 0.6 mg L^(−1) was achieved for SO_(4)^(2−).Tap water was also analyzed using the proposed chip-IC system,and the relative deviations of the quantified concentration were less than 10%when compared with that a commercial IC system.

A high-precision multi-dimensional microspectroscopic technique for morphological and properties analysis of cancer cell

Raman and Brillouin scattering are sensitive approaches to detect chemical composition and mechanical elasticity pathology of cells in cancer development and their medical treatment researches.The application is,however,suffering from the lack of ability to synchronously acquire the scattering signals following three-dimensional(3D)cell morphology with reasonable spatial resolution and signal-to-noise ratio.Herein,we propose a divided-aperture laser differential confocal 3D Geometry-Raman-Brillouin microscopic detection technology,by which reflection,Raman,and Brillouin scattering signals are simultaneously in situ collected in real time with an axial focusing accuracy up to 1 nm,in the height range of 200μm.The divided aperture improves the anti-noise capability of the system,and the noise influence depth of Raman detection reduces by 35.4%,and the Brillouin extinction ratio increases by 22 dB.A high-precision multichannel microspectroscopic system containing these functions is developed,which is utilized to study gastric cancer tissue.As a result,a 25%reduction of collagen concentration,42%increase of DNA substances,17%and 9%decrease in viscosity and elasticity are finely resolved from the 3D mappings.These findings indicate that our system can be a powerful tool to study cancer development new therapies at the sub-cell level.

Brainmask:an ultrasoft and moist microelectrocorticography electrode for accurate positioning and long-lasting recordings

Bacterial cellulose(BC),a natural biomaterial synthesized by bacteria,has a unique structure of a cellulose nanofiberweaved three-dimensional reticulated network.BC films can be ultrasoft with sufficient mechanical strength,strong water absorption and moisture retention and have been widely used in facial masks.These films have the potential to be applied to implantable neural interfaces due to their conformality and moisture,which are two critical issues for traditional polymer or silicone electrodes.In this work,we propose a micro-electrocorticography(micro-ECoG)electrode named“Brainmask”,which comprises a BC film as the substrate and separated multichannel parylene-C microelectrodes bonded on the top surface.Brainmask can not only guarantee the precise position of microelectrode sites attached to any nonplanar epidural surface but also improve the long-lasting signal quality during acute implantation with an exposed cranial window for at least one hour,as well as the in vivo recording validated for one week.This novel ultrasoft and moist device stands as a next-generation neural interface regardless of complex surface or time of duration.

Severe graft-versus-host disease post allogeneic hematopoietic stem cell transplantation due to loss of HLA heterozygosity in recipient lymphocytes after full graft rejection

Germ cell tumors complicated by hematological malignancy(HM)are a rare clinical phenomenon.Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is a potentially effective therapy,but graft-versus-host disease(GVHD)is a life-threatening complication.We report a case of a 13-year-old female patient diagnosed with germ cell tumors followed by acute lymphoblastic leukemia.After chemotherapy,she received allo-HSCT and her chimerism rate decreased rapidly to near zero by 6 months without evidence of HM recurrence.However,she developed severe,multiorgan GVHD-like manifestations.DNA analysis revealed the pathogenesis of GVHD to be loss of HLA heterozygosity in recipient hematopoietic cells.