ROS-mediated Therapeutics Combined with Metal-based Porphyrin Nanoparticles and their Applications in Tumor Treatment.

High concentrations of reactive oxygen species (ROS) can disrupt cell structure and induce apoptosis and necrosis of tumor cells. Photodynamic therapy (PDT) and chemodynamic therapy (CDT) are two cancer treatments mediated by reactive oxygen species. Oxygen molecules (O2 ) are one of the indispensable factors in PDT and hypoxic tumor sites limit its application. However, another ROS-mediated method, CDT, can generate •OH and O2 in situ by Fenton reaction or Fenton-like reaction. Synergistic PDT/CDT therapy is a strategy to overcome the limitations of tumor microenvironment therapy. In this review, PDT and CDT therapies are briefly introduced, with an emphasis on metal-basrd porphyrin nanoparticles constructed in different ways for PDT/CDT dual-mode therapy. By introducing the history and latest design schemes of the treatment model, it provides ideas for researchers engaged in ROS-mediated cancer therapies.

A precise design strategy for a cell-derived extracellular matrix based on CRISPR/Cas9 for regulating neural stem cell function.

The extracellular matrix (ECM) is a natural microenvironment pivotal for stem cell survival, as well as proliferation, differentiation and metastasis, composed of a variety of biological molecular complexes secreted by resident cells in tissues and organs. Heparan sulfate proteoglycan (HSPG) is a type of ECM protein that contains one or more covalently attached heparan sulfate chains. Heparan sulphate chains have high affinity with growth factors, chemokines and morphogens, acting as cytokine-binding domains of great importance in development and normal physiology. Herein, we constructed endogenous HSPG2 overexpression in mouse embryonic fibroblasts based on the CRISPR/Cas9 synergistic activation mediator system and then fabricated a cell-derived HSPG2 functional ECM (ECMHSPG2). The ECMHSPG2 is capable of enriching basic fibroblast growth factor (bFGF), which binds more strongly than the negative control ECM. With a growing bFGF concentration, ECMHSPG2 could better maintain neural stem cell (NSCs) stemness and promote NSC proliferation and differentiation in culture. These findings provide a precise design strategy for producing a specific cell-derived ECM for biomaterials in research and regenerative medicine.

The role of exosomes in central nervous system tissue regeneration and repair.

Exosomes are membrane-bound vesicles secreted by various cell types into the extracellular environment and contain kinds of bioactive molecules. These molecules can mediate various biological processes such as cell differentiation, proliferation, and survival, making them attractive for tissue regeneration and repair. Owing to their nanoscale size, bilayer membrane structure, and receptor-mediated transcytosis, exosomes can cross the blood-brain barrier (BBB) and reach the central nervous system (CNS) tissue. Additionally, exosomes can be loaded with exogenous substances after isolation. It has been suggested that exosomes could be used as natural drug carriers to transport therapeutic agents across the BBB and have great potential for CNS disease therapy by promoting tissue regeneration and repair. Herein, we discuss perspectives on therapeutic strategies to treat neurodegenerative disease or spinal cord injury using a variety of cell types-derived exosomes with kinds of exosomal contents, as well as engineering strategies of specific functional and exosome administration routes.

Enhanced Photodynamic Therapy by Improved Light Energy Capture Efficiency of Porphyrin Photosensitizers.

OPINION STATEMENT: Photodynamic therapy (PDT) has garnered increasing attention in cancer treatment because of its advantages such as minimal invasiveness and selective destruction. With the development of PDT, impressive progress has been made in the preparation of photosensitizers, particularly porphyrin photosensitizers. However, the limited tissue penetration of the activating light wavelengths and relatively low light energy capture efficiency of porphyrin photosensitizers are two major disadvantages in conventional photosensitizers. Therefore, tissue penetration needs to be enhanced and the light energy capture efficiency of porphyrin photosensitizers improved through structural modifications. The indirect excitation of porphyrin photosensitizers using fluorescent donors (fluorescence resonance energy transfer) has been successfully used to address these issues. In this review, the enhancement of the light energy capture efficiency of porphyrins is discussed.

Development and psychometric testing of a scale for assessing the psychological birth trauma.

Background: Psychological birth trauma is widespread in postpartum women, and its harms are serious to mothers' health. Existing tools rely on posttraumatic stress disorder to evaluate, which cannot effectively evaluate its connotation. The aim of this study was to develop a new instrument for use to comprehensively assess the psychological birth trauma level of women after birth and test the scale's psychometric properties. Methods: The scale was developed and evaluated through item generation, expert consultation, pre-survey, and psychometric evaluation. A literature review, focus group, and individual deep semi-structured interviews were utilized to identify the scale items. The expert consultation evaluated the content validity. Psychometric testing was conducted in a convenience sample of 712 mothers within the first 72 h postpartum who were recruited from three hospitals in China. Results: The total Cronbach alpha coefficient of the scale was 0.874. Exploratory factor analysis supported that the final scale consisted of four dimensions and fifteen items. The explanatory variance of the four factors was 66.724%. The four dimensions are named "being neglected," "out of control," "physiological emotional response," and "cognitive behavioral response." The results of the confirmatory factor analysis showed that the fit indices were all at acceptable and good levels. Conclusion: The 15-item Birth Trauma Scale is a valid and reliable tool to evaluate the psychological trauma of mothers who experienced spontaneous childbirth. The scale is a maternal self-assessment scale that can help women understand their mental health. Healthcare providers can identify key populations and intervene with them.

Specific anti-glioma targeted-delivery strategy of engineered small extracellular vesicles dual-functionalised by Angiopep-2 and TAT peptides.

Glioma is one of the primary malignant brain tumours in adults, with a poor prognosis. Pharmacological reagents targeting glioma are limited to achieve the desired therapeutic effect due to the presence of blood-brain barrier (BBB). Effectively crossing the BBB and specifically targeting to the brain tumour are the major challenge for the glioma treatments. Here, we demonstrate that the well-defined small extracellular vesicles (sEVs) with dual-targeting drug delivery and cell-penetrating functions, modified by Angiopep-2 and trans-activator of transcription peptides, enable efficient and specific chemotherapy for glioma. The high efficiency of engineered sEVs in targeting BBB and glioma was assessed in both monolayer culture cells and BBB model in vitro, respectively. The observed high targeting efficiency was re-validated in subcutaneous tumour and orthotopic glioma mice models. After loading the doxorubicin into dual-modified functional sEVs, this specific dual-targeting delivery system could cross the BBB, reach the glioma, and penetrate the tumour. Such a mode of drug delivery significantly improved more than 2-fold survival time of glioma mice with very few side effects. In conclusion, utilization of the dual-modified sEVs represents a unique and efficient strategy for drug delivery, holding great promise for the treatments of central nervous system diseases.

High-efficiency brain-targeted intranasal delivery of BDNF mediated by engineered exosomes to promote remyelination.

The regeneration of myelin sheaths is the ultimate goal of the treatment of demyelination disease, including multiple sclerosis (MS). However, current drugs for MS mainly target the immune system and can only slow down the disease development and do not promote the differentiation of oligodendrocyte precursor cells (OPCs) abundant in the myelin injury region into mature oligodendrocytes to form a new myelin sheath. Brain-derived neurotrophic factor (BDNF) plays an important role in the regulation of OPC proliferation and differentiation into mature oligodendrocytes. Exosomes, a kind of nanoscale membrane vesicle secreted by cells, can be used as potential therapeutic drug delivery vectors for central nervous system diseases. Here, brain-targeted modification and BDNF intracellular-loaded exosomes were produced through engineering HEK293T cells, which can promote the differentiation of OPCs into mature oligodendrocytes in vitro. The intranasal administration of the brain-targeted engineered exosome-mediated BDNF was a highly effective delivery route to the brain and had a significant therapeutic effect on remyelination and motor coordination ability improvement in demyelination model mice. The combination of intranasal administration with brain-targeted and BDNF-loaded designed exosomes provides a strategy for efficient drug delivery and treatment of central nervous system diseases.

Cell-derived extracellular matrix enhanced by collagen-binding domain-decorated exosomes to promote neural stem cells neurogenesis.

Enhancing neurogenesis of neural stem cells (NSCs) is crucial in stem cell therapy for neurodegenerative diseases. Within the extracellular microenvironment, extracellular matrix (ECM) plays a pivotal role in modulating cell behaviors. However, a single ECM biomaterial is not sufficient to establish an ideal microenvironment. As multifunctional nanocarriers, exosomes display tremendous advantages for the treatments of various diseases. Herein, collagen binding domain peptide-modified exosomes (CBD-Exo) were obtained from the SH-SY5Y cell line infected with lentivirus particles encoding CBD-lysosome associated membrane glycoprotein 2b (CBD-Lamp2b) to improve the binding efficiency of exosomes and ECM. An exosomes-functionalized ECM (CBD-Exo/ECM) was then constructed via the interaction between CBD and collagen in ECM. Then, CBD-Exo/ECM was employed as a carrier for NSCs culture. The results showed that CBD-Exo/ECM can support the neurogenesis of NSCs with the percentage of proliferation marker EdU-positive (35.8% ± 0.47% vs 21.9% ± 2.32%) and neuron maker Tuj-1-positive (55.8% ± 0.47% vs 30.6% ± 2.62%) were both significantly increased in the exosomes-functionalized ECM system. This exosomes-functionalized ECM was capable to promote the cell proliferation and accelerate neuronal differentiation of NSCs, providing a potential biomedical material for stem cell application in tissue engineering and regenerative medicine.

Iron Hydroxide/Oxide-Reduced Graphene Oxide Nanocomposite for Dual-Modality Photodynamic and Photothermal Therapy In Vitro and In Vivo.

Minimal invasive phototherapy utilising near-infrared (NIR) laser to generate local reactive oxygen species (ROS) and heat has few associated side effects and is a precise treatment in cancer therapy. However, high-efficiency and safe phototherapeutic tumour agents still need developing. The application of iron hydroxide/oxide immobilised on reduced graphene oxide (FeOxH-rGO) nanocomposites as a therapeutic agent in integration photodynamic cancer therapy (PDT) and photothermal cancer therapy (PTT) was discussed. Under 808 nm NIR irradiation, FeOxH-rGO offers a high ROS generation and light-to-heat conversion efficiency because of its strong NIR absorption. These phototherapeutic effects lead to irreversible damage in FeOxH-rGO-treated T47D cells. Using a tumour-bearing mouse model, NIR ablated the breast tumour effectively in the presence of FeOxH-rGO. The tumour treatment response was evaluated to be 100%. We integrated PDT and PTT into a single nanodevice to facilitate effective cancer therapy. Our FeOxH-rGO, which integrates the merits of FeOxH and rGO, displays an outstanding tumoricidal capacity, suggesting the utilization of this nanocomposites in future medical applications.

Strategy for Designing a Cell Scaffold to Enable Wireless Electrical Stimulation for Enhanced Neuronal Differentiation of Stem Cells.

Electrical stimulation (ES) offers significant advantages in modulating the behavior of stem cells on conductive scaffolds for neural tissue engineering. However, it is necessary to realize wireless ES to avoid the use of external wires in tissues. Thus, herein, a strategy is reported to develop a stem cell scaffold that allows wireless ES. A conductive annular graphene substrate is designed and grown by chemical vapor deposition; this substrate is used as a secondary coil to achieve wireless ES via electromagnetic induction in the presence of a primary coil. The substrate shows excellent biocompatibility for the culture of neural stem cells (NSCs). The results indicate that the applied wireless ES enhances neuronal differentiation, facilitates the formation of neurites, and does not substantially affect the viability and stemness maintenance of NSCs. Collectively, this system provides a strategy for achieving synergy between wireless ES and conductive scaffolds for neural regenerative medicine, which can be further utilized for the regeneration of other tissues.

Correction to: How parental migration affects early social-emotional development of left-behind children in rural China: a structural equation modeling analysis.

The authors would like to correct errors in the publication of the original article. The errors described below and correct details provided.

How parental migration affects early social-emotional development of left-behind children in rural China: a structural equation modeling analysis.

OBJECTIVES: This study assessed the early social-emotional development of left-behind children (LBC) in rural China and determined the mediating factors linking parental migration to LBC's developmental outcome. METHODS: We used cross-sectional data of 845 LBC under 3 years old from five counties in rural China in 2018. Social-emotional problems were assessed by the ages and stages questionnaires: social-emotional. Family structure, function, and child nurturing care practices were measured to explore their roles in potential pathways of parental migration affecting early social-emotional development. RESULTS: 36.4% of LBC were identified with social-emotional problems; the rate was higher among LBC with migrant parents than those with migrant fathers (39.9% vs. 30.5%, adjusted OR: 1.40 [95% CI 1.01, 1.93]). Results of structural equation modeling reveal that caregivers' low education and depressive symptoms, poor migrant-caregiver communication, family poverty, and no assistant caregiving weakened home parenting environment, and then contributed to LBC's social-emotional problems. CONCLUSIONS: LBC in early childhood may be at a high risk of social-emotional problems, which are primarily caused by the transition of family structure and function and consequently weakened home environment.

Autophagy Induced by Simian Retrovirus Infection Controls Viral Replication and Apoptosis of Jurkat T Lymphocytes.

Autophagy and apoptosis are two important evolutionarily conserved host defense mechanisms against viral invasion and pathogenesis. However, the association between the two pathways during the viral infection of T lymphocytes remains to be elucidated. Simian type D retrovirus (SRV) is an etiological agent of fatal simian acquired immunodeficiency syndrome (SAIDS), which can display disease features that are similar to acquired immunodeficiency syndrome in humans. In this study, we demonstrate that infection with SRV-8, a newly isolated subtype of SRV, triggered both autophagic and apoptotic pathways in Jurkat T lymphocytes. Following infection with SRV-8, the autophagic proteins LC3 and p62/SQSTM1 interacted with procaspase-8, which might be responsible for the activation of the caspase-8/-3 cascade and apoptosis in SRV-8-infected Jurkat cells. Our findings indicate that autophagic responses to SRV infection of T lymphocytes promote the apoptosis of T lymphocytes, which, in turn, might be a potential pathogenetic mechanism for the loss of T lymphocytes during SRV infection.

The Regulatory Functionality of Exosomes Derived from hUMSCs in 3D Culture for Alzheimer's Disease Therapy.

Reducing amyloid-ß (Aß) accumulation could be a potential therapeutic approach for Alzheimer's disease (AD). Particular functional biomolecules in exosomes vested by the microenvironment in which the original cells resided can be transferred to recipient cells to improve pathological conditions. However, there are few reports addressing whether exosomes derived from cells cultured on scaffolds with varying dimension can reduce Aß deposition or ameliorate cognitive decline for AD therapy. Herein, both 3D graphene scaffold and 2D graphene film are used as the matrix for human umbilical cord mesenchymal stem cell culture, from which the supernatants are obtained to isolate exosomes. The levels of 195 kinds of miRNAs and proteins, including neprilysin, insulin-degrading enzyme and heat shock protein 70, in 3D-cultured exosomes (3D-Exo) are dramatically different from those obtained from 2D culture. Hence, 3D-Exo could up-regulate the expression of α-secretase and down-regulate the ß-secretase to reduce Aß production in both AD pathology cells and transgenic mice, through their special cargo. With rescuing Aß pathology, 3D-Exo exerts enhanced therapeutic effects on ameliorating the memory and cognitive deficits in AD mice. These findings provide a novel clinical application for scaffold materials and functional exosomes derived from stem cells.

Gentamicin-loaded silk/nanosilver composite scaffolds for MRSA-induced chronic osteomyelitis.

Methicillin-resistant Staphylococcus aureus (MRSA) often induces chronic osteomyelitis and then bone defects. Here, gentamicin-loaded silk/nanosilver composite scaffolds were developed to treat MRSA-induced chronic osteomyelitis. AgNO3 was reduced with silk as a reducing agent in formic acid, forming silver nanoparticles in situ that were distributed uniformly in the composite scaffolds. Superior antibacterial properties against MRSA were achieved for the composite scaffolds, without the compromise of osteogenesis capacity. Then gentamicin was loaded on the scaffolds for better treatment of osteomyelitis. In vivo results showed effective inhibition of the growth of MRSA bacteria, confirming the promising future in the treatment of chronic osteomyelitis.

Homogeneously alloyed nanoparticles of immiscible Ag-Cu with ultrahigh antibacterial activity.

Immiscible bimetallic Ag-Cu system has been synthesized by the pulsed plasma in liquid method with a graph of one pulse duration. Herein, by combining X-ray power diffraction, K-edge X-ray absorption near edge structure and high-resolution transmission electron microscopy, our results indicate that homogeneously alloyed Ag-Cu nanoparticles (Ag-Cu NAs) have the average diameter about 2.1 nm, composed by 48.5 at% Ag and 51.5 at% Cu with chemical analysis and the estimated lattice parameter was 3.873 Å. The antibacterial property of Ag-Cu NAs was detected against E. coli and S. aureus strains according to the colony formed abilities of bacteria on agar plates covered with the nanoparticles. With very short incubation period, Ag-Cu NAs completely inhibited the E. coli and S. aureus growth at an ultralow concentration. The mechanism of antibacterial property of Ag-Cu NAs was performed by the inductively coupled plasma-atomic emission spectrometry and the plane wave pseudopotential method implemented in the CASTEP package based on the density functional theory. The Ag+ dissolution is correlated with antibacterial activity for Ag-Cu NAs-assisted antibacterial treatment. These findings obtained revealed that our Ag-Cu NAs could be served as a containing material of numerous bacteria-free products in order to avoid their bacterial contamination.

One-step synthesis of novel phosphorus nitride dots for two-photon imaging in living cells.

Novel phosphorus nitride dots mainly consisting of N and P with strong fluorescence, excellent dispersibility and outstanding biocompatibility were prepared via a solvothermal method. The phosphorus nitride dots demonstrated great two-photon imaging capability in living cells under 800 nm excitation.

Fluorescent Ag clusters conjugated with anterior gradient-2 antigen aptamer for specific detection of cancer cells.

Anterior gradient protein 2 homolog (AGR) is a potential tumor biomarker and plays an important role in tissue development and regeneration. The intracellular detection of AGR is rarely reported. By conjugating the AGR aptamer with a cytosine base sequence as Ag cluster template, a highly fluorescent probe (MA@AgNCs) was synthesized for targeting intracellular AGR. The MA@AgNCs display a maximum fluorescence peak at 565 nm, and possess an excellent quantum yield (QY = 87.43%), small size, great biocompatibility, low toxicity, and good stability. Moreover, the as synthesized MA@AgNCs show high specificity on recognizing breast cancer cells.

Achyranthes bidentata polypeptides promotes migration of Schwann cells via NOX4/DUOX2-dependent ROS production in rats.

Achyranthes bidentata polypeptides (ABPP), an active polypeptides isolated from the aqueous extract of Achyranthes bidentata Blume, contributes to the regeneration of injured peripheral nerves by promoting migration of Schwann cells (SCs). In this study, we aimed to investigate the possible mechanism underlying the ABPP-induced migration of primary cultured rat SCs. Transwell migration assays indicated that ABPP promoted SCs migration in a concentration-dependent manner by inducing production of NADPH-oxidase (NOX)-derived reactive oxygen species (ROS). Inhibition of ROS production by NOXs inhibitor apocynin (APO) or diphenyleneiodonium (DPI) partially blocked ABPP-mediated SCs migration. Furthermore, by using real-time polymerase chain reaction analysis and siRNA interference technique, we verified the participation of NOX subunit 4 (NOX4) and dual oxidase 2 (DUOX2) in ABPP-induced ROS production and consequential SCs migration. Taken together, these results demonstrated that ABPP promoted SCs migration via NOX4/DUOX2-activated ROS in SCs.

Photothermally controlled drug release system with high dose loading for synergistic chemo-photothermal therapy of multidrug resistance cancer.

Chemotherapy is an important first-line strategy for tumor therapy in cancer treatment, but multidrug resistance (MDR) is a major problem that reduces the efficacy of chemotherapeutics. Herein, we report a novel photothermally controlled intelligent drug release system (AuNP@mSiO2-DOX-FA) with a large amount of drugs loading for synergistic chemo-photothermal therapy of MDR in breast cancer. The nanoplatform utilized gold nanoparticles as a hyperthermia core, and large-mesoporous silica as a shell for doxorubicin (DOX) loading. Benefiting from the thick layer and large pore size, the encapsulation and loading efficiency were as high as 97.7% and 8.84%, respectively. Furthermore, under the trigger of 808 nm near infrared (NIR) light, the released DOX increased significantly at pH 5.0 and reached to 39.0% in 20 min, achieving a facile intelligent control of chemotherapy additional to the photothermal therapy. The viability of MCF-7/ADR cells could be efficiently reduced to 16.9%, demonstrating the proposed photothermally controlled system with synergistic chemo-photothermal therapy has great potential capability to overcome MDR in breast cancer.