Topoisomerase I is an Evolutionarily Conserved Key Regulator for Satellite DNA Transcription.

Repetitive satellite DNAs, divergent in nucleic-acid sequence and size across eukaryotes, provide a physical site for centromere assembly to orchestrate chromosome segregation during the cell cycle. These non-coding DNAs are transcribed by RNA polymerase (RNAP) II and the transcription has been shown to play a role in chromosome segregation, but a little is known about the regulation of centromeric transcription, especially in higher organisms with tandemly-repeated-DNA-sequence centromeres. Using RNA interference knockdown, chemical inhibition and AID/IAA degradation, we show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite on centromeres in human cells. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation on centromeres. Interestingly, in response to DNA double-stranded breaks (DSBs) induced by chemotherapy drugs or CRSPR/Cas9, α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner. These DSB-induced α-satellite RNAs were predominantly derived from the α-satellite high-order repeats of human centromeres and forms into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.

Superhydrophobic, Highly Conductive, and Trilayered Fabric with Connected Carbon Nanotubes for Energy-Efficient Electrical Heating.

Current electrically heated fabrics provide heat in cold climates, suffer from abundant wasted radiant heat energy to the external environment, and are prone to damage by water. Thus, constructing energy-efficient and superhydrophobic conductive fabrics is in high demand. Therefore, we propose an effective and facile methodology to prepare a superhydrophobic, highly conductive, and trilayered fabric with a connected carbon nanotube (CNT) layer and a titanium dioxide (TiO2) nanoparticle heat-reflecting layer. We construct polyamide/fluorinated polyurethane (PA/FPU) nanofibrous membranes via first electrospinning, then performing blade-coating with the polyurethane (PU) solution with CNTs, and finally fabricating FPU/TiO2 nanoparticles via electrospraying. This strategy causes CNTs to be connected to form a conductive layer and enables TiO2 nanoparticles to be bound together to form a porous, heat-reflecting layer. As a consequence, the as-prepared membranes demonstrate high conductivity with an electrical conductivity of 63 S/m, exhibit rapid electric-heating capacity, and exhibit energy-efficient asymmetrical heating behavior, i.e., the heating temperature of the PA/FPU nanofibrous layer reaches more than 83 °C within 90 s at 24 V, while the heating temperature of the FPU/TiO2 layer only reaches 53 °C, as well as prominent superhydrophobicity with a water contact angle of 156°, indicating promising utility for the next generation of electrical heating textiles.

Hepatic LGR4 aggravates cholestasis-induced liver injury in mice.

Current therapy for hepatic injury induced by the accumulation of bile acids is limited. Leucine-rich repeat G protein-coupled receptor 4 (LGR4), also known as GPR48, is critical for cytoprotection and cell proliferation. Here, we reported a novel function for the LGR4 in cholestatic liver injury. In the bile duct ligation (BDL)-induced liver injury model, hepatic LGR4 expression was significantly downregulated. Deficiency of LGR4 in hepatocytes (Lgr4LKO) notably decreased BDL-induced liver injury measured by hepatic necrosis, fibrosis, and circulating liver enzymes and total bilirubin. Levels of total bile acids in plasma and liver were markedly reduced in these mice. However, deficiency of LGR4 in macrophages (Lyz2-Lgr4MKO) demonstrated no significant effect on liver injury induced by BDL. Deficiency of LGR4 in hepatocytes significantly attenuated S1PR2 and the phosphorylation of protein kinase B (AKT) induced by BDL. Recombinant Rspo1 and Rspo3 potentiated the taurocholic acid (TCA)-induced upregulation in S1PR2 and phosphorylation of AKT in hepatocytes. Inhibition of S1PR2-AKT signaling by specific AKT or S1PR2 inhibitors blocked the increase of bile acid secretion induced by Rspo1/3 in hepatocytes. Our studies indicate that the R-spondins (Rspos)-LGR4 signaling in hepatocytes aggravates the cholestatic liver injury by potentiating the production of bile acids in a S1PR2-AKT-dependent manner.NEW & NOTEWORTHY Deficiency of LGR4 in hepatocytes alleviates BDL-induced liver injury. LGR4 in macrophages demonstrates no effect on BDL-induced liver injury. Rspos-LGR4 increases bile acid synthesis and transport via potentiating S1PR2-AKT signaling in hepatocytes.

Entrapment of atmospheric particle bound heavy metals by ferns as evidenced by lead (Pb) isotope and MixSIAR: Implications for improving air quality.

Plant metal uptake can occur through both soil-root and atmospheric transfer from leaves. The latter holds potential implications for development of biofiltration systems. To explore this potential, it is crucial to understand entrapment capacity and metal sources within plants. As ferns absorb materials from atmosphere, this study focuses on two abundant fern species growing in densely populated and highly polluted regions of Eastern India. Gravimetric quantification, elemental concentration and Pb isotopic analyses were performed by segregating the ferns into distinct components: foliage dusts (loose dust (LD) and wax-bound dust (WD)) and plant tissue (leaves and roots). To understand metal sources, the study analyzes soil, and atmospheric particulates (PM10 and dust fall (DF)). Results indicate that, while LDs have soil dust influence, wax entraps atmospheric particulates and translocates them inside the leaves. Furthermore, roots demonstrate dissimilar isotopic ratios from soil, while displaying close association with atmospheric particulates. Isotopic composition and subsequent mixing model reveal dominant contribution from DF in leaves (53-73%) and roots (33-86%). Apart from DF, leaf Pb is sourced from PM10 (21-38%) with minimal contribution from soil (6-10%). Conversely, in addition to dominance from DF, roots source Pb primarily from soil (12-62%) with a meagre 2-8% contribution from PM10.

Nutrients recovery by coupled bioreactor of heterotrophic ammonia assimilation and microbial fuel cell in saline wastewater.

Heterotrophic ammonia assimilation (HAA) process had been widely used in the treatment of high salt wastewater, but the electro enhanced coupling process and electron transfer process were rarely studied. In this study, a HAA process coupled microbial fuel cell (MFC) system was established to treat ammonia-containing wastewater under increasing salinity to achieve nitrogen recovery and electricity generation. Up to 95.4 % NH4+-N and 96.4 % COD removal efficiencies were achieved at 2 % salinity in HAA-MFC. The maximum power density and current density at 2 % salinity were 29.93 mW/m2 and 182.37 mA/m2, respectively. The residual organic matter in the cathode effluent was effectively removed by the anode. The increase of salinity not only enhanced the sludge settling performance and activity, but also promoted the enzyme activity and amino acid production of the ammonia assimilation pathway. Marinobacter and Halomonas were gradually enriched at the anode and cathode with increased salinity to promote ammonia assimilation and electron production. This research offered a promising solution to overcome salinity-related challenges in wastewater treatment and resource recovery.

Diphylleia Grayi-Inspired Intelligent Temperature-Responsive Transparent Nanofiber Membranes.

Nanofiber membranes (NFMs) have become attractive candidates for next-generation flexible transparent materials due to their exceptional flexibility and breathability. However, improving the transmittance of NFMs is a great challenge due to the enormous reflection and incredibly poor transmission generated by the nanofiber-air interface. In this research, we report a general strategy for the preparation of flexible temperature-responsive transparent (TRT) membranes, which achieves a rapid transformation of NFMs from opaque to highly transparent under a narrow temperature window. In this process, the phase change material eicosane is coated on the surface of the polyurethane nanofibers by electrospray technology. When the temperature rises to 37 °C, eicosane rapidly completes the phase transition and establishes the light transmission path between the nanofibers, preventing light loss from reflection at the nanofiber-air interface. The resulting TRT membrane exhibits high transmittance (> 90%), and fast response (5 s). This study achieves the first TRT transition of NFMs, offering a general strategy for building highly transparent nanofiber materials, shaping the future of next-generation intelligent temperature monitoring, anti-counterfeiting measures, and other high-performance devices.

TLN1 synergizes with ITGA5 to ameliorate cardiac microvascular endothelial cell dysfunction.

BACKGROUND: The complex process of atherosclerosis is thought to begin with endothelial cell dysfunction, and advanced atherosclerosis is the underlying cause of coronary artery disease (CAD). Uncovering the underlying mechanisms of CAD-related endothelial cell injury may contribute to the treatment. MATERIALS AND METHODS: Cardiac microvascular endothelial cells (CMVECs) were treated with oxidised low-density lipoprotein (ox-LDL) to mimic an injury model. The involvement of Talin-1 (TLN1) and integrin alpha 5 (ITGA5) in the proliferation, apoptosis, angiogenesis, inflammatory response, and oxidative stress in CMVECs were assessed. RESULTS: TLN1 overexpression assisted CMVECs in resistance to ox-LDL stimulation, with alleviated cell proliferation and angiogenesis, reduced apoptosis, inflammatory response, and oxidative stress. TLN1 overexpression triggered increased ITGA5, and ITGA5 knockdown reversed the effects of TLN1 overexpression on the abovementioned aspects. Together, TLN1 synergized with ITGA5 to ameliorate the dysfunction in CMVECs. CONCLUSIONS: This finding suggests their probable involvement in CAD, and increasing their levels is beneficial to disease relief.

Two-Dimensional Nanofibrous Networks by Superspreading-Based Phase Inversion for High-Efficiency Separation.

Two-dimensional (2D) nanomaterials have been widely applied as building blocks of nanoporous materials for high-precision separations. However, most existing 2D nanomaterials suffer from poor continuity and a lack of interior linking, resulting in deteriorated performance when assembled into macroscopic bulk structures. Here, a unique superspreading-based phase inversion technique is proposed to directly construct 2D nanofibrous networks (NFNs) from a polymer solution. By tailoring capillary behavior, polymer solution droplets evolve into ultrathin liquid films through superspreading; manipulating phase instability, subsequently, enables the liquid film to phase invert into continuous nanostructured networks. The assembled single-layered NFNs possess integrated structural superiorities of 1D nanoscale fiber diameter (∼40 nm) and 2D lateral infinity, exhibiting a weblike nanoarchitecture with extremely small through-pores (∼100 nm). Our NFNs show remarkable performances in air filtration (PM0.3 removal) and water purification (microfiltration level). This creation of such attractive 2D fibrous nanomaterials can pave the way for versatile high-performance separation applications.

CASP1 is a target for combination therapy in pancreatic cancer.

Gemcitabine (GEM) is commonly used as the first-line chemotherapeutic agent for treating pancreatic cancer (PC) patients. However, drug resistance is a major hurdle in GEM-based chemotherapy for PC. Recent studies have shown that pyroptosis, a type of programmed death, plays a significant regulatory role in cancer development and therapy. In this study, we observed an increase in the expression of Caspase-1(CASP1)/Gasdermin-D (GSDMD) in PC and found that high expression of CASP1 and GSDMD was associated with poor overall survival (OS) and progression-free survival (PFS) of PC patients. Knockdown of either CASP1 or GSDMD resulted in the inhibition of cell viability and migration in PC cells. More importantly, the knockdown of CASP1 or GSDMD enhanced GEM-induced cell death in PC cells. Interestingly, subsequent investigations demonstrated that enzymatically active CASP1 promoted GEM-induced cell death in PC cells. The activation of CASP1 by the DPP8/DPP9 inhibitor (Val-boroPro, VbP) increased GEM-induced cell death by inducing pyroptosis. These findings suggest that inhibiting CASP1 to suppress its oncogenic effects or activating it to promote cell pyroptosis both enhance the sensitivity of PC cells to GEM therapy.

Sweat Gland-Inspired Skin-like Fabric with Directional Water Transport and Durability for Efficient Personal Moisture Management.

Directional water transport textiles are an energy-free approach to improving the comfort of the human body. However, existing strategies mainly focus on enhancing the capacity of directional water transport, complicating the preparation process and limiting the long-term durability of textiles. Herein, a skin-like fabric inspired by sweat glands was prepared in one step by patterning printed hydrophobic paste on the fabric. This skin-like fabric has achieved the desired one-way water transport index (R, 721%), air permeability of 104 mm s-1, and water vapor transmission rate (298 g m-2 h-1). More significantly, due to the strong chemical bonds between the fabric and the coating, the skin-like fabric exhibited a high weight retention of 99.4% after 400 abrasion cycles and stable performance (R, 658%) after 25 h of washing. This work proposes a reliable way to prepare high-performance fabrics with durability, which show great potential for applications in functional textiles for personal moisture management.

The strength, position, and width changes of the intertropical convergence zone since the Last Glacial Maximum.

The intertropical convergence zone (ITCZ) plays a key role in regulating tropical hydroclimate and global water cycle through changes in its convection strength, latitudinal position, and width. The long-term variability of the ITCZ, along with the corresponding driving mechanisms, however, remains obscure, mainly because it is difficult to separate different ITCZ variables in paleoclimate proxy records. Here, we report a speleothem oxygen isotope (δ18O) record from southwestern Sulawesi, Indonesia, and compile it with other speleothem records from the Maritime Continent. Using the spatial gradient of speleothem δ18O along a transect across the ITCZ, we constrain ITCZ variabilities over the Maritime Continent during the past 30,000 y. We find that ITCZ convection strength overall intensified from the last glacial period to the Holocene, following changes in climate boundary conditions. The mean position of the regional ITCZ has moved latitudinally no more than 3° in the past 30,000 y, consistent with the deduction from the atmospheric energy framework. However, different from modern observations and model simulations for future warming, the ITCZ appeared narrower during both the late Holocene and most part of the last glacial period, and its expansion occurred during Heinrich stadials and the early-to-mid Holocene. We also find that during the last glacial and deglacial period, prominent millennial-scale ITCZ changes were closely tied to the variability of the Atlantic meridional overturning circulation (AMOC), whereas during the Holocene, they were predominantly modulated by the long-term variability of the Walker circulation.

High-Performance Waterproof, Breathable, and Radiative Cooling Membranes Based on Nanoarchitectured Fiber/Meshworks.

Smart membranes with protection and thermal-wet comfort are highly demanded in various fields. Nevertheless, the existing membranes suffer from a tradeoff dilemma of liquid resistance and moisture permeability, as well as poor thermoregulating ability. Herein, a novel strategy, based on the synchronous occurrence of humidity-induced electrospinning and electromeshing, is developed to synthesize a dual-network structured nanofiber/mesh for personal comfort management. Manipulating the ejection, deformation, and phase separation of spinning jets and charged droplets enables the creation of nanofibrous membranes composed of radiative cooling nanofibers and 2D nanostructured meshworks. With a combination of a true-nanoscale fiber (∼70 nm) in 2D meshworks, a small pore size (0.84 µm), and a superhydrophobic surface (151.9°), the smart membranes present high liquid repellency (95.6 kPa), improved breathability (4.05 kg m-2 d-1), and remarkable cooling performance (7.9 °C cooler than commercial cotton fabrics). This strategy opens up a pathway to the design of advanced smart textiles for personal protection.

EGFR signaling controls directionality of epithelial multilayer formation upon loss of cell polarity.

Apical-basal polarity is maintained by distinct protein complexes that reside in membrane junctions, and polarity loss in monolayered epithelial cells can lead to formation of multilayers, cell extrusion, and/or malignant overgrowth. Yet, how polarity loss cooperates with intrinsic signals to control directional invasion toward neighboring epithelial cells remains elusive. Using the Drosophila ovarian follicular epithelium as a model, we found that posterior follicle cells with loss of lethal giant larvae (lgl) or Discs large (Dlg) accumulate apically toward germline cells, whereas cells with loss of Bazooka (Baz) or atypical protein kinase C (aPKC) expand toward the basal side of wildtype neighbors. Further studies revealed that these distinct multilayering patterns in the follicular epithelium were determined by epidermal growth factor receptor (EGFR) signaling and its downstream target Pointed, a zinc-finger transcription factor. Additionally, we identified Rho kinase as a Pointed target that regulates formation of distinct multilayering patterns. These findings provide insight into how cell polarity genes and receptor tyrosine kinase signaling interact to govern epithelial cell organization and directional growth that contribute to epithelial tumor formation.

Rapid and sensitive detection of Pseudomonas aeruginosa by isothermal amplification combined with Cas12a-mediated detection.

CRISPR based technologies have been used for fast and sensitive detection of pathogens. To test the possibility of CRISPR based detection strategy in Pseudomonas aeruginosa infections, a combined method of recombinase polymerase amplification followed by Cas12a-mediated detection via fluorescence reader or lateral flow biosensor (named Cas12a-RCFL) has been established in this study. The Cas12a-RCFL can detect as low as 50 CFU/mL Pseudomonas aeruginosa. The whole detection process can be finished within one hour with satisfied detection specificity. Cas12a-RCFL also shows good sensitivity of detecting Pseudomonas aeruginosa inStaphylococcus aureus and Acinetobacter baumannii contaminated samples. For the detection of 22 clinical samples, Cas12a-RCFL matches with PCR sequencing result exactly without DNA purification. This Cas12a-RCFL is rapid and sensitive with low cost, which shows good quality to be adopted as a point-of-care testing method.

Identification of m5C-related molecular subtypes and prediction models in the prognosis and tumor microenvironment infiltration of soft tissue sarcoma.

Background: The epigenetic regulator in cancer progression and immune response has been demonstrated recently. However, the potential implications of 5-methylcytosine (m5C) in soft tissue sarcoma (STS) are unclear. Methods: The RNA sequence profile of 911 normal and 259 primary STS tissues were obtained from GTEx and TCGA databases, respectively. We systematically analyzed the m5C modification patterns of STS samples based on 11 m5C regulators, and comprehensively correlated these modification patterns with clinical characteristics, prognosis, and tumor microenvironment (TME) cell-infiltrating. Furthermore, an m5C-related signature was generated using Cox proportional hazard model and validated by the GSE17118 cohort. Results: Two distinct m5C modification patterns (cluster1/2) were discovered. The cluster1 had favorable overall survival, higher immune score, higher expression of most immune checkpoints, and active immune cell infiltration. The GSVA analysis of the P53 pathway, Wnt signaling pathway, G2M checkpoint, mTORC1 signaling, Wnt/ß catenin signaling, and PI3K/AKT/mTOR signaling were significantly enriched in the cluster2. Moreover, 1220 genes were differentially expressed between two clusters, and a m5C prognostic signature was constructed with five m5C-related genes. The signature represented an independent prognostic factor and showed the favorable performance in the GSE17118 cohort. Patients in the low-risk group showed higher immunoscore and higher expression of most immune checkpoints. Further GSVA analysis indicated that the levels of P53 pathway, Wnt signaling pathway, and TGF-ß signaling pathway were different between low- and high-risk groups. Moreover, a nomogram incorporating m5C signature and clinical variables was established and showed well performance. Conclusion: This work showed that the m5C modification plays a significant role in the progression of STS and the formation of TME diversity. Evaluating the m5C modification pattern of tumor will enhance our cognition of TME infiltration characterization to guide more effective immunotherapy strategies.

Function verification of a chlorophyll a/b binding protein gene through a newly established tobacco rattle virus-induced gene silencing system in Kandelia obovata.

As an important mangrove species, Kandelia obovata plays an irreplaceable role in the coastal ecosystem. However, due to a lack of genetic technology, there is limited research on its functional genes. As such, establishing an efficient and rapid functional verification system is particularly important. In this study,tobacco rattle virus (TRV) and the phytoene desaturase gene KoPDS were used as the vector and target gene, respectively, to establish a virus-induced gene silencing system (VIGS) in K. obovata. Besides, the system was also used to verify the role of a Chlorophyll a/b binding protein (Cab) gene KoCAB in leaf carbon sequestration of K. obovata. RNA-Seq and qRT-PCR showed that the highest gene-silencing efficiency could reach 90% after 10 days of inoculation and maintain above 80% after 15 days, which was achieved with resuspension buffer at pH 5.8 and Agrobacterium culture at OD600 of 0.4-0.6. Taken together, the TRV-mediated VIGS system established herein is the first genetic analysis tool for mangroves, which may greatly impel functional genomics studies in mangrove plants.

A Fiber Sliding-Orientation Based Micromechanics Failure Model for Melt-Blown Nonwovens.

The mechanical model of melt-blown nonwovens (MNs) serves as the foundation for performance optimization, which can offer helpful guidance for product material selection, structural design, and cost control. However, it is challenging to describe the micromechanics failure mechanism of MNs using the traditional mechanical model, which aims to match the model curve with the experimental result at the macrolevel. Herein, a micromechanics failure model for MNs based on sliding-orientation competition is developed. Through in situ observations of fiber position changes and the fluctuation of stress-strain curves, fiber sliding and orientation are introduced into the failure process of MNs. Due to fiber bonding and static friction, only orientation happens during the first stage of stretching. In dramatic contrast, the fibers will slide and orient in the second stage of stretching to change their positions in response to the external force. Sliding friction, fiber bonding, and static friction make up the stress of MNs, and the conflict of fiber sliding and orientation causes variations in the stress. The model has been successfully applied to polylactic acid (PLA) MNs, which proves the effectiveness of the model in MNs.

Synthesis of N,Si co-doped carbon dots to establish a fluorescent sensor for Hg(II) detection with triple signal output.

Mercury is a heavy metal with extreme toxicity. Thus, it is of significance to develop an effective method for mercury ion detection with high performance. In this study, carbon dots doped with nitrogen and silicon (N,Si/CQDs) were successfully prepared from folic acid and N-[3-(trimethoxysily)propyl]-ethylenediamine. The N,Si/CQDs show an obvious cyan fluorescence of 460 nm with the radiation of 350 nm. The existence of mercury ions induces the fluorescence quenching of N,Si/CQDs due to photoinduced electron transfer, which was applied for the sensitive sensing of Hg(II). More importantly, the practical application of the N,Si/CQD probe was confirmed by measurements of Hg(II) in real samples of lake water, sorghum and rice. In addition, the N,Si/CQD nanoprobe was integrated on a sensing strip for specific detection of Hg(II). Quantitative measurement of Hg(II) was realized by the outstanding linearity between the diameter (or fluorescence intensity) of the fluorescence quenching ring and the concentration of mercury ions. The sensor shows potential for rapid detection with a triple signal readout on-site and represents a larger step towards practical applications.

Synthesis of rare-earth metal-organic frameworks to construct high-resolution sensing array for multiplex anions detection, cell imaging and blood phosphorus monitoring.

Accurate detection and differentiation of multiple anions is still a difficult problem due to their wide variety, structural similarity, and mutual interference. Hence, four rare-earth metal-organic frameworks (RE-MOFs) including Dy-MOFs, Er-MOFs, Tb-MOFs and Y-MOFs are successfully prepared by using TCPP as the ligand and rare-earth ions as the metal center via coordination chelation. It is found that 7 anions can light up their fluorescence. Thus, a high-resolution sensing array based on RE-MOFs nanoprobes is employed to differentiate these anions from intricate analytes in real-time scenarios. The distinctive host-guest response promotes the RE-MOFs nanoprobes to selectively extract the target anions from the complex samples. By taking advantage of the cross-response between RE-MOFs nanoprobes and anions, it allows to create an array for detecting target analytes using pattern recognition. Additionally, RE-MOFs nanoprobes also facilitate the quantitative analysis of these anions (PO43-, H2PO4-, HPO42-, F-, S2-, CO32- and C2O42-). More importantly, the exceptional effectiveness of this method has been demonstrated through various successful applications, including quality monitoring of 8 toothpaste brands, intracellular phosphate imaging, and blood phosphorus detection in mice with vascular calcification. These findings provide robust evidence for the efficacy and reliability of the RE-MOFs nanoprobes array for anion recognition.

Aortic smooth muscle TRPV4 channels regulate vasoconstriction in high salt-induced hypertension.

Recent studies have focused on the contribution of vascular endothelial transient receptor potential vanilloid 4 (TRPV4) channels to hypertension. However, in hypertension, TRPV4 channels in vascular smooth muscle remain unexplored. In the present study, we performed wire myograph experiments in isolated aortas from endothelial cell specific TRPV4 channel knockout (TRPV4EC-/-) mice to demonstrate that GSK1016790A (a specific TRPV4 channel agonist) triggered aortic smooth muscle-dependent contractions from mice on a normal-salt diet, and the contractions were enhanced in high-salt diet (HSD) mice. Intracellular Ca2+ concentration ([Ca2+]i) and Ca2+ imaging assays showed that TRPV4-induced [Ca2+]i was significantly higher in aortic smooth muscle cells (ASMCs) from HSD-induced hypertensive mice, and application of an inositol trisphosphate receptor (IP3R) inhibitor markedly attenuated TRPV4-induced [Ca2+]i. IP3R2 expression was enhanced in ASMCs from HSD-induced hypertensive mice and the contractile response induced by TRPV4 was inhibited by the IP3R inhibitor. Whole-transcriptome analysis by RNA-seq and western blot assays revealed the involvement of interferon regulatory factor 7 (IRF7) in TRPV4-IRF7-IP3R2 signaling in HSD-induced hypertension. These results suggested that TRPV4 channels regulate smooth muscle-dependent contractions in high salt-induced hypertension, and this contraction involves increased [Ca2+]i, IP3R2, and IRF7 activity. Our study revealed a considerable effect of TRPV4 channels in smooth muscle-dependent contraction in mice during high-salt induced hypertension.