Asymmetric transmission devices empowered by a cascaded structure of a dielectric metasurface-photonic crystal.

In this Letter, we theoretically propose an all-dielectric quasi-three-dimensional subwavelength structure constructed by a dielectric metasurface cascaded with a multilayer photonic crystal (PC) to achieve a high-performance asymmetric optical transmission (AOT). The desired optical control of the AOT is realized by combining the predetermined anomalous beam steering of a phase gradient metasurface with a unique bandgap as well as transmission characteristics of the multilayered stacked PC. The simulated results demonstrate that the proposed AOT device operating at the center wavelength of 633 nm with a circularly polarized state exhibits a high transmission of up to 62.4% with a contrast ratio exceeding 606. The excellent performance of AOT is achieved by making disassembled transverse magnetic and transverse electric polarized light under the same deflection angle concurrently match with respective high-efficient transmission bands in the multilayer PC. Furthermore, dependence of the performance of the proposed device on structural dimensions is also explored. Fortunately, the designed AOT structure is applicable to any linearly polarized light but is accompanied by double diffraction channels as compared to the circularly polarized light case. Owing to its planar configuration, passive operation, and compelling performance under various polarization states, the proposed strategy for achieving AOT paves a new road for realizing high-performance optical metadevices in compact optical systems.

Plasmonic Resonance Coupling of Nanodisk Array/Thin Film on the Optical Fiber Tip for Integrated and Miniaturized Sensing Detection.

Fiber-optic surface plasmon resonance (FOSPR) sensing technology has become an appealing candidate in biochemical sensing applications due to its distinguished capability of remote and point-of-care detection. However, FOSPR sensing devices with a flat plasmonic film on the optical fiber tip are seldom proposed with most reports concentrating on fiber sidewalls. In this paper, we propose and experimentally demonstrate the plasmonic coupled structure of a gold (Au) nanodisk array and a thin film integrated into the fiber facet, enabling the excitation of the plasmon mode on the planar gold film by strong coupling. This plasmonic fiber sensor is fabricated by the ultraviolet (UV) curing adhesive transferring technology from a planar substrate to a fiber facet. The experimental results demonstrate that the fabricated sensing probe has a bulk refractive index sensitivity of 137.28 nm/RIU and exhibits moderate surface sensitivity by measuring the spatial localization of its excited plasmon mode on Au film by layer-by-layer self-assembly technology. Furthermore, the fabricated plasmonic sensing probe enables the detection of bovine serum albumin (BSA) biomolecule with a detection limit of 19.35 µM. The demonstrated fiber probe here provides a potential strategy to integrate plasmonic nanostructure on the fiber facet with excellent sensing performance, which has a unique application prospect in the detection of remote, in situ, and in vivo invasion.

Electrically switchable capabilities of conductive polymers-based plasmonic nanodisk arrays.

The electrically dynamic regulation of plasmonic nanostructures provides a promising technology for integrated and miniaturized electro-optical devices. In this work, we systematically investigate the electrical regulation of optical properties of plasmonic Au nanodisk (AuND) arrays integrated with different conductive polymers, polypyrrole (PPy), polyaniline (PANI), and poly(3,4-ethylenedioxythiophene) (PEDOT), which show their respective superiority of electrical modulation by applying the appropriate low voltages. For the hybrid structure of polymer-coated AuND arrays, its reflection spectrum and corresponding structural color are dynamically modulated by altering the complex dielectric function of the covering nanometer-thick conductive polymers based on the electrically controlled redox reaction. Due to the distinct refractive index responses of different polymers on the external voltage, polymer-coated AuND arrays exhibit different spectral variations, response time, and cycle stability. As a result, the reflection intensity of PPy-coated AuND arrays is mainly tailored by increasing optical absorption of the PPy polymer over a broad spectral range, which is distinguished from the wavelength shift of the resonance modes of AuND arrays induced by the other two polymers. Additionally, AuND arrays integrated with both PANI and PEDOT polymers exhibit a rapid switching time of less than 50 ms, which is 5 times smaller than the case of the PPy polymer. Most importantly, PPy-coated AuND arrays exhibit excellent cycle stability over 50 cycles compared to the other two polymers integrated devices. This work demonstrates a valuable technique strategy to realize high-performance polymer-coated dynamically tunable nanoscale electro-optical devices, which has especially significance for smart windows or dynamic display applications.

Complement factor H genotypes impact risk of age-related macular degeneration by interaction with oxidized phospholipids.

The rs1061170T/C variant encoding the Y402H change in complement factor H (CFH) has been identified by genome-wide association studies as being significantly associated with age-related macular degeneration (AMD). However, the precise mechanism by which this CFH variant impacts the risk of AMD remains largely unknown. Oxidative stress plays an important role in many aging diseases, including cardiovascular disease and AMD. A large amount of oxidized phospholipids (oxPLs) are generated in the eye because of sunlight exposure and high oxygen content. OxPLs bind to the retinal pigment epithelium and macrophages and strongly activate downstream inflammatory cascades. We hypothesize that CFH may impact the risk of AMD by modulating oxidative stress. Here we demonstrate that CFH binds to oxPLs. The CFH 402Y variant of the protective rs1061170 genotype binds oxPLs with a higher affinity and exhibits a stronger inhibitory effect on the binding of oxPLs to retinal pigment epithelium and macrophages. In addition, plasma from non-AMD subjects with the protective genotype has a lower level of systemic oxidative stress measured by oxPLs per apolipoprotein B (oxPLs/apoB). We also show that oxPL stimulation increases expression of genes involved in macrophage infiltration, inflammation, and neovascularization in the eye. OxPLs colocalize with CFH in drusen in the human AMD eye. Subretinal injection of oxPLs induces choroidal neovascularization in mice. In addition, we show that the CFH risk allele confers higher complement activation and cell lysis activity. Together, these findings suggest that CFH influences AMD risk by modulating oxidative stress, inflammation, and abnormal angiogenesis.

The glutamatergic system in the development of stress-induced depression.

Major depression is one of the most prevalent neuropsychological disorders and affects millions worldwide. In response, the monoaminergic system has been proposed to be one of the major focuses for conventional drugs in the treatment of depression, such as selective serotonin reuptake inhibitor (SSRI). Meanwhile, accumulating evidence suggests a paradigm shift from the monoamine system towards the glutamatergic system (Gerard Sanacora, Giulia Treccani, and Maurizio Popoli 2012) due to the long onset of the monoamine system targeting anti-depressant drugs. Both clinical and pre-clinical data support that glutamatergic system dysfunction were involved in the development of depression. Furthermore, therapeutic approaches that manipulating neuronal activity and N-methyl-D-aspartic acid (NMDA) receptor antagonist were shown to have profound effects in the treatment of depression. Here, I systematically reviewed our current understanding of the involvement of glutamatergic system dysregulation in the development of depression, which potentially could provide the mechanistic basis for future treatment development.

Coexistence of papillary thyroid carcinoma and sarcoidosis: a case report and literature review.

Papillary thyroid carcinoma is a differentiated thyroid cancer that arises from thyroid follicular epithelial cells. Sarcoidosis is a multisystem disease of unknown cause, characterized by monocytic infiltration and granuloma formation. We herein report a case of thyroid carcinoma complicated by sarcoidosis. When thyroid nodules and lymph node lesions are suspected, it is essential to avoid fixed thinking, conduct a comprehensive preoperative evaluation, and select the appropriate surgical approach. This can help reduce the likelihood of postoperative complications and improve the patient's quality of life. Therefore, comprehensive diagnosis of the coexistence of papillary thyroid carcinoma and sarcoidosis is crucial.

Multiband and bidirectional multiplexing asymmetric optical transmission empowered by nanograting-coupled defective multilayer photonic crystal.

Asymmetric optical transmission (AOT) has been an enduring hot topic of interest in various fields, including optical communication, information processing, and so on. Particularly, the development of reciprocal micro-nanostructures achieving AOT further facilitates and accelerates the miniaturization and integration of traditional optical components. However, most of these optical components merely consider a single AOT band and transmission in a specified direction, limiting the development of their versatile functions. In this paper, we theoretically propose an all-dielectric metamaterial consisting of a nanograting and a defective multilayer photonic crystal, exhibiting multi-band and bidirectional multiplexing AOT. More specifically, the proposed metamaterial demonstrates both narrowband and wideband AOT for incidence from the nanograting to the photonic crystal, and a completely different narrowband AOT for the opposite incidence, namely, from the photonic crystal to the nanograting. These distinctive AOT spectral features are achieved by matching the diffraction effect of the nanograting with the special energy band of the defective multilayer photonic crystal. Remarkably, the device exhibits a transmittance difference of up to 0.974 and a contrast ratio of up to 0.997 (transmittance ratio of up to 673), with a transmission bandwidth of 62.7 nm for incident light with a wavelength of 624 nm illuminating from the nanograting to the defective multilayer photonic crystal. Furthermore, the bandwidth and number of transmission bands can be flexibly tuned by changing the polarization angle of the incident light, showcasing its excellent polarization multiplexing characteristics. The designed metamaterial provides an effective strategy for the realization of versatile AOT devices and is conducive to expanding the application scenarios of AOT devices.

LordNet: An efficient neural network for learning to solve parametric partial differential equations without simulated data.

Neural operators, as a powerful approximation to the non-linear operators between infinite-dimensional function spaces, have proved to be promising in accelerating the solution of partial differential equations (PDE). However, it requires a large amount of simulated data, which can be costly to collect. This can be avoided by learning physics from the physics-constrained loss, which we refer to it as mean squared residual (MSR) loss constructed by the discretized PDE. We investigate the physical information in the MSR loss, which we called long-range entanglements, and identify the challenge that the neural network requires the capacity to model the long-range entanglements in the spatial domain of the PDE, whose patterns vary in different PDEs. To tackle the challenge, we propose LordNet, a tunable and efficient neural network for modeling various entanglements. Inspired by the traditional solvers, LordNet models the long-range entanglements with a series of matrix multiplications, which can be seen as the low-rank approximation to the general fully-connected layers and extracts the dominant pattern with reduced computational cost. The experiments on solving Poisson's equation and (2D and 3D) Navier-Stokes equation demonstrate that the long-range entanglements from the MSR loss can be well modeled by the LordNet, yielding better accuracy and generalization ability than other neural networks. The results show that the Lordnet can be 40× faster than traditional PDE solvers. In addition, LordNet outperforms other modern neural network architectures in accuracy and efficiency with the smallest parameter size.

The nutritional roles of zinc for immune system and COVID-19 patients.

Zinc (Zn) is a vital micronutrient that strengthens the immune system, aids cellular activities, and treats infectious diseases. A deficiency in Zn can lead to an imbalance in the immune system. This imbalance is particularly evident in severe deficiency cases, where there is a high susceptibility to various viral infections, including COVID-19 caused by SARS-CoV-2. This review article examines the nutritional roles of Zn in human health, the maintenance of Zn concentration, and Zn uptake. As Zn is an essential trace element that plays a critical role in the immune system and is necessary for immune cell function and cell signaling, the roles of Zn in the human immune system, immune cells, interleukins, and its role in SARS-CoV-2 infection are further discussed. In summary, this review paper encapsulates the nutritional role of Zn in the human immune system, with the hope of providing specific insights into Zn research.

Development of double-layer poly (amino acid) modified electrochemical sensor for sensitive and direct detection of betamethasone in cosmetics.

Screening for illegal use of glucocorticoids (GCs) in cosmetics by electrochemical methods is extremely challenging due to the poor electrochemical activity of GCs. In this study, poly-L-Serine/poly-Taurine modified electrode (P(Tau)/P(L-Ser)/GCE) was prepared for sensitive and direct determination of betamethasone in cosmetics by a simple two-step in situ electropolymerization reaction. The relevant parameters of preparation and electroanalytical conditions were respectively studied, including the concentration of polymerization solution, the number of scanning circles and the scanning rate. The SEM and EDS mapping demonstrated successful preparation of P(Tau)/P(L-Ser)/GCE. The electro-catalytic properties of the obtained electrodes were investigated using cyclic voltammetry and differential pulse voltammetry methods, showing a remarkable improvement of sensitivity for the detection of betamethasone due to the synergic effect of both P(L-Ser) and P(Tau). In addition, we investigated the electrochemical reduction of betamethasone on the surface of modified electrode. It was found that the process was controlled by diffusion effect and involved the transfer of two electrons and two protons. Then the electrochemical sensor method based on P(Tau)/P(L-Ser)/GCE was established and delivered a linear response to betamethasone concentration from 0.5 to 20 µg mL-1 with a limit of detection of 32.2 ng mL-1, with excellent recoveries (98.1%-106.8%) and relative standard deviations (＜4.8%). Furthermore, the established electrochemical sensor method was compared with conventional HPLC method. The results showed that both of them were comparable. Moreover, the established electrochemical sensor method was with the merits of short analysis time, environmentally friendly, low cost and easy to achieve in-site detection.

High temperature requirement factor A1 (HTRA1) gene regulates angiogenesis through transforming growth factor-ß family member growth differentiation factor 6.

Genome-wide association study (GWAS) has identified genetic variants in the promoter region of the high temperature requirement factor A1 (HTRA1) gene associated with age-related macular degeneration (AMD). As a secreted serine protease, HTRA1 has been reported to interact with members of the transforming growth factor-ß (TGF-ß) family and regulate their signaling pathways. Growth differentiation factor 6 (GDF6), a member of the TGF-ß family, is involved in ectoderm patterning and eye development. Mutations in GDF6 have been associated with abnormal eye development that may result in microphthalmia and anophthalmia. In this report, we identified a single nucleotide polymorphism (SNP) rs6982567 A/G near the GDF6 gene that is significantly associated with AMD (p value = 3.54 × 10(-8)). We demonstrated that the GDF6 AMD risk allele (rs6982567 A) is associated with decreased expression of the GDF6 and increased expression of HTRA1. Similarly, the HTRA1 AMD risk allele (rs10490924 T) is associated with decreased GDF6 and increased HTRA1 expression. We observed decreased vascular development in the retina and significant up-regulation of GDF6 gene in the RPE layer, retinal and brain tissues in HTRA1 knock-out (htra1(-/-)) mice as compared with the wild-type counterparts. Furthermore, we showed enhanced SMAD signaling in htra1(-/-) mice. Our data suggests a critical role of HTRA1 in the regulation of angiogenesis via TGF-ß signaling and identified GDF6 as a novel disease gene for AMD.

MOTS-c Functionally Prevents Metabolic Disorders.

Mitochondrial-derived peptides are a family of peptides encoded by short open reading frames in the mitochondrial genome, which have regulatory effects on mitochondrial functions, gene expression, and metabolic homeostasis of the body. As a new member of the mitochondrial-derived peptide family, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is regarding a peptide hormone that could reduce insulin resistance, prevent obesity, improve muscle function, promote bone metabolism, enhance immune regulation, and postpone aging. MOTS-c plays these physiological functions mainly through activating the AICAR-AMPK signaling pathways by disrupting the folate-methionine cycle in cells. Recent studies have shown that the above hormonal effect can be achieved through MOTS-c regulating the expression of genes such as GLUT4, STAT3, and IL-10. However, there is a lack of articles summarizing the genes and pathways involved in the physiological activity of MOTS-c. This article aims to summarize and interpret the interesting and updated findings of MOTS-c-associated genes and pathways involved in pathological metabolic processes. Finally, it is expected to develop novel diagnostic markers and treatment approaches with MOTS-c to prevent and treat metabolic disorders in the future.

ZBTB34 is a hepatocellular carcinoma-associated protein with a monopartite nuclear localization signal.

ZBTB34 is a novel zinc finger protein with an unknown function. In this study, the gene expression and survival prognosis of ZBTB34 were analyzed across tumors based on the TCGA datasets. According to the bioinformatics analysis and qPCR results, liver hepatocellular carcinomas exhibit a high level of ZBTB34 expression. Additionally, the experiment supported the bioinformatics analysis findings that ZBTB34 expression was regulated by miR-125b-5p and that ZBTB34 affected ZBTB10, POLR1B, and AUH expression in HepG2 cells. Biological software analysis further revealed that ZBTB34 contains a monopartite nuclear localization signal (NLS). Arginine and lysine inside the putative NLS were substituted using the alanine-scanning mutagenesis method. The findings showed that the ability of ZBTB34 to enter the nucleus was abolished by the alanine substitution of the sequence 320RGGRARQKRA329 and the mutation of Lys327 and Arg328 residues. ZBTB34 was co-immunoprecipitated with importin α1, importin α3, importin α4, and importin ß1, according to the results of the co-immunoprecipitation assay. In conclusion, ZBTB34 is a hepatocellular carcinoma-associated protein with a monopartite NLS. The nuclear import of ZBTB34 is mediated by importin α1, importin α3, importin α4, and importin ß1. ZBTB34 performs its biological functions via a putative miR-125b-5p/ZBTB34/(ZBTB10, POLR1B, and AUH) signaling axis in HepG2 cells.

Hepatocyte-targeted delivery using oleanolic acid-loaded liposomes for enhanced hepatocellular carcinoma therapy.

Drug-loaded liposomes have been shown to be effective in the treatment of hepatocellular carcinoma (HCC). However, the systemic non-specific distribution of drug-loaded liposomes in tumor patients is a critical therapeutic challenge. To address this issue, we developed galactosylated chitosan-modified liposomes (GC@Lipo) that could selectively bind to the asialoglycoprotein receptor (ASGPR), which is highly expressed on the membrane surface of HCC cells. Our study demonstrated that the GC@Lipo significantly enhanced the anti-tumor efficacy of oleanolic acid (OA) by enabling targeted drug delivery to hepatocytes. Remarkably, treatment with OA-loaded GC@Lipo inhibited the migration and proliferation of mouse Hepa1-6 cells by upregulating E-cadherin expression and downregulating N-cadherin, vimentin, and AXL expressions, compared to a free OA solution and OA-loaded liposomes. Furthermore, using an axillary tumor xenograft mouse model, we observed that OA-loaded GC@Lipo led to a significant reduction in tumor progression, accompanied by concentrated enrichment in hepatocytes. These findings strongly support the clinical translation of ASGPR-targeted liposomes for the treatment of HCC.

An essential role of the cysteine-rich domain of FZD4 in Norrin/Wnt signaling and familial exudative vitreoretinopathy.

The Wnt pathway plays important yet diverse roles in health and disease. Mutations in the Wnt receptor FZD4 gene have been confirmed to cause familial exudative vitreoretinopathy (FEVR). FEVR is characterized by incomplete vascularization of the peripheral retina, which can lead to vitreous bleeding, tractional retinal detachment, and blindness. We screened for mutations in the FZD4 gene in five families with FEVR and identified five mutations (C45Y, Y58C, W226X, C204R, and W496X), including three novel mutations (C45Y, Y58C, and W226X). In the retina, Norrin serves as a ligand and binds to FZD4 to activate the Wnt signaling pathway in normal angiogenesis and vascularization. The cysteine-rich domain (CRD) of FZD4 has been shown to play a critical role in Norrin-FZD4 binding. We investigated the effect of mutations in the FZD4 CRD in Norrin binding and signaling in vitro and in vivo. Wild-type and mutant FZD4 proteins were assayed for Norrin binding and Norrin-dependent activation of the canonical Wnt pathway by cell-surface and overlay binding assays and luciferase reporter assays. In HEK293 transfection studies, C45Y, Y58C, and C204R mutants did not bind to Norrin and failed to transduce FZD4-mediated Wnt/ß-catenin signaling. In vivo studies using Xenopus embryos showed that these FZD4 mutations disrupt Norrin/ß-catenin signaling as evidenced by decreased Siamois and Xnr3 expression. This study identified a new class of FZD4 gene mutations in human disease and demonstrates a critical role of the CRD in Norrin binding and activation of the ß-catenin pathway.

Is the combination of acupuncture and Western medicine superior to monotherapy in the treatment of patients with Alzheimer's disease: A protocol for systematic review and network meta-analysis.

BACKGROUND: Alzheimer disease (AD) is a common cause of dementia, and there are still a lack of treatment options to reverse or prevent disease progression. Existing evidence shows that acupuncture has advantages in the treatment of AD, but whether the efficacy of acupuncture belongs to the placebo effect remains controversial, and there is no strict systematic review and network meta-analysis to evaluate the efficacy and safety of acupuncture combined with Western medicine in the treatment of AD. METHODS: From the inception to February 2023, the Embase, Latin American and Caribbean Health Sciences Literature, Medline, the Cochrane Collaboration's Controlled Clinical Trials, Scopus, China Biomedical Literature Database, Wanfang Database, China National Knowledge Infrastructure, and Australian Medical Index will be searched using the key phrases "acupuncture," "warm needling," "electroacupuncture," "Alzheimer disease," and "cohort" for all relevant studies. Quality assessment of all studies included in this review will be independently assessed by 2 reviewers using the Cochrane Collaborations tool. When significant heterogeneity is indicated, we will find the source of heterogeneity by subgroup or sensitivity analysis. DISCUSSION: This study will evaluate the efficacy of acupuncture combined with Western medicine in improving cognitive function and activities of daily living in AD patients. The results of this study will verify whether the efficacy of acupuncture in the treatment of AD belongs to the placebo effect, which will also provide a reference for the clinical use of acupuncture combined with Western medicine in the treatment of AD.

The effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in critically ill patients with acute kidney injury: An observational study using the MIMIC database.

Background: The safety of prescribing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) during acute kidney injury (AKI) remains unclear. We aimed to investigate the associations of ACEI/ARB therapy in AKI with the risk of mortality, acute kidney disease (AKD), and hyperkalemia. Methods: We conducted a retrospective monocentric study, which included patients in Massachusetts between 2008 and 2019 from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Propensity score matching was performed for the endpoint analysis. The association between ACEI/ARB therapy and mortality was assessed using Cox proportional hazards regression models. Logistic regression was used to assess the risk of AKD and hyperkalemia. Results: Among the 19,074 individuals with AKI admitted to the intensive care unit (ICU), 3,244 (17.0%) received ACEI/ARBs, while 15,830 (83.0%) did not. In the propensity score-matched sample of 6,358 individuals, we found a decreased risk of mortality in those who received ACEI/ARBs compared to those who did not (hazard ratio [HR] for ICU mortality: 0.34, 95% confidence interval [CI]: 0.27-0.42); HR for in-hospital mortality: 0.47, 95% CI: 0.39-0.56; HR for 30-day mortality: 0.47, 95% CI: 0.40-0.56; HR for 180-day mortality: 0.53, 95% CI: 0.45-0.62). However, the use of ACEI/ARBs was associated with a higher risk of AKD (risk ratio [RR]: 1.81; 95% CI: 1.55-2.12). There was no significant association between ACEI/ARBs and an increased risk of hyperkalemia (RR: 1.21; 95% CI: 0.96-1.51). Conclusions: ACEI/ARB treatment during an episode of AKI may decrease all-cause mortality, but increases the risk of AKD. Future randomized controlled trials are warranted to validate these findings.

Zbtb34 promotes embryonic stem cell proliferation by elongating telomere length.

Zbtb34 is a novel zinc finger protein, which is revealed by biological software analysis to have 3 zinc fingers, but its functions remain unknown. In this study, mouse Zbtb34 cDNA was amplified by PCR and inserted into the plasmid pEGFP-N1 to generate Zbtb34-EGFP fusion protein. The upregulation of Zbtb34 in mouse embryonic stem cells promoted telomere elongation and increased cell proliferation. In order to understand the above phenomena, the telomere co-immunoprecipitation technique was employed to investigate the relationship between Zbtb34 and telomeres. The results indicated that Zbtb34 could bind to the DNA sequences of the telomeres. Alanine substitution of the third zinc finger abolished such binding. Since Pot1 is the only protein binding to the single-stranded DNA at the end of the telomeres, we further investigated the relationship between Zbtb34 and Pot1. The results revealed that the upregulation of Zbtb34 decreased the binding of Pot1b to the telomeres. Through the upregulation of Pot1b, the binding of Zbtb34 to the telomeres was also reduced. In conclusion, we showed that the main biological function of Zbtb34 was to bind telomere DNA via its third ZnF, competing with Pot1b for the binding sites, resulting in telomere elongation and cell proliferation.

Hydrogel Loaded with VEGF/TFEB-Engineered Extracellular Vesicles for Rescuing Critical Limb Ischemia by a Dual-Pathway Activation Strategy.

Critical limb ischemia (CLI) is the most severe clinical manifestation of peripheral arterial disease, which causes many amputations and deaths. Conventional treatment strategies for CLI (e.g., stent implantation and vascular surgery) bring surgical risk, which are not suitable for each patient. Extracellular vesicles (EVs) can be a potential solution for CLI. Herein, vascular endothelial growth factor (VEGF; i.e., a crucial molecule related to angiogenesis) and transcription factor EB (TFEB; i.e., a pivotal regulator of autophagy) are chosen as the target gene to improve the bioactivity of EVs derived from endothelial cells. The VEGF/TFEB-engineered EVs (Engineered-EVs) are fabricated by genetically engineering the parent cells, and their versatile functions are confirmed using three cell models (human umbilical vein endothelial cells, myoblast, and monocytes). Injectable thermal-responsive hydrogel are then combined with Engineered-EVs to combat CLI. These results reveal that the hydrogel can enhance the stability of Engineered-EVs in vivo and release EVs at different temperatures. Moreover, the results of animal studies indicate that Engineered-EV/Hydrogel can significantly improve neovascularization, attenuate muscle injury, and recover limb function after CLI. Finally, mechanistic studies shed light on the therapeutic effect of Engineered-EV/Hydrogel due to the activated VEGF/VEGFR pathway and autophagy-lysosomal pathway.

Gold embedded chitosan nanoparticles with cell membrane mimetic polymer coating for pH-sensitive controlled drug release and cellular fluorescence imaging.

In this work, gold embedded chitosan nanoparticles (Au@CS NPs) were fabricated by a one-pot method. The benzaldehyde-terminated poly[(2-methacryloyloxy) ethyl phosphorylcholine] (PMPC) was applied to modification of the gold doped chitosan nanoparticles. The obtained Au@CS-PMPC NPs had the diameter of 135 nm with a narrow distribution. The size of the Au@CS-PMPC NPs, as well as the size of the embedded gold NPs, might be well-controlled by adjusting the feeding ratio between chitosan and HAuCl4. Furthermore, the Au@CS-PMPC NPs showed increased colloidal stability, high drug loading content, pH-responsive drug release, excellent biocompatibility and bright fluorescence emission. The results demonstrated that Au@CS-PMPC NPs showed a great potential for tumor therapy via the combination advantages of pH-sensitive controlled drug release and cellular fluorescence imaging.