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.

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.

Staphylotrichum sinense sp. nov., a new hyphomycete (Chaetomiaceae) from China.

Staphylotrichum sinense, a new hyphomycete classified in the Chaetomiaceae (Ascomycota), was isolated from soil in Jianshui county, Yunnan Province. It is characterized by globose and ochreous conidia born laterally on aerial hyphae, and micronematous, unbranched and 0-1-septate conidiophores, sometimes reduced to conidiogenous cells. Morphologically, Staphylotrichum sinense is similar to Staphylotrichum boninense, but it can be distinguished by lacking of macronematous conidiophores and having larger conidia. Phylogenetically Staphylotrichum sinense formed a single clade within Staphylotrichum species, and is closely related to Staphylotrichum boninense and Staphylotrichum brevistipitatum.

An actin filament population defined by the tropomyosin Tpm3.1 regulates glucose uptake.

Actin has an ill-defined role in the trafficking of GLUT4 glucose transporter vesicles to the plasma membrane (PM). We have identified novel actin filaments defined by the tropomyosin Tpm3.1 at glucose uptake sites in white adipose tissue (WAT) and skeletal muscle. In Tpm 3.1-overexpressing mice, insulin-stimulated glucose uptake was increased; while Tpm3.1-null mice they were more sensitive to the impact of high-fat diet on glucose uptake. Inhibition of Tpm3.1 function in 3T3-L1 adipocytes abrogates insulin-stimulated GLUT4 translocation and glucose uptake. In WAT, the amount of filamentous actin is determined by Tpm3.1 levels and is paralleled by changes in exocyst component (sec8) and Myo1c levels. In adipocytes, Tpm3.1 localizes with MyoIIA, but not Myo1c, and it inhibits Myo1c binding to actin. We propose that Tpm3.1 determines the amount of cortical actin that can engage MyoIIA and generate contractile force, and in parallel limits the interaction of Myo1c with actin filaments. The balance between these actin filament populations may determine the efficiency of movement and/or fusion of GLUT4 vesicles with the PM.

A novel simian retrovirus subtype discovered in cynomolgus monkeys (Macaca fascicularis).

A new simian retrovirus (SRV) subtype was discovered in China and the USA from Cambodian-origin cynomolgus monkeys. Histopathological examination from necropsied animals showed multifocal lymphoplasmacystic and histocytic inflammation. The complete genome sequences demonstrated that the US virus isolates were nearly identical (99.91-99.93 %) and differed only slightly (99.13-99.16 % identical) from the China isolate. Phylogenetic analysis showed that the new virus isolates formed a distinct branch of SRV-1 through -7, and therefore were named this subtype, SRV-8. This SRV-8 variant was also phylogenetically and serologically more closely related to SRV-4 than any other SRV subtype.

The protective effects of Achyranthes bidentata polypeptides on rat sciatic nerve crush injury causes modulation of neurotrophic factors.

Pharmacological treatment is a therapeutic approach to improving nerve regeneration and functional recovery after peripheral nerve crush injury. The objective of the present study was to investigate the effects of the polypeptides isolated from Achyranthes bidentata Blume (abbreviated as ABPP) on rat sciatic crush injury and to test the possible involvement of neurotrophic factors. After surgical crush injury, rats received daily intraperitoneal injection of 0.2 ml saline containing 2 mg ABPP, 1 µg nerve growth factor (NGF) or no additive. The results from walking track analysis, electrophysiological assessment and histological evaluation indicated that the repair outcomes by ABPP treatment were close to those by NGF treatment, but better than those by treatment with saline alone. The quantitative real-time RT-PCR was used to monitor the mRNA expression of growth associated protein in the crush nerves and the mRNA expression of NGF, brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), tyrosine kinase (Trk)A and TrkB in the dorsal root ganglia (DRGs) at L4-L6. The mRNA expression of these genes in the crush nerve sample and DRGs sample was higher after treatment with ABPP or NGF than after treatment with saline alone. Our findings suggest that ABPP might protect peripheral nerve against crush injury through stimulating release of neurotrophic factors and the other cytokines.

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.

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.

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.

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.

Distribution and health risk assessment of HCHs in urban soils of Beijing, China.

The concentrations of hexachlorocyclohexanes (HCHs) were investigated in urban soil samples collected from business area, classical garden (CL), culture and educational area, large public green space (LA), residential area, and roadside area in Beijing. HCH concentrations ranged from 0.32 to 136.43 ng/g, with a geometric mean of 3.46 ng/g. The HCH concentrations in CL and LA were much higher than that in the other types of land use, which was due to the usage of HCHs to protect vegetation in CL and LA. Source identification showed that contamination source of HCHs was derived from historical HCHs (including technical HCHs and Lindane) as well as the long-range atmospheric transportation of HCHs. HCH concentrations showed a decreasing trend from the city centre to the suburb, and it increased with the age of the urban area. HCHs were negatively correlated with pH and positively correlated with total organic carbon and black carbon in soils. Health risk assessment with CalTOX and Monte Carlo analysis showed that health risks mainly came from dermal uptake and inhalation exposure pathways, and the total risk values were lower than the acceptable health risk value (10(- 6)). The sensitivity analysis indicated that the reaction half-life of HCHs in soil, fraction dermal uptake from soil, exposure duration, and organic carbon fraction in soil significantly contributed to the variance of the health risk.

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.

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.

Levels, distribution, and health risk of phthalate esters in urban soils of Beijing, China.

The content of phthalate esters (PAEs) was investigated in urban soil samples ( = 127, 0-20 cm) collected from a business area (BU), classical garden (CL), culture and educational area (CU), large public green space (LA), residential area (RE), and roadside area (RO) in Beijing. The sum of all PAE contents ranged from 1.9 to 3141.7 ng/g, with an average of 1139.6 ± 727.6 ng/g. Di-n-butyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) were the major contaminants in the soil samples. The content of DEHP and DBP in the urban soil of Beijing showed decreasing trends from the center of the city to the suburbs, which was probably because the center of the city has a longer history. In addition, higher DBP content also occurred in the south of the city, which was caused by the existence of several factories that produce commodity chemical and building materials in these areas. Because of its greater age, less disturbance from human activity, and high levels of total organic carbon and black carbon in CL, PAE content in CL was the highest among the six types of land use, followed by RE, CU, BU, LA, and RO. Although in 82.6% of the soil samples, DBP content exceeded the recommended allowable soil content in New York, USA, health risk assessment with CalTOX and Monte Carlo analysis showed that the total cancer risk values of PAEs were lower than the acceptable cancer risk value (10(-4)) and that the risk mainly came from dermal uptake and inhalation exposure pathways.

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.

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.

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.