Search Results (11,778)

Milk fat synthesis in dairy cows is a complex process affected by ruminal fermentation, systemic metabolism, and mammary gland activity. To explore the metabolic interplay across these systems, a multi-tissue metabolomics approach (rumen fluid, plasma, and milk) using ultra-high-performance liquid chromatography–mass spectrometry was used to identify metabolic differences between Chinese Holstein cows with high (H-MF, 5.82 ± 0.41%) and low (L-MF, 3.60 ± 0.12%) milk fat content under the same diet. The bovine mammary epithelial cells (BMECs) were also cultured to evaluate the impact of a key metabolite, malic acid (MA), on lipid metabolism. Our findings reveal distinct metabolic profiles across rumen fluid, plasma, and milk, with 96, 109, and 79 differential metabolites, respectively, between the L-MF and H-MF groups. In rumen fluid, H-MF cows showed higher levels of lauric acid and succinic acid, linked to fatty acid biosynthesis, while the L-MF cows had elevated citraconic and orotic acids, associated with amino acid metabolism and liver stress. Plasma from the H-MF cows contained higher β-hydroxybutyric acid, methionine sulfoxide, and phosphatidylcholine, supporting lipogenesis, whereas L-MF plasma showed increased 3-hydroxy-L-proline, indicating tissue catabolism. In milk, the L-MF cows had higher MA, while the H-MF cows exhibited elevated L-carnitine, linked to fatty acid β-oxidation. Metabolite trend analysis during rumen fluid–plasma–milk showed that 211 metabolites were classified into 8 profiles. Profile 1 had the largest number of metabolites whose levels were down-regulated from rumen to plasma and enriched in lipid metabolism. Profile 3 (mainly related to amino acid metabolism) and profile 4 (mainly related to energy metabolism) exhibited opposite trends from plasma to milk. In vitro, 200 μM of MA reduced the triglyceride content in BMECs and down-regulated lipogenic genes and their protein expression levels (fatty acid synthase, stearoyl-CoA desaturase and sterol regulatory element binding protein 1). These results highlight how rumen fluid, plasma, and milk metabolites collectively influence milk fat synthesis, with MA acting as a key regulator of lipid metabolism in mammary epithelial cells. Full article

The 795 nm wavelength corresponds to the D1 transition of rubidium atoms and is widely used in atomic optical pumping, atomic clocks, magnetometers, and precision spectroscopy. For compact free-space collimation, beam shaping, and efficient fiber coupling, edge-emitting semiconductor lasers with reduced fast-axis (vertical) divergence are highly desirable, yet low-divergence designs at 795 nm remain limited. Here, we propose and demonstrate low-divergence photonic-crystal epitaxy (LD–PC) for 795 nm edge-emitting lasers. By engineering a periodic n-side photonic-crystal stack to place the fundamental vertical mode near the photonic band edge, the vertical mode is expanded while maintaining effective modal discrimination. Narrow-ridge Fabry–Pérot lasers based on GaAsP/AlGaAs single-quantum-well epitaxy were fabricated and characterized. The optimized LD–PC device (3 μm ridge width, 1 mm cavity length) delivers 227 mW at 200 mA with a threshold current of 23 mA, a slope efficiency of 1.28 W/A, and a peak wall-plug efficiency of 55% under continuous-wave operation at 25 °C. The measured far-field divergences (FWHMs) are 7.16° and 18.83° in the lateral and vertical directions, respectively, corresponding to a reduction in the vertical divergence from >40° in the reference structure to <20° with LD–PC. These results validate photonic-crystal epitaxy as an effective route toward compact, high-performance, low-divergence 795 nm semiconductor laser sources for rubidium-based atomic systems. Full article

Smart-meter theft detection requires learning from fine-grained electricity consumption data, whose centralized processing poses significant privacy risks. Federated learning (FL) mitigates these risks by decentralizing training, but providing rigorous user-level differential privacy (DP) under non-IID data and heterogeneous client behavior remains challenging. Existing DP-FL approaches rely on fixed global clipping bounds for client updates, which substantially overestimate sensitivity when privacy loss is composed using Rényi Differential Privacy (RDP), zero-Concentrated DP (zCDP), or Moments Accountant (MA) frameworks, leading to excessive noise and degraded utility. This work proposes an adaptive clipping-based RDP accountant that incorporates empirical, round-wise update magnitudes into privacy accounting by rescaling each round’s RDP contribution according to the observed clipping ratio. The method is optimizer-agnostic and is evaluated with FedAvg, FedProx, and SCAFFOLD on the SGCC smart-meter theft dataset under IID and Dirichlet non-IID partitions. Experimental results show consistently tighter privacy bounds and improved model utility compared to classical DP accountants, demonstrating the effectiveness of sensitivity-aware privacy accounting for practical differentially private FL. Full article

A protozoa leads a rapid onset of symptoms, with high mortality rates in the rearing of the planktotrophic larvae of the tropical holothurian Isostichopus fuscus for aquaculture. This study aimed to determine the effect of temperature on the infection parameters and the larvae size with/without parasites in its five development stages: T1–EA (250–300 μm), T2–MA-I (300–600 μm), T3–MA-II (600–900 μm), T4–A (1.1–1.3 mm), and T5–LA (≈500 μm). Eight 500 L conical tanks with filtered and UV-sterilized seawater with 0.2 larvae mL⁻¹ under two temperature treatments (low: 23.0 ± 2.5 °C, high: 27.0 ± 0.5 °C). Thirty larvae per replicate at intervals of 4–5 days were sampled until day 25. A total of 1200 larvae were examined, and a total of 21,715 parasites were counted. A total of 97% of parasites were found under low temperature conditions. The DSI and survival significantly varied in relation to the temperature and time. The highest prevalence and intensity, 62.5 ± 5.7% and 130.5 ± 13.0, respectively, were observed at T4 at low temperature. At 18 d, larvae without parasites were larger (1494.1 ± 52.2 μm) than larvae with parasites (1237.7 ± 24.4 μm, p < 0.05) at 25 d. These findings suggest that elevated temperature functions as a key regulator in mitigating parasitic infections in auricularia larvae of I. fuscus. Full article

The northwestern Amazonian Craton exposed in eastern Colombia preserves a complex Proterozoic tectonothermal history. In this study, we present new zircon and apatite U–Pb geochronological data from orthogneisses of the Guaviare Complex (Termales Gneiss unit) to constrain the timing of crust formation, metamorphism, and subsequent thermal events. Zircon U–Pb data define a dominant concordant population at ca. 1.30 Ga, interpreted as the crystallization age of an igneous protolith. This age is consistent with Mesoproterozoic A-type magmatism previously recognized in the region and consistent with emplacement under intracratonic extensional conditions, as suggested by previous studies. A limited number of discordant zircon analyses indicate Pb loss and/or partial isotopic resetting between ~1.0 and 0.6 Ga, although no well-defined metamorphic zircon population is identified. Meanwhile, apatite U–Pb analyses from key samples yield consistent lower intercept ages between 633 ± 16 Ma and 543 ± 8 Ma, indicating a widespread Ediacaran thermal disturbance that may have affected the Guaviare Complex, temporally overlapping with alkaline magmatism in the northwestern Amazonian Craton, including the San José del Guaviare Nepheline Syenite. However, alternative mechanisms such as fluid-assisted Pb mobility, regional reheating, or prolonged cooling cannot be excluded. Finally, the combined zircon–apatite dataset highlights the value of multi-chronometer approaches for resolving complex thermal histories in cratonic domains. Full article

Electrocatalytic seawater splitting is an ideal strategy for the large-scale production of green hydrogen. Compared to scarce freshwater, oceanic seawater electrolysis represents a game-changer for the hydrogen economy. Herein, we report a cost-effective one-step synthesis of binder-free, self-supported 3D nickel–manganese–cobalt (NiMnCo) coatings on titanium (Ti) substrates and evaluated their electrocatalytic performance for the hydrogen evolution reactions (HERs) in alkaline media (1.0 M KOH), simulated seawater (SSW, 1.0 M KOH + 0.5 M NaCl) and alkaline natural seawater (ASW, 1.0 M KOH + natural seawater). These ternary coatings were electrodeposited on Ti substrates using an electrochemical deposition method via a dynamic hydrogen bubble template (DHBT) technique. The optimized ternary NiMnCo/Ti-2 electrocatalyst exhibited an enhanced HER activity in both alkaline and seawater media, achieving an ultra-low overpotential of 29, 59 and 66 mV to reach the benchmark current density of 10 mA cm⁻² in SSW, ASW and 1.0 M KOH, respectively. This efficient 3D ternary NiMnCo/Ti-2 electrocatalyst demonstrated stable long-term performance at a constant potential of −0.23 V (vs. RHE) and a constant current density of 10 mA cm⁻² for 50 h without any significant degradation. Furthermore, it exhibited long-term stability in alkaline electrolyte and simulated seawater during multi-step chronopotentiometric testing at variable current densities from 20 mA cm⁻² to 100 mA cm⁻² for 18 h. This superior performance can be attributed to its unique intermetallic structure and multi-component composition, which provides good Cl⁻ resistance, electrochemical stability and synergistic effects among its constituents. Therefore, the optimized NiMnCo/Ti-2 electrocatalyst is a promising candidate for practical seawater electrolysis aiming at green hydrogen production. Full article

Isotopic disequilibrium during the formation of high-temperature (HT) metamorphic complexes by anatexis during continental collision is a process that deserves intense discussion since it is fundamental to understand the evolution of continental crust. The axial sector of the Iberian Variscan Belt (IVB) is known by the profusion of synorogenic granites that are sometimes clearly associated with the migmatites composing the HT metamorphic complexes. The Pedregal Migmatitic Complex is located in the autochthonous domain of the IVB and is composed of metatexites and diatexites associated to syntectonic two-mica granites. The anatectic process occurred by dehydration melting of muscovite and biotite with the growth of peritectic minerals such as garnet, K-feldspar, and sillimanite in metatexites; and K-feldspar, sillimanite, and hercynite in diatexites reaching the metamorphic peak at 313.5 ± 0.5 Ma. A process of residuum-melt separation during crustal melting is attested by the Pedregal migmatites, giving origin to metatexites and residual diatexites as indicated by field evidence and their geochemical signature. Zircon oxygen isotopes and inherited zircon ages point to the Douro-Beiras Supergroup metasedimentary sequence (Beiras group) as a possible protolith of the Pedregal diatexites. Conversely, the isotopic composition of the diatexites suggests isotopic disequilibrium caused by residual mineral phases (biotite, monazite and garnet). Full article

An efficient bacteriophage delivery system needs to be developed to overcome the challenges associated with phage instability, rapid diffusion, and loss of infectivity at the infection site. Hydrogels have been found to be potential carriers. Hydrogels have emerged as promising carriers due to their biocompatibility, tunable physicochemical properties and capacity for controlled release. However, the molecular factors that regulate phage–hydrogel interactions remain poorly understood. In this study, we employed an in silico framework combining molecular docking, molecular dynamics (MD) simulations, MM/PBSA binding energy calculations, machine learning-based adhesion prediction, and diffusion modeling to explore phage–hydrogel interactions at the molecular level. Surface-exposed bacteriophage proteins, such as capsid and tail proteins, were evaluated against eight different hydrogel polymers. Binding site analysis revealed the presence of multiple solvent-accessible pockets that can interact with the polymer. Docking studies showed favorable and stable interactions, with hyaluronic acid showing strong binding affinity to multiple phage proteins (−5.5 to −5.7 kcal/mol) and GelMA showing high affinity to the capsid gp10 protein (−5.6 kcal/mol). The integrity of the structural complexes was further confirmed by 100 ns MD simulations, stable RMSD and RMSF trajectories, compact structural conformations, and favorable MM/PBSA binding energies. Machine learning classification successfully differentiated high- and low-adhesion systems and identified hydrogen bonding and electrostatic interactions as key determinants of sustained yet reversible phage retention. Collectively, our findings suggest that the hydrogels enriched with charged and polar functional groups can facilitate stable but non-destructive phage binding, enabling controlled and sustained release. This study provides mechanistic insights into rational hydrogel design for phage delivery systems and highlights the potential of high-throughput computational strategies to accelerate the development of optimized phage therapeutics. Full article

Background: Oral progestogens, including megestrol acetate (MA) and medroxyprogesterone acetate (MPA), have largely been superseded by aromatase inhibitors, tamoxifen, and selective oestrogen receptor degraders (SERDs) in oestrogen receptor-positive (ER-positive) metastatic breast cancer. However, they remain an option as late-line therapy after failure of standard treatments. Contemporary data are limited, particularly in patients previously treated with CDK4/6 inhibitors. Methods: We conducted a multi-site retrospective analysis of patients with ER-positive metastatic breast cancer treated with MA or MPA between 2014 and 2024 at four hospital sites across London, United Kingdom. Patients were identified using pharmacy dispensing records. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and Cox regression. Subgroup analyses included prior CDK4/6 inhibitor exposure, histology and liver metastases. Results: A total of 116 patients were included. Median PFS was 2.4 months (95% CI 2.2–2.9), and median OS was 3.3 months (95% CI 2.7–4.9). Prior CDK4/6 inhibitor exposure was associated with shorter PFS (1.9 vs. 2.8 months; HR 1.59; 95% CI 1.08–2.35, p = 0.019) and a trend toward shorter OS (3.1 vs. 3.6 months; HR 1.18, 95% CI 0.80–1.75, p = 0.41). Similarly, liver metastases were associated with shorter PFS (2.3 vs. 2.8 months; HR 1.78, 95% CI 1.12–2.85, p = 0.015), with a trend toward worse OS (3.1 vs. 4.9 months; HR 1.45, 95% CI 0.93–2.25, p = 0.103). A subset of patients derived prolonged benefit, with a 6-month PFS rate of 16%. Toxicity was manageable; thromboembolic events and oedema occurred in 9% and 11% of patients respectively. Appetite improvement was reported in 10%. Conclusions: MA and MPA demonstrated modest but clinically relevant late-line activity in heavily pretreated, endocrine-refractory ER-positive metastatic breast cancer. While prior exposure to CDK4/6 inhibitors was associated with shorter PFS, patients without liver metastases appeared to derive the greatest benefit. These findings support a role for oral progestogens in selected patients who have exhausted standard therapeutic options. Full article

Pinoresinol diglucoside (PDG), one of the major lignans isolated from E. ulmoides Oliver bark, has various pharmacological functions, including antihypertension and prevention of osteoporosis. However, the glycosyltransferase-encoding gene (GT) involved in regulating the glycosylation of pinoresinol to form PDG has not been reported in E. ulmoides. In this study, we screened and cloned the EuGT8 gene from E. ulmoides based on our transcriptome data. The expression pattern of the EuGT8 gene exhibited a strong positive correlation with dynamic changes in the PDG contents in three different organs of E. ulmoides. The expression level of the EuGT8 gene and PDG content were significantly decreased in asODN-EuGT8-treated shoot tips in comparison with the control group. Prokaryotic expression of the EuGT8 gene revealed that the purified EuGT8 protein could catalyze the conversion of pinoresinol into PDG. In addition, we performed transcriptional and metabolomic analyses to compare the differences between transgenic Arabidopsis and WT plants. A total of 1799 DEGs and 294 DEMs were identified in transgenic and WT plants. KEGG enrichment analysis showed that the DEGs were mainly enriched in phenylpropanoid biosynthesis, secondary metabolite biosynthesis, and starch/sucrose metabolism pathways. The DEMs were mainly enriched in ABC transporters, aminoacyl-tRNA biosynthesis, biosynthesis of amino acids, phenylpropanoid biosynthesis, and flavone and flavonol biosynthesis pathways. Correlation analysis between DEGs and DEMs identified a total of 231 DEGs associated with 38 DEMs, which were mainly distributed in multiple metabolic pathways. This finding provides both theoretical insights and genetic resources for breeding high-PDG E. ulmoides varieties, facilitating marker-assisted selection (MAS) and promoting sustainable E. ulmoides production in Guizhou. Full article

The timing of uranium mineralization in the Xiangshan ore field has long been controversial. Although various geochronometers have been applied by previous researchers, including pyrite Rb-Sr, mica Ar-Ar, and fluorite Sm-Nd, the results remain inconsistent and inconclusive. In recent years, the discovery of abundant Pb-Zn veins in the deeper parts of the Xiangshan ore field has further complicated the interpretation of its metallogenic history. In this study, abundant vein-type hydrothermal apatites closely associated with U-Pb-Zn polymetallic mineralization were identified in both uranium and Pb-Zn ore veins. Combined major-element Electron Probe Microprobe Analysis (EPMA), Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) U-Pb dating, and trace-element analysis were conducted on these apatite grains. The results suggest a mineralization age of 130.9 ± 1.1 Ma for the Shannan uranium deposit, which is consistent with the previously reported apatite U-Pb age of 131.3 ± 7.2 Ma from the Zoujiashan uranium deposit and coincides with the main pulse of volcanic-intrusive activity in the Xiangshan ore field (133–137 Ma). The deep Niutoushan Pb-Zn deposit suggests a younger mineralization age of 124.5 ± 1.3 Ma, which is consistent with a thermal event age of 125.6 Ma determined by zircon fission-track dating and the zircon LA-ICP-MS U-Pb age of late-stage granite porphyry (125.4 ± 1.0 Ma). These ages may constrain the timing of U-Pb-Zn polymetallic mineralization in the Xiangshan ore field. Both magmatic and hydrothermal apatites are classified as fluorapatite and exhibit similar chondrite-normalized rare earth element (REE) patterns. Compared with magmatic apatites, hydrothermal apatites are characterized by elevated Th, U, Ca, and Sr contents, depletion in light rare earth elements (LREEs), Mn, and Na, and distinctly lower Th/U ratios. On major-element variation diagrams, magmatic and hydrothermal apatites define coherent trends but display clear compositional differences related to their formation stages. Apatites from uranium ore veins show strongly negative Eu anomalies and weakly positive Ce anomalies, similar to magmatic apatites. In contrast, apatites from Pb-Zn ore veins display positive Eu anomalies and weakly negative Ce anomalies, with lower Mn and Ga contents and higher SO₃ contents relative to both magmatic apatites and hydrothermal apatites from uranium ore veins. These features indicate that the ore-forming fluids during Pb-Zn mineralization were characterized by significantly higher oxygen fugacity than those during uranium mineralization and magmatism. Combined with published Sr isotopic data for the Xiangshan ore field, we propose that both uranium and Pb-Zn mineralization were genetically linked to the prolonged magmatic evolution of the deep volcanic-intrusive complex. The subsequent incursion of meteoric water modified the physicochemical conditions of the ore-forming system, particularly during the formation of the Pb-Zn mineralization. Full article

The Mahuaping deposit is the largest Be-W-F deposit in the Jinshajiang–Ailaoshan metallogenic belt, Sanjiang region, SW China, with more than 72,700 t WO₃, 41700 t BeO and 2.3 Mt CaF₂. Despite recent studies, the ore-forming process of the Mahuaping deposit remains poorly understood, limiting further insight into its genesis. In this study, a new muscovite Rb-Sr age and elemental compositions of beryl have been reported to constrain the mineralization age and evolution of ore-forming fluids. Muscovite Rb-Sr isochron dating reveals the mineralization age of the Mahuaping Be-W-F deposit is 28.0 ± 1.5 Ma, indicating the formation of the Mahuaping deposit is probably related to the magmatism caused by the sinistral shearing of crust in the Oligocene. LA-ICP-MS elemental mapping and spot analysis suggest the mechanisms for the incorporation of trace elements into the beryl lattice primarily involve two substitution types: Be²⁺ ↔ Li⁺ + Na⁺/Cs⁺ in the crystal core, and Al³⁺ ↔ (Fe²⁺/Mg²⁺) + (Na⁺/Cs⁺/Rb⁺) occurring in both the core and rim. The enrichment of Fe²⁺ is responsible for the blue coloration observed in beryl. The compositional variation from core to rim in beryl crystal indicates the initial ore-forming fluid of the Mahuaping deposit is reducing and acidic, and dominantly originated from magmatic fluids derived from the highly evolved magma. During the evolution, in addition to the continuous mixing of meteoric water, due to pulsating exsolution, the magmatic fluids were also replenished into the ore-forming fluid, enhancing water/rock interaction. Full article

Adverse drug reaction (ADR) detection is essential for ensuring drug safety and effective pharmacovigilance. The rapid growth of users’ medication reviews posted on social media has introduced a valuable new data source for ADR detection. However, the large scale and high noise inherent in social media text pose substantial challenges to existing detection methods. Although large language models (LLMs) exhibit strong robustness to noisy and interfering information, they are often limited by issues such as stochastic outputs and hallucinations. To address these challenges, this paper proposes two generative detection frameworks based on Chain of Thought (CoT), namely LLaMA-DetectionADR for Supervised Fine-Tuning (SFT) and DetectionADRGPT for low-resource in-context learning. LLaMA-DetectionADR automatically generates CoT reasoning sequences to construct an instruction tuning dataset, which is then used to fine-tune the LLaMA3-8B model via Quantized Low-Rank Adaptation (QLoRA). In contrast, DetectionADRGPT leverages clustering algorithms to select representative unlabeled samples and enhances in-context learning by incorporating CoT reasoning paths together with their corresponding labels. Experimental results on the Twitter and CADEC social media datasets show that LLaMA-DetectionADR achieves excellent performance, with F1 scores of 92.67% and 86.13%, respectively. Meanwhile, DetectionADRGPT obtains competitive F1 scores of 87.29% and 82.80% with only a few labeled examples, approaching the performance of fully supervised advanced models. The overall results demonstrate the effectiveness and practical value of the proposed CoT-based generative frameworks for ADR detection from social media. Full article

Dynamic fee market mechanisms, exemplified by EIP-1559, have been extensively studied for Ethereum’s 12 s block environment but remain uncharacterized at sub-second timescales. We present an agent-based simulation study of an EIP-1559 adaptation for Injective, a Layer 1 blockchain combining native EVM compatibility with CometBFT consensus, operating at 600 ms block times. Across twelve simulation runs (four parameter configurations × three demand scenarios), our analysis yields three findings: (1) temporal smoothing mechanisms (MA-25, 25-block trailing average) produce mixed effects in sub-second environments with up to 47% basefee overshoot during spam attacks and slight smoothing elsewhere, making per-block mechanisms preferable for consistent performance; (2) transitioning from 150M (66.66% target) to 300M (50% target) configuration reduces peak fees by 31% during variable demand; during spam attacks, the 300M configuration peaks 32% higher but recovers faster with block capacity as the primary driver for spam throughput; and (3) per-block mechanisms establish initial spam barriers within 17–32 s versus Ethereum’s 4–6 min, economically justifying lower minimum fees. We provide the first systematic sub-second EIP-1559 analysis and a parameter optimization framework for high-throughput chains. With proper tuning, dynamic fee mechanisms are compatible with high-throughput architectures. Full article

The proliferation of intelligent edge devices demands compact, low-power hardware capable of dynamically switching between sensing, logic, and learning tasks—a versatility that traditional multi-chip solutions fundamentally lack. Here, we demonstrate a reconfigurable spin–orbit torque (SOT) device based on an FeTb/Ru/Co synthetic antiferromagnetic (SAF) heterostructure. By modulating the input current amplitude, the device dynamically switches between two distinct operating modes: saturation and activation. In the saturation regime (>80 mA), deterministic magnetization reversal enables Boolean logic operations (AND, NOR). In the activation regime (<80 mA), gradual, non-volatile conductance modulation emulates synaptic plasticity. Benefiting from the strong antiferromagnetic coupling and near-zero net magnetization of the SAF structure, all operations are achieved without external magnetic fields. This single-device, dual-mode reconfigurable architecture establishes a new paradigm for high-density, low-power, multifunctional in-memory computing units, with promise for advancing adaptive edge computing chips. Full article