UBES: Unified scatter correction using ultrafast Boltzmann equation solver for conebeam CT.

A semi-analytical solution to the unified Boltzmann equation is constructed to exactly describe the scatter distribution on a flat-panel detector for high-quality conebeam CT (CBCT) imaging. The solver consists of three parts, including the phase space distribution estimator, the effective source constructor and the detector signal extractor. Instead of the tedious Monte Carlo solution, the derived Boltzmann equation solver achieves ultrafast computational capability for scatter signal estimation by combining direct analytical derivation and time-efficient one-dimensional numerical integration over the trajectory along each momentum of the photon phase space distribution. The execution of scatter estimation using the proposed ultrafast Boltzmann equation solver (UBES) for a single projection is finalized in around 0.4 seconds. We compare the performance of the proposed method with the state-of-the-art schemes, including a time-expensive Monte Carlo (MC) method and a conventional kernel-based algorithm using the same dataset, which is acquired from the CBCT scans of a head phantom and an abdominal patient. The evaluation results demonstrate that the proposed UBES method achieves comparable correction accuracy compared with the MC method, while exhibits significant improvements in image quality over learning and kernel-based methods. With the advantages of MC equivalent quality and superfast computational efficiency, the UBES method has the potential to become a standard solution to scatter correction in high-quality CBCT reconstruction.

Quantitative analysis of molecular transport in the extracellular space using physics-informed neural network.

The brain extracellular space (ECS), an irregular, extremely tortuous nanoscale space located between cells or between cells and blood vessels, is crucial for nerve cell survival. It plays a pivotal role in high-level brain functions such as memory, emotion, and sensation. However, the specific form of molecular transport within the ECS remain elusive. To address this challenge, this paper proposes a novel approach to quantitatively analyze the molecular transport within the ECS by solving an inverse problem derived from the advection-diffusion equation (ADE) using a physics-informed neural network (PINN). PINN provides a streamlined solution to the ADE without the need for intricate mathematical formulations or grid settings. Additionally, the optimization of PINN facilitates the automatic computation of the diffusion coefficient governing long-term molecule transport and the velocity of molecules driven by advection. Consequently, the proposed method allows for the quantitative analysis and identification of the specific pattern of molecular transport within the ECS through the calculation of the Péclet number. Experimental validation on two datasets of magnetic resonance images (MRIs) captured at different time points showcases the effectiveness of the proposed method. Notably, our simulations reveal identical molecular transport patterns between datasets representing rats with tracer injected into the same brain region. These findings highlight the potential of PINN as a promising tool for comprehensively exploring molecular transport within the ECS.

Phototherapy for age-related brain diseases: Challenges, successes and future.

Brain diseases present a significant obstacle to both global health and economic progress, owing to their elusive pathogenesis and the limited effectiveness of pharmaceutical interventions. Phototherapy has emerged as a promising non-invasive therapeutic modality for addressing age-related brain disorders, including stroke, Alzheimer's disease (AD), and Parkinson's disease (PD), among others. This review examines the recent progressions in phototherapeutic interventions. Firstly, the article elucidates the various wavelengths of visible light that possess the capability to penetrate the skin and skull, as well as the pathways of light stimulation, encompassing the eyes, skin, veins, and skull. Secondly, it deliberates on the molecular mechanisms of visible light on photosensitive proteins, within the context of brain disorders and other molecular pathways of light modulation. Lastly, the practical application of phototherapy in diverse clinical neurological disorders is indicated. Additionally, this review presents novel approaches that combine phototherapy and pharmacological interventions. Moreover, it outlines the limitations of phototherapeutics and proposes innovative strategies to improve the treatment of cerebral disorders.

Federated Domain Adaptation via Transformer for Multi-Site Alzheimer's Disease Diagnosis.

In multi-site studies of Alzheimer's disease (AD), the difference of data in multi-site datasets leads to the degraded performance of models in the target sites. The traditional domain adaptation method requires sharing data from both source and target domains, which will lead to data privacy issue. To solve it, federated learning is adopted as it can allow models to be trained with multi-site data in a privacy-protected manner. In this paper, we propose a multi-site federated domain adaptation framework via Transformer (FedDAvT), which not only protects data privacy, but also eliminates data heterogeneity. The Transformer network is used as the backbone network to extract the correlation between the multi-template region of interest features, which can capture the brain abundant information. The self-attention maps in the source and target domains are aligned by applying mean squared error for subdomain adaptation. Finally, we evaluate our method on the multi-site databases based on three AD datasets. The experimental results show that the proposed FedDAvT is quite effective, achieving accuracy rates of 88.75%, 69.51%, and 69.88% on the AD vs. NC, MCI vs. NC, and AD vs. MCI two-way classification tasks, respectively.

Effect of Physiotherapy Interventions on Motor Symptoms in People With Parkinson's Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effectiveness of different types of physiotherapy interventions in people with Parkinson's disease (PD). DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: Five databases (PubMed, Embase, Cochrane Library, CINAHL and Web of Science Core Collection) were searched for relevant RCTs published from database inception to July 14, 2022. Reviewers independently screened the literature, extracted data, and assessed the literature quality according to the Cochrane Collaboration Risk of Bias Tool and PEDro Scale. This meta-analysis was conducted using RevMan 5.4.1 and reported in compliance with the PRISMA statement. RESULTS: Forty-two RCTs with 2,530 participants were included. Across all types of physiotherapy, strength training, mind-body exercise, aerobic exercise, and non-invasive brain stimulation (NiBS) were effective in improving motor symptoms as measured by the (Movement Disorders Society-) Unified PD Scale, whereas balance and gait training (BGT) and acupuncture were not. The pooled results showed that the change in mind-body exercise (MD = -5.36, 95% CI [-7.97 to -2.74], p < .01, I2 = 68%) and NiBS (MD = -4.59, 95% CI [-8.59 to -0.59], p = .02, I2 = 78%) reached clinical threshold, indicating clinically meaningful improvements. Considering the effectiveness of the interventions on motor symptoms, balance, gait and functional mobility, mind-body exercise was recommended the most. CONCLUSIONS: Exercise appears to be a better form of physiotherapy than NiBS and acupuncture for improving motor function. Mind-body exercise showed beneficial effects on motor symptoms, balance, gait and functional mobility in people with PD, and is worthy of being promoted.

Understanding the research on tracking, diagnosing, and intervening in sleep disorders using mHealth apps: Bibliometric analysis and systematic reviews.

Objectives: In solving the global challenge of sleep disorders, Mobile Health app is one of the important means to monitor, diagnose, and intervene in sleep disorders. This study aims to (1) summarize the status and trends of research in this field; (2) assess the production and usage of sleep mHealth apps; (3) calculate the conversion rate of grants that the proportion of newly developed apps from being funded and developed to published on application stores. Methods: Using bibliometric and content analysis methods, based on "Research Paper-Product Output-Product Application" chain and considering the "Research Grants" of articles, we conducted a systematic review of eight databases, to identify relevant studies over the last decade. Results: Over the past decade, 1399 authors published 313 papers in 182 journals and conferences. The number of publications increased with an average annual growth of 41.6%. The current focus area is research using cognitive behavioral therapy to intervene in sleep. Sleep-staging tracking is a shortcoming of this field. A total 368 sleep mHealth apps (233 newly developed and 135 existing) were examined in 313 papers; 323 grants supported 178 articles (56.9%). Only 12 of the newly developed apps are used in the real world, resulting in a 9% grant conversion rate. Conclusions: In the last decade, the field of tracking, diagnosing, and intervening in sleep disorders using mHealth apps has shown a trend of rapid development. However, the conversion rate of products from being funded and developed for use by end-users is low.

Epidural Pulsation Accelerates the Drainage of Brain Interstitial Fluid.

Unhindered transportation of substances in the brain extracellular space (ECS) is essential for maintaining brain function. Regulation of transportation is a novel strategy for treating ECS blockage-related brain diseases, but few techniques have been developed to date. In this study, we established a novel approach for accelerating the drainage of brain interstitial fluid (ISF) in the ECS using minimally invasive surgery, in which a branch of the external carotid artery is separated and implanted epidurally (i.e., epidural arterial implantation [EAI]) to promote a pulsation effect on cerebrospinal fluid (CSF) in the frontoparietal region. Tracer-based magnetic resonance imaging was used to evaluate the changes in ISF drainage in rats 7 and 15 days post-EAI. The drainage of the traced ISF from the caudate nucleus to ipsilateral cortex was significantly accelerated by EAI. Significant increases in the volume fraction of the ECS and molecular diffusion rate were demonstrated using the DECS-mapping technique, which may account for the mechanisms underlying the changes in brain ISF. This study provides a novel perspective for encephalopathy treatment via the brain ECS.

Mining the Influencing Factors and Their Asymmetrical Effects of mHealth Sleep App User Satisfaction From Real-world User-Generated Reviews: Content Analysis and Topic Modeling.

BACKGROUND: Sleep disorders are a global challenge, affecting a quarter of the global population. Mobile health (mHealth) sleep apps are a potential solution, but 25% of users stop using them after a single use. User satisfaction had a significant impact on continued use intention. OBJECTIVE: This China-US comparison study aimed to mine the topics discussed in user-generated reviews of mHealth sleep apps, assess the effects of the topics on user satisfaction and dissatisfaction with these apps, and provide suggestions for improving users' intentions to continue using mHealth sleep apps. METHODS: An unsupervised clustering technique was used to identify the topics discussed in user reviews of mHealth sleep apps. On the basis of the two-factor theory, the Tobit model was used to explore the effect of each topic on user satisfaction and dissatisfaction, and differences in the effects were analyzed using the Wald test. RESULTS: A total of 488,071 user reviews of 10 mainstream sleep apps were collected, including 267,589 (54.8%) American user reviews and 220,482 (45.2%) Chinese user reviews. The user satisfaction rates of sleep apps were poor (China: 56.58% vs the United States: 45.87%). We identified 14 topics in the user-generated reviews for each country. In the Chinese data, 13 topics had a significant effect on the positive deviation (PD) and negative deviation (ND) of user satisfaction. The 2 variables (PD and ND) were defined by the difference between the user rating and the overall rating of the app in the app store. Among these topics, the app's sound recording function (ß=1.026; P=.004) had the largest positive effect on the PD of user satisfaction, and the topic with the largest positive effect on the ND of user satisfaction was the sleep improvement effect of the app (ß=1.185; P<.001). In the American data, all 14 topics had a significant effect on the PD and ND of user satisfaction. Among these, the topic with the largest positive effect on the ND of user satisfaction was the app's sleep promotion effect (ß=1.389; P<.001), whereas the app's sleep improvement effect (ß=1.168; P<.001) had the largest positive effect on the PD of user satisfaction. The Wald test showed that there were significant differences in the PD and ND models of user satisfaction in both countries (all P<.05), indicating that the influencing factors of user satisfaction with mHealth sleep apps were asymmetrical. Using the China-US comparison, hygiene factors (ie, stability, compatibility, cost, and sleep monitoring function) and 2 motivation factors (ie, sleep suggestion function and sleep promotion effects) of sleep apps were identified. CONCLUSIONS: By distinguishing between the hygiene and motivation factors, the use of sleep apps in the real world can be effectively promoted.

Disulfide-containing polymer delivery of C527 and a Platinum(IV) prodrug selectively inhibited protein ubiquitination and tumor growth on cisplatin resistant and patient-derived liver cancer models.

USP1 (Ubiquitin-specific protease 1) is closely related to the prognosis of patients with liver cancer and plays an important role in DNA damage repair. C527 is a selective USP1 inhibitor (USP1i), which can regulate the protein ubiquitination to effectively inhibit the proliferation of cancer cells. However, its clinical application is hindered due to the poor water solubility and lack of tumor targeting. Moreover, the efficacy of single use of USP1i is still limited. Herein, a glutathione (GSH) sensitive amphiphilic polymer (poly (2-HD-co-HPMDA)-mPEG, PHHM) with disulfide bonds in the main chain was designed to encapsulate the USP1i as well as platinum (IV) prodrug (Pt (IV)-C12), resulting in the formation of composite nanoparticles, i.e., NP-Pt-USP1i. NP-Pt-USP1i can inhibit the DNA damage repair by targeting USP1 by the encapsulated USP1i, which ultimately increases the sensitivity of tumor cells to cisplatin and enhances the anti-cancer efficacy of cisplatin. Finally, an intraperitoneal tumor mice model and a patient-derived xenograft (PDX) of liver cancer mice model were established to prove that NP-Pt-USP1i could effectively inhibit the tumor growth. This work further validated the possibility of therapeutically target USP1 by USP1i in combination with DNA damaging alkylating agents, which could become a promising cancer treatment modality in the future.

Effectiveness of telehealth-based exercise interventions on pain, physical function and quality of life in patients with knee osteoarthritis: A meta-analysis.

OBJECTIVE: The objective of the study was to evaluate the effectiveness of telehealth-based exercise intervention on pain, physical function and quality of life in patients with knee osteoarthritis. DESIGN: A systematic review and meta-analysis of randomised controlled trials (RCTs). METHODS: Six databases (PubMed, Embase, Cochrane Library, CINAHL, PEDro and Web of Science Core Collection) were searched for relevant randomised controlled trials published from database inception to 3 June 2021. Reviewers independently screened the literature, extracted data and used the Cochrane Collaboration Risk of Bias Tool for quality assessment. A meta-analysis and subgroup analyses, stratified by control condition, intervention duration and delivery type, were conducted by Revman 5.4. The study was reported in compliance with PRISMA statement. RESULTS: A total of 9 independent RCTs with 861 participants were included. The meta-analysis showed that the telehealth-based exercise interventions significantly reduced pain in KOA patients (SMD = -0.28, 95% CI [-0.49, -0.08], p < .01) and produced similar effects to controls in terms of physical function and quality of life. Subgroup analysis revealed that telehealth-based exercise interventions were superior to the use of exercise booklet and usual care in terms of pain and physical function and were similar to face-to-face exercise treatment; a long-term (>3 months) intervention and the use of web and smartphone APPs to deliver exercise interventions were associated with better pain relief and physical function. CONCLUSIONS: Telehealth-based exercise intervention is an effective strategy for KOA management during the COVID-19 epidemic, and it is significantly better than usual care in reducing knee pain and improving physical function and was able to achieve the effects of traditional face-to-face exercise treatment. Although the duration and type of delivery associated with the effect of the intervention have been identified, patient preference and acceptability need to be considered in practice.

Glutathione-Responsive Nanoparticles of Camptothecin Prodrug for Cancer Therapy.

Camptothecin (CPT) is a potent chemotherapeutic agent for various cancers, but the broader application of CPT is still hindered by its poor bioavailability and systemic toxicity. Here, a prodrug that releases CPT in response to glutathione (GSH), which is commonly overexpressed by cancer cells is reported. Through assembling with PEGylated lipids, the prodrug is incorporated within as-assembled nanoparticles, affording CPT with a prolonged half-life in blood circulation, enhanced tumor targetingability, and improved therapeutic efficacy. Furthermore, such prodrug nanoparticles can also promote dendritic cell maturation and tumor infiltration of CD8+ T cells, providing a novel strategy to improve the therapeutic efficacy of CPT.

A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer.

Current therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II-III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)-0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3-41.3). RCB-0/I is 55.7% (95% CI, 44.7-66.1). ORR is 87.4%, (95% CI, 78.1-93.2) and bpCR is 35.4% (95% CI, 25.8-46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC.

DLGAP1-AS2 promotes human colorectal cancer progression through trans-activation of Myc.

Substantial evidence suggests that non-coding RNA plays a vital role in human cancer, especially long non-coding RNA (lncRNA) with a length greater than 200nt. Herein, we found a lncRNA facilitating human colorectal cancer (CRC) progression. DLGAP1-AS2 was significantly increased in CRC tissues and cell lines. Knockdown of DLGAP1-AS2 inhibited CRC cell proliferation, migration, invasion in vitro, and tumor growth in vivo. The subcellular localization of DLGAP1-AS2 was translocated from the cytoplasm of normal cells to the nucleus of CRC cells due to reduced levels of N6-methyladenosine (m6A) modification. Further, through the screening of a series of signal pathways, we found that Myc pathway was involved in the effect of DLGAP1-AS2. Silencing of DLGAP1-AS2 markedly reduced Myc mRNA and protein levels. Blockade of Myc effectively abolished the enhanced aggressive behaviors of CRC cells caused by DLGAP1-AS2 overexpression. Mechanistically, DLGAP1-AS2 directly bound CTCF, a well-known transcriptional repressor of Myc, resulting in reduced binding of CTCF on Myc promoter and activating Myc transcription. The second hairpin structure of DLGAP1-AS2 was critical for the interaction between DLGAP1-AS2 and CTCF in the nucleus. Taken together, our study reveals the oncogenic regulatory axis of DLGAP1-AS2/CTCF/Myc in CRC, implying a promising targeted therapy for clinical application.

New insight into brain disease therapy: nanomedicines-crossing blood-brain barrier and extracellular space for drug delivery.

INTRODUCTION: Brain diseases including brain tumor, Alzheimer's disease, Parkinson's disease, etc. are difficult to treat. The blood-brain barrier (BBB) is a major obstacle for drug delivery into the brain. Although nano-package and receptor-mediated delivery of nanomedicine markedly increases BBB penetration, it yet did not extensively improve clinical cure rate. Recently, brain extracellular space (ECS) and interstitial fluid (ISF) drainage in ECS have been found to determine whether a drug dissolved in ISF can reach its target cells. Notably, an increase in tortuosity of ECS associated with slower ISF drainage induced by the accumulated harmful substances, such as: amyloid-beta (Aß), α-synuclein, and metabolic wastes, causes drug delivery failure. AREAS COVERED: The methods of nano-package and receptor-mediated drug delivery and the penetration efficacy of nanomedicines across BBB and ECS are assessed. EXPERT OPINION: Invasive delivering drug via ECS and noninvasive near-infrared photo-sensitive nanomedicines may provide a promising benefit to patients with brain disease.

Activating cGAS-STING pathway with ROS-responsive nanoparticles delivering a hybrid prodrug for enhanced chemo-immunotherapy.

cGAS-STING pathway, as an essential intracellular immune response pathway, has attracted much attention in tumor immunotherapy. However, low metabolic stability of conventional STING agonists limits their clinical application. Recent study shows that chemotherapeutic drugs cisplatin and camptothecin (CPT) can activate cGAS-STING pathway and induce immune response by DNA damage. Nevertheless, the ability of chemotherapeutic drugs to activate STING is so weak that new strategies are required to improve drug delivery efficiency for enhanced DNA damage, and then efficiently activate cGAS-STING pathway. Herein, we have developed a hybrid platinum prodrug (CPT-Pt (IV)) which can be triggered to release cisplatin and CPT in tumor cells. CPT-Pt (IV) with high hydrophobicity is further self-assembled with a ROS sensitive polymer (P1) and mPEG2k-DSPE into ROS responsive nanoparticles (NPs). NPs could accumulate in the tumor site to release cisplatin and CPT, resulting in DNA double damage and finally activating cGAS-STING pathway, inducing DC cells maturation and increasing tumor infiltration of CD8+ T cells on colorectal cancer mouse model. This study showed that common DNA targeted drugs can activate the cGAS-STING pathway in situ via nano delivery system, and enhance the effect of chemotherapy and immunotherapy, which provide a new strategy for clinical antitumor therapy.

Identifying major impact factors affecting the continuance intention of mHealth: a systematic review and multi-subgroup meta-analysis.

The mobile health (mHealth) industry is an enormous global market; however, the dropout or continuance of mHealth is a major challenge that is affecting its positive outcomes. To date, the results of studies on the impact factors have been inconsistent. Consequently, research on the pooled effects of impact factors on the continuance intention of mHealth is limited. Therefore, this study aims to systematically analyze quantitative studies on the continuance intention of mHealth and explore the pooled effect of each direct and indirect impact factor. Until October 2021, eight literature databases were searched. Fifty-eight peer-reviewed studies on the impact factors and effects on continuance intention of mHealth were included. Out of the 19 direct impact factors of continuance intention, 15 are significant, with attitude (ß = 0.450; 95% CI: 0.135, 0.683), satisfaction (ß = 0.406; 95% CI: 0.292, 0.509), health empowerment (ß = 0.359; 95% CI: 0.204, 0.497), perceived usefulness (ß = 0.343; 95% CI: 0.280, 0.403), and perceived quality of health life (ß = 0.315, 95% CI: 0.211, 0.412) having the largest pooled effect coefficients on continuance intention. There is high heterogeneity between the studies; thus, we conducted a subgroup analysis to explore the moderating effect of different characteristics on the impact effects. The geographic region, user type, mHealth type, user age, and publication year significantly moderate influential relationships, such as trust and continuance intention. Thus, mHealth developers should develop personalized continuous use promotion strategies based on user characteristics.

Evaluation of SARS-CoV-2-Neutralizing Nanobody Using Virus Receptor Binding Domain-Administered Model Mice.

Due to the rapid spread of coronavirus disease 2019 (COVID-19), there is an urgent requirement for the development of additional diagnostic tools for further analysis of the disease. The isolated nanobody Nb11-59 binds to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) with high affinity to neutralize the virus and block the angiotensin-converting enzyme 2- (ACE2-) RBD interaction. Here, we introduce a novel nanobody-based radiotracer named 68Ga-Nb1159. The radiotracer retained high affinity for the RBD and showed reliable radiochemical characteristics both in vitro and in vivo. Preclinical positron emission tomography (PET) studies of 68Ga-Nb1159 in mice revealed its rapid clearance from circulation and robust uptake into the renal and urinary systems. Fortunately, 68Ga-Nb1159 could specifically reveal the distribution of the RBD in mice. This study also helped to evaluate the pharmacodynamic effects of the neutralizing nanobody. Moreover, 68Ga-Nb1159 may be a promising tool to explore the distribution of the RBD and improve the understanding of the virus. In particular, this study identified a novel molecular radioagent and established a reliable evaluation method for specifically investigating the RBD through noninvasive and visual PET technology.

Preventive effects of a standardized flavonoid extract of safflower in rotenone-induced Parkinson's disease rat model.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that occurs after Alzheimer's disease. Rotenone is a neurotoxin commonly used in creating PD models. Safflower (Carthamus tinctorius L.) contains some flavonoids that are effective against neurodegenerative diseases, and it has long been used in the treatment of cerebrovascular diseases in China. In this study, we investigated the preventive effect of safflower standardized flavonoid extract (SAFE) on a rotenone-induced PD rat model. The results showed that SAFE (17.5, 35, or 70 mg kg-1·day-1) treatment modified the progressive loss in body weight, alleviated behavioral deficits, and promoted survival, especially in the middle-dose SAFE (35 mg kg-1·day-1) group. SAFE treatment significantly modifies the progressive decrease in the level of DA and its metabolites, DOPAC and HVA, 5-HT and its metabolite 5-HIAA in the St, and levels of TH-positive DA-ergic neurons in the SNpc. SAFE also inhibited the decrease in TH and DA levels and increase in Ach content in the St. SAFE (35 mg kg-1·day-1) group treatment modifying the rotenone-induced downregulation of JAK2, STAT3, and ɑ7-nAChR, and also modifying the increase in ACh in the hippocampus. SAFE preventive treatment can also partially inhibit changes in the ECS parameters associated with PD. The marker components of SAFE such as Kaempferol 3-O-rutinoside or anhydrosafflor yellow B can bind with TH, JAK2, STAT3, and ɑ7-nAChR based on molecular docking analyses. Current studies have shown that SAFE is a potential candidate for the prevention of PD.

Polymeric Nanoreactors with Chemically Tunable Redox Responsivity.

Bioresponsive nanomaterials are increasingly important in a variety of applications such as disease imaging, drug delivery, and tissue engineering. However, it remains a big challenge to manipulate response efficacy of such materials for performance optimization in a highly complex milieu in vivo. Here, we developed chemically adjustable nanoreactors (CANs) with the structure of polymeric cores and albumin shells to achieve tunable redox responsivity. In vitro characterization demonstrates stable, spherical nanoparticles of the CANs with a particle size of about 50 nm. The fluorescence activation ratios of the CANs are determined by various albumin modification densities on the shell. Meanwhile, the response sensitivity of the CANs to GSH levels (0.6-4 mM) can be tuned by acid-base properties of polymeric blocks in the core. This unique tunable redox responsivity enables the CANs suitable for probe optimization in cancer imaging both in vivo and at histological levels. Overall, this study offers a new design strategy for manipulation on performance of core/shell nanoreactors or bioresponsive nanomaterials.