Engineering Core/Ligands Interfacial Anchors of Nanoparticles for Efficiently Inhibiting Both Aß and Amylin Fibrillization.

Accurate construction of artificial nano-chaperones' structure is crucial for precise regulation of protein conformational transformation, facilitating effective treatment of proteopathy. However, how the ligand-anchors of nano-chaperones affect the spatial conformational changes in proteins remains unclear, limiting the development of efficient nano-chaperones. In this study, three types of gold nanoparticles (AuNPs) with different core/ligands interface anchor structures (Au─NH─R, Au─S─R, and Au─C≡C─R, R = benzoic acid) are synthesized as an ideal model to investigate the effect of interfacial anchors on Aß and amylin fibrillization. Computational results revealed that the distinct interfacial anchors imparted diverse distributions of electrostatic potential on the nanointerface and core/ligands bond strength of AuNPs, leading to differential interactions with amyloid peptides. Experimental results demonstrated that all three types of AuNPs exhibit site-specific inhibitory effects on Aß40 fibrillization due to preferential binding. For amylin, amino-anchored AuNPs demonstrate strong adsorption to multiple sites on amylin and effectively inhibit fibrillization. Conversely, thiol- and alkyne-anchored AuNPs adsorb at the head region of amylin, promoting folding and fibrillization. This study not only provided molecular insights into how core/ligands interfacial anchors of nanomaterials induce spatial conformational changes in amyloid peptides but also offered guidance for precisely engineering artificial-chaperones' nanointerfaces to regulate the conformational transformation of proteins.

Construction of Two-Dimensional Organometallic Coordination Networks with Both Organic Kagome and Semiregular Metal Lattices on Au(111).

Two-dimensional metal-organic networks (2D MONs) having heterogeneous coordination nodes (HCNs) could exhibit excellent performance in catalysis and optoelectronics because of the unbalanced electron distribution of the coordinating metals. Therefore, the design and construction of 2D MONs with HCNs are highly desirable but remain challenging. Here, we report the construction of 2D organometallic coordination networks with an organic Kagome lattice and a semiregular metal lattice on Au(111) via the in situ formation of HCNs. Using a bifunctional precursor 1,4-dibromo-2,5-diisocyanobenzene, the coordination of isocyano with Au adatom on a room-temperature Au(111) yielded metal-organic coordination chains with isocyano-Au-isocyano nodes. In contrast, on a high-temperature Au(111), a selective debromination/coordination cascade reaction occurred, affording 2D organometallic coordination networks with phenyl-Au-isocyano nodes. By combining scanning tunneling microscopy and density functional theory calculations, we determined the structures of coordination products and the nature of coordination nodes, demonstrating a thermodynamically favorable pathway for forming the phenyl-Au-isocyano nodes.

Evolution of catalyst design for controlled synthesis of chiral single-walled carbon nanotubes.

Single-walled carbon nanotubes (SWCNTs) possess superb properties originating from their unique chiral structures. However, accurately controlling the structure of SWCNTs remains challenging due to the structural similarities of their chiral structures, which hinders their widespread application in various fields, particularly in electronics. In recent years, much effort has been devoted to preparing single chiral SWCNTs by adopting three constructive strategies, including growth condition control for structurally unstable liquid catalysts, employing stable solid catalyst design, and pre-synthesis of carbon seeds with a well-defined shape. This review comprehensively discusses the state-of-the-art developments in these approaches as well as their advantages and disadvantages. Moreover, insights into the key challenges and future directions are provided for acquiring chirally pure SWCNTs.

Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling.

Recent advances in chemical proteomics have focused on developing chemical probes that react with nucleophilic amino acid residues. Although histidine is an attractive candidate due to its importance in enzymatic catalysis, metal binding and protein-protein interaction, its moderate nucleophilicity poses challenges. Its modification is frequently influenced by cysteine and lysine, which results in poor selectivity and narrow proteome coverage. Here we report a singlet oxygen and chemical probe relay labelling method that achieves high selectivity towards histidine. Libraries of small-molecule photosensitizers and chemical probes were screened to optimize histidine labelling, enabling histidine profiling in live cells with around 7,200 unique sites. Using NMR spectroscopy and X-ray crystallography, we characterized the reaction mechanism and the structures of the resulting products. We then applied this method to discover unannotated histidine sites key to enzymatic activity and metal binding in select metalloproteins. This method also revealed the accessibility change of histidine mediated by protein-protein interaction that influences select protein subcellular localization, underscoring its capability in discovering functional histidines.

Ligand-Enabled ortho-Selective C-H Olefination of Tertiary Aniline Derivatives.

A highly ortho-selective CAr-H olefination of tertiary anilines without a directing group was developed. This reaction tolerated various substituted arenes and olefin coupling partners, affording ortho-olefination products in moderate to good yields. Preliminary mechanistic studies showed that N-Ac-d-Ala, Ag2CO3, and BQ were the key factors for tuning the regioselectivity from para to ortho. Density functional theory was used to achieve a theoretical understanding of the ortho selectivity.

Detection and comparison of tumor cell-associated microbiota from different compartments of colorectal cancer.

Introduction: Intratumoral microbes play an important role in the development of colorectal cancer (CRC). However, studying intratumoral microbes in CRC faces technical challenges, as tumor microbe communities are often contaminated by fecal microbes due to the structure of the gut folds and villi. The present study aimed to develop a new method for isolating tumor cell-associated microbiota and comparing microbial populations from different compartments. Materials and methods: The distribution of intestinal bacteria was detected using immunohistochemistry combined with 5R-16s rRNA gene sequencing to explore the effects of the sampling site and number of washes on the detection of microbiota. The 5R-16s rRNA gene sequencing was performed using 44 samples from 11 patients with CRC, including CRC tumor tissues (TT), normal tissues adjacent to CRC (NT), tumor cells (TC), and normal cells (NC). TC and NC were obtained from the TT and NT using an enzymatic digestion method. The microbiota and their potential functions in the four groups were analyzed and compared to determine the differential microbiota related to CRC. Results: Bacteria were mainly distributed in the feces covering intestinal tissues and in the epithelial cells and macrophages within the tissues. Different sampling sites and number of washes led to detection of different microbiota distributions. Although the cleaning method could be controlled, sampling sites varied and led to different microbiota distributions. The phyla of Firmicutes and Bacteroidetes were highly abundant in the conventionally used tissue samples, whereas Proteobacteria was the most abundant phyla in the cell samples isolated with the new method (i.e., after cell enzymatic hydrolysis). Detection of CRC cell-associated microbiota using a cell enzymatic digestion method showed that some bacteria, such as Fusobacterium, Eikenella, Shewanella, and Listeria, were more abundant in TT than NT, whereas the abundance of Akkermansia was lower in TT than NT. The tumor/normal ratios of some bacteria, such as Gemella, Escherichia, Shigella, and Blautia, were different between the cell and tissue samples. Conclusion: The cell enzymatic digestion method reduced fecal bacterial contamination, enabling low biomass intratumoral microbiota to be detected and allowing prediction of bacterial distributions.

Objectivization study of acupuncture Deqi and brain modulation mechanisms: a review.

Deqi is an important prerequisite for acupuncture to achieve optimal efficacy. Chinese medicine has long been concerned with the relationship between Deqi and the clinical efficacy of acupuncture. However, the underlying mechanisms of Deqi are complex and there is a lack of systematic summaries of objective quantitative studies of Deqi. Acupuncture Deqi can achieve the purpose of treating diseases by regulating the interaction of local and neighboring acupoints, brain centers, and target organs. At local and neighboring acupoints, Deqi can change their tissue structure, temperature, blood perfusion, energy metabolism, and electrophysiological indicators. At the central brain level, Deqi can activate the brain regions of the thalamus, parahippocampal gyrus, postcentral gyrus, insular, middle temporal gyrus, cingulate gyrus, etc. It also has extensive effects on the limbic-paralimbic-neocortical-network and default mode network. The brain mechanisms of Deqi vary depending on the acupuncture techniques and points chosen. In addition, Deqi 's mechanism of action involves correcting abnormalities in target organs. The mechanisms of acupuncture Deqi are multi-targeted and multi-layered. The biological mechanisms of Deqi are closely related to brain centers. This study will help to explore the mechanism of Deqi from a local-central-target-organ perspective and provide information for future clinical decision-making.

Changes in corneal endothelial cells after scleral-sutured fixation of intraocular lens in children with congenital ectopia lentis: a 2-year follow-up.

PURPOSE: To investigate the changing patterns of corneal endothelial cells and the associated factors in children with congenital ectopia lentis (CEL) after scleral-sutured fixation of intraocular lens (SSFIOL). SETTING: Zhongshan ophthalmic center, Guangzhou, China. DESIGN: Retrospective study. METHODS: Patients were divided into the surgery group and the control group. Central endothelial cell density (ECD), coefficient of variation in cell size (CV), the percentage of hexagonal cells (hexagonality, HEX), average cell size (AVG) and central corneal thickness (CCT) were analyzed for both group at baseline and each follow-up visit. Clinic characteristic, ocular parameters, IOL decentration and IOL tilt of patients in the surgery group were collected. Multiple linear regression was performed to assess the potential associated factors for the postoperative changes in corneal endothelial cells in the surgery group. RESULTS: After 2-year follow-up, the decline of ECD was 17.8% (95%CI: -21.8 to -13.9) in the surgery group and -3.1% (95%CI: -5.2 to -1.0) in the control group(P<0.001), while the increase of AVG was 24.3%(17.1to 31.6) in the surgery group and 2.7%(1.0 to 4.5) in the control group (P<0.001). Multivariate analysis showed that AL≥24mm and WTW<12.2mm were significantly associated with greater loss of ECD (ß=-241.41, 95% CI: -457.91 to -24.91, P=0.030 and ß=251.63, 95% CI: 42.10 to 461.17,P=0.020, respectively) and AL≥ 24mm was significantly positively associated with the increase of AVG (ß=34.81, 95% CI: 0.90 to 68.71, P=0.044). CONCLUSIONS: SSFIOL has a significant impact on corneal endothelium in children with CEL. More attention should be paid to monitor postoperative corneal endothelium change during long-term follow-up in CEL children, especially for those with longer AL and smaller WTW.

Solid-liquid redistribution and degradation of antibiotics during hydrothermal treatment of sewage sludge: Interaction between biopolymers and antibiotics.

Waste activated sludge serves an important reservoir for antibiotics within wastewater treatment plants, and understanding the occurrence and evolution of antibiotics during sludge treatment is crucial to mitigate the potential risks of subsequent resource utilization of sludge. This study explores the degradation and transformation mechanisms of three typical antibiotics, oxytetracycline (OTC), ofloxacin (OFL), and azithromycin (AZI) during sludge hydrothermal treatment (HT), and investigates the influence of biopolymers transformation on the fate of these antibiotics. The findings indicate that HT induces a shift of antibiotics from solid-phase adsorption to liquid-phase dissolution in the initial temperature range of 25-90 °C, underscoring this phase's critical role in preparing antibiotics for subsequent degradation phases. Proteins (PN) and humic acids emerge as crucial for antibiotic binding, facilitating their redistribution within sludge. Specifically, the binding capacity sequence of biopolymers to antibiotics is as follows: OFL>OTC>AZI, highlighting that OFL-biopolymers display stronger electrostatic attraction, more available adsorption sites, and more stable binding strength. Furthermore, antibiotic degradation mainly occurs above 90 °C, with AZI being the most temperature-sensitive, degrading 92.97% at 180 °C, followed by OTC (91.26%) and OFL (52.51%). Concurrently, the degradation products of biopolymers compete for active sites to form novel amino acid-antibiotic conjugates, which inhibits the further degradation of antibiotics. These findings illuminate the effects of biopolymers evolution on intricate dynamics of antibiotics fate in sludge HT and are helpful to optimize the sludge HT process for effective antibiotics abatement.

Metagenomic and metabolomic analyses reveal differences in rumen microbiota between grass- and grain-fed Sanhe heifers.

Introduction: The aim of this study was to investigate the effects of diets on the composition and function of rumen microbiome and metabolites in Sanhe heifers. Methods: Metagenomic and metabolomic analyses were performed using rumen fluid samples collected from Sanhe heifers (n = 20) with similar body weights and ages from grass-fed and grain-fed systems. Results: The grain-fed group exhibited more intensive rumen fermentation than the grass-fed group. However, the grass-fed group exhibited carbohydrate metabolism and methane production higher than that of the grain-fed group; these increases were observed as a higher abundance of various bacterial phyla (Firmicutes, Bacteroidetes, Actinobacteria, Lentisphaerae, and Verrucomicrobia), families (Lachnospiraceae, Eubacteriaceae, and Eggerthellaceae), and the archaeal family Methanobacteriaceae. A comparison of genes encoding carbohydrate-active enzymes, using Kyoto Encyclopedia of Genes and Genome profiles, revealed noteworthy differences in the functions of rumen microbiota; these differences were largely dependent on the feeding system. Conclusion: These results could help manipulate and regulate feed efficiency in Sanhe cattle.

Evaluation mechanism of sustainable development level for the cities in the Yangtze River Economic Belt under the dual-carbon policy.

Low carbon sustainable development (LCSD) has become an inevitable choice, for which China has put forward a "dual-carbon" policy. The purpose of this study is to capture the interaction between the environment and the economy in the context of this goal, thus evaluating LCSD level from a systematic perspective. This paper proposes a super slack based measurement (SBM) model with a non-equal weight structure to assess the LCSD level. Firstly, a maximum influence minimum redundancy (MIMR) index selection algorithm is designed to establish input and output index systems, which avoids redundancy indexes. Secondly, the objective function of the original super SBM employs an equal weight structure, which leads results inadequately reflect the research preferences. Therefore, the weights of indexes are introduced to form an improved super SBM. Finally, 40 cities along the Yangtze River Economic Belt (YREB) are selected for empirical analysis. Results show that (1) the LCSD level of YRBE decreases from downstream to upstream to midstream; (2) Jiangsu, Zhejiang, and Sichuan provinces have higher LCSD levels, while Hunan and Jiangxi provinces have lower levels; and (3) up to 2021, there are 32 effective cities and 8 ineffective cities. The research implies that balancing the economy-environment relationship is crucial for higher efficiency. The LCSD evaluation method not only reflects the coordination level between the economy and the environment, but also integrates the research preference into the results, providing decision support for the government to formulate carbon reduction policies and allocate resources.

Fusion of multi-source relationships and topology to infer lncRNA-protein interactions.

Long non-coding RNAs (lncRNAs) are important factors involved in biological regulatory networks. Accurately predicting lncRNA-protein interactions (LPIs) is vital for clarifying lncRNA's functions and pathogenic mechanisms. Existing deep learning models have yet to yield satisfactory results in LPI prediction. Recently, graph autoencoders (GAEs) have seen rapid development, excelling in tasks like link prediction and node classification. We employed GAE technology for LPI prediction, devising the FMSRT-LPI model based on path masking and degree regression strategies and thereby achieving satisfactory outcomes. This represents the first known integration of path masking and degree regression strategies into the GAE framework for potential LPI inference. The effectiveness of our FMSRT-LPI model primarily relies on four key aspects. First, within the GAE framework, our model integrates multi-source relationships of lncRNAs and proteins with LPN's topological data. Second, the implemented masking strategy efficiently identifies LPN's key paths, reconstructs the network, and reduces the impact of redundant or incorrect data. Third, the integrated degree decoder balances degree and structural information, enhancing node representation. Fourth, the PolyLoss function we introduced is more appropriate for LPI prediction tasks. The results on multiple public datasets further demonstrate our model's potential in LPI prediction.

Is there a causal association between gestational diabetes mellitus and immune mediators? A bidirectional Mendelian randomization analysis.

Background: Diabetes that only appears or is diagnosed during pregnancy is referred to as gestational diabetes mellitus (GDM). The maternal physiological immune profile is essential for a positive pregnancy outcome. However, the causal relationship between GDM and immunophenotypes is not fully defined. Methods: Based on the high-density genetic variation data at the genome-wide level, we evaluated the logical associations between 731 specific immune mediators and GDM using bidirectional Mendelian randomization (MR). The inverse variance weighted (IVW) was the main method employed for MR analysis. We performed multiple methods to verify the robustness and dependability of the MR results, and sensitivity measures were applied to rule out potential heterogeneity and horizontal pleiotropy. Results: A substantial causal association between several immune mediators and GDM was detected. After FDR testing, HLA DR++ monocyte %leukocyte and HLA DR on plasmacytoid DC were shown to increase the risk of GDM; in contrast, CD127 on CD28+ CD45RA+ CD8br and CD19 on PB/PC were shown to attenuate the effect of GDM. Moreover, the progression of GDM has been shown to decrease the maternal levels of CD39+ activated Treg AC, CD39+ activated Treg %CD4 Treg, CD39+ resting Treg AC, CD39+ resting Treg %CD4 Treg, and CD39+ CD8BR %T cell. Conclusions: Our findings support a possible causal association between GDM and various immunophenotypes, thus facilitating the provision of multiple options for preventive recognition as well as for the diagnostic and therapeutic management of GDM in clinical practice.

Strongly plasticized gelatin-based hydrogel for flexible encapsulation of complex-shaped electronic devices.

The growth of environmentally sensitive complex-shaped electronic devices (ECEDs) has led to a surging demand for flexible electromagnetic wave (EMW) absorbers. Herein, the water loss property of hydrogel was ingeniously applied for the flexible encapsulation (FE) of ECEDs. To be specific, saturated state (SGT) hydrogels were prepared by chemical cross-linking, and the hydrogen bond dissipation network promoted FE. Additionally, SGT has an effective absorption bandwidth (EAB) of 6.04 GHz at 1.65 mm due to the presence of dipole polarization. With the loss of water, SGT transitions to its natural state (NGT), and the decreasing conductivity leads to better impedance matching. NGT exhibited a broader EAB (9.20 GHz at 2.65 mm) and also strength and lightness (density of 0.3 g cm-3). Furthermore, the semi-automatic reversible cyclic transformation between SGT and NGT gels further broadens application scenarios. GT gel combines self-encapsulation and self-optimized performance as a potential EMW absorber for FE.

Emission behaviors from ZnO microwire pumped CsPbBr3 perovskite microwire.

Perovskite semiconductor materials have attracted significant attention in the fields of photovoltaics and luminescence due to their excellent photoelectric properties, such as high carrier mobility, high absorption coefficient, and high fluorescence quantum yield. In particular, low-dimensional metal-halide perovskite microcrystalline materials have been reported to exhibit low-dimensional lasing phenomena and laser devices due to their high gain and widely tunable bandgap. In this Letter, one-dimensional (1-D) ZnO microwires with their ultraviolet lasing emissions are utilized as an excitation source to pump CsPbBr3 microwire on hybrid ZnO-CsPbBr3 microscale structures. At higher excitation, the amplified spontaneous emission (ASE) behaviors from CsPbBr3 microwire are realized with ultralow threshold by indirect pumping from the ZnO lasing emission for the first time, to the best of our knowledge. In comparison, the ASE behaviors from the CsPbBr3 microwire directly pumped by Nd:YAG Q-switched laser and continuous wave laser are also performed at room temperature. There are also no multimode lasing behaviors observed. The paper provides a new method to achieve a low threshold on-chip microlaser by a high-quality perovskite micro-nano structure.

Clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma.

The clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma (ND-DLBCL) remains largely unexplored. One hundred ND-DLBCL patients were consecutively enrolled as training cohort and another 26 ND-DLBCL patients were prospectively enrolled in validation cohort. CSF-ctDNA positivity (CSF(+)) was identified in 25 patients (25.0%) in the training cohort and 7 patients (26.9%) in the validation cohort, extremely higher than CNS involvement rate detected by conventional methods. Patients with mutations of CARD11, JAK2, ID3, and PLCG2 were more predominant with CSF(+) while FAT4 mutations were negatively correlated with CSF(+). The downregulation of PI3K-AKT signaling, focal adhesion, actin cytoskeleton, and tight junction pathways were enriched in CSF(+) ND-DLBCL. Furthermore, pretreatment CSF(+) was significantly associated with poor outcomes. Three risk factors, including high CSF protein level, high plasma ctDNA burden, and involvement of high-risk sites were used to predict the risk of CSF(+) in ND-DLBCL. The sensitivity and specificity of pretreatment CSF-ctDNA to predict CNS relapse were 100% and 77.3%. Taken together, we firstly present the prevalence and the genomic and transcriptomic landscape for CSF-ctDNA(+) DLBCL and highlight the importance of CSF-ctDNA as a noninvasive biomarker in detecting and monitoring of CSF infiltration and predicting CNS relapse in DLBCL.

Selective venous sampling for secondary hypertension.

Selective venous sampling (SVS), an invasive radiographic procedure that depends on contrast media, holds a unique role in diagnosing and guiding the treatment of certain types of secondary hypertension, particularly in patients who may be candidates for curative surgery. The adrenal venous sampling (AVS), in particular, is established as the gold standard for localizing and subtyping primary aldosteronism (PA). Throughout decades of clinical practice, AVS could be applied not only to PA but also to other endocrine diseases, such as adrenal Cushing syndrome (ACS) and Pheochromocytomas (PCCs). Notably, the application of AVS in ACS and PCCs remains less recognized compared to PA, with the low success rate of catheterization, the controversy of results interpretation, and the absence of a standardized protocol. Additionally, the AVS procedure necessitates enhancements to boost its success rate, with several helpful but imperfect methods emerging, yet continued exploration remains essential. We also observed renal venous sampling (RVS), an operation akin to AVS in principle, serves as an effective means of diagnosing renin-dependent hypertension, aiding in the identification of precise sources of renin excess and helping the selection of surgical candidates with renin angiotensin aldosterone system (RAAS) abnormal activation. Nonetheless, further basic and clinical research is needed. Selective venous sampling (SVS) can be used in identifying cases of secondary hypertension that are curable by surgical intervention. Adrenal venous sampling (AVS) and aldosterone measurement for classificatory diagnosis of primary aldosteronism (PA) are established worldwide. While its primary application is for PA, AVS also holds the potential for diagnosing other endocrine disorders, including adrenal Cushing's syndrome (ACS) and pheochromocytomas (PCCs) through the measurements of cortisol and catecholamine respectively. In addition, renal venous sampling and renin measurement can help to diagnose renovascular hypertension and reninoma.

Comparison of Facial Aesthetic Evaluation Given by Patients with Cleft Lip and/or Palate and Professionals: A Systematic Review.

OBJECTIVE: To compare the differences of facial aesthetic evaluation between patients with Cleft Lip and/or Palate (CL/P) and professionals for the treatment outcome of CL/P. DESIGN: This systematic review was conducted on MedLine, Web of Science, Embase and Cochrane Library databases. The Risk of Bias in Non-randomized Studies of Intervention (ROBINS-I) tool was used to evaluate the included researches. SETTING: Not applicable. PATIENTS, PARTICIPANTS: Patients with CL/P and professionals. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The facial aesthetic evaluation of patients with CL/P and professionals. RESULTS: Among the 1695 literatures retrieved, 22 articles were included, including 974 patients with CL/P and 251 professionals. The bias risk assessment on 21 articles was rated "Moderate" and only one article was rated "Serious". Due to the high heterogeneity of the included studies, meta-analysis was not possible, so descriptive analysis was conducted. Among the included studies, two articles indicated similar views from both groups, 19 noted differences between the two groups, of which three articles indicated more positive evaluation by professionals and nine articles indicated more positive evaluation by patients. CONCLUSIONS: The available data indicate that there is a difference between patients with CL/P and professionals in the aesthetic evaluation, but it is not clear which group is more positive. During the treatment of patients with CL/P, apart from the objective aesthetic evaluation, professionals should fully consider subjective ideas and self-assessment of patients, in order to improve the quality of life for patients.

Enhancing pathological complete response prediction in breast cancer: the role of dynamic characterization of DCE-MRI and its association with tumor heterogeneity.

BACKGROUND: Early prediction of pathological complete response (pCR) is important for deciding appropriate treatment strategies for patients. In this study, we aimed to quantify the dynamic characteristics of dynamic contrast-enhanced magnetic resonance images (DCE-MRI) and investigate its value to improve pCR prediction as well as its association with tumor heterogeneity in breast cancer patients. METHODS: The DCE-MRI, clinicopathologic record, and full transcriptomic data of 785 breast cancer patients receiving neoadjuvant chemotherapy were retrospectively included from a public dataset. Dynamic features of DCE-MRI were computed from extracted phase-varying radiomic feature series using 22 CAnonical Time-sereis CHaracteristics. Dynamic model and radiomic model were developed by logistic regression using dynamic features and traditional radiomic features respectively. Various combined models with clinical factors were also developed to find the optimal combination and the significance of each components was evaluated. All the models were evaluated in independent test set in terms of area under receiver operating characteristic curve (AUC). To explore the potential underlying biological mechanisms, radiogenomic analysis was implemented on patient subgroups stratified by dynamic model to identify differentially expressed genes (DEGs) and enriched pathways. RESULTS: A 10-feature dynamic model and a 4-feature radiomic model were developed (AUC = 0.688, 95%CI: 0.635-0.741 and AUC = 0.650, 95%CI: 0.595-0.705) and tested (AUC = 0.686, 95%CI: 0.594-0.778 and AUC = 0.626, 95%CI: 0.529-0.722), with the dynamic model showing slightly higher AUC (train p = 0.181, test p = 0.222). The combined model of clinical, radiomic, and dynamic achieved the highest AUC in pCR prediction (train: 0.769, 95%CI: 0.722-0.816 and test: 0.762, 95%CI: 0.679-0.845). Compared with clinical-radiomic combined model (train AUC = 0.716, 95%CI: 0.665-0.767 and test AUC = 0.695, 95%CI: 0.656-0.714), adding the dynamic component brought significant improvement in model performance (train p < 0.001 and test p = 0.005). Radiogenomic analysis identified 297 DEGs, including CXCL9, CCL18, and HLA-DPB1 which are known to be associated with breast cancer prognosis or angiogenesis. Gene set enrichment analysis further revealed enrichment of gene ontology terms and pathways related to immune system. CONCLUSION: Dynamic characteristics of DCE-MRI were quantified and used to develop dynamic model for improving pCR prediction in breast cancer patients. The dynamic model was associated with tumor heterogeniety in prognostic-related gene expression and immune-related pathways.

Inhibition Studies of Expansion Damage in Medium-Low Reactivity Limestone by Fly Ash.

Expansion damage in medium-low reactivity dolomite limestone poses significant challenges in construction and engineering projects. This study investigates the potential of fly ash in inhibiting expansion damage in such limestone formations based on RILEM AAR-5 method. Through a series of laboratory experiments, various proportions of fly ash instead of cement, respectively, were prepared and subjected to varying alkali content conditions immersion tests to simulate expansion conditions. The expansion rates and extents were monitored and compared between pure limestone samples and those mixed with different proportions of fly ash. Additionally, scanning electron microscopy (SEM) analysis was employed to investigate the microstructure of the dolomite limestone-fly ash mixtures to understand the inhibition mechanisms. Results indicate that fly ash demonstrates promising inhibitory effects on expansion damage in medium-low reactivity dolomite limestone across the addition of 40% fly ash and alkali content of 0.70%. The reaction products are calcite, brucite, and a mixture of Mg-Si-Al phases and the reaction area is within 100 µm from the boundary when the cement alkali content is 1.50% without any fly ash. However, no reaction products were found at the boundary after adding 40% fly ash when lowering the cement alkali content to 0.70%. This research contributes to a better understanding of the interaction between fly ash and dolomite limestone in inhibiting expansion damage, providing valuable insights for engineering applications.