Search Results (890)

Background/Objectives: The aim of this study was to assess NB CE-Chirps for diagnosing Superior Semicircular Canal Dehiscence Syndrome (SSCDS) with cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs), and to compare them with Tone Bursts (TBs). Methods: Nine subjects diagnosed with SSCDS were included (four men/five women, median = 61 years, range = 31–79 years). Intensity thresholds at 500 Hz were investigated with both stimuli. A response was also sought when NB CE-Chirps and TBs were delivered at 4000 Hz for c and oVEMPs. Results: Both 500 Hz TBs and 500 Hz NB CE-Chirps significantly differentiated affected ears from healthy ears for cVEMPs (p < 10⁻³ in both cases) and oVEMPs (p < 10⁻³ in both cases). Furthermore, we observed significantly lower intensity thresholds in SSCDS ears with 500 Hz NB CE-Chirps than with 500 Hz TBs for both cVEMPs (p < 10⁻³) and oVEMPs (p = 0.036). Regarding the response rate at 4000 Hz, only TBs consistently showed a response in 100% of cases for the affected ears, with no response in healthy ears for both cVEMPs and oVEMPs. However, there was no significant difference between the response rates obtained at 4000 Hz using TBs and NB CE-Chirps in affected ears (p = 1.000 for cVEMPs and p = 1.000 for oVEMPs). Conclusions: Searching for intensity thresholds with NB CE-Chirps 500 Hz in cVEMPs and oVEMPs is an effective method for diagnosing SSCDS, likely with better frequency specificity than with 500 Hz TBs. Stimulation at 4000 Hz with both TBs and NB CE-Chirps appears to be a promising test for easily screening this syndrome, reducing both sound exposure and the duration of the examination. The possibility to reduce rise time in 4000 Hz TBs may favor this stimulus over NB CE-Chirps at this frequency for this disease. These results should be confirmed in larger cohorts including patients with more severe forms. Full article

This study focuses on the spatial variation in seed germination characteristics of Picea glauca and P. mariana, prominent and widespread species within the Canadian boreal forest. The main objective was to determine seed germination requirements of geographically distinct seed collections of P. glauca and P. mariana. A total of 73 collections of P. glauca and 62 collections of P. mariana were selected across Canada and tested for germination under various temperatures. Base temperature (T_b) and thermal time required to reach 50% germination (TH₅₀) were derived from thermal model parameters for all seed collections. Correlation analyses between seed germination traits, geographic, and climatic variables were conducted. Base temperatures for germination of P. glauca ranged from 5.2 to 11.9 °C while P. mariana had base temperatures ranging from 6.2 to 12.8 °C, indicating a broader temperature range for the former to initiate germination. Optimal germination temperatures ranged from 15 to 20 °C for P. glauca and from 17.5 to 30 °C for P. mariana. Thermal time requirements for 50% germination were higher for P. glauca than for P. mariana, indicating that the former takes longer to germinate under the same temperature conditions. Latitudinal-related variables such as temperature of sites had a stronger influence on germination relative to precipitation or potential evaporation and affected seed viability, final germination and germination capacity of all seed sources. Seed viability was lower in northern seed collections and germination capacity was diminished at lower temperatures for both species. The results from this study can be built into models predicting shifts in boreal forest species under climate change. Full article

Tributyrin (TB), as a novel feed additive, holds broad market prospects and is crucial for promoting fish growth and maintaining intestinal health. We first identified the fatty acid metabolism-related gene cpt1b in the intestines of mandarin fish (Siniperca chuatsi) from the TB-supplemented group. A total of 600 mandarin fish (200.0 ± 5.0 g) were evenly allocated into three groups. The control group (C) received only the standard extruded feed, while the experimental groups were supplemented with tributyrin (TB) at concentrations of 500 mg/kg (T1 group) and 1000 mg/kg (T2 group), respectively. Cloning yielded a 2364 bp open reading frame (ORF) encoding 787 amino acids, with the gene possessing two conserved transmembrane domains. Phylogenetic analysis further indicated a close phylogenetic relationship between largemouth blackbass (Micropterus salmoides) and mandarin fish. Tissue distribution and intestinal enzyme activity analyses revealed that supplementation with varying concentrations of TB upregulates cpt1b gene expression in different tissues, while modulating intestinal digestive enzyme and antioxidant enzyme activities. Our findings suggest a potential mechanism involving enhanced intestinal enzyme activity, reduced fat accumulation, increased expression of lipid oxidation-related genes, and accelerated TB degradation in the intestine. Full article

Bovine purified protein derivative (PPD-B), a crude protein extract from Mycobacterium bovis cultures, has been the standard reagent for delayed-type hypersensitivity (DTH) testing in cattle, but its undefined composition and variability compromise reproducibility and specificity. To address these limitations, we developed and evaluated RRbTB-E, a recombinant fusion protein comprising ESAT-6, as a defined alternative for skin testing. RRbTB-E was produced in Escherichia coli, purified by affinity chromatography, and characterized by SDS-PAGE and Western blot. In M. bovis-sensitized guinea pigs, RRbTB-E induced robust DTH reactions comparable to PPD-B, with consistent performance across six independent experiments and long-term stability after storage at 4–8 °C for more than 900 days. Furthermore, RRbTB-E did not induce significant reactions in non-sensitized or Mycobacterium avium–sensitized animals, confirming antigenic specificity. RRbTB-E also elicited DTH responses in Mycobacterium tuberculosis–sensitized guinea pigs. In naturally infected cattle, it triggered responses similar in magnitude to PPD-B, while remaining negative in non-infected animals. These findings support RRbTB-E as a stable, reproducible, and specific candidate for standardized intradermal testing in bovine tuberculosis diagnosis. Full article

Antimicrobial resistance (AMR) threatens global health, particularly through the rise of multidrug-resistant tuberculosis (MDR-TB) and other critical bacterial infections such as methicillin-resistant Staphylococcus aureus (MRSA). Rifamycins remain frontline antibiotics but are increasingly undermined by resistance. Here, we introduce a click-enabled platform for the synthesis of C8-functionalized rifamycins, which can be converted in a single additional step into efficacious 3′-hydroxy-5′-aminobenzoxazinorifamycins (bxRifs) and enzymatically into 25-deacetylated rifamycins (deAcRifs), providing access to novel antibacterial scaffolds that expand beyond the scope of traditional C8 modifications. Accordingly, we establish a modular strategy for late-stage analog development of the complex natural product rifamycin S, wherein azido and alkyne functionalities are installed via tailored core chemistry and converted into 1,2,3-triazoles through copper(I)-catalyzed click chemistry. Another key feature of this work is the development of systematic HPLC purification methods, enabling the isolation of analytically pure compounds despite structural complexity. The resulting analogs exhibit distinct antibacterial profiles, notably against Gram-positive bacteria including MRSA and Streptococcus mutans, informing structure–activity relationships and offering a foundation for further optimization. This approach supports the rapid diversification of rifamycin scaffolds to combat the escalating threat of AMR, while also establishing a foundation for future discovery through bioorthogonal applications. Full article

Background/Objectives: Current musculoskeletal health assessment expanded beyond bone mineral density (BMD) at central DXA to include, for instance, trabecular bone score (TBS) and emergent biomarkers, such as adipokines and myokines (e.g., irisin) assays. A current gap in their application is reflected in limited research regarding adrenal tumors, especially non-functional adrenal tumors/mild autonomous cortisol secretion (NFATs/MACS). To assess this current gap, we aimed to explore beyond BMD, specifically, TBS and circulating irisin, in relation to the adrenal status in NFATs/MACS. Methods: This is a prospective, cross-sectional, single-center, exploratory study, conducted between October 2024 and December 2025. Results: A total of 81 menopausal women were included (mean age of 63.26 ± 8.82 years, 15.86 ± 9.5 years since menopause, average BMI of 30.69 ± 5.76 kg/sqcm. Out of them, 33.33% had NFATs/MCAS (group AI) and 66.67% were controls (group C), with similar age, years since menopause, and BMI. The prevalence of type 2 diabetes was 66.67% versus 68.52% (p = 0.865). TBS correlated with lumbar BMD/T-score (N = 33), while age and lumbar BMD were independent TBS predictors (N = 81), but not type 2 diabetes nor NFAs/MCAS. TBS correlated with the five-year age groups (r = −0.273, p = 0.003). Irisin correlated with osteocalcin (r = −0.252, p = 0.007), P1NP (r = −0.187, p = 0.049) and CrossLaps (r = −0.209, p = 0.026) in tumor-free controls. In the AI group, a higher irisin was associated with a higher second-day cortisol after 1 mg DST (r = 0.11, p = 0.584) and a lower ACTH (r = −0.716, p < 0.001). The rate of low TBS (based on 1.350 cutoffs) was 48.15% versus 38.89% in group AI versus C. In the AI group, patients with low TBS had lower osteocalcin, P1NP, and CrossLaps than those with normal TBS, with a similar rate of type 2 diabetes (which might reduce the bone turnover markers) and MACS-positive prevalence (between 25 and 28%). Conclusions: The median glycated hemoglobin A1c (5.78% versus 5.93%, p = 0.94) and median HOMA-IR (1.53 versus 1.42, p = 0.948) suggest a certain level of glucose control, which might not be reflected in severely damaged bone microarchitecture, as shown by TBS. Irisin may be one of the additional factors in these tumors reflecting the hormonal burden. Irisin was statistically significantly elevated with the increase in BMI groups. To our best awareness, this is the first synchronous analysis of TBS and irisin levels in this type of tumor to address the bone status in relation to the glucose profile and adrenal panel. Noting this is an exploratory, hypothesis-generating study, further research will highlight the true value of TBS and irisin for practitioners in the adrenal field, including multi-layered models of bone status prediction. Full article

Background/Objectives: Pulmonary tuberculosis (TB) is accompanied by inflammation-driven hypercoagulability and increased venous thromboembolism risk. We investigated whether the natural anticoagulants protein C and free protein S are reduced in active TB and whether baseline levels are associated with bacillary burden, treatment response, CT evolution, and pulmonary embolism (PE). Methods: We conducted a prospective cohort study in Romania, including 63 adults with newly diagnosed, bacteriologically confirmed, drug-susceptible pulmonary TB and 30 TB-free controls (October 2024–December 2025). Venous blood was collected at baseline (before anti-TB therapy) and at 6 months to quantify inflammatory and coagulation parameters, protein C, and free protein S. Sputum AFB smear was assessed at baseline, 2 months, and 6 months; chest CT was performed at baseline and 6 months. Propensity score matching (age, sex, BMI, smoking) and multivariable regression were used to account for confounding. Logistic regression and ROC analyses evaluated the prediction of BK persistence. Results: Compared with controls, TB patients had substantially lower baseline protein C and free protein S levels, and higher D-dimer levels (all p < 0.001). In matched multivariable models, TB status remained independently associated with lower baseline natural anticoagulant levels. Lower baseline protein C and free protein S clustered with higher inflammatory markers and higher bacillary burden, and independently predicted BK persistence at 2 and 6 months (OR per 1%-point increase ~0.93–0.95 for protein C and ~0.92–0.94 for free protein S; all p < 0.001). Discrimination for BK persistence was high (AUCs ~0.88–0.89). Lower baseline levels of natural anticoagulants were also associated with greater residual CT abnormalities at 6 months. PE cases had significantly lower protein C and free protein S than PE-free patients. Conclusions: Active pulmonary TB is associated with marked depletion of protein C and free protein S. Baseline reductions identify patients with higher inflammatory/coagulation activation, higher bacillary burden, delayed microbiological clearance, more residual CT disease, and PE, supporting their potential role as adjunct risk-stratification biomarkers. Full article

Background: Bone-seeking radiopharmaceuticals based on bisphosphonates enable targeted therapy of skeletal metastases. They are suitable carriers for therapeutic radionuclides such as terbium-161 (¹⁶¹Tb), a β⁻ emitter that additionally releases short-range conversion and Auger electrons, which may enhance radiation dose delivery to small lesions. This study explored the potential of the well-established DOTA conjugated bisphosphonate BPAMD (4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10 tetraazacyclododec-1-yl)acetic acid) radiolabeled with ¹⁶¹Tb as a bone-targeted radiopharmaceutical, focusing on the theranostic and radiophysical advantages conferred by the radionuclide. Methods: BPAMD was radiolabeled with ¹⁶¹Tb and ¹⁷⁷Lu under mild conditions (pH 4.5, 95 °C, 30 min); subsequently, the radiochemical purity was assessed by radio-TLC. Physicochemical properties (charge, lipophilicity, protein binding), in vitro stability (saline and human serum, 48 h), and hydroxyapatite (HAP) binding were evaluated for [¹⁶¹Tb]Tb-BPAMD. Biodistribution was investigated in healthy Wistar rats (n = 3 per time point) at 2 h, 24 h, and 7 days post-injection. Computational density functional theory (DFT) analyses were performed to explore the coordination chemistry of Tb³⁺ and Lu³⁺ with BPAMD. Results: Both complexes achieved a radiochemical yield of greater than 98%. [¹⁶¹Tb]Tb-BPAMD exhibited negative charge, high hydrophilicity (logP = −3.92 ± 0.13), low protein binding (19.07 ± 1.01%), excellent radiochemical stability under simulated physiological conditions (>97% at 48 h), and strong hydroxyapatite affinity (>98% with ≥10 mg HAP). Biodistribution showed high, stable bone uptake (8.06% ID/g at 2 h; 6.70% ID/g at 24 h; 5.31% ID/g at 7 d) with rapid blood clearance (<0.001% ID/g at 24 h) and low non-target retention. To contextualize its performance, [¹⁶¹Tb]Tb-BPAMD was compared with [¹⁷⁷Lu]Lu-BPAMD, which demonstrated similarly strong skeletal retention (8.74% ID/g at 2 h; 8.08% ID/g at 24 h; 5.25% ID/g at 7 d) but comparatively higher non-target organ uptake. DFT calculations indicate that both Tb³⁺ and Lu³⁺ favor octa-coordinated BPAMD complexes. Conclusions: [¹⁶¹Tb]Tb-BPAMD exhibits excellent radiochemical and pharmacokinetic properties, with enhanced biodistribution selectivity over [¹⁷⁷Lu]Lu-BPAMD. Combined with the radiobiological advantages of ¹⁶¹Tb, it represents a promising theranostic candidate for targeted therapy of bone metastases. Full article

Pulmonary tuberculosis (TB) remains a major global health challenge. The molecular and metabolic responses of monocyte-derived macrophages (MDMs), which are critical for host defense against Mycobacterium tuberculosis (Mtb), are not fully characterized. A murine pulmonary TB model was established by intravenous injection of BALB/c mice with the attenuated Mtb strain H37Ra; controls received saline. After 8 weeks, lung MDMs were isolated for integrated transcriptomic and untargeted metabolomic profiling. Transcriptomic analysis identified 3970 differentially expressed genes (DEGs) in infected MDMs, including upregulated Ptpn1, Dgat2, and Alox5ap and downregulated Cyld, Zfp61, and Mapk11. Metabolomic profiling revealed 113 differentially accumulated metabolites (DAMs). Taurocholic acid and linoleic acid were identified as potential diagnostic biomarkers, both achieving an area under the curve (AUC) of 1.0 in ROC analysis. Integrated omics analysis showed a positive correlation between linoleic acid levels and the expression of Tbxas1, Acaa1b, and Acox1, implicating lipid metabolic pathways in the host response to TB. This multi-omics study delineates key molecular and metabolic alterations in lung MDMs during TB infection. The identified metabolites, taurocholic acid and linoleic acid, show promise as biomarkers, while dysregulated linoleic acid metabolism represents a potential target for novel diagnostic and therapeutic strategies against TB. Full article

Aiming at cemented tailings backfill (CTB) damage and collapse induced by secondary stope blasting in the sublevel open stoping with a subsequent filling method, a new CTB damage control technology termed “Synergistic Utilization of Cumulative Blasting Damage (SU-CBD)” is proposed. First, theoretical analysis is conducted to reveal the influence mechanism of rock mass damage accumulation on its blastability, verifying the feasibility of the SU-CBD technology. Subsequently, based on the LS-DYNA R11.1 software and RHT material model, a numerical model is established, and the small restart technique is adopted to realize the continuous simulation of multi-row blasting. By comparing the rock mass fragmentation ratio, energy distribution, and CTB damage degree among different charge structure schemes, the optimal charge structure combination is obtained. To address the issues of retained rock mass damage and overbreak caused by multiple blasting operations, a dynamic adjustment method for blasthole row spacing is proposed, with the optimal row spacing increment determined as 1.0 m. To verify the technical effectiveness, field industrial tests are carried out in Stope No. 5 of the 4500 m–4550 m mining level in the Bangzhong Zinc-Copper Mine. The results show that the optimized blasting scheme keeps the CTB intact without collapse and achieves uniform ore fragmentation, and the oversize ore ratio (particle size > 50 cm) is only 2.4%, with the numerical simulation results in good agreement with the field test results. The research indicates that the SU-CBD technology can effectively reduce the powder factor and CTB blasting damage while ensuring the blasting fragmentation effect, providing reliable blasting design support for the secondary stope. Full article

To assess digestate’s efficacy as a fertilizer for basil development, a two-year pot experiment was established, comprising four fertilization treatments: namely, mineral fertilizer (F), digestate (D), combined mineral fertilizer and digestate (1:1, FD), and unfertilized control (C). Key metrics assessed included plant height, chlorophyll concentration index (CCI), total biomass (TB), leaf production (LP), essential oil yield, and composition. Post-harvest analysis evaluated nutrient and heavy metal content and pathogen contamination in the growing substrate and leaves. FD treatment produced the highest TB (68.2 g plant⁻¹) and LP (52.7 g plant⁻¹). Digestate application substantially enhanced substrate nutrient availability, increasing extractable phosphorus by 68.5%, potassium by 134.4%, and organic matter by 54.7%. The essential oil yield was significantly higher in the control plants. whereas different fertilization regimes altered secondary metabolite synthesis. Specifically, fertilization with digestate favored sesquiterpenes synthesis, inorganic fertilization enhanced methyleugenol and β-farnesene synthesis, and the control showed higher limonene, eugenol, and linalool. Heavy metal accumulation in the growing substrate was negligible, remaining well within regulatory limits. Salmonella spp., were not detected. Pathogen concentration in the growing substrate was low, while Enterococcus faecalis levels were marginally below EU safety limits (100 cfu g⁻¹) on the leaves. Continuous monitoring of soil chemical properties and plant products after digestate application is essential to ensure soil health and food safety. Full article

Early and rapid diagnosis of drug resistance in tuberculosis (TB) plays a key role in reducing the spread of resistance and enabling effective treatment. The aim of this study was to investigate mutations in drug resistance-associated gene regions of Mycobacterium tuberculosis complex (MTBC) isolates resistant to at least two first-line anti-tuberculosis drugs through sequence analysis, in order to characterize the core molecular features of these strains in the region and to identify previously unreported, geographically distinct novel mutation sites. The drug susceptibility of 23 clinical isolates was assessed using the BACTEC MGIT 960 system, and resistance-associated point mutations were identified through DNA sequence analysis and comparison with GenBank reference sequences. AAG → AGG mutation was detected in the rpsL gene region at codon 43 (n = 7) and codon 88 (n = 1). Additionally, GAG → GCG point mutation was identified at codon 70 (n = 2), representing a new region not previously reported in the literature. The most frequent mutation was AGC → ACC at katG codon 315 (n = 10), followed by a C → T substitution at position −15 of the inhA promoter region (n = 4). Additionally, TCG → TTG at rpoB codon 531 (n = 4) and ATG → GTG at embB codon 306 (n = 1) were detected. The detection of resistance-associated mutations is essential for controlling drug-resistant tuberculosis. In this study, a novel rpsL mutation (GAG → GCG) at codon 70 and a previously unreported codon 88 mutation in our country were identified, contributing to the understanding of molecular resistance mechanisms and epidemiology. Full article

With the increase in human space activities, there is a significant amount of space debris as well as defunct satellites that seriously threaten the safety of spacecraft in their orbits. The laser ranging technique is one of the most accurate methods of ground-based space target observation. Therefore, it is very meaningful to study efficient tracking and observation methods for defunct satellites and space debris. In this paper, time bias, which is in advance of the actual observation, was added by analyzing the deviation of the orbit prediction such as the time bias and range bias of the runaway space objects. A new method was used for the determination of the TB and RB in real-time tracking and in data processing. The data produced from the observation of the out-of-control targets, such as the Topex satellite and CZ-2C Long March Launch Vehicle, were presented and analyzed. Taking the laser ranging data of the Topex satellite obtained on 19 November 2019, as an example, the result of the first observation circle provided the initial time bias value for the second observation circle, proving that the laser ranging method for runaway space objects is effective. The results of this paper can effectively improve the acquisition efficiency of the defunct satellites. Full article

In the context of deep mining and green low-carbon transition, this study characterizes the thermo-mechanical evolution and fracture mechanisms of cemented tailings backfill (CTB) through systematic experiments conducted at 20–60 °C across 3–28 days. Results demonstrate that strength and elastic modulus follow a unimodal dependence on temperature, peaking at 40 °C. Gaussian modeling reveals that curing times narrow the thermal tolerance window, with the elastic modulus exhibiting higher sensitivity to overheating. A consistent “pre-peak activity window” is identified in AE responses, characterized by b-value drops and an increase in tensile event proportions from 66% to 83%. A composite AE damage index (ADI) is introduced to systematically precede macroscopic failure, with thresholds of ADI ≥ 0.60 and 0.70 indicating accelerated crack propagation and imminent instability, respectively. Microstructural analysis confirms that 40 °C promotes C-S-H and fine ettringite bridging, whereas temperatures ≥ 50 °C induce Ca(OH)₂ coarsening and enhanced pore connectivity, triggering early tensile-dominated degradation. This study establishes a “temperature → hydration/porosity → AE response → mechanical evolution” pathway, providing an optimal curing window of 40 ± 5 °C and an ADI-based early-warning criterion for temperature-adaptive CTB design and on-site safety management. Full article

Tannin-boron (TB) treatment is an effective method for enhancing the biological resistance of some types of wood, although knowledge regarding its efficacy as a preservative in a wider range of wood is limited. In this study, we investigated the effects of TB treatment on the mechanical and microscopic properties, and on biological resistance of six types of wood (Pinus massoniana Lamb., Cunninghamia lanceolata (Lamb.) Hook, Pseudotsuga menziesii (Mirb.) Franco, Intsia bijuga (Colebr.) Kuntze, Tectona grandis L. f., and Quercus mongolica Fisch. ex Ledeb.). The results showed that the six types of wood exhibited different boron retention after leaching, with the highest retention rate, 21.85%, observed in P. massoniana. The TB treatment did not significantly alter the original density and compressive strength of the wood, except in the case of I. bijuga, where the compressive strength significantly decreased after treatment. Scanning electron microscopy revealed that TB preservative is attached around the tracheids of softwood, or deposited within the vessels of hardwood. No-choice feeding tests showed that the TB-treated wood exhibited high resistance to Coptotermes formosanus with a maximum weight loss of 2.5%. TB treatment significantly improved the resistance of P. massoniana, C. lanceolata, P. menziesii, and T. grandis to Trametes hirsuta. These results demonstrate the potential usefulness of TB preservatives in different wood types. Full article