Search Results (2,426)

Autophagy-mitophagy pathways are essential for regulating immune homeostasis. However, their contribution to population-level chronic low-grade systemic inflammation (SI) remains unclear. The objective was to investigate the association between variation in the genes related to the autophagy-mitophagy pathways and SI, and to examine whether lifestyle factors modify this relationship. We conducted genome-wide association studies and gene-set enrichment analyses using data from the Korean Genome and Epidemiology Study (KoGES, n = 28,102) and UK Biobank (UKBB, n = 343,892). SI was defined as an elevated white blood cell count or high-sensitivity C-reactive protein. Using Core Longevity State Vectors (CLSVs)—gene sets representing immune-longevity pathways derived from comparative transcriptomic analysis—we tested six pathways and constructed a weighted genetic risk score (GRS) from significant variants. Gene–lifestyle interactions were examined with respect to major dietary and lifestyle factors. Among six CLSVs, only CLSV-2 (mitophagy and autophagy) showed a significant association with SI (β = 0.425, p = 0.008). Six single nucleotide polymorphisms (SNPs) in autophagy-mitophagy genes (INPP5D, ATG16L1, ATG7, AP3S1, OPTN, and VPS33A) were associated with SI in KoGES (p < 5 × 10⁻⁵), and ten SNPs (genes selected in KoGES plus RAB7A, ATG12, VPS33A, BECN1) reached genome-wide significance in UKBB (p < 5 × 10⁻⁸). A higher GRS was associated with increased SI in both cohorts and was strongly associated with metabolic syndrome (MetS, OR = 1.91 in KoGES; OR = 1.62 in UKBB). SI was characterized by neutrophilia with relative lymphopenia. In UKBB, significant gene–lifestyle interactions were observed for diet, physical activity, smoking, and alcohol (p < 0.01). Favorable lifestyle factors reduced SI most effectively in individuals with protective genotypes. Among individuals with a high vegetable/fruit intake, SI prevalence was 35%, 36%, and 38% in the negative-, zero-, and positive-GRS groups, respectively, compared with 36%, 45%, and 48% in the low-intake groups. In conclusion, genetic variations in autophagy-mitophagy pathways specifically influence SI. Genetic predisposition substantially modifies the benefits of lifestyle, underscoring the importance of integrating genetic and lifestyle factors in understanding SI susceptibility. Full article

Canine parvovirus (CPV) is a major pathogen causing severe gastroenteritis in dogs. Since its emergence, CPV has undergone continuous evolution, leading to the predominance of variants such as CPV-2a, CPV-2b, and CPV-2c. To characterize the genetic features and evolutionary trends of CPV-2 at a regional level, 775 fecal samples were collected from domestic and stray dogs with suspected CPV-2 infection in Shanghai between 2016 and 2025. The overall positivity rate was 23.2% (180/775); incidence was substantially higher in stray dogs (30.2%) than in domestic dogs (15.9%). Thirty-one CPV-2 strains were successfully isolated. Temporal analysis revealed a pronounced genotype shift: isolates from 2016 to 2020 were predominantly New CPV-2a, whereas CPV-2c became the dominant genotype from 2021 through 2025. Sequence analysis identified the polymorphism of VP2 gene and characteristic mutations F267Y, Y324I, N426E, Q370R and A440T in CPV-2c strains. A novel I447M mutation was detected in several isolates. Phylogenetic analysis showed that Shanghai isolates formed distinct clusters; CPV-2c strains were closely related to the Asian lineage. Structural modeling indicated that mutations at residues L87M, T101I, Y267F, A297S, G300A, Y305D, I324Y, Q370R, N426E, A440T, and I447M may alter the tertiary structure of the VP2 protein, potentially affecting antigenicity and receptor recognition. Collectively, these results demonstrate the complete genotype replacement of CPV-2 in Shanghai; CPV-2c is now predominant. Identification of the novel I447M mutation and structural analysis of key amino acid substitutions provide insight into CPV molecular evolution. These findings suggest that vaccines primarily based on older CPV-2 or CPV-2b genotypes offer suboptimal protection, highlighting the need for updated vaccine strategies targeting prevalent CPV-2c variants. Full article

The paper presents the results of numerical and experimental investigations of a novel low-profile piezoelectric inertial linear actuator designed for a high-payload application. The actuator structure is based on a rectangular piezoelectric bimorph plate with centrally located trapezoidal toothed rings. The actuator operates in the second longitudinal vibration mode of the plate, which is excited by a sawtooth electric signal. Trapezoidal teeth are used to transfer longitudinal vibrations of the plate to the slider and, this way, generate linear motion. The use of trapezoidal teeth reduces the stumbling effect at high preload forces and as a result increases the actuator’s ability to operate under high preload forces and drive higher payloads. Numerical simulations indicated that the actuator exhibits a resonance frequency of 68.49 kHz, with the trapezoidal tooth achieving a maximum displacement amplitude of 188.25 µm at a voltage of 200 V_p-p. Furthermore, numerical analysis revealed that the trapezoidal tooth deflection in the out-of-plane direction under an axial load of 25 N reached 2.07 nm/N, demonstrating structural stability under high preload conditions. The results of experimental investigations have shown that the actuator can provide up to 75.16 mm/s at a linear motion speed of 200 V_p-p and an output force of 18.88 N at the same excitation signal amplitude. In addition, the 15 N load actuator was indicated to achieve a linear motion accuracy of 11.5 µm per step. Full article

In recent years, pigeon rotavirus A (PiRVA) infection, an important emerging disease, has posed a major threat to the healthy development of the pigeon industry and public health. Therefore, developing an accurate, rapid and convenient detection method for this virus is vital for monitoring and early diagnosis of the disease. In this study, on the basis of the ORF sequence characteristics of the PiRVA VP6 gene, crRNA and reverse transcription recombinase-aided amplification (RT-RAA) primers were designed. On the basis of the CRISPR/Cas12a system, for the first time, the RT-RAA-CRISPR/Cas12a rapid detection method of PiRVA was established by combining RT-RAA and lateral flow strips. This method could specifically detect PiRVA, and there was no cross-reaction with other common viruses originating from pigeons. The minimum detection limit was 16.8 copies/μL, and the results of the intrabatch and interbatch repeated tests were consistent. Moreover, the method established in this study and the previously established common PCR method were used to analyse 56 clinical tissue samples from racing pigeons and domestic pigeons collected in 2025. The positive rates of racing pigeon and domestic pigeon samples detected by PCR were 17.6% and 12.8%, respectively, and the positive rates of racing pigeon and meat pigeon samples detected by the RT-RAA-CRISPR/Cas12a method were 23.5% and 17.9%, respectively, indicating that PiRVA infection occurs in both racing pigeon and domestic pigeon populations in China. In summary, the PiRVA RT-RAA-CRISPR/Cas12a detection method established in this study has good specificity, sensitivity, and reproducibility, and allows visualization of the results, which can be used for field applications. This study provides technical support for epidemiological surveillance and etiological research on PiRVA. Full article

Background and Objectives: To evaluate and compare the accuracy (trueness and precision) and scanning speed of three intraoral scanners: Medit i700, Primescan 1, and COXO DL-300P, under standardized clinical conditions, using a digitized high-precision analog impression as the reference. Materials and Methods: A patient requiring fixed prosthetic treatment on natural abutments (2.5, 2.7, 3.5, 3.8) was selected. Ten sequential full-arch scans were performed with each scanner in rotating order. Scanning time was recorded for each full-arch acquisition. Accuracy analysis focused on regions of interest: the upper jaw included abutments with adjacent mucosa, the lower jaw included only abutment surfaces. A VPS impression was taken, poured in type IV stone, and digitized with a high-accuracy desktop scanner to serve as the reference. All datasets were analyzed in Geomagic Control X, and statistics were performed using MedCalc (α = 0.05). Results: Upper Jaw (Abutments and Mucosa): The Medit i700 achieved the highest trueness (100.3 ± 6.6 µm), outperforming Primescan and COXO (p = 0.008). COXO showed the best precision, while Primescan demonstrated the greatest variability (p < 0.0001). Primescan produced the fastest scans (72.5 ± 3.8 s) (p = 0.001). Lower Jaw: (Abutment Surface Only): Medit yielded superior trueness (193.1 ± 63.4 µm) compared with Primescan and COXO (p = 0.005). Precision varied significantly among devices, with COXO presenting the greatest inconsistency (p = 0.0004). Scan times did not differ significantly (p = 0.068). Conclusions: Medit i700 demonstrated the highest trueness, Primescan delivered the fastest scans but variable results, and COXO showed acceptable but inconsistent precision. Full article

Background: Chicken infectious anemia virus (CIAV) is a globally significant immunosuppressive pathogen that causes substantial economic losses to the poultry industry, with particularly severe outbreaks in China in recent years. Given the limitations of existing vaccines, especially the residual virulence associated with live attenuated vaccines, there is an urgent need to develop novel, safer, and more effective vaccine strategies. Methods: In this study, the VP1 and VP2 genes of CIAV were cloned and expressed in Escherichia coli to develop a cost-effective subunit vaccine. Since VP1 primarily formed inclusion bodies, a “VP2-assisted co-refolding” strategy was employed. This involved denaturing VP1 and refolding it via gradient dialysis in the presence of soluble VP2, thereby leveraging VP2’s natural chaperone-like function to restore conformational epitopes. The refolded VP1/VP2 protein complexes, emulsified at different ratios, were used to immunize 3-day-old specific pathogen-free (SPF) chickens, followed by challenge with a virulent CIAV strain. Results: The vaccine formulation with a VP1:VP2 ratio of 1:1 provided the best protection, achieving 71.4% (5/7) protective efficacy, as evidenced by significantly reduced thymic atrophy and a higher thymus index. Conclusions: These findings validate the feasibility of using an economical prokaryotic expression system combined with a rational protein refolding strategy to produce a protective subunit vaccine candidate against CIAV, offering a promising alternative for disease control. Full article

Bluetongue virus (BTV), with a genome of ten double-stranded RNA segments (S1–S10), is an emerging animal pathogen causing major economic losses in livestock worldwide. BTV replication involves RNA-RNA and RNA–protein interactions, with RNA-binding proteins, VP6 and NS2 playing key roles in genome assembly and RNA packaging. To explore the dynamics of RNA segment interactions and the roles of VP6 and NS2 in RNA complex formation, we used RNA fluorescence in situ hybridization chain reaction (HCR), along with site-specific mutagenesis and reverse genetics. We found that RNA segments interact sequentially, from the smallest (S10) to the largest (S1), forming a single complex that includes the entire genome. This process is independent of VP6 or NS2, although NS2 enhances the assembly of larger segments. Additionally, we show that VP6 binds to +ssRNAs before their incorporation into viral assembly factories (inclusion bodies/VIBs). These findings reveal that RNA-RNA interactions, rather than primary replicase proteins, govern the sorting and recruitment of genome segments. Our data offer new insights into BTV RNA packaging, showing that genome segments destined for packaging and dsRNA synthesis are segregated through complex formation, distinct from +ssRNAs used in protein synthesis, including those encoding the replicase complex. Full article

Background: Coxsackievirus B2 (CVB2) causes a range of diseases, including hand, foot, and mouth disease; myocarditis; acute flaccid paralysis; meningitis; and encephalitis. However, no specific antiviral drugs or vaccines are currently available for CVB2. Methods: We used plaque purification, virus titre determination, and serial passaging to screen and identify an inactivated CVB2 vaccine candidate strain, KM31-C05, which exhibited high viral titres and good genetic stability. Comprehensive biological characterization of this candidate strain was performed, including phylogenetic analysis, virulence assessment in BALB/c mice, one-step growth curve analysis, optimization of the multiplicity of infection, as well as determination of viral load, pathological evaluation, and immunohistochemical analysis in tissues of BALB/c suckling mice post-challenge. An experimental inactivated vaccine was prepared using KM31-C05 to evaluate its immunogenicity and protective efficacy. Results: The viral titres of KM31-C05 reached 10⁸ CCID50/mL. After 20 serial passages, only three amino acid mutations were identified (VP3-G165V, VP1-N84K, and VP1-D129N). Although the two VP1 mutations were located in surface-exposed loops, the strain maintained high neutralizing titres across passages, indicating good genetic stability. However, whether these sites affect virulence and replication requires further investigation. Phylogenetic analysis revealed that this strain belonged to genotype C, which is consistent with the strains circulating in mainland China in recent years. The experimental inactivated vaccine prepared from KM31-C05 induced effective neutralizing antibodies (1:128–1:256) in BALB/c mice and provided complete protection to suckling mice against lethal challenge with this CVB2 strain in maternal antibody protection experiments. Conclusions: KM31-C05 demonstrates potential as a CVB2 vaccine candidate in China and provides a theoretical basis for the development of a CVB2 vaccine. Full article

Background: The combination of photodynamic therapy (PDT) and immunotherapy has been explored as an innovative approach to enhance efficacy against tumors. However, PDT shows limited effectiveness in treating deep-seated tumors, as light and lasers do not sufficiently penetrate tissue. Methods: Herein, we introduced a nanocarrier (NP_VR) via self-assembly, using an amphiphilic copolymer to co-deliver the hydrophobic photosensitizer verteporfin (VP) and the immunoadjuvant imiquimod (R837). Results: Our X-ray-induced photodynamic therapy (X-PDT) mechanism induced NP_VR to generate a large amount of cytotoxic reactive oxygen species (ROS), which directly killed cancer cells. Moreover, the released R837 facilitated immunogenic cell death following the X-PDT process and promoted the maturation of dendritic cells (DCs), thereby eliciting immune responses against malignant triple-negative breast cancer (TNBC). In animal experiments, the combined therapy using NP_VR showed a tumor growth inhibition rate of ~70%. Conclusions: This novel strategy opens new avenues to designing next-generation nanomedicines for use in immunotherapy and other combination therapies. Full article

We report on the isolation and comprehensive genomic and biochemical characterization of Aspergillus fumigatus VP2T, a thermophilic filamentous fungus recovered from Himalayan Forest soil with exceptional lignocellulolytic capacity. Whole-genome sequencing revealed a 32.1 Mb genome encoding 12,675 predicted genes, including an extensive repertoire of >300 carbohydrate-active enzymes (CAZymes). Notably, the genome harbors multiple auxiliary activity enzymes, including AA9-family lytic polysaccharide monooxygenases and several cellobiose dehydrogenases (CDHs), supporting oxidative–hydrolytic synergism during biomass degradation. Submerged fermentation using a cellulose–wheat bran–rice straw substrate induced high enzyme titers, including 33 U/mL endoglucanase and 131 U/mL CDH, exceeding activities commonly reported for both native and engineered fungal strains. Although exoglucanase (0.02 U/mL) and xylanase (14.22 U/mL) activities were comparatively modest, the strain VP2T demonstrated superior hydrolysis of untreated rice straw, achieving a 1.89-fold increase in saccharification efficiency relative to the commercial enzyme cocktail Cellic^® CTec2. Scanning electron microscopy confirmed extensive disruption of lignocellulosic architecture, consistent with enhanced enzyme accessibility and oxidative fiber loosening. Collectively, genomic evidence and functional assays identify A. fumigatus VP2T as a redox-optimized, moderately thermophilic biocatalyst suited for low-pH lignocellulose conversion. This study highlights the value of exploring thermophilic fungal biodiversity to discover native strains with inherent oxidative capacity, offering promising alternatives to pretreatment-intensive biorefinery processes and informing the rational development of tailored enzyme systems. Full article

Viewport prediction is a key component in tile-based 360° video streaming. Existing viewport prediction models based on Long Short-term Memory Networks (LSTM) or Transformer typically output a single deterministic future trajectory through deterministic mapping, which fails to capture the inherent randomness in viewing behavior. Moreover, when encoding trajectory features, such models often map trajectory coordinates directly into a high-dimensional space while neglecting the spatial information inherent in the coordinates themselves. Additionally, they exhibit limitations in capturing cross-modal relationships between visual and trajectory features. To address these issues, this paper proposes DiffVP, a diffusion model for viewport prediction in 360° videos. Under the constraints of viewing historical trajectories and video saliency maps, DiffVP leverages Denoising Diffusion Implicit Models (DDIMs) to model future viewing trajectories in the form of probability distributions, generating diverse and reasonable prediction results. In the denoising network, DiffVP employs Explicit Coordinate-Time Encoding (ECTE) to model the temporal dependencies of trajectories and the spatial relationships among coordinates; moreover, a Coordinate-Aware Saliency Features Fusion (CASF) module is proposed to achieve cross-modal alignment and interactive fusion of saliency and trajectory features. Experimental results on three public datasets demonstrate that DiffVP achieves the best accuracy for 2–5 s viewport prediction without sacrificing the performance of short-term (<1 s) prediction. Full article

This study investigates the influence of varying positive–negative polarity ratios (EP:EN) on melt pool evolution during alternating current CMT (VP-CMT) arc additive manufacturing through a combined experimental and numerical approach. A multi-layer single-track droplet-melt pool coupling model was established, revealing the regulatory mechanisms governing melt pool flow, temperature distribution, and dimensional changes. These are driven by differences in arc morphology, heat input, and mechanical forces during EP and EN phases. Results indicate that molten pool flow is primarily governed by wire feed, retraction, and Marangoni forces. During the EP phase, arc divergence and elevated heat input result in significantly higher flow velocities than in the EN phase. Molten pool length increases with rising EP proportion, exhibiting periodic dynamic variations. Lateral flow intensity intensifies as EP ratio increases, directly influencing cladding layer morphology. This study provides theoretical basis for optimising additive manufacturing quality by adjusting the EP:EN ratio. Full article

The predatory bug Arma custos (Hemiptera: Pentatomidae) is a natural enemy insect capable of preying on over 40 types of agricultural and forestry pests. Here, we describe the characteristics of the morphology and ultrastructure of its venom apparatus visualized using light and electron microscopy. Light microscopy revealed that the venom apparatus of A. custos consists of a pair of main gland and tubular accessory gland. The main gland consist of two lobes, the anterior main gland (AMG) and posterior main gland (PMG). Between the two lobes of the main gland, there is a strong constriction, characterizing a hilum (Hi) where two separate ducts, the venom duct of the main gland (VD) and the duct connecting the accessory gland to the main gland (AMD), are inserted. The VD extends toward the head and connects to the venom pump (VP), while the AMD extends toward the thorax and connects to the accessory gland (AG). Ultrastructural examination of the venom glands reveals that the AMG and PMG consist of a layer of cubic or spherical glandular cells forming a large circular lumen, while the AG exhibits two narrow lumens. The secretory cytoplasm of AMG, PMG, and AG contains a well-developed rough endoplasmic reticulum, along with mitochondria, nuclei, secretory vesicles, autophagosomes, and secretory granules. However, significant differences exist in the ultrastructural characteristics among the three glands. Unlike glandular secretory cells in the venom glands, the ultrastructure of VD, and AMD reveals only well-developed nuclei, mitochondria, and elaborate plasma membrane folds. These results indicate that venom proteins are synthesized and stored by the AMG, PMG, and AG, while the VD and AMD ducts are responsible for transporting the venom. Full article

To identify BKPyV, the VP1 protein sequence was analyzed and classified into genotypes in 246 RTRs before and after RTx from deceased donors during a one-year observation period. Quantitative assessment of BKPyV was conducted via qPCR. Prior to RTx, genotypes I and IV were identified in the urine (7.27 × 10⁶; 1.20 × 10⁵) and in serum (5.75 × 10⁴; 1.12 × 10⁴). After RTx, genotype I was predominant; identification of DNAuria-BKPyV (62.07%) and BKPyV-DNAemia (55.56%) peaked after three months, and the highest DNAuria-BKPyV titer was also observed after three months (6.48 × 10⁹), whereas the BKPyV-DNAemia titer did not peak until after six months (2.21 × 10⁷). The highest number of copies of genotype IV in the urine was observed after six months (9.54 × 10⁹), while the highest titer in the serum was not observed until after 12 months (3.88 × 10⁶). DNAuria-BKPyV precedes BKPyV-DNAemia, affects a larger group of patients, and has a greater and more easily detected viral load, which makes it not only an earlier marker, but the key predictive marker of greater clinical value than later detection of BKPyV-DNAemia alone. Early monitoring of DNAuria-BKPyV should be the basis of classical screening, and not merely an addition to it, and therapeutic interventions should be undertaken early to prevent nephropathy. Full article

Background and Aims: Permanent pacemaker (PM) implantation is an established treatment for symptomatic bradycardia. However, chronic right ventricular pacing (RVP) is associated with increased morbidity and mortality due to electrical and mechanical dyssynchrony, leading to pacing-induced cardiomyopathy (PICM). Prognostic markers for identifying patients at high risk of PICM remain scarce. This study compares patients with low (<30%) and high (≥30%) RVP burden with respect to echocardiographic parameters and clinical outcomes. Methods: This retrospective, double-blinded, single-center study included 105 patients who underwent dual-chamber PM implantation. RVP burden, left ventricular ejection fraction (LVEF), global longitudinal strain (LV-GLS), and all-cause mortality were assessed to evaluate the impact of RVP on LV function and clinical outcomes. Results: At baseline, the mean LVEF was 61 ± 6% and LV-GLS was 18 ± 4%. LVEF declined in seven patients (6.7%) during a mean follow-up of 30 ± 14 months, with a mean reduction from 56.1 ± 4.9% to 40.1 ± 5.0% (median 55% to 41%), thereby fulfilling the prespecified PICM definition (≥10% decrease from baseline >50%, excluding alternative causes). Of the 105 patients, 58 (55%) were classified into the low RVP group (<30%) and 47 (45%) into the high VP group (≥30%). High VP burden was associated with deterioration in both LVEF (6/47 [13%] vs. 1/58 [2%], p < 0.05) and LV-GLS (28/47 [60%] vs. 16/58 [28%], p < 0.001). In multivariable analysis, baseline LV-GLS was significantly associated with subsequent LVEF decline (OR 1.410, 95% CI 1.201–1.610, p < 0.001), and high VP burden was linked to LV-GLS decline (OR 1.358, 95% CI 1.160–1.534, p < 0.01). Kaplan–Meier analysis showed that time to LVEF deterioration (7 events) was significantly shorter in the high VP burden group (45.2 ± 2.9 vs. 55.7 ± 1.0 months, p < 0.05). Early LV-GLS decline within 1 year predicted subsequent LVEF deterioration (HR 7.210, 95% CI 4.239–9.516, p < 0.05), with a significantly shorter time to LVEF deterioration in these patients (34.7 ± 4.2 vs. 53.7 ± 1.4 months, p < 0.001). All-cause mortality did not differ significantly between high and low VP burden groups (p = 0.2). Conclusions: In patients with normal preimplant LVEF and ≥30% RVP, LV-GLS decline of >10% from baseline serves as an early and sensitive marker for subsequent LVEF deterioration and is associated with adverse outcomes. Early LV-GLS monitoring may help identify patients at higher risk for progressive ventricular dysfunction. Full article