Pressure-Dependent Superconductivity in Topological Dirac Semimetal SrCuBi.

The discovery of superconducting states in diverse topological materials generates a burgeoning interest to explore a topological superconductor and to realize a fault-tolerant topological quantum computation. A variety of routes to realize topological superconductors are proposed, and many types of topological materials are developed. However, a pristine topological material with a natural superconducting state is relatively rare as compared to topological materials with artificially induced superconductivity. Here, it is reported that the planar honeycomb structured 3D topological Dirac semimetal (TDS) SrCuBi, which is the Zintl phase, shows a natural surface superconductivity at 2.1 K under ambient pressure. It is clearly identified from theoretical calculations that a topologically nontrivial state exists on the (100) surface. Further, its superconducting transition temperature (Tc) increases by applying pressure, exhibiting a maximal Tc of 4.8 K under 6.2 GPa. It is believed that this discovery opens up a new possibility of exploring exotic Majorana fermions at the surface of 3D TDS superconductors.

Ultrathin, Transferred Layers of Silicon Oxynitrides as Tunable Biofluid Barriers for Bioresorbable Electronic Systems.

Bio/ecoresorbable electronic systems create unique opportunities in implantable medical devices that serve a need over a finite time period and then disappear naturally to eliminate the need for extraction surgeries. A critical challenge in the development of this type of technology is in materials that can serve as thin, stable barriers to surrounding ground water or biofluids, yet ultimately dissolve completely to benign end products. This paper describes a class of inorganic material (silicon oxynitride, SiON) that can be formed in thin films by plasma-enhanced chemical vapor deposition for this purpose. In vitro studies suggest that SiON and its dissolution products are biocompatible, indicating the potential for its use in implantable devices. A facile process to fabricate flexible, wafer-scale multilayer films bypasses limitations associated with the mechanical fragility of inorganic thin films. Systematic computational, analytical, and experimental studies highlight the essential materials aspects. Demonstrations in wireless light-emitting diodes both in vitro and in vivo illustrate the practical use of these materials strategies. The ability to select degradation rates and water permeability through fine tuning of chemical compositions and thicknesses provides the opportunity to obtain a range of functional lifetimes to meet different application requirements.

First-order quantum phase transition in the hybrid metal-Mott insulator transition metal dichalcogenide 4Hb-TaS2.

Coupling together distinct correlated and topologically nontrivial electronic phases of matter can potentially induce novel electronic orders and phase transitions among them. Transition metal dichalcogenide compounds serve as a bedrock for exploration of such hybrid systems. They host a variety of exotic electronic phases, and their Van der Waals nature enables to admix them, either by exfoliation and stacking or by stoichiometric growth, and thereby induce novel correlated complexes. Here, we investigate the compound 4Hb-TaS2 that interleaves the Mott-insulating state of 1T-TaS2 and the putative spin liquid it hosts together with the metallic state of 2H-TaS2 and the low-temperature superconducting phase it harbors using scanning tunneling spectroscopy. We reveal a thermodynamic phase diagram that hosts a first-order quantum phase transition between a correlated Kondo-like cluster state and a depleted flat band state. We demonstrate that this intrinsic transition can be induced by an electric field and temperature as well as by manipulation of the interlayer coupling with the probe tip, hence allowing to reversibly toggle between the Kondo-like cluster and the depleted flat band states. The phase transition is manifested by a discontinuous change of the complete electronic spectrum accompanied by hysteresis and low-frequency noise. We find that the shape of the transition line in the phase diagram is determined by the local compressibility and the entropy of the two electronic states. Our findings set such heterogeneous structures as an exciting platform for systematic investigation and manipulation of Mott-metal transitions and strongly correlated phases and quantum phase transitions therein.

Physical processing for decellularized nerve xenograft in peripheral nerve regeneration.

In severe or complex cases of peripheral nerve injuries, autologous nerve grafts are the gold standard yielding promising results, but limited availability and donor site morbidity are some of its disadvantages. Although biological or synthetic substitutes are commonly used, clinical outcomes are inconsistent. Biomimetic alternatives derived from allogenic or xenogenic sources offer an attractive off-the-shelf supply, and the key to successful peripheral nerve regeneration focuses on an effective decellularization process. In addition to chemical and enzymatic decellularization protocols, physical processes might offer identical efficiency. In this comprehensive minireview, we summarize recent advances in the physical methods for decellularized nerve xenograft, focusing on the effects of cellular debris clearance and stability of the native architecture of a xenograft. Furthermore, we compare and summarize the advantages and disadvantages, indicating the future challenges and opportunities in developing multidisciplinary processes for decellularized nerve xenograft.

Battery-Free, Wireless, Cuff-Type, Multimodal Physical Sensor for Continuous Temperature and Strain Monitoring of Nerve.

Peripheral nerve injuries cause various disabilities related to loss of motor and sensory functions. The treatment of these injuries typically requires surgical operations for improving functional recovery of the nerve. However, capabilities for continuous nerve monitoring remain a challenge. Herein, a battery-free, wireless, cuff-type, implantable, multimodal physical sensing platform for continuous in vivo monitoring of temperature and strain from the injured nerve is introduced. The thin, soft temperature, and strain sensors wrapped around the nerve exhibit good sensitivity, excellent stability, high linearity, and minimum hysteresis in relevant ranges. In particular, the strain sensor integrated with circuits for temperature compensation provides reliable, accurate strain monitoring with negligible temperature dependence. The system enables power harvesting and data communication to wireless, multiple implanted devices wrapped around the nerve. Experimental evaluations, verified by numerical simulations, with animal tests, demonstrate the feasibility and stability of the sensor system, which has great potential for continuous in vivo nerve monitoring from an early stage to complete regeneration.

Steady-state memory-phenotype conventional CD4+ T cells exacerbate autoimmune neuroinflammation in a bystander manner via the Bhlhe40/GM-CSF axis.

Memory-phenotype (MP) CD4+ T cells are a substantial population of conventional T cells that exist in steady-state mice, yet their immunological roles in autoimmune disease remain unclear. In this work, we unveil a unique phenotype of MP CD4+ T cells determined by analyzing single-cell transcriptomic data and T cell receptor (TCR) repertoires. We found that steady-state MP CD4+ T cells in the spleen were composed of heterogeneous effector subpopulations and existed regardless of germ and food antigen exposure. Distinct subpopulations of MP CD4+ T cells were specifically activated by IL-1 family cytokines and STAT activators, revealing that the cells exerted TCR-independent bystander effector functions similar to innate lymphoid cells. In particular, CCR6high subpopulation of MP CD4+ T cells were major responders to IL-23 and IL-1ß without MOG35-55 antigen reactivity, which gave them pathogenic Th17 characteristics and allowed them to contribute to autoimmune encephalomyelitis. We identified that Bhlhe40 in CCR6high MP CD4+ T cells as a key regulator of GM-CSF expression through IL-23 and IL-1ß signaling, contributing to central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis. Collectively, our findings reveal the clearly distinct effector-like heterogeneity of MP CD4+ T cells in the steady state and indicate that CCR6high MP CD4+ T cells exacerbate autoimmune neuroinflammation via the Bhlhe40/GM-CSF axis in a bystander manner.

Field-linear anomalous Hall effect and Berry curvature induced by spin chirality in the kagome antiferromagnet Mn3Sn.

During the past two decades, it has been established that a non-trivial electron wave-function topology generates an anomalous Hall effect (AHE), which shows itself as a Hall conductivity non-linear in magnetic field. Here, we report on an unprecedented case of field-linear AHE. In Mn3Sn, a kagome magnet, the out-of-plane Hall response, which shows an abrupt jump, was discovered to be a case of AHE. We find now that the in-plane Hall response, which is perfectly linear in magnetic field, is set by the Berry curvature of the wavefunction. The amplitude of the Hall response and its concomitant Nernst signal exceed by far what is expected in the semiclassical picture. We argue that magnetic field induces out-of-plane spin canting and thereafter gives rise to nontrivial spin chirality on the kagome lattice. In band structure, we find that the spin chirality modifies the topology by gapping out Weyl nodal lines unknown before, accounting for the AHE observed. Our work reveals intriguing unification of real-space Berry phase from spin chirality and momentum-space Berry curvature in a kagome material.

Isotropic conductive paste for bioresorbable electronics.

Bioresorbable implantable medical devices can be employed in versatile clinical scenarios that burden patients with complications and surgical removal of conventional devices. However, a shortage of suitable electricalinterconnection materials limits the development of bioresorbable electronic systems. Therefore, this study highlights a highly conductive, naturally resorbable paste exhibiting enhanced electrical conductivity and mechanical stability that can solve the existing problems of bioresorbable interconnections. Multifaceted experiments on electrical and physical properties were used to optimize the composition of pastes containing beeswax, submicron tungstenparticles, and glycofurol. These pastes embody isotropic conductive paths for three-dimensional interconnects and function as antennas, sensors, and contact pads for bioresorbable electronic devices. The degradation behavior in aqueous solutions was used to assess its stability and ability to retain electrical conductance (∼7 â€‹kS/m) and structural form over the requisite dissolution period. In vitro and in vivo biocompatibility tests clarified the safety of the paste as an implantable material.

Battery-Free, Wireless, Ionic Liquid Sensor Arrays to Monitor Pressure and Temperature of Patients in Bed and Wheelchair.

Repositioning is a common guideline for the prevention of pressure injuries of bedridden or wheelchair patients. However, frequent repositioning could deteriorate the quality of patient's life and induce secondary injuries. This paper introduces a method for continuous multi-site monitoring of pressure and temperature distribution from strategically deployed sensor arrays at skin interfaces via battery-free, wireless ionic liquid pressure sensors. The wirelessly delivered power enables stable operation of the ionic liquid pressure sensor, which shows enhanced sensitivity, negligible hysteresis, high linearity and cyclic stability over relevant pressure range. The experimental investigations of the wireless devices, verified by numerical simulation of the key responses, support capabilities for real-time, continuous, long-term monitoring of the pressure and temperature distribution from multiple sensor arrays. Clinical trials on two hemiplegic patients confined on bed or wheelchair integrated with the system demonstrate the feasibility of sensor arrays for a decrease in pressure and temperature distribution under minimal repositioning.

Humanized V(D)J-rearranging and TdT-expressing mouse vaccine models with physiological HIV-1 broadly neutralizing antibody precursors.

Antibody heavy chain (HC) and light chain (LC) variable region exons are assembled by V(D)J recombination. V(D)J junctional regions encode complementarity-determining-region 3 (CDR3), an antigen-contact region immensely diversified through nontemplated nucleotide additions ("N-regions") by terminal deoxynucleotidyl transferase (TdT). HIV-1 vaccine strategies seek to elicit human HIV-1 broadly neutralizing antibodies (bnAbs), such as the potent CD4-binding site VRC01-class bnAbs. Mice with primary B cells that express receptors (BCRs) representing bnAb precursors are used as vaccination models. VRC01-class bnAbs uniformly use human HC VH1-2 and commonly use human LCs Vκ3-20 or Vκ1-33 associated with an exceptionally short 5-amino-acid (5-aa) CDR3. Prior VRC01-class models had nonphysiological precursor levels and/or limited precursor diversity. Here, we describe VRC01-class rearranging mice that generate more physiological primary VRC01-class BCR repertoires via rearrangement of VH1-2, as well as Vκ1-33 and/or Vκ3-20 in association with diverse CDR3s. Human-like TdT expression in mouse precursor B cells increased LC CDR3 length and diversity and also promoted the generation of shorter LC CDR3s via N-region suppression of dominant microhomology-mediated Vκ-to-Jκ joins. Priming immunization with eOD-GT8 60mer, which strongly engages VRC01 precursors, induced robust VRC01-class germinal center B cell responses. Vκ3-20-based responses were enhanced by N-region addition, which generates Vκ3-20-to-Jκ junctional sequence combinations that encode VRC01-class 5-aa CDR3s with a critical E residue. VRC01-class-rearranging models should facilitate further evaluation of VRC01-class prime and boost immunogens. These new VRC01-class mouse models establish a prototype for the generation of vaccine-testing mouse models for other HIV-1 bnAb lineages that employ different HC or LC Vs.

Open thoracic surgical implantation of cardiac pacemakers in rats.

Genetic engineering and implantable bioelectronics have transformed investigations of cardiovascular physiology and disease. However, the two approaches have been difficult to combine in the same species: genetic engineering is applied primarily in rodents, and implantable devices generally require larger animal models. We recently developed several miniature cardiac bioelectronic devices suitable for mice and rats to enable the advantages of molecular tools and implantable devices to be combined. Successful implementation of these device-enabled studies requires microsurgery approaches that reliably interface bioelectronics to the beating heart with minimal disruption to native physiology. Here we describe how to perform an open thoracic surgical technique for epicardial implantation of wireless cardiac pacemakers in adult rats that has lower mortality than transvenous implantation approaches. In addition, we provide the methodology for a full biocompatibility assessment of the physiological response to the implanted device. The surgical implantation procedure takes ~40 min for operators experienced in microsurgery to complete, and six to eight surgeries can be completed in 1 d. Implanted pacemakers provide programmed electrical stimulation for over 1 month. This protocol has broad applications to harness implantable bioelectronics to enable fully conscious in vivo studies of cardiovascular physiology in transgenic rodent disease models.

Proximity-magnetized quantum spin Hall insulator: monolayer 1 T' WTe2/Cr2Ge2Te6.

Van der Waals heterostructures offer great versatility to tailor unique interactions at the atomically flat interfaces between dissimilar layered materials and induce novel physical phenomena. By bringing monolayer 1 T' WTe2, a two-dimensional quantum spin Hall insulator, and few-layer Cr2Ge2Te6, an insulating ferromagnet, into close proximity in an heterostructure, we introduce a ferromagnetic order in the former via the interfacial exchange interaction. The ferromagnetism in WTe2 manifests in the anomalous Nernst effect, anomalous Hall effect as well as anisotropic magnetoresistance effect. Using local electrodes, we identify separate transport contributions from the metallic edge and insulating bulk. When driven by an AC current, the second harmonic voltage responses closely resemble the anomalous Nernst responses to AC temperature gradient generated by nonlocal heater, which appear as nonreciprocal signals with respect to the induced magnetization orientation. Our results from different electrodes reveal spin-polarized edge states in the magnetized quantum spin Hall insulator.

Non-Palladium-Catalyzed Approach to the Synthesis of (E)-3-(1,3-Diarylallylidene)Oxindoles.

Two novel synthetic approaches for synthesizing (E)-3-(1,3-diarylallylidene)oxindoles from oxindole were developed. All previously reported methods for synthesizing 3-(1,3-diarylallylidene)oxindoles utilized palladium-catalyzed reactions as a key step to form this unique skeleton. Despite high efficiency, palladium-catalyzed reactions have limitations in terms of substrate scope. Especially, an iodoaryl moiety cannot be introduced by the previous methods due to its high reactivity toward the palladium catalyst. Our Knoevenagel/allylic oxidation/Wittig and Knoevenagel/aldol/dehydration strategies complement each other and show broad substrate scope, including substrates with iodoaryl groups. The current methods utilized acetophenones, benzylidene phosphonium ylides, and benzaldehydes that are commercially available or easily accessible. Thus, the current synthetic approaches to (E)-3-(1,3-diarylallyldiene)oxindoles are readily amendable for variety of oxindole derivatives.

Electroceuticals for peripheral nerve regeneration.

Electroceuticals provide promising opportunities for peripheral nerve regeneration, in terms of modulating the extensive endogenous tissue repair mechanisms between neural cell body, axons and target muscles. However, great challenges remain to deliver effective and controllable electroceuticals via bioelectronic implantable device. In this review, the modern fabrication methods of bioelectronic conduit for bridging critical nerve gaps after nerve injury are summarized, with regard to conductive materials and core manufacturing process. In addition, to deliver versatile electrical stimulation, the integration of implantable bioelectronic device is discussed, including wireless energy harvesters, actuators and sensors. Moreover, a comprehensive insight of beneficial mechanisms is presented, including up-to-datein vitro, in vivoand clinical evidence. By integrating conductive biomaterials, 3D engineering manufacturing process and bioelectronic platform to deliver versatile electroceuticals, the modern biofabrication enables comprehensive biomimetic therapies for neural tissue engineering and regeneration in the new era.

Antibodies from primary humoral responses modulate the recruitment of naive B cells during secondary responses.

Vaccines generate high-affinity antibodies by recruiting antigen-specific B cells to germinal centers (GCs), but the mechanisms governing the recruitment to GCs on secondary challenges remain unclear. Here, using preclinical SARS-CoV and HIV mouse models, we demonstrated that the antibodies elicited during primary humoral responses shaped the naive B cell recruitment to GCs during secondary exposures. The antibodies from primary responses could either enhance or, conversely, restrict the GC participation of naive B cells: broad-binding, low-affinity, and low-titer antibodies enhanced recruitment, whereas, by contrast, the high titers of high-affinity, mono-epitope-specific antibodies attenuated cognate naive B cell recruitment. Thus, the directionality and intensity of that effect was determined by antibody concentration, affinity, and epitope specificity. Circulating antibodies can, therefore, be important determinants of antigen immunogenicity. Future vaccines may need to overcome-or could, alternatively, leverage-the effects of circulating primary antibodies on subsequent naive B cell recruitment.

Unleashing cell-penetrating peptide applications for immunotherapy.

With the advent of cancer immunotherapy, immunomodulation has emerged as an important strategy for the treatment of various diseases. We review recent advances in clinical trials of cell-penetrating peptide (CPP) applications for immunotherapy and also discuss their challenges and opportunities for preclinical studies in various immune diseases. CPP conjugation to antigenic peptides or proteins can enable efficient antigen uptake and cross-presentation by antigen-presenting cells (APCs), which induce both humoral and cytotoxic responses. In addition, CPP-coupled immune modulators can enhance antitumor immunity or anti-inflammatory effects to regulate allergies and autoimmunity. Given their huge advantages in overcoming delivery barriers, CPP-based strategies for immunomodulation could extend drug optimization and advance immunotherapy in various human diseases.

Exchange-biased topological transverse thermoelectric effects in a Kagome ferrimagnet.

Kagome metal TbMn6Sn6 was recently discovered to be a ferrimagnetic topological Dirac material by scanning tunneling microscopy/spectroscopy measurements. Here, we report the observation of large anomalous Nernst effect and anomalous thermal Hall effect in this compound. The anomalous transverse transport is consistent with the Berry curvature contribution from the massive Dirac gaps in the 3D momentum space as demonstrated by our first-principles calculations. Furthermore, the transverse thermoelectric transport exhibits asymmetry with respect to the applied magnetic field, i.e., an exchange-bias behavior. Together, these features place TbMn6Sn6 as a promising system for the outstanding thermoelectric performance based on anomalous Nernst effect.

CPP Applications in Immune Modulation and Disease Therapy.

About 30 years ago, the discovery of CPP improved the therapeutic approach to treat diseases and extended the range of potential targets to intracellular molecules. There are potential drug candidates for FDA approval based on active studies in basic research, preclinical, and clinical trials. Various attempts by CPP application to control the diseases such as allergy, autoimmunity, cancer, and infection demonstrated a strategy to make a new drug pipeline for successful discovery of a biologic drug for immune modulation. However, there are still no CPP-based drug candidates for immune-related diseases in the clinical stage. To control immune responses successfully, not only increasing delivery efficiency of CPPs but also selecting potential target cells and cargoes could be important issues. In particular, as it becomes possible to control intracellular targets, efforts to find various novel potential target are being attempted. In this chapter, we focused on CPP-based approaches to treat diseases through modulation of immune responses and discussed for perspectives on future direction of the research for successful application of CPP technology to immune modulation and disease therapy in clinical trial.

Skin-Integrated Devices with Soft, Holey Architectures for Wireless Physiological Monitoring, With Applications in the Neonatal Intensive Care Unit.

Continuous monitoring of vital signs is an essential aspect of operations in neonatal and pediatric intensive care units (NICUs and PICUs), of particular importance to extremely premature and/or critically ill patients. Current approaches require multiple sensors taped to the skin and connected via hard-wired interfaces to external data acquisition electronics. The adhesives can cause iatrogenic injuries to fragile, underdeveloped skin, and the wires can complicate even the most routine tasks in patient care. Here, materials strategies and design concepts are introduced that significantly improve these platforms through the use of optimized materials, open (i.e., "holey") layouts and precurved designs. These schemes 1) reduce the stresses at the skin interface, 2) facilitate release of interfacial moisture from transepidermal water loss, 3) allow visual inspection of the skin for rashes or other forms of irritation, 4) enable triggered reduction of adhesion to reduce the probability for injuries that can result from device removal. A combination of systematic benchtop testing and computational modeling identifies the essential mechanisms and key considerations. Demonstrations on adult volunteers and on a neonate in an operating NICUs illustrate a broad range of capabilities in continuous, clinical-grade monitoring of conventional vital signs, and unconventional indicators of health status.