Resonance Analysis Research Articles

Automated diagnosis and grading of lumbar intervertebral disc degeneration based on a modified YOLO framework

BackgroundThe high prevalence of low back pain has led to an increasing demand for the analysis of lumbar magnetic resonance (MR) images. This study aimed to develop and evaluate a deep-learning-assisted automated system for diagnosing and grading lumbar intervertebral disc degeneration based on lumbar T2-weighted sagittal and axial MR images.MethodsThis study included a total of 472 patients who underwent lumbar MR scans between January 2021 and November 2023, with 420 in the internal dataset and 52 in the external dataset. The MR images were evaluated and labeled by experts according to current guidelines, and the results were considered the ground truth. The annotations included the Pfirrmann grading of disc degeneration, disc herniation, and high-intensity zones (HIZ). The automated diagnostic model was based on the YOLOv5 network, modified by adding an attention module in the Cross Stage Partial part and a residual module in the Spatial Pyramid Pooling-Fast part. The model’s diagnostic performance was evaluated by calculating the precision, recall, F1 score, and area under the receiver operating characteristic curve.ResultsIn the internal test set, the model achieved precisions of 0.78–0.91, 0.90–0.92, and 0.82 and recalls of 0.86–0.91, 0.90–0.93, and 0.81–0.88 for disc degeneration grading, disc herniation diagnosis, and HIZ detection, respectively. In the external test set, the precision values for disc degeneration grading, herniation diagnosis, and HIZ detection were 0.73–0.87, 0.86–0.92, and 0.74–0.84 and recalls were 0.79–0.87, 0.88–0.91, and 0.77–0.78, respectively.ConclusionThe proposed model demonstrated a relatively high diagnostic and classification performance and exhibited considerable consistency with expert evaluation.

Functional assessment of genetic variants in thrombomodulin detected in patients with bleeding and thrombosis.

Thrombomodulin (TM) expressed on endothelial cells regulates coagulation. Specific nonsense variants in the TM gene, THBD, result in high soluble TM levels causing rare bleeding disorder. In contrast, though THBD variants have been associated with venous thromboembolism, this association remains controversial. A multigene panel was used to diagnose 601 patients with inherited bleeding or thrombotic disorders. This resulted in the identification of 8 THBD variants for six patients with a thrombotic (C175S, A282P, L433P, P501L, G502R, P508L) and two patients with a bleeding (P260A, T478I) phenotype. These were all classified as variants of uncertain significance, and we here aimed to assess their functional role in coagulation. For this purpose, soluble and cell membrane-bound recombinant TM were produced in Expi293FTM cells. L433P TM showed a marked decrease in the inhibition of thrombin generation and complete inhibition of protein C and TAFI activation. Soluble C175S TM showed decreased inhibition of thrombin generation and protein C activation, while no effect was observed for membrane-bound TM. For the other TM variants, no effect on thrombin generation nor protein C or TAFI activation could be observed. Surface plasmon resonance analysis showed absent thrombin-TM binding in the presence of L433P, as this residue is located at their interaction site. In conclusion, our study shows functional effects of L433P TM and potentially also C175S TM that are compatible with an increased thrombosis risk. THBD variants are rare but can be relevant to both bleeding and thrombosis. Functional assays for these variants are critical to understand their role.

Fabrication of Z-Scheme MIL-125/Ag/BiOBr Heterojunctions with Enhanced Photocatalytic Reduction of Cr6.

Herein, first, MIL-125 samples were synthesized via a hydrothermal method. Then, Ag species were doping on the surface of MIL-125 samples via the photolysis of silver nitrate. Finally, the Z-scheme MIL-125/Ag/BiOBr composite was synthesized via a directed liquid assembly method. The structure, morphology, and optical properties of the prepared samples were investigated via X-ray diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, energy-dispersive X-ray spectroscopic mapping, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, N2 adsorption-desorption analysis, ultraviolet-visible spectroscopy, photoluminescence spectroscopy, surface photovoltage analysis, transient photocurrent response analysis, electrochemical impedance spectroscopy, and electron spin resonance analysis. Photocatalytic experiments indicated that the photocatalytic Cr6+ reduction efficiency of MIL-125/Ag/BiOBr heterojunctions was 85.7% at pH = 6, which was approximately 5.5 and 2.2 times higher than that using BiOBr and MIL-125 alone, respectively. This performance was attributed to the intimate interfacial contact between MIL-125 and BiOBr and the doping of Ag species, which increased the transfer and separation of photogenerated carriers and inhibited the recombination of electrons and holes. Furthermore, the possible photocatalytic Cr6+ reduction mechanism of the Z-scheme MIL-125/Ag/BiOBr photocatalyst was proposed.

Measurement and Analysis of Interconnects' Resonance and Signal/Power Integrity Degradation in Glass Packages.

In this article, resonance phenomena of high-speed interconnects and power delivery networks in glass packages are measured and analyzed. The resonances are generated in the interconnection by the physical dimension, cancelation of reactance components, and modes. When the resonances are generated in the operation frequency band, the signal/power integrity of the interconnect can be affected. As such, resonances generated in high-speed interconnects increase insertion loss, which degrades signal integrity. Also, resonances of the power delivery network (PDN) associated with boundary conditions increase PDN impedance, which degrades power integrity by generating power/ground noise and return current discontinuity of through vias. Recently, glass packaging has been gaining more attention due to its advantages associated with low substrate loss and large dimensions compared to silicon wafers. However, the low loss of the substrate and process variation may affect the resonance properties of interconnects. The resonance impacts on signal/power integrity must be analyzed, and mitigation plans should be proposed to maximize the advantages of the glass packaging technology. To analyze the resonance impacts on signal/power integrity, various glass package test vehicles are designed and fabricated. The fabricated test vehicles include transmission lines, PDNs, and patterns to measure an interaction between the through via and PDN. First, transmission line patterns that have 50-ohm characteristic impedance are measured. Due to the process variations, quarter-wave resonances are monitored, and at those frequencies, a sharp increase in insertion loss is observed, which deteriorates the signal integrity of the interconnect. Various PDN patterns are measured in the frequency domain, and regardless of the PDN shape, PDN impedance peaks are observed at the mode resonance frequencies. Due to a low-loss characteristic of the glass substrate, sharp PDN impedance peaks are generated at these frequencies. Also, at these frequencies, both signal and power integrity degradations are measured and analyzed. To fully benefit from the advantages of glass packaging technology, a thorough electrical performance analysis should be conducted to avoid resonances in the target frequency range.

MOF scaffold for anchoring platinum-nickel nanoparticles with enhanced oxidase-like activity to improve lateral flow immunoassay diagnosis.

Noble metal nanoparticles have attracted tremendous attention as the promising signal reporters for catalytic-colorimetric lateral flow immunoassay (LFIA). However, it remains great challenges for improving their stability and catalytic activity. Herein, first, a kind of porphyrinic based metal-organic framework (MOF) was used as a carrier for loading platinum (Pt) nanoparticles to avoid its aggregation. Moreover, nickel (Ni) atoms were dopped into Pt nanoparticles to adjust crystal structure, thus greatly improving catalytic activity. The resulting MOF@PtNi nanocomposite showed enhanced colorimetric signal brightness and excellent oxidase-like activity, which can improve sensitivity via amplifying the color signal. The catalytic mechanism was further studied by scavenger and electron paramagnetic resonance analysis. Furthermore, integrated with the competitive immunization LFIA platform, the high sensitivity colorimetric detection of human immunoglobulin G was realized with a detection limit of 0.378ng/mL and 0.269ng/mL for pre- and post-catalytic detection, respectively. In addition, this MOF@PtNi based catalytic-colorimetric LFIA was used for detection of clinical serum samples and the results agreed well with that measured by the standard method. Therefore, this study helps open up the application of proposed catalytic-colorimetric nanocomposite in the ultrasensitive LFIA for point-of-care diseases diagnosis.

Effect of K2CO3 on konjac glucomannan/κ-carrageenan-based camellia oil Pickering emulsion gel for the development of fat analogs.

Konjac glucomannan (KGM) undergoes deacetylation in alkaline conditions, while κ-carrageenan (CRG) is sensitive to potassium ions. This study examines the influence of K2CO3 on the mechanical properties of KGM/CRG-based camellia oil Pickering emulsion gels. Texture analysis and rheological testing revealed that the addition of K2CO3 significantly enhanced the mechanical properties of emulsion gels. Texture parameters, such as the hardness, gumminess, and chewiness of the gel, were closer to those of pork back fat when the K2CO3 concentration was 0.2M. The addition of K2CO3 enhance the intermolecular crosslinking within the gel and formed a more uniform and dense gel network, promoting gelation and structural stability, which were confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, and microstructural analysis. Besides, low-field nuclear magnetic resonance and thermogravimetric analyses indicated that the addition of K2CO3 reduced the water mobility of the gel and improved its thermal stability. Physicochemical and color analysis results showed that the energy value of the camellia oil Pickering emulsion gel was only 15.9% that of pork back fat, and its appearance was closer to that of pork back fat than hydrogels. This study provides technical support for the use of KGM/CRG-based camellia oil Pickering emulsion gels as fat analogs.

Generation of glucosylantimycins by heterologous expression of a promiscuous glycosyltransferase in a deepsea-derived Streptomyces.

Antimycins are a class of depsipeptide compounds that exhibit diverse bioactivities. However, their potential clinical applications are hampered by high cell toxicities. Glycosylation usually has profound impacts on the physicochemical properties, bioactivities and toxicities of natural products. In this study, we overexpressed an artificial glycosyltransferase (GT) gene sbmGT1 in deepsea-derived Streptomyces albus ZH66, leading to the discovery of three new antimycin derivatives glucosylantimycins A, B and C (1-3). Their structures were determined by a combination of spectroscopic methods, including high resolution electrospray ionisation mass spectrometry (HRESIMS) and nuclear magnetic resonance (NMR) analysis. The glycosylation remarkably improved the water solubility but simultaneously reduced the cytotoxicities of antimycins towards human cervix epidermoid carcinoma (HeLa) and human hepatic carcinoma (HepG2) cell lines.

Microwave-assisted extraction of dandelion root polysaccharides: Extraction process optimization, purification, structural characterization, and analysis of antioxidant activity.

This study aimed to establish a microwave-assisted method (MAE) for the efficient extraction of polysaccharides from dandelion roots. This study investigated the molecular structure and bioactivity of the polysaccharides from dandelion roots. Extraction conditions were optimized using response surface methodology (RSM). The microwave extraction conditions were set to an extraction time of 42 min, an extraction temperature of 80 °C, and a solid-liquid ratio (g/mL) of 1:33. Under the optimized conditions, the highest dandelion root polysaccharides (DRP) yield was achieved (24.85 ± 0.457 %). Water-pure DRP (DRPw) and NaCl-pure DRP (DRPs) were purified by activated carbon decolorization and DEAE fiber column chromatography. The molecular weights of DRPw and DRPs were 8653 Da and 5930 Da, respectively. The Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) analyses confirmed the existence of α- and β-pyranose in DRPw and DRPs. The results of X-ray diffraction (XRD) and scanning electron microscopy (SEM) showed that DRPw and DRPs were semi-crystalline substances with irregular shapes and rough surfaces. Bioactivity assays revealed the good antioxidant activities of DRPw and DRPs. The present study provides useful information about DRP as natural antioxidants for the benefit of food.

Investigating the Role of Aniline Structure in Improving Proton Exchange Membranes for High Conductivity.

Polybenzothiazole exhibits high proton conductivity; however, its rigid backbone limits its applicability, necessitating processes such as modification or doping. The aniline structure can participate in various reactions, including nucleophilic or electrophilic substitution reactions, salt formation, and acylation reactions. In this experiment, an aniline structure is integrated into the main chain of sulfonated polybenzothiazole to investigate the potential of aniline for enhancing proton exchange membranes. The incorporation of the aniline structure is confirmed through infrared and nuclear magnetic resonance analyses. A comparison of different proportions of aniline revealed that 12.5% aniline increased the tensile modulus to 274.40MPa and the elongation at break to 6.26%. Furthermore, the water absorption rate reached 65.73%, while the expansion rate remained at 25%. The aniline structure exhibits inherent basicity and utilizes phosphoric acid adsorption to enhance proton conductivity. After aniline adsorbs phosphoric acid, the proton conductivity peaks at 0.157 Scm-1. Additionally, the introduction of amino groups provides further modification potential to the main chain of polybenzothiazole.

GENI as an AMPK Activator Binds α and γ Subunits and Improves the Memory Dysfunction of Alzheimer's Disease Mouse Models via Autophagy and Neuroprotection.

Geniposidic 4-isoamyl ester (GENI) with anti-aging effects is a new iridoid glycoside derivative from Gardenia jasminoides Ellis found in our previous study. In this study, to indicate whether this compound has anti-Alzheimer's disease (AD) effect, the galactose-induced AD mice and naturally aging mice with AD were used to do drug efficacy evaluation. Furthermore, the Western blot, small interfering RNA (siRNA), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CESTA), liquid chromatography-tandem mass spectrometry (LC/MS-MS), adenosine 5'-monophosphate-activated protein kinase (AMPK) mutants and surface plasmon resonance (SPR) analysis were utilized to clarify the mechanism of action and identify target protein of this molecule. GENI exerts anti-AD efficacy in galactose-induced AD mice and naturally aging mice with AD through neuroprotection and modification of autophagy and neuron inflammation. Moreover, AMPK as the target protein of GENI to produce an anti-AD effect is identified and the ASP148, ASP157, and ASP166 of the AMPK α subunit and lysine (LYS)148, aspartic acid (ASP)156, LYS309, and ASP316 in the AMPK γ subunit as binding sites are confirmed. Meanwhile, the AMPK/unc-51-like autophagy-activating kinase 1 (ULK1)/microtubule-associated protein 1 light chain 3 beta (LC3B) and AMPK/mammalian target of rapamycin (mTOR) signaling pathways involved in anti-AD effects of GENI. The findings provide a new perspective on treating neurodegenerative diseases by activating AMPK for the energy metabolism disorder.

Activation of ClO2 by Nanoscale Zero-Valent Iron for Efficient Soil Polycyclic Aromatic Hydrocarbon Degradation: New Insight into the Relative Contribution of Fe(IV) and Hydroxyl Radicals.

Recently, the activation of chlorine dioxide (ClO2) by metal(oxide) for soil remediation has gained notable attention. However, the related activation mechanisms are still not clear. Herein, the variation of iron species and ClO2, the generated reactive oxygen species, and the toxicity of the degradation intermediates were explored and evaluated with nanoscale zero-valent iron (nFe0) being employed to activate ClO2 for soil polycyclic aromatic hydrocarbon (PAH) removal. With an optimized ClO2/nFe0 molar ratio of 15:1 and a soil/water ratio of 3:1, the degradation efficiency of phenanthrene improved 12% in comparison with that of a ClO2-alone system. The presence of nFe0 significantly promoted ClO2 consumption (improved 85.4%) but restrained ClO2- generation (reduced 22.5%). The surface Fe(II) and soluble Fe(II) in the ClO2/nFe0 system was 2.0-fold and 2.8-fold that in the nFe0 system after 2 min. Electron paramagnetic resonance analysis, along with quenching experiments, revealed that Fe(IV), HOCl, and •OH dominated phenanthrene degradation in a ClO2/nFe0 system, with oxidation contributions, respectively, of 34.3%, 52.8% and 12.9%. The degradation intermediates of PAHs in the ClO2/nFe0 system had lower estimated toxicity than those of the ClO2 system. The lettuces grown in ClO2/nFe0-treated soil displayed better results in bioassay indexes than those grown in ClO2-treated soil. This study offers new perspectives for the remediation of organic-pollutant-contaminated soil by using metal-activated ClO2 technology.

Acaricidal mechanism and active compounds of Ligusticum striatum methanol extract against Dermatophagoides farinae

Dermatophagoides farinae is a species closely linked to human health. This study investigated the acaricidal efficacy of methanol extracts from 18 traditional Chinese medicinal plants against D. farinae. The extract from Ligusticum striatum DC. exhibited the highest acaricidal properties. Sequential extraction was applied to reveal the active component in the ethyl acetate extract, identified as senkyunolide A (SEA) by liquid chromatography–mass spectrometry (LC–MS) and nuclear magnetic resonance (NMR) analyses. Transcriptomic analysis was performed following SEA exposure for 6, 12, and 24 h, revealing a total of 8212, 4000, and 10 940 differentially expressed genes (DEGs) in D. farinae, respectively. Gene Ontology (GO) enrichment analysis indicated that the DEGs in the three time periods were mainly enriched in cellular processes, binding and catalytic activity, and cell and cellular parts. Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis identified substantial changes in the oxidative phosphorylation pathway over the three time periods. These findings suggest that the acaricidal mechanism of SEA may disrupt energy metabolism, leading to metabolic disorders. SEA also exhibited an inhibitory effect on carboxylesterase among the detoxification enzyme genes, as well as an up-regulatory effect on calmodulin (CaM), which may lead to nerve cell death, ultimately resulting in the mortality of D. farinae.

Parametric study of quarter-wave resonators for sound-proofing building structures

This study investigates the parametric analysis of a quarter-wave resonator integrated into a brick structure for optimized acoustic isolation in buildings. Starting with a brick of 100 mm thickness and period, the quarter-wave resonator was designed and parametrized. The optimization process yielded significant results, achieving an attenuation of approximately -87 dB with a bandgap width of 82%, surpassing the -72.55 dB attenuation provided by the mass law of the brick alone. These findings highlight the potential of the optimized resonator structure to enhance acoustic isolation, making it a promising solution for noise control in urban environments.

Mechanism Analysis of Modal Resonance in Converter-based Power Systems

Mechanism Analysis of Modal Resonance in Converter-based Power Systems

Phytochemical profiling, spectroscopic identification of active compounds, and mechanism of the anticandidal properties of Datura stramonium L. using SwissADMET prediction and molecular docking analysis

BackgroundDatura stramonium L., a wild-growing herb, has been traditionally used to treat various ailments, including toothache, asthma, rheumatism, epilepsy, and alopecia. Scientific evidence supports its anticancer, anti-inflammatory, anti-asthmatic, anticholinergic, antifungal, and antibacterial properties. AimThis study aimed to isolate, characterize, and identify the most potent anticandidal compounds inhibiting the growth of Candida spp., while also predicting their drug-likeness and toxicity profiles. MethodThe anticandidal activity of D. stramonium leaf extracts was assessed using the Agar well-diffusion method and minimum inhibitory concentration (MIC) was determined by the broth dilution method. The most active extract was selected for column chromatography. Different fractions were collected and screened against pathogenic Candida spp. The most active fraction was subjected to Gas chromatography-Mass spectrometry (GC-MS), Fourier Transform-Infrared Spectroscopy (FT-IR), and Nuclear Magnetic Resonance (NMR) analysis. Additionally, computational tools such as molecular docking and ADMET prediction provided further insights into the molecular interactions between the target enzymes. ResultsIn vitro anticandidal activity demonstrated that the ethyl acetate extract exhibited significant activity against human pathogenic Candida spp., with the highest zones of inhibition against Candida guilliermondii (20.33±0.56 mm), Candida tropicalis (16.33±0.58 mm), and Candida albicans (14.66±1.05 mm), with a minimum inhibitory concentration (MIC) value of 25 ug/ml. Additionally, the most potent fraction (F8) obtained from the Column revealed significant anticandidal activity. GC-MS analysis of the F8 fraction indicated the presence of 23 compounds, with the major compounds being Phthalic acid, di(2-propylpentyl) ester (Compound 1), Pentadecane (Compound 2), Octadecane (Compound 3), Benzoic acid, 3-Amino-5-Hydroxy-, Methyl ester (Compound 4), and 1,2-Benzenedicarboxylic acid, bis (2-ethylhexyl) ester (Compound 5). This study reports all 23 compounds from D. stramonium for the first time. Furthermore, NMR studies confirmed the presence of Phthalic acid, di(2-propylpentyl) ester as the most abundant compound, designated as compound 1. Finally, docking analysis revealed that compound 1 showed good binding affinities for the tested enzymes, with the highest binding scores of -7.084 Kcal/mol and -7.030 Kcal/mol with Lanosterol 14-alpha demethylase (PDB ID: 5JLC, 5TZ1). The results of the in silico pharmacokinetic and drug-likeness properties indicated that compound 1 is a potential anticandidal drug candidate. ConclusionThis study highlights that 23 compounds were reported from the leaf extract of D. stramonium for the first time. The findings suggest that compound 1 can be considered a new anticandidal drug candidate.

Topological structure, rheological characteristics and biological activities of exopolysaccharides produced by Saccharomyces cerevisiae ADT

Saccharomyces cerevisiae ADT is an edible fungus, with limited research on its exopolysaccharides (EPS). Three types of exopolysaccharides (EPS60, EPS80, and EPS100) were obtained through multiple purification steps using varying concentrations of ethanol in this study. The topological structure, rheological properties, and biological characteristics of EPS were investigated. High performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and nuclear magnetic resonance (NMR) analyses indicated that the three EPS are primarily made up of mannose with a small amount of glucose. Acetyl groups were also found, along with the presence of α-type pyranose and β-type pyranose. The Congo Red test and X-ray diffraction results reflected the absence of a triple helix structure and crystal properties. Atomic force microscopy (AFM) revealed the self-assembly of three exopolysaccharides into various topological structures under different concentration gradients, and a clear network structure of entangled chains was observed. EPS60, EPS80 and EPS100 displayed pseudoplasticity, weak gel behavior and thermal stability. Significantly, EPS exhibited antioxidant activity in a dose-dependent manner and showed no acute cytotoxicity to RAW264.7 and HEK293T cells. Therefore, EPS in this study is anticipated to be utilized in natural antioxidants, medications, and functional materials.

Disruption of a potential disulfide bond of Cys65-Cys141 on the structure and stability of globin X from zebrafish.

Globin X is a newly discovered member of the globin family, while its structure and function are not fully understood. In this study, we performed protein modelling studies using Alphafold3 and molecular dynamics simulations, which suggested that the protein adopts a typical globin fold, with the formation of a potential disulfide bond of Cys65 and Cys141. To elucidate the role of this unique disulfide in protein structure and stability, we constructed a double mutant of C65S/C141S by mutating the two cysteine residues to serine. As suggested by protein mass, ultraviolet-visible (UV-Vis) and circular dichroism (CD) spectroscopy analyses, the potential disulfide bond has minimal effect on the overall protein structure, but its absence reduces the protein stability. Electron paramagnetic resonance (EPR) analysis also revealed an increase in the proportion of high-spin state heme iron, which accelerates the rate of heme degradation in reaction with H2O2. This study highlights the critical role of the Cys65-Cys141 in maintaining the stability of globin X and the bis-His heme coordination state, providing insights into the structure-function relationship of the newly discovered globin.

Atractylodin alleviates polycystic ovary syndrome by inhibiting granule cells ferroptosis through pyruvate dehydrogenase kinase 4-mediated JAK-STAT3 pathway.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, and its close relationship with oxidative stress has been well-documented. Atractylodin (ATR) plays a role in the treatment of many diseases through its antioxidant function. However, its function in PCOS remains unexplored. In this study, the function and underlying mechanisms of ATR in mitigating PCOS symptoms were investigated. A mouse model of PCOS induced using DHEA and a high-fat diet was established, and many factors such as hormone levels (FSH, LH, testosterone, and progesterone), the estrous cycle, and ovarian shape were evaluated. In vitro, PCOS model was established by DHEA-induced KGN cell, and the effects of ATR on ferroptosis and oxidative stress markers were explored. Specifically, the viability of KGN cells treated with ATR was assessed using the CCK-8 assay, and the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) were measured to evaluate oxidative stress. Expression of ferroptosis-related genes (NRF2, GPX4, SLC7A11) and PDK4 was analyzed by qRT-PCR and Western blotting. PDK4's interaction with ATR was examined through molecular docking and confirmed by surface plasmon resonance (SPR) analysis. Our data show that the treatment of ATR markedly increased hormone levels and improved normal estrous cycles. Moreover, ATR was found to improve ovarian morphology by decreasing cystic dilatation and increasing the number of corpora lutea. Mechanistically, our research found that ATR regulates the expression of PDK4 by binding to its GLY331 and inhibits granulosa cell ferroptosis by regulating the JAK-STAT3 pathway mediated by PDK4. In conclusion, our study suggest that ATR may be a therapeutic option for managing PCOS and PDK4 could be a target for the development of new drugs for PCOS.

Versatile electrospun cobalt-doped carbon films for rapid antibiotic degradation.

This study presents a novel approach to water contamination remediation by developing cobalt-doped carbon nanofiber films using electrospun ZIF-67 precursors, aiming to degrade tetracycline hydrochloride (TCH) and other antibiotics. This method uniquely combines the advantages of metal-organic frameworks (MOFs) and electrospinning to enhance catalytic performance, demonstrating significant innovation in environmental catalysis. The research systematically evaluated the impact of various factors on the catalytic activity of carbonized PAN@ZIF-67 films (CPZF), including carbonization temperature, ZIF-67 content, and PMS dosage. Notably, the CPZF catalyst with 11% ZIF-67 content (named as CPZF-11%) achieved an impressive 99.7% degradation of TCH within just 10 min under visible light and PMS activation, highlighting its superior catalytic efficiency. The study revealed that CPZF-11% exhibited excellent stability and recyclability, maintaining near 100% degradation rates even after six cycles. This catalytic performance is attributed to the synergistic effect of photogenerated electrons and PMS activation, leading to the formation of reactive oxygen species (ROS) such as sulfate radicals and singlet oxygen. The research further elucidated the degradation pathways and intermediate products through quenching experiments and electron paramagnetic resonance (EPR) analysis. The findings demonstrate the broad applicability of CPZF/Vis/PMS in various water matrices, including tap water and wastewater, underscoring its potential for real-world applications in wastewater treatment. This innovative integration of MOFs and electrospinning offers a promising strategy for developing efficient, recyclable, and high-performance catalysts for environmental remediation.

Novel design of potent anti-tumour activity of IL-2 prodrug by FAPα-mediated activation

Interleukin-2 (IL-2) is a T cell growth factor that is essential for the proliferation of T cells and the generation of effector and memory cells. The antitumor activity of high-dose IL-2 therapy requires maintaining the affinity between IL-2 and IL2-Rα, which can also bring serious toxic side effects. To address this issue, we designed ZGP-Cysteamine-IL-2-K64C and (ZGP-Cysteamine)2-IL-2-(K43C, K64C) based on the strategy of FAPα enzyme-activated prodrugs, and investigated their anti-tumour activity and side effects. In vitro FAPα enzyme cleavage results indicated that the side-chain modified ZGP-Cysteamine moiety could be precisely recognized and cleaved by FAPα, thereby restoring the activity of native IL-2 capable of binding to IL-2Rα in the tumour microenvironment, where it promotes the expansion of CD8+ T cells. Meanwhile, surface plasmon resonance analysis revealed that, compared to wt-IL-2, both ZGP-Cysteamine-IL-2-K64C and (ZGP-Cysteamine)2-IL-2-(K43C, K64C) exhibited significantly reduced affinity for IL-2Rα, while their affinity for IL-2Rβγ remained unchanged. Remarkably, ZGP-Cysteamine-IL-2-K64C and (ZGP-Cysteamine)2-IL-2-(K43C, K64C) almost completely eliminated the pulmonary edema and vascular permeability. Furthermore, the combination of ZGP-Cysteamine-IL-2-K64C and PD-1 blockade showed robust anti-tumour activity in mice tumour models. Our study provides new insights into the structural design of IL-2 prodrug with low side effect and robust anti-tumour efficacy.