Characterization of local white matter microstructural alterations in Alzheimer's disease: A reproducible study.

Alzheimer's disease (AD) is a neurodegenerative disease with a close association with microstructural alterations in white matter (WM). Current studies lack the characterization and further validation of specific regions in WM fiber tracts in AD. This study subdivided fiber tracts into multiple fiber clusters on the basis of automated fiber clustering and performed quantitative analysis along the fiber clusters to identify local WM microstructural alterations in AD. Diffusion tensor imaging data from a public dataset (53 patients with AD and 70 healthy controls [HCs]) and a clinical dataset (27 patients with AD and 19 HCs) were included for mutual validation. Whole-brain tractograms were automatically subdivided into 800 clusters through the automatic fiber clustering approach. Then, 100 segments were divided along the clusters, and the diffusion properties of each segment were calculated. Results showed that patients with AD had significantly lower fraction anisotropy (FA) and significantly higher mean diffusivity (MD) in some regions of the fiber clusters in the cingulum bundle, uncinate fasciculus, external capsule, and corpus callosum than HCs. Importantly, these changes were reproducible across the two datasets. Correlation analysis revealed a positive correlation between FA and Mini-Mental State Examination (MMSE) scores and a negative correlation between MD and MMSE in these clusters. The accuracy of the constructed classifier reached 89.76% with an area under the curve of 0.93. This finding indicates that this study can effectively identify local WM microstructural changes in AD and provides new insight into the analysis and diagnosis of WM abnormalities in patients with AD.

Portable biosensor-based oral pathogenic bacteria detection for community and family applications.

Detection of oral pathogens is essential in the management of oral diseases, as their occurrence and progression are closely linked to an imbalance in these microorganisms. Detection techniques such as microbial cultures, enzyme-linked immunosorbent assays and polymerase chain reactions are highly dependent on complex testing procedures and specialized laboratory equipment, making prevention and early diagnosis of oral diseases difficult. To comprehensively implement oral disease prevention and early diagnosis in social groups, there is an urgent need for portable testing methods for oral pathogenic bacteria that can be applied in community and home settings. In this review, several common portable biosensors for pathogenic bacteria are first described. Based on the goal of achieving primary prevention and diagnosis of oral diseases, we elaborate and summarize portable biosensors for common oral pathogenic bacteria in terms of how to achieve portability of the technique. This review aims to reflect the current status of portable biosensors for common oral pathogens and to lay the foundation for the further realization of portable detection of oral pathogens.

Discovery of novel triazine derivatives as potent retinoic acid receptor-related orphan receptor γt (RORγt) inverse agonists.

Retinoic Acid Receptor-Related Orphan Receptor γt (RORγt) has been exploited as a promising target for the new small molecule therapeutics to treat inflammatory and autoimmune diseases via modulating the interleukin-17 (IL-17) production by T helper 17 (Th17) cells. Herein, we reported a series of triazine-based derivatives as novel RORγt inverse agonists. By screening of our in-house compound library, the hit compound 1 was identified with weak RORγt inhibitory activity. Subsequently, we engineered detailed structural modifications to explore the structure-activity relationships (SARs) of triazines derivatives, which led to discovery of a number of potent RORγt inverse agonists with IC50 values in the range of 7 nM-50 nM in RORγt dual FRET assay. Among them, compound 14g displayed potent RORγt inverse agonistic activity with an IC50 value of 22.9 nM in dual FRET assay. In a cell-based reporter gene assay, compound 14g showed an IC50 value of 0.428 µM and maximum inhibition rate of 108.9%. Compound 14g also exhibited good metabolic stability and a decent pharmacokinetic profile with a low clearance (CL = 0.229 L/h/kg) and a reasonable oral exposure (AUC0-Last = 5058 ng/mL*h). Most importantly, 14g alleviated the severity of imiquimod-induced psoriasis in mice. Taken together, triazine-based derivatives represent a new chemical class of RORγt inverse agonists as potential therapeutic agents against autoimmune diseases.

Self-Immolative Polythiophene for Sunlight Inactivation of Harmful Cyanobacteria.

Harmful cyanobacterial blooms and the released microcystins (MCs) caused serious environmental and public health concerns to drinking water safety. Photo-oxidation is an appealing treatment option and alternative to conventional flocculation and microbial antagonists, but the performances of current photosensitizers (either inorganic or organic) are unsatisfactory. Here, a polythiophene photosensitizer (PT10) with both high yield of reactive oxygen species (ROS) production (mainly 1O2, ΦΔ = 0.51, > 8 h continuous generation) and moderate photostability was used as a powerful algaecide to inhibit Microcystis aeruginosa. Due to the positive charge of PT10, the algal cells were quickly flocculated, followed by efficient inactivation in 4 h under white light irradiation (96.7%, 10 mW/cm2). Meanwhile, PT10 was self-immolated in about 6 h. Upon biosafety evaluation with adult zebrafish, the low toxicity of PT10 and the degradation products of PT10 and algae (early logarithmic growth stage) were confirmed. In addition, microcystin-LR (MC-LR), a toxic microcystin that will be released during the destruction of the algal cells, was also degraded. Therefore, PT10-based photoinactivation of M. aeruginosa featured both high performance and low secondary pollution. In real-world aquatic systems, PT10 was confirmed to be capable of sunlight-assisted inactivation of M. aeruginosa and prevent algal blooms, thus making it appealing for environmental remediation.

Dynamically Visualized Mechano-Responsive Supramolecular Self-Assembly System for Small Molecule Release.

The mechano-responsiverelease of small molecules has received extensive attention in ultrasound (US)-controlled drug release in recent years because it can achieve non-invasive, spatiotemporally controlled precise drug release. However, the vast majority of small molecules mechano-release reported so far are based on polymer systems, which suffer from complex preparations and single mechano-response. Here, an isoguanosine (isoG) visualized mechano-responsive supramolecular self-assembly (isoG-VMRSS) system was successfully constructed by a one-pot reaction. It is completely composed of small molecules, which allows for multiple mechano-responsive releases of isoG (at least 9 times) and ultimately has potential for application in US drug release. A combined experimental-computational approach reveals the supramolecular network structure (formed by the joint action of related metal coordination bonds, boronate ester bonds and hydrogen bonds mediated by isoG) gradually formed inside the system is the underlying internal mechanism. Therefore, it provides a new and effective idea of small molecule release in the field of mechanochemistry.

Discovery of novel BTK PROTACs with improved metabolic stability via linker rigidification strategy.

Bruton's Tyrosine Kinase (BTK) functions as a key regulator of B-cell receptor (BCR) signaling pathway, which is frequently hyperactivated in a variety of lymphoma cancers. Using Proteolysis Targeting Chimera (PROTAC) technology, we have recently discovered a highly potent ARQ-531-derived BTK PROTAC 6e, inducing effective degradation of both wild type (WT) and C481S mutant BTK proteins. However, the poor metabolic stability of PROTAC 6e have limited its further in vivo studies. Herein, we present our structure-activity relationship (SAR) studies on modifying PROTAC 6e using linker rigidification strategy to identify a novel cereblon (CRBN)-recruiting compound 3e that induced BTK degradation in a concentration-dependent manner but had no effect on reducing the level of CRBN neo-substrates. Moreover, compound 3e suppressed the cell growth more potently than the small molecule inhibitors ibrutinib and ARQ-531 in several cells. Furthermore, compound 3e with the rigid linker displayed a significantly improved metabolic stability profile with the T1/2 increased to more than 145 min. Overall, we discovered a highly potent and selective BTK PROTAC lead compound 3e, which could be further optimized as potential BTK degradation therapy for BTK-associated human cancers and diseases.

Discovery of Pyridinone Derivatives as Potent, Selective, and Orally Bioavailable Adenosine A2A Receptor Antagonists for Cancer Immunotherapy.

Recent studies and clinical evidence have strongly supported the development of adenosine A2A receptor (A2AR) antagonists as novel approaches for cancer immunotherapy. By screening our in-house compound library, a pyridinone hit compound (1) with weak A2AR antagonistic activity was identified. Further structure-activity relationship studies revealed a series of pyridinone derivatives with strong potency. Compound 38 stood out with a potent A2AR antagonistic activity (IC50 = 29.0 nM), good mouse liver microsomal metabolic stability (t1/2 = 86.1 min), and excellent oral bioavailability (F = 86.1%). Of note, 38 effectively enhanced the activation and killing ability of T cells in vitro by down-regulation of immunosuppressive molecules (LAG-3 and TIM-3) and up-regulation of effector molecules (GZMB, IFNG, and IL-2). Moreover, 38 exhibited excellent in vivo antitumor activity with a tumor growth inhibition (TGI) of 56.0% in the MC38 tumor model via oral administration, demonstrating its potential as a novel A2AR antagonist candidate for cancer immunotherapy.

A simple method for fabricating drugs containing a cis-o-diol structure into guanosine-based supramolecular hydrogels for drug delivery.

Supramolecular hydrogels are attractive biomaterials for local drug delivery owing to their excellent self-healing, injectable, biodegradable, and biocompatible properties. However, traditional drug-loading approaches based on non-covalent encapsulation and covalent bonding have shown problems such as rapid or difficult drug release, complex reaction processes, low reaction efficiency, and decreased drug activity. Therefore, there is a need to find a simple and efficient method to load drugs into hydrogels, which possess stable drug release ability without impairing drug efficacy. In this study, we introduce dynamic borate ester bonds via a simple one-pot method to load cis-o-diol-containing drugs into guanosine (G)-based supramolecular hydrogels. The experimental results confirm that the dynamic covalent borate ester bonds are formed based on the cis-o-diol groups of the drug and the G in these hydrogels. Meanwhile, the as-prepared G-based hydrogels not only possess self-healing properties and injectability but also have satisfactory biodegradability and biocompatibility. Additionally, the drug can be released from the G-based hydrogel according to the pH-responsive cleavage of the borate ester bonds without affecting drug activity. Overall, these results indicate that the simple one-pot method of utilizing the dynamic borate bond can provide a valuable reference for the design of hydrogel dosage forms.

Correlation research of susceptibility single nucleotide polymorphisms and the severity of clinical symptoms in attention deficit hyperactivity disorder.

Objective: To analyze the correlation between susceptibility single nucleotide polymorphisms (SNPs) and the severity of clinical symptoms in children with attention deficit hyperactivity disorder (ADHD), so as to supplement the clinical significance of gene polymorphism and increase our understanding of the association between genetic mutations and ADHD phenotypes. Methods: 193 children with ADHD were included in our study from February 2017 to February 2020 in the Children's ADHD Clinic of the author's medical institution. 23 ADHD susceptibility SNPs were selected based on the literature, and multiple polymerase chain reaction (PCR) targeted capture sequencing technology was used for gene analysis. A series of ADHD-related questionnaires were used to reflect the severity of the disease, and the correlation between the SNPs of specific sites and the severity of clinical symptoms was evaluated. R software was used to search for independent risk factors by multivariate logistic regression and the "corplot" package was used for correlation analysis. Results: Among the 23 SNP loci of ADHD children, no mutation was detected in 6 loci, and 2 loci did not conform to Hardy-Weinberg equilibrium. Of the remaining 15 loci, there were 9 SNPs, rs2652511 (SLC6A3 locus), rs1410739 (OBI1-AS1 locus), rs3768046 (TIE1 locus), rs223508 (MANBA locus), rs2906457 (ST3GAL3 locus), rs4916723 (LINC00461 locus), rs9677504 (SPAG16 locus), rs1427829 (intron) and rs11210892 (intron), correlated with the severity of clinical symptoms of ADHD. Specifically, rs1410739 (OBI1-AS1 locus) was found to simultaneously affect conduct problems, control ability and abstract thinking ability of children with ADHD. Conclusion: There were 9 SNPs significantly correlated with the severity of clinical symptoms in children with ADHD, and the rs1410739 (OBI1-AS1 locus) may provide a new direction for ADHD research. Our study builds on previous susceptibility research and further investigates the impact of a single SNP on the severity of clinical symptoms of ADHD. This can help improve the diagnosis, prognosis and treatment of ADHD.

The long-range white matter microstructural alterations in drug-naive children with ADHD: A tract-based spatial statistics study.

BACKGROUND: To investigate WM alterations, particularly the changes in long-range fibers, in drug-naive children with attention deficit hyperactivity disorder (ADHD), we conducted tract-based spatial statistics (TBSS) analysis on diffusion tensor imaging (DTI) data. MATERIALS AND METHODS: In this study, 57 children with ADHD and 41 healthy controls (HCs) were enrolled. None of the enrolled ADHD children received any medication before data collection. WM changes were then correlated with clinical symptoms, including the hyperactivity index score and the impulsivity score. RESULTS: ADHD children demonstrated decreased FA in the right forceps major, left inferior fronto-occipital fasciculus, and left genu Internal capsule. Moreover, higher RD was observed in the right forceps major, superior longitudinal fasciculus, and forceps major. The results of linear regression analysis including learning problem score, hyperactivity index score and impulsivity score showed that higher earning problem and hyperactivity/impulsivity symptom scores were negatively correlated with the mean FA value in the right forceps major, left IFOF and left genu Internal capsule. CONCLUSION: Our results demonstrate that microstructural WM alterations and changes in the long-range WM connections are present in children with ADHD. We speculate that these changes may relate to the symptoms of hyperactivity and impulsivity.

Nitro-Activated Nucleobase Exchange in the Synthesis of 2'-Fluoro-2'-Deoxyribonucleosides.

Functionalized nucleosides bearing pyrimidine or purine bases can be prepared by activation of accessible pyrimidine nucleosides and subsequent transglycosylation. Nitration of lumicitabine, a 2'-fluoro-2'-deoxycytidine class antiviral agent, and its 2'-fluoro-2'-deoxyuridine precursor produce the same 5-nitro-2'-fluoro-2'-deoxyuridine. Under Vorbrüggen conditions, 5-nitrouracil serves as the leaving nucleobase and enables exchange with pyrimidine and purine nucleobases to anomeric 2'-fluoro-2'-deoxyribonucleosides in favor of ß-anomers generally. The strategy is also applied in the isotopic labeling of 2'-fluoro-2'-deoxyuridines.

Polythiophene as a near full pH photo-antimicrobial.

Microbial infections are currently one of the world's major public health concerns, the evolution of which has resulted in the development of multiple tolerances (not just drug or antibiotic resistance), including pH (from extremely acidic to alkaline). Currently various types of antimicrobials have been developed. Although effective, they seldom work in the full pH range due to the existence of acid-/base-reaction sites. Here, we found that polythiophene (PT10), a cationic polymer, was capable of both broad-spectrum photo-antimicrobial activity (Gram positive, Gram negative, Fungal, and cyano-bacteria) and broad pH responsiveness (constant 1O2 generation at pH 2-13). The half-maximal inhibitory concentrations (IC50) of PT10 for bacteria living in acidic, neutral, and alkaline media were generally lower than 2 µg mL-1 (except M. aeruginosa, pH 12, ∼30 µg mL-1), which were much lower than common antibiotics and other photosensitizers. Besides, the excellent photostability of PT10 allowed long-term light irradiation for antimicrobial performance. In real-world applications, PT10 was explored for the successful in vivo therapy of oral Candidiasis infection under extreme acidic conditions (pH < 3) and the removal of M. aeruginosa at pH 12. Such near full pH, broad-spectrum photo-antimicrobial activity of polythiophene is appealing for extremely acidic or alkaline applications, such as oral infections, vaginitis, and blooms.

Universal "Three-in-One" Matrix to Maximize Reactive Oxygen Species Generation from Food and Drug Administration-Approved Photosensitizers for Photodynamic Inactivation of Biofilms.

Biofilms, an accumulation of microorganisms, cause persistent bacterial infection and low cure rate due to the remarkable drug resistance. Photodynamic inactivation (PDI) is a promising treatment modality for bacterial infections, but the formation of biofilms raises new challenges for photosensitizers (PSs), particularly the reactive oxygen species (ROS) generation efficiency. Herein, through targeting the Jablonski energy diagram, we proposed a universal "three-in-one" matrix of Gd3+-ADP assembly for encapsulation and fixing of PSs to inhibit non-radiative transitions and promoting intersystem crossing (ISC) by the heavy atom and paramagnetic effects of Gd3+, eventually resulted in boosted ROS generation from the existing PSs (1.5-9.0-fold). Particularly, photophysical studies indicated that the matrix resulted in simultaneous ISC promotion and triplet-state lifetime lengthening, which is essential for ROS boosting. The PDI performance of the matrix was confirmed through fast and effective elimination of bacterial biofilms in 10-30 min. Moreover, successful therapy of a Pseudomonas aeruginosa biofilm-infected all-thickness third-degree burn wound was achieved within 11 days with Ce 6@CNs (matrix) but not feasible for matrix-free PSs (Ce 6 only), which highlighted the role of "three-in-one" matrix in ROS boosting.

Different effects of the DRD4 genotype on intrinsic brain network connectivity strength in drug-naïve children with ADHD and healthy controls.

The dopamine D4 receptor gene (DRD4) has been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). Recent studies have linked DRD4 to functional connectivity among specific brain regions. The current study aimed to compare the effects of the DRD4 genotype on functional integrity in drug-naïve ADHD children and healthy children. Resting-state functional MRI images were acquired from 49 children with ADHD and 37 healthy controls (HCs). We investigated the effects of the 2-repeat allele of DRD4 on brain network connectivity in both groups using a parameter called the degree of centrality (DC), which indexes local functional relationships across the entire brain connectome. A voxel-wise two-way ANCOVA was performed to examine the diagnosis-by-genotype interactions on DC maps. Significant diagnosis-by-genotype interactions with DC were found in the temporal lobe, including the left inferior temporal gyrus (ITG) and bilateral middle temporal gyrus (MTG) (GRF corrected at voxel level p < 0.001 and cluster level p < 0.05, two-tailed). With the further subdivision of the DC network according to anatomical distance, additional brain regions with significant interactions were found in the long-range DC network, including the left superior parietal gyrus (SPG) and right middle frontal gyrus (MFG). The post-hoc pairwise analysis found that altered network centrality related to DRD4 differed according to diagnostic status (p < 0.05). This genetic imaging study suggests that the DRD4 genotype regulates the functional integration of brain networks in children with ADHD and HCs differently. This may have important implications for our understanding of the role of DRD4 in altering functional connectivity in ADHD subjects.

[Research Progress in Biomimetic Synthesis of Nano-Hydroxyapatite in Bone Tissue Engineering].

Nano hydroxyapatite (nHAp), a main component of the inorganic composition of human bones and teeth, is widely used in bone tissue engineering, bone defect repair and replacement, for example, for its biocompatibility, bioactivity, bioaffinity and the ability to induce bone regeneration. Nano hydroxyapatite contains calcium and phosphorus, elements that can be replaced through the normal metabolic channels of the human body. Therefore, after implantation, it can be partially or completely absorbed and replaced by human tissues and can effectively assist bone regeneration, which makes it an ideal material for bone repair. However, traditional nHAp material is brittle and hard to be degraded in human body. In addition, nHAp has poor stability due to its high surface energy and tendency for agglomeration, which causes rapid attenuation of its mechanical strength and limits its clinical application. At present, the mechanical properties and biocompatibility of nHAp can be effectively improved by loading the related growth factors, proteins, peptides and other bioactive molecules, so as to better meet the biological requirements of bone repair materials. However, the traditional physicochemical modification methods are complicated and may interfere with the bioactivity of nHAp. It is simple to biomimetically synthesize nanomaterials by direct utilization of the molecular recognition and self-assemble capabilities of biomolecules or living microorganisms. Furthermore, the properties of the synthesized nanomaterials are stable, and the method has been extensively studied in recent years. Due to the unique crystaline structure and physicochemical properties of nHAp, results of a large number of studies have shown that its affinity with biological molecules can be used to produce bioactive nHAp by biomimetic synthesis methods. Biomimetically synthesized nHAp is expected to become the mainstream bone tissue engineering scaffold material. Analyzing and summarizing the biomimetic synthetic process and the characteristics of different nHAp materials will facilitate further development of bone defect repair materials with better mechanical and biological properties. Herein we reviewed methods of biomimetic synthesis of nHAp based on different biomolecular templates. Furthermore, we also discussed applications of biomimetic synthesized nHAp in bone tissue engineering, which can used as reference information for further research and development of new-generation bone repair biomaterials.

Altered Variability and Concordance of Dynamic Resting-State fMRI Indices in Patients With Attention Deficit Hyperactivity Disorder.

Objective: Attention deficit hyperactivity disorder (ADHD) is a commonly diagnosed neuropsychiatric disorder in children, which is characterized by inattention, hyperactivity and impulsivity. Using resting-state functional magnetic resonance imaging (R-fMRI), the alterations of static and dynamic characteristics of intrinsic brain activity have been identified in patients with ADHD. Yet, it remains unclear whether the concordance among indices of dynamic R-fMRI is altered in ADHD. Methods: R-fMRI scans obtained from 50 patients with ADHD and 28 healthy controls (HC) were used for the current study. We calculated the regional dynamic changes in brain activity indices using the sliding-window method and compared the differences in variability of these indices between ADHD patients and HCs. Further, the concordance among these dynamic indices was calculated and compared. Finally, the relationship between variability/concordance of these indices and ADHD-relevant clinical test scores was investigated. Results: Patients with ADHD showed decreased variability of dynamic amplitude of low-frequency fluctuation (dALFF) in the left middle frontal gyrus and increased one in right middle occipital gyrus, as compared with the HCs. Besides, ADHD patients showed decreased voxel-wise concordance in the left middle frontal gyrus. Further, lower voxel-wise concordance in ADHD's left middle frontal gyrus was associated with more non-perseverative errors in Wisconsin Card Sorting Test, which reflects worse cognitive control. Conclusion: Our findings suggest that variability and concordance in dynamic brain activity may serve as biomarkers for the diagnosis of ADHD. Further, the decreased voxel-wise concordance is associated with deficit in cognitive control in ADHD patients.

Aptamer-mediated synthesis of multifunctional nano-hydroxyapatite for active tumour bioimaging and treatment.

OBJECTIVES: The nano-hydroxyapatite (nHAp) is widely used to develop imaging probes and drug carriers due to its excellent bioactivity and biocompatibility. However, traditional methods usually need cumbersome and stringent conditions such as high temperature and post-modification to prepare the functionalized nHAp, which do not benefit the particles to enter cells due to the increased particle size. Herein, a biomimetic synthesis strategy was explored to achieve the AS1411-targeted tumour dual-model bioimaging using DNA aptamer AS1411 as a template. Then, the imaging properties and the biocompatibility of the synthesized AS-nFAp:Gd/Tb were further investigated. MATERIALS AND METHODS: The AS-nFAp:Gd/Tb was prepared under mild conditions through a one-pot procedure with AS1411 as a template. Besides, the anticancer drug DOX was loaded to AS-nFAp:Gd/Tb so as to achieve the establishment of a multifunctional nano-probe that integrated the tumour diagnosis and treatment. The AS-nFAp:Gd/Tb was characterized by transmission electron microscopy (TEM), energy disperse X-ray Spectroscopy (EDS) mapping, X-ray photoelectron spectroscopy (XPS) spectrum, X-ray diffraction (XRD), fourier-transformed infrared (FTIR) spectroscopy, capillary electrophoresis analyses, zeta potential and particle sizes. The in vitro magnetic resonance imaging (MRI) and fluorescence imaging were performed on an MRI system and a confocal laser scanning microscope, respectively. The potential of the prepared multifunctional nHAp for a targeted tumour therapy was investigated by a CCK-8 kit. And the animal experiments were conducted on the basis of the guidelines approved by the Animal Care and Use Committee of Sichuan University, China. RESULTS: In the presence of AS1411, the as-prepared AS-nFAp:Gd/Tb presented a needle-like morphology with good monodispersity and improved imaging performance. Furthermore, due to the specific binding between AS1411 and nucleolin up-expressed in cancer cells, the AS-nFAp:Gd/Tb possessed excellent AS1411-targeted fluorescence and MRI imaging properties. Moreover, after loading chemotherapy drug DOX, in vitro and in vivo studies showed that DOX@AS-nFAp:Gd/Tb could effectively deliver DOX to tumour tissues and exert a highly effective tumour inhibition without systemic toxicity compared with pure DOX. CONCLUSIONS: The results indicated that the prepared multifunctional nHAp synthesized by a novel biomimetic strategy had outstanding capabilities of recognition and treatment for the tumour and had good biocompatibility; hence, it might have a potential clinical application in the future.

Larger thalamus correlated with inattentive severity in the inattentive subtype of ADHD without comorbidity.

Previous studies of brain structural abnormalities in attention-deficit/hyperactivity disorder (ADHD) samples scarcely excluded comorbidity or analyzed them in subtypes. This study aimed to identify neuroanatomical alterations related to diagnosis and subtype of ADHD participants without comorbidity. In our cross-sectional analysis, we used T1-weighted structural MRI images of individuals from the ADHD-200 database. After strict exclusion, 121 age-matched children with uncomorbid ADHD (54 with ADHD-inattentive [iADHD] and 67 with ADHD-combined [cADHD]) and 265 typically developing control subjects (TDC) were included in current investigation. The established method of voxel-based morphometry (VBM8) was used to assess global brain volume and regional grey matter volume (GM). Our results showed that the ADHD patients had more regional GM in the bilateral thalamus relative to the controls. Post hoc analysis revealed that regional GM increase only linked to the iADHD subtype in the right thalamus and precentral gyrus. Besides, the right thalamus volume was positively related to inattentive severity in the iADHD. There were no group differences in global volume. Our results provide preliminary evidence that cerebral structural alterations are tied to uncomorbid ADHD subjects and predominantly attribute to iADHD subtype. Furthermore, the volume of the right thalamus may be relevant to inattentive symptoms in iADHD possibly related to a lack of inhibition of irrelevant sensory input.

Homogeneous Visual and Fluorescence Detection of Circulating Tumor Cells in Clinical Samples via Selective Recognition Reaction and Enzyme-Free Amplification.

Here we report a simple all-nucleic-acid enzyme-free catalyzed hairpin assembly assisted amplification strategy with quantum dots (QDs) as the nanoscale signal reporter for homogeneous visual and fluorescent detection of A549 lung cancer cells from clinical blood samples. This work was based on the phenomenon that CdTe QDs can selectively recognize Ag+ and C-Ag+-C and by using mucin 1 as the circulating tumor cells (CTCs) marker and aptamer as the recognition probe. Under optimized conditions, the limits of detections as low as 0.15 fg/mL of mucin 1 and 3 cells/mL of A549 cells were achieved with fluorescence signals. A 1 fg/mL concentration of mucin 1 and 100 cells/mL of A549 can be distinguished by the naked eye. This method was used to quantitatively analyze CTCs in 51 clinical whole blood samples of patients with lung cancer. The levels of CTCs detected in clinical samples by this method were consistent with those obtained using the folate receptor-polymerase chain reaction clinical test kit and correlated with radiologic and pathological findings.

Synthesis and Antitumor Application of Antiangiogenetic Gold Nanoclusters.

Conventional antiangiogenetic inhibitors suffered from poor delivery problems that result in unsatisfactory antitumor treatment efficacy. Although the liposomes or nanomaterial-based delivery systems can improve the therapeutic efficacy of antiangiogenic molecules, the assembly process is far too complex. Herein, a nanomaterial or a new nanodrug that could work without the help of a carrier and could be easily synthesized is needed. Au nanoclusters (AuNCs) are a kind of ideal nanostructures that could spontaneously enter into the cell and could be synthesized by a relatively easy one-pot method. Here, changing the traditional ligand glutathione (GSH) into an anti-Flt1 peptide (AF) has enriched the newly synthesized AF@AuNCs with targeted antiangiogenic properties. Based on the specific binding between AF and vascular endothelial growth factor receptor 1 (VEGFR1), the interaction between VEGFR1 and its ligands could be blocked. Furthermore, the expression of VEGFR2 could be downregulated. Compared with pure AF peptide- and GSH-participated AuNCs (GSH@AuNCs), AF@AuNCs were more effective in inhibiting both tube formation and migration of the endothelial cells in vitro. Furthermore, the in vivo chick embryo chorioallantoic membrane (CAM) experiment and antitumor experiment were conducted to further verify the enhanced antiangiogenesis and tumor inhibition effect of AF@AuNCs. Our findings provide promising evidence of a carrier-free nanodrug for tumors and other vascular hyperproliferative diseases.