Abnormal stability of dynamic functional architecture in drug-naïve children with attention-deficit/hyperactivity disorder.

Background And Aims: Attention-deficit/hyperactivity disorder (ADHD) is most commonly diagnosed neurodevelopmental disorder in childhood, characterized by developmentally inappropriate inattention and/or hyperactivity/impulsivity symptoms. Static and dynamic functional connectivity (FC) studies have revealed brain dysfunction in ADHD. However, few studies have estimated the stability of dynamic functional architecture of children with ADHD.

The association of motor reserve and clinical progression in Parkinson's disease.

Objective: To explore the association of motor reserve (MR) and clinical progression in Parkinson's disease.

Methods: This longitudinal study using data from the Parkinson's progression markers initiative. Patients with de novo PD who underwent dopamine transporter scans at baseline and finished at least five years clinical follow-up assessments (including motor, cognitive, and non-motor symptoms) were included.

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.

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.

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.

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 O, Φ = 0.

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.

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.

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

Recent studies and clinical evidence have strongly supported the development of adenosine A receptor (AR) antagonists as novel approaches for cancer immunotherapy. By screening our in-house compound library, a pyridinone hit compound () with weak AR antagonistic activity was identified. Further structure-activity relationship studies revealed a series of pyridinone derivatives with strong potency.

A simple method for fabricating drugs containing a -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.

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.

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.

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 β-anomers generally.

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.

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 Gd-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 Gd, eventually resulted in boosted ROS generation from the existing PSs (1.

[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.

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

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.

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.

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.

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 T-weighted structural MRI images of individuals from the ADHD-200 database.

Homogeneous Visual and Fluorescence Detection of Circulating Tumor Cells in Clinical Samples 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.

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.

Enriched Au nanoclusters with mesoporous silica nanoparticles for improved fluorescence/computed tomography dual-modal imaging.

Objectives: Au nanoclusters (AuNCs) have been used widely in fluorescence bio-imaging because of their good fluorescence, small particle size and non-cytotoxicity. AuNCs are also efficient in computed tomography (CT) imaging. Hence, a dual-modal imaging probe can be constructed without any complicated modification processes by exploiting the excellent performance of AuNCs.

Filter-Assisted Separation of Multiple Nanomaterials: Mechanism and Application in Atomic/Mass Spectrometry/Fluorescence Label-Free Multimode Bioassays.

Atomic spectrometry (AS) has been widely used in bioassay, but it requires steps to immobilize or separate the signal molecules. In this work, based on the phenomenon that the filter membrane can selectively separate multiple nanomaterials (nanoparticles (NPs) and quantum dots (QDs)) and its related ions, including poly(thymine)-templated Cu NPs and free Cu, Ag NPs and free Ag, CdTe QDs and Cd, we constructed multimode and label-free biosensors by chemical vapor generation-atomic fluorescence spectrometry (CVG-AFS), inductively coupled plasma mass spectrometry (ICP-MS), and fluorescence. In this strategy, terminal deoxynucleotidyl transferase (TdT) and polynucleotide kinase (PNK), HO, and mucin 1 can be sensitively detected using Cu, Ag, and Cd as the signal probe, respectively.

Halo-fluorescein for photodynamic bacteria inactivation in extremely acidic conditions.

Aciduric bacteria that can survive in extremely acidic conditions (pH < 4.0) are challenging to the current antimicrobial approaches, including antibiotics and photodynamic bacteria inactivation (PDI). Here, we communicate a photosensitizer design concept of halogenation of fluorescein for extremely acidic PDI.