Microarrow sensor array with enhanced skin adhesion for transdermal continuous monitoring of glucose and reactive oxygen species

Conventional blood sampling for glucose detection is prone to cause pain and fails to continuously record glucose fluctuations in vivo.Continuous glucose monitoring based on implantable electrodes could induce pain and potential tissue inflammation,and the presence of reactive oxygen species(ROS)due to inflammationmay affect glucose detection.Microneedle technology is less invasive,yet microneedle adhesion with skin tissue is limited.In this work,we developed a microarrow sensor array(MASA),which provided enhanced skin surface adhesion and enabled simultaneous detection of glucose and H_(2)O_(2)(representative of ROS)in interstitial fluid in vivo.The microarrows fabricated via laser micromachining were modified with functional coating and integrated into a patch of a three-dimensional(3D)microneedle array.Due to the arrow tip mechanically interlocking with the tissue,the microarrow array could better adhere to the skin surface after penetration into skin.The MASA was demonstrated to provide continuous in vivo monitoring of glucose and H_(2)O_(2) concentrations,with the detection of H_(2)O_(2) providing a valuable reference for assessing the inflammation state.Finally,the MASA was integrated into a monitoring system using custom circuitry.This work provides a promising tool for the stable and reliable monitoring of blood glucose in diabetic patients.

Semi-implantable device based on multiplexed microfilament electrode cluster for continuous monitoring of physiological ions

Modern medicine is increasingly interested in advanced sensors to detect and analyze biochemical indicators.Ion sensors based on potentiometric methods are a promising platform for monitoring physiological ions in biological subjects.Current semi-implantable devices are mainly based on single-parameter detection.Miniaturized semi-implantable electrodes for multiparameter sensing have more restrictions on the electrode size due to biocompatibility considerations,but reducing the electrode surface area could potentially limit electrode sensitivity.This study developed a semi-implantable device system comprising a multiplexed microfilament electrode cluster(MMEC)and a printed circuit board for real-time monitoring of intra-tissue K^(+),Ca^(2+),and Na^(+)concentrations.The electrode surface area was less important for the potentiometric sensing mechanism,suggesting the feasibility of using a tiny fiber-like electrode for potentiometric sensing.The MMEC device exhibited a broad linear response(K^(+):2–32 mmol/L;Ca^(2+):0.5–4 mmol/L;Na^(+):10–160 mmol/L),high sensitivity(about 20–45 mV/decade),temporal stability(>2weeks),and good selectivity(>80%)for the above ions.In vitro detection and in vivo subcutaneous and brain experiment results showed that the MMEC system exhibits good multi-ion monitoring performance in several complex environments.This work provides a platform for the continuous real-time monitoring of ion fluctuations in different situations and has implications for developing smart sensors to monitor human health.

Self-Healing,Self-Adhesive and Stable Organohydrogel-Based Stretchable Oxygen Sensor with High Performance at Room Temperature

With the advent of the 5G era and the rise of the Internet of Things,various sensors have received unprecedented attention,especially wearable and stretchable sensors in the healthcare field.Here,a stretchable,self-healable,self-adhesive,and room-temperature oxygen sensor with excellent repeatability,a full concentration detection range(0-100%),low theoretical limit of detection(5.7 ppm),high sensitivity(0.2%/ppm),good linearity,excellent temperature,and humidity tolerances is fabricated by using polyacrylamide-chitosan(PAM-CS)double network(DN)organohydrogel as a novel transducing material.The PAM-CS DN organohydrogel is transformed from the PAM-CS composite hydrogel using a facile soaking and solvent replacement strategy.Compared with the pristine hydrogel,the DN organohydrogel displays greatly enhanced mechanical strength,moisture retention,freezing resistance,and sensitivity to oxygen.Notably,applying the tensile strain improves both the sensitivity and response speed of the organohydrogel-based oxygen sensor.Furthermore,the response to the same concentration of oxygen before and after self-healing is basically the same.Importantly,we propose an electrochemical reaction mechanism to explain the positive current shift of the oxygen sensor and corroborate this sensing mechanism through rationally designed experiments.The organohydrogel oxygen sensor is used to monitor human respiration in real-time,verifying the feasibility of its practical application.This work provides ideas for fabricating more stretchable,self-healable,self-adhesive,and high-performance gas sensors using ion-conducting organohydrogels.

Three-dimensional constitutive model for magneto-mechanical deformation of NiMnGa ferromagnetic shape memory alloy single crystals

Existing experimental results have shown that four types of physical mechanisms, namely, martensite transformation, martensite reorientation, magnetic domain wall motion and magnetization vector rotation, can be activated during the magneto-mechanical deformation of NiMnGa ferromagnetic shape memory alloy (FSMA) single crystals. In this work, based on irreversible thermodynamics, a three-dimensional (3D) single crystal constitutive model is constructed by considering the aforementioned four mechanisms simultaneously. Three types of internal variables, i.e., the volume fraction of each martensite variant, the volume fraction of magnetic domain in each variant and the deviation angle between the magnetization vector, and easy axis are introduced to characterize the magneto-mechanical state of the single crystals. The thermodynamic driving force of each mechanism and the thermodynamic constraints on the constitutive model are obtained from Clausius's dissipative inequality and constructed Gibbs free energy. Then, thermodynamically consistent kinetic equations for the four mechanisms are proposed, respectively. Finally, the ability of the proposed model to describe the magneto-mechanical deformation of NiMnGa FSMA single crystals is verified by comparing the predictions with corresponding experimental results. It is shown that the proposed model can quantitatively capture the main experimental phenomena. Further, the proposed model is used to predict the deformations of the single crystals under the non-proportional mechanical loading conditions.

Semi-Implantable Bioelectronics

Developing techniques to effectively and real-time monitor and regulate the interior environment of biological objects is significantly important for many biomedical engineering and scientific applications, including drug delivery, electrophysiological recording and regulation of intracellular activities. Semi-implantable bioelectronics is currently a hot spot in biomedical engineering research area, because it not only meets the increasing technical demands for precise detection or regulation of biological activities, but also provides a desirable platform for externally incorporating complex functionalities and electronic integration. Although there is less definition and summary to distinguish it from the well-reviewed non-invasive bioelectronics and fully implantable bioelectronics, semi-implantable bioelectronics have emerged as highly unique technology to boost the development of biochips and smart wearable device. Here, we reviewed the recent progress in this field and raised the concept of “Semi-implantable bioelectronics”, summarizing the principle and strategies of semi-implantable device for cell applications and in vivo applications, discussing the typical methodologies to access to intracellular environment or in vivo environment, biosafety aspects and typical applications. This review is meaningful for understanding in-depth the design principles, materials fabrication techniques, device integration processes, cell/tissue penetration methodologies, biosafety aspects, and applications strategies that are essential to the development of future minimally invasive bioelectronics.

贵州省黔西县二叠系龙潭组主采煤层微量元素分布特征及制约因素探讨

黔西县是贵州主要的产煤县之一,煤炭资源丰富,煤层主要产于二叠系上统龙潭组(P31)地层中,属于织纳煤田。通过对主要矿区主采煤层系统取样分析,研究了不同煤层、不同矿区微量元素空间分布特征;与相邻的大方、赫章等区域煤层中微量元素含量对比发现,在陆源供给多的三角洲平原环境形成的煤层中微量元素含量相对高,在受海水影响较大的潮坪环境煤层中微量元素相对含量低,揭示了研究区陆源物质供给母岩——玄武岩具有较高的微量元素地球化学背景是其主要制约因素。个别煤层中有害元素Pb、Tl等含量高,是后期热液活动和断裂构造影响的结果。

Progress in the “brain-derived neurotrophic factor hypothesis of depression”

The traditional ＂brain-derived neurotrophic factor （BDNF） hypothesis of depression＂ proposes that impairment of the BDNF signaling pathway in the hippocampus and prefrontal cortex participates in the pathophysiology of depression, and antidepressants act by recovering/enhancing BDNF signal transduction. Recent studies have suggested that BDNF signaling pathways exert more diverse and complex effects on depression onset and antidepressant therapy than originally thought, which include： （1） inhibition of the BDNF-TrkB signaling pathway in the hippocampus and/or prefrontal cortex does not induce the depression-like behavioral phenotype, but significantly diminishes therapeutic effects, which suggests that the BDNF-TrkB signaling pathway lacks direct or key effects on occurrence of emotional disorders, whereas an intact and normal BDNF-TrkB signaling pathway is necessary for antidepressant therapy. （2） The BDNF-TrkB signaling pathway exhibits opposite regulatory effects on depressive behavior in the hippocampus-prefrontal cortex network and mesolimbic system, which suggests that BDNF regulates emotion by affecting the emotion-related neural network, but not a single brain region. （3） The BDNF-TrkB and proBDNF-p75Nm signaling pathways in the brain, respectively, enhance and suppress hippocampal neural plasticity, which demonstrated that different BDNF signaling pathways interact and restrict each other in the regulation of neural plasticity and emotional behaviors. （4） BDNF gene polymorphism might be associated with susceptibility to depression. These new findings extend our understanding of neuronal pathways and mechanisms of action of BDNF signaling and contribute to improved views to traditional ＂neurotrophic factor hypothesis of depression＂.

In-Cell Nanoelectronics:Opening the Door to Intracellular Electrophysiology

Establishing a reliable electrophysiological recording platform is crucial for cardiology and neuroscience research.Noninvasive and label-free planar multitransistors and multielectrode arrays are conducive to perform the large-scale cellular electrical activity recordings,but the signal attenua-tion limits these extracellular devices to record subthreshold activities.In recent decade,in-cell nanoelectronics have been rapidly developed to open the door to intracellular electrophysi-ology.With the unique three-dimensional nanotopography and advanced penetration strategies,high-throughput and high-fidelity action potential like signal recordings is expected to be realized.This review summarizes in-cell nanoelectronics from versatile nano-biointerfaces,penetration strategies,active/pas-sive nanodevices,systematically analyses the applications in electrogenic cells and especially evaluates the influence of nanodevices on the high-quality intracellular electrophysiological signals.Further,the opportunities,challenges and broad prospects of in-cell nanoelectronics are prospected,expecting to promote the development of in-cell electrophysiological platforms to meet the demand of theoretical investigation and clinical application.

Minimally invasive technology for continuous glucosemonitoring

Introduction Despite the numerous breakthroughs made in medical and biomedical technologies,biosensing underneath the skin without any associated pain still sounds like a dream yet to be realized.Minimally invasive biosensors refer to functional or electronic sensors that can contact the interior environment of living organisms and their biological tissues,while the connected bulk devices remain on the surface of the biological objects[1].Minimally invasive biosensors are currently a key research area because they can not only meet the increasing technical demands to precisely detect biological activities inside biological objects,but also provide an ideal platform to externally incorporate complicated functionalities and electronic integration[2].The current development level of minimally invasive sensing still necessitates solving the constraints and bottlenecks in the three aspects of functionalities,sensitivity and biocompatibility[3].In this perspective,we select minimally invasive sensors as a representative research object with the aim to solve the limitations of current diabetes diagnosis and treatment approaches.

Survey-Based Analysis of Water Consumption Law in High-Rise Public Buildings and Water-Saving Performance of Pressure-Reducing Measures

Facing the contradiction of water scarcity and water wastage in most cities of China, this study aims at probing into the factors influencing water-use efficiency and assessing water-saving potential by adopting pressure control measures based on field survey conducted in 23 high-rise buildings in Suqian, China and laboratory tests. Results showed that per capita water consumption (PCWC) exceeding water consumption norms is common in these buildings. The hourly water consumption variation law is quite different among different types of buildings. These differences should be considered in designing building water supply systems to lower water and energy consumption. On the basis of correlation analysis, the order of factors influencing the PCWC follows average tap water pressure, percapita building area, and building age, suggesting pressure management in high-rise buildings is a key water-saving measure. Field tests of outflow characteristics under different water pressures indicated that over-pressure outflow (OPO) is a common cause of water wastage in buildings, however, no branch pipe pressure control measures were found in all the surveyed buildings. Laboratory tests showed that branch pipe pressure-reducing measures can lower water consumption and improve the comfortability of use as well. Therefore, in addition to applying high efficiency water-saving devices, we strongly recommend that branch pipe pressure-reducing measures should be strictly implemented in designing new building water supply systems and reconstruction of existing old building water supply systems, thereby, promoting water, energy saving and development of green building.

Wear-resistant Ag-MAX phase 3D interpenetrating-phase composites:Processing,structure,and properties

Electrical contact materials are generally Ag-or Cu-based composites and play a critical role in ensuring the reliability and efficiency of electrical equipments and electronic instruments.The MAX(M is an early transition metal,A is an element from III or IV main groups,and X is carbon or/and nitrogen)phase ceramics display a unique combination of properties and may serve as an ideal reinforcement phase for electrical contact materials.The biological materials evolved in nature generally exhibit three-dimensional(3D)interpenetrating-phase architectures,which may offer useful inspiration for the architectural design of electrical contact materials.Here,a series of bi-continuous Ag-Ti_(3)SiC_(2) MAX phase composites with high ceramic contents exceeding 50 vol.%and having micron-and ultrafine-scaled 3D interpenetrating-phase architectures,wherein both constituents were continuous and mutually interspersed,were exploited by pressureless infiltration of Ag melt into partially sintered Ti_(3)SiC_(2) scaffolds.The mechanical and electrical properties as well as the friction and wear performance of the composites were investigated and revealed to be closely dependent on the ceramic contents and characteristic structural dimensions.The composites exhibited a good combination of properties with high hardness over 2.3 GPa,high flexural strength exceeding 530 MPa,decent fracture toughness over 10 MPa·m^(1/2),and good wear resistance with low wear rate at an order of 10^(-5)mm^(3)/(N·m),which were much superior compared to the counterparts made by powder metallurgy methods.In particular,the hardness,electrical conductivity,strength,and fracture toughness of the composites demonstrated a simultaneous improvement as the structure was refined from micron-to ultrafine-scales at equivalent ceramic contents.The good combination of properties along with the facile processing route makes the Ag-Ti_(3)SiC_(2)3D interpenetrating-phase composites appealing for electrical contact applications.

Multichannel microneedle dry electrode patches for minimally invasive transdermal recording of electrophysiological signals

The collection of multiple-channel electrophysiological signals enables a comprehensive understanding of the spatial distribution and temporal features of electrophysiological activities.This approach can help to distinguish the traits and patterns of different ailments to enhance diagnostic accuracy.Microneedle array electrodes,which can penetrate skin without pain,can lessen the impedance between the electrodes and skin;however,current microneedle methods are limited to single channels and cannot achieve multichannel collection in small areas.Here,a multichannel(32 channels)microneedle dry electrode patch device was developed via a dimensionality reduction fabrication and integration approach and supported by a self-developed circuit system to record weak electrophysiological signals,including electroencephalography(EEG),electrocardiogram(ECG),and electromyography(EMG)signals.The microneedles reduced the electrode–skin contact impedance by penetrating the nonconducting stratum corneum in a painless way.The multichannel microneedle array(MMA)enabled painless transdermal recording of multichannel electrophysiological signals from the subcutaneous space,with high temporal and spatial resolution,reaching the level of a single microneedle in terms of signal precision.The MMA demonstrated the detection of the spatial distribution of ECG,EMG and EEG signals in live rabbit models,and the microneedle electrode(MNE)achieved better signal quality in the transcutaneous detection of EEG signals than did the conventional flat dry electrode array.This work offers a promising opportunity to develop advanced tools for neural interface technology and electrophysiological recording.

Identification of TMEM217 as a novel prognostic biomarker and potential therapeutic target in acute myeloid leukemia

Despite remarkable advances in molecular and cell biology of acute myeloid leukemia(AML),AML patients still frequently relapse and have low 5-year overall survival(OS)rates.1 It is worth noting that a recent study from the registry or clinical trial compilation has reported an improvement in the OS of adult AML patients,especially those under 60 years of age.

Infliximab treatment in two Chinese patients with psoriatic arthritis

Psoriatic arthritis(PsA) is a rheumatoid factor(RF)-seronegative systemic inflammatory disorder associated with psoriasis.Current treatment for PsA in China is still focused on disease modifying anti-rheumatic drugs(DMARDs).In this paper,we report two Chinese patients with active longstanding PsA treated with infliximab,a human-mouse chimeric monoclonal antibody against tumor necrosis factor alpha(TNF-α).The results show that infliximab acted quickly and effectively in relieving peripheral and axial symptoms and refractory skin lesions,even in recombinant human TNF-α receptor(rhTNFR)-resistant case.The take-home message from our cases is that infliximab is a useful therapeutic option for refractory PsA,especially when a patient has a combination of psoriasis and psoriatic arthritis.Further local evidence and experience must be accumulated in order to make anti-TNF-α therapy more accessible to PsA patients in China.

Investigation on the Anisotropic Transformation Surfaces of Super-Elastic NiTi Shape Memory Alloys Under Multiaxial Cyclic Loading Conditions

The cyclic transformation behaviors of polycrystalline super-elastic NiTi shape memory alloys (SMAs)under multiaxial loading paths with different angles between axial and torsional loading orientations were experimentally investigated.The experimental results showed that the start stresses of forward and reverse transformations decreased with the increase'in the number of cycles and exhibit obvious anisotropic evolutions.The start stresses of forward and reverse transformations in the tensile and torsional directions did not satisfy the yon Mises criterion.The shape of transformation surface during the forward and reverse transformations evolved with the increase in the number of cycles.Then,new cyclic anisotropic transformation surfaces were established by introducing an anisotropic tensor into the von Mises equivalent stress based on a typical transformation criterion related to J2 and J3.Moreover,the evolution equations of material parameters used in the proposed transformation surfaces were established to describe the subsequent evolutions of transformation surfaces.Finally,the start stresses of forward and reverse transformations predicted using the proposed transformation surfaces were compared with the experimental results.It shows that the proposed transformation surfaces can reasonably describe the start stresses of forward and reverse transformations,which are helpful for establishing a three-dimensional cyclic constitutive model to describe the cyclic transformation behaviors of super-elastic NiTi SMAs.

3D-assembled microneedle ion sensor-based wearable system for the transdermal monitoring of physiological ion fluctuations

Monitoring human health is of considerable significance in biomedicine.In particular,the ion concentrations in blood are important reference indicators related to many diseases.Microneedle array-based sensors have enabled promising breakthroughs in continuous health monitoring due to their minimally invasive nature.In this study,we developed a microneedle sensing-array integrated system to continuously detect subcutaneous ions to monitor human health status in real time based on a fabrication strategy for assembling planar microneedle sheets to form 3D microneedle arrays.The limitations of preparing 3D microneedle structures with multiple electrode channels were addressed by assembling planar microneedle sheets fabricated via laser micromachining;the challenges of modifying closely spaced microneedle tips into different functionalized types of electrodes were avoided.The microneedle sensing system was sufficiently sensitive for detecting real-time changes in Ca^(2+),K^(+),and Na^(+) concentrations,and it exhibited good detection performance.The in vivo results showed that the ion-sensing microneedle array successfully monitored the fluctuations in Ca^(2+),k^(+),and Na^(+) in the interstitial fluids of rats in real time.By using an integrated circuit design,we constructed the proposed microneedle sensor into a wearable integrated monitoring system.The integrated system could potentially provide information feedback for diseases related to physiological ion changes.

Effects of frozen storage on texture,chemical quality indices and sensory properties of crisp Nile tilapia fillets

Crisp Nile tilapia(Oreochromis niloticus)is a kind of valuable fish product with high muscle firmness and crispiness texture.However,with the change of physicochemical in crisp Nile tilapia,the frozen storage parameters and quality would be different comparing to normal Nile tilapia.Thus,the aim of this study was to analyze the changes in texture,chemical quality indices and volatile compounds of Nile tilapia fillets during frozen storage.The remaining storage time of the crisp Nile tilapia fillets could be estimated within 120 days.During frozen storage,fillets resulted in softer started at 90-day,and 36.75%,45.74%,48.81%and 20.37%reduction of hardness,springiness,gumminess and chewiness were observed at 120-day.Thiobarbituric acid reactive substances(TBARS)for frozen samples showed similar with fresh fillets within 60 days,while the TBARS was 1.97 folds higher than fresh one at 120-day.Low-field nuclear magnetic resonance(LF-NMR)indicated that the water loss of Nile tilapia fillets was significant changed at 120-day,which reduced more than 12.5%water out of weight.The volatile compound analysis showed that more free fatty acid will be detected at 120-day comparing to the fresh fillets.The combined results demonstrated that the crisp Nile tilapia fillets had the best quality before 60 days frozen storage then loss of some quality properties in longer freezing.Thus,these results identified the ideal storage strategy for the preservation of crisp Nile tilapia without affecting sensory appeal and commercial value.

Self-healable, recyclable, ultrastretchable, and high-performanceNO_(2) sensors based on an organohydrogel for room and sub-zero temperature and wireless operation

To date,development of high-performance,stretchable gas sensors operating at and below room temperature(RT)remains a challenge in terms of traditional sensing materials.Herein,we report on a high-performance NO_(2) gas sensor based on a self-healable,recyclable,ultrastretchable,and stable polyvinyl alcohol–cellulose nanofibril double-network organohydrogel,which features ultrahigh sensitivity(372%/ppm),low limit of detection(2.23 ppb),relatively fast response and recovery time(41/144 s for 250 ppb NO_(2)),good selectivity against interfering gases(NH3,CO_(2),ethanol,and acetone),excellent reversibility,repeatability,and long-term stability at RT or even at−20°C.In particular,this sensor shows outstanding stability against large deformations and mechanical damages so that it works normally after rapid self-healing or remolding after undergoing mechanical damage without significant performance degradation,which has major advantages compared to state-of-the-art gas sensors.The high NO_(2) sensitivity and selectivity are attributed to the selective redox reactions at the threephase interface of gas,gel,and electrode,which is even boosted by applying tensile strain.With a specific electrical circuit design,a wireless NO_(2) alarm system based on this sensor is created to enable continuous,real-time,and wireless NO_(2) detection to avoid the risk of exposure to NO_(2) higher than threshold concentrations.

lontophoresis-driven microneedle patch for the active transdermal delivery of vaccine macromolecules

COVID-19 has seriously threatened public health,and transdermal vaccination is an effective way to prevent pathogen infection.Microneedles(MNs)can damage the stratum corneum to allow passive diffusion of vaccine macromolecules,but the delivery effciency is low,while iontophoresis can actively promote transdermal delivery but fails to transport vaccine macromolecules due to the barrier of the stratum corneum.Herein,we developed a wearable iontophoresis-driven MN patch and its iontophoresis-driven device for active and effcient transdermal vaccine macromolecule delivery.Polyacrylamide/chitosan hydrogels with good biocompatibility,excellent conductivity,high elasticity,and a large loading capacity were prepared as the key component for vaccine storage and active iontophoresis.The transdermal vaccine delivery strategy of the iontophoresis-driven MN patch is“press and poke,iontophoresis-driven delivery,and immune response”.We demonstrated that the synergistic effect of MN puncture and iontophoresis significantly promoted transdermal vaccine delivery effciency.In vitro experiments showed that the amount of ovalbumin delivered transdermally using the iontophoresis-driven MN patch could be controlled by the iontophoresis current.In vivo immunization studies in BALB/c mice demonstrated that transdermal inoculation of ovalbumin using an iontophoresis-driven MN patch induced an effective immune response that was even stronger than that of traditional intramuscular injection.Moreover,there was little concern about the biosafety of the iontophoresis-driven MN patch.This delivery system has a low cost,is user-friendly,and displays active delivery,showing great potential for vaccine self-administration at home.

Fabrication of textured Ti2AlC lamellar composites with improved mechanical properties

Textured Ti2AlC lamellar composites have been successfully fabricated by a new method in the present work.The composites exhibit high compressive strength of ca 2 GPa,fracture toughness of 8.5 MPa m1/2(//c-axis),flexural strength of 735 MPa(//c-axis)and high hardness of 7.9 GPa(//c-axis).The strengthening mechanisms were discussed.The sintering and densification process was investigated and crystal orientation and microstructure were studied by electron backscattered diffraction techniques.The synthesis temperature is reduced to 1200?C by using high surface-to-volume ratio Ti2AlC nano flakes.The Lotgering orientation factor of Ti2 AlC and Ti3 AlC2{00 l}planes in the textured top surface reaches 0.74 and 0.49,respectively.This new route may shed light on resolving the difficulties encountered in large scale fabrication of textured MAX phases.