Effect of glycation with three polysaccharides on the structural and emulsifying properties of ovalbumin.

Herein, three types of ovalbumin (OA)-polysaccharide conjugates were prepared with three polysaccharides (XG: xanthan gum; GG: guar gum; KGM: konjac glucomannan) for the fish oil emulsion stabilization. The glycation did not change the spectra bands and secondary structure percentages of OA, whereas it decreased the molecular surface hydrophobicity of OA. The initial emulsion droplet sizes were dependent on the polysaccharide types, OA preparation concentrations, polysaccharide: OA mass ratios, and glycation pH. The emulsion stability was mainly dependent on the polysaccharide types, polysaccharide: OA mass ratios, and glycation pH. However, it was minorly dependent on the OA preparation concentrations. The emulsions stabilized by conjugates with high polysaccharide: OA mass ratios (e.g., ≥3:5 for OA-GG) or appropriate glycation pH (e.g., 5.0-6.1 for OA-XG) showed no obvious creaming during the room temperature storage. This work provided basic knowledge on the structural modification and functional application of a protein.

Pre-analytical stability and physiological fluctuations affect plasma steroid hormone outcomes: A real-world study.

Since steroids are crucial for diagnosing endocrine disorders, the lack of research on factors that affect hormone levels makes interpreting the results difficult. Our study aims to assess the stability of the pre-analytical procedure and the impact of hormonal physiological fluctuations using real-world data. The datasets were created using 12,418 records from individuals whose steroid hormone measurements were taken in our laboratory between September 2019 and March 2024. 22 steroid hormones in plasma by a well-validated liquid chromatography tandem mass spectrometry method were measured. After normalization transformation, outlier removal, and z-score normalization, generalized additive models were constructed to evaluate preanalytic stability and age, sex, and sample time-dependent hormonal fluctuations. Most hormones exhibit significant variability with age, particularly steroid hormone precursors, sex hormones, and certain corticosteroids such as aldosterone. 18-hydroxycortisol, 18-oxocortisol. Sex hormones varied between males and females. Levels of certain hormones, including cortisol, cortisone, 11-deoxycortisol, 18-hydroxycortisol, 18-oxocortisol, corticosterone, aldosterone, estrone, testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, 11-ketotestosterone, and 11-hydroxytestosterone, fluctuated with sampling time. Moreover, levels of pregnenolone and progesterone decreased within 1 hour of sampling, with pregnenolone becoming unstable with storage time at 4 degrees after centrifugation, while other hormone levels remained relatively stable for a short period of time without or after centrifugation of the sample. This is the first instance real-world data has been used to assess the pre-analytic stability of plasma hormones and to evaluate the impact of physiological factors on steroid hormones.

Effects of the extraction temperatures on the protein contents, gelatin purities, physicochemical properties, and functional properties of tilapia scale gelatins.

Herein, the effects of the extraction temperatures (45, 55, 65, 75, and 85 °C) on the protein contents, gelatin purities, physicochemical properties, and functional properties of tilapia scale gelatins were studied. Among these temperatures, 65 °C was the best extraction temperature to obtain good production yield (16.0 % ± 0.3 %), good protein contents (excellent total amino acid composition of 94.20 ± 0.76 g/100 g of gelatin, the highest hydrophobic amino acids percentage of 32.68 ± 0.24 g/100 g of gelatin), appropriate ATR-FTIR spectra peaks (Amides A, B, I, II, and III), high ß-sheet percentage (38.2 % ± 1.3 %), the highest purity of the gelatin structures (280, 140, and 125 kDa), the lowest nanoparticle sizes in atomic force microscopy results, the highest water-holding capacity (25.3 % ± 0.9 %), the highest fat-binding capacity (16.9 % ± 0.1 %), high foaming properties (foaming capacity of 151.7 % ± 7.6 % and foaming stability of 145.8 % ± 6.3 %), the lowest interfacial tension (2.1 ± 0.2 mN/m), the lowest emulsifying activity index (16.5 % ± 0.9 %), the highest emulsifying stability index (88.9 % ± 5.1 %), highest emulsion viscosity (1462 ± 17 mPa·s at the rotary speed of 6 rpm), the lowest initial droplet sizes, and lowest emulsion creaming index (6.9 % ± 0.7 %). This work provided a useful guide to choosing extraction temperature for gelatin extraction and a useful theory on the relationship between compositions and properties of a protein sample.

Acupuncture modulates emotional network resting-state functional connectivity in patients with insomnia disorder: a randomized controlled trial and fMRI study.

BACKGROUND: Insomnia disorder (ID) is one of the most common sleep problems, usually accompanied by anxiety and depression symptoms. Functional magnetic resonance imaging (fMRI) study suggests that both poor sleep quality and negative emotion are linked to the dysregulation of brain network related to emotion processing in ID patients. Acupuncture therapy has been proven effective in improving sleep quality and mood of ID patients, but the involved neurobiological mechanism remains unclear. We aimed to investigate the modulation effect of acupuncture on resting-state functional connectivity (rsFC) of the emotional network (EN) in patients experiencing insomnia. METHODS: A total of 30 healthy controls (HCs) and 60 ID patients were enrolled in this study. Sixty ID patients were randomly assigned to real and sham acupuncture groups and attended resting-state fMRI scans before and after 4 weeks of acupuncture treatment. HCs completed an MRI/fMRI scan at baseline. The rsFC values within EN were calculated, and Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), Hyperarousal Scale (HAS), and actigraphy data were collected for clinical efficacy evaluation. RESULTS: Resting-state FC analysis showed abnormalities in rsFC centered on the thalamus and dorsolateral prefrontal cortex within EN of ID patients compared to HCs. After real acupuncture treatment, rsFC of the anterior cingulate cortex, hippocampus, and amygdala were increased compared with the sham acupuncture group (p < 0.05, FDR corrected). In real acupuncture group, the rsFC value was decreased between left amygdala and left thalamus after 4 weeks of treatment compared with baseline. A trend of correlation was found that the increased rsFC value between the right amygdala and left hippocampus was positively correlated with the decreased HAMA scores across all ID patients, and the decreased left amygdala rsFC value with the left thalamus was negatively correlated with the increased sleep efficiency in the real acupuncture group. CONCLUSION: Our findings showed that real acupuncture could produce a positive effect on modulating rsFC within network related to emotion processing in ID patients, which may illustrate the central mechanism underlying acupuncture for insomnia in improving sleep quality and emotion regulation. TRIAL REGISTRATION: http://www.chictr.org.cn ., ChiCTR1800015282, 20/03/2018.

Syndecan-1 as a predictor of vulnerable atherosclerotic plaques.

Aims: Cardiovascular disease remains a major global health concern, with atherosclerosis (AS) being a significant contributor. Vulnerable plaques play a critical role in acute cardiovascular events. Syndecan-1 (SDC-1), a vital membrane proteoglycan in the vascular endothelial glycocalyx, is believed to be associated with plaque progression. However, its precise relationship with severity and vulnerability of atherosclerotic plaque remains unclear. This study aimed to investigate SDC-1 expression and its potential correlation with plaque vulnerability in ApoE-/- atherosclerosis mouse model. Methods and results: Eight-week-old mice were induced into the AS model using a high-fat diet (HFD) and/or partial ligation of the left common carotid artery (PLCA), with a chow diet (CD) control group. After 16 weeks, plaques in the aortic root showed the following order: HFD + PLCA group > HFD group > CD + PLCA group > CD group. Immunohistochemistry revealed heightened accumulation of lipid/foam cells and CD68-labeled macrophages in the plaques, elevated vascular endothelial growth factor (VEGF), and matrix Metalloproteinase-9 (MMP-9) in the HFD + PLCA group's plaques, along with reduced collagen and α-SMA-labeled smooth muscle cells, resulting in the highest vulnerability index value. Immunohistofluorescence analysis of frozen plaque sections showed significantly higher SDC-1 expression in the AS mice group compared to the CD group, both positively correlated with plaque vulnerability. Serum analysis demonstrated elevated levels of SDC1, sphingosine 1-phosphate (S1P), and VEGF-A in the AS mice, all positively correlated with plaque vulnerability. Multivariate analysis identified SDC1 as an independent predictor of plaque vulnerability. Conclusion: This study enhances our understanding of plaque vulnerability mechanisms and presents SDC1 as a potential biomarker for atherosclerosis. These findings underscore the importance of addressing modifiable risk factors, such as diet and hemodynamics and suggest the utility of serum SDC1 as a valuable clinical marker. Ultimately, these insights may lead to more effective strategies in combating cardiovascular diseases and improving patient outcomes.

miR-148b-5p regulates hypercalciuria and calcium-containing nephrolithiasis.

Calcium-containing stones represent the most common form of kidney calculi, frequently linked to idiopathic hypercalciuria, though their precise pathogenesis remains elusive. This research aimed to elucidate the molecular mechanisms involved by employing urinary exosomal microRNAs as proxies for renal tissue analysis. Elevated miR-148b-5p levels were observed in exosomes derived from patients with kidney stones. Systemic administration of miR-148b-5p in rat models resulted in heightened urinary calcium excretion, whereas its inhibition reduced stone formation. RNA immunoprecipitation combined with deep sequencing identified miR-148b-5p as a suppressor of calcitonin receptor (Calcr) expression, thereby promoting urinary calcium excretion and stone formation. Mice deficient in Calcr in distal epithelial cells demonstrated elevated urinary calcium excretion and renal calcification. Mechanistically, miR-148b-5p regulated Calcr through the circRNA-83536/miR-24-3p signaling pathway. Human kidney tissue samples corroborated these results. In summary, miR-148b-5p regulates the formation of calcium-containing kidney stones via the circRNA-83536/miR-24-3p/Calcr axis, presenting a potential target for novel therapeutic interventions to prevent calcium nephrolithiasis.

Resveratrol stimulates brown of white adipose via regulating ERK/DRP1-mediated mitochondrial fission and improves systemic glucose homeostasis.

PURPOSE: Diabetes mellitus and metabolic homeostasis disorders may benefit from white adipose tissue (WAT) browning, which is associated with mitochondrial fission. Resveratrol, a dietary polyphenol, exhibits beneficial effects against abnormalities related to metabolic diseases. However, it remains unknown whether resveratrol contributes to WAT browning by regulating mitochondrial fission. METHODS: We administered resveratrol (0.4% mixed with control) to db/db mice for 12 weeks, measuring body weight, oral glucose tolerance, insulin tolerance, and histological changes. The uncoupling protein 1 (UCP1) and dynamin-related protein 1 (DRP1) expressions in the epididymal WAT were assessed via immunoblotting. RESULTS: We found that resveratrol improved systemic glucose homeostasis and insulin resistance in db/db mice, which was associated with increased UCP1 in epididymal WAT. Resveratrol-treated mice exhibited more fragmented mitochondria and increased phosphorylation of DRP1 in the epididymal WAT of the db/db mice. These results were further confirmed in vitro, where resveratrol induced extracellular signal-regulated kinase (ERK) signaling activation, leading to phosphorylation of DRP1 at the S616 site (p-DRP1S616) and mitochondrial fission, which was reversed by an ERK inhibitor in 3T3-L1 adipocytes. CONCLUSION: Resveratrol plays a role in regulating the phosphorylation of ERK and DRP1, resulting in the promotion of beige cells with epididymal WAT and the improvement of glucose homeostasis. Our present study provides novel insights into the potential mechanism of resveratrol-mediated effects on WAT browning, suggesting that it is, at least in part, mediated through ERK/DRP1-mediated mitochondrial fission.

Osteogenic differentiation of bone mesenchymal stem cells on linearly aligned triangular micropatterns.

Mesenchymal stem cells (MSCs) hold promise for regenerative medicine, particularly for bone tissue engineering. However, directing MSC differentiation towards specific lineages, such as osteogenic, while minimizing undesired phenotypes remains a challenge. Here, we investigate the influence of micropatterns on the behavior and lineage commitment of rat bone marrow-derived MSCs (rBMSCs), focusing on osteogenic differentiation. Linearly aligned triangular micropatterns (TPs) and circular micropatterns (CPs) coated with fibronectin were fabricated to study their effects on rBMSC morphology and differentiation and the underlying mechanobiological mechanisms. TPs, especially TP15 (15 µm), induced the cell elongation and thinning, while CPs also promoted the cell stretching, as evidenced by the decreased circularity and increased aspect ratio. TP15 significantly promoted osteogenic differentiation, with increased expression of osteogenic genes (Runx2, Spp1, Alpl, Bglap, Col1a1) and decreased expression of adipogenic genes (Pparg, Cebpa, Fabp4). Conversely, CPs inhibited both osteogenic and adipogenic differentiation. Mechanistically, TP15 increased Piezo1 activity, cytoskeletal remodeling including the aggregates of F-actin and myosin filaments at the cell periphery, YAP1 nuclear translocation, and integrin upregulation. Piezo1 inhibition suppressed the osteogenic genes expression, myosin remodeling, and YAP1 nuclear translocation, indicating Piezo1-mediated the mechanotransduction in rBMSCs on TPs. TP15 also induced osteogenic differentiation of BMSCs from aging rats, with upregulated Piezo1 and nuclear translocation of YAP1. Therefore, triangular micropatterns, particularly TP15, promote osteogenesis and inhibit adipogenesis of rBMSCs through Piezo1-mediated myosin and YAP1 pathways. Our study provides novel insights into the mechanobiological mechanisms governing MSC behaviors on micropatterns, offering new strategies for tissue engineering and regenerative medicine.

The Complete Mitogenome of Apostasia fujianica Y.Li & S.Lan and Comparative Analysis of Mitogenomes across Orchidaceae.

Apostasia fujianica belongs to the genus Apostasia and is part of the basal lineage in the phylogenetic tree of the Orchidaceae. Currently, there are only ten reported complete mitochondrial genomes in orchids, which greatly hinders the understanding of mitochondrial evolution in Orchidaceae. Therefore, we assembled and annotated the mitochondrial genome of A. fujianica, which has a length of 573,612 bp and a GC content of 44.5%. We annotated a total of 44 genes, including 30 protein-coding genes, 12 tRNA genes, and two rRNA genes. We also performed relative synonymous codon usage (RSCU) analysis, repeat sequence analysis, intergenomic transfer (IGT) analysis, and Ka/Ks analysis for A. fujianica and conducted RNA editing site analysis on the mitochondrial genomes of eight orchid species. We found that most protein-coding genes are under purifying selection, but nad6 is under positive selection, with a Ka/Ks value of 1.35. During the IGT event in A. fujianica's mitogenome, the trnN-GUU, trnD-GUC, trnW-CCA, trnP-UGG, and psaJ genes were identified as having transferred from the plastid to the mitochondrion. Compared to other monocots, the family Orchidaceae appears to have lost the rpl10, rpl14, sdh3, and sdh4 genes. Additionally, to further elucidate the evolutionary relationships among monocots, we constructed a phylogenetic tree based on the complete mitogenomes of monocots. Our study results provide valuable data on the mitogenome of A. fujianica and lay the groundwork for future research on genetic variation, evolutionary relationships, and breeding of Orchidaceae.

Complex coacervation of low methoxy pectin with three types of gelatins for the encapsulation of fish oil.

Herein, the complex coacervation of low methoxy pectin (LMP) with three types of gelatins was explored to encapsulate fish oil. The fish oil@gelatin-LMP complex coacervates with good precipitation separation could be obtained at low gelatin concentrations (Fish gelatin, FG: 10-80 mg/mL; porcine skin gelatin, PSG: 10-40 mg/mL; bovine skin gelatin, BSG: 10-80 mg/mL), high gelatin: fish oil mass ratios (4:1-1:1), appropriate gelatin: LMP mass ratios (3:1-12:1 for FG and PSG, 6:1 for BSG), and appropriate pH (FG: 4.90-5.50; PSG: 4.80-5.40; BSG: 4.10-4.50). FG induced similar loading ability, lower encapsulation ability, and comparable peroxide values to the mammalian gelatins. FG induced higher or similar free fatty acid released percentages to mammalian gelatins in the in vitro gastrointestinal model at low gelatin concentrations (10-40 mg/mL). These results provided useful information to understand the protein-polysaccharide complex coacervation to encapsulate oil-based bioactive substances.

The value of 3D printing model combined PCNL in kidney stones: a systematic review and meta-analysis.

INTRODUCTION: With the continuous advancement of medical imaging, 3D printing technology is emerging. This technology allows for the representation of complex objects in a model form. This research aims to delve into the irreplaceable value of percutaneous nephrolithotomy (PCNL) in conjunction with 3D printed models in urinary stone surgery. This forward-looking approach provides doctors with a new perspective, enabling them to plan and execute surgeries with greater precision, ultimately delivering a safer and more efficient treatment experience for patients. We evaluated the literature on PCNL for the kidney stones with the introduction of 3D printing models and conducted a meta-analysis. The assessed parameters included stone clearance rate, operation time, hospital stay, blood loss, puncture accuracy, and the rate of complications. EVIDENCE ACQUISITION: We systematically searched the EMBASE, PubMed, Cochrane Library, SCIE, and Chinese Biomedical Literature Search databases for articles related to PCNL (Percutaneous Nephrolithotomy) with 3D printing models from January 2000 to January 2023. Data were managed and screened using Excel . Meta-analysis was performed for operation time, stone clearance rate, blood loss, puncture accuracy, length of hospital stay, and complications in PCNL combined with 3D printing model for kidney stone treatment. The quality of included articles was assessed using the risk of bias tool by the Cochrane Collaboration. Sensitivity analysis was conducted to assess the reliability of the results. Data were recorded using StataSE 17 software, and publication bias was examined using Egger's linear regression test. EVIDENCE SYNTHESIS: We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to conduct a systematic search and screening of literature relevant to the use of 3D printed models in the treatment of kidney stones. We conducted an extensive literature search across several major academic databases, including EMBASE, PubMed, Cochrane Library, SCIE, and Chinese Biomedical Literature Search databases, to ensure comprehensive coverage of relevant studies. Following the PRISMA process of screening and analysis, we ultimately included 10 randomized controlled trials with a combined sample of 608 for systematic review. CONCLUSIONS: Across these studies, we identified the introduction of 3D printing models prior to surgery for kidney stones resulted in significant advantages for the experimental group compared to the control group in terms of operation time, stone clearance rates, puncture accuracy, hospital stay, blood loss, and the incidence of complications, providing valuable insights for further research and clinical practice.

Genome-Wide Identification and Expression Pattern Analysis of GATA Gene Family in Orchidaceae.

The GATA transcription factors play crucial roles in plant growth, development, and responses to environmental stress. Despite extensive studies of GATA genes in many plants, their specific functions and mechanisms in orchids remain unexplored. In our study, a total of 149 GATA genes were identified in the genomes of seven sequenced orchid species (20 PeqGATAs, 23 CgGATAs, 24 CeGATAs, 23 DcaGATAs, 20 DchGATAs, 27 DnoGATAs, and 12 GelGATAs), classified into four subfamilies. Subfamily I typically contains genes with two exons, while subfamily II contains genes with two or three exons. Most members of subfamilies III and IV have seven or eight exons, with longer introns compared to subfamilies I and II. In total, 24 pairs (CgGATAs-DchGATAs), 27 pairs (DchGATAs-DnoGATAs), and 14 pairs (DnoGATAs-GelGATAs) of collinear relationships were identified. Cis-acting elements in GATA promoters were mainly enriched in abscisic acid (ABA) response elements and methyl jasmonate (MeJA) elements. Expression patterns and RT-qPCR analysis revealed that GATAs are involved in the regulation of floral development in orchids. Furthermore, under high-temperature treatment, GL17420 showed an initial increase followed by a decrease, GL18180 and GL17341 exhibited a downregulation followed by upregulation and then a decrease, while GL30286 and GL20810 displayed an initial increase followed by slight inhibition and then another increase, indicating diverse regulatory mechanisms of different GATA genes under heat stress. This study explores the function of GATA genes in orchids, providing a theoretical basis and potential genetic resources for orchid breeding and stress resistance improvement.

Genome-Based Identification of the Dof Gene Family in Three Cymbidium Species and Their Responses to Heat Stress in Cymbidium goeringii.

As an important genus in Orchidaceae, Cymbidium has rich ecological diversity and significant economic value. DNA binding with one zinc finger (Dof) proteins are pivotal plant-specific transcription factors that play crucial roles in the growth, development, and stress response of plants. Although the Dof genes have been identified and functionally analyzed in numerous plants, exploration in Orchidaceae remains limited. We conducted a thorough analysis of the Dof gene family in Cymbidium goeringii, C. ensifolium, and C. sinensis. In total, 91 Dof genes (27 CgDofs, 34 CeDofs, 30 CsDofs) were identified, and Dof genes were divided into five groups (I-V) based on phylogenetic analysis. All Dof proteins have motif 1 and motif 2 conserved domains and over half of the genes contained introns. Chromosomal localization and collinearity analysis of Dof genes revealed their evolutionary relationships and potential gene duplication events. Analysis of cis-elements in CgDofs, CeDofs, and CsDofs promoters showed that light-responsive cis-elements were the most common, followed by hormone-responsive elements, plant growth-related elements, and abiotic stress response elements. Dof proteins in three Cymbidium species primarily exhibit a random coil structure, while homology modeling exhibited significant similarity. In addition, RT-qPCR analysis showed that the expression levels of nine CgDofs changed greatly under heat stress. CgDof03, CgDof22, CgDof27, CgDof08, and CgDof23 showed varying degrees of upregulation. Most upregulated genes under heat stress belong to group I, indicating that the Dof genes in group I have great potential for high-temperature resistance. In conclusion, our study systematically demonstrated the molecular characteristics of Dof genes in different Cymbidium species, preliminarily revealed the patterns of heat stress, and provided a reference for further exploration of stress breeding in orchids.

Effects of edge disorder on the stability of quantum oscillations in two-dimensional coupled systems.

This paper utilizes the theory of quantum diffusion to analyze the electron probability and spreading width of a wavepacket on each layer in a two-dimensional (2D) coupled system with edge disorder, aiming to clarify the effects of edge disorder on the stability of the electron periodic oscillations in 2D coupled systems. Using coupled 2D square lattices with edge disorder as an example, we show that, the electron probability and wavepacket spreading width exhibit periodic oscillations and damped oscillations, respectively, before and after the wavepacket reaches the boundary. Furthermore, these electron oscillations exhibit strong resistance against disorder perturbation with a longer decay time in the regime of large disorder, due to the combined influences of ordered and disordered site energies in the central and edge regions. Finally, we numerically verified the universality of the results through bilayer graphene, demonstrating that this anomalous quantum oscillatory behavior is independent of lattice geometry. Our findings are helpful in designing relevant quantum devices and understanding the influence of edge disorder on the stability of electron periodic oscillations in 2D coupled systems.

Heat stress reprograms herbivory-induced defense responses in potato plants.

Climate change is predicted to increase the occurrence of extreme weather events such as heatwaves, which may thereby impact the outcome of plant-herbivore interactions. While elevated temperature is known to directly affect herbivore growth, it remains largely unclear if it indirectly influences herbivore performance by affecting the host plant they feed on. In this study, we investigated how transient exposure to high temperature influences plant herbivory-induced defenses at the transcript and metabolic level. To this end, we studied the interaction between potato (Solanum tuberosum) plants and the larvae of the potato tuber moth (Phthorimaea operculella) under different temperature regimes. We found that P. operculella larvae grew heavier on leaves co-stressed by high temperature and insect herbivory than on leaves pre-stressed by herbivory alone. We also observed that high temperature treatments altered phylotranscriptomic patterns upon herbivory, which changed from an evolutionary hourglass pattern, in which transcriptomic responses at early and late time points after elicitation are more variable than the ones in the middle, to a vase pattern. Specifically, transcripts of many herbivory-induced genes in the early and late defense stage were suppressed by HT treatment, whereas those in the intermediate stage peaked earlier. Additionally, we observed that high temperature impaired the induction of jasmonates and defense compounds upon herbivory. Moreover, using jasmonate-reduced (JA-reduced, irAOC) and -elevated (JA-Ile-elevated, irCYP94B3s) potato plants, we showed that high temperature suppresses JA signaling mediated plant-induced defense to herbivore attack. Thus, our study provides evidences on how temperature reprograms plant-induced defense to herbivores.

Podophyllotoxin derivatives-tubulin complex reveals a potential binding site of tubulin polymerization inhibitors in α-tubulin adjacent to colchicine site.

The colchicine site of ß-tubulin has been proven to be essential binding sites of microtubule polymerization inhibitors. Recent studies implied that GTP pocket of α-tubulin adjacent to colchicine sites is a potential binding site for developing tubulin polymerization inhibitors. However, the structural basis for which type of structural fragments was more beneficial for enhancing the affinity of α-tubulin is still unclear. Here, podophyllotoxin derivatives-tubulin complex crystals indicated that heterocyclic with the highly electronegative and small steric hindrance was conducive to change configuration and enhance the affinity of the residues in GTP pocket of α-tubulin. Triazole with lone-pairs electrons and small steric hindrance exhibited the strongest affinity for enhancing affinity of podophyllotoxin derivatives by forming two hydrogen bonds with αT5 Ser178. Pyrimidine with the secondary strong affinity could bind Asn101 to make the αH7 configuration deflection, which reduces the stability of tubulin result in its depolymerization. Conversely, 4ß-quinoline-podophyllotoxin with the weakest affinity did not interact with α-tubulin. The molecular dynamics simulation and protein thermal shift results showed that 4ß-triazole-podophyllotoxin-tubulin was the most stable mainly due to two hydrogen bonds and the higher van der Waals force. This work provided a structural basis of the potential binding sites for extending the α/ß-tubulin dual-binding sites inhibitors design strategy.

Relations between near-field enhancements and Purcell factors in hybrid nanostructures of plasmonic antennas and dielectric cavities.

Strong near-field enhancements (NFEs) of nanophotonic structures are believed to be closely related to high Purcell factors (FP). Here, we theoretically show that the correlation is partially correct; the extinction cross section (σ) response is also critical in determining FP. The divergence between NFE and FP is especially pronounced in plasmonic-dielectric hybrid systems, where the plasmonic antenna supports dipolar plasmon modes and the dielectric cavity hosts Mie-like resonances. The cavity's enhanced-field environment can boost the antenna's NFEs, but the FP is not increased concurrently due to the larger effective σ that is intrinsic to the FP calculations. Interestingly, the peak FP for the coupled system can be predicted by using the NFE and σ responses. Furthermore, the limits for FP of coupled systems are considered; they are determined by the sum of the FP of a redshifted (or modified, if applicable) antenna and an individual cavity. This contrasts starkly with the behavior of NFE which is closely associated with the multiplicative effects of the NFEs provided by the antenna and the dielectric cavity. The differing behaviors of NFE and FP in hybrid cavities have varied impacts on relevant nanophotonic applications such as fluorescence, Raman scattering and enhanced light-matter interactions.