Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis.

BACKGROUND: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear. METHODS: We tested a novel "all-in-one" strategy consisting of sequential CD7 CAR T-cell therapy and haploidentical HSCT in 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. After CAR T-cell therapy led to complete remission with incomplete hematologic recovery, patients received haploidentical HSCT without pharmacologic myeloablation or GVHD prophylaxis drugs. Toxic effects and efficacy were closely monitored. RESULTS: After CAR T-cell therapy, all 10 patients had complete remission with incomplete hematologic recovery and grade 4 pancytopenia. After haploidentical HSCT, 1 patient died on day 13 of septic shock and encephalitis, 8 patients had full donor chimerism, and 1 patient had autologous hematopoiesis. Three patients had grade 2 HSCT-associated acute GVHD. The median follow-up was 15.1 months (range, 3.1 to 24.0) after CAR T-cell therapy. Six patients remained in minimal residual disease-negative complete remission, 2 had a relapse of CD7-negative leukemia, and 1 died of septic shock at 3.7 months. The estimated 1-year overall survival was 68% (95% confidence interval [CI], 43 to 100), and the estimated 1-year disease-free survival was 54% (95% CI, 29 to 100). CONCLUSIONS: Our findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is safe and effective, with remission and serious but reversible adverse events. This strategy offers a feasible approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT. (Funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province; ClinicalTrials.gov numbers, NCT04599556 and NCT04538599.).

Comprehensive genomic profiling of small bowel adenocarcinoma by tissue and plasma biopsy.

Small bowel adenocarcinoma (SBA) is a rare and aggressive malignancy with limited treatment options and poor prognosis. The molecular landscape and immunological characteristics of SBA are poorly understood. Here, we performed comprehensive mutation profiling of tissue and plasma biopsies from 143 and 42 patients with SBA. Analysis showed that SBA had a distinct mutation spectrum from left- and right-sided colorectal carcinoma. Plasma biopsy had high concordance with tissue biopsy for single nucleotide variants and structural variants, but low concordance for copy number variations, which showed that plasma biopsy can be an alternative to tissue biopsy. Moreover, we analyzed the association of TMB with clinical and molecular features, and found that TMB was significantly higher in tumors with DNA damage response alterations. Our findings provide valuable insights into the molecular and immunological features of SBA and demonstrate the potential of plasma biopsy as a non-invasive method for SBA diagnosis and treatment.

Genome-wide identification and transcriptome profiling expression analysis of the U-box E3 ubiquitin ligase gene family related to abiotic stress in maize (Zea mays L.).

BACKGROUND: The U-box gene family encodes E3 ubiquitin ligases involved in plant hormone signaling pathways and abiotic stress responses. However, there has yet to be a comprehensive analysis of the U-box gene family in maize (Zea mays L.) and its responses to abiotic stress. RESULTS: In this study, 85 U-box family proteins were identified in maize and were classified into four subfamilies based on phylogenetic analysis. In addition to the conserved U-box domain, we identified additional functional domains, including Pkinase, ARM, KAP and Tyr domains, by analyzing the conserved motifs and gene structures. Chromosomal localization and collinearity analysis revealed that gene duplications may have contributed to the expansion and evolution of the U-box gene family. GO annotation and KEGG pathway enrichment analysis identified a total of 105 GO terms and 21 KEGG pathways that were notably enriched, including ubiquitin-protein transferase activity, ubiquitin conjugating enzyme activity and ubiquitin-mediated proteolysis pathway. Tissue expression analysis showed that some ZmPUB genes were specifically expressed in certain tissues and that this could be due to their functions. In addition, RNA-seq data for maize seedlings under salt stress revealed 16 stress-inducible plant U-box genes, of which 10 genes were upregulated and 6 genes were downregulated. The qRT-PCR results for genes responding to abiotic stress were consistent with the transcriptome analysis. Among them, ZmPUB13, ZmPUB18, ZmPUB19 and ZmPUB68 were upregulated under all three abiotic stress conditions. Subcellular localization analysis showed that ZmPUB19 and ZmPUB59 were located in the nucleus. CONCLUSIONS: Overall, our study provides a comprehensive analysis of the U-box gene family in maize and its responses to abiotic stress, suggesting that U-box genes play an important role in the stress response and providing insights into the regulatory mechanisms underlying the response to abiotic stress in maize.

Genomic landscape defines peritoneal metastatic pattern and related target of peritoneal metastasis in colorectal cancer.

The primary objective of this study is to develop a prediction model for peritoneal metastasis (PM) in colorectal cancer by integrating the genomic features of primary colorectal cancer, along with clinicopathological features. Concurrently, we aim to identify potential target implicated in the peritoneal dissemination of colorectal cancer through bioinformatics exploration and experimental validation. By analyzing the genomic landscape of primary colorectal cancer and clinicopathological features from 363 metastatic colorectal cancer patients, we identified 22 differently distributed variables, which were used for subsequent LASSO regression to construct a PM prediction model. The integrated model established by LASSO regression, which incorporated two clinicopathological variables and seven genomic variables, precisely discriminated PM cases (AUC 0.899; 95% CI 0.860-0.937) with good calibration (Hosmer-Lemeshow test p = .147). Model validation yielded AUCs of 0.898 (95% CI 0.896-0.899) and 0.704 (95% CI 0.622-0.787) internally and externally, respectively. Additionally, the peritoneal metastasis-related genomic signature (PGS), which was composed of the seven genes in the integrated model, has prognostic stratification capability for colorectal cancer. The divergent genomic landscape drives the driver genes of PM. Bioinformatic analysis concerning these driver genes indicated SERINC1 may be associated with PM. Subsequent experiments indicate that knocking down of SERINC1 functionally suppresses peritoneal dissemination, emphasizing its importance in CRCPM. In summary, the genomic landscape of primary cancer in colorectal cancer defines peritoneal metastatic pattern and reveals the potential target of SERINC1 for PM in colorectal cancer.

Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer.

The increase in the detection rate of synchronous multiple primary lung cancer (MPLC) has posed remarkable clinical challenges due to the limited understanding of its pathogenesis and molecular features. Here, comprehensive comparisons of genomic and immunologic features between MPLC and solitary lung cancer nodule (SN), as well as different lesions of the same patient, were performed. Compared with SN, MPLC displayed a lower rate of EGFR mutation but higher rates of BRAF, MAP2K1, and MTOR mutation, which function exactly in the upstream and downstream of the same signaling pathway. Considerable heterogeneity in T cell receptor (TCR) repertoire exists among not only different patients but also among different lesions of the same patient. Invasive lesions of MPLC exhibited significantly higher TCR diversity and lower TCR expansion than those of SN. Intriguingly, different lesions of the same patient always shared a certain proportion of TCR clonotypes. Significant clonal expansion could be observed in shared TCR clonotypes, particularly in those existing in all lesions of the same patient. In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.

Comparison of Anti-Icing, Antifouling, and Anticorrosion Performances of the Superhydrophobic and Lubricant-Infused Coatings Based on a Hollow-Structured Kapok Fiber.

The superhydrophobic surface and slippery liquid-infused porous surface (SLIPS)/lubricant-infused surface (LIS) have attracted increasing attention owing to their multifunctionality. However, their practical applications face several problems such as complex and inefficient preparation technology, loss of lubricant, and fragile microstructures. Therefore, new strategies for preparing microstructures must be developed for constructing superhydrophobic and lubricant-infused coatings. Herein, a low-cost and high-efficiency method for developing superhydrophobic and lubricant-infused coatings based on in situ grown TiO2 on the surface of a hollow kapok fiber (KF) is reported. The anti-icing, antifouling, and anticorrosion performance of the superhydrophobic and lubricant-infused coatings are compared. The superhydrophobic coating reduces the formation and accumulation of ice. The lubricant-infused coating exhibits an extremely low ice adhesion strength and durable anti-icing properties. The superhydrophobic and lubricant-infused coatings show the outstanding antifouling property of diatom; the superhydrophobic surface exhibits superior stability over LIS without an external force field. The lubricant-infused coating shows excellent corrosion resistance and durability when immersed in a 3.5% NaCl solution. The superhydrophobic coating loses its protection as a result of the corrosion media permeating the metal substrate via the electrolytic cell and coating interface, and the lubricant-infused coating provides lasting corrosion resistance because of the lubricant filling into the interface. Although the superhydrophobic coating is fragile and the lubricant-infused coating will lose lubricant, this simple and convenient approach can be repeated to keep the coatings active. This study provides new inspiration for the fabrication of superhydrophobic surfaces and LIS based on natural products.

A Novel Hydrophobic Polyimide Film with Sag Structure Derived from Multi-Hybrid Strategy.

Polyimide (PI) film with hydrophilic greatly limits their application in the field of microelectronic device packaging. A novel hydrophobic PI film with sag structure and improved mechanical properties is prepared relying on the reaction between anhydride-terminated isocyanate-based polyimide (PIY) containing a seven-membered ring structure and the amino-terminated polyamide acid (PAA) via multi-hybrid strategy, this work named it as hybrid PI film and marked it as PI-PIY-X. PI-PIY-30 showed excellent hydrophobic properties, and the water contact angle could reach to 102°, which is 20% and 55% higher than simply PI film and PIY film, respectively. The water absorption is only 1.02%, with a decrease of 49% and 53% compared with PI and PIY. Due to that the degradation of seven-membered ring and generation of carbon dioxide led to the formation of sag structure, the size of sag structures is ≈16.84 and 534.55 nm for in-plane and out-plane direction, which are observed on surface of PI-PIY-30. Meanwhile, PI-PIY-30 possessed improved mechanical properties, and the tensile strength is 109.08 MPa, with 5% and more than 56% higher than that of pure PI and PIY film, showing greatly application prospects in the field of integrated circuit.

Acute Tai Chi Chuan exercise enhances sustained attention and elicits increased cuneus/precuneus activation in young adults.

BACKGROUND: The potential for acute exercise to enhance attention has been discussed in the literature. However, the neural mechanisms by which acute exercise affects attention remain elusive. METHOD: In this study, we first identified an optimized acute Tai Chi Chuan (ATCC) exercise protocol that enhances sustained attention performance and then aimed to determine the neural substrates of exercise-enhanced attention. Reaction time (RT) from the psychomotor vigilance test (PVT) was used to evaluate sustained attention. In Experiment 1, improvements in RTs were compared among six different exercise protocols. In Experiment 2, the participants completed the PVT in an MRI scanner on both rest and exercise days. RESULTS: Experiment 1 showed that practicing TCC 3 times for a total of 20 minutes, followed by 10-minute rest periods, resulted in the largest improvements in RTs. Experiment 2 showed that ATCC enhanced sustained attention, as evidenced by shorter RTs, and resulted in greater cuneus/precuneus activation after exercise than in the rest condition. Exercise-induced changes in brain activities across a distributed network exhibited significant correlations with attention. CONCLUSION: Therefore, this study indicates that ATCC effectively enhances sustained attention and underscores the key role of the cuneus/precuneus and frontoparietal-cerebellar regions in facilitating vigilance among young adults.

Loading of Single Atoms of Iron, Cobalt, or Nickel to Enhance the Electrocatalytic Hydrogen Evolution Reaction of Two-Dimensional Titanium Carbide.

The rational design of advanced electrocatalysts at the molecular or atomic level is important for improving the performance of hydrogen evolution reactions (HERs) and replacing precious metal catalysts. In this study, we describe the fabrication of electrocatalysts based on Fe, Co, or Ni single atoms supported on titanium carbide (TiC) using the molten salt method, i.e., TiC-FeSA, TiC-CoSA, or TiC-NiSA, to enhance HER performance. The introduction of uniformly distributed transition-metal single atoms successfully reduces the overpotential of HERs. Overpotentials of TiC-FeSA at 10 mA cm-2 are 123.4 mV with 61.1 mV dec-1 Tafel slope under acidic conditions and 184.2 mV with 85.1 mV dec-1 Tafel slope under alkaline conditions, which are superior to TiC-NiSA and TiC-CoSA. TiC samples loaded with transition-metal single atoms exhibit high catalytic activity and long stability under acidic and basic conditions. Density functional theory calculations indicate that the introduction of transition-metal single atoms effectively reduces the HER barrier of TiC-based electrocatalysts.

Identification and Expression Analysis of the Nucleotidyl Transferase Protein (NTP) Family in Soybean (Glycine max) under Various Abiotic Stresses.

Nucleotidyl transferases (NTPs) are common transferases in eukaryotes and play a crucial role in nucleotide modifications at the 3' end of RNA. In plants, NTPs can regulate RNA stability by influencing 3' end modifications, which in turn affect plant growth, development, stress responses, and disease resistance. Although the functions of NTP family members have been extensively studied in Arabidopsis, rice, and maize, there is limited knowledge about NTP genes in soybeans. In this study, we identified 16 members of the NTP family in soybeans, including two subfamilies (G1 and G2) with distinct secondary structures, conserved motifs, and domain distributions at the protein level. Evolutionary analysis of genes in the NTP family across multiple species and gene collinearity analysis revealed a relatively conserved evolutionary pattern. Analysis of the tertiary structure of the proteins showed that NTPs have three conserved aspartic acids that bind together to form a possible active site. Tissue-specific expression analysis indicated that some NTP genes exhibit tissue-specific expression, likely due to their specific functions. Stress expression analysis showed significant differences in the expression levels of NTP genes under high salt, drought, and cold stress. Additionally, RNA-seq analysis of soybean plants subjected to salt and drought stress further confirmed the association of soybean NTP genes with abiotic stress responses. Subcellular localization experiments revealed that GmNTP2 and GmNTP14, which likely have similar functions to HESO1 and URT1, are located in the nucleus. These research findings provide a foundation for further investigations into the functions of NTP family genes in soybeans.

MicroRNA-143 acts as a tumor suppressor through Musashi-2/DLL1/Notch1 and Musashi-2/Snail1/MMPs axes in acute myeloid leukemia.

BACKGROUND: The previous studies have revealed that abnormal RNA-binding protein Musashi-2 (MSI2) expression is associated with cancer progression through post-transcriptional mechanisms, however mechanistic details of this regulation in acute myeloid leukemia (AML) still remain unclear. Our study aimed to explore the relationship between microRNA-143 (miR-143) and MSI2 and to clarify their clinical significance, biological function and mechanism. METHODS: Abnormal expression of miR-143 and MSI2 were evaluated in bone marrow samples from AML patients by quantitative real time-PCR. Effects of miR-143 on regulating MSI2 expression were investigated using luciferase reporter assay. Functional roles of MSI2 and miR-143 on AML cell proliferation and migration were determined by CCK-8 assay, colony formation, and transwell assays in vitro and in mouse subcutaneous xenograft and orthotopic transplantation models in vivo. RNA immunoprecipitation, RNA stability measurement and Western blotting were performed to assess the effects of MSI2 on AML. RESULTS: We found that MSI2 was significantly overexpressed in AML and exerted its role of promoting AML cell growth by targeting DLL1 and thereby activating Notch signaling pathway. Moreover, we found that MSI2 bound to Snail1 transcript and inhibited its degradation, which in turn upregulated the expression of matrix metalloproteinases. We also found that MSI2 targeting miR-143 is downregulated in AML. In the AML xenograft mouse model, overexpression of MSI2 recapitulated its leukemia-promoting effects, and overexpression of miR-143 partially attenuated tumor growth and prevented metastasis. Notably, low expression of miR-143, and high expression of MSI2 were associated with poor prognosis in AML patients. CONCLUSIONS: Our data demonstrate that MSI2 exerts its malignant properties via DLL1/Notch1 cascade and the Snail1/MMPs axes in AML, and upregulation of miR-143 may be a potential therapeutic approach for AML.

Polo-like kinase 1 promotes pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a lethal vascular disease with limited therapeutic options. The mechanistic connections between alveolar hypoxia and PH are not well understood. The aim of this study was to investigate the role of mitotic regulator Polo-like kinase 1 (PLK1) in PH development. METHODS: Mouse lungs along with human pulmonary arterial smooth muscle cells and endothelial cells were used to investigate the effects of hypoxia on PLK1. Hypoxia- or Sugen5416/hypoxia was applied to induce PH in mice. Plk1 heterozygous knockout mice and PLK1 inhibitors (BI 2536 and BI 6727)-treated mice were checked for the significance of PLK1 in the development of PH. RESULTS: Hypoxia stimulated PLK1 expression through induction of HIF1α and RELA. Mice with heterozygous deletion of Plk1 were partially resistant to hypoxia-induced PH. PLK1 inhibitors ameliorated PH in mice. CONCLUSIONS: Augmented PLK1 is essential for the development of PH and is a druggable target for PH.

Upregulation of EphA2 is associated with apoptosis in response to H2O2 and UV radiation-induced cataracts.

In this article, we examine the role of erythropoietin-producing hepatocellular receptor A2 (EphA2) in the apoptosis of lens epithelial cells (LECs) in H2O2 and UV radiation-induced cataracts. We treated SRA01/04 cells with H2O2 or ultraviolet (UV) radiation to create a cataract cell model. We constructed a cataract lens model by exposing mice to UV radiation. We used CCK8 assays, Annexin V-FITC analysis, and immunohistochemical staining to explore proliferation and apoptosis of the cataract model. Thereafter, we used quantitative real-time PCR (qPCR) analysis, Western blot assays, and immunofluorescence to determine gene and protein expression levels. We also employed Crispr/Cas9 gene editing to create an EphA2 knockout in SRA01/04 cells. Results: H2O2 or UV radiation induced SRA01/04 cells showed EphA2 gene upregulation. CCK8 and apoptosis assays showed that EphA2 over-expression (OE) reduced epithelial cell apoptosis, but knockout of EphA2 induced it in response to H2O2 and UV radiation, respectively. Mutation of the EphA2 protein kinase domain (c.2003G > A, p. G668D) had a limited effect on cell apoptosis. In vivo, the EphA2 protein level increased in the lenses of UV-treated mice. Our results showed that EphA2 was upregulated in SRA01/04 cells in response to H2O2 and UV radiation. Mutation of the EphA2 protein kinase domain (c.2003G > A, p. G668D) had a limited effect on H2O2 and UV radiation-induced cell apoptosis. We confirmed this change with an experiment on UV-treated mice. The present study established a novel association between EphA2 and LEC apoptosis.

Cytokine release syndrome was an independent risk factor associated with hypoalbuminemia for patients with relapsed/refractory hematological malignancies after CAR-T cell therapy.

BACKGROUND & AIMS: This study aims to assess the nutritional status of patients during the different phases of the Chimeric Antigen Receptor (CAR)-T cell therapy and to identify prominent risk factors of hypoalbuminemia in patients after CAR-T treatment. The clinical consequences of malnutrition in cancer patients have been highlighted by growing evidence from previous clinical studies. Given CAR-T cell therapy's treatment intensity and possible side effects, it is important to provide patients with sufficient medical attention and support for their nutritional well-being. METHODS: This study was conducted from May 2021 to December 2021 among patients undergoing CAR-T cell therapy at the Bone Marrow Transplantation Center in The First Affiliated Hospital of Zhejiang University School of Medicine. Logistic regression analysis was performed to investigate the risk factors associated with hypoalbuminemia. Participants were divided into the cytokine release syndrome (CRS) group (n = 60) and the non-CRS group (n = 11) to further analyze the relationship between hypoalbuminemia and CRS. RESULTS: CRS (OR = 13.618; 95% CI = 1.499-123.709; P = 0.013) and baseline albumin (ALB) (OR = 0.854; 95% CI = 0.754-0.967; P = 0.020) were identified as the independent clinical factors associated with post-CAR-T hypoalbuminemia. According to the nadir of serum albumin, hypoalbuminemia occurred most frequently in patients with severe CRS (78.57%). The nadir of serum albumin (r = - 0.587, P < 0.001) and serum albumin at discharge (r = - 0.315, P = 0.01) were negatively correlated for the duration of CRS. Furthermore, patients with hypoalbuminemia deserved longer hospitalization (P = 0.04). CONCLUSIONS: CRS was identified as a significant risk factor associated with post-CAR-T hypoalbuminemia. An obvious decline in serum albumin was observed as the grade and duration of CRS increase. However, further research is still needed to elucidate the mechanisms of CRS-associated hypoalbuminemia.

Comparative genomics studies on the stk gene family in vertebrates: From the bighead carp (Hypophthalmichthys nobilis) genome.

The mammalian sterile 20-like (MST) family belongs to the serine/threonine protein kinase (STK) superfamily and participates in a variety of biological processes, such as cell apoptosis, polarity, migration, immune regulation, inflammatory responses, and cancer. In the economically important bighead carp (Hypophthalmichthys nobilis), the STK gene family and immune-related biological functions may be helpful in increasing its economic yield. However, the comprehensive role of STKs in the bighead carp remains unclear. In this study, the five stk sequences from the bighead carp were divided into two classes: stk3/4 and stk24/25/26. Gene structure and motif prediction analyses confirmed that stk is conserved in the bighead carp. Compared to 26 other vertebrate species, teleosts (including bighead carp) possess more stk members because of teleost-specific whole-genome duplication. Synteny analysis revealed that stk3, stk24, stk25, and stk26 have been relatively conserved in bighead carp during evolution. Meanwhile, stk4 was lost in most Cyprinid species, including bighead carp, during evolution. RNA-seq data revealed that STK expression was associated with various pathogens, and the expression of these STKs (Hnstk3, Hnstk24a, Hnstk24b, Hnstk25, and Hnstk26) was different in seven tissues of bighead carp. In addition, we showed that STK expression levels were dramatically altered in the head kidney and that stk24 was involved in defense against Aeromonas hydrophila. This study provides a molecular basis for the analysis of stk function in bighead carp, and can be used as a reference for further phylogenomics.

Visible light-induced cascade N-alkylation/amidation reaction of quinazolin-4(3H)-ones and related N-heterocycles.

An efficient and visible light-promoted cascade N-alkylation/amidation of quinazolin-4(3H)-ones with benzyl halides and allyl halides has been described for the first time to provide a convenient access to quinazoline-2,4(1H,3H)-diones. This cascade N-alkylation/amidation reaction shows good functional group tolerance and could also be applied to N-heterocycles such as benzo[d]thiazoles, benzo[d]imidazoles, and quinazolines. Control experiments show that K2CO3 plays an important role in this transformation.

Structural Design and Research Progress of Thermally Conductive Polyimide Film - A Review.

Currently, heat accumulation has seriously affected the stabilities and life of electronic devices. Polyimide (PI) film with high thermal conductivity coefficient (λ) has long been held up as an ideal solution for heat dissipation. Based on the thermal conduction mechanisms and classical thermal conduction models, this review presents design ideas of PI films with microscopically ordered liquid crystalline structures which are of great significance for breaking the limit of λ enhancement and describes the construction principles of thermal conduction network in high-λ filler strengthened PI films. Furthermore, the effects of filler type, thermal conduction paths, and interfacial thermal resistances on thermally conductive behavior of PI film are systematically reviewed. Meanwhile, this paper summarizes the reported research and provides an outlook on the future development of thermally conductive PI films. Finally, it is expected that this review will give some guidance to future studies in thermally conductive PI film.

Acute and continuous exposure of airborne fine particulate matter (PM2.5): diverse outer blood-retinal barrier damages and disease susceptibilities.

BACKGROUND: The association between air pollution and retinal diseases such as age-related macular degeneration (AMD) has been demonstrated, but the pathogenic correlation is unknown. Damage to the outer blood-retinal barrier (oBRB), which consists of the retinal pigment epithelium (RPE) and choriocapillaris, is crucial in the development of fundus diseases. OBJECTIVES: To describe the effects of airborne fine particulate matter (PM2.5) on the oBRB and disease susceptibilities. METHODS: A PM2.5-exposed mice model was established through the administration of eye drops containing PM2.5. Optical coherence tomography angiography, transmission electron microscope, RPE immunofluorescence staining and Western blotting were applied to study the oBRB changes. A co-culture model of ARPE-19 cells with stretching vascular endothelial cells was established to identify the role of choroidal vasodilatation in PM2.5-associated RPE damage. RESULTS: Acute exposure to PM2.5 resulted in choroidal vasodilatation, RPE tight junctions impairment, and ultimately an increased risk of retinal edema in mice. These manifestations are very similar to the pachychoroid disease represented by central serous chorioretinopathy (CSC). After continuous PM2.5 exposure, the damage to the RPE was gradually repaired, but AMD-related early retinal degenerative changes appeared under continuous choroidal inflammation. CONCLUSION: This study reveals oBRB pathological changes under different exposure durations, providing a valuable reference for the prevention of PM2.5-related fundus diseases and public health policy formulation.

ß-Cyclodextrin Polymer-Based Fluorescence Enhancement Strategy via Host-Guest Interaction for Sensitive Assay of SARS-CoV-2.

Nucleocapsid protein (N protein) is an appropriate target for early determination of viral antigen-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have found that ß-cyclodextrin polymer (ß-CDP) has shown a significant fluorescence enhancement effect for fluorophore pyrene via host-guest interaction. Herein, we developed a sensitive and selective N protein-sensing method that combined the host-guest interaction fluorescence enhancement strategy with high recognition of aptamer. The DNA aptamer of N protein modified with pyrene at its 3' terminal was designed as the sensing probe. The added exonuclease I (Exo I) could digest the probe, and the obtained free pyrene as a guest could easily enter into the hydrophobic cavity of host ß-CDP, thus inducing outstanding luminescent enhancement. While in the presence of N protein, the probe could combine with it to form a complex owing to the high affinity between the aptamer and the target, which prevented the digestion of Exo I. The steric hindrance of the complex prevented pyrene from entering the cavity of ß-CDP, resulting in a tiny fluorescence change. N protein has been selectively analyzed with a low detection limit (11.27 nM) through the detection of the fluorescence intensity. Moreover, the sensing of spiked N protein from human serum and throat swabs samples of three volunteers has been achieved. These results indicated that our proposed method has broad application prospects for early diagnosis of coronavirus disease 2019.

Platinum Nanoparticles Loaded Graphitic Carbon Nitride Nanosheets with Enhanced Peroxidase-like Activity for H2O2 and Oxidase-Based Sensing.

Platinum nanoparticles (PtNPs) are classical peroxidase-like nanozyme; self-agglomeration of nanoparticles leads to the undesirable reduction in stability and catalytic activity. Herein, a hybrid peroxidase-like nanocatalyst consisting of PtNPs in situ growing on g-C3N4 nanosheets with enhanced peroxidase-mimic catalytic activity (PtNP@g-C3N4 nanosheets) was prepared for H2O2 and oxidase-based colorimetric assay. g-C3N4 nanosheets can be used as carriers to solve the problem of poor stability of PtNPs. We observed that the catalytic ability could be maintained for more than 90 days. PtNP@g-C3N4 nanosheets could quickly catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB), and the absorbance of blue color oxidized TMB (oxTMB) showed a robust linear relationship with the concentration of H2O2 (the detection limit (LOD): 3.33 µM). By utilizing H2O2 as a mediator, this strategy can be applied to oxidase-based biomolecules (glucose, organophosphorus, and so on, that generate or consume hydrogen peroxide) sensing. As a proof of concept, a sensitive assay of cholesterol that combined PtNP@g-C3N4 nanosheets with cholesterol oxidase (ChOx) cascade catalytic reaction was constructed with an LOD of 9.35 µM in a widespread range from 10 to 800 µM (R2 = 0.9981). In addition, we also verified its ability to detect cholesterol in fetal bovine serum. These results showed application prospect of PtNP@g-C3N4 nanosheets-based colorimetry in sensing and clinical medical detection.