An antioxidant feedforward cycle coordinated by linker histone variant H1.2 and NRF2 that drives nonsmall cell lung cancer progression.

Nonsmall cell lung cancer (NSCLC) is highly malignant with limited treatment options, platinum-based chemotherapy is a standard treatment for NSCLC with resistance commonly seen. NSCLC cells exploit enhanced antioxidant defense system to counteract excessive reactive oxygen species (ROS), which contributes largely to tumor progression and resistance to chemotherapy, yet the mechanisms are not fully understood. Recent studies have suggested the involvement of histones in tumor progression and cellular antioxidant response; however, whether a major histone variant H1.2 (H1C) plays roles in the development of NSCLC remains unclear. Herein, we demonstrated that H1.2 was increasingly expressed in NSCLC tumors, and its expression was correlated with worse survival. When crossing the H1c knockout allele with a mouse NSCLC model (KrasLSL-G12D/+), H1.2 deletion suppressed NSCLC progression and enhanced oxidative stress and significantly decreased the levels of key antioxidant glutathione (GSH) and GCLC, the catalytic subunit of rate-limiting enzyme for GSH synthesis. Moreover, high H1.2 was correlated with the IC50 of multiple chemotherapeutic drugs and with worse prognosis in NSCLC patients receiving chemotherapy; H1.2-deficient NSCLC cells presented reduced survival and increased ROS levels upon cisplatin treatment, while ROS scavenger eliminated the survival inhibition. Mechanistically, H1.2 interacted with NRF2, a master regulator of antioxidative response; H1.2 enhanced the nuclear level and stability of NRF2 and, thus, promoted NRF2 binding to GCLC promoter and the consequent transcription; while NRF2 also transcriptionally up-regulated H1.2. Collectively, these results uncovered a tumor-driving role of H1.2 in NSCLC and indicate an "H1.2-NRF2" antioxidant feedforward cycle that promotes tumor progression and chemoresistance.

Permanent fluidic magnets for liquid bioelectronics.

Brownian motion allows microscopically dispersed nanoparticles to be stable in ferrofluids, as well as causes magnetization relaxation and prohibits permanent magnetism. Here we decoupled the particle Brownian motion from colloidal stability to achieve a permanent fluidic magnet with high magnetization, flowability and reconfigurability. The key to create such permanent fluidic magnets is to maintain a stable magnetic colloidal fluid by using non-Brownian magnetic particles to self-assemble a three-dimensional oriented and ramified magnetic network structure in the carrier fluid. This structure has high coercivity and permanent magnetization, with long-term magnetization stability. We establish a scaling theory model to decipher the permanent fluid magnet formation criteria and formulate a general assembly guideline. Further, we develop injectable and retrievable permanent-fluidic-magnet-based liquid bioelectronics for highly sensitive, self-powered wireless cardiovascular monitoring. Overall, our findings highlight the potential of permanent fluidic magnets as an ultrasoft material for liquid devices and systems, from bioelectronics to robotics.

Loss of renal tubular G9a benefits acute kidney injury by lowering focal lipid accumulation via CES1.

Surgery-induced renal ischemia and reperfusion (I/R) injury and nephrotoxic drugs like cisplatin can cause acute kidney injury (AKI), for which there is no effective therapy. Lipid accumulation is evident following AKI in renal tubules although the mechanisms and pathological effects are unclear. Here, we report that Ehmt2-encoded histone methyltransferase G9a is upregulated in patients and mouse kidneys after AKI. Renal tubular specific knockout of G9a (Ehmt2Ksp ) or pharmacological inhibition of G9a alleviates lipid accumulation associated with AKI. Mechanistically, G9a suppresses transcription of the lipolytic enzyme Ces1; moreover, G9a and farnesoid X receptor (FXR) competitively bind to the same promoter regions of Ces1. Ces1 is consistently observed to be downregulated in the kidney of AKI patients. Pharmacological inhibition of Ces1 increases lipid accumulation, exacerbates renal I/R-injury and eliminates the beneficial effects on AKI observed in Ehmt2Ksp mice. Furthermore, lipid-lowering atorvastatin and an FXR agonist alleviate AKI by activating Ces1 and reducing renal lipid accumulation. Together, our results reveal a G9a/FXR-Ces1 axis that affects the AKI outcome via regulating renal lipid accumulation.

Implantable Triboelectric Nanogenerators for Self-Powered Cardiovascular Healthcare.

Triboelectric nanogenerators (TENGs) have gained significant traction in recent years in the bioengineering community. With the potential for expansive applications for biomedical use, many individuals and research groups have furthered their studies on the topic, in order to gain an understanding of how TENGs can contribute to healthcare. More specifically, there have been a number of recent studies focusing on implantable triboelectric nanogenerators (I-TENGs) toward self-powered cardiac systems healthcare. In this review, the progression of implantable TENGs for self-powered cardiovascular healthcare, including self-powered cardiac monitoring devices, self-powered therapeutic devices, and power sources for cardiac pacemakers, will be systematically reviewed. Long-term expectations of these implantable TENG devices through their biocompatibility and other utilization strategies will also be discussed.

Planar oligomerization of reconfigurable gold nanorod dimers.

Reconfigurable chiral plasmonic complexes are fabricated by planar assembly of multiple individual gold nanorod dimers using DNA origami templates. Additionally, each chiral center can be controlled to switch among achiral, left-handed, and right-handed states. We demonstrate that their overall circular dichroism is determined by the coupling of individual chiral centers and is heavily influenced by the precise number and arrangement of these centers. Our study offers a novel self-assembly method for constructing intricate and dynamic chiral plasmonics as well as investigating the interactions among several plasmonic chiral centers.

Piezoelectric nanogenerators for personalized healthcare.

The development of flexible piezoelectric nanogenerators has experienced rapid progress in the past decade and is serving as the technological foundation of future state-of-the-art personalized healthcare. Due to their highly efficient mechanical-to-electrical energy conversion, easy implementation, and self-powering nature, these devices permit a plethora of innovative healthcare applications in the space of active sensing, electrical stimulation therapy, as well as passive human biomechanical energy harvesting to third party power on-body devices. This article gives a comprehensive review of the piezoelectric nanogenerators for personalized healthcare. After a brief introduction to the fundamental physical science of the piezoelectric effect, material engineering strategies, device structural designs, and human-body centered energy harvesting, sensing, and therapeutics applications are also systematically discussed. In addition, the challenges and opportunities of utilizing piezoelectric nanogenerators for self-powered bioelectronics and personalized healthcare are outlined in detail.

Giant magnetoelastic effect in soft systems for bioelectronics.

The magnetoelastic effect-the variation of the magnetic properties of a material under mechanical stress-is usually observed in rigid alloys, whose mechanical modulus is significantly different from that of human tissues, thus limiting their use in bioelectronics applications. Here, we observed a giant magnetoelastic effect in a soft system based on micromagnets dispersed in a silicone matrix, reaching a magnetomechanical coupling factor indicating up to four times more enhancement than in rigid counterparts. The results are interpreted using a wavy chain model, showing how mechanical stress changes the micromagnets' spacing and dipole alignment, thus altering the magnetic field generated by the composite. Combined with liquid-metal coils patterned on polydimethylsiloxane working as a magnetic induction layer, the soft magnetoelastic composite is used for stretchable and water-resistant magnetoelastic generators adhering conformably to human skin. Such devices can be used as wearable or implantable power generators and biomedical sensors, opening alternative avenues for human-body-centred applications.

Finite Assembly of Three-Dimensional DNA Hierarchical Nanoarchitectures through Orthogonal and Directional Bonding.

Reliable orthogonal bonding with precise and flexible orientation control would be ideal for building finite complex nanostructures via self-assembly. Employing a three-dimensional (3D) DNA origami, hexagonal prism DNA origami (HDO), as building block, we demonstrate it is practical to construct finite hierarchical nanoarchitectures with complicated conformations through orthogonal and directional bonding. The as-designed HDO building block has twelve prescribed directional valences in 3D space and each of them supports two opposite orientations, yielding the capability to generate abundant directional bonding. Meanwhile, we minimize the thorny non-specific interactions among HDOs and enable the orthogonal bonding between any two valences based on self-similar designing. Consequently, various hierarchical nanostructures are prepared at will simply by the combination of HDOs with appropriate valences. We believe this route towards hierarchically assembly is inspiring and hope it will facilitate the fabrication of functional superstructures.

Nickel/Cobalt Molybdate Hollow Rods Induced by Structure and Defect Engineering as Exceptional Electrode Materials for Hybrid Supercapacitor.

Oxygen defects and hollow structures positively impact pseudocapacitive properties of diffusion/surface-controlled processes, a component of critical importance when building high-performance supercapacitors. Hence, we fabricated hollow nickel/cobalt molybdate rods with O-defects (D-H-NiMoO4 @CoMoO4 ) through a soft-template and partial reduction method, enhancing D-H-NiMoO4 @CoMoO4 's electrochemical performance, yielding a specific capacitance of 1329 F g-1 , and demonstrating excellent durability with 95.8 % capacity retention after 3000 cycles. D-H-NiMoO4 @CoMoO4 was used as the positive electrode to construct an asymmetric supercapacitor, displaying an energy density of up to 34.13 Wh kg-1 and demonstrating good predisposition towards practical applications. This work presents an effective approach to fabricate and use hollow nickel/cobalt molybdate rods with O-defects as pseudocapacitor material for high-performance capacitive energy storage devices.

Hollow Tobacco Mosaic Virus Coat Protein Assisted Self-Assembly of One-Dimensional Nanoarchitectures.

Herein, an efficient strategy to fabricate well-organized one-dimensional (1D) inorganic nanostructures is demonstrated by utilizing the hollow tobacco mosaic virus coat protein (TMVCP) as a restrictive template. Considering the advantages of the unique hollow structure and the dynamic self-assembly attribute of TMVCP, foreign nano-objects are successfully encapsulated and conveniently assembled into highly organized 1D chainlike structures in the cavity of the TMVCP multimer (TMV disk). Different kinds of functional nanoparticles, such as gold nanoparticles (AuNPs) and silver sulfide quantum dots (Ag2S QDs), are used to demonstrate the successful construction of ordered 1D nanochains in high yields. Notably, binary nanochains of such different kinds of nanoparticles are also constructed through co-assembling the TMV disk-coated AuNPs and Ag2S QDs. Further, the TMV-assisted AuNP nanochains are grown into the 1D nanowires through in situ Au deposition owing to the spatial confinement of the TMVCP cavity. Together, our findings indicate that the TMV-assisted self-assembly approach, resulting in higher yields and better controllability over the other reported studies based on directly mineralizing the metal architectures in the TMV nanorods, provides enormous potential toward the fabrication of highly complex hybrid-metal nanostructures.

Programming Dynamic Assembly of Viral Proteins with DNA Origami.

Biomolecular assembly in biological systems is typically a complex dynamic process regulated by the exchange of molecular information between biomolecules such as proteins and nucleic acids. Here, we demonstrate a nucleic-acid-based system that can program the dynamic assembly process of viral proteins. Tobacco mosaic virus (TMV) genome-mimicking RNA is anchored on DNA origami nanostructures via hybridization with a series of DNA strands which also function as locks that prevent the packaging of RNA by the TMV proteins. The selective, sequential releasing of the RNA via toehold-mediated strand displacement allows us to program the availability of RNA and subsequently the TMV growth in situ. Furthermore, the programmable dynamic assembly of TMV on DNA templates also enables the production of new DNA-protein hybrid nanostructures, which are not attainable by using previous assembly methods.

Interfacially Bridging Covalent Network Yields Hyperstable and Ultralong Virus-Based Fibers for Engineering Functional Materials.

We present a strategy of interfacially bridging covalent network within tobacco mosaic virus (TMV) virus-like particles (VLPs). We arranged T103C cysteine to laterally conjugate adjacent subunits. In the axis direction, we set A74C mutation and systematically investigated candidate from E50C to P54C as the other thiol function site, for forming longitudinal disulfide bond chains. Significantly, the T103C-TMV-E50C-A74C shows the highest robustness in assembly capability and structural stability with the largest length, for TMV VLP to date. The fibers with lengths from several to a dozen of micrometers even survive under pH 13. The robust nature of this TMV VLP allows for reducer-free synthesis of excellent electrocatalysts for application in harshly alkaline hydrogen evolution.

DNA-Based Adaptive Plasmonic Logic Gates.

Self-assembled plasmonic logic gates that read DNA molecules as input and return plasmonic chiroptical signals as outputs are reported. Such logic gates are achieved on a DNA-based platform that logically regulate the conformation of a chiral plasmonic nanostructure, upon specific input DNA strands and internal computing units. With systematical designs, a complete set of Boolean logical gates are realized. Intriguingly, the logic gates could be endowed with adaptiveness, so they can autonomously alter their logics when the environment changes. As a demonstration, a logic gate that performs AND function at body temperature while OR function at cold storage temperature is constructed. In addition, the plasmonic chiroptical output has three distinctive states, which makes a three-state molecular logic gate readily achievable on this platform. Such DNA-based plasmonic logic gates are envisioned to execute more complex tasks giving these unique characteristics.

Toward Precise Manipulation of DNA-Protein Hybrid Nanoarchitectures.

Nucleic acids and proteins are the two primary building materials of living organisms. Over the past decade, artificial DNA-protein hybrid structures have been pursued for a wide range of applications. DNA nanotechnology, in particular, has dramatically expanded nanoscale molecule engineering and contributed to the spatial arrangement of protein components. Strategies for designing site-specific coupling of DNA oligomers to proteins are needed in order to allow for precise control over stoichiometry and position. Efforts have also been focused on coassembly of protein-DNA complexes by engineering their fundamental molecular recognition interactions. This Concept focuses on the precise manipulation of DNA-protein nanoarchitectures. Particular attention is paid to site-selectivity within DNA-protein conjugates, regulation of protein orientation using DNA scaffolds, and coassembly principles upon unique structural motifs. Current challenges and future directions are also discussed in the design and application of DNA-protein nanoarchitectures.

Dual Functional Modification of Alkaline Amino Acids Induces the Self-Assembly of Cylinder-Like Tobacco Mosaic Virus Coat Proteins into Gear-Like Architectures.

Herein, the assembly of 3D uniform gear-like architectures is demonstrated with a tobacco mosaic virus (TMV) disk as a building block. In this context, the intrinsic behavior of the TMV disk that promotes its assembly into nanotubes is altered by a synergistic effect of dual functional modifications at the 53rd arginine mutation and the introduction of lysine groups in the periphery at 1st and 158th positions of the TMV disk, which results in the formation of 3D gear-like superstructures. Therein, the 53rd arginine moiety significantly strengthens the linkage between TMV disks in the alkaline environment through hydrogen bond interactions. The charge of lysine-modified lateral surfaces is partially neutralized in the alkaline solution, which induces the TMV disk to form a gear-like architecture to maintain its structural stability by exploiting the electrostatic repulsion between neighboring TMV disks. This study not only provides explicit evidence regarding the molecular-level understanding of how the modification of site-specific amino acid affects the assembly of resultant superstructures but also encourages the fabrication of functional protein-based nanoarchitectures.

Recent Advances in Stretchable Supercapacitors Enabled by Low-Dimensional Nanomaterials.

Supercapacitors (SCs) have shown great potential for mobile energy storage technology owing to their long-term durability, electrochemical stability, structural simplicity, as well as exceptional power density without much compromise in the energy density and cycle life parameters. As a result, stretchable SC devices have been incorporated in a variety of emerging electronics applications ranging from wearable electronic textiles to microrobots to integrated energy systems. In this review, the recent progress and achievements in the field of stretchable SCs enabled by low-dimensional nanomaterials such as polypyrrole, carbon nanotubes, and graphene are presented. First, the three major categories of stretchable supercapacitors are discussed: double-layer supercapacitors, pseudo-supercapacitors, and hybrid supercapacitors. Then, the representative progress in developing stretchable electrodes with low-dimensional (0D, 1D, and 2D) nanomaterials is described. Next, the design strategies enabling the stretchability of the devices, including the wavy-shape design, wire-shape design, textile-shape design, kirigami-shape design, origami-shape design, and serpentine bridge-island design are emphasized, with the aim of improving the electrochemical performance under the complex stretchability conditions that may be encountered in practical applications. Finally, the newest developments, major challenges, and outlook in the field of stretchable SC development and manufacturing are discussed.

An attention-based approach for assessing the effectiveness of emotion-evoking in immersive environment.

Visual stimuli within an immersive virtual environment impact human perception and behavior in notably different ways compared to the real world. Previous studies have presented evidence indicating that individuals in various emotional states exhibit an unconscious attentional bias toward either positive or negative stimuli. However, whether these findings can be replicated within an immersive virtual environment remains uncertain. In this study, we devised an attention-based experiment to explore whether the correlation between participants' emotional states and the valence of visual stimuli influences their attentional bias. Participants (n=28) viewed 360-degree videos with varying valence levels (positive and negative) to evoke emotions. Subsequently, we utilized standard emotional human faces as stimuli to assess how the consistency in video valence and emotional faces affects reaction time (RT) in Go tasks and error rates in No-go tasks. We employed the Ex-Gaussian approach to analyze the RT data. The parameters-mu (µ), sigma (σ), and tau (τ)-were computed to denote response speed and attentional lapses, respectively. Our findings revealed a significant increase in tau (τ) when the valence of the video and emotional faces aligned. This suggests that the Go/No-go paradigm is effective in evaluating the impact of emotion-evoking stimuli within an immersive environment.

Secondary Phase Precipitation in Fe-22Mn-9Al-0.6C Low-Density Steel during Continuous Cooling Process.

Secondary phase precipitation in Fe-22Mn-9Al-0.6C low-density steel was investigated during a continuous cooling process with different cooling rates through a DIL805A thermal expansion dilatometer, and the changes in microstructures and hardness by different cooling rates were discussed. The results showed that the matrix of the Fe-22Mn-9Al-0.6C was composed of austenite and δ-ferrite; moreover, the secondary phases included κ-carbide, ß-Mn and DO3 at room temperature. The precipitation temperatures of 858 °C, 709 °C and 495 °C corresponded to the secondary phases B2, κ-carbide and ß-Mn, respectively, which were obtained from the thermal expansion curve by the tangent method. When the cooling rate was slow, it had enough time to accommodate C-poor and Al-rich regions in the austenite due to amplitude modulation decomposition. Furthermore, the Al enrichment promoted δ-ferrite formation. Meanwhile, the subsequent formation of κ-carbide and ß-Mn occurred through the continuous diffusion of C and Mn into austenite. In addition, the hardness of austenite was high at 0.03 °C/s due to the κ-carbide and ß-Mn production and C enrichment, and it was inversely proportional to the cooling rate. It can be concluded that the presence of κ-carbide, DO3 and ß-Mn produced at the austenitic/ferrite interface when the cooling rate was below 0.1 °C/s resulted in κ-carbide and ß-Mn precipitating hardly at cooling rates exceeding 0.1 °C/s, which provides a guideline for the industrial production of Fe-Mn-Al-C low-density steel in the design of the hot working process.

Cellular ATP redistribution achieved by deleting Tgparp improves lignocellulose utilization of Trichoderma under heat stress.

BACKGROUND: Thermotolerance is widely acknowledged as a pivotal factor for fungal survival across diverse habitats. Heat stress induces a cascade of disruptions in various life processes, especially in the acquisition of carbon sources, while the mechanisms by which filamentous fungi adapt to heat stress and maintain carbon sources are still not fully understood. RESULTS: Using Trichoderma guizhouense, a representative beneficial microorganism for plants, we discover that heat stress severely inhibits the lignocellulases secretion, affecting carbon source utilization efficiency. Proteomic results at different temperatures suggest that proteins involved in the poly ADP-ribosylation pathway (TgPARP and TgADPRase) may play pivotal roles in thermal adaptation and lignocellulose utilization. TgPARP is induced by heat stress, while the deletion of Tgparp significantly improves the lignocellulose utilization capacity and lignocellulases secretion in T. guizhouense. Simultaneously, the absence of Tgparp prevents the excessive depletion of ATP and NAD+, enhances the protective role of mitochondrial membrane potential (MMP), and elevates the expression levels of the unfolded protein response (UPR)-related regulatory factor Tgire. Further investigations reveal that a stable MMP can establish energy homeostasis, allocating more ATP within the endoplasmic reticulum (ER) to reduce protein accumulation in the ER, thereby enhancing the lignocellulases secretion in T. guizhouense under heat stress. CONCLUSIONS: Overall, these findings underscored the significance of Tgparp as pivotal regulators in lignocellulose utilization under heat stress and provided further insights into the molecular mechanism of filamentous fungi in utilizing lignocellulose.

Efficacy of electrical stimulation for post-stroke motor dysfunction: A protocol for systematic review and network meta-analysis.

OBJECTIVE: This study aims to analyze the efficacy and safety of different electrical stimulation treatments for post-stroke motor dysfunction, and to quantitatively analyze the advantages between them and their possible benefits for patients. METHODS: We will systematically search seven databases. All of them will be retrieved from inception to 15, April 2024. Two reviewers will evaluation the risk of bias in all included studies with the version 2 of the Cochrane risk-of-bias assessment tool. Data synthesis will be performed using a random-effects model of network meta-analysis to compare the efficacy and safety of different electrical stimulation therapies. The surface under the cumulative ranking curve was used to indicate the possibility of the pros and cons of the intervention. The strength of evidence will be assessed by the Grading of Recommendations, Assessment, Development, and Evaluation framework. DISCUSSION: This study will provide evidence that electrical stimulation therapy can effectively improve motor function in stroke patients and will also provide some valuable references for clinical decision-making and treatment guidelines. TRIAL REGISTRATION: PROSPERO registration number: CRD42023459102.