Photodynamic micelles for amyloid β degradation and aggregation inhibition

Polymeric micelles loaded with chlorin e6 and Tanshinone I (TAS) were prepared and employed for photodegrading amyloid β (Aβ) aggregates and inhibiting Aβ fibrillation

Multifunctional peptide-assembled micelles for simultaneously reducing amyloid-β and reactive oxygen species.

The excessive production and deposition of amyloid-β (Aβ) is one of the most important etiologies of Alzheimer's disease (AD). The interaction between Aβ and metal ions produces aberrant reactive oxygen species (ROS), which induce oxidative stress and accelerate the progression of AD. To reduce Aβ plaques and ROS to maintain their homeostasis is an emerging and ingenious strategy for effective treatment of AD. Herein, we report the rational design of multifunctional micelles (MPGLT) based on a polymer-grafted peptide to simultaneously clear Aβ and ROS for AD therapy. The MPGLT integrating three functional peptides as a ROS scavenger (tk-GSH), β-sheet breaker (LP) and an autophagy activator (TK) respectively, could capture and degrade Aβ. Meanwhile, the tk-GSH on the surface of MPGLT effectively scavenges the intracellular ROS. Consequently, MPGLT reduced the cytotoxicity of Aβ and ROS. In vivo animal studies using an AD mouse model further showed that MPGLT could transport across the blood-brain barrier for decreasing the Aβ plaque and eliminating ROS in vivo. This peptide micelle-based synergistic strategy may provide novel insight for AD therapy

Social Exclusion Modulates Priorities of Attention Allocation in Cognitive Control

Many studies have investigated how exclusion affects cognitive control and have reported inconsistent results. However, these studies usually treated cognitive control as a unitary concept, whereas it actually involved two main sub-processes: conflict detection and response implementation. Furthermore, existing studies have focused primarily on exclusion’s effects on conscious cognitive control, while recent studies have shown the existence of unconscious cognitive control. Therefore, the present study investigated whether and how exclusion affects the sub-processes underlying conscious and unconscious cognitive control differently. The Cyberball game was used to manipulate social exclusion and participants subsequently performed a masked Go/No-Go task during which event-related potentials were measured. For conscious cognitive control, excluded participants showed a larger N2 but smaller P3 effects than included participants, suggesting that excluded people invest more attention in conscious conflict detection, but less in conscious inhibition of impulsive responses. However, for unconscious cognitive control, excluded participants showed a smaller N2 but larger P3 effects than included participants, suggesting that excluded people invest less attention in unconscious conflict detection, but more in unconscious inhibition of impulsive responses. Together, these results suggest that exclusion causes people to rebalance attention allocation priorities for cognitive control according to a more flexible and adaptive strategy

Intermittent parathyroid hormone (PTH) promotes cementogenesis and alleviates the catabolic effects of mechanical strain in cementoblasts

Abstract Background External root resorption, commonly starting from cementum, is a severe side effect of orthodontic treatment. In this pathological process and repairing course followed, cementoblasts play a significant role. Previous studies implicated that parathyroid hormone (PTH) could act on committed osteoblast precursors to promote differentiation, and inhibit apoptosis. But little was known about the role of PTH in cementoblasts. The purpose of this study was to investigate the effects of intermittent PTH on cementoblasts and its influence after mechanical strain treatment. Results Higher levels of cementogenesis- and differentiation-related biomarkers (bone sialoprotein (BSP), osteocalcin (OCN), Collagen type I (COL1) and Osterix (Osx)) were shown in 1–3 cycles of intermittent PTH treated groups than the control group. Additionally, intermittent PTH increased alkaline phosphatase (ALP) activity and mineralized nodules formation, as measured by ALP staining, quantitative ALP assay, Alizarin red S staining and quantitative calcium assay. The morphology of OCCM-30 cells changed after mechanical strain exertion. Expression of BSP, ALP, OCN, osteopontin (OPN) and Osx was restrained after 18 h mechanical strain. Furthermore, intermittent PTH significantly increased the expression of cementogenesis- and differentiation-related biomarkers in mechanical strain treated OCCM-30 cells. Conclusions Taken together, these data suggested that intermittent PTH promoted cementum formation through activating cementogenesis- and differentiation-related biomarkers, and attenuated the catabolic effects of mechanical strain in immortalized cementoblasts OCCM-30

Ultrasensitive detection of ribonucleic acid biomarkers using portable sensing platforms based on organic electrochemical transistors

The analysis of ribonucleic acid (RNA) plays an important role in the early diagnosis of diseases and will greatly benefit patients with a higher cure rate. However, the low abundance of RNA in physiological environments requires ultrahigh sensitivity of a detection technology. Here, we construct a portable and smart-phone-controlled biosensing platform based on disposable organic electrochemical transistors for ultrasensitive analysis of microRNA (miRNA) biomarkers within 1 h. Due to their inherent amplification function, the devices can detect miRNA cancer biomarkers from little-volume solutions with concentrations down to 10–14 M. The devices can distinguish blood miRNA expression levels at different cancer stages using a 4T1 mouse tumor model. The technique for ultrasensitive and fast detection of RNA biomarkers with high selectivity opens a window for mobile diagnosis of various diseases with low cost

Self‐Cooperative Prodrug Nanovesicles Migrate Immune Evasion to Potentiate Chemoradiotherapy in Head and Neck Cancer

Abstract Chemoradiotherapy is the standard of care for the clinical treatment of locally advanced head and neck cancers. However, the combination of ion radiation with free chemotherapeutics yields unsatisfactory therapeutic output and severe side effects due to the nonspecific biodistribution of the anticancer drugs. Herein, a self‐cooperative prodrug nanovesicle is reported for highly tumor‐specific chemoradiotherapy. The nanovesicles integrating a prodrug of oxaliplatin (OXA) can passively accumulate at the tumor site and penetrate deep into the tumor mass via matrix metalloproteinase 2‐mediated cleavage of the polyethylene glycol corona. The OXA prodrug can be restored inside the tumor cells with endogenous glutathione to trigger immunogenic cell death (ICD) of the tumor cells and sensitize the tumor to ion radiation. The nanovesicles can be further loaded with the JAK inhibitor ruxolitinib to abolish chemoradiotherapy‐induced programmed death ligand 1 (PD‐L1) upregulation on the surface of the tumor cells, thereby prompting chemoradiotherapy‐induced immunotherapy by blocking the interferon gamma‐Janus kinase‐signal transducer and activator of transcription axis. The prodrug nanoplatform reported herein might present a novel strategy to cooperatively enhance chemoradiotherapy of head and cancer and overcome PD‐L1‐dependent immune evasion

The Divergent Effects of Fear and Disgust on Inhibitory Control: An ERP Study

<div><p>Negative emotional stimuli have been shown to attract attention and impair executive control. However, two different types of unpleasant stimuli, fearful and disgusting, are often inappropriately treated as a single category in the literature on inhibitory control. Therefore, the present study aimed to investigate the divergent effects of fearful and disgusting distracters on inhibitory control (both conscious and unconscious inhibition). Specifically, participants were engaged in a masked Go/No-Go task superimposed on fearful, disgusting, or neutral emotional contexts, while event-related potentials were measured concurrently. The results showed that for both conscious and unconscious conditions, disgusting stimuli elicited a larger P2 than fearful ones, and the difference waves of P3 amplitude under disgusting contexts were smaller than that under fearful contexts. These results suggest that disgusting distracters consume more attentional resources and therefore impair subsequent inhibitory control to a greater extent. This study is the first to provide electrophysiological evidence that fear and disgust differently affect inhibitory control. These results expand our understanding of the relationship between emotions and inhibitory control.</p></div

A Self-Assembled Ratiometric Polymeric Nanoprobe for Highly Selective Fluorescence Detection of Hydrogen Peroxide

In this study, a dual-emission fluorescence resonance energy transfer (FRET) polymeric nanoprobe by single-wavelength excitation was developed for sensitive and selective hydrogen peroxide (H₂O₂) detection. Polymeric nanoprobe was prepared by simple self-assembly of functional lipopolymers, which were 4-carboxy-3-fluorophenylboronic acid (FPBA)-modified DSPE-PEG (DSPE-PEG-FPBA) and 7-hydroxycoumarin (HC)-conjugated DSPE-PEG (DSPE-PEG-HC). Subsequent binding of alizarin red S (ARS) to FPBA endowed the nanoprobe with a new fluorescence emission peak at around 600 nm. Because of the perfect match of the fluorescence emission spectra of HC with the absorbance spectra of ARS-FPBA, FRET was achieved between them. The sensing strategy for H₂O₂ was based on H₂O₂-induced deboronation reaction and boronic acid-mediated ARS fluorescence. Interaction between phenylboronic acid and ARS was revisited herein and it was found that electron-donating or -withdrawing group on phenylboronic acid (PBA) has significant influence on the fluorescence property of ARS, which enabled sensitive and selective H₂O₂ sensing. The nanoprobe displayed two well-separated emission bands (150 nm), providing high specificity and sensitivity for ratiometric detection of H₂O₂. Further application was exploited for the determination of glucose and the results demonstrated that the proposed strategy showed ratiometric response capability for glucose detection. The current method does not involve complicated organic synthesis and opens a new avenue for the construction of multifunctional polymeric fluorescent nanoprobe