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The enhancement of saltiness induced by odrants perceived from the retronasal cavity during Larou oral processing was analyzed. During the oral processing of Xiangtan Larou, the smoky attribute was the dominant when chewing 0-15 times, followed by the savory (15-24 times) and meaty (24-42 times). Partial least squares analysis predicted 33 aroma compounds from the retronasal cavity significantly (p < 0.05) contributing to the aroma perception. A total of 12 aroma compounds with saltiness-enhancement ability were confirmed by odorant-NaCl mixture model experiments. Results revealed that 2-methoxy-4-vinylphenol (1.00-1000.00 µg/L) had the strongest enhancing effect on saltiness at NaCl (2969.85 mg/L), followed by diallyl sulfide (0.156-2.50 µg/L), 2,5-dimethylthiophene (0.156-50.00 µg/L), 2,6-dimethylphenol (1.00-100.00 µg/L), 2,5-dimethylpyrazine (0.391-50.00 µg/L), and 2,3-butanedione (0.50-100.0 µg/L). The sulfur-containing, nitrogen-containing, and phenolic odorants with savory, roasty, sulfide, meaty or smoky, attributes showed the better ability in saltiness enhancement.

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Deciphering cell identity genes is pivotal to understanding cell differentiation, development, and many diseases involving cell identity dysregulation. Here, we introduce SCIG, a machine-learning method to uncover cell identity genes in single cells. In alignment with recent reports that cell identity genes are regulated with unique epigenetic signatures, we found cell identity genes exhibit distinctive genetic sequence signatures, e.g., unique enrichment patterns of cis-regulatory elements. Using these genetic sequence signatures, along with gene expression information from single-cell RNA-seq data, enables SCIG to uncover the identity genes of a cell without a need for comparison to other cells. Cell identity gene score defined by SCIG surpassed expression value in network analysis to uncover master transcription factors regulating cell identity. Applying SCIG to the human endothelial cell atlas revealed that the tissue microenvironment is a critical supplement to master transcription factors for cell identity refinement. SCIG is publicly available at https://github.com/kaifuchenlab/SCIG , offering a valuable tool for advancing cell differentiation, development, and regenerative medicine research.

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Three ball-milling methodologies were developed to synthesize bespoke multi-metallic K-doped Cu-Fe/ZnO-Al2O3 catalysts for the hydrogenation of carbon dioxide. The catalytic performance of the catalysts was benchmarked against their solution-based counterparts. The catalysts synthesized by ball milling are greener, showing smaller particles, with different selectivity towards oxygenate products.

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PURPOSE: To identify symptom clusters (SCs) in lung cancer patients undergoing chemotherapy and explore their impact on health-related quality of life (HRQoL). METHODS: Patients were invited to complete the Chinese version of the M.D. Anderson Symptom Inventory with the Lung Cancer Module and the Quality of Life Questionnaire-core 30. Network analysis was employed to identify SCs. The associations between SCs and each function of HRQoL were examined using the Pearson correlation matrix. Multiple linear regression was applied to analyze the influencing factors of each function of HRQoL. RESULTS: A total of 623 lung cancer patients who were receiving chemotherapy were recruited. The global health status of lung cancer patients was 59.71 ± 21.09, and 89.73% of patients developed symptoms. Three SCs (Somato-psychological SC, Respiratory SC, and Gastrointestinal SC) were identified, and Somato-psychological SC and Gastrointestinal SC were identified as influencing factors for HRQoL in lung cancer patients. CONCLUSION: Most lung cancer patients who undergo chemotherapy experience a range of symptoms, which can be categorized into three SCs. The Somato-psychological SC and Gastrointestinal SC negatively impacted patients' HRQoL. Health care providers should prioritize monitoring these SCs to identify high-risk patients early and implement targeted preventive and intervention measures for each SC, aiming to alleviate symptom burden and enhance HRQoL.

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Actin depolymerizing factors (ADFs), as the important actin-binding proteins (ABPs) with depolymerizing/severing actin filaments, play a critical role in plant growth and development, and in response to biotic and abiotic stresses. However, the information and function of the ADF family in melon remains unclear. In this study, 9 melon ADF genes (CmADFs) were identified, distributed in 4 subfamilies, and located on 6 chromosomes respectively. Promoter analysis revealed that the CmADFs contained a large number of cis-acting elements related to hormones and stresses. The similarity of CmADFs with their Arabidopsis homologue AtADFs in sequence, structure, important sites and tissue expression confirmed that ADFs were conserved. Gene expression analysis showed that CmADFs responded to low and high temperature stresses, as well as ABA and SA signals. In particular, CmADF1 was significantly up-regulated under above all stress and hormone treatments, indicating that CmADF1 plays a key role in stress and hormone signaling responses, so CmADF1 was selected to further study the mechanism in plant tolerance low temperature. Under low temperature, virus-induced gene silencing (VIGS) of CmADF1 in oriental melon plants showed increased sensitivity to low temperature stress. Consistently, the stable genetic overexpression of CmADF1 in Arabidopsis improved their low temperature tolerance, possibly due to the role of CmADF1 in the depolymerization of actin filaments. Overall, our findings indicated that CmADF genes, especially CmADF1, function in response to abiotic stresses in melon.

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Flexible electronic sensing and energy storage technology impose heightened demands on the mechanical and stable properties of gel electrolyte materials. Lignocellulosic nanofiber (LCNF) present a promising avenue for improving the properties of electrolyte networks and mechanical strength. In this study, LCNF derived from hemp fibers was prepared using lactic acid/choline chloride deep eutectic solvent (DES) through a combination of cooking and colloid mill mechanical treatment to achieve nanocellulose with a high aspect ratio and uniform dimensions. The outcomes demonstrated that LCNF, a width of below 20 nm and a length of over 5 µm, can be effectively produced through the DES cooking pretreatment in conjunction with colloid mill mechanical treatment. Meanwhile, DES lignin possessed a purity of ∼90 % and was obtained as a by-product. Subsequently, the as-prepared LCNF was integrated as a nanofiller into gel electrolyte. Ag-L NPs/LCNF/DES/PAA exhibited dense porous structures and showcased exceptional properties, including a high conductivity exceeding 10 mS/cm and remarkable adhesion strength surpassing 100 KPa. The presence of LCNF allowed Ag-L NPs/LCNF/DES/PAA to achieve strains above 1000 % and compression properties over 1000 KPa. The supercapacitor based on this assembly had a high specific capacitance of 271 F g-1 at 0.5 A g-1), along with an impressive capacity retention rate reaching ∼100 % after 3000 cycles. This investigation offers valuable insights into the utilization of lignocellulosic multi-component approaches in the development of flexible electronic devices.

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Purpose: To investigate and analyse the status quo of the self-management of patients living with HIV/AIDS (PLWHA) and its influencing factors and to provide the basis for formulating intervention strategies. Methods: In this cross-sectional study, 300 PLWHA who visited the Infection Center of Beijing Youan Hospital, Capital Medical University between September 2021 and December 2021 were enrolled using the convenience sampling method. Demographic characteristics and disease-related data were collected for each participant. The HIV/AIDS Self-Management Scale was used to evaluate the self-management ability of PLWHA. Results: A total of 251 male and 49 female PLWHA were included in this study, with an average age of 39.08 ± 12.09 years and an average disease duration of 9.61 ± 37.04 months. Univariate analysis showed that the PLWHA's place of residence, educational level, physical condition, family relations, duration of HIV disease, receipt or not of antiviral therapy and knowledge of disease had an influence on the scores of the HIV Self-Management Scale (all p < 0.05). The results of the self-management scores indicated that the total score for self-management was 41.5 ± 6.4 points, with a scoring rate of 69.6%, which was at a medium level. Long-term self-management had the highest scoring rate (12.2 ± 2.5 points), followed by daily health management (22.3 ± 4.3 points), and social support for self-management had the lowest scoring (5.1 ± 0.9 points). Multivariable analysis showed that the self-management ability of PLWHA was related to educational level, duration of disease and family relations (R2 = 0.67, F = 121.7, p < 0.05). Conclusion: The self-management level of patients with AIDS, especially the social support of daily health management and self-management, needs to be further improved. Educational level, duration of disease and family relations are important factors influencing the self-management of PLWHA.

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BACKGROUND This study aimed to evaluate the effectiveness of implementing evidence-based preoperative nursing interventions in reducing postoperative infections and intensive care unit (ICU) length of stay among liver transplant recipients. MATERIAL AND METHODS A controlled study was conducted, comparing postoperative outcomes between an intervention group receiving standardized, evidence-based preoperative care and a control group receiving routine preoperative care. Patients undergoing elective liver transplantation from September 2020 to March 2021 were included and assigned to either the intervention or control group. The intervention group received preoperative interventions based on best available evidence, while the control group received standard preoperative care. The primary outcomes measured were postoperative infection rates and length of ICU stay. RESULTS In the control group the overall Intensive Care Unit (ICU) length of stay was 3 days and the infection rate was 33.30%, while in the intervention group it was 3 days and 13.80% (P<0.05). There was no significant difference in the length of ICU stay between the control and the intervention groups (P>0.05). There was a significant improvement in the awareness, acceptance, and compliance of doctors and nurses. CONCLUSIONS Using the best evidence-based intervention for preoperative nursing of liver transplantation patients can standardize preoperative nursing behavior. Although we did not find significant differences in outcomes before and after the intervention, it is necessary to prevent postoperative infection and improve nursing compliance.

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Background: GLP-1 receptor agonists (GLP-1 RA) have been proven to treat several metabolic diseases; however, the effects of GLP-1 RA on polycystic ovary syndrome (PCOS) remain unclear. Here, we aimed to investigate whether semaglutide, a novel GLP-1 RA, could alleviate ovarian inflammation in PCOS mice. Methods: Female C57BL/6J mice were subcutaneously injected with dehydroepiandrosterone for 21 days to establish the PCOS model. Then the mice were randomly divided into three groups: PCOS group (n = 6), S-0.42 group (semaglutide 0.42 mg/kg/w, n = 6), and S-0.84 group (semaglutide 0.84 mg/kg/w, n = 6). The remaining six mice were used as controls (NC). After 28 days of intervention, serum sex hormones and inflammatory cytokine levels were measured. Hematoxylin and eosin staining was used to observe the ovarian morphology. Immunohistochemical staining was used to detect the relative expression of CYP19A1, TNF-α, IL-6, IL-1ß, and NF-κB in ovaries. CYP17A1 and StAR were detected using immunofluorescence staining. Finally, the relative expressions of AMPK, pAMPK, SIRT1, NF-κB, IκBα, pIκBα, TNF-α, IL-6, and IL-1ß were measured using Western blotting. Results: First, after intervention with semaglutide, the weight of the mice decreased, insulin resistance improved, and the estrous cycle returned to normal. Serum testosterone and IL-1ß levels decreased significantly, whereas estradiol and progestin levels increased significantly. Follicular cystic dilation significantly improved. The expression of TNF-α, IL-6, IL-1ß, NF-κB, CYP17A1, and StAR in the ovary was significantly downregulated, whereas CYP19A1 expression was upregulated after the intervention. Finally, we confirmed that semaglutide alleviates ovarian tissue inflammation and improves PCOS through the AMPK/SIRT1/NF-κB signaling pathway. Conclusion: Semaglutide alleviates ovarian inflammation via the AMPK/SIRT1/NF­κB signaling pathway in PCOS mice.

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Potato is one of the four staple food crops in the world. It has a wide range of cultivation, high yield, and high nutritional value. Enhancing the photosynthesis of potato is particularly important as it leads to an increase in the potato yield. The light-harvesting pigment-binding protein complex is very important for plant photosynthesis. We identified 12 Stlhcb gene family members from the potato variety "Atlantic" using transcriptome sequencing and bioinformatics. The proteins encoded by the Stlhcb gene family have between 3358 and 4852 atomic number, a relative molecular weight between 24060.16 and 34624.54 Da, and an isoelectric point between 4.99 and 8.65. The RT-qPCR results showed that the 12 Stlhcb genes were expressed in a tissue-specific and time-dependent fashion under low light. The relative expression of the Stlhcb genes in the leaves was significantly higher than that in the stems and roots, and the relative expression of these genes first increased and then decreased with the prolongation of light exposure time. The Stcp24 gene with the highest expression was cloned, and an expression vector was constructed. A subcellular localization analysis was performed in tobacco and an overexpression experiment was performed in potato using an Agrobacterium-mediated method. The subcellular localization analysis showed that the protein encoded by Stcp24 was located in chloroplasts as expected. Overexpression of Stcp24 in transgenic potato increased the yield of potatoes and the content of chlorophyll a and b; increased the net photosynthetic rate, transpiration rate, stomatal conductance, electron transport efficiency, and semi-saturated light intensity; and promoted photosynthesis and plant growth. This study provides a reference for the study of the function of the potato light-harvesting pigment-binding protein gene family. It lays a foundation for further study of the mechanism of the photosynthesis of potato, improvement of the light energy utilization of potato, and molecular breeding of potato.

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OBJECTIVES: This study aimed to summarize the most effective evidence on nonpharmacological interventions for the fatigue-pain-sleep disturbance symptom cluster in lung cancer patients and to provide evidence-based management methods for clinical team and lung cancer patients. METHODS: Guided by the "6S" pyramid model, we retrieved evidence on fatigue, pain, and sleep disturbance management from relevant websites and databases, and unpublished gray literature was also searched. The time frame of the search ranged from database establishment to September 30, 2023. Two researchers independently evaluated the literature quality using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) for guidelines, and the Assessment of Multiple Systematic Reviews II (AMSTAR II) for systematic reviews. Two people independently extracted and summarized the evidence according to the first principle of high-quality evidence and newly published evidence. The included evidence was graded by the JBI Evidence Pre-Grading System. RESULTS: A total of 52,238 articles were retrieved, of which 60 articles, including 18 guidelines, 18 JBI best practice recommendations, one Up To Date clinical practice, and 23 systematic reviews, were included. Overall, 49 pieces of evidence from six dimensions-screening, assessment, management, education, referral, and follow-up-were summarized. Forty-three pieces of evidence were level 1, three pieces of evidence were level 4, and three pieces of evidence were level 5. CONCLUSIONS: The best 49 pieces of evidence on nonpharmacological interventions for the fatigue-pain-sleep disturbance symptom cluster in lung cancer patients were summarized in this study, and these nonpharmacological interventions are scientific and comprehensive. IMPLICATIONS FOR NURSING PRACTICE: This study can provide guidance for clinical team to improve the fatigue-pain-sleep disturbance symptom cluster management. These evidence items can be implemented by clinical team to reduce the symptom burden and improve the self-management ability of symptoms in lung cancer patients.

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BACKGROUND: Depression is prevalent among lung cancer patients undergoing chemotherapy, and the symptom cluster of fatigue-pain-insomnia may influence their depression. Identifying characteristics of patients with different depression trajectories can aid in developing more targeted interventions. This study aimed to identify the trajectories of depression and the fatigue-pain-insomnia symptom cluster, and to explore the predictive factors associated with the categories of depression trajectories. METHODS: In this longitudinal study, 187 lung cancer patients who were undergoing chemotherapy were recruited and assessed at the first (T1), second(T2), and fourth(T3) months using the Patient Health Questionnaire-9 (PHQ-9), the Brief Pain Inventory (BPI), the Brief Fatigue Inventory (BFI), and the Athens Insomnia Scale (AIS). Growth Mixture Model (GMM) and Latent Class Analysis (LCA) were used to identify the different trajectories of the fatigue-pain-insomnia symptom cluster and depression. Binary logistic regression was utilized to analyze the predictive factors of different depressive trajectories. RESULTS: GMM identified two depressive trajectories: a high decreasing depression trajectory (40.64%) and a low increasing depression trajectory (59.36%). LCA showed that 48.66% of patients were likely members of the high symptom cluster trajectory. Binary logistic regression analysis indicated that having a history of alcohol consumption, a higher symptom cluster burden, unemployed, and a lower monthly income predicted a high decreasing depression trajectory. CONCLUSIONS: Depression and fatigue-pain-insomnia symptom cluster in lung cancer chemotherapy patients exhibited two distinct trajectories. When managing depression in these patients, it is recommended to strengthen symptom management and pay particular attention to individuals with a history of alcohol consumption, unemployed, and a lower monthly income.

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Fusarium oxysporum is an asexual filamentous fungus that causes vascular wilt in hundreds of crop plants and poses a threat to public health through Fusariosis. F. oxysporum f. sp. conglutinans strain Fo5176, originally isolated from Brassica oleracea, is pathogenic to Arabidopsis, making it a model pathosystem for dissecting the molecular mechanisms underlying host-pathogen interactions. Assembling the F. oxysporum genome is notoriously challenging due to the presence of repeat-rich accessory chromosomes. Here, we report a gap-free genome assembly of Fo5176 using PacBio HiFi and Hi-C data. The 69.56 Mb assembly contained 18 complete chromosomes, including all centromeres and most telomeres (20/36), representing the first gap-free genome sequence of a pathogenic F. oxysporum strain. In total, 21,460 protein-coding genes were annotated, a 26.3% increase compared to the most recent assembly. This high-quality reference genome for F. oxysporum f. sp. conglutinans Fo5176 provides a valuable resource for further research into fungal pathobiology and evolution.

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Rice stripe virus (RSV) establishes infection in the ovaries of its vector insect, Laodelphax striatellus. We demonstrate that RSV infection delays ovarian maturation by inhibiting membrane localization of the vitellogenin receptor (VgR), thereby reducing the vitellogenin (Vg) accumulation essential for egg development. We identify the host protein L. striatellus Rab1 protein (LsRab1), which directly interacts with RSV nucleocapsid protein (NP) within nurse cells. LsRab1 is required for VgR surface localization and ovarian Vg accumulation. RSV inhibits LsRab1 function through two mechanisms: NP binding LsRab1 prevents GTP binding, and NP binding LsRab1-GTP complexes stimulates GTP hydrolysis, forming an inactive LsRab1 form. Through this dual inhibition, RSV infection prevents LsRab1 from facilitating VgR trafficking to the cell membrane, leading to inefficient Vg uptake. The Vg-VgR pathway is present in most oviparous animals, and the mechanisms detailed here provide insights into the vertical transmission of other insect-transmitted viruses of medical and agricultural importance.

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PURPOSE: The aim of this study was to observe the influence of differential nutritional status on bone age (BA) change according to body mass index (BMI) and analyze the risk of advanced bone age in children with overweight and obesity. METHODS: In total 23,305 children from Beijing were included in this cross-sectional study. Childhood overweight and obesity were defined according to the China and World Health Organization growth criteria. The data were analyzed by the R coding platform version 4.3.0. RESULTS: Under the Chinese criteria, 29%, 15%, and 4% of boys with overweight; 33%, 33%, and 3% of boys with obesity; 39%, 25%, and 2% of girls with overweight; and 37%, 42% and 1% of girls with obesity had advanced, significantly advanced and delayed BA, respectively. After adjustment, overweight (odds ratio, 95% confidence interval, P under the Chinese criteria: 2.52, 2.30-2.75, <0.001 and 4.54, 4.06-5.09, <0.001) and obesity (4.31, 3.85-4.82, <0.001 and 14.01, 12.39-15.85, <0.001) were risk factors for both advanced BA and significantly advanced BA. CONCLUSIONS: Different nutritional statuses lead to differences in children's BA development. Children with overweight and obesity have higher rates of advanced BA under two growth criteria, and girls have more advances in BA than boys do. Overweight and obesity are risk factors for advanced BA.

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Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.

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BACKGROUND: Research in functional asymmetry of Major Depressive Disorder (MDD) under different tasks is crucial for clinical diagnose. METHODS: Fifty individuals with MDD and twenty healthy controls (HCS) were recruited for hemodynamic data collection under four fNIRS tasks (Emotional picture, Verbal fluency, Fingering and Negative emotional picture description task). Integral values and functional connectivity strength were employed to probe neural activation and functional connectivity in frontal and temporal lobes in MDD. Following, asymmetry characteristic of the frontal cortex between MDD and HCS under four tasks were carefully analyzed and compared. RESULTS: Individuals with MDD demonstrated heightened connectivity between the frontal and right temporal lobes and reduced connectivity between the frontal and left temporal lobes compared to HCS in all tasks. Additionally, MDD exhibited attenuated activation in the left frontal lobes and exaggerated activation in the right frontal lobes, diverging from HCS. Furthermore, the disparities in left-right asymmetry characteristic of frontal cortex activation between MDD and HCS were more pronounced during the combined task. LIMITATIONS: Further research is required to grasp the neurophysiological mechanisms governing left-right asymmetry across various tasks and the influence of task-induced brain fatigue on cerebral cortex hemodynamics in MDD. CONCLUSION: The left-right asymmetry feature provides valuable neurophysiological insights for diagnosing MDD clinically. Variations in activation patterns and functional connectivity features between MDD and HCS are closely tied to the task chosen. Thus, in clinical practice, carefully selecting appropriate fNIRS tasks and relevant features can significantly improve the diagnostic accuracy of MDD.

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The objective of this study was to explore the influence of different factors on the aggregation effect on hemoglobin (Hb) and enzymes during the preparation of Polyhemoglobin-Superoxide dismutase-Catalase-Carbonic anhydrase (PolyHb-SOD-CAT-CA). Several factors including temperatures, pH values, Glutaraldehyde (GDA) amounts and enzymes amounts were investigated systematically to study their effects on the enzymes recoveries and polymerization rates including the Superoxide dismutase (SOD), Catalase (CAT) and Carbonic anhydrase (CA), as well as their effects on the molecular weight distribution of PolyHb-SOD-CAT-CA. Then the oxygen affinity and methemoglobin (MetHb) contents of obtained PolyHb-SOD-CAT-CA were measured to evaluate the effects of enzyme crosslinking on the properties of Polyhemoglobin (PolyHb) moieties in the molecular structure of obtained PolyHb-SOD-CAT-CA conjugate. The results showed that the enzyme recoveries and polymerization rates could be decreased with the temperatures increasing and could be generally kept stable in the physiological pH conditions, but presented only slight changes among the investigated enzyme amounts ranges. Although the GDA concentration increasing could promote the enzyme polymerization rates, the enzyme recoveries decreased in whole. The polymerization rate and molecular size of PolyHb-SOD-CAT-CA conjugate increased with the elevation of temperature and the concentration of GDA. Lastly, the P50 values, Hill coefficients, and MetHb contents of PolyHb-SOD-CAT-CA conjugate with different enzyme crosslinking degrees exhibited no obvious differences with each other. In conclusion, the polymerization reactions between enzymes and Hb molecules could be remarkably affected by temperatures, pH values, and GDA amounts, and the enzyme crosslinking presented no obvious effects on the Hb properties, especially about the oxygen affinity and oxidation degrees.

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This work employs a saltiness-guided separation combined with UPLC-QTOF-MS to identify the key saltiness-enhancing substances in Maillard reaction products derived from chicken breast hydrolysate (CBH-MRPs). Thirteen compounds in the U3 fraction exhibited significant saltiness-enhancing abilities, which increased the saltiness intensity of NaCl (3 g/L) from 2.80 to 3.35-3.88. Interactions between the compounds and NaCl were evaluated using the S-curve method. The results showed that five compounds (5'-GMP, 5'-IMP, L-glutamic acid, L-lactic acid, and L-carnosine) and one compound (glutamine) exhibited synergistic and additive effects with NaCl, respectively, at tested concentrations. Notably, 5'-GMP/5'-IMP/glutamine and L-carnosine/L-lactic acid demonstrated better saltiness-enhancing abilities at their suprathreshold and subthreshold levels, respectively. Molecular docking results showed that hydrogen bonding was the key force for docking. Residues Cys475, Glu378, and Trp236 were the primary binding sites of the transmembrane channel-like protein 4 (TMC4). These results contribute to a better understanding of the saltiness modulating mechanisms of CBH-MRPs.

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Transcription factors play an essential role in pattern formation during early embryo development, generating a strikingly fast and precise transcriptional response that results in sharp gene expression boundaries. To characterize the steps leading up to transcription, we performed a side-by-side comparison of the nuclear dynamics of two morphogens, a transcriptional activator, Bicoid (Bcd), and a transcriptional repressor, Capicua (Cic), both involved in body patterning along the anterior-posterior axis of the early Drosophila embryo. We used a combination of fluorescence recovery after photobleaching, fluorescence correlation spectroscopy, and single-particle tracking to access a wide range of dynamical timescales. Despite their opposite effects on gene transcription, we find that Bcd and Cic have very similar nuclear dynamics, characterized by the coexistence of a freely diffusing monomer population with a number of oligomeric clusters, which range from low stoichiometry and high mobility clusters to larger, DNA-bound hubs. Our observations are consistent with the inclusion of both Bcd and Cic into transcriptional hubs or condensates, while putting constraints on the mechanism by which these form. These results fit in with the recent proposal that many transcription factors might share a common search strategy for target gene regulatory regions that makes use of their large unstructured regions, and may eventually help explain how the transcriptional response they elicit can be at the same time so fast and so precise.