Search Results (606)

Background: The early-life gut microbiota plays a critical role in programming intestinal barrier function and immune homeostasis, with profound implications for long-term host health. However, the effects of early-life compound probiotic intervention on the maturation of intestinal barrier function and the underlying molecular mechanisms remain incompletely understood, particularly in large-animal models relevant to human physiology. Methods: In this preclinical study, 3627 neonatal piglets—a well-established translational model for human infant gut development—were orally administered a novel compound probiotic formulation comprising Bifidobacterium longum subsp. infantis BZ, Lactobacillus plantarum LZ, and Pediococcus acidilactici PZ during early life. A total of 1512 fecal samples collected at seven time points from birth to day 180 were analyzed by 16S rRNA sequencing, and 525 samples from three developmental windows (days 10, 25, and 70) were subjected to LC-MS-based metabolomics. The candidate metabolite indole-3-lactic acid (ILA) was further mechanistically validated in a DSS-induced colitis mouse model and in IPEC-J2 cells. Results: Early-life probiotic intervention significantly enhanced intestinal barrier integrity, as evidenced by improved intestinal morphology and upregulated expression of tight junction proteins—zonula occludens-1 (ZO-1), occludin (OCLN), and Claudin-1 (CLDN1)—in the jejunum (p < 0.05). Notably, intervention at birth was more effective than post-weaning administration, and two administrations (birth + weaning) yielded superior outcomes compared with a single administration (p < 0.05). Microbiome analysis revealed enhanced microbial diversity and enrichment of beneficial genera during the juvenile-to-adult transition (p < 0.05). Metabolomic profiling identified ILA as a signature metabolite consistently elevated by probiotic supplementation. Conclusions: These findings provide evidence that early-life compound probiotic intervention is associated with improved intestinal barrier maturation, with ILA identified as a key candidate metabolite that may mediate this effect, as supported by functional validation in murine and cellular models. This provides a mechanistic rationale for probiotic-based strategies to support intestinal health in human infants during critical developmental windows. Full article

Warm-season precipitation over Sichuan, China, is jointly modulated by complex terrain, monsoon water vapor transport, and local convective activities, leading to significant spatiotemporal heterogeneity. However, radar observations over mountainous areas are frequently impaired by terrain blockage, beam shielding, and insufficient network coverage, which cause missing data and spatial discontinuity, thereby restricting the accurate monitoring of precipitation systems. To alleviate these problems, this study develops an Efficient Multi-Scale Attention (EMA) U-Net model integrated with Digital Elevation Model (DEM) information, termed EMA-U-Net-DEM, to retrieve radar composite reflectivity by utilizing multi-channel observations from the Fengyun-4A (FY-4A) Advanced Geostationary Radiation Imager (AGRI). In the experiments, FY-4A AGRI multi-spectral measurements were used as model inputs, while radar composite reflectivity products from the Severe Weather Automatic Nowcasting (SWAN) system were applied as reference labels. The modeling and validation were carried out using warm-season (June–August) datasets over Sichuan Province. The results indicate that the proposed EMA-U-Net-DEM exhibits better performance than the traditional U-Net and several typical attention-based benchmark models. Quantitatively, the model achieves a root mean square error (RMSE) of 6.728 dBZ, a mean absolute error (MAE) of 4.788 dBZ, a coefficient of determination $R^2$ of 0.656, a peak signal-to-noise ratio (PSNR) of 25.243 dB, and a structural similarity index measure (SSIM) of 0.793. Categorical verification further reveals that the model yields the highest critical success indices (CSI) of 0.850, 0.560, and 0.364 in the reflectivity ranges of 0–25 dBZ, 25–45 dBZ, and 45–70 dBZ, respectively, demonstrating its superior ability in characterizing weak precipitation backgrounds, moderate precipitation structures, and intense convective cores. The performance enhancements are mainly attributed to the strengthened multi-scale feature extraction by the EMA module and the effective topographic constraints introduced by DEM data. This study confirms that the fusion of FY-4A multi-spectral observations and topographic information can effectively improve radar composite reflectivity retrieval over complex terrain, providing a feasible solution for precipitation monitoring, quantitative precipitation estimation, and severe weather nowcasting in mountainous regions with limited radar coverage. Full article

Sclerotinia sclerotiorum causes destructive sclerotinia stem rot and severe yield losses in global rapeseed production. The Bacillus biocontrol strain YZUS007 serves as an eco-friendly alternative to synthetic fungicides, yet its control efficacy fluctuates under complex field conditions. This study aimed to investigate whether low-dose ZnO NPs could enhance the biocontrol efficacy of YZUS007 and to elucidate the underlying mechanisms. We isolated and identified the antagonistic strain Bacillus siamensis YZUS007 from the rhizosphere soil of healthy Brassica napus, which exhibited an in vitro pathogen inhibition rate of 78.4 ± 0.7%. Pot tests showed that YZUS007 (BC) achieved 60.79% control efficacy, whereas the YZUS007 + 20 μg/mL ZnO NPs group (BZ) reached 74.68%. Cell-free filtrate of YZUS007 (EC) had a 50.44% control efficacy, and filtrate with ZnO NPs (EZ) increased efficacy to 58.08%. LC-MS/MS identified four extracellular metabolites with increased relative abundances: cinnamic acid, sesamol, patchouli alcohol and 2-phenylbutyric acid. The combined treatment boosted defense enzyme activities and induced higher expression of the defense-related genes RBOH, PR1 and WRKY33. Collectively, low-concentration ZnO NPs significantly enhanced the biocontrol performance of YZUS007 by promoting antifungal metabolite accumulation, providing a low-dose, nanomaterial-assisted strategy for sustainable sclerotinia rot management. Full article

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), affects more than 6 million people worldwide, predominantly in Latin America. Current chemotherapy relies on Benznidazole (Bz) and Nifurtimox, which are associated with adverse effects and limited efficacy during chronic infection, underscoring the need for new therapeutic options. Natural products remain an important source of bioactive molecules for antiparasitic drug discovery. In this study, 34 extracts obtained from 18 Brazilian plant species were evaluated for anti-T. cruzi activity. After cytotoxicity assessment, extracts were screened against intracellular amastigotes (Tulahuen strain, DTU VI) and bloodstream trypomastigotes (Y strain, DTU II). Most samples exhibited low toxicity toward mammalian cells (LC₅₀ > 120 μg/mL). Among them, the inflorescence extract of Piper claussenianum (Miq.) C. DC. (PCFLD) showed the highest activity. At 20 μg/mL, PCFLD reduced intracellular parasite burden by 94%, with an EC₅₀ of 3.6 ± 0.36 μg/mL and a selectivity index of 20. Against trypomastigotes, the extract displayed an EC₅₀ of 11.56 ± 5.88 μg/mL and a selectivity index of 11. In an acute murine model, PCFLD (10 mg/kg/day) reduced peak parasitemia by 40%, outperforming Bz at the same dose. These findings identify P. claussenianum as a promising source of anti-T. cruzi compounds. Full article

This study investigates the time-dependent corrosion behavior of 6060 aluminum profiles subjected to three industrially relevant surface treatments: clear anodizing, black anodizing, and pre-anodizing followed by polyester powder coating during 30 days of immersion in NaCl solution. Electrochemical Impedance Spectroscopy combined with equivalent electrical circuit modeling was used to monitor corrosion evolution and identify the governing degradation mechanisms. Black-anodized specimens exhibited the highest initial corrosion resistance during the first 4 days of immersion, while clear-anodized specimens provided superior protection between 7 and 15 days due to the formation of a more protective inner oxide layer. Both anodized systems showed evidence of repassivation during prolonged exposure through corrosion product accumulation within the porous oxide structure. The pre-anodized/powder-coated system delayed corrosion initiation beyond 15 days, demonstrating the highest long-term barrier performance. Dynamic perpendicular impact loading after corrosion exposure revealed significant differences in mechanical durability: clear-anodized specimens maintained coating integrity up to 15 days, whereas black-anodized specimens experienced complete coating removal, associated with corrosion-induced microcracks and void formation observed by SEM. Overall, clear anodizing provided the best balance between corrosion resistance and post-corrosion mechanical durability, while the pre-anodized/powder-coated system offered the greatest long-term corrosion protection, demonstrating that the optimum surface treatment depends on the intended service conditions. Full article

Background/Objectives: Due to advances in paleogenetic research, a substantial amount of data has been accumulated on the Y-chromosome of the ancient Scytho-Siberian population that inhabited South Siberia and the adjacent territories of modern Mongolia and North-West China. It became possible to compare the Y-chromosomes of ancient men and modern Tuvans of various clans. Methods: We analyzed Y-SNPs and Y-STRs of ancient and modern samples. Results: During Tuvan ethnogenesis, the total frequency of the haplogroups Q and R1a dropped from 85% in Scytho-Siberian populations to 35% in modern Tuvans. Today, the gene pool of Tuvans is dominated by haplogroups N-P43, N-M178 and O-M175, which remain undetected in the samples from the Scytho-Siberian period. An analysis of the Y-STR phylogenetic networks that integrated data on Y-STR haplotypes and Y-SNPs of the Q and R1a haplogroup branches of both ancient and modern specimens provides findings that should be interpreted as broad phylogenetic affinities consistent with the paternal lineage continuity of haplogroups Q-YP1102 and R1a-Y39884. At the same time, the TMRCA estimate for the Y-STR cluster of the dominant branch of haplogroup Q in modern Tuvans, Q-YP1102-YP1691, is only 670 ± 130 YBP. Clusters of Y-STR haplotypes of the R1a-Y39884, R1a-YP1506, and R1a-YP1543 branches in modern Tuvans are also young and date back to between 1200 and 400 YBP. The Scytho-Siberian haplogroups R1a-YP1272, Q-BZ180, and N-Y147969 were not found in our sample set of modern Tuvans (n = 633). Conclusions: Haplogroups Q-YP1102 and R1a-Y39884 originated in Siberia and their branches are typical for the modern indigenous populations of South and West Siberia. Q-YP1102 marks the Yeniseian substrate and R1a-Y39884 was common in the ancient Siberian Andronovo culture. Overall, the gene pool of the Tuvan population was shaped (at least since the Scytho-Siberian period) by close interactions with the gene pools of Siberia and West Mongolia. However, the resolution of Y-SNP and Y-STR genotyping, as well as the limited sample size of ancient samples and their location in a limited area of the Eerbek River valley, do not allow us to conclude about the direct inheritance of modern Tuvan lineages from the ancient Scytho-Siberian population. Full article

Background: Volumetric absorptive microsampling (VAMS) is an emerging tool for therapeutic drug monitoring (TDM) of several drugs including antiseizure medications (ASMs). Here, we compared the concentrations of carbamazepine (CBZ), levetiracetam (LEV), lacosamide (LCS), topiramate (TPR) and the benzodiazepine (BZ) clobazam (CLB) in plasma and VAMS samples. Methods: VAMS samples were collected by fingerprick in pediatric patients followed at our center. Patients were also subjected to conventional venous blood sampling. Plasma and VAMS samples were analyzed by using a UHPLC-MS/MS validated kit for AEs and BZs (ClinMass LC-MS/MS Complete Kit^®). A cross-validation analysis was performed by using Spearman correlation (rho), Deming regression and Bland–Altman plots. Results: Two analytical methods for measuring selected AEs and BZs in VAMS samples were developed and validated in accordance with the ICH M10 guidelines. Based on Bland–Altman results, a satisfactory agreement was observed between VAMS and plasma for CBZ, LCS, TPR, LEV and N-CLB. Considering the absence of interchangeability between capillary blood and plasma levels for CBZ-Diol, -Epoxi and CLB, a blood to plasma ratio was used to convert VAMS values into estimated plasma concentrations. Comparison of estimated vs. observed plasma results showed a successful predictive performance for this conversion approach. Conclusions: A positive agreement between plasma and VAMS was found for CBZ, LCS, TPR, LEV and N-CLB. Conversely, a conversion factor based on blood to plasma ratio should be adopted to convert CBZ-Diol, -Epoxi and CLB VAMS results into estimated plasma concentrations. This study confirmed the utility of VAMS for TDM of selected ASMs in pediatric patients during routine clinical practice. Full article

Low-density granulocytes (LDGs) have been implicated in the pathogenesis of several autoimmune diseases, yet their role in Sjögren’s disease (SjD) remains poorly understood. We enrolled 90 SjD patients and 30 healthy controls (HCs) and identified LDGs as CD14^−/lowCD15⁺ cells by flow cytometry, with intracellular interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) staining, and further analyzed CD16 as a maturation marker in LDGs and T helper 17 (Th17) cell frequency. LDG percentages were significantly elevated in active SjD compared with inactive patients (p < 0.001) and HCs (p < 0.0001), and correlated positively with EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) (r = 0.355, p = 0.0006), erythrocyte sedimentation rate (ESR) (r = 0.325, p = 0.0061), γ-globulin (r = 0.334, p = 0.0177), and Th17 frequency (r = 0.537, p = 0.0068). LDG expansion was accompanied by enrichment of immature CD16^−/low cells (r = −0.798, p = 0.0100). Patients with renal or pulmonary involvement showed higher LDG levels (p = 0.0004), and in SjD -associated interstitial lung disease (SjD-ILD) patients, LDG percentage showed a positive but non-significant trend with serum Krebs von den Lungen-6 (KL-6) levels (r = 0.497, p = 0.102). LDG levels decreased following treatment in longitudinally followed patients, and LDGs from active patients exhibited higher IL-6 and TNF-α production ratios relative to monocytes than those from inactive patients. Stratification by LDG levels revealed significant associations with disease activity, laboratory parameters, and organ involvement. These findings suggest that LDGs are associated with disease activity and organ involvement, may serve as potential biomarkers, and may contribute to the pathogenesis of SjD. Full article

Precipitation nowcasting plays an important role in mitigating the impacts of extreme weather events on social production and daily life. However, existing methods still face two major limitations. (1) Convolutional neural network-based methods are insufficient in modeling the temporal dependencies of radar echo sequences, which may lead to information loss in the prediction results. (2) Most existing methods enlarge the receptive field by stacking convolutional layers. This strategy makes it difficult to obtain a truly global receptive field and effectively model global dependencies, resulting in limited accuracy in heavy rainfall prediction. In addition, spatiotemporal information at different time steps is not fully integrated, and the multi-scale directional features of rainbands are often ignored. To address these issues, this paper proposes ST-TriMambaUNet, which consists of an encoder, a decoder, and a feature enhancement module. First, a Spatiotemporal Fusion Attention (STFA) was designed, including global spatial attention and temporal attention. It can effectively learn long-range spatial correlations and capture the temporal dependencies of radar echo sequences in a parallel manner. Second, a Multi-Scale Interaction Mamba (MSIM) module was developed with three branches. The first branch leverages Mamba to model global spatiotemporal dependencies with linear complexity. The second branch promotes spatiotemporal information interaction through channel shuffle and further combines Mamba to model global spatiotemporal dependencies. The third branch designs Multi-Scale Directional Convolution (MSDC) to learn the multi-scale directional features of rainbands. Finally, the features from the three branches are dynamically fused through the designed adaptive gated fusion mechanism. This enhances the model’s representation capability for strong-echo core regions and multi-scale precipitation band structures. Experimental results on two public datasets, SEVIR and CIKM, demonstrated that the proposed ST-TriMambaUNet achieved clear advantages in both overall prediction accuracy and heavy rainfall scenarios. In particular, under the high-threshold precipitation scenarios of SEVIR (160, 181, and 219), the CSI was improved by up to 10.19%. In the heavy rainfall scenario of CIKM at 40 dBZ, CSI, POD, and HSS were improved by 5.29%, 8.07%, and 4.65%, respectively. Full article

White-nose syndrome (WNS), caused by the psychrophilic fungus Pseudogymnoascus destructans, poses a severe threat to wild bat populations. Caves serve as unique microecosystems. Exploring antagonistic microorganisms and their volatile antifungal compounds within these native environments has emerged as a promising ecological control strategy. In this study, we isolated four antagonistic bacterial strains from bat cave soil that completely inhibit P. destructans. Additionally, we identified benzaldehyde (BzH) and 2,5-dimethylpyrazine (2,5-DMP) as their primary antifungal volatile organic compounds (VOCs). Combined physiological, biochemical, and multi-omics analyses revealed that these two VOCs disrupt the structural integrity of the fungal cell wall and membrane. This disruption triggers abnormal energy metabolism and compensatory ATP accumulation, leading to a significant intracellular burst of reactive oxygen species and the impairment of primary antioxidant defenses. This sustained oxidative stress causes irreversible DNA damage, endoplasmic reticulum stress, and basal metabolic dysfunction. Consequently, this cascade induces apoptosis and significantly downregulates the expression of essential virulence genes. In conclusion, this study systematically elucidates the molecular network through which VOCs released by cave soil microorganisms antagonize P. destructans. These findings provide a theoretical foundation and candidate intervention molecules for the contactless biocontrol of WNS. Full article

Background/Objectives: Improving the health literacy (HL) of adolescents and parents is an actual theme and needs detailed investigation in a bilingual region. Methods: In this cross-sectional school-recruited sample, parental and adolescent HL were associated with adolescent mental health screening outcomes. Exploratory indirect-effect models suggested possible pathways for future longitudinal research. About 3229 questionnaires provided information. Standardized internationally validated instruments were used. Parental and self-reported data were compared; the associations of HL with social support, problematic Internet use, questionnaire language, and mental health screening outcomes were explored. Results: Adolescents’ HL was associated with questionnaire language, with higher scores observed for German (23.1% high HL) than for Italian (14.3%). Higher levels of HL among both parents and adolescents were related to better mental health screening outcomes in adolescents with higher associations to adolescents’ HL. Social support and problematic Internet use were associated with both mental health screening outcomes and parental- and self-reported HL. HL related partly to the observed. Higher parental education was related to better parental HL and higher parental response rates. Conclusions: Enhancing HL among parents and adolescents through school-based programs needs language and education specific interventions. In the bilingual context of South Tyrol, the introduction of a bilingual program needs to be accompanied by scientific investigations, targeting language specific needs and differences. Existing international German school-based programs can be the basis for developing interventions to fit the Italian healthcare and educational system. South Tyrol offers the unique opportunity to introduce a scientific-based bilingual HL concept at schools. Enhancing information seeking and appraisal strategies in adolescents may be essential. Full article

Progressive stamping is a high-efficiency sheet metal forming method in the automotive and mass production industries, where material characteristics significantly influence process stability, cutting force, tool life, and final part quality. Herein, we report the effects of the chemical composition and mechanical properties of DD11 low-carbon steel on punching force during progressive stamping. Ten DD11 material batches with varying chemical compositions and mechanical properties were subjected to experimental investigation. Material characterization involved spectroscopic chemical analysis, tensile testing in accordance with ISO 6892-1, and hardness measurement. Punching tests were performed with a Zwick BZ2-MMAG100.SH01 universal testing machine that incorporates a punch–die assembly to study force–displacement behavior under controlled conditions. The cutting curves of these materials were analyzed to determine the maximum cutting and fracture loads, which were then statistically correlated with the materials’ chemical and mechanical parameters. The results indicated that tensile strength and yield strength are the strongest statistically significant contributors to the maximum cutting load and the fracture point, and that the correlation coefficients for these measurements were +0.866 and +0.869, respectively. Carbon, chromium, and silicon showed the most positive effect on cutting resistance; whereas, titanium was negatively associated with each of the tested responses among chemical composition measures. But none of the chemical factors were statistically significant. The analysis also showed that material hardness yields the highest predictive performance for cutting force behavior (Pearson correlation coefficients up to 0.935 and a regression coefficient of R² = 0.875). Results of this study show that DD11 cutting behavior at progressive stamping is controlled primarily by strength-dependent mechanical characteristics rather than chemical composition variations. Full article

Here we describe a compact radiofrequency (RF) magnetic field generator designed to generate fields within millimeter-scale volumes. The device consists of printed multilayer circuit board (PCB) coils stacked in a paired parallel configuration. Compared to conventional solenoidal systems, this architecture significantly reduces device size, sample volume, and power requirements. We characterize the RF response of the system, including impedance and scattering parameters, and describe the behavior near ~330 kHz, which overlaps with frequencies common in magnetic nanoparticle heating, magnetic actuation, and other applications requiring localized fields. Electromagnetic modeling is used to evaluate magnetic field amplitude and spatial homogeneity (finding a maximum local deviation from the mean field of 5.5%). The mean B_z field across a 5 mm × 5 mm ROI centered between paired PCBs was 6.3 ± 0.1 mT/A (compared to 6.1 ± 1.0 mT/A measured experimentally). These results demonstrate operating parameters consistent with nanoparticle heating applications for PCB-based coil pairs. Full article

This study investigates the low-latitude ionospheric response over the Eastern Hemisphere during two successive geomagnetic storms on 12–13 November 2025. BDS-GEO observations from 20 GNSS stations, CODE GIM data, Swarm satellite observations, and simulations from the TIEGCM and HWM14 models were integrated to investigate regional ionospheric disturbances, single-station responses, and Equatorial Ionization Anomaly (EIA) evolution. During the first storm, with SYM-H reaching −254 nT, EIA intensification and poleward expansion beyond ±20° magnetic latitude were observed, with VTEC approaching 100 TECU at stations over Australia and rTEC exceeding 80% over Australia and the adjacent Pacific Ocean. Swarm observations showed TEC decreases within the EIA crest region and TEC increases in the surrounding areas. In contrast, the second storm, with SYM-H reaching −154 nT, produced disturbances with lower amplitudes, mainly characterized by localized positive TEC anomalies near the magnetic equator within 100°E–180°E, together with negative TEC anomalies in the surrounding low-latitude regions. The first storm was associated with southward IMF Bz reaching −54 nT and electrodynamic uplift related to PPEF, which contributed to the superfountain effect, whereas the second storm was influenced by residual disturbed neutral winds, reduced O/N₂ ratios at low latitudes, and the preconditioned ionospheric state inherited from the first storm. These results demonstrate that successive geomagnetic storms can produce different ionospheric responses in terms of intensity, spatial morphology, and driving mechanisms, highlighting the event dependence and regional variability of low-latitude ionospheric storm responses. BDS-GEO observations offer distinct advantages for monitoring localized ionospheric disturbances over the Eastern Hemisphere. Full article

Background: Benzimidazole (BZ) resistance in the gastrointestinal nematode Haemonchus contortus is a major constraint to sheep production worldwide. However, data on the prevalence and molecular mechanisms of resistance in Yili Prefecture, Xinjiang—a key livestock region in Northwestern China—remain limited. This study aimed to determine the frequency of BZ resistance-associated single nucleotide polymorphisms (SNPs) in H. contortus populations from Zhaosu and Tekesi counties. Methods: Adult male worms (n = 150) were collected from naturally infected sheep at local abattoirs. Species identity was confirmed morphologically by sequencing the internal transcribed spacer 2 (ITS-2) region. A 385 bp fragment of the isotype-1 β-tubulin gene was amplified and sequenced to detect SNPs at codons 167 (F167Y), 198 (E198A), and 200 (F200Y). Results: The F167Y mutation was absent in all individuals. In contrast, the E198A mutation occurred at exceptionally high frequencies, with resistant allele frequencies (RAF) of 64.7% in Zhaosu and 52.7% in Tekesi. The F200Y mutation showed clear geographical variation: it remained low in Zhaosu (RAF = 9.3%) but was substantially higher in Tekesi (RAF = 33.3%). Haplotype analysis revealed that resistance in Zhaosu was driven primarily by the E198A mutation, whereas the Tekesi population exhibited complex patterns of co-selection of both E198A and F200Y, with a high proportion of double-heterozygous individuals (29.3%). Conclusions: This study provides comprehensive molecular evidence of severe BZ resistance in H. contortus populations from Zhaosu and Tekesi counties, Yili Prefecture. The marked predominance of the E198A mutation, together with the emergence of multi-locus resistance in Tekesi, indicates a rapid escalation of resistance beyond historical levels. These findings suggest that benzimidazoles are likely ineffective in this region and highlight the urgent need to revise local parasite control strategies. Full article