Enzymatic independent role of sphingosine kinase 2 in regulating the expression of type I interferon during influenza A virus infection.

Influenza virus has the ability to circumvent host innate immune system through regulating certain host factors for its effective propagation. However, the detailed mechanism is still not fully understood. Here, we report that a host sphingolipid metabolism-related factor, sphingosine kinase 2 (SPHK2), upregulated during influenza A virus (IAV) infection, promotes IAV infection in an enzymatic independent manner. The enhancement of the virus replication is not abolished in the catalytic-incompetent SPHK2 (G212E) overexpressing cells. Intriguingly, the sphingosine-1-phosphate (S1P) related factor HDAC1 also plays a crucial role in SPHK2-mediated IAV infection. We found that SPHK2 cannot facilitate IAV infection in HDAC1 deficient cells. More importantly, SPHK2 overexpression diminishes the IFN-ß promoter activity upon IAV infection, resulting in the suppression of type I IFN signaling. Furthermore, ChIP-qPCR assay revealed that SPHK2 interacts with IFN-ß promoter through the binding of demethylase TET3, but not with the other promoters regulated by TET3, such as TGF-ß1 and IL6 promoters. The specific regulation of SPHK2 on IFN-ß promoter through TET3 can in turn recruit HDAC1 to the IFN-ß promoter, enhancing the deacetylation of IFN-ß promoter, therefore leading to the inhibition of IFN-ß transcription. These findings reveal an enzymatic independent mechanism on host SPHK2, which associates with TET3 and HDAC1 to negatively regulate type I IFN expression and thus facilitates IAV propagation.

BAP1 loss confers sensitivity to bromodomain and extra-terminal inhibitors in renal cell carcinoma.

The tumor suppressor gene BRCA1 associated protein-1 (BAP1) is frequently mutated in renal cell carcinoma (RCC). BAP1 loss-of-function mutations are associated with poor survival outcomes. However, personalized therapy for BAP1-mutated RCC is currently not available. Previously, we found that BAP1 loss renders RCC cells more sensitive to bromodomain and extra-terminal (BET) inhibitors, as demonstrated in both cell culture and xenografted nude mice models. Here, we demonstrate that BAP1 loss in murine RCC cells enhances sensitivity to BET inhibitors in ectopic and orthotopic allograft models. While BAP1 deletion suppresses RCC cell survival in vitro, it does not impede tumor growth in immunocompetent murine models. Thus, the effect of BAP1 loss on the interactions between tumor cells and host microenvironment plays a predominant role in RCC growth, highlighting the importance of utilizing immunocompetent animal models to assess the efficacy of potential anticancer therapies. Mechanistically, BAP1 deletion compromises DNA repair capacity, rendering RCC cells more vulnerable to DNA damage induced by BET inhibitors. Our results indicate that BET inhibitors show promise as targeted therapy for BAP1-deficient RCC.

Diosmetin as a promising natural therapeutic agent: In vivo, in vitro mechanisms, and clinical studies.

Diosmetin, a natural occurring flavonoid, is primarily found in citrus fruits, beans, and other plants. Diosmetin demonstrates a variety of pharmacological activities, including anticancer, antioxidant, anti-inflammatory, antibacterial, metabolic regulation, cardiovascular function improvement, estrogenic effects, and others. The process of literature search was done using PubMed, Web of Science and ClinicalTrials databases with search terms containing Diosmetin, content, anticancer, anti-inflammatory, antioxidant, pharmacological activity, pharmacokinetics, in vivo, and in vitro. The aim of this review is to summarize the in vivo, in vitro and clinical studies of Diosmetin over the last decade, focusing on studies related to its anticancer, anti-inflammatory, and antioxidant activities. It is found that DIO has significant therapeutic effects on skin and cardiovascular system diseases, and its research in pharmacokinetics and toxicology is summarized. It provides the latest information for researchers and points out the limitations of current research and areas that should be strengthened in future research, so as to facilitate the relevant scientific research and clinical application of DIO.

Enhancingß-Ga2O3-film ultraviolet detectors via RF magnetron sputtering with seed layer insertion onc-plane sapphire substrate.

Gallium oxide (Ga2O3) possesses a band gap of approximately 4.9 eV, aligning its detection wavelength within the solar-blind region, making it an ideal semiconductor material for solar-blind photodetectors. This study aims to enhance the performance of Ga2O3ultraviolet (UV) detectors by pre-depositing a Ga2O3seed layer on ac-plane sapphire substrate. The x-ray diffraction and x-ray photoelectron spectroscopy analyses validated that the deposited films, following high-temperature annealing, comprisedß-Ga2O3. Comparing samples with and without a 20 nm seed layer, it was found that the former exhibited fewer oxygen defects and substantially improved crystal quality. The incorporation of the seed layer led to the realization of detectors with remarkably low dark current (≤15.3 fA). Moreover, the photo-to-dark current ratio was enhanced by 30% (surpassing 1.3 × 104) and the response/recovery time reduced to 0.9 s/0.01 s, indicating faster performance. Furthermore, these detectors demonstrated higher responsivity (4.8 mA W-1), improved detectivity (2.49 × 1016Jones), and excellent solar-blind characteristics. This study serves as a foundational stepping toward achieving high-qualityß-Ga2O3thin film and UV detector arrays.

Research on optimal operation of cascade pumping stations based on an improved sparrow search algorithm.

For the low efficiency and large loss of cascade pumping stations, aiming to maximize system efficiency, an optimized scheduling model of cascade pumping stations is established with consideration of multiple constraints, and the optimal scheduling method based on the improved sparrow search algorithm (BSSA) is proposed. The BSSA is initialized by the Bernoulli chaotic map to solve the insufficient initial diversity of the sparrow search algorithm (SSA). The random boundary strategy is introduced to avoid local optimum when dealing with the scheduling problem of pumping stations. The performance and improvement strategy of BSSA are verified by eight benchmark functions. Results show that BSSA has better convergence accuracy and faster speed. BSSA is applied to a three-stage pumping station considering three flow conditions, and compared with the current scheme, particle swarm optimization and genetic algorithm optimization schemes, the operation efficiency of SSA can be increased by 0.72-0.96%, and operation cost can be reduced by ¥263,000/a-¥363,300/a. On this basis, the improvement of 0.04-0.30% and ¥14,800/a-¥109,900/a can be further achieved by the BSSA, which confirms the feasibility and effectiveness of BSSA to solve the pumping station optimal scheduling problem. The findings present useful reference for the optimized scheduling of pumping station system.

Reciprocal positive regulation between BRD4 and YAP in GNAQ-mutant uveal melanoma cells confers sensitivity to BET inhibitors.

Uveal melanoma (UM) is the most common intraocular cancer in adults. UMs are usually initiated by a mutation in GNAQ or GNA11 (encoding Gq or G11, respectively), unlike cutaneous melanomas (CMs), which usually carry a BRAF or NRAS mutation. Currently, there are no clinically effective targeted therapies for UM carrying Gq/11 mutations. Here, we identified a causal link between Gq activating mutations and hypersensitivity to bromodomain and extra-terminal (BET) inhibitors. BET inhibitors transcriptionally repress YAP via BRD4 regardless of Gq mutation status, independently of Hippo core components LATS1/2. In contrast, YAP/TAZ downregulation reduces BRD4 transcription exclusively in Gq-mutant cells and LATS1/2 double knockout cells, both of which are featured by constitutively active YAP/TAZ. The transcriptional interdependency between BRD4 and YAP identified in Gq-mutated cells is responsible for the preferential inhibitory effect of BET inhibitors on the growth and dissemination of Gq-mutated UM cells compared to BRAF-mutated CM cells in both culture cells and animal models. Our findings suggest BRD4 as a viable therapeutic target for Gq-driven UMs that are addicted to unrestrained YAP function.

PTEN loss confers sensitivity to rapalogs in clear cell renal cell carcinoma.

Rapalogs (everolimus and temsirolimus) are allosteric mTORC1 inhibitors and approved agents for advanced clear cell renal cell carcinoma (ccRCC), although only a subset of patients derive clinical benefit. Progress in genomic characterization has made it possible to generate comprehensive profiles of genetic alterations in ccRCC; however, the correlations between recurrent somatic mutations and rapalog efficacy remain unclear. Here, we demonstrate by using multiple patient-derived ccRCC cell lines that compared to PTEN-proficient cells, PTEN-deficient cells exhibit hypersensitivity to rapalogs. Rapalogs inhibit cell proliferation by inducing G0/G1 arrest without inducing apoptosis in PTEN-deficient ccRCC cell lines. Using isogenic cell lines generated by CRISPR/Cas9, we validate the correlation between PTEN loss and rapalog hypersensitivity. In contrast, deletion of VHL or chromatin-modifying genes (PBRM1, SETD2, BAP1, or KDM5C) fails to influence the cellular response to rapalogs. Our mechanistic study shows that ectopic expression of an activating mTOR mutant (C1483F) antagonizes PTEN-induced cell growth inhibition, while introduction of a resistant mTOR mutant (A2034V) enables PTEN-deficient ccRCC cells to escape the growth inhibitory effect of rapalogs, suggesting that PTEN loss generates vulnerability to mTOR inhibition. PTEN-deficient ccRCC cells are more sensitive to the inhibitory effects of temsirolimus on cell migration and tumor growth in zebrafish and xenograft mice, respectively. Of note, PTEN protein loss as detected by immunohistochemistry is much more frequent than mutations in the PTEN gene in ccRCC patients. Our study suggests that PTEN loss correlates with rapalog sensitivity and could be used as a marker for ccRCC patient selection for rapalog therapy.

BAP1 loss augments sensitivity to BET inhibitors in cancer cells.

The tumor suppressor gene BAP1 encodes a widely expressed deubiquitinase for histone H2A. Both hereditary and acquired mutations are associated with multiple cancer types, including cutaneous melanoma (CM), uveal melanoma (UM), and clear cell renal cell carcinoma (ccRCC). However, there is no personalized therapy for BAP1-mutant cancers. Here, we describe an epigenetic drug library screening to identify small molecules that exert selective cytotoxicity against BAP1 knockout CM cells over their isogenic parental cells. Hit characterization reveals that BAP1 loss renders cells more vulnerable to bromodomain and extraterminal (BET) inhibitor-induced transcriptional alterations, G1/G0 cell cycle arrest and apoptosis. The association of BAP1 loss with sensitivity to BET inhibitors is observed in multiple BAP1-deficient cancer cell lines generated by gene editing or derived from patient tumors as well as immunodeficient xenograft and immunocompetent allograft murine models. We demonstrate that BAP1 deubiquitinase activity reduces sensitivity to BET inhibitors. Concordantly, ectopic expression of RING1A or RING1B (H2AK119 E3 ubiquitin ligases) enhances sensitivity to BET inhibitors. The mechanistic study shows that the BET inhibitor OTX015 exerts a more potent suppressive effect on the transcription of various proliferation-related genes, especially MYC, in BAP1 knockout cells than in their isogenic parental cells, primarily by targeting BRD4. Furthermore, ectopic expression of Myc rescues the BET inhibitor-sensitizing effect induced by BAP1 loss. Our study reveals new approaches to specifically suppress BAP1-deficient cancers, including CM, UM, and ccRCC.

Spontaneous Formation of Ordered Magnetic Domains by Patterning Stress.

The formation of ordered magnetic domains in thin films is important for the magnetic microdevices in spin-electronics, magneto-optics, and magnetic microelectromechanical systems. Although inducing anisotropic stress in magnetostrictive materials can achieve the domain assembly, controlling magnetic anisotropy over microscale areas is challenging. In this work, we realized the microscopic patterning of magnetic domains by engineering stress distribution. Deposition of ferromagnetic thin films on nanotrenched polymeric layers induced tensile stress at the interfaces, giving rise to the directional magnetoelastic coupling to form ordered domains spontaneously. By changing the periodicity and shape of nanotrenches, we spatially tuned the geometric configuration of domains by design. Theoretical analysis and micromagnetic characterization confirmed that the local stress distribution by the topographic confinement dominates the forming mechanism of the directed magnetization.

Wrinkled Titanium Carbide (MXene) with Surface Charge Polarizations through Chemical Etching for Superior Electromagnetic Interference Shielding.

Despite the fact that the high conductivity of two-dimensional laminated transition metal carbides/nitrides (MXenes) contributes to the outstanding electromagnetic interference (EMI) shielding by the reflection of electromagnetic waves (EWs), it is difficulty to improve EMI shielding by pursuing higher conductivity due to the limitation of intrinsic properties. Here, we achieve superior EMI shielding by introducing the absorption of EWs in MXenes with micro-sized wrinkles which are induced by abundant Ti vacancies under chemical etching. The shielding effectiveness is up to 107 dB at a thickness of 20 µm. Combining with atomic-scale structure observation and the first-principles calculations, it is concluded that the promotion of EMI shielding originates from the resonant absorption of formed electric dipoles induced by the asymmetrical distribution of charge densities near Ti vacancies. Our results could open a new vista for developing two-dimensional EMI shielding materials.

Low-Field-Triggered Large Magnetostriction in Iron-Palladium Strain Glass Alloys.

Development of miniaturized magnetostriction-associated devices requires low-field-triggered large magnetostriction. In this study, we acquired a large magnetostriction (800 ppm) triggered by a low saturation field (0.8 kOe) in iron-palladium (Fe-Pd) alloys. Magnetostriction enhancement jumping from 340 to 800 ppm was obtained with a slight increase in Pd concentration from 31.3 to 32.3 at. %. Further analysis showed that such a slight increase led to suppression of the long-range ordered martensitic phase and resulted in a frozen short-range ordered strain glass state. This strain glass state possessed a two-phase nanostructure with nanosized frozen strain domains embedded in the austenite matrix, which was responsible for the unique magnetostriction behavior. Our study provides a way to design novel magnetostrictive materials with low-field-triggered large magnetostriction.

Performance optimization of dye-sensitized solar cells by multilayer gradient scattering architecture of TiO2 microspheres.

TiO2 microspheres (TMSs) with unique hierarchical structure and unusual high specific surface area are synthesized and incorporated into a photoanode in various TMS multilayer gradient architectures to form novel photoanodes and dye-sensitized solar cells (DSSCs). Significant influences of these architectures on the photoelectric properties of DSSCs are obtained. The DSSC with the optimal TMS gradient-ascent architecture of M036 has the largest amounts of dye absorption, strongest light absorption, longest electron lifetime and lowest electron recombination, and thus exhibits the maximum short circuit current density (Jsc) of 16.49 mA cm-2 and photoelectric conversion efficiency (η) of 7.01%, notably higher than those of conventional DSSCs by 21% and 22%, respectively. These notable improvements in the properties of DSSCs can be attributed to the TMS gradient-ascent architecture of M036 which can most effectively increase dye absorption and localize incident light within the photoanode by the light scattering of TMSs, and thus utilize the incident light thoroughly. This study provides an optimized and universal configuration for the scattering microspheres incorporated in the hybrid photoanode, which can significantly improve the performance of DSSCs.

Plasmonic-resonance-based ternary composite complementary enhancement of the performance of dye-sensitized solar cells.

Graphene (G), TiO2 fusiform nanorods (TiO2NRs) adsorbed with Au nanoparticles (AuNPs) are prepared and blended as multifunctional materials into TiO2 nanocrystalline film to form a novel ternary (G-TiO2NRs-Au) composite photoanode in dye-sensitized solar cells (DSSCs). The effects of G-TiO2NRs-Au on the properties of the photoanode and DSSC are investigated. Results show that, by blending G-TiO2NRs-Au, the light absorption and scattering of the photoanode are obviously improved, and the charge transfer resistance R2 and electron recombination are decreased, resulting in a significant enhancement in the short-circuit current density (J sc) and the photoelectric conversion efficiency (PCE) of the DSSCs. The maximum J sc of 17.66 mA cm(-2) and PCE of 8.56% are obtained in the optimal G-TiO2NRs-Au-based DSSC, about 33.6% and 35.0% higher than that obtained in the conventional TiO2-based DSSC. This significant improvement in the performance of the DSSC can be attributed to the ternary composite complementary effects of multi-functions from the surface plasmon resonance of AuNPs, light scattering of TiO2NRs, and the improved dye loading and fast electron transmission channel from graphene. This study provides an effective way of ternary composite complementary enhancement of the J sc and PCE of the DSSCs.

Research on temperature detection method of liquor distilling pot feeding operation based on a compressed algorithm.

In the process of feeding the distilling bucket after vapor detection, the existing methods can only realize the lag detection after the steam overflow, and can not accurately detect the location of the steam, etc. At the same time, in order to effectively reduce the occupancy of the computational resources and improve the deployment performance, this study established infrared image dataset of fermented grains surface, and fused the YOLO v5n and the knowledge distillation and the model pruning algorithms, and an lightweight method YOLO v5ns-DP was proposed as as a model for detecting temperature changes in the surface layer of fermented grains during the process of feeding the distilling. The experimental results indicated that the improvement makes YOLOv5n improve its performance in all aspects. The number of parameters, GLOPs and model size of YOLO v5ns-DP have been reduced by 28.6%, 16.5%, and 26.4%, respectively, and the mAP has been improved by 0.6. Therefore, the algorithm is able to predict in advance and accurately detect the location of the liquor vapor, which effectively improves the precision and speed of the detection of the temperature of the surface fermented grains , and well completes the real-time detecting task.

Emerging therapeutic strategies for metastatic uveal melanoma: Targeting driver mutations.

Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults. Although primary UM can be effectively controlled, a significant proportion of cases (40% or more) eventually develop distant metastases, commonly in the liver. Metastatic UM remains a lethal disease with limited treatment options. The initiation of UM is typically attributed to activating mutations in GNAQ or GNA11. The elucidation of the downstream pathways such as PKC/MAPK, PI3K/AKT/mTOR, and Hippo-YAP have provided potential therapeutic targets. Concurrent mutations in BRCA1 associated protein 1 (BAP1) or splicing factor 3b subunit 1 (SF3B1) are considered crucial for the acquisition of malignant potential. Furthermore, in preclinical studies, actionable targets associated with BAP1 loss or oncogenic mutant SF3B1 have been identified, offering promising avenues for UM treatment. This review aims to summarize the emerging targeted and epigenetic therapeutic strategies for metastatic UM carrying specific driver mutations and the potential of combining these approaches with immunotherapy, with particular focus on those in upcoming or ongoing clinical trials.

Self-Delivery Nanobooster to Enhance Immunogenic Cell Death for Cancer Chemoimmunotherapy.

Inducing immunogenic cell death (ICD) is a promising strategy for cancer immunotherapy. Shikonin (SHK), a naphthoquinone compound from Lithospermum erythrorhizon, can stimulate antitumor immunity by inducing ICD. Nevertheless, the immunogenicity of tumor cells killed by SHK is weak. Endoplasmic reticulum (ER) stress is an important intracellular pathway of the ICD effect. Curcumin (CUR) can directly induce ER stress by disrupting Ca2+ homeostasis, which might enhance SHK-induced ICD effect. A self-delivery ICD effect nanobooster (CS-PEG NPs) was developed by the self-assembly of SHK (ICD inducer) and CUR (ICD enhancer) with the assistance of DSPE-PEG2K for cancer chemoimmunotherapy. CS-PEG NPs possessed effective CT26 tumor cell cellular uptake and tumor accumulation ability. Moreover, enhanced cytotoxicity against tumor cells and apoptosis promotion were achieved due to the synergistic effect of CUR and SHK. Notably, CS-PEG NPs induced obvious Ca2+ homeostasis disruption, ER stress, and ICD effect. Subsequently, the neoantigens produced by the robust ICD effect in vivo promoted dendritic cell maturation, which further recruited and activated cytotoxic T lymphocytes. Superior antitumor efficacy and systemic antitumor immunity were observed in the CT26-bearing BALB/c mouse model without side effects in major organs. This study offers a promising self-delivery nanobooster to induce strong ICD effect and antitumor immunity for cancer chemoimmunotherapy.

Vortex-based soft magnetic composite with ultrastable permeability up to gigahertz frequencies.

Soft magnetic materials with stable permeability up to hundreds of megahertz (MHz) are urgently needed for integrated transformers and inductors, which are crucial in the more-than-Moore era. However, traditional frequency-stable soft magnetic ferrites suffer from low saturation magnetization and temperature instability, making them unsuitable for integrated circuits. Herein, we fabricate a frequency-stable soft magnetic composite featuring a magnetic vortex structure via cold-sintering, where ultrafine FeSiAl particles are magnetically isolated and covalently bonded by Al2SiO5/SiO2/Fe2(MoO4)3 multilayered heterostructure. This construction results in an ultrastable permeability of 13 up to 1 gigahertz (GHz), relatively large saturation magnetization of 105 Am2/kg and low coercivity of 48 A/m, which we ascribe to the elimination of domain walls associated with almost uniform single-vortex structures, as observed by Lorentz transmission electron microscopy and reconstructed by micromagnetic simulation. Moreover, the ultimate compressive strength has been simultaneously increased up to 337.1 MPa attributed to the epitaxially grown interfaces between particles. This study deepens our understanding on the characteristics of magnetic vortices and provides alternative concept for designing integrated magnetic devices.

Highly anisotropic Fe3C microflakes constructed by solid-state phase transformation for efficient microwave absorption.

Soft magnetic materials with flake geometry can provide shape anisotropy for breaking the Snoek limit, which is promising for achieving high-frequency ferromagnetic resonances and microwave absorption properties. Here, two-dimensional (2D) Fe3C microflakes with crystal orientation are obtained by solid-state phase transformation assisted by electrochemical dealloying. The shape anisotropy can be further regulated by manipulating the thickness of 2D Fe3C microflakes under different isothermally quenching temperatures. Thus, the resonant frequency is adjusted effectively from 9.47 and 11.56 GHz under isothermal quenching from 700 °C to 550 °C. The imaginary part of the complex permeability can reach 0.9 at 11.56 GHz, and the minimum reflection loss (RLmin) is -52.09 dB (15.85 GHz, 2.90 mm) with an effective absorption bandwidth (EAB≤-10 dB) of 2.55 GHz. This study provides insight into the preparation of high-frequency magnetic loss materials for obtaining high-performance microwave absorbers and achieves the preparation of functional materials from traditional structural materials.

High-performance sono-piezoelectric nanocomposites enhanced by interfacial coupling effects for implantable nanogenerators and actuators.

Transcutaneous energy-harvesting technology based on ultrasound-driven piezoelectric nanogenerators is the most promising technology in medical and industrial applications. Based on ultrasonic coupling effects at the interfaces, the interfacial architecture is a critical parameter to attain desirable electromechanical properties of nanocomposites. Herein, we successfully synthesized core-conductive shell-structured BaTiO3@Carbon [BT@Carbon] nanoparticles [NPs] as nanofillers to design implantable poly(vinylidenefluoride-co-chlorotrifluoroethylene)/BT@Carbon [P(VDF-CTFE)/BT@Carbon] piezoelectric nanogenerators (PENGs) and actuators for harvesting ultrasound (US) underneath the skin. For US-driven PENGs, the electrons and holes are generated not only from the interfaces between the BT@Carbon NPs and the matrix, but also from the dipoles vibrating in the smaller lamellae of ferroelectric ß-phase crystals in poled nanocomposites. Remarkably, P(VDF-CTFE)/BT@Carbon piezoelectric nanogenerators could attain an extraordinary output power of 521 µW cm-2 under ultrasound stimulation, which is far greater than that of force-induced PVDF-based nanogenerators and other ultrasound-driven triboelectric generators. Furthermore, the US-PENG actuator system, which is composed of an amplifier and a microcontroller, could efficiently convert ultrasonic energy into electricity or instructions to switch on/off small electronics in the tissues and organs of mice. Finally, the nanocomposite-based US-driven PENGs have a good biocompatibility, with no cytotoxicity or immune response in vivo, indicating their potential for developing wireless power generators and actuators for medical implant devices.

Identification and characterization of Varicella Zoster Virus circular RNA in lytic infection.

This study investigates the role of circular RNAs (circRNAs) in the context of Varicella-Zoster Virus (VZV) lytic infection. We employ two sequencing technologies, short-read sequencing and long-read sequencing, following RNase R treatment on VZV-infected neuroblastoma cells to identify and characterize both cellular and viral circRNAs. Our large scanning analysis identifies and subsequent experiments confirm 200 VZV circRNAs. Moreover, we discover numerous VZV latency-associated transcripts (VLTs)-like circRNAs (circVLTslytic), which contain multiple exons and different isoforms within the same back-splicing breakpoint. To understand the functional significance of these circVLTslytic, we utilize the Bacteria Artificial Chromosome system to disrupt the expression of viral circRNAs in genomic DNA location. We reveal that the sequence flanking circVLTs' 5' splice donor plays a pivotal role as a cis-acting element in the formation of circVLTslytic. The circVLTslytic is dispensable for VZV replication, but the mutation downstream of circVLTslytic exon 5 leads to increased acyclovir sensitivity in VZV infection models. This suggests that circVLTslytic may have a role in modulating the sensitivity to antiviral treatment. The findings shed new insight into the regulation of cellular and viral transcription during VZV lytic infection, emphasizing the intricate interplay between circRNAs and viral processes.