ACR benchmark testing of a novel high-speed ring-gantry linac kV-CBCT system.

A new generation cone-beam computed tomography (CBCT) system with new hardware design and advanced image reconstruction algorithms is available for radiation treatment simulation or adaptive radiotherapy (HyperSight CBCT imaging solution, Varian Medical Systems-a Siemens Healthineers company). This study assesses the CBCT image quality metrics using the criteria routinely used for diagnostic CT scanner accreditation as a first step towards the future use of HyperSight CBCT images for treatment planning and target/organ delineations. Image performance was evaluated using American College of Radiology (ACR) Program accreditation phantom tests for diagnostic computed tomography systems (CTs) and compared HyperSight images with a standard treatment planning diagnostic CT scanner (Siemens SOMATOM Edge) and with existing CBCT systems (Varian TrueBeam version 2.7 and Varian Halcyon version 2.0).  Image quality performance for all Varian HyperSight CBCT vendor-provided imaging protocols were assessed using ACR head and body ring CT phantoms, then compared to existing imaging modalities. Image quality analysis metrics included contrast-to-noise (CNR), spatial resolution, Hounsfield number (HU) accuracy, image scaling, and uniformity. All image quality assessments were made following the recommendations and passing criteria provided by the ACR. The Varian HyperSight CBCT imaging system demonstrated excellent image quality, with the majority of vendor-provided imaging protocols capable of passing all ACR CT accreditation standards. Nearly all (8/11) vendor-provided protocols passed ACR criteria using the ACR head phantom, with the Abdomen Large, Pelvis Large, and H&N vendor-provided protocols produced HU uniformity values slightly exceeding passing criteria but remained within the allowable minor deviation levels (5-7 HU maximum differences). Compared to other existing CT and CBCT imaging modalities, both HyperSight Head and Pelvis imaging protocols matched the performance of the SOMATOM CT scanner, and both the HyperSight and SOMATOM CT substantially surpassed the performance of the Halcyon 2.0 and TrueBeam version 2.7 systems. Varian HyperSight CBCT imaging system could pass almost all tests for all vendor-provided protocols using ACR accreditation criteria, with image quality similar to those produced by diagnostic CT scanners and significantly better than existing linac-based CBCT imaging systems.

Liquid Glycan Array.

The M13 phage platform is a stable and monodisperse nanoscale carrier, which can be modified with different molecules by chemical conjugation strategies. Here, we describe M13 phage acylated on pVIII protein with a dibenzocyclooctyne reacting with azido glycan to yield 30-1500 copy numbers of glycan per phage and monitored by MALDI-TOF spectrometry to generate multivalent glycoconjugates that contain desired densities of glycans. We prepared the liquid glycan arrays (LiGA) such that both the structure and density of glycans were encoded in the DNA of the bacteriophage. The LiGA can be used to validate the binding properties of glycans to purified lectins and explore the effect of glycan density on such binding. From a mixture of multivalent glycan probes, LiGAs can also identify the glycoconjugates with optimal avidity necessary for binding to lectins on living cells in vitro and live animals in vivo.

Breast Reconstruction Complications After Postmastectomy Proton Radiation Therapy for Breast Cancer.

Purpose: Our purpose was to report complications requiring surgical intervention among patients treated with postmastectomy proton radiation therapy (PMPRT) for breast cancer in the setting of breast reconstruction (BR). Methods and Materials: Patients enrolled on a prospective proton registry who underwent BR with immediate autologous flap, tissue expander (TE), or implant in place during PMPRT (50/50.4 Gy +/- chest wall boost) were eligible. Major reconstruction complication (MRC) was defined as a complication requiring surgical intervention. Absolute reconstruction failure was an MRC requiring surgical removal of BR. A routine revision (RR) was a plastic surgery refining cosmesis of the BR. Kaplan-Meier method was used to assess disease outcomes and MRC. Cox regression was used to assess predictors of MRC. Results: Seventy-three courses of PMPRT were delivered to 68 women with BR between 2013 and 2021. Median follow-up was 42.1 months. Median age was 47 years. Fifty-six (76.7%) courses used pencil beam scanning PMPRT. Of 73 BR, 29 were flaps (39.7%), 30 implants (41.1%), and 14 TE (19.2%) at time of irradiation. There were 20 (27.4%) RR. There were 9 (12.3%) MRC among 5 implants, 2 flaps, and 2 TE, occurring a median of 29 months from PMPRT start. Three-year freedom from MRC was 86.9%. Three (4.1%) of the MRC were absolute reconstruction failure. Complications leading to MRC included capsular contracture in 5, fat necrosis in 2, and infection in 2. On univariable analysis, BR type, boost, proton technique, age, and smoking status were not associated with MRC, whereas higher body mass index trended toward significance (hazard ratio, 1.07; 95% CI, 0.99-1.16; P = .10). Conclusions: Patients undergoing PMPRT to BR had a 12.3% incidence of major complications leading to surgical intervention, and total loss of BR was rare. MRC rates were similar among reconstruction types. Minor surgery for RR is common in our practice.

Five-Year Outcomes of a Phase 1/2 Trial of Accelerated Partial Breast Irradiation Using Proton Therapy for Women With Stage 0-IIA Breast Cancer.

Purpose: We report the results of a phase 1/2 trial of external beam partial breast radiation using proton therapy. Methods and Materials: Eligible patients included stage 0-IIA breast cancer pTis-T2, N0, and size ≤3 cm. Proton beam radiation was used to deliver 3.85 Gy twice daily to 38.5 Gy. The phase 1 portion determined feasibility based on criteria of successful plan creation, treatment delivery, and acute toxicity grade ≥3 in ≤20% of patients. The phase 2 portion had efficacy goals of acute toxicity grade ≥3 in ≤20% of patients and observing physician-rated cosmesis of excellent or good >85% of patients at 2 years. Results: From April 2013 to March 2015, there were 12 patients enrolled onto the phase 1 portion, and the preplanned analysis of feasibility was met in all 4 required criteria. From July 2015 through December 2019 there were 28 patients with 29 treated breasts (1 bilateral) enrolled onto the phase 2 portion of the trial out of 45 originally planned. The trial was closed to accrual because of the coronavirus pandemic and not reopened. Thirty-eight breasts were treated with double-scattering and 3 pencil-beam scanning protons. The median follow-up of the 40 patients is 5.4 years (range, 2.3-8.6 years). There was 1 local recurrence. There was no grade ≥3 acute or late toxicity. At baseline all patients had physician-rated cosmesis good or excellent but at 2 years was excellent in 56%, good in 19%, and fair in 25%. Conclusions: Proton-accelerated partial breast irradiation delivered with a twice-daily fractionation was feasible and associated with very low acute and long-term toxicity. However, the trial did not meet goals for cosmesis outcomes and was closed prematurely. Future study is needed to determine whether pencil-beam scanning protons or different fractionation could improve these outcomes.

Glucose metabolism in posterior cingulate cortex has supplementary value to predict the progression of cognitively unimpaired to dementia due to Alzheimer's disease: an exploratory study of 18F-FDG-PET.

Amyloid-ß (Aß) and tau are important biomarkers to predict the progression of cognitively unimpaired (CU) to dementia due to Alzheimer's disease (AD), according to the diagnosis framework from the US National Institute on Aging and the Alzheimer's Association (NIA-AA). However, it is clinically difficult to predict those subjects who were already with Aß positive (A +) or tau positive (T +). As a typical characteristic of neurodegeneration in the diagnosis framework, the hypometabolism of the posterior cingulate cortex (PCC) has significant clinical value in the early prediction and prevention of AD. In this paper, we proposed the glucose metabolism in the PCC as a biomarker supplement to Aß and tau biomarkers. First, we calculated the standard uptake value ratio (SUVR) of PCC based on fluorodeoxyglucose positron emission computed tomography (FDG PET) imaging. Secondly, we performed Kaplan-Meier (KM) survival analyses to explore the predictive performance of PCC SUVR, and the hazard ratio (HR) was calculated. Finally, we performed Pearson correlation analyses to explore the physiological significance of PCC SUVR. As a result, the PCC SUVR showed a consistent downward trend along the AD continuum. KM analyses showed better predictive performance when we combined PCC SUVR with cerebro-spinal fluid (CSF) Aß42 (from HR = 2.56 to 3.00 within 5 years; from HR = 2.76 to 4.20 within 10 years) and ptau-181 (from 2.83 to 3.91 within 5 years; from HR = 2.32 to 4.17 within 10 years). There was a slight correlation between Aß42/Aß40 and PCC SUVR (r = 0.14, p = 0.02). In addition, several cognition scales were also correlated to PCC SUVR (from r = -0.407 to 0.383, p < 0.05). Our results showed that glucose metabolism in PCC may be a potential biomarker supplement to the Aß and tau biomarkers to predict the progression of CU to AD.

Characterization of Cherenkov imaging parameters and positional constraints on an O-ring linear accelerator.

Objective. With the introduction of Cherenkov imaging technology on the Halcyon O-ring linear accelerator platform, we seek to demonstrate the imaging feasibility and optimize camera placement.Approach. Imaging parameters were probed by acquiring triggering data Cherenkov image frames for simplistic beams on the Halcyon and comparing the analyzed metrics with those from the TrueBeam platform. Camera position was analyzed by performing 3D rendering of patient treatment plans for various sites and iterating over camera positions to assess treatment area visibility.Main results. Commercial Cherenkov imaging systems are compatible with the pulse timing of the Halcyon, and this platform design favorably impacts signal to noise in Cherenkov image frames. Additionally, ideal camera placement is treatment site dependent and is always within a biconical zone of visibility centered on the isocenter. Visibility data is provided for four treatment sites, with suggestions for camera placement based on room dimensions. Median visibility values were highest for right breast plans, with values of 80.33% and 68.49% for the front and rear views respectively. Head and neck plans presented with the lowest values at 26.44% and 38.18% respectively.Significance. This work presents the first formal camera positional analysis for Cherenkov imaging on any platform and serves as a template for performing similar work for other irradiation platforms. Additionally, this study confirms the Cherenkov imaging parameters do not need to be changed for optimal imaging on the Halcyon. Lastly, the presented methodology provides a framework which could be further expanded to other optical imaging systems which rely on line of sight visibility to the patient.

Effect of polysaccharides on conformational changes and functional properties of protein-polyphenol binary complexes: A comparative study.

This study aimed to investigate the effect of different polysaccharides on the binding behavior and functional properties of soybean protein isolate (SPI)-quercetin (Que) complex. The binding behavior was assessed using multi-spectral technique with the Stern-Volmer equation, which confirmed the presence of static fluorescence quenching in Que and SPI. The addition of sodium alginate (SA) resulted in a reduction of the binding affinity between SPI and Que, while dextran (DX) exhibited some promoting effect. A slight blue shift was observed in amide I and amide II bands, indicating the presence of hydrophobic and electrostatic interactions. Circular dichroism spectra revealed the ordered structures transformed into a more disordered state when polysaccharides were added, leading to an increase in random coils (SA: 18.5 %, DX: 15.4 %). Docking and dynamic simulations demonstrated that SA displayed greater stability within the hydrophobic compartments of SPI than DX, increased rigidity and stability of the SPI structure in SPI-Que-SA complexes. Electrostatic forces played a significant role between SPI and SA, while van der Waals forces were the main driving forces in SPI-DX complexes. Overall, the introduction of SA led to a looser and stable structure of SPI-Que complexes, resulting in an improvement of their emulsifying, foaming, and antioxidant properties.

Positron Emission Tomography (PET)/Computed Tomography (CT) Imaging in Radiation Therapy Treatment Planning: A Review of PET Imaging Tracers and Methods to Incorporate PET/CT.

Purpose: Positron emission tomography (PET)/computed tomography (CT) has become a critical tool in clinical oncology with an expanding role in guiding radiation treatment planning. As its application and availability grows, it is increasingly important for practicing radiation oncologists to have a comprehensive understanding of how molecular imaging can be incorporated into radiation planning and recognize its potential limitations and pitfalls. The purpose of this article is to review the major approved positron-emitting radiopharmaceuticals clinically being used today along with the methods used for their integration into radiation therapy including methods of image registration, target delineation, and emerging PET-guided protocols such as biologically-guided radiation therapy and PET-adaptive therapy. Methods and Materials: A review approach was utilized using collective information from a broad review of the existing scientific literature sourced from PubMed search with relevant keywords and input from a multidisciplinary team of experts in medical physics, radiation treatment planning, nuclear medicine, and radiation therapy. Results: A number of radiotracers imaging various targets and metabolic pathways of cancer are now commercially available. PET/CT data can be incorporated into radiation treatment planning through cognitive fusion, rigid registration, deformable registration, or PET/CT simulation techniques. PET imaging provides a number of benefits to radiation planning including improved identification and delineation of the radiation targets from normal tissue, potential automation of target delineation, reduction of intra- and inter-observer variability, and identification of tumor subvolumes at high risk for treatment failure which may benefit from dose intensification or adaptive protocols. However, PET/CT imaging has a number of technical and biologic limitations that must be understood when guiding radiation treatment. Conclusion: For PET guided radiation planning to be successful, collaboration between radiation oncologists, nuclear medicine physicians, and medical physics is essential, as well as the development and adherence to strict PET-radiation planning protocols. When performed properly, PET-based radiation planning can reduce treatment volumes, reduce treatment variability, improve patient and target selection, and potentially enhance the therapeutic ratio accessing precision medicine in radiation therapy.

Acute and long-term toxicity of whole pelvis proton radiation therapy for definitive or adjuvant management of gynecologic cancers.

OBJECTIVE: To characterize long-term toxicity and disease outcomes with whole pelvis (WP) pencil beam scanning proton radiation therapy (PBS PRT) for gynecologic malignancies. METHODS: We reviewed 23 patients treated from 2013 to 2019 with WP PBS PRT for endometrial, cervical, and vaginal cancer. We report acute and late Grade (G)2+ toxicities, graded by Common Terminology Criteria for Adverse Events, Version 5. Disease outcomes were assessed by Kaplan-Meier method. RESULTS: Median age was 59 years. Median follow up was 4.8 years. 12 (52.2%) had uterine cancer, 10 (43.5%) cervical, 1 (4.3%) vaginal. 20 (86.9%) were treated post-hysterectomy. 22 (95.7%) received chemotherapy, 12 concurrently (52.2%). The median PBS PRT dose was 50.4GyRBE (range, 45-62.5). 8 (34.8% had para-aortic/extended fields. 10 (43.5%) received brachytherapy boost. Median follow up was 4.8 years. 5-year actuarial local control was 95.2%, regional control 90.9%, distant control 74.7%, both disease control and progression-free survival 71.2%. Overall survival was 91.3%. In the acute period, 2 patients (8.7%) had G2 genitourinary (GU) toxicity, 6 (26.1%) had gastrointestinal (GI) G2-3 toxicity, 17 (73.9%) had G2-4 hematologic (H) toxicity. In the late period, 3 (13.0%) had G2 GU toxicity, 1 (4.3%) had G2 GI toxicity, 2 (8.7%) had G2-3H toxicity. The mean small bowel V15Gy was 213.4 cc. Mean large bowel V15 Gy was 131.9 cc. CONCLUSIONS: WP PBS PRT for gynecologic malignancies delivers favorable locoregional control. Rates of GU and GI toxicity are low. Acute hematologic toxicity was most common, which may be related to the large proportion of patients receiving chemotherapy.

Comparison of surface dose during whole breast radiation therapy on Halcyon and TrueBeam using Cherenkov imaging.

The emergence of the Halcyon linear accelerator has allowed for increased patient throughput and improved treatment times for common treatment sites in radiation oncology. However, it has been shown that this can lead to increased surface dose in sites like breast cancer compared with treatments on conventional machines with flattened radiation beams. Cherenkov imaging can be used to estimate surface dose by detection of Cherenkov photons emitted in proportion to energy deposition from high energy electrons in tissue. Phantom studies were performed with both square beams in reference conditions and with clinical treatments, and dosimeter readings and Cherenkov images report higher surface dose (25% for flat phantom entrance dose, 5.9% for breast phantom treatment) from Halcyon beam deliveries than for equivalent deliveries from a TrueBeam linac. Additionally, the first Cherenkov images of a patient treated with Halcyon were acquired, and superficial dose was estimated.

MCP-1 levels in astrocyte-derived exosomes are changed in preclinical stage of Alzheimer's disease.

Background: Alzheimer's disease (AD) is the most common form of dementia in older adults. There is accumulating evidence that inflammatory processes play a critical role in AD pathogenesis. In this study, we investigated whether inflammatory factors in plasma and astrocyte-derived exosomes (ADEs) from plasma are differentially expressed in the early stages of AD and their potential role in pathological processes in the AD continuum. Method: We included 39 normal controls (NCs), 43 participants with subjective cognitive decline (SCD), and 43 participants with amnestic mild cognitive impairment (aMCI)/AD. IL-6, IL-8, and MCP-1 in plasma and ADEs from plasma were evaluated using a commercial multiplex Luminex-based kit. Results: Pairwise comparisons between the groups showed no significant differences in plasma levels of IL-6, IL-8, or MCP-1. However, ADEs in the SCD group showed an increase in MCP-1 levels compared to the NC group. To differentiate the preclinical group, discriminant analysis was performed using sex, age, years of education, and genotype. This revealed a difference between the SCD and NC groups (area under the curve: 0.664). A Spearman correlation analysis of MCP-1 in plasma and ADEs showed no or weak correlation in the SCD (R = 0.150, p = 0.350) and aMCI/AD (R = 0.310, p = 0.041) groups, while a positive correlation in the NC group (R = 0.360, p = 0.026). Conclusion: Plasma IL-6, IL-8, and MCP-1 levels were not significantly different. However, the concentration of MCP-1 in ADEs is slightly altered during the preclinical phase of AD, which could be a potential role of the central neuron system (CNS) immune response in the AD continuum. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT03370744.

Progress in blood biomarkers of subjective cognitive decline in preclinical Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disease that gradually impairs cognitive functions. Recently, there has been a conceptual shift toward AD to view the disease as a continuum. Since AD is currently incurable, effective intervention to delay or prevent pathological cognitive decline may best target the early stages of symptomatic disease, such as subjective cognitive decline (SCD), in which cognitive function remains relatively intact. Diagnostic methods for identifying AD, such as cerebrospinal fluid biomarkers and positron emission tomography, are invasive and expensive. Therefore, it is imperative to develop blood biomarkers that are sensitive, less invasive, easier to access, and more cost effective for AD diagnosis. This review aimed to summarize the current data on whether individuals with SCD differ reliably and effectively in subjective and objective performances compared to cognitively normal elderly individuals, and to find one or more convenient and accessible blood biomarkers so that researchers can identify SCD patients with preclinical AD in the population as soon as possible. Owing to the heterogeneity and complicated pathogenesis of AD, it is difficult to make reliable diagnoses using only a single blood marker. This review provides an overview of the progress achieved to date with the use of SCD blood biomarkers in patients with preclinical AD, highlighting the key areas of application and current challenges.

Associations Between Levels of Peripheral NCAPH2 Promoter Methylation and Different Stages of Alzheimer's Disease: A Cross-Sectional Study.

BACKGROUND: Several studies have examined NCAPH2 methylation in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD), but little is known of NCAPH2 methylation in subjective cognitive decline (SCD). OBJECTIVE: To examine whether methylation of peripheral NCAPH2 are differentially changed at various phases of AD, and whether it could serve as a diagnostic biomarker for SCD. METHODS: A total of 40 AD patients, 52 aMCI patients, 148 SCD patients, and 193 cognitively normal controls (NCs) were recruited in the current case-control study. Besides, 54 cognitively normal individuals have received amyloid positron emission tomography (amyloid PET) scans. Using bisulfite pyrosequencing method, we measured blood DNA methylation in the NCAPH2 gene promoter. RESULTS: The main outcomes were: 1) For SCD, there was no significant difference between SCD and NC regarding NCAPH2 methylation; 2) For aMCI, NCAPH2 methylation at CpG2 were significantly lower in aMCI compared with NC and SCD in the entire population and male subgroup; 3) For AD, NCAPH2 methylation at CpG1 were significantly lower in AD compared with NC among females; 4) A relationship with apolipoprotein E (APOE) ɛ4 status was shown. Receiver operating characteristic (ROC) analysis by combining NCAPH2 methylation, age, education, and APOEɛ4 status could distinguish between patients with aMCI (area under the curve (AUC): 0.742) and AD (AUC: 0.873) from NCs. CONCLUSION: NCAPH2 methylation levels were altered at the aMCI and AD stage and may be convenient and cost-effective biomarkers of AD and aMCI.

Association of plasma BDNF levels with different stages of Alzheimer's disease: a cross-sectional study.

BACKGROUND: Growing evidence shows that the expression of brain-derived neurotrophic factor (BDNF) is altered in the peripheral blood of participants with Alzheimer's disease (AD). It is unclear, however, whether altered BDNF expression is also observed in the early stages of AD. METHODS: In the present study, 138 normal controls (NC), 57 participants with subjective cognitive decline (SCD), and 37 participants with amnestic mild cognitive impairment (aMCI) and AD were included. Plasma BDNF protein levels were assessed using a commercial multiplex Luminex-based kit. Patient samples were also probed for the presence of BDNF gene variant rs6265. RESULTS: Pairwise comparisons between the groups showed that there was not a significant difference in BDNF levels when comparing SCD with NC and when comparing SCD with aMCI/AD, but BDNF levels in aMCI/AD samples were increased when compared with NC samples. For models differentiating clinical groups, discriminant analysis was performed by including education, APOE genotype, and BDNF levels in the model. This approach distinguishes participants with SCD (AUC = 0.630) and aMCI/AD (AUC = 0.665) from NC. CONCLUSION: Our results suggest that expression of BDNF in plasma is altered at the clinical stage of AD.

Cerebrospinal Fluid sTREM2 in Alzheimer's Disease Is Associated with Both Amyloid and Tau Pathologies but not with Cognitive Status.

BACKGROUND: Cerebrospinal fluid (CSF) soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is considered a biomarker of microglial activation. The relationships between CSF sTREM2 levels and Alzheimer's disease (AD) CSF core biomarkers, cognitive status, and neurodegeneration remain unclear. OBJECTIVE: To assess the association between CSF sTREM2 levels and AD progression and other AD hallmarks. METHODS: Using the Alzheimer's Disease Neuroimaging Initiative database, we investigated 1,035 participants, including 310 cognitively normal controls, 527 patients with mild cognitive impairment, and 198 patients with dementia. They were grouped according to CSF pathology (A/T profile) severity. CSF sTREM2 levels were compared between the groups, and linear regression analysis was performed to evaluate the factors affecting sTREM2 levels. The predictive effectiveness of sTREM2 levels was tested, and the correlation with other indicators was explored. The increase rate was assessed using linear mixed-effects models. RESULTS: Higher CSF sTREM2 levels were associated with older age as well as higher CSF p-tau or t-tau and amyloid-ß levels (all p < 0.001), but not with cognitive status. sTREM2 levels were not correlated with the baseline or longitudinal scale and neuroimaging result changes, and could not predict clinical conversion, but were correlated with multiple non-amyloid-ß and non-tau CSF cytokines related to inflammation and neurodegeneration (p < 0.0001). The increased sTREM2 expression rate did not change among groups. CONCLUSION: CSF sTREM2 levels were jointly determined by age, amyloid-ß, and tau pathologies, leading to complex AD cognitive continuum changes. Although sTREM2 levels could not predict cognitive deterioration and neurodegeneration, they could reflect the microglial state as a non-specific biomarker.

Study on the binding behavior and functional properties of soybean protein isolate and ß-carotene.

This study focused on the non-covalent interaction between soybean protein isolate (SPI) and ß-carotene (BC). The conformational changes of SPI with ß-carotene in varying proportions (BC/SPI: 2%, 4%, 6%, 8%, and 10%) were investigated by multi-spectroscopy and molecular docking. Results showed that the quenching mode is static quenching and binding affinity increased with temperature. The stoichiometry was 1:1, indicating there was only one binding site in SPI. The binding was based on entropy and primarily driven by hydrophobic interactions and its binding constant was in the order of 104 L⋅mol-1. The addition of the ß-carotene affected the secondary structure of SPI resulting in an increase in α-Helix and a decrease in random coil and ß-turn content, indicating protein aggregated and hydrophobic interactions occurred. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) verified that no new larger molecular weight substance was formed and no covalent interaction existed. Molecular docking corroborated that electrostatic and hydrophobic interactions were both involved in the formation of complexes, where hydrophobic interaction was the dominant one. Moreover, ß-carotene improved 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, foaming capacity, and emulsifying stability of SPI. These findings provide useful information about the interaction mechanism of SPI and ß-carotene, which contributes to the further development and application of SPI products rich in ß-carotene in the food industry.

Changes on the conformational and functional properties of soybean protein isolate induced by quercetin.

The conformational changes and functional properties of SPI induced by quercetin was investigated via fourier transform infrared (FTIR) spectroscopy, fluorescence spectroscopy, circular dichroism (CD) spectroscopy and molecular docking. A decrease in the fluorescence intensity and a blue shift in the maximum wavelength were observed due to the binding process with fluorescent residues. The analysis of Stern-Volmer equation showed that the fluorescence quenching induced by quercetin took the form of static quenching, and the binding stoichiometry between SPI and quercetin was 1:1. The values of ΔH and ΔS were both positive illustrating that hydrophobic interaction was the primary binding force between quercetin and SPI. Results of FTIR and CD indicated that the binding with quercetin changed the secondary structure of SPI, resulting in a partially unfolded and more flexible structure. SDS-PAGE confirmed there was no covalent interaction between the two constituents. Molecular docking demonstrated that there were stable configurations and high matching degrees in both 11S and 7S proteins with quercetin via hydrogen bonds and hydrophobic interactions. Meanwhile, modification by quercetin enhanced the foaming and emulsifying capacities of SPI. These findings might provide theory reference for elucidation the mechanism of polyphenols-proteins interaction and development of related food additive products in future.

ß-Amyloid promotes platelet activation and activated platelets act as bridge between risk factors and Alzheimer's disease.

Alzheimer's disease (AD) is an evolving challenge that places an enormous burden on families and society. The presence of obvious brain ß-amyloid (Aß) deposition is a premise to diagnose AD, which induces the subsequent tau hyperphosphorylation and neurodegeneration. Platelets are the primary source of circulating amyloid precursor protein (APP). Upon activation, they can secrete significant amounts of Aß into the blood, which can be actively transported to the brain across the blood-brain barrier and promote amyloid deposition. In this review, we summarized the changes in the platelet APP metabolic pathway in patients with AD and further comprehensively explored the targets and downstream events of Aß-activated platelets. In addition, we attempted to clarify whether patients with AD are in a state of general platelet activation, with inconsistent results. Considering the increasingly evident bidirectional relationship between AD and vascular events, we speculate that the AD pathology alone seems to be insufficient to induce the general activation of platelets; however, the intervention of third-party factors, such as atherosclerosis, exposes the extracellular matrix and leads to platelet activation, further promoting AD progression. Therefore, we proposed a framework in which the relationship between platelets and AD is indirect and mediated by vascular factors. Therapies targeting platelets and interventions for vascular risk factors are likely to contribute to the prevention and treatment of AD.

Combining PET with MRI to improve predictions of progression from mild cognitive impairment to Alzheimer's disease: an exploratory radiomic analysis study.

Background: This study aimed to explore the potential of a combination of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and magnetic resonance imaging (MRI) to improve predictions of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). The predictive performances and specific associated biomarkers of these imaging techniques used alone (single-modality imaging) and in combination (dual-modality imaging) were compared. Methods: This study enrolled 377 patients with MCI and 94 healthy control participants from 2 medical centers. Enrolment was based on the patients' brain MRI and PET images. Radiomic analysis was performed to evaluate the predictive performance of dual-modality 18F-FDG PET and MRI scans. Regions of interest (ROIs) were determined using an a priori brain atlas. Radiomic features in these ROIs were extracted from the MRI and 18F-FDG PET scan data. These features were either concatenated or used separately to select features and construct Cox regression models for prediction in each modality. Harrell's concordance index (C-index) was then used to assess the predictive accuracies of the resulting models, and correlations between the MRI and 18F-FDG PET features were evaluated. Results: The C-indices for the two test datasets were 0.77 and 0.80 for dual-modality 18F-FDG PET/MRI, 0.75 and 0.73 for single-modality 18F-FDG PET, and 0.74 and 0.76 for single-modality MRI. In addition, there was a significant correlation between the crucial image signatures of the different modalities. Conclusions: These results indicate the value of imaging features in monitoring the progress of MCI in populations at high risk of developing AD. However, the incremental benefit of combining 18F-FDG PET and MRI is limited, and radiomic analysis of a single modality may yield acceptable predictive results.