APOE ε4 is risk for cognitive decline even in normal aging, but its effect on the whole-brain functional connectivity (FC) among time in young adults remain elusive. This study aimed to validate the time-by-APOE ε4 interaction on brain FC of this specific population. Longitudinal changes in neuropsychological assessments and resting-state functional magnetic resonance imaging in 26 ε4 carriers and 26 matched non-ε4 carriers were measured for about 3 years. Whole-brain FC was calculated, and a full factorial design was used to compare the difference among groups. Two-sample t test was used for post-hoc analysis. Pearson’s correlation analysis was conducted to investigate the relationships between FC and cognitive tests. Of 26 specially appointed ROIs, left superior temporal gyrus (TG) was most sensitive to the effect of time-by-gene interaction. Specifically, the alteration of FC was distributed between the left TG and right TG with GRF correction (voxel-P < 0.001, cluster-P < 0.05), and decreased in ε4 carriers while increased in non-ε4. The main effect of gene showed ε4 carriers has lower FC between left TG and right middle frontal gyrus as compared with non-ε4 both at baseline and follow-up study; ε4 carriers has lower FC between left TG and right supramarginal as compared with non-ε4 at baseline, but no difference in follow-up study. The time-by-APOE ε4 interaction on brain FC was demonstrated at a young age, and left TG was the earliest affected brain regions. The young adult ε4 carriers experience decreased FC among time in the absence overt clinical symptoms.

AIMS:Cardiac cycle morphological changes can accelerate plaque growth proximal to myocardial bridging (MB) in the left anterior descending artery (LAD). To assess coronary computed tomography angiography (CCTA)-based vascular radiomics for predicting proximal plaque development in LAD MB. METHODS AND RESULTS:Patients with repeated CCTA scans showing LAD MB without proximal plaque in index CCTA were included from Jinling Hospital as a development set. They were divided into training and internal testing in an 8:2 ratio. Patients from four other tertiary hospitals were set as external validation set. The endpoint was proximal plaque development of LAD MB in follow-up CCTA. Four vascular radiomics models were built: MB centreline (MB CL), proximal MB CL (pMB CL), MB cross-section (MB CS), and proximal MB CS (pMB CS), whose performances were evaluated using area under the receiver operating characteristic curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI). In total, 295 patients were included in the development (n = 192; median age, 54 ± 11 years; 137 men) and external validation sets (n = 103; median age, 57 ± 9 years; 57 men). The pMB CS vascular radiomics model exhibited higher AUCs in training, internal test, and external sets (AUC = 0.78, 0.75, 0.75) than the clinical and anatomical model (all P < 0.05). Integration of the pMB CS vascular radiomics model significantly raised the AUC of the clinical and anatomical model from 0.56 to 0.75 (P = 0.002), along with enhanced NRI [0.76 (0.37-1.14), P < 0.001] and IDI [0.17 (0.07-0.26), P < 0.001] in the external validation set. CONCLUSION:The CCTA-based pMB CS vascular radiomics model can predict plaque development in LAD MB.

In recent years, branched or star-shaped Au nanostructures composed of core and protruding arms have attracted much attention due to their unique optical properties and morphology. As the clinically adapted nanoagent, prussian blue (PB) has recently gained widespread attention in cancer theranostics with potential applications in magnetic resonance (MR) imaging. In this article, we propose a hybrid star gold nanostructure（Au-star@PB）as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI)/ photoacoustic imaging（PAI） and photothermal therapy (PTT) of tumors. Importantly, the Au-star@PB nanoparticles function as effective MRI/PA contrast agents in vivo by increasing T1-weighted MR/PAI signal intensity and as effective PTT agents in vivo by decreasing the tumor volume in MCF-7 tumor bearing BALB / c mouse model as well as in vitro by lessening tumor cells growth rate. Interestingly, we found the main photothermal effect of Au-star@PB is derived from Au-star, but not PB. In summary, the hybrid structure of Au-star@PB NPs with good biological safety, significant photostability, dual imaging capability, and high therapeutic efficiency, might offer a novel avenue for the future diagnosis and treatment of cancer.

Recently, the study of the relationship between lipid metabolism and cancer has evolved. The characteristics of intratumoral and peritumoral fat are distinct and changeable during cancer development. Subcutaneous and visceral adipose tissue are also associated with cancer prognosis. In non-invasive imaging, fat quantification parameters such as controlled attenuation parameter, fat volume fraction, and proton density fat fraction from different imaging methods complement conventional images by providing concrete fat information. Therefore, measuring the changes of fat content for further understanding of cancer characteristics has been applied in both research and clinical settings. In this review, the authors summarize imaging advances in fat quantification and highlight their clinical applications in cancer precaution, auxiliary diagnosis and classification, therapy response monitoring, and prognosis.

BackgroundSjögren’s syndrome (SjS) associated with systemic lupus erythematosus (SjS-SLE) was considered a standalone but often-overlooked entity.PurposeTo assess altered spontaneous brain activity in SjS-SLE and SjS using amplitude of low-frequency fluctuation (ALFF).Material and MethodsSixteen patients with SjS-SLE, 17 patients with SjS, and 17 matched controls underwent neuropsychological tests and subsequent resting-state functional magnetic resonance imaging (fMRI) examinations. The ALFF value was calculated based on blood oxygen level dependent (BOLD) fMRI. Statistical parametric mapping was utilized to analyze between-group differences and multiple comparison was corrected with Analysis of Functional NeuroImages 3dClustSim. Then, the ALFFs of brain regions with significant differences among the three groups were correlated to corresponding clinical and neuropsychological variables by Pearson correlation.ResultsALFF differences in the bilateral precuneus/posterior cingulate cortex (PCC), right parahippocampal gyrus/caudate/insula, and left insula were found among the three groups. Both SjS-SLE and SjS displayed decreased ALFF in the right parahippocampal gyrus, right insula, and left insula than HC. Moreover, SjS-SLE showed wider decreased ALFF in the bilateral precuneus and right caudate, while the SjS group exhibited increased ALFF in the bilateral PCC. Additionally, patients with SjS-SLE exhibited lower ALFF values in the bilateral PCC and precuneus than SjS. Moreover, ALFF values in the right parahippocampal gyrus and PCC were negatively correlated to fatigue score and disease duration, respectively, in SjS-SLE.ConclusionSjS-SLE and SjS exhibited common and different alteration of cerebral functional segregation revealed by AlFF analysis. This result appeared to indicate that SjS-SLE might be different from SjS with a neuroimaging standpoint.

Individuals with subjective cognitive decline (SCD) are more likely to develop into Alzheimer disease (AD) in the future. Resting-state functional magnetic resonance imaging (rs-fMRI) studies have shown alterations of intrinsic brain activity (IBA) in SCD individuals. However, rs-fMRI studies to date have mainly focused on static characteristics of IBA, with few studies reporting dynamics- and concordance-related changes in IBA indices in SCD individuals. To investigate these aberrant changes, a temporal dynamic analysis of rs-fMRI data was conducted on 94 SCD individuals (71.07 ± 6.18 years, 60 female), 75 (74.36 ± 8.42 years, 35 female) mild cognitive impairment (MCI) patients, and 82 age-, gender-, and education-matched controls (NCs; 73.88 ± 7.40 years, 49 female) from the Alzheimer's Disease Neuroimaging Initiative database. The dynamics and concordance of the rs-fMRI indices were calculated. The results showed that SCD individuals had a lower amplitude of low-frequency fluctuations dynamics in bilateral hippocampus (HP)/parahippocampal gyrus (PHG)/fusiform gyrus (FG) and bilateral cerebellum, a lower fractional amplitude of low-frequency fluctuation dynamics in bilateral precuneus (PreCu) and paracentral lobule, and a lower regional homogeneity dynamics in bilateral cerebellum, vermis, and left FG compared with the other two groups, whereas those in MCI patients were higher (Gaussian random field–corrected, voxel-level P < 0.001, cluster-level P < 0.05). Furthermore, SCD individuals had higher concordance in bilateral HP/PHG/FG, temporal lobe, and left midcingulate cortex than NCs, but those in MCI were lower than those in NCs. No correlation between concordance values and neuropsychological scale scores was found. SCD individuals showed both dynamics and concordance-related alterations in IBA, which indicates a compensatory mechanism in SCD individuals. Temporal dynamics analysis offers a novel approach to capturing brain alterations in individuals with SCD.

Background: Hypothesis-driven functional connectivity (FC) analyses have revealed abnormal functional interaction of regions or networks involved in pain processing in episodic migraine patients. We aimed to investigate the resting-state FC patterns in episodic migraine by combining data-driven voxel-wise degree centrality (DC) calculation and seed-based FC analysis. Methods: Thirty-nine patients suffering from episodic migraine without aura and 35 healthy controls underwent clinical assessment and functional MRI. DC was analyzed voxel-wise and compared between groups, and FC of regions with DC differences were further examined using a seed-based approach. Results: Compared with the control group, the migraine group showed increased and decreased DC in the right posterior insula and left crus I, respectively. Seed-based FC analyses revealed that migraine patients demonstrated increased right posterior insula connections with the postcentral gyrus, supplementary motor area/paracentral lobule, fusiform gyrus and temporal pole. The left crus I showed decreased FC with regions of the default mode network (DMN), including the medial prefrontal cortex (mPFC), angular gyrus, medial and lateral temporal cortex in patients with migraine. Furthermore, pain intensity positively correlated with DC in the right amygdala/parahippocampal gyrus, and migraine frequency negatively correlated with FC between the left crus I and mPFC. Conclusion: Patients with episodic migraine without aura have increased FC with the right posterior insula and decreased FC within the DMN, which may underlie disturbed sensory integration and cognitive processing of pain. The left crus I-mPFC connectivity may be a useful biomarker for assessing migraine frequency.

Background Episodic migraine (EM) is associated with alterations in functional connectivity of several regions or resting-state networks, but it is not well known how large-scale functional connectivity pattern of the whole brain is affected in chronic migraine (CM). Methods Fifty-six migraineurs without aura (39 with EM, 17 with CM) and 35 healthy controls (HC) underwent clinical assessment and resting-state functional MRI. Functional connectivity density (FCD) was calculated in a voxel-wise way to examine large-scale brain network property over the whole brain. Results Compared with HC, both migraine groups showed increased local FCD in the left orbital frontal gyrus (OFG), right hippocampus/parahippocampal gyrus (HP/PHG), cerebellum, and decreased local FCD in the bilateral dorsolateral prefrontal cortex. Local FCD of the left OFG increased in CM compared to EM. In comparison with HC, EM showed increased local FCD in the left middle temporal gyrus, and CM exhibited decreased local FCD in the left sensorimotor cortex and bilateral precuneus. Furthermore, relative to HC, EM showed increased distant FCD in the right PHG while CM showed increased distant FCD in the right HP and OFG. Importantly, majority of the observed local and distant FCD alterations were associated with migraine frequency across all migraineurs. Conclusion Patients with higher migraine frequency present more extensive and pronounced functional connectivity dysfunctions in regions involved in pain processing and modulation. FCD, especially local FCD may be a sensitive biomarker for examining the neural mechanism of migraine.

目的 运用静息态功能磁共振成像(resting-state functional magnetic resonance imaging,rs-fMRI)脑功能网络分析技术,探讨2型糖尿病(type 2 diabetes mellitus,T2DM)患者的脑功能网络改变.材料与方法前瞻性收集24例T2DM患者与26名健康志愿者进行3.0 T MRI扫描,获得受试者的rs-fMRI数据.将自动解剖标签(automated anatomical labeling,AAL)模板定义的90个大脑区域作为复杂网络的节点,利用Pearson相关建立90个节点之间的相关关联.选定阈值,构建病变组和对照组受试者的无向网络,得到量化的网络指标——平均效率,聚类系数、节点度分布和模块化组织.结果 在不同的阈值条件下,病变组脑功能网络的全局效率及平均聚类系数较对照组变小(P＜0.05);病变组节点度大于8.5的节点较对照组少;病变组的脑功能网络模块数较对照组多,且病变组每个模块的组分都发生了改变.结论 T2DM患者脑功能网络的全局效率及聚类系数下降,T2DM患者脑功能网络的模块数量及各模块组分发生改变,提示:(1) T2DM患者脑功能连接受损;(2)与疾病相关的某些功能皮层发生改变和重组,局部脑区可能出现功能代偿;(3)脑功能网络分析技术为T2DM患者提供了无创性评估中枢改变的新方法.

Neuroimaging studies have implicated abnormal brain microstructure in episodic migraine (EM), but whether the pattern is altered during migraine chronification is not well known. Fifty-six patients with migraine without aura, including 39 EM patients and 17 chronic migraine (CM) patients, and 35 healthy controls (HCs) were enrolled. Voxel-based morphometry analysis was performed to assess gray matter (GM) volume differences among groups and their association with clinical feature was examined. Compared with the HC group, both migraine groups showed increased GM volume in the periaqueductal grey matter (PAG) and decreased GM volume in the anterior cingulate cortex (ACC). The left hippocampus/parahippocampal gyrus (PHG) volume of the HC group was smaller than that of the EM group, but was larger than that of the CM group. For the dorsolateral prefrontal cortex (dlPFC), the EM group showed the smallest GM volume while the CM group had the largest volume. Higher headache frequency was associated with greater GM volume in the PAG and dlPFC, but was associated with smaller GM volume in the ACC and hippocampus/PHG across all patients. GM volume changes in regions involved in pain generation and control are potential neural mechanism underlying migraine, and are associated with migraine types and headache frequency.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. It is known that hyaluronic acid (HA) binds CD44 receptors, which are overexpressed on the surface of TNBC cells. To optimize the targeting ability of HA, in this study we coated gold nanobipyramids (GBPs) with high and low molecular weight HA (380 kDa and 102 kDa), named GBPs@h-HA and GBPs@l-HA, respectively. GBPs@l-HA and GBPs@h-HA had excellent stability when dispersed in water and PBS (pH 7.4) for seven days. The HA density was calculated by the ratio of HA to GBPs@l-HA and GBPs@h-HA, which was 13.22 and 4.77, respectively. The two nanoparticles displayed good photostability, which was evaluated by their photothermal performance and similar biocompatibility. Inductively coupled plasma atomic emission spectrometry (ICP-AES) revealed superior cellular uptake of GBPs@h-HA over GBPs@l-HA. Upon 808 nm laser irradiation, the GBPs@h-HA also showed higher therapeutic efficacy than GBPs@l-HA both in vitro and in vivo. Overall, our study demonstrates that the molecular weight of HA plays an important role in the targeting ability and thus photothermal therapeutic efficacy of HA-coated gold nanobipyramids.

This study aims to explore the hippocampus-based functional connectivity patterns in young, healthy APP and/or presenilin-1/2 mutation carriers and APOE ε4 subjects. Seventy-eight healthy young adults (33 male, mean age 24.0 ± 2.2 years; 18 APP and/or presenilin1/2 mutation carriers [APP/presenilin-1/2 group], 30 APOE ε4 subjects [APOE ε4 group], and 30 subjects without the above-mentioned genes [control group]) underwent resting-state functional MR imaging and neuropsychological assessments. Bilateral hippocampus functional connectivity patterns were compared among three groups. The brain regions with statistical differences were then extracted, and correlation analyses were performed between Z values of the brain regions and neuropsychological results. Compared with control group, both APOE ε4 group and APP/presenilin-1/2 group showed increased functional connectivity in medial prefrontal cortex and precuneus for the seeds of bilateral hippocampi. The APOE ε4 group displayed increased functional connectivity from bilateral hippocampi to the left middle temporal gyrus compared with the control group. Moreover, compared with the APP/presenilin-1/2 group, the APOE ε4 group also had markedly increased functional connectivity in right hippocampus-left middle temporal gyrus. The Z values of right hippocampus-left middle temporal gyrus correlated with various neuropsychological results across all the subjects, as well as in APOE ε4 group. Young healthy adults carrying APOE ε4 and APP/presenilin-1/2 displayed different hippocampus functional connectivity patterns, which may underlie the discrepant mechanisms of gene-modulated cognitive dysfunction in Alzheimer’s disease.

Neuroinflammation has an important influence in pathogenesis of acute hepatic encephalopathy (AHE). 11C-PK11195 and 18F-DPA-714 targeted to translocator protein (TSPO) have potential application in positron emission tomography (PET) as a molecular probe of neuroinflammation. The aim of this study was to compare these two radiotracers and their effectiveness in detecting neuroinflammation for the imaging of AHE rat models. Furthermore, using the new radiotracer 18F-DPA-714, we analyzed the effectiveness of therapeutic treatment for neuroinflammation in AHE. First, we performed a comparative study of 11C-PK1195 and 18F-DPA-714 PET to image neuroinflammation in AHE rats induced by thioacetamide. Twenty-four rats were divided into either control group (n = 12) or AHE group (n = 12). Next, each group was subdivided depending on the radiotracer used during PET imaging (n = 6). Radiotracer uptake values encompassing the whole brain were compared. Lastly, we used the optimized tracer to monitor anti-neuroinflammation effects in AHE-induced rats. Forty-six rats were divided into four groups: [normal saline (NS) group (n = 13), minocycline (MINO) group (n = 11), dexamethasone (DEXA) group (n = 11), MINO+DEXA group (n = 11)]. 18F-DPA-714 PET was performed and the uptake values were calculated. The rotarod test, biochemical indices, and histopathological examinations were quantitatively measured and compared. AHE rats showed reduced motor ability, elevated ammonia levels, and higher liver function indices (all P < 0.05) with unchanged inflammatory factors (all P > 0.05), compared to control group. Both 11C-PK11195 and 18F-DPA-714 PET can detect neuroinflammation of AHE rats. Behavioral studies showed that MINO and/or DEXA improved the motor ability in AHE rats (P < 0.05); however, no differences were found for liver function or inflammatory markers among the four groups (all P > 0.05). The average uptake values of whole brain and multiple brain areas in the MINO+DEXA group were lower compared to all other groups (all P < 0.05), which was demonstrated by CD11b stains of microglia. Our results show that both 11C-PK11195 and 18F-DPA-714 PET can detect neuroinflammation in AHE-induced rat models. Additionally, the combined use of minocycline and dexamethasone can effectively inhibit neuroinflammation in AHE-induced rats, which can be sensitively monitored by 18F-DPA-714 PET.

A variety of nanocarriers have been designed to deliver photosensitizers (PSs) and promote the clinical applications of photodynamic therapy (PDT). However, most of them suffer from insufficient loading capability, premature leakage, and/or unstable therapeutic efficacy. Herein, we constructed a novel nanocomposite (TGP@MOS) with a benzene-bridged mesoporous organosilica shell and a triangular gold nanoprism core. The TGP@MOS could load model PS molecules, zinc phthalocyanine (ZnPc), with high loading capacity (11.8 wt%) and minimal premature leakage (only 2.6% after incubation in PBS with 10% FBS for 60 h) viaπ-π stacking interactions and hydrophobic interactions. We demonstrated that the obtained TGP@MOS-ZnPc could realize timely coordinated photodynamic/photothermal therapy upon single irradiation, and thus stabilize and maximize the therapeutic efficacy of phototherapy both in vitro and in vivo. Other advantages of TGP@MOS-ZnPc include excellent water solubility, stability, hemocompatibility and biocompatibility.

Enhancing the tumor-targeting delivery of chemotherapeutic drugs is important yet challenging for improving therapeutic efficacy and reducing the side effects. Here, we first construct a drug delivery system for targeting tumor acidic microenvironment by modification of pH (low) insertion peptide (pHLIP) on mesoporous organosilica nanoparticles (MONs). The MONs has thioether-bridged framework, uniform diameter (60 nm), good biocompatibility, and high doxorubicin (DOX) loading capacity (334 mg/g). The DOX loaded in the pHLIP modified MONs can be released responsive to glutathione and low pH circumstance, ensuring the chemotherapeutic drug exerts higher cytotoxic effects to cancer cells than normal cells because of high intracellular GSH of tumor cells and low pH of tumor microenvironment. Moreover, the engineered MONs exhibit higher cellular uptake in pH 6.5 medium by MDA-MB-231 and MCF-7 cells than the particles decorated with polyethylene glycol (PEG). Importantly, the pHLIP-mosaic MONs with DOX displays better cytotoxic effects against the breast cancer cells in pH 6.5 medium than pH 7.4 medium. The in vivo experiments demonstrate that the pHLIP modified MONs are accumulated in the orthotopic breast cancer via targeting to acidic tumor microenvironment while no serious pathogenic effects was observed. After loading DOX, the pHLIP-modified MONs display better therapeutic effects than the control groups on the growth of MCF-7 breast cancers, showing promise for enhancing chemotherapy.

Herein, we demonstrate a coating-etching strategy to directly synthesize hollow Prussian blue (PB) nanocubes with well-dispersed Ag nanoparticles (denoted as Ag-HPB). The method is accomplished by introduction of PB precursors, K3Fe(CN)6 and Fe3+ into a reaction system containing AgNO3 and ascorbic acid, in which a series reactions contain formation of Ag nanoparticles, coating of PB on the nanoparticles, and diffusion of Ag into the PB frameworks occur. The strategy for preparation of the hollow structured Ag-HPB is intrinsically simple and does not require pre-preparation of any sacrificial templates or toxic etching agents. The obtained Ag-HPB nanocubes possess uniform size (69 nm), well-defined hollow structure, strong near-infrared photothermal conversion capacity, and excellent photoacoustic and magnetic resonance imaging abilities. Furthermore, an injectable photothermal implants are prepared for the first time by mixing the Ag-HPB nanocubes with clinically used biological glue, which significantly enhance photothermal anti-tumor efficacy, showing great potential for clinical tumor treatment.

hMLH1 is one of the mismatch genes closely related to the occurrence of gastric cancer. Epigenetic regulation may play more important roles than gene mutations in DNA damage repair genes to drive carcinogenesis. In this article, we discuss the role of epigenetic changes, especially histone modifications in the regulation of hMLH1 alternative splicing. Our results showed that hMLH1 delEx10, delEx11, delEx10-11, delEx16 and delEx17 transcripts were ubiquitous in sporadic Chinese gastric cancer patients and gastric cancer cell lines. Lower level of H4K16ac and H3ac was detected in hMLH1 exon 10-11 region in gastric cancer cell lines when compared with human gastric mucosal epithelial cell line GES-1. A significant decrease of hMLH1 delEx11 and delEx10-11 was observed in gastric cancer cell lines after trichostatin A treatment. H3K36me3 and H3K4me2 levels were lower in hMLH1 exon 10-11 and exon 16-17 regions in gastric cancer lines when compared with GES-1. Aberrant transcripts such as hMLH1 delEx11 and delEx10-11 were significantly higher in gastric cancer cell lines after small interfering RNA-mediated knockdown of SETD2 (the specific methyltransferase of H3K36). The hMLH1 delEx10 and delEx10-11 transcripts were increased after interference of SRSF2. Taken together, our study demonstrates that lower level of histone acetylation and specific histone methylation such as H3K36me3 correlate with aberrant transcripts in hMLH1 exon 10-11 region. SRSF2 may be involved in these specific exons skipping as well.

In this study, we used resting-state functional magnetic resonance imaging to explore the genetic effects of amyloid precursor protein (APP) or presenilins mutation and apolipoprotein E (APOE) ε4 on the default-mode network (DMN) in cognitively intact young adults (24.1 ± 2.5 years). Both the APP or presenilin-1/2 group and the APOE ε4 group had significantly lower DMN functional connectivity (FC) in the some brain regions like precuneus/middle cingulate cortices (PCu/MCC) than controls (AlphaSim corrected, P < 0.05). Only a lower FC tendency was demonstrated (control < APOE ε4 < APP or presenilin-1/2 group). Moreover, lower FC in PCu/MCC is correlated with some neuropsychological assessments such as similarity test in APOE ε4 group. These findings indicate that DMN FC alteration in APP or presenilin-1/2 or APOE ε4 subjects is prior to the occurrence of neurological alterations and clinical symptoms, and DMN FC might be a valuable biomarker to detect genetic risk in the preclinical stage.

Objective: To explore genetic effects of amyloid precursor protein (APP), presenilin-1/2 and apolipoprotein E (APOE) s4 on brain structural and functional alterations in cognitively normal young adults. Materials and methods: Eighty healthy adults (mean age 24.0 +/- 2.5 years; n = 18, APP/presenilin-1/2 group; n = 31, APOE epsilon 4 group; n = 31, control group [without above-mentioned gene mutation]) underwent high resolution Tl-weighted 3D anatomical imaging, resting-state functional MR imaging and neuropsychological assessments. We used voxel-based morphometry and regional homogeneity (ReHo) algorithms to investigate brain structural and functional changes among three groups, and performed correlation analyses between the brain regions with statistically significant difference and neuropsychological results. Results: No brain structural changes were found, however, ReHo values were increased in right parietal-frontal lobes in APOE epsilon 4 group, and decreased in the left middle temporal gyrus in APP/presenilin-1/2 group compared with controls (all P < 0.05). Compared with APOE epsilon 4 group, decreased ReHo values of bilateral temporal lobes were shown in APP/presenilin-1/2 group (P < 0.05). ReHo values of right superior frontal gyrus in APOE s4 group positively correlated with neuropsychological tests scores(P < 0.05). Conclusion: Cognitively normal young adults carrying APOE s4 or APP/presenilin-1/2 had different spontaneous brain activity patterns without cerebral structural differences.

Two-dimensional (2D) MoS2 nanosheets have attracted increasing attention in recent years owing to their various fascinating properties, particularly excellent near-infrared (NIR) photothermal feature. In this study, we synthesized a novel NIR-light-triggered drug-delivery system by wrapping MoS2 nanosheets around doxorubicin (Dox)-loaded periodic mesoporous organosilicas (PMOs) and then decorating with polyethylene glycol (PEG) to form a PMO-Dox@MoS2-PEG nanoplatform for the first time. The obtained PMO-Dox@MoS2-PEG nanoplatforms had a uniform diameter (326 nm), high Dox loading capacity (160 μg mg-1 PMOs), excellent photothermal transformation ability, and good dispersibility in physiological conditions. Note that the Dox was almost completely blocked in the PMO-Dox@MoS2-PEG nanoplatforms, and the photothermal effect of the MoS2 nanosheets could efficiently trigger the release of Dox under an 808 nm laser irradiation. Simultaneously, the PMO-Dox@MoS2-PEG nanoplatforms realized a combined chemotherapy and photothermal therapy for liver cancer cells and breast cancer cells upon NIR laser irradiation. Compared with the single photothermal therapy or chemotherapy, the combined treatment had an improved synergistic therapeutic efficacy. We believe the NIR-light-triggered drug-delivery system with synergistic chemo-photothermal therapeutic property provides a promising strategy for cancer treatment.