A Rare Earth Chalcogenide Nonlinear Optical Crystal KLaGeS4: Achieving Good Balance among Band Gap, Second Harmonic Generation Effect, and Birefringence.

Midinfrared nonlinear optical (NLO) rare earth chalcogenides have attracted extensive research interest in recent several decades. Employing charge-transfer engineering strategy in the early stage, rigid tetrahedral [GeS4] was introduced into rare-earth sulfides to synthesize KYGeS4, which had an enlarged band gap while maintaining a strong second harmonic generation (SHG) effect. Based on KYGeS4, La was equivalently substituted to successfully synthesize KLaGeS4 with a stronger SHG effect (dij = 1.2 × AgGaS2) and lower cost. Meanwhile, a larger band gap (Eg = 3.34 eV) was retained and realized phase matching (Δn = 0.098 @ 1064 nm). KLaGeS4 enabled an effective balance among band gap, SHG effect, and birefringence, making it a promising candidate for infrared NLO optical materials among various rare-earth sulfides.

Treefrog-Inspired Flexible Electrode with High Permeability, Stable Adhesion, and Robust Durability.

Long-term continuous monitoring (LTCM) of physiological electrical signals is an effective means for detecting several cardiovascular diseases. However, the integrated challenges of stable adhesion, low impedance, and robust durability under different skin conditions significantly hinder the application of flexible electrodes in LTCM. This paper proposes a structured electrode inspired by the treefrog web, comprising dispersed pillars at the bottom and asymmetric cone holes at the top. Attachment structures with a dispersed pillar improve the contact stability (adhesion increases 2.79/13.16 times in dry/wet conditions compared to an electrode without structure). Improved permeable duct structure provides high permeability (12 times compared to cotton). Due to high adhesion and permeability, the electrode's durability is 40 times larger than commercial Ag/AgCl electrodes. The treefrog web-like electrode has great advantages in permeability, adhesion, and durability, resulting in prospects for application in physiological electrical signal detection and a new design idea for LTCM wearable dry electrodes.

Bioinspired Suspended Sensing Membrane Array with Modulable Wedged-Conductive Channels for Crosstalk-Free and High-Resolution Detection.

High spatial-resolution detection is essential for biomedical applications and human-machine interaction. However, as the sensor array density increases, the miniaturization will lead to interference between adjacent units and deterioration in sensing performance. Here, inspired by the cochlea's sensing structure, a high-density flexible pressure sensor array featuring with suspended sensing membrane with sensitivity-enhanced customized channels is presented for crosstalk-free and high-resolution detection. By imitating the basilar membrane attached to spiral ligaments, a sensing membrane is fixed onto a high-stiffness substrate with cavities, forming a stable braced isolation to provide an excellent crosstalk-free capability (crosstalk coefficient: 47.24 dB) with high-density integration (100 units within 1 cm2). Similar to the opening of ion channels in hair cells, the wedge-type expansion of the embedded cracks introduced by stress concentration structures enables a high sensitivity (0.19 kPa-1) and a large measuring range (400 kPa). Finally, it demonstrates promising applications in distributed displays and the condition monitoring of medical-surgical intubation.

Shear Flow-Assembled Janus Membrane with Bifunctional Osteogenic and Antibacterial Effects for Guided Bone Regeneration.

Guided bone regeneration (GBR) membranes that reside at the interface between the bone and soft tissues for bone repair attract increasing attention, but currently developed GBR membranes suffer from relatively poor osteogenic and antibacterial effects as well as limited mechanical property and biodegradability. We present here the design and fabrication of a bifunctional Janus GBR membrane based on a shear flow-driven layer by a layer self-assembly approach. The Janus GBR membrane comprises a calcium phosphate-collagen/polyethylene glycol (CaP@COL/PEG) layer and a chitosan/poly(acrylic acid) (CHI/PAA) layer on different sides of a collagen membrane to form a sandwich structure. The membrane exhibits good mechanical stability and tailored biodegradability. It is found that the CaP@COL/PEG layer and CHI/PAA layer contribute to the osteogenic differentiation and antibacterial function, respectively. In comparison with the control group, the Janus GBR membrane displays a 2.52-time and 1.84-time enhancement in respective volume and density of newly generated bone. The greatly improved bone repair ability of the Janus GBR membrane is further confirmed through histological analysis, and it has great potential for practical applications in bone tissue engineering.

Fluorescent-protein co-expression to select CHO cells expressing high quantities of vaccine antigens.

Cell line development for production of vaccine antigens or therapeutic proteins typically involves transfection, selection, and enrichment for high-expressing cells. Enrichment methods include minipool enrichment, antibody-based enrichment, and enrichment based on co-expressed fluorescent biosensor proteins. However, these methods have limitations regarding labor and cost intensity, the generation of antibodies and assurance of their viral safety, and potential expression-interference or signal-saturation of the co-expressed fluorescent protein. To improve the method of fluorescent-protein co-expression, expression constructs were created that constitutively express a model vaccine antigen together with one of three fluorescent proteins having translation initiation controlled by a wildtype or mutant internal ribosome entry site (IRES), for a total of six constructs. The constructs were transfected into Chinese hamster ovary cells (CHO) cells, enriched for high fluorescence, cultured, and tested in a mini bioreactor to identify the most promising construct. The fluorescent protein, Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) with a mutant IRES performed best and was further tested with three additional vaccine antigens. Across the four vaccine antigens, the FUCCI fluorescent protein yielded productivity enhancements, without the need for generating an antibody and assuring its viral safety. Furthermore, FUCCI protein was present in negligible quantities in the cell supernatant, indicating a low risk for contaminating drug substances or vaccine antigen.

Flexible Grid Graphene Electrothermal Films for Real-Time Monitoring Applications.

Flexible electrothermal films are crucial for protecting equipment and systems in cold weather, such as ice blockages in natural gas pipelines and icing on aircraft wings. Therefore, a flexible electric heater is one of the essential devices in industrial operations. One of the main challenges is to develop flexible electrothermal films with low operating voltage, high steady-state temperature, and good mechanical stability. In this study, a flexible electrothermal film based on graphene-patterned structures was manufactured by combining the laser induction method and the transfer printing process. The grid structure design provides accurate real-time monitoring for the application of electrothermal films and shows potential in solving problems related to deicing and clearing ice blockages in pipelines. The flexible electrothermal film can reach a high heating temperature of 165 °C at 15 V and exhibits sufficient heating stability. By employing a simple and efficient method to create a flexible, high-performance electrothermal film, we provide a reliable solution for deicing and monitoring applications.

The effect of marathon running on the lower extremity kinematics and muscle activities during walking and running tasks.

Patellofemoral pain syndrome (PFPS) is a common injury among runners, and it is thought that abnormal lower extremity biomechanics contribute to its development. However, the relationship between biomechanical changes after a marathon and PFPS injury remains limited. This study aims to investigate whether differences in knee and hip kinematics and lower extremity muscle activities exist in recreational runners before and after a marathon. Additionally, it aims to explore the relationship between these biomechanical changes and the development of PFPS injury. 12 recreational runners participated in the study. Kinematics and muscle activities of the lower extremity were recorded during walking (5 km/h) and running (10 km/h) tasks within 24 hours before and within 5 hours after a marathon. After the marathon, there was a significant decrease in peak knee flexion (walking: p = 0.006; running: p = 0.006) and an increase in peak hip internal rotation (walking: p = 0.026; running: p = 0.015) during the stance phase of both walking and running compared to before the marathon. The study demonstrates a decrease in knee flexion and an increase in hip internal rotation during the stance phase of gait tasks after completing a marathon, which may increase the risk of developing PFPS injury.

PROTAC-mediated NR4A1 degradation as a novel strategy for cancer immunotherapy.

An effective cancer therapy requires killing cancer cells and targeting the tumor microenvironment (TME). Searching for molecules critical for multiple cell types in the TME, we identified NR4A1 as one such molecule that can maintain the immune suppressive TME. Here, we establish NR4A1 as a valid target for cancer immunotherapy and describe a first-of-its-kind proteolysis-targeting chimera (PROTAC, named NR-V04) against NR4A1. NR-V04 degrades NR4A1 within hours in vitro and exhibits long-lasting NR4A1 degradation in tumors with an excellent safety profile. NR-V04 inhibits and frequently eradicates established tumors. At the mechanistic level, NR-V04 induces the tumor-infiltrating (TI) B cells and effector memory CD8+ T (Tem) cells and reduces monocytic myeloid-derived suppressor cells (m-MDSC), all of which are known to be clinically relevant immune cell populations in human melanomas. Overall, NR-V04-mediated NR4A1 degradation holds promise for enhancing anticancer immune responses and offers a new avenue for treating various types of cancers such as melanoma.

Integrating photothermal and plasmonic catalysis induced by near-infrared light for efficient reduction of 4-nitrophenol.

The reduction of 4-nitrophenol (4-NP) into 4-aminophenol (4-AP) is an important reaction in both chemical manufacturing and environmental protection. The design of a highly active, multifunctional and reusable catalyst for efficient 4-NP decontamination/valorization is therefore crucial to bring in economic and societal benefits. Herein, we achieve an efficient plasmonic-photothermal catalyst of Pd nanoparticles by growing them on graphene-polyelectrolytes self-assembly nanolayers via an in situ green reduction approach using polyelectrolyte as the reductant. The as-fabricated catalyst shows high catalytic behaviors and good stability (maintained over 92.5 % conversion efficiency after ten successive cycles) for 4-NP reduction under ultra-low catalyst dose. The rate constant and turnover frequency were calculated at 0.197 min-1 and 7.79 mmol g-1 min-1, respectively, which were much higher than those of most reported catalysts. Moreover, the as-prepared catalyst exhibited excellent photothermal conversion efficiency of ∼77 % and boosted 4-NP reduction by ∼2-fold under near-infrared irradiation (NIR). This study provides valuable insights into the design of greener catalytic materials and facilitates the development of multifunctional plasmonic-photothermal catalysts for diverse environmental, chemical, and energy applications using NIR.

Promoting Piezocatalytic H2 O2 Production in Pure Water by Loading Metal-Organic Cage-Modified Gold Nanoparticles on Graphitic Carbon Nitride.

Piezocatalytic hydrogen peroxide (H2 O2 ) production is a green synthesis method, but the rapid complexation of charge carriers in piezocatalysts and the difficulty of adsorbing substrates limit its performance. Here, metal-organic cage-coated gold nanoparticles are anchored on graphitic carbon nitride (MOC-AuNP/g-C3 N4 ) via hydrogen bond to serve as the multifunctional sites for efficient H2 O2 production. Experiments and theoretical calculations prove that MOC-AuNP/g-C3 N4 simultaneously optimize three key parts of piezocatalytic H2 O2 production: i) the MOC component enhances substrate (O2 ) and product (H2 O2 ) adsorption via host-guest interaction and hinders the rapid decomposition of H2 O2 on MOC-AuNP/g-C3 N4 , ii) the AuNP component affords a strong interfacial electric field that significantly promotes the migration of electrons from g-C3 N4 for O2 reduction reaction (ORR), iii) holes are used for H2 O oxidation reaction (WOR) to produce O2 and H+ to further promote ORR. Thus, MOC-AuNP/g-C3 N4 can be used as an efficient piezocatalyst to generate H2 O2 at rates up to 120.21 µmol g-1 h-1 in air and pure water without using sacrificial agents. This work proposes a new strategy for efficient piezocatalytic H2 O2 synthesis by constructing multiple active sites in semiconductor catalysts via hydrogen bonding, by enhancing substrate adsorption, rapid separation of electron-hole pairs and preventing rapid decomposition of H2 O2 .

Piezoelectric Drop-on-Demand Inkjet Printing with Ultra-High Droplet Velocity.

Improving droplet velocity as much as possible is considered as the key to improving both printing speed and printing distance of the piezoelectric drop-on-demand inkjet printing technology. There are 3 tough and contradictory issues that need to be addressed simultaneously, namely, the actuation pressure of the piezoelectric printhead, satellite droplets, and the air resistance, which seems almost impossible to achieve with classical methods. Herein, a novel solution is introduced. By modulating the positive crosstalk effect inside and outside the printhead, self-tuning can be achieved, including self-reinforcing of the actuation pressure, self-restraining of satellite droplets, and self-weakening of the air resistance, thereby greatly improving droplet velocity. Based on these mechanisms, waveform design methods for different inks and printheads are investigated. The results demonstrate that monodisperse droplet jetting with a maximum velocity of 27.53 m/s can be achieved, reaching 3 to 5 times that of the classical method (5 to 8 m/s). Correspondingly, the printing speed and distance can be simultaneously increased by almost 10 times, demonstrating an ability of direct printing on irregular surface. Meanwhile, the compatibility of ink materials is expanded, as the Ohnesorge number and the viscosity of printable inks for the printhead used are increased from 0.36-0.72 to 0.03-1.18 and from 10-12 cp to 1-40.3 cp, respectively, even breaking the traditional limitations of the piezoelectric printing technology (Ohnesorge number of 0.1 to 1; viscosity of 1 to 25 cp). All the above provide a new perspective for improving droplet velocity and may even offer a game-changing choice for expanding the boundaries of the piezoelectric drop-on-demand inkjet printing technology.

Unmanned Aerial Vehicle-Based Compressed Data Acquisition for Environmental Monitoring in WSNs.

With the increasing concerns for the environment, the amount of the data monitored by wireless sensor networks (WSNs) is becoming larger and the energy required for data transmission is greater. However, sensor nodes have limited storage capacity and battery power. The WSNs are faced with the challenge of handling larger data volumes while minimizing energy consumption for transmission. To address this issue, this paper employs data compression technology to eliminate redundant information in the environmental data, thereby reducing energy consumption of sensor nodes. Additionally, an unmanned aerial vehicle (UAV)-assisted compressed data acquisition algorithm is put forward. In this algorithm, compressive sensing (CS) is introduced to decrease the amount of data in the network and the UAV serves as a mobile aerial base station for efficient data gathering. Based on CS theory, the UAV selectively collects measurements from a subset of sensor nodes along a route planned using the optimized greedy algorithm with variation and insertion strategies. Once the UAV returns, the sink node reconstructs sensory data from these measurements using the reconstruction algorithms. Extensive experiments are conducted to verify the performance of this algorithm. Experimental results show that the proposed algorithm has lower energy consumption compared to other approaches. Furthermore, we employ different data reconstruction algorithms to recover data and discover that the data can be better reconstructed in a shorter time.

Electrically active smart adhesive for a perching-and-takeoff robot.

Perching-and-takeoff robot can effectively economize onboard power and achieve long endurance. However, dynamic perching on moving targets for a perching-and-takeoff robot is still challenging due to less autonomy to dynamically land, tremendous impact during landing, and weak contact adaptability to perching surfaces. Here, a self-sensing, impact-resistant, and contact-adaptable perching-and-takeoff robot based on all-in-one electrically active smart adhesives is proposed to reversibly perch on moving/static dry/wet surfaces and economize onboard energy. Thereinto, attachment structures with discrete pillars have contact adaptability on different dry/wet surfaces, stable adhesion, and anti-rebound; sandwich-like artificial muscles lower weight, enhance damping, simplify control, and achieve fast adhesion switching (on-off ratio approaching ∞ in several seconds); and the flexible pressure (0.204% per kilopascal)-and-deformation (force resolution, <2.5 millinewton) sensor enables the robot's autonomy. Thus, the perching-and-takeoff robot equipped with electrically active smart adhesives exhibits tremendous advantages of soft materials over their rigid counterparts and promising application prospect of dynamic perching on moving targets.

Smart Manipulation of Complex Optical Elements via Contact-adaptive Dry Adhesives.

The implementation of complex, high-precision optical devices or systems, which have vital applications in the aerospace, medical, and military fields, requires the ability to reliably manipulate and assemble optical elements. However, this is a challenging task as these optical elements require contamination-free and damage-free manipulation and come in a variety of sizes and shapes. Here, a smart, contact-adaptive adhesive based on magnetic actuation is developed to address this challenge. Specifically, the surface bio-inspired adhesives made of fluororubber facilitate contamination-free and damage-free adhesion. The stiffness modulation of packaged magnetorheological grease based on the magnetorheological effect endows the smart adhesive with a high conformability to the optical elements in the soft state, a high grip force in the stiff state, and the ability to quickly release the optical elements in the recovered soft state. The smart adhesive provides a versatile solution for reliably and quickly manipulating and assembling multiscale optical elements with planar or complex 3D shapes without causing surface contamination or damage. These extraordinary capabilities are demonstrated by the manipulation and assembly of various optical elements, such as convex/concave/ball lenses and extremely complex-shaped light guide plates. The proposed smart adhesive is a promising candidate for conventional optical element manipulation technologies.

Micropatterned Fluororubber-Based Dry Adhesive for Pan-Semiconductor Production Line with Complicated Operating Conditions.

The efficient and safe manipulation of precision materials (such as thin and fragile wafers and glass substrates for flat panel displays) under complicated operating conditions with vacuum, high temperature, and low preload stress is an essential task for pan-semiconductor production lines. However, current manipulation approaches such as suction-based gripping (invalid under vacuum conditions) and mechanical clamping (stress concentration at the contact interfaces) are challenged to satisfy such complex requirements. Herein, fluororubber (FKM) is employed as an adhesive material to overcome such challenges due to its outstanding thermostability, availability under vacuum environments, and high adhesion at low contacting preloads. However, the adhesion of the FKM film decreases significantly with increasing temperature (decrease by 84.83% at 245 °C). Consequently, a micropatterned FKM-based dry adhesive (MFA) fabricated by laser etching is developed. The experimental results reveal that MFAs are efficient in restraining adhesion attenuation at high temperatures (minimum 15% decrease at 245 °C). The numerical analysis and in situ observations reveal the mechanism of the MFAs in restraining adhesion attenuation. The contamination-free and high adhesion at low contacting preload of MFAs can be of great interest in pan-semiconductor production lines that require complicated operating conditions on temperature, vacuum, and interface stress.

Unleashing the Power of NR4A1 Degradation as a Novel Strategy for Cancer Immunotherapy.

An effective cancer therapy requires both killing cancer cells and targeting tumor-promoting pathways or cell populations within the tumor microenvironment (TME). We purposely search for molecules that are critical for multiple tumor-promoting cell types and identified nuclear receptor subfamily 4 group A member 1 (NR4A1) as one such molecule. NR4A1 has been shown to promote the aggressiveness of cancer cells and maintain the immune suppressive TME. Using genetic and pharmacological approaches, we establish NR4A1 as a valid therapeutic target for cancer therapy. Importantly, we have developed the first-of-its kind proteolysis-targeting chimera (PROTAC, named NR-V04) against NR4A1. NR-V04 effectively degrades NR4A1 within hours of treatment in vitro and sustains for at least 4 days in vivo, exhibiting long-lasting NR4A1-degradation in tumors and an excellent safety profile. NR-V04 leads to robust tumor inhibition and sometimes eradication of established melanoma tumors. At the mechanistic level, we have identified an unexpected novel mechanism via significant induction of tumor-infiltrating (TI) B cells as well as an inhibition of monocytic myeloid derived suppressor cells (m-MDSC), two clinically relevant immune cell populations in human melanomas. Overall, NR-V04-mediated NR4A1 degradation holds promise for enhancing anti-cancer immune responses and offers a new avenue for treating various types of cancer.

CMC Strategies and Advanced Technologies for Vaccine Development to Boost Acceleration and Pandemic Preparedness.

This review reports on an overview of key enablers of acceleration/pandemic and preparedness, covering CMC strategies as well as technical innovations in vaccine development. Considerations are shared on implementation hurdles and opportunities to drive sustained acceleration for vaccine development and considers learnings from the COVID pandemic and direct experience in addressing unmet medical needs. These reflections focus on (i) the importance of a cross-disciplinary framework of technical expectations ranging from target antigen identification to launch and life-cycle management; (ii) the use of prior platform knowledge across similar or products/vaccine types; (iii) the implementation of innovation and digital tools for fast development and innovative control strategies.

Expert consensus on the clinical application of ormutivimab injection for use against the rabies virus.

BACKGROUND: There are no local or international guidelines or consensus on the use of mAbs against the rabies virus. RESEARCH DESIGN AND METHODS: An expert group in the field of rabies prevention and control formulated the consensus presented in this paper. RESULTS: Class III exposed persons to rabies for the first time; Identify type II exposed persons with immune deficiency; those who are first exposed to Class II and re-exposed to Class III within 7 days. They can use ormutivimab injection after completing the PEP wound treatment. In the case of injection restrictions or a wound that is difficult to detect, it is recommended that the entire Ormutivimab dose be infiltrated close to the wound. For severe multi-wound bites, the recommended dosage of ormutivimab is 20 IU/kg. If the recommended dose cannot meet all of the wound infiltration requirements, appropriate dilution can be conducted at a dilution ratio of 3 ~ 5 times. If the requirements for infiltration cannot be met after dilution, it is recommended that the dosage be increased with caution (maximum dosage, 40 IU/kg). The use of Ormutivimab is safe and effective without any contraindications by all age groups. CONCLUSIONS: This consensus standardizes clinical use of Ormutivimab, improves post-exposure prophylaxis of rabies in China, reduces infection rate.

Bioinspired Dry Adhesives for Highly Adaptable and Stable Manipulating Irregular Objects under Vibration.

For dry adhesive-based operation, highly adaptable and stable manipulation is important but also challenging, especially for irregular objects with complex surface (such as abrupt profile and acute projection) under vibration-inducing environments. Here, a multi-scale adhesive structure, with mechanically isolated energy-absorbing backing, based on the synergistic action of microscale contact end (seta), mesoscale supporting layer (lamella), and macroscopic backing (muscle tissues) of gecko's sole, is proposed. Top layer of mushroom-like micro tips provides dry adhesion via mimicking gecko's seta, and bottom layer of physical cuts and porous feature achieves the interfacial mechanical decoupling and crack inhibition via mimicking the non-continuous distributing of lamella and compliance of muscle. The proposed dry adhesive exhibits excellent adaptable adhesion to various objects with curved or irregular surfaces, even for that with abrupt contours, as well as an amazing stable anti-vibration ability, opening a new avenue for the development of dry adhesive-based device or system.

Electrowetting-assisted printing of 3D-architectured microelectrodes inside flexible piezoelectric films for sensitive, robust responses to bending deformation.

The voltage outputs of flexible piezoelectric films after bending deformation have always been limited by two factors, including the incompatible polarization direction with bending strain and the interfacial fatigue failure between the piezoelectric films and the electrode layers, largely hindering the applications in wearable electronics. Herein, we demonstrate a new piezoelectric film design, where 3D-architectured microelectrodes are fabricated inside a piezoelectric film by electrowetting-assisted printing of conductive nano-ink into the pre-formed meshed microchannels in the piezoelectric film. The 3D architectures increase the piezoelectric output of a typical P(VDF-TrFE) film by more than 7 fold compared with the conventional planar design at the same bending radius, and, more importantly, decrease the output attenuation down to only 5.3% after 10 000 bending cycles, less than one third of that for the conventional design. The dependence of piezoelectric outputs on feature sizes of 3D microelectrodes was investigated numerically and experimentally, providing a route for optimizing the 3D architecture design. Different composite piezoelectric films with internal 3D-architectured microelectrodes were fabricated, exhibiting improved piezoelectric outputs under bending deformations, demonstrating that our printing methods could have broad applications in various fields. The fabricated piezoelectric films, worn on human fingers, are used for remotely controlling the robot hand gestures by human-machine interaction; furthermore, the fabricated piezoelectric patches are used to successfully sense the pressure distribution by integrating with spacer arrays to convert the pressing movement into bending deformation, demonstrating the enormous potential of our piezoelectric films in practical applications.