A SU6668 pure nanoparticle-based eyedrops: toward its high drug Accumulation and Long-time treatment for corneal neovascularization.

Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.

TEMPO-Oxidized Nanocellulose Films Modified by Tea Saponin Derived from Camellia oleifera: Physicochemical, Mechanical, and Antibacterial Properties.

Nanocellulose materials have been widely used in biomedicine, food packaging, aerospace, composite material, and other fields. In this work, cellulose obtained from Camellia shells through alkali boiling and subbleaching was micro-dissolved and regenerated using the DMAc (N,N-Dimethylacetamide)/LiCl system, and TOCNs (TEMPO-oxidized cellulose nanofibers) with different degrees of oxidation. The membrane was prepared by filtration of polytetrafluoroethylene (pore size 0.1 µm), and the oxidized nanocellulose film was obtained after drying, Then, the crystallinity, mechanical properties and oxygen barrier properties of the TOCN film were investigated. Furthermore, based on TS (tea saponin) from Camellia oleifera seed cake and TOCNs, TS-TOCN film was prepared by the heterogeneous reaction. The TS-TOCN film not only shows excellent oxygen barrier properties (the oxygen permeability is 2.88 cc·m-2·d-1) but also has good antibacterial effects on both Gram-negative and Gram-positive bacteria. The antibacterial property is comparable to ZnO-TOCN with the same antibacterial content prepared by the in-situ deposition method. Antioxidant activity tests in vitro showed that TS-TOCN had a significant scavenging effect on DPPH (2,2-Diphenyl-1-picrylhydrazyl) radicals. This design strategy makes it possible for inexpensive and abundant Camellia oleifera remainders to be widely used in the field of biobased materials.

Konjac glucomannan films incorporated pectin-stabilized Mandarin oil emulsions: Structure, properties, and application in fruit preservation.

To enhance the water-resistance and antibacterial properties of KGM films, mandarin oil (MO), was directly emulsified by pectin and then dispersed to the KGM matrix. The effect of MO concentration (0, 0.5, 1.0, 1.5, and 2 wt%) on the performance of the film-forming emulsions as well as the emulsion films was investigated. The results revealed that pectin could encapsulate and protect MO, and KGM as film matrix could further contributed to the high stability of the film-forming emulsions. The FT-IR, XRD, and SEM suggested that MO stabilized by pectin was uniformly distributed in the KGM matrix. The compatibility and good interaction between KGM and pectin contributed to highly dense and compact structure. Furthermore, increasing the concentration of MO effectively improved water-resistance, oxygen barrier, and antimicrobial activity of the KGM based films. The 1.5 wt% MO loaded KGM film had the highest tensile strength (72.22 MPa) and water contact angle (θ = 95.73°), reduced the WVP and oxygen permeability by about 25.8 % and 32.8 times, respectively, prolonged the shelf life of strawberries for 8 days. As demonstrated, the 1.5 wt% MO-loaded KGM film has considerable potential for high-performance natural biodegradable active films to ensure food safety and reduce environmental impacts.

Enhanced removal of trace thallium by photo-promoted adsorption using Prussian blue@filter papers: Performance and mechanistic insights.

Developing highly efficient adsorbents for the removal of trace thallium(I) (Tl+) is crucial for addressing environmental challenges. In this study, we successfully synthesized cubic Prussian blue (PB) loading on filter papers using an intermediate layer (dopamine/polyethyleneimine) via in-situ methods. The as-prepared PB-modified FP demonstrated outstanding anti-interference properties and light-enhanced adsorption performance for Tl+ (0.5 mg/L) under ultraviolet (UV) irradiation, exhibiting twice the effectiveness compared to dark conditions, even in acidic and coexisting ionic environments. This indicated its suitability for treating complex Tl+-contaminated water. Notably, the removal efficiency for trace Tl+ was almost 100%, with a maximum experimental adsorption capacity of 86.2 mg/g after 1-h photo-promoted adsorption under 365 nm UV. Characterization results supported a proposed photo-driven redox mechanism that elucidated the interaction between Tl+ and PB-modified FP. Specifically, the accelerated Fe(III) to Fe(II) redox reaction facilitated Tl+ accommodation on the surface and/or lattice of PB, enhancing Tl+ adsorption by compensating for missed positive charges. This study provides valuable insights into utilizing PB-based materials to enhance the photo-enhanced Tl+ adsorption capacity in a cost-effective, easy-to-synthesize, and environmentally friendly manner.

Revolutionizing eye care: the game-changing applications of nano-antioxidants in ophthalmology.

Since the theory of free radical-induced aging was proposed in 1956, it has been constantly proven that reactive oxygen species (ROS) produced by oxidative stress play a vital role in the occurrence and progression of eye diseases. However, the inherent limitations of traditional drug therapy hindered the development of ophthalmic disease treatment. In recent years, great achievements have been made in the research of nanomedicine, which promotes the rapid development of safe theranostics in ophthalmology. In this review, we focus on the applications of antioxidant nanomedicine in the treatment of ophthalmology. The eye diseases were mainly classified into two categories: ocular surface diseases and posterior eye diseases. In each part, we first introduced the pathology of specific diseases about oxidative stress, and then presented the representative application examples of nano-antioxidants in eye disease therapy. Meanwhile, the nanocarriers that were used, the mechanism of function, and the therapeutic effect were also presented. Finally, we summarized the latest research progress and limitations of antioxidant nanomedicine for eye disease treatment and put forward the prospects of future development.

A Synergistic Therapy With Antioxidant and Anti-VEGF: Toward its Safe and Effective Elimination for Corneal Neovascularization.

Corneal neovascularization (CNV) is one of the leading causes of blindness in the world. In clinical practice; however, it remains a challenge to achieve a noninvasive and safe treatment. Herein, a biocompatible shell with excellent antioxidant and antivascularity is prepared by co-assembly of epigallocatechin gallate/gallic acid and Cu (II). After loading glucose oxidase (GOx) inside, the shell is modified with dimeric DPA-Zn for codelivering vascular endothelial growth factor (VEGF) small interfering RNA (VEGF-siRNA). Meanwhile, the Arg-Gly-Asp peptide (RGD) peptide-engineered cell membranes coating improves angiogenesis-targeting and is biocompatible for the multifunctional nanomedicine (CEGs/RGD). After eye drops administration, CEGs/RGD targets enrichment in neovascularization and CEGs NPs enter cells. Then, the inner GOx consumes glucose with a decrease in local pH, which in turn leads to the release of EGCE and VEGF-siRNA. As a result, the nanomedicines significantly reduce angiogenesis and inhibit CNV formation through synergistic effect of antioxidant and antivascular via down-regulation of cluster of differentiation 31 and VEGF. The nanomedicine represents a safe and efficient CNV treatment through the combined effect of antioxidant/gene, which provides important theoretical and clinical significance.

ICG-based laser treatments for ophthalmic diseases: Toward their safe and rapid strategy.

The eye is a very important organ, and keratitis, corneal neovascularization, floaters, age-related macular degeneration, and other vision problems have seriously affected people's quality of life. Among the ophthalmic treatments, laser photocoagulations have been proposed and have shown therapeutic effects in clinical settings. However, corneal thinning and bleeding lesions induced by laser damage have led to limit its applications. To treat the issues of traditional hyperthermia treatments, photosensitizers [e.g., indocyanine green (ICG)] have been investigated to increase the therapeutic effects of corneal neovascularization and choroidal neovascularization. In the recent study, with the help of ICG, laser-induced nanobubble was proposed to treat vitreous opacities. The developed strategies could enlarge the effect of laser irradiation and reduce the side effects, so as to expand the scope of laser treatments in clinical ophthalmic diseases.

Self-Assembled MoS2 Cladding for Corrosion Resistant and Frequency-Modulated Electromagnetic Wave Absorption Materials from X-Band to Ku-Band.

Reasonable composition design and controllable structure are effective strategies for harmonic electromagnetic wave (EMW) adsorption of multi-component composites. On this basis, the hybrid MoS2 /CoS2 /VN multilayer structure with the triple heterogeneous interface is prepared by simple stirring hydrothermal, which can satisfy the synergistic interaction between different components and obtain excellent EMW absorption performance. Due to the presence of multiple heterogeneous interfaces, MoS2 /CoS2 /VN composites will produce strong interfacial polarization, while the defects in the sample will become the center of polarization, resulting in dipole polarization. Due to the excellent structural design of MoS2 /CoS2 /VN composite material, MoS2 /CoS2 /VN composite material not only has good conductive loss and polarization loss, but also can maintain excellent stability in simulated seawater, and enhance corrosion resistance. The MoS2 /CoS2 /VN composite with dual functions of corrosion resistant and microwave absorption achieves a minimum reflection loss (RL) of -50.48 dB and an effective absorption bandwidth of up to 5.76 GHz, covering both the X-band and Ku-band. Finally, this study provides a strong reference for the development of EMW absorption materials based on transition metal nitrides.

Sensing and Stimulation Applications of Carbon Nanomaterials in Implantable Brain-Computer Interface.

Implantable brain-computer interfaces (BCIs) are crucial tools for translating basic neuroscience concepts into clinical disease diagnosis and therapy. Among the various components of the technological chain that increases the sensing and stimulation functions of implanted BCI, the interface materials play a critical role. Carbon nanomaterials, with their superior electrical, structural, chemical, and biological capabilities, have become increasingly popular in this field. They have contributed significantly to advancing BCIs by improving the sensor signal quality of electrical and chemical signals, enhancing the impedance and stability of stimulating electrodes, and precisely modulating neural function or inhibiting inflammatory responses through drug release. This comprehensive review provides an overview of carbon nanomaterials' contributions to the field of BCI and discusses their potential applications. The topic is broadened to include the use of such materials in the field of bioelectronic interfaces, as well as the potential challenges that may arise in future implantable BCI research and development. By exploring these issues, this review aims to provide insight into the exciting developments and opportunities that lie ahead in this rapidly evolving field.

Phototoxicity effects of NIR-irradiated cesium tungsten oxide (Cs0.33WO3) nanoparticles on zebrafish embryos: A direct immersion study.

Nanoparticles (NPs) with feature sizes ranging between 1 nm and 100 nm have increasingly gained momentum for their versatile functionality as the pharmaceutical agents in many branches of biomedical research and clinical experiments. However, NPs' inherent material toxicity and the concomitant adverse effects of their function, such as photo-physical properties, often remain a major concern over the issues of environmental safety and human health, and require a thorough assessment before a wide-spread usage can be complied. This research herein investigates the intrinsic and photothermal toxicity of Cs0.33WO3 NPs solution in zebrafish larvae through a direct immersion method. Experimentally, the survival, hatching and malformation rates of zebrafish embryo/larvae as functions of the NP feature sizes, concentration and duration of photothermal dose were examined and analyzed. This study verified that the Cs0.33WO3 NPs has an intrinsic toxicity on a scale of a fraction of 1 mg/ml, and the phototoxicity effect of the NIR-irradiated NPs, when irradiated for 30 min, can affect the embryogenesis of zebrafish larvae and causes 60% and 50% in the survival and delayed hatching rates, respectively, as well as a severe malformation.

Effects of Overt and Relational Bullying on Adolescents' Subjective Well-Being: The Mediating Mechanisms of Social Capital and Psychological Capital.

Based on the social and psychological capital framework, this study aimed to investigate the direct effect of bullying on adolescents' subjective well-being and to reveal the potential psychosocial mechanisms in this relationship. Through the multi-stage cluster random sampling procedure, a cross-sectional survey was conducted among 728 adolescents from Hebei Province in China. Structural equation modeling was adopted for data analysis. After controlling for sociodemographic variables, the results indicated that only relational bullying had a significant negative effect on adolescents' subjective well-being. Moreover, social capital and psychological capital mediated the relationship between relational bullying and adolescents' subjective well-being. This study expands our understanding of the influencing mechanisms from bullying victimization to subjective well-being and also provides practical implications for future social policy development and relevant interventions.

Examining the mediator and moderator of the link between Migration-Related stress and depression amongst Chinese migrant children.

Migration-related stress is detrimental to children's mental health, yet little is known about the potential mechanisms behind this association. This study examines the mediating role of inflow city identity in the association between migration-related stress and depression and the moderating role of social participation amongst Chinese migrant children. A sample of 484 migrant children aged 8-17 years is randomly recruited through a cross-sectional survey in Kunming, China. Inflow city identity partially mediates the association between migration-related stress and migrant children's depression. Moreover, social participation moderates the above relationship. The direct and indirect effects are significant for migrant children with low social participation but insignificant for migrant children with high social participation. This study deepens the theoretical understanding of the underlying mechanism between migration stress and psychological distress and provides practical implications for preventing mental disorders in Chinese migrant children.

Fear of cancer recurrence is related to the efficacy of immunotherapy and quality of life in patients with NSCLC during the COVID-19 pandemic in China.

The outbreak of the COVID-19 pandemic has greatly impacted patients with non-small cell lung cancer (NSCLC), making the fear of cancer recurrence (FCR) more pronounced. We explored the effects of FCR on immunotherapy efficacy and quality of life during the COVID-19 pandemic in China among the 124 NSCLC patients enrolled in this study. Quality of life and immunotherapy efficacy were compared between high- and low-FCR groups after completing 4-6 courses of treatment or cancer progression. Worse immunotherapy efficacy and quality of life were reported for the high-FCR group than for the low-FCR group. These findings emphasize the need to pay close attention to the level of FCR in NSCLC patients. Efforts should be taken to alleviate FCR levels among NSCLC patients. Moreover, research is needed to investigate the possible link between immunotherapy efficacy and FCR.

Exploration of Mutated Genes and Prediction of Potential Biomarkers for Childhood-Onset Schizophrenia Using an Integrated Bioinformatic Analysis.

Childhood-onset schizophrenia (COS) is an unusual severe neurodevelopmental disorder of unknown etiology. In this study, we aimed to survey the missense variants in new cases of COS and also identify possible pathology biomarkers for COS. We found one list of mutated genes such as TTN, MUC12, and MUC2, which are the candidates to be involved in the etiology of COS. Next, we used WGSNA to predict COS disease-related genes and identified differential DNA methylation among COS disease groups, COS dangerous groups, and normal groups and found eight methylation sites that can be used as the diagnostic biomarkers. A total of six key genes are obtained through the intersection analysis between weighted correlation network analysis (WGCNA) mode, methylation-related genes, and differentially expressed genes (DGenes). These genes may play important roles in the progression of COS and serve as the potential biomarkers for future diagnosis. Our results might help to design the molecule or gene-targeted drugs for COS.

Trace element accumulation from swine feeds to feces in Chinese swine farms: Implication for element limits.

Trace elements like copper and zinc are supplemented in swine feeds to suppress bacteria and/or promote growth. Due to low absorption rates, trace elements are highly concentrated in swine feces, posing a risk to soil and human health if applied to agricultural fields. In the present study, the concentrations of six trace elements (Cu, Zn, As, Cd, Pb, and Cr) in pig feed and feces were evaluated by sample analysis and data from the literature. The feed-to-feces and feces-to-compost enrichment factors of the trace elements were determined to back-calculate safe concentrations in feed needed to meet permissible trace element concentrations in organic fertilizers. The Cu and Zn concentrations in feeds were the highest, being statistically significantly higher in starter pig feeds than in grower-finisher feeds. Copper exceeded feed limits mainly in the feeds of finisher pigs and sows, while exceedance for Zn occurred in almost all feed samples. Concentrations above the limits were also observed for Pb and Cr impurities in mineral feed supplements. The highest Cu and Zn concentrations in feces were observed for starter pigs. Moreover, significant enrichment of trace elements from feeds to feces was found, with enrichment factors calculated as: 4.68-6.11 for Cu, 3.43-4.60 for Zn, 2.30-3.12 for As, 2.89-4.63 for Cd, 2.45-5.00 for Pb, and 3.32-5.00 for Cr. On this basis, the recommended calculated limits for Cu, Zn, As, Cd, Pb, and Cr in feeds for different ages of pigs were 41-53, 130-175, 2-3, 0.3-0.5, 5-10, and 15-23 mg/kg, respectively. Priority index calculations and the calculated recommended limits indicated that Cu in starter pig feeds and Cd in starter and breeding pig feeds should be prioritized for reduction to enable feces compost to be utilized safely in agricultural land amendment. Integr Environ Assess Manag 2022;18:978-987. © 2021 SETAC.

Anti-BCMA CAR-T Cell Therapy in Relapsed or Refractory Multiple Myeloma Patients with Impaired Renal Function.

Anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy is effective and well-tolerated for refractory or relapsed multiple myeloma (RRMM). The purpose of the present study was to analyze efficacy in RRMM patients with renal impairment treated by anti-BCMA CAR-T cell therapy. A total of 59 RRMM patients were selected, and divided into impaired renal function (IRF) group [baseline estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 (n=18)] and normal renal function (NRF) group (baseline eGFR ≥ 90 mL/min/1.73 m2, n=41). For patients with IRF, eGFR at the 6th month post-CAR-T cells infusion was significantly higher than the baseline (P<0.05). The multivariate analysis showed that light chain type and beta-2 micro-globulin (beta-2M) were associated factors with the decrease of serum creatinine. Median progression-free survival (PFS) in the NRF group and IRF group was 266 days and 181 days respectively. Overall survival (OS) in the NRF group and IRF group was 877 days and 238 days respectively. There was no significant difference in the objective response rate (ORR) between the IRF group and the NRF group. It is suggested that CAR-T cells therapy could improve the renal function during the treatment of RRMM. The renal function could be more significantly improved in RRMM patients with light chain type than with other types.

Clozapine Metabolism in East Asians and Caucasians: A Pilot Exploration of the Prevalence of Poor Metabolizers and a Systematic Review.

PURPOSE/BACKGROUND: In clozapine therapeutic drug monitoring (TDM) studies, Chinese reached the same concentrations using half the dosage Caucasians use. Defining clozapine poor metabolizers (PMs) requires stratification by ethnicity, smoking, and sex. METHODS/PROCEDURES: After sex and smoking stratification in 129 Chinese inpatients (mean, 8.8 TDM samples per patient), we explored the association between the total concentration-dose (C/D) ratio and CYP1A2 (*1C, *1F, and *7) and CYP2C19 alleles (*2 and *3). A systematic literature review identified 22 clozapine TDM prior studies (13 in Caucasians and 7 in East Asians). FINDINGS/RESULTS: In our Chinese sample, the mean total clozapine C/D ratio (ng/mL per mg/d) was 1.96 for 22 male smokers, 2.07 for 5 female smokers, 2.47 for 36 male nonsmokers, and 2.95 for 66 female nonsmokers. CYP1A2 *1C had no significant effects, and CYP1A2 *1F had small effects. Five clozapine PMs (4%) needed low clozapine doses of 75 to 115 mg/d to get therapeutic concentrations. Using the same methodology in a published Italian sample, we found 5 PMs (3.3% of 152). In the systematic review, the clozapine C/D ratio (ng/mL per mg/d) was higher when comparing: (1) weighted mean values of 1.57 in 876 East Asians versus 1.07 in 1147 Caucasians and (2) ranks of 8 East Asians versus 13 Caucasian samples (P < 0.001). IMPLICATIONS/CONCLUSIONS: Future TDM studies need to further explore the frequency of clozapine PMs after sex and smoking stratification in East Asian and Caucasian patients. Compared with Caucasians, East Asians appear to have a clinically relevant decrease in clozapine clearance.

Elevated heat shock proteins in bipolar disorder patients with hypothalamic pituitary adrenal axis dysfunction.

BACKGROUND: Heat shock proteins (HSP) might be useful as biomarkers for bipolar disorder (BD) which would be clinically valuable since no reliable biomarker for BD has so far been identified. The purpose of this study was to assess the heat shock proteins CPN10, CPN60, and CPN70 as potential biomarkers of BD. METHODS: The study included 100 BD patients recruited from a hospital during 2012 and 2013. The study also included 94 healthy controls. Among the BD patients, 33 had abnormal hypothalamic-pituitary-adrenal (HPA) axis activity. Blood samples were obtained from the patients and controls. The chemiluminescence method, mass spectrometry, and flow cytometry were used for analysis. RESULTS: The BD patients compared with the controls had a significantly lower level of CPN10 and significantly higher levels of CPN60 and CPN70. The BD patients with abnormal HPA axis activity had a significantly lower level of CPN60 compared with the normal HPA axis activity group of BD patients. The CPN60 level significantly inversely correlated with adrenocorticotropic hormone (ACTH) level in patients with bipolar depression and in patients with bipolar hypomania, and CPN70 significantly correlated with ACTH level in patients with bipolar depression and hypomania. CONCLUSIONS: Our findings suggest that the heat shock proteins CPN10, CPN60, and CPN70 might have potential as biomarkers for BD and CPN60 blood level might distinguish patients with abnormal HPA axis activity from those with normal HPA axis activity.