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Tumor vascular blockade is a promising strategy for adjuvant cancer treatment. In this work, a self-delivery nanomedicine is developed based on a vascular disruptor and photosensitizer for tumor synergistic therapy. Specifically, this nanomedicine (designated as CeCA) is comprised of combretastatin A4 (CA4) and chlorine e6 (Ce6) by self-assembly technique. Among which, CA4 could not only induce tubulin inhibition for chemotherapy but also disrupt the vasculature to cause tumor hemorrhage. Moreover, Ce6 is able to generate lots of singlet oxygen (

Long noncoding RNAs (lncRNAs) exert essential effects in regulating myocardial ischemia/reperfusion (MI/R)-induced injury. This work intended to explore the functions of lncRNA SOX2-OT and its regulatory mechanism within MI/R-induced injury. In this study, gene expression was determined by RT-qPCR. Western blotting was applied for the detection of protein levels. Pro-inflammatory cytokine concentrations, cardiomyocyte viability, and apoptosis were detected via ELISA, CCK-8 and flow cytometry. In the in vitro model, SOX2-OT and YY1 were both upregulated, while miR-186-5p was downregulated. SOX2-OT knockdown attenuated oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cardiomyocyte dysregulation through relieving inflammation, promoting proliferation, and reducing apoptosis in OGD/R-treated H2C9 cells. SOX2-OT positively regulated YY1 expression via miR-186-5p. Moreover, miR-186-5p inhibition or YY1 upregulation abolished the effects of SOX2-OT blocking on the inflammatory responses, proliferation, and apoptosis of OGD/R-challenged H2C9 cells. In conclusion, our results, for the first time, demonstrated that SOX2-OT inhibition attenuated MI/R injury in vitro via regulating the miR-186-5p/YY1 axis, offering potential therapeutic targets for MI/R injury treatment.

The optimum multiparameter (OMP) method was often used to determine the percentages of water masses based on temperature, salinity and other parameters, like nutrient or dissolved oxygen (DO). There are a number of water masses in the East China Sea (ECS), a marginal sea of the western Pacific Ocean. However, it is difficult to clarify the proportion of water masses using traditional parameters, such as temperature, salinity, nutrient or DO because of the occurring of intensive biogeochemical processes in the near shore and shelf areas. Here, we reported the use of 234U/238U activity ratio embedded in the OMP method. The results indicate that seawater in the northern ECS mainly consisted of the estuarine water of Changjiang River (CEW), Kuroshio water (KW), and Yellow Sea Coastal Current (YSCC). In March 2017, the CEW only influenced the offshore waters shallower than 30 m; the KW affected the east edge and the YSCC contributed more than 75% in the northern ECS.

Materials that exhibit X-ray-excited luminescence have great potential in radiation detection, security inspection, biomedical applications and X-ray astronomy1–5. However, high-performance materials are almost exclusively limited to ceramic scintillators, which are typically prepared under high temperatures6. Herein we report metal-free organic phosphors based on a molecular design that supports efficient triplet exciton harvesting to enhance radioluminescence. These organic scintillators exhibit a detection limit of 33 nGy s–1, which is 167 times lower than the standard dosage for X-ray medical examination and we demonstrate their potential application in X-ray radiography. These findings provide a fundamental design principle and new route for the creation of promising alternatives to incumbent inorganic scintillators. Furthermore, they offer new opportunities for development of flexible, stretchable X-ray detectors and imagers for non-destructive radiography testing and medical imaging. Organic, metal-free materials that act as efficient X-ray scintillators could bring new opportunities for X-ray imaging.

Effective charge separation is essential in plasmon-mediated photochemistry and is usually achieved by constructing plasmon–semiconductor interfaces, which is usually challenging. In this work, by monitoring the plasmon-mediated silver oxidation with in situ Raman spectroscopy, we demonstrate that the adsorbed thiophenol molecules could modulate the rate of photochemical reactions by tuning the charge separation at the plasmon–molecule interfaces. It is found that the thiophenol molecules with strong electron-withdrawing or donating functional groups could accelerate or decelerate the rate of plasmon-mediated silver oxidation, respectively. Owing to the easy tuning of the electronic structures of organic molecules via substitution, our method provides a versatile and convenient approach for the fine modulation of plasmon-mediated photochemical reactions.

Background: Subjective cognitive decline (SCD) is considered as the first symptomatic manifestation of Alzheimer’s disease (AD), which is also affected by different cultural backgrounds. Establishing cross-cultural prediction models of SCD is challenging. Objective: To establish prediction models of SCD available for both the Chinese and European populations. Methods: In this project, 330 SCD from China and 380 SCD from Germany are intended to be recruited. For all participants, standardized assessments, including clinical, neuropsychological, apolipoprotein E (APOE) genotype, blood, and multi-parameter magnetic resonance imaging (MRI) at baseline will be conducted. Participants will voluntarily undergo amyloid positron emission tomography (PET) and are classified into amyloid-β (Aβ) positive SCD (SCD+) and Aβ negative SCD (SCD-). First, baseline data of all SCD individuals between the two cohorts will be compared. Then, key features associated with brain amyloidosis will be extracted in SCD+ individuals, and the diagnosis model will be established using the radiomics method. Finally, the follow-up visits will be conducted every 12 months and the primary outcome is the conversion to mild cognitive impairment or dementia. After a 4-year follow-up, we will extract factors associated with the conversion risk of SCD using Cox regression analysis. Results: At present, 141 SCD from China and 338 SCD from Germany have been recruited. Initial analysis showed significant differences in demographic information, neuropsychological tests, and regional brain atrophy in SCD compared with controls in both cohorts. Conclusion: This project may be of great value for future implications of SCD studies in different cultural backgrounds. Trial registration: ClinicalTrials.gov, NCT04696315. Registered 3 January 2021.

This study aimed to investigate the effect of PRECEDE-PROCEED-Model-based health education on the life quality of patients with gastric cancer after surgery. Also, the effect of this model was evaluated on 5-HTT gene expression as a gene related to depression. For this purpose, a total of 32 gastric cancer patients who were hospitalized in this hospital between March 2019 and September 2020 were enrolled in this study after surgery and, according to the time of admission, were divided into the control group and observation group, with 16 patients in each group. Patients in the control group were nursed regularly, while those in the observation group, in addition to the regular nursing, would receive the PRECEDE-PROCEED-Model-based health education. Post-surgery life quality of patients in two groups was compared from the following aspects: Rehabilitation process, pain assessment, rate of complications and The Short-Form (SF-36) Health Survey. The expression of the 5-HTT gene was performed by the Real-time qPCR technique. The results of this study showed that after surgery, the extubation time and the time of hospital discharge of patients in the observation group were all earlier than those in the control group, while the score of pain assessment and rate of complication was much lower in the observation group, and the SF-36 score of patients was much higher (all P < 0.05). The results of 5-HTT gene expression showed that there was no significant difference between the control and observation groups before the intervention. But one month after the intervention, gene expression in the observation group was significantly reduced compared to the control group (p

Background Brain-derived neurotrophic factor (BDNF) is vital for neuronal survival and growth, regulation of synaptic plasticity, and cognitive function. Previous studies examined the role of BDNF in susceptibility to attention deficit hyperactivity disorder (ADHD). The current study examined the association between BDNF gene polymorphisms and ADHD in Chinese children. Methods Participants were 195 medication-naive ADHD children and 263 unaffected healthy controls. ADHD symptoms were diagnosed using the Vanderbilt ADHD Diagnostic Parental Rating Scale according to the Diagnostic and Statistical Manual of Mental Disorders-5. Five BDNF single nucleotide polymorphisms were detected using improved multiplex ligation detection reaction. Alleles and genotype frequency were examined using Chi-square tests. Correlations were examined using multivariate logistic regression analysis in the ADHD and control groups. Results The results revealed that rs12291186 with one or both mutated allele(s) was significantly associated with reduced likelihood of ADHD (OR = 0.13, 95% CI: 0.02–0.77) and ADHD-Combined (OR = 0.10, 95% CI: 0.01–0.85). Children with genotype AA or CA in rs10835210 exhibited increased risk of ADHD (OR = 3.29, 95% CI: 1.03–10.55) and ADHD-Combined (OR = 4.45, 95% CI: 1.10–17.96) compared with genotype CC children. No significant associations were found between rs6265, rs7103411, rs7103873 polymorphisms and ADHD. Limitations Participants were recruited from urban areas. We were unable to examine all potential confounding factors. Conclusions BDNF gene polymorphisms of rs12291186 and rs10835210 were related to the occurrence of ADHD. These findings provide new insight on mechanisms underlying BDNF gene in ADHD.

Sporadic degenerative ataxia patients fall into 2 major groups: multiple system atrophy with predominant cerebellar ataxia (MSA-C) and sporadic adult-onset ataxia (SAOA). Both groups have cerebellar volume loss, but little is known about the differential involvement of gray and white matter in MSA-C when compared with SAOA.The objective of this study was to identify structural differences of brain gray and white matter between both patient groups.We used magnetic resonance imaging to acquire T1-weighted images and diffusion tensor images from 12 MSA-C patients, 31 SAOA patients, and 55 healthy controls. Magnetic resonance imaging data were analyzed with voxel-based-morphometry, tract-based spatial statistics, and tractography-based regional diffusion tensor images analysis.Whole-brain and cerebellar-focused voxel-based-morphometry analysis showed gray matter volume loss in both patient groups when compared with healthy controls, specifically in the cerebellar areas subserving sensorimotor functions. When compared with controls, the SAOA and MSA-C patients showed white matter loss in the cerebellum, whereas brainstem white matter was reduced only in the MSA-C patients. The tract-based spatial statistics revealed reduced fractional anisotropy within the pons and cerebellum in the MSA-C patients both in comparison with the SAOA patients and healthy controls. In addition, tractography-based regional analysis showed reduced fractional anisotropy along the corticospinal tracts in MSA-C, but not SAOA.Although in our cohort extent and distribution of gray and white matter loss were similar between the MSA-C and SAOA patients, magnetic resonance imaging data showed prominent microstructural white matter involvement in the MSA-C patients that was not present in the SAOA patients. Our findings highlight the significance of microstructural white matter changes in the differentiation between both conditions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Deubiquitinases (DUBs) and noncoding RNAs have been the subjects of recent extensive studies regarding their roles in lung cancer, but the mechanisms involved are largely unknown. In our study, we used The Cancer Genome Atlas data set and bioinformatics analyses and identified USP21, a DUB, as a potential contributor to oncogenesis in non-small-cell lung cancer (NSCLC). We further demonstrated that USP21 was highly expressed in NSCLCs. We then conducted a series of in vitro and in vivo assays to explore the effect of USP21 on NSCLC progression and the underlying mechanism involved. USP21 promoted NSCLC cell proliferation, migration, and invasion and in vivo tumor growth by stabilizing a well-known oncogene, Yin Yang-1 (YY1), via mediating its deubiquitination. Furthermore, YY1 transcriptionally regulates the expression of SNHG16. Moreover, StarBase bioinformatics analyses predicted that miR-4500 targets SNHG16 and USP21. A series of in vitro experiments indicated that SNHG16 increased the expression of USP21 through miR-4500. In summary, the USP21/YY1/SNHG16 axis plays a role in promoting the progression of NSCLC. Therefore, the USP21/YY1/SNHG16/miR-4500 axis may be a potential therapeutic target in NSCLC treatment., Lung cancer: Targeting a vicious circle Therapies targeting a molecular feedback loop involved in tumor growth may prove valuable for treating non-small-cell lung cancer. Fangbao Ding, Jianbing Huang, and co-workers at Shanghai Jiao Tong University in Shanghai, China, have shown how an enzyme called USP21 promotes cancer cell proliferation and tumor growth in non-small-cell lung cancer. The team took cancerous and non-cancerous lung tissue samples from 42 patients, and analyzed the expression and behavior of USP21. The enzyme was highly expressed in cancerous tissues, where it stabilized a known gene with the potential to cause cancer called YY1. This gene also regulated the expression of a particular RNA molecule, which in turn worked to increase levels of USP21. This cyclical process encouraged the proliferation, migration and invasion of non-small-cell lung cancer cells, and may provide a future therapeutic target.

Restricted by the energy-gap law, the development of bright near-infrared (near-IR) fluorescent luminophors in the solid state remains a challenge. Herein, we report a new design strategy for realizing high brightness and deep-red/near-IR-emissive organic molecules based on the incorporation of a hybridized local and charge-transfer (HLCT) state and separated dimeric stacks into one aggregate. Experimental and theoretical analyses show that this combination not only contributes to high photoluminescent quantum yields (PLQYs) but also significantly lessens the energy gap. The fluorophore BTA-TPA exhibits excellent fluorescence performance, achieving a PLQY of 54.8% for the fluorescence peak at 690 nm, which is among the highest reported for near-IR fluorescent excimers. In addition, because of its bioimaging performance, the designed luminophor has potential for use as a deep-red fluorescent probe for biomedical applications. This research opens the door for developing deep-red/near-IR emissive materials with high PLQYs., A strategy is proposed to realize high-efficiency, solid-state and NIR-emissive organic molecules based on HLCT state and separated dimeric stacks.

Although photodynamic therapy (PDT) has been well-known as a promising anti-tumor treatment, its limited therapeutic efficiency remains to be a large challenge. In this study, a carrier free nanomedicine (designated as PyroMor) is developed to greatly initiate cell apoptosis and paraptosis for synergistic cancer therapy. Pyropheophorbide-a (Pyro) and morusin (Mor) are capable of self-assembling into PyroMor, which has been testified to have superiority of improved stability, cellular internalization, and biocompatibility. Because of efficient cellular uptake behavior, PyroMor could induce cellular paraptosis by Mor-caused vacuolation in mitochondria, ER and cytoplasm, contributing to improving the PDT efficacy of Pyro. Therefore, self-delivery PyroMor is able to accomplish synergistic anti-tumor effect via stimulation of cell apoptosis as well as paraptosis. In addition, in vivo studies also clarify that PyroMor presents passive tumor targeting delivery, leading to robust repressive effect on tumor proliferation with negligible systemic toxicity. This strategy of combined cancer therapy by initiating both cell apoptosis and paraptosis extremely benefits to the development of precise and effective cancer therapy in clinic.

Objective. To investigate the value of apparent diffusion coefficient (ADC) value of endometrial cancer (EC) primary lesion and magnetic resonance imaging (MRI) three-dimensional (3D) radiomics features combined with clinical parameters for preoperative prediction of pelvic lymph node metastasis (PLNM). Methods. A total of 136 patients with EC confirmed by postoperative pathology were retrospectively reviewed and analyzed. Patients were randomly divided into training set (n = 95) and test set (n = 41) at a ratio of 7 : 3. Radiomics features based on T2WI, DWI, and contrast-enhanced T1WI (CE-T1WI) sequence were extracted and screened, and then radiomics score (Rads-score) was calculated. Clinical parameters and ADC value of EC primary lesion were measured and collected, and their correlation with PLNM was analyzed. Receiver operating characteristic (ROC) curve was plotted to assess the diagnostic efficacy of the model. A nomogram for PLNM was created based on the multivariate logistic regression model. Results. The ADC value of the EC primary lesion showed inverse correlation with PLNM, while CA125 and Rads-score were positively associated with PLNM. A predictive model was proposed based on ADC value, Rads-score, CA125, and MR-reported pelvic lymph node status (PLNS) for PLNM in EC. The area under the curve (AUC) of the model is 0.940; the sensitivity and specificity (87.1% and 90.6%) of the model were significantly higher than that of the MRI morphological signs. Conclusion. A combination of ADC value, MRI 3D radiomics features of the EC primary lesion, and clinical parameters generated a prediction model for PLNM in EC and had a good diagnostic performance; it was a useful supplement to MR-reported PLNS based on MRI morphological signs.

Lymph node (LN) staging plays an important role in treatment decision-making. Current problem is that preoperative detection of LN involvement is always highly challenging for radiologists.To explore the value of the nomogram model combining intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and radiomics features from the primary lesion of rectal adenocarcinoma in assessing the non-enlarged lymph node metastasis (N-LNM) preoperatively.Retrospective.A total of 126 patients (43% female) comprising a training group (n = 87) and a validation group (n = 39) with pathologically confirmed rectal adenocarcinoma.A 3.0 Tesla (T); TBased on pathological analysis of the surgical specimen, patients were classified into negative LN (LN-) and positive LN (LN+) groups. Apparent diffusion coefficient (ADC), diffusion coefficient (D), pseudo diffusion coefficient (D*) and microvascular volume fraction (f) values of primary lesion of rectal adenocarcinoma were measured. Three-dimensional (3D) radiomics features were measured on TGeneral_univariate_analysis and multivariate logistic regression were used for radiomics features selection. The performance of the nomogram was assessed by the receiver operating characteristic (ROC) curve, calibration, and decision curve analysis (DCA).The LN+ group had a significantly lower D* value ([13.20 ± 13.66 vs. 23.25 ± 18.71] × 10The nomogram model including IVIM-DWI and MRI radiomics features in the primary lesion of rectal adenocarcinoma was associated with the N-LNM.4 TECHNICAL EFFICACY: Stage 2.

Effective charge separation is essential in plasmon-mediated photochemistry and is usually achieved by constructing plasmon-semiconductor interfaces, which is usually challenging. In this work, by monitoring the plasmon-mediated silver oxidation with

Purpose To evaluate the feasibility of apparent diffusion coefficient (ADC) value combined with texture analysis (TA) in preoperatively predicting the expression levels of Ki-67 and p53 in endometrial carcinoma (EC) patients. Methods Clinical, pathological and MRI findings of 110 EC patients were analyzed retrospectively. The expression levels of Ki-67 and p53 in EC tissues were detected by immunohistochemistry. ADC value was calculated, and three-dimensional (3D) texture features were measured on T2-weighted images (T2WI), diffusion-weighted images (DWI), and contrast-enhanced T1-weighted images (CE-T1WI). The univariate and multivariate logistic regression and cross-validations were used for the selection of texture features. The receiver operating characteristic (ROC) curve was performed to estimate the diagnostic efficiency of prediction model by the area under the curve (AUC) in the training and validation cohorts. Results Significant differences of the ADC values were found in predicting Ki-67 and p53 (P=0.039, P=0.007). The AUC of the ADC value in predicting the expression levels of Ki-67 and p53 were 0.698, 0.853 and 0.626, 0.702 in the training and validation cohorts. The AUC of the TA model based on T2WI, DWI, CE-T1WI, and ADC value combined with T2WI + DWI + CE-T1WI in the training and validation cohorts for predicting the expression of Ki-67 were 0.741, 0.765, 0.733, 0.922 and 0.688, 0.691, 0.651, 0.938, respectively, and for predicting the expression of p53 were 0.763, 0.805, 0.781, 0.901 and 0.796, 0.713, 0.657, 0.922, respectively. Conclusion ADC values combined with TA are beneficial for predicting the expression levels of Ki-67 and p53 in EC patients before surgery, and they provide higher auxiliary diagnostic values for clinical application.

Objective. Exploring functional connectivity (FC) alterations is important for the understanding of underlying neuronal network alterations in subjective cognitive decline (SCD). The objective of this study was to prove that dynamic FC can better reflect the changes of brain function in individuals with SCD compared to static FC, and further to explore the association between FC alterations and amyloid pathology in the preclinical stage of Alzheimer’s disease. Approach. A total of 101 normal control (NC) subjects, 97 SCDs, and 55 cognitive impairment (CI) subjects constituted the whole-cohort. Of these, 29 NCs and 52 SCDs with amyloid images were selected as the sub-cohort. First, independent components (ICs) were identified by IC analysis and static and dynamic FC were calculated by pairwise correlation coefficient between ICs. Second, FC alterations were identified through group comparison, and seed-based dynamic FC analysis was done. Analysis of variance was used to compare the seed-based dynamic FC maps and measure the group or amyloid effects. Finally, correlation analysis was conducted between the altered dynamic FC and amyloid burden. Main results. The results showed that 42 ICs were revealed. Significantly altered dynamic FC included those between the salience/ventral attention network, the default mode network, and the visual network. Specifically, the thalamus/caudate (IC 25) drove the hub role in the group differences. In the seed-based dynamic FC analysis, the dynamic FC between the thalamus/caudate and the middle temporal/frontal gyrus was observed to be higher in the SCD and CI groups. Moreover, a higher dynamic FC between the thalamus/caudate and visual cortex was observed in the amyloid positive group. Finally, the altered dynamic FC was associated with the amyloid global standardized uptake value ratio (SUVr). Significance. Our findings suggest SCD-related alterations could be more reflected by dynamic FC than static FC, and the alterations are associated with global SUVr.

IntroductionExploring functional connectivity (FC) alterations is important for the understanding of underlying neuronal network alterations in subjective cognitive decline (SCD). The objective of this study was to discover stable and subtle dynamic functional connectivity (FC) changes in the preclinical stage of Alzheimer’s disease (AD), and to explore the associations between dynamic FCs and amyloid accumulation.MethodsNinety-seven normal control (NC) subjects, 101 subjective cognitive decline (SCD) subjects, and 55 cognitive impairment (CI) subjects with neuropsychological assessments and resting-state functional magnetic resonance images constituted the whole cohort. Of these, 29 NCs and 52 SCDs with amyloid images were selected as the sub-cohort. First, independent components (ICs) identified by group independent component analysis (ICA) were used to define static and dynamic brain networks. Static and sliding-window dynamic FCs were then calculated. Second, the connection between each pair of ICs was compared between groups in the two cohorts. Hubs were obtained and considered as seeds in the subsequent seed-based dynamic FC analysis. One-way analysis of variance (ANOVA) was used to compare the seed-based dynamic FC maps between groups in the whole cohort, while a 2×2 ANOVA model was used to measure the group or amyloid effects in the sub-cohort. Post-hoc analysis was applied, and differences were considered significant if the cluster-level FWE-corrected p-value was less than 0.001. Finally, correlation analysis was conducted between the altered dynamic FCs, neuropsychological assessments, and amyloid burden.ResultsThe results showed that 42 ICs were revealed. Compared with the static FCs, the dynamic FCs were found to be more stable and sensitive between groups. The effective dynamic FCs included those between the salience/ventral attention network, the default mode network, and the visual network. Specifically, the dynamic FC of the thalamus/caudate (IC 25) drove the hub role in the group differences between the NC and SCD groups. In the seed-based dynamic FC analysis, the dynamic FC between the thalamus/caudate and the middle temporal/frontal gyrus was observed to be higher in the SCD and CI groups in the whole cohort. Moreover, a higher dynamic FC between the thalamus/caudate and visual cortex was observed in the amyloid positive group. Finally, the altered dynamic FC was associated with the amyloid global level standardized uptake value ratio.ConclusionOur findings indicate that dynamic FCs can reflect subtle changes in the preclinical stage of AD.

Neuroimaging studies have shown topological disruptions of both functional and structural whole-brain networks in major depressive disorder (MDD). This study examined common and specific alterations between these two types of networks and whether the alterations were differentially involved in the two hemispheres. Multimodal MRI data were collected from 35 MDD patients and 35 healthy controls, whose functional and structural hemispheric networks were constructed, characterized, and compared. We found that functional brain networks were profoundly altered at multiple levels, while structural brain networks were largely intact in patients with MDD. Specifically, the functional alterations included decreases in intra-hemispheric (left and right) and inter-hemispheric (heterotopic) functional connectivity; decreases in local, global and normalized global efficiency for both hemispheric networks; increases in normalized local efficiency for the left hemispheric networks; and decreases in intra-hemispheric integration and inter-hemispheric communication in the dorsolateral superior frontal gyrus, anterior cingulate gyrus and hippocampus. Regarding hemispheric asymmetry, largely similar patterns were observed between the functional and structural networks: the right hemisphere was over-connected and more efficient than the left hemisphere globally; the occipital and partial regions exhibited leftward asymmetry, and the frontal and temporal sites showed rightward lateralization with regard to regional connectivity profiles locally. Finally, the functional–structural coupling of intra-hemispheric connections was significantly decreased and correlated with the disease severity in the patients. Overall, this study demonstrates modality- and hemisphere-dependent and invariant network alterations in MDD, which are helpful for understanding elaborate and characteristic patterns of integrative dysfunction in this disease.