Sm(â ¢), Gd(â ¢), and Eu(â ¢) complexes with 8-hydroxyquinoline derivatives as potential anticancer agents via inhibiting cell proliferation, blocking cell cycle, and inducing apoptosis in NCI-H460 cells.

Four lanthanide complexes with 8-hydroxyquinoline-2-aldehyde-2-hydrazinopyridine (H-L1), 8-hydroxyquinoline-2-aldehyde-2-hydrazimidazole (H-L2): [Sm(L1)2][Sm(L1)(NO3)3]·CHCl3·2CH3OH (1), [Gd(L1)2][Gd(L1)(NO3)3]·CHCl3·2CH3OH (2), [Sm(L2)(NO3)2]2·CH3OH (3), and [Eu(L2)(NO3)2]2·CH3OH (4) were synthesized and characterized. In vitro cytotoxicity evaluation showed that the ligands and four lanthanide complexes exhibited cytotoxicity to the five tested tumor cell lines. Among them, complex 1 showed the best antiproliferative activity against NCI-H460 tumor cells. Mechanistic studies demonstrated that complex 1 arrested the cell cycle of NCI-H460 cells in G1 phase and induced mitochondria-mediated apoptosis, which resulted in the loss of mitochondrial membrane potential, enhanced intracellular Ca2+ levels and reactive oxygen species generation. In addition, complex 1 affected the expression levels of intracellular apoptosis-related proteins and activated the caspase-3/9 in NCI-H460 cells. Therefore, complex 1 is a potential anticancer agent.

Molecular Dynamics Simulation Model of Alkali Metal Reduction of Gaseous Halides and Reaction Mechanism Analysis.

The reaction of gaseous hydrogen halides with alkali metals provides a new pathway for producing hydrogen. The structure and reactivity of alkali metals are crucial for the reduction of gaseous halides. However, traditional gas-phase reaction models fail to provide insights into the dynamic processes occurring during alkali metal reactions. In this paper, based on the reaction between Hydrogen fluoride (HF) and alkali metal sodium (Na), we have established a metallic Na slab. HF molecules were randomly inserted above the surface of the Na slab, creating a reaction model for the reduction of HF by metallic Na. The reaction of HF on the Na surface was calculated using first-principles molecular dynamics. The configuration and reaction of the Na surface and HF molecules at different times were judged by analyzing the radial distribution function and mean squared displacement. Na atoms reacted with HF to produce intermediate NaFH, and then the F-H bond broke to form NaF and H. The F-H bond breaking of intermediate NaFH was the key step, and the kinetic parameters of this key step were calculated.

Development and Validation of a Computed Tomography-Based Model for Noninvasive Prediction of the T Stage in Gastric Cancer: Multicenter Retrospective Study.

BACKGROUND: As part of the TNM (tumor-node-metastasis) staging system, T staging based on tumor depth is crucial for developing treatment plans. Previous studies have constructed a deep learning model based on computed tomographic (CT) radiomic signatures to predict the number of lymph node metastases and survival in patients with resected gastric cancer (GC). However, few studies have reported the combination of deep learning and radiomics in predicting T staging in GC. OBJECTIVE: This study aimed to develop a CT-based model for automatic prediction of the T stage of GC via radiomics and deep learning. METHODS: A total of 771 GC patients from 3 centers were retrospectively enrolled and divided into training, validation, and testing cohorts. Patients with GC were classified into mild (stage T1 and T2), moderate (stage T3), and severe (stage T4) groups. Three predictive models based on the labeled CT images were constructed using the radiomics features (radiomics model), deep features (deep learning model), and a combination of both (hybrid model). RESULTS: The overall classification accuracy of the radiomics model was 64.3% in the internal testing data set. The deep learning model and hybrid model showed better performance than the radiomics model, with overall classification accuracies of 75.7% (P=.04) and 81.4% (P=.001), respectively. On the subtasks of binary classification of tumor severity, the areas under the curve of the radiomics, deep learning, and hybrid models were 0.875, 0.866, and 0.886 in the internal testing data set and 0.820, 0.818, and 0.972 in the external testing data set, respectively, for differentiating mild (stage T1~T2) from nonmild (stage T3~T4) patients, and were 0.815, 0.892, and 0.894 in the internal testing data set and 0.685, 0.808, and 0.897 in the external testing data set, respectively, for differentiating nonsevere (stage T1~T3) from severe (stage T4) patients. CONCLUSIONS: The hybrid model integrating radiomics features and deep features showed favorable performance in diagnosing the pathological stage of GC.

Catalytic conversion of soluble aniline into insoluble N-phenylphenazine for wastewater treatments.

Aniline, a common pollutant in industrial wastewater, requires an effective treatment method with minimal chemical usage. In this study, a two-stage catalytic oligomerization process has been developed to address this issue by converting soluble aniline into insoluble oligomers for wastewater treatment. In the first stage, aniline is oxidized using hydrogen peroxide (H2O2) and a green catalyst, iron tetraamido macrocyclic ligand (Fe-TAML) to form aniline tetramers or pentamers. In the second stage, these oligoanilines undergo further oxidation with H2O2 alone at a higher temperature, resulting in the formation of N-phenylphenazine or its derivatives. These macrocyclic compounds precipitate from the wastewater due to π- π stacking, allowing easy separation through decantation or gravity filtration. After process optimization, only 3 mg/L of Fe-TAML and 2 g/L of H2O2 are required to treat 1 g/L of aniline, achieving a remarkable 96.8% aniline removal efficiency and a 62.5% precipitate yield. This two-stage oxidation approach shows promise for treating aniline and similar aromatic compounds in real industrial wastewater.

Correlation between medical coping style and mindfulness level of hospitalized elderly: implications for enhancing psychological well-being.

BACKGROUND: The mindfulness level of hospitalized elderly is influenced by factors such as physical health, emotional resilience, and social support. However, little is known regarding the relationship between medical coping styles and mindfulness levels of hospitalized elderly. The aims of this study were to explore the association between medical coping styles and mindfulness levels in hospitalized elderly patients, with a focus on identifying actionable strategies to enhance patient well-being. METHODS: A survey of 253 elderly patients was conducted in the Department of Geriatrics of a 3 A hospital in Tangshan from September to November 2022 using the General Questionnaire, Medical Coping Style Scale (MCMQ), and Mindfulness-Attention Awareness Scale (MAAS). RESULTS: The average mindfulness level score of the hospitalized elderly was (59.71 ± 13.90), with a scoring rate of 66.34%, at a moderate mindfulness level. This study revealed a strong positive correlation (r = 0.725, P < 0.05) between confrontation coping and mindfulness, highlighting the importance of promoting active coping strategies to improve mindfulness levels in elderly patients. CONCLUSION: The mindfulness level of the hospitalized elderly shows potential for improvement, their coping styles are closely related to their mindfulness level, and positive coping styles can help improve the mindfulness level of the hospitalized elderly. This study suggested that medical staff can consider formulating targeted interventions, contingent upon available resources and training, guide patients to establish positive coping styles, and improve the mindfulness level of hospitalized elderly people.

CAF-secreted LOX promotes PD-L1 expression via histone Lactylation and regulates tumor EMT through TGFß/IGF1 signaling in gastric Cancer.

In gastric cancer treatment, cancer-associated fibroblasts (CAF) may significantly influence the efficacy of immune checkpoint inhibitors by modulating PD-L1 expression. However, the precise mechanisms remain unclear. This study aims to explore the relationship between CAF and PD-L1 expression, providing new insights for improving PD-L1-targeted therapies. Using primary fibroblasts, transcriptome sequencing, ChIP-qPCR, and a lung metastasis model, we discovered that CAF secrete lysyl oxidase (LOX), which activates the TGFß signaling pathway in gastric cancer cells, thereby promoting insulin-like growth factor 1(IGF1) expression. Upregulation of IGF1 enhances gastric cancer cell migration, epithelial-mesenchymal transition (EMT), and glycolysis. Additionally, we found that lactate accumulation leads to lysine 18 lactylation on histone H3 (H3K18la), which enriches at the PD-L1 promoter region, thus promoting PD-L1 transcription. These findings suggest that CAF may diminish the effectiveness of PD-1/PD-L1 blockade immunotherapy through LOX-induced glycolysis and lactate accumulation. Consequently, we have constructed a model of the interactions among CAF, lactate, and PD-L1 in gastric cancer progression, providing new experimental evidence for PD-L1-based immunotherapy.

Frequency modulation increases the specificity of time-resolved connectivity: A resting-state fMRI study.

Representing data using time-resolved networks is valuable for analyzing functional data of the human brain. One commonly used method for constructing time-resolved networks from data is sliding window Pearson correlation (SWPC). One major limitation of SWPC is that it applies a high-pass filter to the activity time series. Therefore, if we select a short window (desirable to estimate rapid changes in connectivity), we will remove important low-frequency information. Here, we propose an approach based on single sideband modulation (SSB) in communication theory. This allows us to select shorter windows to capture rapid changes in the time-resolved functional network connectivity (trFNC). We use simulation and real resting-state functional magnetic resonance imaging (fMRI) data to demonstrate the superior performance of SSB+SWPC compared to SWPC. We also compare the recurring trFNC patterns between individuals with the first episode of psychosis (FEP) and typical controls (TC) and show that FEPs stay more in states that show weaker connectivity across the whole brain. A result exclusive to SSB+SWPC is that TCs stay more in a state with negative connectivity between subcortical and cortical regions. Based on all the results, we argue that SSB+SWPC is more sensitive for capturing temporal variation in trFNC.

Lactate's impact on immune cells in sepsis: unraveling the complex interplay.

Lactate significantly impacts immune cell function in sepsis and septic shock, transcending its traditional view as just a metabolic byproduct. This review summarizes the role of lactate as a biomarker and its influence on immune cell dynamics, emphasizing its critical role in modulating immune responses during sepsis. Mechanistically, key lactate transporters like MCT1, MCT4, and the receptor GPR81 are crucial in mediating these effects. HIF-1α also plays a significant role in lactate-driven immune modulation. Additionally, lactate affects immune cell function through post-translational modifications such as lactylation, acetylation, and phosphorylation, which alter enzyme activities and protein functions. These interactions between lactate and immune cells are central to understanding sepsis-associated immune dysregulation, offering insights that can guide future research and improve therapeutic strategies to enhance patient outcomes.

Efficacy of tissue-bone homeostasis manipulation on the gait and knee function for the patients with knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Knee osteoarthritis (KOA) was characterized by pain and limited joint function, which seriously affected the quality of life of patients. The vast majority of KOA was closely related to degeneration of the patellofemoral joint and abnormal patellar movement trajectory. Tissue-bone homeostasis manipulation (TBHM) could correct abnormal patellar movement trajectory on the basis of loosening soft tissue. However, there was little strong evidence to verify its efficacy on the patients with KOA. The study objective was to explore the efficacy of the TBHM on gait and knee function in the patients with KOA. METHODS: Sixty KOA patients were randomly assigned to either the joint mobilization (n = 30) or TBHM (n = 30) group. The joint mobilization group received joint mobilization, while the TBHM group received TBHM. For two groups, the patients participated in 30 min rehabilitation sessions thrice per week for 12 weeks. The primary outcome was biomechanical gait outcomes during walking, including step length, step velocity, double support, knee range of motion (ROM), and knee adduction moment (KAM). The secondary outcomes were the Western Ontario and McMaster Index (WOMAC) and 36-Item short- form health survey (SF-36), which reflected improvements in knee function and quality of life, respectively. At baseline and 12 weeks, evaluations were conducted and compared between groups. RESULTS: After a 12-week intervention, significant group differences were observed in KAM (p = 0.018), WOMAC-Pain (p = 0.043) and WOMAC-Stiffness (p = 0.026). A noteworthy finding was the presence of a significant interaction effect between group and time specifically observed in step velocity during gait (p = 0.046), WOMAC-Function (p = 0.013) and SF-36 (p = 0.027). Further analysis revealed a significant difference in step velocity (p = 0.034), WOMAC-Function (p = 0.025) and SF-36 (p = 0.042) during post-assessment between the two groups. Moreover, a significant time effect was observed across all outcomes of the two groups (p < 0.05). CONCLUSION: The TBHM intervention has better improved the gait, knee function, and quality of life in the patients with KOA. TRIAL REGISTRATION: ITMCTR, ITMCTR2200005507. Registered 06/01/2022, http://itmctr.ccebtcm.org.cn/zh-CN/Home/ProjectView?pid=09cdadad-0aef-41ee-81bd-a8dceb63f7f5 .

Human 8-Oxoguanine Glycosylase OGG1 Cleaves Abasic Sites and Covalently Conjugates to 3'-DNA Termini via Cysteine and Histidine Addition.

8-Oxoguanine glycosylase 1 (OGG1) repairs the major oxidative DNA damage, 8-oxo-2'-deoxyguanosine. It has been reported that OGG1 incises the most frequently formed DNA lesion, apurinic/apyrimidinic (AP) site, and in the process a stable DNA-OGG1 cross-link is formed. However, the chemical structure of the adduct is not characterized. Here, we report that DNA-OGG1 cross-links result from cysteine and histidine addition to incised AP sites at 3'-DNA termini.

Efficient urinary stone type prediction: a novel approach based on self-distillation.

Urolithiasis is a leading urological disorder where accurate preoperative identification of stone types is critical for effective treatment. Deep learning has shown promise in classifying urolithiasis from CT images, yet faces challenges with model size and computational efficiency in real clinical settings. To address these challenges, we developed a non-invasive prediction approach for determining urinary stone types based on CT images. Through the refinement and improvement of the self-distillation architecture, coupled with the incorporation of feature fusion and the Coordinate Attention Module (CAM), we facilitated a more effective and thorough knowledge transfer. This method circumvents the extra computational expenses and performance reduction linked with model compression and removes the reliance on external teacher models, markedly enhancing the efficacy of lightweight models. achieved a classification accuracy of 74.96% on a proprietary dataset, outperforming current techniques. Furthermore, our method demonstrated superior performance and generalizability on two public datasets. This not only validates the effectiveness of our approach in classifying urinary stones but also showcases its potential in other medical image processing tasks. These results further reinforce the feasibility of our model for actual clinical deployment, potentially assisting healthcare professionals in devising more precise treatment plans and reducing patient discomfort.

Temporal trend and attributable risk factors of Alzheimer's disease and other dementias burden in China: Findings from the Global Burden of Disease Study 2021.

INTRODUCTION: We examined the burden of Alzheimer's disease and other dementias (ADOD) and attributable factors at the national and provincial levels in China. METHODS: Using the Global Burden of Diseases Study 2021, we estimated incidence, prevalence, mortality rate, disability-adjusted life years (DALYs), and the ratio of years lived with disability (YLD) to DALYs for ADOD in China. Estimated annual percentage changes (EAPCs) were used to quantify the temporal trends from 1990 to 2021. RESULTS: In 2021, China experienced the highest ADOD burden among Group of 20 member nations. The EAPCs for age-standardized rates for incidence, age-standardized rates for prevalence, and age-standardized mortality rate were 0.41 (uncertainty intervals [UIs] 0.34-0.49); 0.44 (UI: 0.36-0.52); and -0.19 (UI: -0.23 to -0.15), respectively. Between 1990 and 2021, the number of people with ADOD increased by 322.18% and DALYs associated with ADOD increased by 272.71%; most of these increases were explained by population aging. DISCUSSION: Considering the aging Chinese population, targeted strategies to prevent dementia are urgently needed. HIGHLIGHTS: China experienced the highest dementia burden among Group of 20 member nations. High body mass index, high fasting plasma glucose, and smoking were major risk factors for Alzheimer's disease and other dementias (ADOD) burden. Since 1990, the incidence and prevalence of ADOD increased substantially in China. The mortality rate related to ADOD decreased consistently. Considering the aging Chinese population, targeted strategies are urgently needed.

The AP-2 Family of Transcription Factors-Still Undervalued Regulators in Gastroenterological Disorders.

Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the TFAP2A/B/C/D/E genes have been identified in humans, i.e., AP-2α/ß/γ/δ/ε. In general, the first three TFs have been studied more thoroughly than AP-2δ or AP-2ε. Currently, there is a relatively limited body of literature focusing on the AP-2 family in the context of gastroenterological research, and a comprehensive overview of the existing knowledge and recommendations for further research directions is lacking. Herein, we have collected available gastroenterological data on AP-2 TFs, discussed the latest medical applications of each family member, and proposed potential future directions. Research on AP-2 in gastrointestinal tumors has predominantly been focused on the two best-described family members, AP-2α and AP-2γ. Surprisingly, research in the past decade has highlighted the importance of AP-2ε in the drug resistance of gastric cancer (GC) and colorectal cancer (CRC). While numerous questions about gastroenterological disorders await elucidation, the available data undoubtedly open avenues for anti-cancer targeted therapy and overcoming chemotherapy resistance. In addition to gastrointestinal cancers, AP-2 family members (primarily AP-2ß and marginally AP-2γ) have been associated with other health issues such as obesity, type 2 diabetes, liver dysfunction, and pseudo-obstruction. On the other hand, AP-2δ has been poorly investigated in gastroenterological disorders, necessitating further research to delineate its role. In conclusion, despite the limited attention given to AP-2 in gastroenterology research, pivotal functions of these transcription factors have started to emerge and warrant further exploration in the future.

A natural acylphloroglucinol exerts anti-erythroleukemia effects via targeting STAT3 and p38-MAPK, and inhibiting PI3K/AKT/mTOR signaling pathway.

Erythroleukemia, a subtype of acute myeloid leukemia (AML), is a life-threatening malignancy that affects the blood and bone marrow. Despite the availability of clinical treatments, the complex pathogenesis of the disease and the severe side effects of chemotherapy continue to impede therapeutic progress in leukemia. In this study, we investigated the antitumor activity of L76, an acylphloroglucinol compound derived from Callistemon salignus DC., against erythroleukemia, along with its underlying mechanisms. MTT assays were performed to evaluate the inhibitory effects of L76 on cancer cell viability, while flow cytometry was used to analyze apoptosis and cell cycle arrest in HEL cells. The molecular mechanisms of L76 were further explored using Western blotting, microscopic analysis, and cellular thermal shift assays (CETSA). Our in vitro experiments demonstrated that L76 inhibits proliferation, induces G1/S cell cycle arrest, and promotes apoptosis in human leukemia cells. Mechanistically, L76 exerts its effects by targeting STAT3 and p38-MAPK, and by inhibiting the PI3K/AKT/mTOR signaling pathway. In conclusion, this study highlights the potential of L76 as an anti-erythroleukemia agent, demonstrating its ability to target STAT3 and p38-MAPK, and to inhibit the PI3K/AKT/mTOR signaling pathway. These findings suggest that L76 could be a promising candidate for the treatment of erythroleukemia.

Interplanting potato with grapes improved yield and soil nutrients by optimizing the interactions of soil microorganisms and metabolites.

Interplanting crops is the best method to grow crops synergistically for better utilization of land and agro-resources. Grape (Vitis vinifera) and potato (Solanum tuberosum L.) have highly efficient agricultural planting systems in China, however, how soil physicochemical properties and soil microbial communities and metabolites affect the output of grape-potato interplanting remained unknown. In this study, we employed three planting patterns (CK: grape monocropping; YY: grape interplanted with potato (variety 'Favorita'); LS: grape interplanted with potato (variety 'Longshu7')) at two experimental sites i.e., the Huizhou (2022) site and the Qingyuan site (2023). The grape variety for all planting patterns was 'Sunshine Rose'. Soil samples (top 0-20 cm) at both sites were collected to observe the diversity of bacterial communities and soil metabolites. Our findings revealed that, compared with monocropping, the interplanted systems resulted in higher concentrations of total nitrogen, available phosphorus, and available potassium and enhanced the activities of acid phosphatase, urease, and protease. The potato root exudates also altered the relative abundance of Bacillus, Kaistobacter, and Streptomyces in the rhizosphere. Among the soil metabolites, lipids and organic acids showed the most significant changes. Notably, 13-L-hydroperoxylinoleic acid is the key differentially abundant metabolite involved in the regulation of linoleic acid metabolism pathways. The association analyses of the metabolome, microbiome, and soil physicochemical properties revealed that the interactions of microbes and metabolites resulted in differences in the soil nutrient content, whereas the interactions of 13-L-hydroperoxylinoleic acid and Firmicutes improved the soil nutrient levels and bacterial composition in the interplanting systems. In summary, our findings demonstrated that intercropping grapes with potato 'Favorita' was better with respect to improving soil nutrients, soil enzyme activity, the diversity of soil bacteria, and soil metabolites without causing adverse impacts on grape yield. Overall, this study explained the physiological mechanisms by which soil microorganisms and metabolites promote potato growth in grape interplanting and provided new perspectives for the utilization of soil resources in vineyards.

LncRNA MIAT suppresses inflammation in LPS-induced J774A.1 macrophages by promoting autophagy through miR-30a-5p/SOCS1 axi.

Accumulated data implicate that long noncoding RNA (lncRNA) plays a pivotal role in rheumatoid arthritis (RA), potentially serving as a competitive endogenous RNA (ceRNA) for microRNAs (miRNAs). The lncRNA myocardial infarction-associated transcript (MIAT) has been demonstrated to regulate inflammation. However, the role of MIAT in the inflammation of RA remains inadequately explored. This study aims to elucidate MIAT's role in the inflammation of lipopolysaccharide (LPS)-induced macrophages and to uncover the underlying molecular mechanisms. We observed heightened MIAT expression in LPS-induced J774A.1 cells and collagen-induced arthritis mouse models, in contrast to the expression pattern of miR-30a-5p. Silencing MIAT resulted in increased expression of the inflammatory cytokines IL-1ß and TNF-α. Simultaneously, MIAT interference significantly impeded macrophage autophagy, evidenced by decreased expression of autophagy-related markers LC3-II and Beclin-1, alongside increased levels of p62 in LPS-induced J774A.1 cells. Notably, MIAT functioned as a ceRNA, sponging miR-30a-5p and exerting a negative regulatory influence on its expression. SOCS1 emerged as a target of miR-30a-5p, modulated by MIAT. Mechanistically, inhibiting miR-30a-5p reversed the impact of MIAT deficiency in promoting LPS-induced inflammation, while SOCS1 knockdown countered the cytokine inhibitory effect induced by silencing miR-30a-5p. In summary, this study indicates that lncRNA MIAT suppresses inflammation in LPS-induced J774A.1 macrophages by stimulating autophagy through the miR-30a-5p/SOCS1 axis. This suggests that MIAT holds promise as a potential therapeutic target for RA inflammation.

Lysosome-Associated Membrane Protein Targeting Strategy Improved Immunogenicity of Glycoprotein-Based DNA Vaccine for Marburg Virus.

Marburg hemorrhagic fever (MHF) is a fatal infectious disease caused by Marburg virus (MARV) infection, and MARV has been identified as a priority pathogen for vaccine development by the WHO. The glycoprotein (GP) of MARV mediates viral adhesion and invasion of host cells and therefore can be used as an effective target for vaccine development. Moreover, DNA vaccines have unique advantages, such as simple construction processes, low production costs, and few adverse reactions, but their immunogenicity may decrease due to the poor absorption rate of plasmids. Lysosome-associated membrane protein 1 (LAMP1) can direct antigens to lysosomes and endosomes and has great potential for improving the immunogenicity of nucleic acid vaccines. Therefore, we constructed a DNA vaccine based on a codon-optimized MARV GP (ID MF939097.1) fused with LAMP1 and explored the effect of a LAMP targeting strategy on improving the immunogenicity of the MARV DNA vaccine. ELISA, ELISpot, and flow cytometry revealed that the introduction of LAMP1 into the MARV DNA candidate vaccine improved the humoral and cellular immune response, enhanced the secretion of cytokines, and established long-term immune protection. Transcriptome analysis revealed that the LAMP targeting strategy significantly enriched antigen processing and presentation-related pathways, especially the MHC class II-related pathway, in the candidate vaccine. Our study broadens the strategic vision for enhanced DNA vaccine design and provides a promising candidate vaccine for MHF prevention.

Expression of a Recombinant Cholesterol Esterase from Mustela putorius furo in Pichia pastoris and Its Applicability for γ-Oryzanol Hydrolysis.

Ferulic acid (FA) exhibits antioxidant and anti-inflammatory properties, making it valuable for numerous industrial applications. Traditionally, FA is produced by the alkaline hydrolysis of γ-oryzanol, which is typically associated with wastewater generation. Recently, an increasing demand of natural FA necessitates its green production via enzymatic hydrolysis of γ-oryzanol, a mixture comprising triterpene alcohol ferulates and phytosteryl ferulates. Thus far, γ-oryzanol can be hydrolyzed by only four commercial cholesterol esterases with low yields. Herein, we report a recombinant cholesterol esterase from Mustela putorius furo (MPFCE) for the enzymatic hydrolysis of γ-oryzanol. The enzyme yielded 25.5% FA, which is the highest reported through enzymatic means thus far. The hydrolysis profile revealed that the enhanced yield primarily resulted from the near-complete hydrolysis of phytosteryl ferulates, together with slight hydrolysis of triterpene alcohol ferulates. MPFCE serves as a potential candidate for the enzymatic production of FA through targeted hydrolysis of γ-oryzanol.

The dark side of climate policy uncertainty: Hindering energy transition by shaping environmental taxes effectiveness.

Climate policy uncertainty (CPU) may have an adverse impact on the environment by interfering with the effectiveness of environmental policies, but there is currently little evidence to support this indirect effect. By incorporating CPU into the transition function, this paper utilizes the panel smooth transition regression (PSTR) to dynamically analyze how CPU affects the relationship between environmental taxes (ETR) and energy transition. When CPU exceeds the threshold, the promoting effect of ETR on energy transition weakens or reverses. The robustness of the main conclusions is demonstrated by establishing a PSTR estimator with the instrumental variable. This paper also constructs a counterfactual scenario, showing that CPU reduces the positive impact of ETR on renewable energy consumption and generation by 7.6% and 3.5%, respectively. Further analysis indicates that this negative effect arises because CPU likely increases investment risk, particularly for long-term green projects, thereby inhibiting the clean energy market and energy-related green technological innovation. Heterogeneity analysis find that the weakening effect of CPU on the effectiveness of ETR is stronger in countries with low energy resource endowment, high energy intensity, and lower economic development levels, underscoring the need for tailored policy approaches. This research emphasizes that for countries with ambitious energy transition goals, climate policy stability is crucial for ensuring the healthy development of environmental taxes policy and renewable energy markets.

Determining the Degree of Sulfo-tag Conjugation to AAV5 Vectors by LC-HRMS and Evaluating the Effects on Antibody Binding Affinity and Bridging Assay Sensitivity.

Pre-existing anti-AAV antibodies can be detected using ligand binding-based assay formats. One such format is the MSD-based bridging assay, which uses sulfo-tag-labeled AAV vectors as detection reagents. However, no method has been developed to accurately measure the degree of sulfo-tag labeling on AAV vectors. To fill this gap, we developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method to assess the degree of labeling (DoL) of sulfo-tag on AAV5 vectors, enabling the measurement of the DoL on AAV5 at six increasing levels of sulfo-tag challenge ratio. In addition, a Biacore-based assay was used to evaluate the binding affinity between an anti-AAV5 monoclonal antibody and various sulfo-tag labeled AAV5 vectors. The results indicated that increased DoL of sulfo-tag labeling on AAV5 did not compromise the binding affinity.Our study further employed the MSD-bridging assay to detect the binding Signal/Noise (S/N) ratios of four anti-AAV5 monoclonal antibodies (mAbs) to various sulfo-tag-labeled AAV5 vectors. The findings revealed a strong correlation between the degree of sulfo-tag labeling and both the S/N ratios and the sensitivity of MSD bridging assays. This result underscores the importance of optimizing the labeling of detection reagents to enhance assay sensitivity for detecting anti-AAV5 antibodies.