Hairpin-Empowered Invasive Reaction Combined with Catalytic Hairpin Assembly Cascade Amplification for the Specific Detection of Single-Nucleotide Polymorphisms.

Single-nucleotide polymorphism (SNP) is widely used in the study of disease-related genes and in the genetic study of animal and plant strains. Therefore, SNP detection is crucial for biomedical diagnosis and treatment as well as for molecular design breeding of animals and plants. In this regard, this article describes a novel technique for detecting SNP using flap endonuclease 1 (FEN 1) as a specific recognition element and catalytic hairpin assembly (CHA) cascade reaction as a signal amplification strategy. The mutant target (MT) was hybridized with a biotin-modified upstream probe and hairpin-type downstream probe (DP) to form a specific three-base overlapping structure. Then, FEN 1 was employed for three-base overlapping structure-specific recognition, namely, the precise SNP site identification and the 5' flap of DP dissociation. After dissociation, the hybridized probes were magnetically separated by a streptavidin-biotin complex. Especially, the ability to establish such a hairpin-type DP provided a powerful tool that could be used to hide the cut sequence (CS) and avoid false-positive signals. The cleaved CS initiated the CHA reaction and allowed superior fluorescence signal generation. Owing to the high specificity of FEN 1 for single base recognition, only the MT could be distinguished from the wild-type target and mismatched DNA. Owing to the dual signal amplification, as low as 0.36 fM MT and 1% mutation abundance from the mixtures could be detected, respectively. Furthermore, it could accurately identify SNPs from human cancer cells, as well as soybean leaf genome extracts. This strategy paves the way for the development of more precise and sensitive tools for diagnosing early onset diseases as well as molecular design breeding tools.

In silico bioactivity prediction of proteins interacting with graphene-based nanomaterials guides rational design of biosensor.

Graphene-based nanomaterials have attracted significant attention for their potentials in biomedical and biotechnology applications in recent years, owing to the outstanding physical and chemical properties. However, the interaction mechanism and impact on biological activity of macro/micro biomolecules still require more concerns and further research in order to enhance their applicability in biosensors, etc. Herein, an integrated method has been developed to predict the protein bioactivity performance when interacting with nanomaterials for protein-based biosensor. Molecular dynamics simulation and molecular docking technique were consolidated to investigate several nanomaterials: C60 fullerene, single-walled carbon nanotube, pristine graphene and graphene oxide, and their effect when interacting with protein. The adsorption behavior, secondary structure changes and protein bioactivity changes were simulated, and the results of protein activity simulation were verified in combination with atomic force spectrum, circular dichroism spectrum fluorescence and electrochemical experiments. The best quantification alignment between bioactivity obtained by simulation and experiment measurements was further explored. The two proteins, RNase A and Exonuclease III, were regarded as analysis model for the proof of concept, and the prediction accuracy of protein bioactivity could reach up to 0.98. The study shows an easy-to-operate and systematic approach to predict the effects of graphene-based nanomaterials on protein bioactivity, which holds guiding significance for the design of protein-related biosensors. In addition, the proposed prediction model is not limited to carbon-based nanomaterials and can be extended to other types of nanomaterials. This facilitates the rapid, simple, and low-cost selection of efficient and biosafe nanomaterials candidates for protein-related applications in biosensing and biomedical systems.

A prospective study of two-dimensional ultrasonography combined with shear wave elastography for pregnancy-related diastasis recti abdominis.

Objectives: To compare the inter-rectus distance (IRD), rectus abdominis thickness (RAT), and stiffness in women during pregnancy and postpartum and identify the risk and protective factors affecting diastasis recti abdominis (DRA). Materials and methods: A total of 171 pregnant women who volunteered to participate in this study were recruited. Using an ultrasonographic diagnostic instrument with shear wave elastography function, IRD, RAT and the Young's modulus of the rectus abdominis muscles were measured at 12 weeks, 37 weeks of pregnancy, and 6 weeks postpartum. Results: The IRD at 37 weeks was significantly higher than that at 12 weeks and then decreased at 6 weeks postpartum, but it was still higher than that at 12 weeks (p < 0.001). RAT and Young's modulus decreased significantly at 37 weeks compared with those at 12 weeks and then recovered at 6 weeks postpartum, but they were lower than those at 12 weeks (p < 0.001). IRD at 12 weeks was significantly higher in multiparae than in primiparae (p < 0.001). Moreover, positive correlation between the RAT and Young's modulus of rectus abdominis muscles at 12 and 37 weeks of gestation and 6 weeks postpartum (p < 0.001) was observed. Multiple linear regression analysis showed that the regression equation was significant (f = 24.856, p < 001). Conclusion: Our study identified differences in IRD, thickness and stiffness of the rectus abdominis muscle between early and advanced pregnancy and the postpartum period. The risk and protective factors of DRA may guide pregnant women's protection and treatment.

Research on spacecraft in orbit perception based on artificial neural networks and digital twin technology using grating arrays.

In order to improve the safety of spacecraft, the research on artificial neural network and digital twin technology based on, to our best knowledge, a novel fiber Bragg grating (FBG) sensor array is proposed for intelligent sensing monitoring of spacecraft on-orbit collisions. Femtosecond FBG arrays were fabricated on the novel oxide-doped fiber by point-by-point writing technique. The femtosecond FBG is analyzed using the time-dependent perturbation theory of quantum mechanics. The FBG array can achieve high-temperature measurement of 1100 °C and large strain measurement of 15000 µÎµ. The sensing arrays were deployed on the surface of the spacecraft. Constructed the multi-layer perceptron neural network structure and convolutional neural network structure. 1200 samples were trained. Conducted model accuracy testing. The accuracy rate is above 98%, and accuracy verification has been implemented. The digital twin model was designed based on various data such as strain and temperature of the spacecraft structure under impact monitored by FBG sensors. A precise mapping has been formed between the physical entities of spacecraft and digital twins. Empower spacecraft with functions such as self-monitoring, judgment, and response. To ensure the stable and safe operation of spacecraft.

Solid rocket motor propellant health monitoring based on oxide-doped curved long-period fiber grating.

A kind of curved long-period fiber grating(CLPFG) engraved by CO2 laser based on oxide-doped fiber was designed to monitor the structural integrity of propellant. The mechanical damage characteristics of the propellant were analyzed. The sensor model is constructed and the refractive index modulation characteristics of the CLPFG are analyzed. The strain coupling characteristics and the strain transfer efficiency of the interface between the CLPFG and the propellant are clarified. Propellant modules with implanted CLPFG were fabricated. The novel grating sensor has been effectively coated and structurally packaged. Conducted experiments on strain and temperature of propellant modules. The large strain measurement of propellant from 0 µÎµ to 24000 µÎµ is realized. Solved the thorny problem of large strain measurement for propellants. In addition, the temperature discrimination measurement in the temperature range of 30 ℃ to 250 ℃ can be realized. Sensor exhibit extremely high stability characteristics and has good compatibility with propellants. The sensor implantation and extraction structure has been designed to improve the survival rate of the sensor inside the solid rocket motors (SRM). Sensors can accurately measure the mechanical and thermal state parameters of propellants, providing effective data support for the health management of SRM.

The effects of respiratory muscle training on respiratory function and functional capacity in patients with early stroke: a meta-analysis.

BACKGROUND: Respiratory muscle training is a continuous and standardized training of respiratory muscles, but the evidence of the effects on early stroke patients is not clear. This meta-analysis aimed to investigate the effects of respiratory muscle training on respiratory function and functional capacity in patients with early stroke. METHODS: PubMed, Embase, PEDro, ScienceDirect, AMED, CINAHL, and China National Knowledge Infrastructure databases were searched from inception to December 8, 2023 for articles about studies that 1) stroke patients with age ≥ 18 years old. Early stroke < 3 months at the time of diagnosis, 2) respiratory muscle training, including inspiratory and expiratory muscle training, 3) the following measurements are the outcomes: respiratory muscle strength, respiratory muscle endurance, pulmonary function testing, dyspnea fatigue score, and functional capacity, 4) randomized controlled trials. Studies that met the inclusion criteria were extracted data and appraised the methodological quality and risk of bias using the Physiotherapy Evidence Database scale and the Cochrane Risk of Bias tool by two independent reviewers. RevMan 5.4 with a random effect model was used for data synthesis and analysis. Mean differences (MD) or standard mean differences (SMD), and 95% confidence interval were calculated (95%CI). RESULTS: Nine studies met inclusion criteria, recruiting 526 participants (mean age 61.6 years). Respiratory muscle training produced a statistically significant effect on improving maximal inspiratory pressure (MD = 10.93, 95%CI: 8.51-13.36), maximal expiratory pressure (MD = 9.01, 95%CI: 5.34-12.69), forced vital capacity (MD = 0.82, 95%CI: 0.54-1.10), peak expiratory flow (MD = 1.28, 95%CI: 0.94-1.63), forced expiratory volume in 1 s (MD = 1.36, 95%CI: 1.13-1.59), functional capacity (SMD = 0.51, 95%CI: 0.05-0.98) in patients with early stroke. Subgroup analysis showed that inspiratory muscle training combined with expiratory muscle training was beneficial to the recovery of maximal inspiratory pressure (MD = 9.78, 95%CI: 5.96-13.60), maximal expiratory pressure (MD = 11.62, 95%CI: 3.80-19.43), forced vital capacity (MD = 0.87, 95%CI: 0.47-1.27), peak expiratory flow (MD = 1.51, 95%CI: 1.22-1.80), forced expiratory volume in 1 s (MD = 0.76, 95%CI: 0.41-1.11), functional capacity (SMD = 0.61, 95%CI: 0.08-1.13), while inspiratory muscle training could improve maximal inspiratory pressure (MD = 11.60, 95%CI: 8.15-15.05), maximal expiratory pressure (MD = 7.06, 95%CI: 3.50-10.62), forced vital capacity (MD = 0.71, 95%CI: 0.21-1.21), peak expiratory flow (MD = 0.84, 95%CI: 0.37-1.31), forced expiratory volume in 1 s (MD = 0.40, 95%CI: 0.08-0.72). CONCLUSIONS: This study provides good-quality evidence that respiratory muscle training is effective in improving respiratory muscle strength, pulmonary function, and functional capacity for patients with early stroke. Inspiratory muscle training combined with expiratory muscle training seems to promote functional recovery in patients with early stroke more than inspiratory muscle training alone. TRIAL REGISTRATION: Prospero registration number: CRD42021291918.

A novel biomimetic electrochemical taste-biosensor based on conformational changes of the taste receptor.

Taste sensor, a useful tool which could detect and identify thousands of different chemical substances in liquid environments, has attracted continuous concern from beverage and foodstuff industry and its consumers. Although many taste sensing methods have been extensively developed, the assessment of tastant content remains challenging due to the limitations of sensor selectivity and sensitivity. Here we present a novel biomimetic electrochemical taste-biosensor based on bioactive sensing elements and immune amplification with nanomaterials carrier to address above concerns, while taking sweet taste perception as a model. The proposed biosensor based on ligand binding domain (T1R2 VFT) of human sweet taste receptor protein showed human mimicking character and initiated the application of immune recognition in gustation biosensor, which can precisely and sensitively distinguish sweet substances against other related gustation substances with detection limit of 5.1 pM, far less than that of taste sensors without immune amplification whose detection limit was 0.48 nM. The performance test demonstrated the biosensor has the capacity of monitoring the response of sweet substances in real food environments, which is crucial in practical. This biomimetic electrochemical taste-biosensor can work as a new screening platform for newly developed tastants and disclose sweet perception mechanism.

Equivalent circuit model of the traveling wave electrode for lithium niobate thin film Mach-Zehnder modulators.

We propose an equivalent circuit model of the traveling wave electrode for lithium niobate thin film (TFLN) Mach-Zehnder modulators, in which the distributed capacitance and conformal mapping techniques are applied to calculate the microwave refractive index, microwave loss, and characteristic impedance. Their accuracies are verified by comparing with the results of the finite element method, and the relative errors are less than 3.282%, 1.776%, and 5.334%, respectively. The influence of the electrode's structural parameters on the modulation performances is analyzed, and a 3 dB modulation bandwidth around 84 GHz with an 8-mm-long traveling wave electrode is obtained.

A Self-Adaptive Dual-ILRO Clock-Recovery Technique for Two-Tone Battery-Free Crystal-Free Neural-Recording SoC.

Wireless implantable devices are widely used in medical treatment, which should meet clinical constraints such as longevity, miniaturization, and reliable communication. Wireless power transfer (WPT) can eliminate the battery to reduce system size and prolong device life, while it's challenging to generate a reliable clock without a crystal. In this work, we propose a self-adaptive dual-injection-locked-ring-oscillator (dual-ILRO) clock-recovery technique based on two-tone WPT and integrate it into a battery-free neural-recording SoC. The 2[Formula: see text]-order inter-modulation (IM2) component of the two WPT tones is extracted as a low-frequency reference for battery-free SoC, and the proposed self-adaptive dual-ILRO technique extends the lock range to ensure an anti-interference PVT-robust clock generation. The neural-recording SoC includes a low-noise signal acquisition unit, a power management unit, and a backscatter circuit to perform neural signal recording, wireless power harvesting, and neural data transmission. Benefiting from the 6.4 µW low power of the clock recovery circuit, the overall SoC power is cut down to 49.8 µW. In addition, the proposed clock-recovery technique enables both signal acquisition and uplink communication to perform as well as that synchronized by an ideal clock, i.e., an effective number of 9.6 bits and a bit error rate (BER) less than 4.8 × 10-7 in chip measurement. The SoC takes a die area of 2.05 mm 2, and an animal test is conducted in a Sprague-Dawley rat to validate the wireless neural-recording performance, compared to a crystal-synchronized commercial chip.

Rationally Designed Dual Base Pair Mismatch Enables Toehold-Mediated Strand Displacement to Efficiently Recognize Single-Nucleotide Polymorphism without Enzymes.

The efficiency of the enzyme-free toehold-mediated strand displacement (TMSD) technique is often insufficient to detect single-nucleotide polymorphism (SNP) that possesses only single base pair mismatch discrimination. Here, we report a novel dual base pair mismatch strategy enabling TMSD biosensing for SNP detection under enzyme-free conditions when coupled with catalytic hairpin assembly (CHA) and fluorescence resonance energy transfer (FRET). The strategy is based on a competitive strand displacement reaction mechanism, affected by the thermodynamic stability originating from rationally designed dual base pair mismatch, for the specific recognition of mutant-type DNA. In particular, enzyme-free nucleic acid circuits, such as CHA, emerge as a powerful method for signal amplification. Eventually, the signal transduction of this proposed biosensor was determined by FRET between streptavidin-coated 605 nm emission quantum dots (605QDs, donor) and Cy5/biotin hybridization (acceptor, from CHA) when incubated with each other. The proposed biosensor displayed high sensitivity to the mutant target (MT) with a detection concentration down to 4.3 fM and led to high discrimination factors for all types of mismatches in multiple sequence contexts. As such, the application of this proposed biosensor to investigate mechanisms of the competitive strand displacement reaction further illustrates the versatility of our dual base pair mismatch strategy, which can be utilized for the creation of a new class of biosensors.

Research on an Enhanced Detuned-Loading Effect in Integrated Two-Section DFB Lasers with High Modulation Bandwidths.

A novel high-speed directly modulated two-section distributed-feedback (TS-DFB) semiconductor laser based on the detuned-loading effect is proposed and simulated. A grating structure is designed by the reconstruction-equivalent-chirp (REC) technique. A π phase shift is introduced into the reflection grating, which can provide a narrow-band reflection region with a sharp falling slope on both sides of the reflection spectrum, thus enhancing the detuned-loading effect. Owing to its unique dual-falling-edges structure, the bandwidth can be improved even when the lasing wavelength shifts beyond the left falling edge due to a thermal effect in the actual test, in which condition the detuned-loading effect can be used twice, which greatly improves the yield. The modulation bandwidth is increased from 17.5 GHz for a single DFB laser to around 24 GHz when the lasing wavelength is located on the left falling edge of the TS-DFB laser based on the detuned-loading effect, and it can be increased to 22 GHz for the right side. An eight-channel laser array with precise wavelength spacing is investigated, with a side-mode suppression ratio (SMSR) >36 dB. In addition, TS-DFB lasers with uniform reflection gratings are studied, and simulated results show that the modulation characteristic is far inferior to the laser with a phase-shifted grating reflector.

A FEN 1-driven DNA walker-like reaction coupling with magnetic bead-based separation for specific SNP detection.

Single-nucleotide polymorphism (SNP) plays a key role in the carcinogenesis of the human genome, and understanding the intrinsic relationship between individual genetic variations and carcinogenesis lies heavily in the establishment of a precise and sensitive SNP detection platform. Given this, a powerful and reliable SNP detection platform is proposed by a flap endonuclease 1 (FEN 1)-driven DNA walker-like reaction coupling with a magnetic bead (MB)-based separation. A carboxyfluorescein (FAM)-labeled downstream probe (DP) was decorated on a streptavidin magnetic bead (SMB). The target DNA, as a walker strand, was captured by hybridization with DP and an upstream probe (UP) to form a three-base overlapping structure and execute the walking function on the surface of SMB. FEN 1 was employed to specifically recognize the three-base overlapping structure and cut the 5'flap at the SNP site to report the walking event and signal amplification. Considering the fact that the fluorescence was labeled on the cleavage and uncleavage sequences of DP and the target DNA-triggered walking event was undistinguishable from the mixtures, magnetic separation came in handy for cleavage probe (CP) isolation and discrimination of the amplified signal from the background signal. In comparison with the conventional DNA walker reaction, this strategy was coupling with SMB-based separation, thus promising a powerful and reliable method for SNP detection and signal amplification.

Millimeter-wave generation based on a monolithic dual-wavelength DFB laser with four phase-shifted sampled gratings and equivalent chirp technology.

A dual-wavelength DFB laser array based on four phase-shifted grating and equivalent chirp technology is first proposed, fabricated, and experimentally demonstrated. The dual-wavelength emitting is achieved by symmetrically introducing two π phase shifts into a chirped four phase-shifted sampled grating cavity. Meanwhile, the beating signal of the dual-wavelength output is stabilized by applying an electro-absorption modulator integrated at the rear of the cavity. Under different grating chirp rates, a series of RF signals from 66.8 GHz to 73.6 GHz with a linewidth of less than 210 kHz is obtained.

Four-channel all-optical wavelength conversion unit based on nonlinear effect of three-section monolithically integrated semiconductor lasers.

A simple and highly efficient four-channel all-optical wavelength conversion based on four-wave mixing effect of the directly modulated three-section monolithically integrated semiconductor laser is proposed and experimentally investigated. For this wavelength conversion unit, the spacing of the wavelength can be adjusted by tuning the bias current of the lasers and setting it to be 0.4 nm (50 GHz) as a demonstration is this work. A 50 Mbps 16-QAM signal centers at 4-8 GHz is experimentally switched to a targeted path. Up- or downconversion depends on a wavelength-selective switch, and the conversion efficiency can reach up to -2 to 0 dB. This work provides a new technology for photonic radio-frequency switching matrix and contributes to the integrated implementation of satellite transponders.

Simple multi-band linearly frequency-modulated signal generation with a multiplying bandwidth based on a gain-switching laser.

Multi-band linearly frequency-modulated (LFM) signal generation with a multiplying bandwidth is proposed and experimentally demonstrated. It is a simple photonics method based on the gain-switching state in a distributed feedback semiconductor laser without a complex external modulator and high-speed electrical amplifiers. With N comb lines, the carrier frequency and bandwidth of generated LFM signals are N times those of the reference signal. (N is the number of comb lines.) The number of bands and time-bandwidth products (TBWPs) of the generated signals could be easily adjusted by tuning the reference signal from an arbitrary waveform generator. Three-band LFM signals with carrier frequencies ranging from the X-band to K-band are given as an example, and the TBWP up to 20000. The results of auto-correlations of the generated waveforms are also given.

Interaction of air pollution and meteorological factors on IVF outcomes: A multicenter study in China.

BACKGROUND: Previous studies revealed associations between air-pollutant exposure and in vitro fertilization (IVF) outcomes. However, modification effects of air pollution on IVF outcomes by meteorological conditions remain elusive. METHODS: This multicenter retrospective cohort study included 15,217 women from five northern Chinese cities during 2015-2020. Daily average concentrations of air pollutants (PM2.5, PM10, O3, NO2, SO2, and CO) and meteorological factors (temperature, relative humidity, wind speed, and sunshine duration) during different exposure windows were calculated as individual approximate exposure. Generalized estimating equations models and stratified analyses were conducted to assess the associations of air pollution and meteorological conditions with IVF outcomes and estimate potential interactions. RESULTS: Positive associations of wind speed and sunshine duration with pregnancy outcomes were detected. In addition, we observed that embryo transfer in spring and summer had a higher likelihood to achieve a live birth compared with winter. Exposure to PM2.5, SO2, and O3 was adversely correlated with pregnancy outcomes in fresh IVF cycles, and the associations were modified by air temperature, relative humidity, and wind speed. The inverse associations of PM2.5 and SO2 exposure with biochemical pregnancy were stronger at lower temperatures and humidity. Negative associations of PM2.5 with clinical pregnancy were only significant at lower temperatures and wind speeds. Moreover, the effects of O3 on live birth were enhanced by higher wind speed. CONCLUSIONS: Our results suggested that the associations between air-pollutant exposure and IVF outcomes were modified by meteorological conditions, especially temperature and wind speed. Women undergoing IVF treatment should be advised to reduce outdoor time when the air quality was poor, particularly at lower temperatures.

Interface debonding monitoring of solid rocket motor based on femtosecond grating array.

During the whole life cycle of solid rocket motor (SRM), shell damage and propellant interface debonding will occur, which will destroy the structural integrity of SRM. Therefore, it is necessary to monitor the SRM health status, and the existing nondestructive testing technology and the designed optical fiber sensor cannot meet the monitoring requirements. In order to solve this problem, this paper uses femtosecond laser direct writing technology to write high contrast short femtosecond grating array. A new packaging method is proposed to enable the sensor array to measure 9000 µÎµ. It solves the grating chirp phenomenon caused by stress concentration in the SRM, and breaks through the key technology of fiber optic sensor implantation in the SRM. The shell pressure test and strain monitoring inside the SRM during long-term storage are realized. For the first time, the experiments of tearing and shearing specimens were simulated. Compared with the results of computed tomography, it proves the accuracy and progressiveness of implantable optical fiber sensing technology. Combined with theory and experiment, the problem of SRM life cycle health monitoring is solved.

Controlled growth of titanium dioxide nanotubes for doxorubicin loading and studies of in vitro antitumor activity.

Titanium dioxide (TiO2) materials are suitable for use as drug carriers due to their natural biocompatibility and nontoxicity. The aim of the study presented in this paper was to investigate the controlled growth of TiO2 nanotubes (TiO2 NTs) of different sizes via an anodization method, in order to delineate whether the size of NTs governs their drug loading and release profile as well as their antitumor efficiency. TiO2 NTs were tailored to sizes ranging from 25 nm to 200 nm according to the anodization voltage employed. The TiO2 NTs obtained by this process were characterized using scanning electron microscopy, transmission electron microscopy, and dynamic light scattering The larger TiO2 NTs exhibited greatly improved doxorubicin (DOX)-loading capacity (up to 37.5 wt%), which contributed to their outstanding cell-killing ability, as evidenced by their lower half-maximal inhibitory concentration (IC50). Comparisons were carried out of cellular uptake and intracellular release rates of DOX for large and small TiO2 NTs loaded with DOX. The results showed that the larger TiO2 NTs represent a promising therapeutic carrier for drug loading and controlled release, which could improve cancer treatment outcomes. Therefore, TiO2 NTs of larger size are useful substances with drug-loading potency that may be used in a wide range of medical applications.

Whole exome sequencing reveals novel variants associated with diminished ovarian reserve in young women.

Background: Diminished ovarian reserve is one of the most important causes of female infertility. In the etiology study of DOR, besides age, it is known that chromosomal abnormality, radiotherapy, chemotherapy and ovarian surgery can result in DOR. For young women without obvious risk factors, gene mutation should be considered as a possible cause. However, the specific molecular mechanism of DOR has not been fully elucidated. Methods: In order to explore the pathogenic variants related to DOR, twenty young women under 35 years old affected by DOR without definite factors damaging ovarian reserve were recruited as the research subjects, and five women with normal ovarian reserve were recruited as the control group. Whole exome sequencing was applied as the genomics research tool. Results: As a result, we obtained a set of mutated genes that may be related to DOR, where the missense variant on GPR84 was selected for further study. It is found that GPR84Y370H variant promotes the expression of proinflammatory cytokines (TNF-α, IL12B, IL-1ß) and chemokines (CCL2, CCL5), as well as the activation of NF-κB signaling pathway. Conclusion: In conclusion, GPR84Y370H variant was identified though analysis for WES results of 20 DOR patients. The deleterious variant of GPR84 could be the potential molecular mechanism of non-age-related pathological DOR through its role in promoting inflammation. The findings of this study can be used as a preliminary research basis for the development of early molecular diagnosis and treatment target selection of DOR.

BmCPV replication is suppressed by the activation of the NF-κB/autophagy pathway through the interaction of vsp21 translated by vcircRNA_000048 with ubiquitin carboxyl-terminal hydrolase.

Bombyx mori cypovirus (BmCPV), a typical double-stranded RNA virus, was demonstrated to generate a viral circRNA, vcircRNA_000048, which encodes a vsp21 with 21 amino acid residues to suppress viral replication. However, the regulatory mechanism of vsp21 on virus infection remained unclear. This study discovered that vsp21 induces reactive oxygen species (ROS) generation, activates autophagy, and attenuates virus replication by inducing autophagy. Then we confirmed that the effect of vsp21-induced autophagy on viral replication was attributed to the activation of the NF-κB signaling pathway. Furthermore, we clarified that vsp21 interacted with ubiquitin carboxyl-terminal hydrolase (UCH) and that ubiquitination and degradation of phospho-IκB-α were enhanced by vsp21 via competitive binding to UCH. Finally, we validated that vsp21 activates the NF-κB/autophagy pathway to suppress viral replication by interacting with UCH. These findings provided new insights into regulating viral multiplication and reovirus-host interaction.