Unique Response Research Articles

Unveiling the Intercompartmental Signaling Axis: Mitochondrial to ER Stress Response (MERSR) and its Impact on Proteostasis.

Maintaining protein homeostasis is essential for cellular health. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response, activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPR ER ), suggesting the presence of a Mitochondria to ER Stress Response (MERSR). During MERSR, the IRE1 branch of UPR ER is inhibited, introducing a previously unknown regulatory component of MCSR. Moreover, proteostasis is enhanced through the upregulation of the PERK-eIF2α signaling pathway, increasing phosphorylation of eIF2α and improving the ER's ability to handle proteostasis. MERSR activation in both polyglutamine and amyloid-beta peptide-expressing C. elegans disease models also led to improvement in both aggregate burden and overall disease outcome. These findings shed light on the coordination between the mitochondria and the ER in maintaining cellular proteostasis and provide further evidence for the importance of intercompartmental signaling.

Individually Addressable Multitouch Sensors Using a Sweep Signal for Minimal Wiring Complexity

Although touch sensing has been developed rapidly, it is difficult to design a simple circuit or a system that contains many sensors; the numbers of wires increase in proportion to the number of sensors. Although efforts have been made to reduce the number of wires, multi-touch measurements are still challenging because it is difficult to decouple multi-touch signals. Here, we apply FDM (Frequency Division Multiplexing) to SFCS (Swept Frequency Capacitive Sensing) when developing a sensor system capable of multi-touch with minimal wiring complexity. The sensor system can be extended in series and arrays by connecting multiple sensors using only two wires. A signal generated via frequency sweeping is expressed as a unique response in a specific frequency domain using a multi-band band-stop filter. Considering such unique touch responses, each capacitive multi-touch sensor is individually addressable, thereby allowing touch to be detected regardless of sensor location.

Nicotinamide Mononucleotide (NMN) Works in Type 2 Diabetes through Unexpected Effects in Adipose Tissue, Not by Mitochondrial Biogenesis.

Nicotinamide mononucleotide (NMN) has emerged as a promising therapeutic intervention for age-related disorders, including type 2 diabetes. In this study, we confirmed the previously observed effects of NMN treatment on glucose uptake and investigated its underlying mechanisms in various tissues and cell lines. Through the most comprehensive proteomic analysis to date, we discovered a series of novel organ-specific effects responsible for glucose uptake as measured by the IPGTT: adipose tissue growing (suggested by increased protein synthesis and degradation and mTOR proliferation signaling upregulation). Notably, we observed the upregulation of thermogenic UCP1, promoting enhanced glucose conversion to heat in intermuscular adipose tissue while showing a surprising repressive effect on mitochondrial biogenesis in muscle and the brain. Additionally, liver and muscle cells displayed a unique response, characterized by spliceosome downregulation and concurrent upregulation of chaperones, proteasomes, and ribosomes, leading to mildly impaired and energy-inefficient protein synthesis machinery. Furthermore, our findings revealed remarkable metabolic rewiring in the brain. This involved increased production of ketone bodies, downregulation of mitochondrial OXPHOS and TCA cycle components, as well as the induction of well-known fasting-associated effects. Collectively, our data elucidate the multifaceted nature of NMN action, highlighting its organ-specific effects and their role in improving glucose uptake. These findings deepen our understanding of NMN's therapeutic potential and pave the way for novel strategies in managing metabolic disorders.

Social context in stress and autism: comparing physiological profiles across two social paradigms in youth with and without autism spectrum disorder

BackgroundThe social world is often stressful for individuals with autism spectrum disorder (ASD). Research shows youth with ASD demonstrate physiological hyperreactivity to some social stressors (e.g., interaction) but not others (e.g., evaluation); therefore, this study examined diagnosis (ASD or typical development (TD)), social context, perceived anxiety, and physiological responsivity across multiple stress systems; namely, the hypothalamic pituitary adrenal (HPA) axis and autonomic nervous system (ANS). MethodThis study examined 244 ten-to-thirteen-year-olds with ASD (N = 140) or TD (N = 104). Physiological responses, measured by salivary cortisol, heart rate (HR), and respiratory sinus arrhythmia (RSA), were assessed before and after a social evaluative threat paradigm (Trier Social Stress Test; TSST) and social interaction (Trier Social Stress Test- Friendly; TSST-F). Mediation models examined the relationships between anxiety, diagnosis, and physiology. ResultsSignificant three-way interactions were observed for cortisol (p = 0.007) and HR (p = 0.002), suggesting diagnostic groups respond differently across context and time points. There was no significant interaction for RSA (p = 0.149), although ASD youth had significantly lower RSA overall (p = 0.038). State and trait anxiety did not mediate the relationship between diagnosis and physiology (all p > 0.05). ConclusionsFindings emphasize the critical role of context and a multisystem approach in examination of physiological social stress in youth with ASD. Results provide a foundation to elucidate unique response patterns across physiological systems to more precisely identify those with heightened physiological arousal across social contexts. It is proposed that future identification of subtypes may ultimately inform approaches for enhancing social engagement.

Semiconductive Biomaterials for Pathological Bone Repair and Regeneration

AbstractBone implant biomaterials are among the most used materials for clinical application. Despite significant advances in biocompatibility and osteoconductivity, conventional biomaterials lack the ability to cope with the pathological microenvironment (inflammation, infection, residual tumors, etc.) during bone repair. Semiconductor implant materials have unique electrical, optical, ultrasound, and thermal response properties, which facilitate non‐invasively and controllably dynamic repair of pathological bone defects. In this review, the design and synthesis of a new generation of semiconductor‐driven bone implant materials are summarized, the mechanism of action of semiconductive biomaterials' functional interfaces and the dynamic repair process of bone tissues are discussed, and new strategies for the problems encountered during clinical osseointegration is provided. Finally, the review outlooks the future of functional semiconductive implants for bone defect repair.

BECC438b TLR4 agonist supports unique immune response profiles from nasal and muscular DTaP pertussis vaccines in murine challenge models.

The protection afforded by acellular pertussis vaccines wanes over time, and there is a need to develop improved vaccine formulations. Options to improve the vaccines involve the utilization of different adjuvants and administration via different routes. While intramuscular (IM) vaccination provides a robust systemic immune response, intranasal (IN) vaccination theoretically induces a localized immune response within the nasal cavity. In the case of a Bordetella pertussis infection, IN vaccination results in an immune response that is similar to natural infection, which provides the longest duration of protection. Current acellular formulations utilize an alum adjuvant, and antibody levels wane over time. To overcome the current limitations with the acellular vaccine, we incorporated a novel TLR4 agonist, BECC438b, into both IM and IN acellular formulations to determine its ability to protect against infection in a murine airway challenge model. Following immunization and challenge, we observed that DTaP + BECC438b reduced bacterial burden within the lung and trachea for both administration routes when compared with mock-vaccinated and challenged (MVC) mice. Interestingly, IN administration of DTaP + BECC438b induced a Th1-polarized immune response, while IM vaccination polarized toward a Th2 immune response. RNA sequencing analysis of the lung demonstrated that DTaP + BECC438b activates biological pathways similar to natural infection. Additionally, IN administration of DTaP + BECC438b activated the expression of genes involved in a multitude of pathways associated with the immune system. Overall, these data suggest that BECC438b adjuvant and the IN vaccination route can impact efficacy and responses of pertussis vaccines in pre-clinical mouse models.

Right ventricular cardiomyocyte expansion accompanies cardiac regeneration in newborn mice after large left ventricular infarcts.

Cauterization of the root of the left coronary artery (LCA) in the neonatal heart on postnatal day 1 (P1) resulted in large, reproducible lesions of the left ventricle (LV), and an attendant marked adaptive response in the right ventricle (RV). The response of both chambers to LV myocardial infarction involved enhanced cardiomyocyte (CM) division and binucleation, as well as LV revascularization, leading to restored heart function within 7 days post surgery (7 dps). By contrast, infarction of P3 mice resulted in cardiac scarring without a significant regenerative and adaptive response of the LV and the RV, leading to subsequent heart failure and death within 7 dps. The prominent RV myocyte expansion in P1 mice involved an acute increase in pulmonary arterial pressure and a unique gene regulatory response, leading to an increase in RV mass and preserved heart function. Thus, distinct adaptive mechanisms in the RV, such as CM proliferation and RV expansion, enable marked cardiac regeneration of the infarcted LV at P1 and full functional recovery.

Anomalous time-reversal symmetric non-Hermitian systems

The conditions for the emergence of the non-Hermitian skin effect, as a unique physical response of non-Hermitian systems, have now become one of the hot research topics. In this paper, we study the novel physical responses of non-Hermitian systems with anomalous time-reversal symmetry, in both one dimension and two dimensions. Specifically, we focus on whether the systems will exhibit a non-Hermitian skin effect. We employ the theory of generalized Brillouin zone and also numerical methods to show that the anomalous time-reversal symmetry can prevent the skin effect in one-dimensional non-Hermitian systems, but is unable to exert the same effectiveness in two-dimensional cases.

Chitosan-initiated gold nanoparticles with enhanced fluorescence for unique Fe3+/PPi sensing and photothermal therapy

The design of surface ligands is crucial for ligand-protected gold nanoparticles (AuNPs). Herein, following the principle of green synthesis, environmentally friendly gold nanoparticles (AuNPs@His@CC, AuHC) were fabricated based on dual ligands of histidine and carboxylated chitosan. AuHC showed the advantages of low toxicity, good photoluminescent stability and ideal biocompatibility. Compared with single histidine-coated gold nanoclusters (AuNCs@His, AuH), AuHC presented enhanced fluorescence attributed to the addition of chitosan. The blue-emitting AuHC has a unique response to Fe3+ with detection limits as low as 9.51 nM. Interestingly, the quenched fluorescence of AuHC–Fe3+ system could be restored through the introduction of PPi with a detection limit of 10.6 μM. So an “on-off-on” fluorescence sensing platform was achieved. Apart from good optical properties and sensing, the designed AuHC demonstrated outstanding photothermal conversion efficiency (27.8 %), which made it ideal material for thermal ablation of tumor. To be specific, after laser irradiation (660 nm, 0.78 W cm−2, 10 min) of AuHC, the survival rate of HeLa cells as a tumor cell model decreased to 12.7 %, indicating that AuHC has a significant tumor inhibition effect in vitro. Besides, AuHC also could be a befitting candidate for overcoming drug-resistant tumor cells such as MCF-7/ADR cells. Notably, AuHC can markedly ablate solid tumors in 4T1 tumor-bearing mice after laser irradiation (660 nm, 0.78 W cm−2, 10 min). Hence this work provides insight into the design of multifunctional AuNPs platform for simultaneously integrating the ion sensing and photothermal therapy of cancer.

IMN041 is an immunotherapeutic and an effective treatment in mouse xenograft models of pancreatic cancer, renal cancer and triple negative breast cancer

BackgroundiMN013 (5-aza-2',2'-difluorodeoxycytidine), a DNA methyl transferase inhibitor and ribonucleotide reductase inhibitor, and its prodrug iMN041 (3',5'-di-trimethylsilyl-2',2'-difluro-5- azadeoxycytidine), have been shown to be active in mouse xenograft models of hematogenous and solid tumors. In a xenograft of non-small cell lung cancer (NCI-H460), iMN041 treated mice demonstrated a marked inflammatory response upon analysis of tumor histology, which was hypothesized to be mediated by upregulation of natural killer (NK) cells. This study aimed to characterize the antitumor immune responses generated by iMN041 and test the efficacy iMN041 in solid tumors with poor prognosis.MethodsIn the Renca syngeneic mouse model, tumors were harvested following two doses of iMN041 or vehicle control, and analyzed by fluorescent-activated cell sorting for an antitumor immune response. iMN041 was also tested for tumor growth inhibition and animal survival for up to 42 days in xenograft models of pancreatic, renal, and triple negative breast cancer.ResultsTumors from mice implanted with the Renca cell line and treated with iMN041 demonstrated an increase in granzyme B in NK (p = 0.024) and NKT cells (p = 0.004), an increase in the ratios of CD8-T to regulatory T cells (Treg) (p = 0.0026) and CD4-T to Treg cells (p = 0.022) and a decrease in myeloid-derived suppressor cells (p = 0.040), compared to vehicle controls. A significant decrease in MAGE-A positive tumor cells in treated mice, concordant with a proportional decrease in all live tumor cells, suggests that these cells are one of the main targets of the activated immune system. Xenograft models of the triple negative breast cancer cell line DU4475, renal cancer cell lines 786-O and Caki-1, and pancreatic cancer cell lines CFPAC-1 and SW1990, demonstrated significantly lower tumor volumes, and, where there were a sufficient number of events, significantly improved survival in treated mice compared to vehicle control mice.ConclusionsIn mouse cancer models, iMN041 is an effective treatment for solid tumors mediated in part through a unique antitumor immune response.

Exploring the impedance-matching effect in terahertz reflection imaging of skin tissue.

Terahertz (THz) electromagnetic waves, known for their unique response to water, offer promising opportunities for next-generation biomedical diagnostics and novel cancer therapy technologies. This study investigated the impedance-matching effect, which enhances the efficiency of THz wave delivery into tissues and compensates for the signal distortion induced by the refractive index mismatch between the target and the sample substrate. Three candidate biocompatible materials, water, glycerol, and petroleum jelly were applied to a skin phantom and compared using THz two-dimensional imaging and time-of-flight imaging methods. Finally, we successfully demonstrated impedance-matching effect on mouse skin tissues.

Negative poisson’s ratio behavior of Al4Li9 alloy

The negative Poisson’s ratio behavior in three-dimensional crystalline materials is a novel phenomenon. Deepening the research into the theoretical mechanisms that govern the negative Poisson’s ratio behavior offers valuable insights for the design and application of advanced auxetic materials. In this study, we construct the atomic model of Al4Li9 alloy based on experimental results and investigate the direction-dependent mechanical properties using the molecular statics simulations and density functional theory calculations. Our theoretical investigation reveals that a unique charge response within the analogous honeycomb structural unit in the Al4Li9 alloy results in a distinct exhibit of the significant negative Poisson’s ratio property during deformation.

Strong chirality and asymmetric transmission effect in twisted bilayer α-MoO3 in terahertz band

Chirality and asymmetric transmission have wide-ranging applications in fields such as optics, chemical synthesis, pharmaceutical research, biological analysis, materials science and communication technology. In this work, we have demonstrated a terahertz (THz) device with strong chirality and asymmetric transmission effect based on a twisted bilayer α-MoO3. The unique optical response can be realized by adjusting structural parameters such as the thicknesses of the layers as well as the angle of relative rotation. It is found that the proposed structure achieves a giant circular dichroism (CD) value of 0.81 at 9.8 THz, which originates from the symmetry breaking of the structure. The phenomenon has been approved by the polarization conversion and the distributions of the electric field. In addition, the device exhibits the asymmetric transmission effect for circularly polarized wave incidence. The results show that the forward and backward transmissivity of circularly polarized waves with different handedness exhibit a significant difference of up to 0.55 at 9.2 THz. This work simultaneously achieves chirality and asymmetric transmission effect in the terahertz band, which paves the way for developing terahertz devices capable of chirality manipulation and optical isolation.

Mechanical response of human thoracic spine ligaments under quasi-static loading: An experimental study

PurposeThis study aimed to investigate the geometrical and mechanical properties of human thoracic spine ligaments subjected to uniaxial quasi-static tensile test. MethodsFour human thoracic spines, obtained through a body donation program, were utilized for the study. The anterior longitudinal ligament (ALL), posterior longitudinal ligament (PLL), capsular ligament (CL), ligamenta flava (LF), and the interspinous ligament and supraspinous ligament complex (ISL + SSL), were investigated. The samples underwent specimen preparation, including dissection, cleaning, and reinforcement, before being immersed in epoxy resin. Uniaxial tensile tests were performed using a custom-designed mechanical testing machine equipped with an environmental chamber (T = 36.6 °C; humidity 95%). Then, the obtained tensile curves were averaged preserving the characteristic regions of typical ligaments response. ResultsGeometrical and mechanical properties, such as initial length and width, failure load, and failure elongation, were measured. Analysis of variance (ANOVA) revealed significant differences among the ligaments for all investigated parameters. Pairwise comparisons using Tukey's post-hoc test indicated differences in initial length and width. ALL and PLL exhibited higher failure forces compared to CL and LF. ALL and ISL + SSL demonstrated biggest failure elongation. Comparisons with other studies showed variations in initial length, failure force, and failure elongation across different ligaments. The subsystem (Th1 – Th6 and Th7 – Th12) analysis revealed increases in initial length, width, failure force, and elongation for certain ligaments. ConclusionsVariations of both the geometric and mechanical properties of the ligaments were noticed, highlighting their unique characteristics and response to tensile force. Presented results extend very limited experimental data base of thoracic spine ligaments existing in the literature. The obtained geometrical and mechanical properties can help in the development of more precise human body models (HBMs).

Light-Driven Sign Inversion of Circularly Polarized Luminescence Enabled by Dichroism Modulation in Cholesteric Liquid Crystals.

Stimuli-responsive circularly polarized luminescence (CPL) materials show great promise in applying information encryption and anticounterfeiting. Herein, light-driven CPL sign inversion is achieved by combining a photoresponsive achiral negative dichroic dye (KG) and a static achiral positive dichroic dye (NR) as dopants at the 0.5:0.5 weight ratio into the cholesteric liquid crystal (CLC) host. The side chains of KG undergo trans/cis isomerization after 365nm UV light irradiation, leading to the dichroism (SF) decrease. The |glum| value of CLC doping with KG (CLC-KG) weakens from 0.67 to 0.28 in response to the order degree change. Taking advantage of its unique CPL response property, the light-driven CPL sign inversion is achieved (from -0.20/0.14 to 0.02/-0.04) by incorporating NR (0.5:0.5) into the CLC-KG with helical superstructure static. Based on the synergistic use of circular polarization and responsiveness state as cryptographic primitives, the multidimensional information encryption CLC system can be realized.

From Tradition to Transformation: The Social Entrepreneurial Journey of Japanese Women

The purpose of the study is to understand how Japanese women become social entrepreneurs. The challenges in fostering women’s entrepreneurship include socio-cultural traditional views on women’s roles and expectations and insufficient support systems. Despite such challenges, the rise of Japanese women as social entrepreneurs has been observed in recent years as a unique response to natural disasters and crisis situations, such as the Tohoku earthquake in 2011 and the Kumamoto earthquake in 2016. Women felt the need to make positive changes and assist their country to build back. However, limited research exists that examines Japanese women social entrepreneurs’ development throughout their lives. Women social entrepreneurs may have gone through critically reflective moments through significant life events, which can eventually change the course of their professional paths. The methods of the study include in-depth, individual interviews with five women entrepreneurs, field observations, and a review of documents, including women’s organization websites, news articles, and social media. These findings provide both practical and scholarly insights that can be useful for the field of adult education and human resource development and women’s studies, highlighting how women maneuver challenging conditions, and how they effectively learn and transition from such challenges to become successful social entrepreneurs.

Structural and mechanical roles of wood polymer assemblies in softwood revealed by gradual removal of polysaccharides or lignin

A deep understanding of the inherent roles of wood polymers such as cellulose, hemicelluloses, and lignin in the hierarchical structure of wood is of key importance for advancing functional wood-based materials but is currently lacking. To address this gap, we clarified the underexplored contributions of wood polymer assemblies to the structural support and compressive properties of wood by chemically removing polysaccharides or lignin from wood blocks of a conifer Cryptomeria japonica. Compositional and structural evaluations revealed that cellulose, hemicelluloses, and lignin contributed to the dimensional stability of wood, especially that the polysaccharide network at cell corners sustained the honeycomb cell structure. Wood polymer assemblies featuring the anatomical structure of wood were also evaluated in terms of compressive properties. The modulus and strength reflected the density and anisotropy, whereas fracture behavior was well characterized by each wood polymer assembly through the classification of stress–strain curves based on principal component analysis. The difference in fracture behaviors indicated that the rigid lignin and flexible cellulose assemblies, possibly mediated by hemicelluloses, complementarily determine the unique compressive response of wood. These findings enable the adjustment of wood functionality and the selection of composite components for wood modification while inspiring the development of novel wood applications.

Real-time passive seismic monitoring using DAS — Today's solutions and remaining challenges

Distributed acoustic sensing (DAS) has been widely studied, and it has been applied in several areas of seismology. Passive seismic monitoring is one of the areas in which the application of DAS is considered. Common challenges of DAS in geophysics include its unique response, redundant but relatively low signal-to-noise ratio measurement, and high throughput of data from the acquisition system. Here, we introduce our recent attempts to address these challenges in the implementation of real-time DAS passive seismic monitoring. Survey design is a critical step in evaluating the capability and limitation of the sensor network, and it is the same in DAS. The survey design algorithm is updated considering DAS response, and we observe the unique nature of a DAS network compared to a geophone network. Considering real-time monitoring, the large volume of DAS data creates a bottleneck if we simply apply an existing real-time processing model. To accomplish real-time processing, we distributed computation between a well site and processing center. At the well site, the traditional signal enhancement, as well as deep learning-aided signature detection, are performed. The number of traces is reduced, while information is enhanced. Then, the processing result is transmitted to the processing center to complete event-location and magnitude computations. We review the technology and discuss remaining challenges in passive seismic monitoring while leveraging DAS-acquired data.

Jellyfish-inspired smart tetraphenylethene lipids with unique AIE fluorescence, thermal response, and cell membrane interaction.

Smart lipids with fluorescence emission, thermal response, and polyethylene glycolation (PEGylation) functions can be highly valuable for formulation, image-traceable delivery, and targeted release of payloads. Herein, a series of jellyfish-shaped amphiphiles with a tetraphenylethene (TPE) core and four symmetrical amphiphilic side chains were conveniently synthesized and systematically investigated as smart lipids. Compared with regular amphiphilic TPE lipids and phospholipids, the unprecedented jellyfish-shaped molecular geometry was found to enable a series of valuable capabilities, including sensitive and responsive aggregation-induced emission of fluorescence (AIE FL) and real-time FL monitoring of drug uptake. Furthermore, the jellyfish-shaped geometry facilitated the concentration-dependent aggregation from unimolecular micelles at low concentrations to "side-by-side" spherical aggregates at high concentrations and a unique mode of AIE. In addition, the size and the arrangement of the amphiphilic side chains were found to dominate the aggregate stability, cell uptake, and thus the cytotoxicity of the amphiphiles. This study has unprecedentedly developed versatile smart TPE lipids with precise structures, and unique physicochemical and biological properties while the peculiar structure-property relationship may shed new light on the design and application of AIE fluorophores and functional lipids in biomedicine and materials science.

Bidirectional optical response hydrogel with adjustable human comfort temperature for smart windows.

Smart windows are effective in reducing the energy consumption of air conditioning and lighting systems, while contributing to maintaining the comfort zone of temperature in the indoor environment. Currently used smart windows mainly rely on traditional single-phase thermochromic material in which only one abrupt optical change occurs during temperature changes, and their inherent characteristics may not be suited for a practical balance of energy saving and privacy protection. Here, we developed a novel bidirectional optically responsive smart window (BSW) with unique bidirectional optical response features by introducing sodium dodecyl sulfate (SDS)/potassium tartrate (PTH) micelles into PNIPAM hydrogel to form a composite hydrogel, which was encapsulated in two glass panels. The upper critical solution temperature (UCST) and lowest critical solution temperature (LCST) of the material can be individually adjusted and are capable of matching the human comfort zone of temperature. In addition, the smart window exhibits remarkable transparency (92.5%), visible light transmission ratio (Tlum = 91.31%), and excellent solar modulation (ΔTsol,UCST = 76.34%, ΔTsol,LCST = 76.75%). Moreover, it possesses selectivity in transmitting light in the infrared band of solar radiation and can complete the "transparent-opaque" transition in a very narrow temperature range (<1 °C). When at comfortable temperatures, the highly transparent smart windows facilitate interior light and appreciation of the view. At low temperatures, SDS/PTH micelles aggregate to form large micelles, blocking the transmission of light and protecting customer privacy. At high temperatures, PNIPAM can undergo a "sol-gel" transition, thus blocking incident solar radiation. Taken together, these proposed materials with bidirectional optical response characteristics would be harnessed as a promising platform for building energy conservation, anti-counterfeiting, information encryption, and temperature monitoring.