Mutant huntingtin protein induces MLH1 degradation, DNA hyperexcision, and cGAS-STING-dependent apoptosis.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (HTT) gene. The repeat-expanded HTT encodes a mutated HTT (mHTT), which is known to induce DNA double-strand breaks (DSBs), activation of the cGAS-STING pathway, and apoptosis in HD. However, the mechanism by which mHTT triggers these events is unknown. Here, we show that HTT interacts with both exonuclease 1 (Exo1) and MutLα (MLH1-PMS2), a negative regulator of Exo1. While the HTT-Exo1 interaction suppresses the Exo1-catalyzed DNA end resection during DSB repair, the HTT-MutLα interaction functions to stabilize MLH1. However, mHTT displays a significantly reduced interaction with Exo1 or MutLα, thereby losing the ability to regulate Exo1. Thus, cells expressing mHTT exhibit rapid MLH1 degradation and hyperactive DNA excision, which causes severe DNA damage and cytosolic DNA accumulation. This activates the cGAS-STING pathway to mediate apoptosis. Therefore, we have identified unique functions for both HTT and mHTT in modulating DNA repair and the cGAS-STING pathway-mediated apoptosis by interacting with MLH1. Our work elucidates the mechanism by which mHTT causes HD.

The mismatch recognition protein MutSα promotes nascent strand degradation at stalled replication forks.

Mismatch repair (MMR) is a replication-coupled DNA repair mechanism and plays multiple roles at the replication fork. The well-established MMR functions include correcting misincorporated nucleotides that have escaped the proofreading activity of DNA polymerases, recognizing nonmismatched DNA adducts, and triggering a DNA damage response. In an attempt to determine whether MMR regulates replication progression in cells expressing an ultramutable DNA polymerase ɛ (Polɛ), carrying a proline-to-arginine substitution at amino acid 286 (Polɛ-P286R), we identified an unusual MMR function in response to hydroxyurea (HU)-induced replication stress. Polɛ-P286R cells treated with hydroxyurea exhibit increased MRE11-catalyzed nascent strand degradation. This degradation by MRE11 depends on the mismatch recognition protein MutSα and its binding to stalled replication forks. Increased MutSα binding at replication forks is also associated with decreased loading of replication fork protection factors FANCD2 and BRCA1, suggesting blockage of these fork protection factors from loading to replication forks by MutSα. We find that the MutSα-dependent MRE11-catalyzed fork degradation induces DNA breaks and various chromosome abnormalities. Therefore, unlike the well-known MMR functions of ensuring replication fidelity, the newly identified MMR activity of promoting genome instability may also play a role in cancer avoidance by eliminating rogue cells.

lncRNA SYTL5-OT4 promotes vessel co-option by inhibiting the autophagic degradation of ASCT2.

AIMS: Vessel co-option is responsible for tumor resistance to antiangiogenic therapies (AATs) in patients with colorectal cancer liver metastasis (CRCLM). However, the mechanisms underlying vessel co-option remain largely unknown. Herein, we investigated the roles of a novel lncRNA SYTL5-OT4 and Alanine-Serine-Cysteine Transporter 2 (ASCT2) in vessel co-option-mediated AAT resistance. METHODS: SYTL5-OT4 was identified by RNA-sequencing and verified by RT-qPCR and RNA fluorescence in situ hybridization assays. The effects of SYTL5-OT4 and ASCT2 on tumor cells were investigated by gain- and loss-of-function experiments, and those of SYTL5-OT4 on ASCT2 expression were analyzed by RNA immunoprecipitation and co-immunoprecipitation assays. The roles of SYTL5-OT4 and ASCT2 in vessel co-option were detected by histological, immunohistochemical, and immunofluorescence analyses. RESULTS: The expression of SYTL5-OT4 and ASCT2 was higher in patients with AAT-resistant CRCLM. SYTL5-OT4 enhanced the expression of ASCT2 by inhibiting its autophagic degradation. SYTL5-OT4 and ASCT2 promoted vessel co-option by increasing the proliferation and epithelial-mesenchymal transition of tumor cells. Combination therapy of ASCT2 inhibitor and antiangiogenic agents overcame vessel co-option-mediated AAT resistance in CRCLM. CONCLUSION: This study highlights the crucial roles of lncRNA and glutamine metabolism in vessel co-option and provides a potential therapeutic strategy for patients with AAT-resistant CRCLM.

Plasma exosome miRNA-26b-3p derived from idiopathic short stature impairs longitudinal bone growth via the AKAP2/ERK1/2 axis.

BACKGROUND: Currently, the etiology of idiopathic short stature (ISS) is still unclear. The poor understanding of the molecular mechanisms of ISS has largely restricted this strategy towards safe and effective clinical therapies. METHODS: The plasma exosomes of ISS children were co-cultured with normal human chondrocytes. The differential expression of exosome miRNA between ISS and normal children was identified via high-throughput microRNA sequencing and bioinformatics analysis. Immunohistochemistry, In situ hybridization, RT-qPCR, western blotting, luciferase expression, and gene overexpression and knockdown were performed to reveal the key signaling pathways that exosome miRNA of aberrant expression in ISS children impairs longitudinal bone growth. RESULTS: Chondrocytes proliferation and endochondral ossification were suppressed after coculture of ISS plasma exosomes with human normal chondrocytes. High-throughput microRNA sequencing and RT-qPCR confirmed that plasma exosome miR-26b-3p was upregulated in ISS children. Meanwhile, exosome miRNA-26b-3p showed a high specificity and sensitivity in discriminating ISS from normal children. The rescue experiment showed that downregulation of miR-26b-3p obviously improved the repression of chondrocyte proliferation and endochondral ossification caused by ISS exosomes. Subsequently, miR-26b-3p overexpression inhibited chondrocyte proliferation and endochondral ossification once again. In situ hybridization confirmed the colocalization of miR-26b-3p with AKAP2 in chondrocytes. In vitro and in vivo assay revealed exosome miRNA-26b-3p impairs longitudinal bone growth via the AKAP2 /ERK1/2 axis. CONCLUSIONS: This study is the first to confirm that miR-26b-3p overexpression in ISS plasma exosomes leads to disorders in proliferation and endochondral ossification of growth plate cartilage via inhibition of AKAP2/ERK1/2 axis, thereby inducing ISS. This study provides a new research direction for the etiology and pathology of ISS and a new idea for the biological treatment of ISS.

High-Efficiency Directional Ejection of Coalesced Drops on a Circular Groove.

Coalescence-induced drop jumping has received significant attention in the past decade. However, its application remains challenging as a result of the low energy conversion efficiency and uncontrollable drop jumping direction. In this work, we report the high-efficiency coalescence-induced drop jumping with tunable jumping direction via rationally designed millimeter-sized circular grooves. By increasing the surface-droplet impact site area and restricting the oscillatory deformation, the energy conversion efficiency of the jumping droplet reaches 43.5%, 600% as high as the conventional superhydrophobic surfaces. The droplet jumping direction can be tuned from 90° to 60° by varying the principal curvature of the circular groove, while the energy conversion efficiency remains unchanged. We show through theoretical analysis and numerical simulations that the directional jumping mainly originates from reallocation of droplet momentum enabled by the asymmetric liquid bridge impact. Our study demonstrates a simple yet effective method for fast, efficient, and directional droplet removal, which warrants promising applications in jumping droplet condensation, water harvesting, anti-icing, and self-cleaning.

One-step synthesis of N, S-doped carbon dots with orange emission and their application in tetracycline antibiotics, quercetin sensing, and cell imaging.

Water soluble N, S-doped carbon dots (N, S-CDs) with orange emission were synthesized from basic fuchsin and sulfosalicylic acid by the typical hydrothermal route. Based on the inner filter effect (IFE), the prepared N, S-CDs can be innovatively developed as an effective "signal-off" multifunctional sensing platform for sensitive determination of tetracycline antibiotics (for example, chlortetracycline (CTC)) and quercetin. The proposed sensor was utilized to realize the determination of CTC in water and milk samples and quercetin in beer sample (λex = 375 nm, λem = 605 nm) with satisfactory recoveries and relative standard deviations (RSD). The linear range and detection limit (LOD) of CTC is 1.24-165 µM and 32.36 nM, respectively. For quercetin, the linear ranges are 0.98-34 µM and 34-165 µΜ, and the LOD is 6.87 nM (3σ/m). By virtue of the good biocompatibility and long-wavelength emission, N, S-CDs were also used in the imaging of oocystis cells and yeast cells, which demonstrated promising applicability for bio-imaging and sensing. In this paper, N, S-doped carbon dots (N, S-CDs) with orange emission (λem = 605 nm) were synthesized from basic fuchsin and sulfosalicylic acid. Based on the inner filter effect (IFE), the prepared N, S-CDs can be innovatively developed as an effective "signal-off" multifunctional sensing platform for the sensing of tetracycline antibiotics (for example: chlortetracycline (CTC)) and quercetin. The sensor has been successfully applied to the determination of CTC in water and milk samples and quercetin in beer sample (λex = 375 nm, λem = 605 nm). The linear range and detection limit (LOD) of CTC is 1.24-165 µM and 32.36 nM respectively. For quercetin, the linear ranges are 0.98-34 µM and 34-165 µΜ, and the LOD is 6.87 nM (3σ/m). In addition, due to the characteristics of good biocompatibility and long-wavelength emission, the N, S-CDs were also used in the imaging of oocystis cells and yeast cells, which demonstrated promising applicability for bioimaging and sensing.

Quantum Confined Tomonaga-Luttinger Liquid in Mo6Se6 Nanowires Converted from an Epitaxial MoSe2 Monolayer.

Confining interacting particles in one-dimension (1D) changes the electronic behavior of the system fundamentally, which has been studied extensively in the past. Examples of 1D metallic systems include carbon nanotubes, quasi-1D organic conductors, metal chains, and domain boundary defects in monolayer thick transition-metal dichalcogenides such as MoSe2. Here single and bundles of Mo6Se6 nanowires were fabricated through annealing a MoSe2 monolayer grown by molecular-beam epitaxy on graphene. Conversion from two-dimensional (2D) MoSe2 film to 1D Mo6Se6 nanowire is reversible. Mo6Se6 nanowires form preferentially at the Se-terminated zigzag edges of MoSe2 and stitch to it via two distinct atomic configurations. The Mo6Se6 wire is metallic and its length is tunable, which represents one of few 1D systems that exhibit properties pertinent to quantum confined Tomonaga-Luttinger liquid, as evidenced by scanning tunneling microscopic and spectroscopic studies.

One-Step Hydrothermal Approach to Synthesis Carbon Dots from D-Sorbitol for Detection of Iron(III) and Cell Imaging.

A facile and economic approach to synthesis highly fluorescence carbon dots (CDs) via one-step hydrothermal treatment of D-sorbitol was presented. The as-synthesized CDs were characterized by good water solubility, well monodispersion, and excellent biocompatibility. Spherical CDs had a particle size about 5 nm and exhibited a quantum yield of 8.85% at excitation wavelength of 360 nm. In addition, the CDs can serve as fluorescent probe for sensitive and selective detection of Fe3+ ions with the detection limit of 1.16 µM. Moreover, the potential of the as-prepared carbon dots for biological application was confirmed by employing it for fluorescence imaging in MCF-7 cells.

Energy-Efficient Oil-Water Separation of Biomimetic Copper Membrane with Multiscale Hierarchical Dendritic Structures.

Membrane-based materials with special surface wettability have been applied widely for the treatment of increasing industrial oily waste water, as well as frequent oil spill accidents. However, traditional technologies are energy-intensive and limited, either by fouling or by the inability of a single membrane to separate all types of oil-water mixtures. Herein, a biomimetic monolayer copper membrane (BMCM), composed of multiscale hierarchical dendritic structures, is cleverly designed and successfully fabricated on steel mesh substrate. It not only possesses the ability of energy-efficient oil-water separation but also excellent self-recovery anti-oil-fouling properties (<150 s). The BMCM even keeps high separation efficiency (>93%) after ten-time cycling tests. More importantly, it retains efficient oil-water separation capacity for five different oils. In fact, these advanced features are benefited by the synergistic effect of chemical compositions and physical structures, which is inspired by the typical nonwetting strategy of butterfly wing scales. The findings in this work may inspire a facile but effective strategy for repeatable and antipollution oil-water separation, which is more suitable for various applications under practical conditions, such as wastewater treatment, fuel purification, separation of commercially relevant oily water, and so forth.

A High-Transmission, Multiple Antireflective Surface Inspired from Bilayer 3D Ultrafine Hierarchical Structures in Butterfly Wing Scales.

A high-transmission, multiple antireflective surface inspired by bilayer 3D ultrafine hierarchical structures in butterfly wing scales is fabricated on a glass substrate using wet chemical biomimetic fabrication. Interestingly, the biomimetic antireflective surface exhibits excellent antireflective properties and high transmission, which provides better characteristics than the butterfly wings and can significantly reduce reflection without losing transparency. These findings offer a new path for generating nanostructured antireflectors with high transmission properties.

A highly selective dual-signal response ratiometric fluorescence sensing strategy for malachite green in fish based on carbon dots/copper nanoclusters nanocomposite.

Malachite green (MG), a widely used antiparasitic agent, poses health risks to human due to its genotoxic and carcinogenic properties. Herein, a stable dual-emission fluoroprobe of carbon dots/copper nanoclusters is prepared for highly selective detection of MG based on the inner filter effect. This probe exhibits characteristic emission bands at 435 and 625 nm when excited at 376 nm. After adding MG, the both emission signals were significantly quenched, and the ratio of fluorescence intensity (F435/F625) was linearly related to the concentration of MG in the range of 0.05-40 µmol L-1 with a limit of detection of 18.2 nmol L-1. Meanwhile, the two signals exhibit linear relationships with the concentration of MG, respectively, and the corresponding detection results were consistent. The fluoroprobe was successfully used for the detection of MG in fish samples with the recoveries ranging from 96.0% to 103.8% and a relative standard deviation of <3.3%.

Additive Manufacturing Provides Infinite Possibilities for Self-Sensing Technology.

Integrating sensors and other functional parts in one device can enable a new generation of integrated intelligent devices that can perform self-sensing and monitoring autonomously. Applications include buildings that detect and repair damage, robots that monitor conditions and perform real-time correction and reconstruction, aircraft capable of real-time perception of the internal and external environment, and medical devices and prosthetics with a realistic sense of touch. Although integrating sensors and other functional parts into self-sensing intelligent devices has become increasingly common, additive manufacturing has only been marginally explored. This review focuses on additive manufacturing integrated design, printing equipment, and printable materials and stuctures. The importance of the material, structure, and function of integrated manufacturing are highlighted. The study summarizes current challenges to be addressed and provides suggestions for future development directions.

Bio-inspired copper ion-chelated chitosan coating modified UHMWPE fibers for enhanced interfacial properties of composites.

Ultra-high molecular weight polyethylene (UHMWPE) fibers are broadly applied in lightweight and high-strength composite fiber materials. However, the development of UHMWPE fibers is limited by their smooth and chemically inert surfaces. To address the issues, a modified UHMWPE fibers material has been fabricated through the chelation reaction between Cu2+ and chitosan coatings within the surface of fibers after plasma treatment, which is inspired by the hardening mechanism, a crosslinked network between metal ions and proteins/polysaccharides of the tips and edges in arthropod-specific cuticular tools. The coatings improve the surface wettability and interfacial bonding ability, which are beneficial in extending the application range of UHMWPE fibers. More importantly, compared to the unmodified UHMWPE fiber cloths, the tensile property of the modified fiber cloths is increased by 18.89% without damaging the strength, which is infrequent in modified UHMWPE fibers. Furthermore, the interlaminar shear strength and fracture toughness of the modified fibers laminate are increased by 37.72% and 135.90%, respectively. These improvements can be attributed to the synergistic effects between the surface activity and the tiny bumps of the modified UHMWPE fibers. Hence, this work provides a more straightforward and less damaging idea of fiber modification for manufacturing desirable protective and medical materials.

High-Fidelity, Low-Hysteresis Bionic Flexible Strain Sensors for Soft Machines.

Stretchable flexible strain sensors based on conductive elastomers are rapidly emerging as a highly promising candidate for popular wearable flexible electronic and soft-mechanical sensing devices. However, due to the intrinsic limitations of low fidelity and high hysteresis, existing flexible strain sensors are unable to exploit their full application potential. Herein, a design strategy for a successive three-dimensional crack conductive network is proposed to cope with the uncoordinated variation of the output resistance signal arising from the conductive elastomer. The electrical characteristics of the sensor are dominated by the successive crack conductive network through a greater resistance variation and a concise sensing mechanism. As a result, the developed elastomer bionic strain sensors exhibit excellent sensing performance in terms of a smaller overshoot response, a lower hysteresis (∼2.9%), and an ultralow detection limit (0.00179%). What's more, the proposed strategy is universal and applicable to many conductive elastomers with different conductive fillers (including 0-D, 1-D, and 2-D conductive fillers). This approach improves the sensing signal accuracy and reliability of conductive elastomer strain sensors and holds promising potential for various applications in the fields of e-skin and soft robotic systems.

Investigating Novel Therapeutic Approaches for Idiopathic Short Stature: Targeting siRNA and Growth Hormone Delivery to the Growth Plate Using Exosome Nanoparticles.

Idiopathic short stature (ISS) is a common childhood condition with largely unknown underlying causes. Recent research highlights the role of circulating exosomes in the pathogenesis of various disorders, but their connection to ISS remains unexplored. In the experiments, human chondrocytes are cocultured with plasma exosomes from ISS patients, leading to impaired chondrocyte growth and bone formation. Elevated levels of a specific long non-coding RNA (lncRNA), ISSRL, are identified as a distinguishing factor in ISS, boasting high specificity and sensitivity. Silencing ISSRL in ISS plasma exosomes reverses the inhibition of chondrocyte proliferation and bone formation. Conversely, overexpression of ISSRL in chondrocytes impedes their growth and bone formation, revealing its mechanism of action through the miR-877-3p/GZMB axis. Subsequently, exosomes (CT-Exo-siISSRL-oeGH) with precise cartilage-targeting abilities are engineered, loaded with customized siRNA for ISSRL and growth hormone. This innovative approach offers a therapeutic strategy to address ISS by rectifying abnormal non-coding RNA expression in growth plate cartilage and delivering growth hormone with precision to promote bone growth. This research provides valuable insights into ISS diagnosis and treatment, highlighting the potential of engineered exosomes.

Fabrication of ß-cyclodextrin-polyacrylamide/covalent organic framework hydrogel at room temperature for the efficient removal of triazole fungicides from environmental water.

Triazole is frequently-used fungicide, which can leach into surface water through farmland and cause serious environmental pollution. Continuous exposure to triazole fungicides may cause harm to human health. Herein, ß-cyclodextrin-polyacrylamide/covalent organic framework (ß-CD-PAAM/TFPB-BD) hydrogel was fabricated at room temperature and used for the efficient removal of triazole fungicides. It displayed a short adsorption equilibrium time (50 min) and a total qe of 79.92 mg g-1. The adsorption process for triazole fungicides on ß-CD-PAAM/TFPB-BD hydrogel conforms to the pseudo-second-order kinetic model and Freundlich model. The prepared hydrogel was recyclable and resistant to salt, high temperature, acid, and alkali. The reusability of fabricated sorbent can be achieved (i.e., five extraction cycles) for removal of target fungicides. Moreover, the ß-CD-PAAM/TFPB-BD hydrogel was successfully applied to remove triazole fungicides in environmental water with removal efficiency ranging from 79.4% to 99.0%.

Effectiveness of non-pharmacological therapies on cognitive function in patients with dementia-A network meta-analysis of randomized controlled trials.

Objective: Non-pharmacological therapies (NPTs) have received increasing attention from researchers as a category of treatment to improve cognitive impairment in patients with dementia because of their fewer side effects. In this study, photobiomodulation (PBM), enriched environment (EE), exercise therapy (ET), computerized cognitive training (CCT), and cognitive stimulation therapy (CST) were selected to compare the effects of NPTs that improve dementia by quantifying information from randomized controlled trials (RCTs). Methods: We did a systematic review and network meta-analysis. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure Database, Wan Fang Database, Chinese Biomedical Literature Database, Web of Science, and VIP Database from the time of database creation to 1 August 2022. Two investigators independently screened the literature, extracted information, and assessed the RCTs' quality with the Cochrane Collaboration Network Risk of Bias 2.0. Network meta-analysis was performed using R language (X64 version 4.1.3) and STATA 17.0. Results: We identified 1,268 citations and of these included 38 trials comprising 3,412 participants. For improving dementia, the results of the network meta-analysis showed that compared with the control group (CON), PBM (SMD = 0.90, 95% CI: 0.43-1.37), EE (SMD = 0.71, 95% CI: 0.02-1.41), ET (SMD = 0.42, 95% CI: 0.16-0.68), and CST (SMD = 0.36, 95% CI: 0.11-0.62) were significantly different (P < 0.05); There was no significant difference in CCT (SMD = 0.41, 95% CI: -0.07-0.88) (P > 0.05). The ranked results showed that PBM has more potential to be the best intervention (P = 0.90). In addition, there was a significant difference between PBM and CST in improving cognitive function (SMD = 0.54, 95% CI: 0.00; 1.08, P < 0.05). Conclusion: In this study, NPTs have excellent potential to improve cognition in people with dementia, and PBM may have more significant benefits in improving cognition than the other four NPTs. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022363746.

Beauvericin suppresses the proliferation and pulmonary metastasis of osteosarcoma by selectively inhibiting TGFBR2 pathway.

Osteosarcoma (OS) patients, particularly those with distant metastasis, experience rapid progression and derive poor survival benefits from traditional therapies. Currently, effective drugs for treating patients with metastatic OS remain scarce. Here, we found that the cyclic hexadepsipeptide beauvericin (BEA) functioned as a new selective TGFBR2 inhibitor with potent antiproliferative and antimetastatic activities against OS cells. Functionally, BEA inhibited TGF-ß signaling-mediated proliferation, invasiveness, mesenchymal phenotype, and extracellular matrix remodeling of OS cells, and suppressed tumor growth and reduced pulmonary metastasis in vivo. Mechanistic investigation revealed that BEA selectively and directly bound to Asn 332 of TGFBR2 and inhibited its kinase activity, thereby suppressing the aggressive progression of OS cells. Together, our study identifies an innovative and natural selective TGFBR2 inhibitor with effective antineoplastic activity against metastatic OS and demonstrates that targeting TGFBR2 could be a potential therapeutic strategy for metastatic OS.

One-Step Fabrication of Hot-Water-Repellent Surfaces.

Hot-water repellency is of great challenge on traditional superhydrophobic surfaces due to the condensation of tiny droplets within the cavities of surface textures, which builds liquid bridges to connect the substrate and hot water and thus destroys the surface water-repellence performance. For the unique structural features and scales, current approaches to fabricate surfaces with hot-water repellency are always complicated and modified by fluorocarbon. Here, we propose a facile and fluorine-free one-step vapor-deposition method for fabricating excellent hot-water-repellent surfaces, which at room temperature even repel water droplets of temperature up to 90 °C as well as other normal-temperature droplets with surface tension higher than 48.4 mN/m. We show that whether the unique hot-water repellency is achieved depends on a trade-off between the solid-liquid contact time and hot-vapor condensation time, which determines the probability of formation of liquid bridges between the substrate and hot-water. Moreover, the designed surfaces exhibit excellent self-cleaning performance in some specific situations, such as oil medium, hot water and condensation environments. We envision that this facile and fluorine-free strategy for fabricating excellent hot-water-repellent surfaces could be valuable in popularizing their practical applications.

Degradable Bioinspired Hypersensitive Strain Sensor with High Mechanical Strength Using a Basalt Fiber as a Reinforced Layer.

Flexible strain sensors have received extensive attention due to their broad application prospects. However, a majority of present flexible strain sensors may fail to maintain normal sensing performances upon external loads because of their low strength and thus their performances are affected drastically with increasing loads, which severely restricts large-area popularization and application. Scorpions with hypersensitive vibration slit sensilla are coincident with a similar predicament. Herein, it is revealed that scorpions intelligently use risky slits to detect subtle vibrations, and meanwhile, the distinct layered composites of the main body of this organ prevent catastrophic failure of the sensory structure. Furthermore, the extensive use of flexible sensors will generate a mass of electronic waste just as obsoleting silicon-based devices. Considering mechanical properties and environmental issues, a flexible strain sensor based on an elastomer (Ecoflex)-wrapped fabric with the woven structure was designed and fabricated. Note that introducing a "green" basalt fiber (BF) into a degradable elastomer can effectively avoid environmental issues and significantly enhance the mechanical properties of the sensor. As a result, it shows excellent sensitivity (gauge factor (GF) ∼138.10) and high durability (∼40,000 cycles). Moreover, the reduced graphene oxide (RGO)/BF/Ecoflex flexible strain sensor possesses superior mechanical properties (tensile strength ∼20 MPa) and good flexibility. More significantly, the sensor can maintain normal performances under large external tensions, impact loads, and even underwater environments, providing novel design principles for environmentally friendly flexible sensors under extremely harsh environments.