Giant retinal pigment epithelium tears with membranous nephropathy: a case report and literature review.

BACKGROUND: Kidney and eye diseases may be closely linked. Tears of the retinal pigment epithelium (RPE) have been reported to be related to kidney diseases, such as IgA nephropathy and light-chain deposition disease. However, pigment epithelium tears associated with membranous nephropathy have not been reported or systematically analysed. CASE PRESENTATION: A 68-year-old man presented with decreased right eye visual acuity. Optical coherence tomography (OCT) revealed cystic macular edema, localized serous detachment of the retina and loss of the outer retinal structure in the right eye and retinal pigment epithelium detachment (PED) combined with serous detachment of the retina in the left eye. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) revealed giant RPE tears in the right eye and exudative age-related macular degeneration in the left eye. The patient also suffered from severe membranous nephropathy-autoimmune glomerulonephritis. Renal biopsy immunofluorescence revealed a roughly granular pattern, with immunoglobulin G (IgA), immunoglobulin G (IgG), IgM, complement C3(Components 3), λ light chain and κ light chain subepithelial staining. CONCLUSIONS: It is hypothesized that severe membranous nephropathy caused immune complex deposition on the surface of Bruch membrane, resulting in weakened adhesion between the RPE and Bruch membrane and impaired RPE pump function, combined with age-related macular degeneration, leading to giant RPE tears in the right eye. Close attention should be given to the ocular condition of patients with membranous nephropathy to facilitate timely treatment and avoid serious consequences.

Grid-less wideband direction of arrival estimation based on variational Bayesian inference.

Many recent works have addressed the problem of wideband direction of arrival (DOA) estimation using grid-less sparse techniques, and these methods have been shown to outperform the traditional wideband DOA estimation methods. However, these methods often suffer from the problem of requiring manual parameter tuning or high computational complexity, which reduces their practicality. To alleviate this problem, a grid-less wideband DOA estimation method based on variational Bayesian inference is proposed in this paper. The method approximates the posterior probability density function of DOA with the help of variational Bayesian inference, which does not require manual adjustment of parameters and can obtain accurate DOA estimation results with low computational complexity. Numerical simulations and real measurement data processing show that the proposed method has a higher DOA estimation accuracy than other grid-less wideband methods while providing higher computational speed.

SLCO1B1 Polymorphisms are Associated with the Susceptibility to Pulmonary Tuberculosis in Chinese Females.

This study aimed to evaluate the role of SLCO1B1 polymorphisms in pulmonary tuberculosis (PTB) risk among Chinese patients. This study comprised 600 PTB patients (mean age: 37.43 ± 12.73 years) and 600 healthy controls (mean age: 37.39 ± 12.57 years) from a Chinese population. The SLCO1B1 rs2306283 and rs4149056 polymorphisms were detected using TaqMan genotyping assay. Chi-square (χ2) test was applied to calculate the Hardy-Weinberg Equilibrium (HWE) among controls. Logistic regression analysis was used to examine the odds ratio (OR) and 95% confidence interval (CI). After adjustment for age and gender, the frequency of rs4149056-C was significantly higher in PTB group (P = 0.017, OR = 1.375, 95% CI 1.058-1.786); meanwhile, rs4149056 was associated with increased PTB risk in dominant model (P = 0.015, OR = 1.424, 95% CI 1.072-1.892). The frequency and genotype of rs2306283 showed no significant difference between the two groups. In stratified analysis, rs2306283-GG showed notable susceptibility to PTB (P = 0.027, OR = 1.563, 95% CI 1.051-2.323 in recessive model) in females; rs4149056-C was also significantly higher in female PTB group (P = 0.039, OR = 1.741, 95% CI 1.028-2.948). Neither of rs2306283 and rs4149056 polymorphisms was associated with PTB risk in males. A haplotype analysis showed that patients carrying at least one SLCO1B1*15 haplotype had higher PTB risk (P = 0.004, OR = 1.527, 95% CI 1.145-2.034). SLCO1B1 polymorphisms are associated with the susceptibility to pulmonary tuberculosis in Chinese females.

Boosting chemotherapy of bladder cancer cells by ferroptosis using intelligent magnetic targeting nanoparticles.

A versatile nano-delivery platform was reported to enhance the tumor suppression effect of chemotherapy by augmenting tumor cells' ferroptosis. The platform consists of pomegranate-like magnetic nanoparticles (rPAE@SPIONs) fabricated by encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) within a reduced poly(ß-amino ester)s-PEG amphiphilic copolymer (rPAE). The resulting platform exhibits several functionalities. Firstly, it promotes the doxorubicin (DOX) release by leveraging the mild hyperthermia generated by NIR irradiation. Secondly, it triggers ferroptosis in tumor cells, inducing their demise. Thirdly, it induces polarization of macrophages towards an anti-tumor M1 phenotype, contributing to ferroptosis of tumor cells and enhanced tumor cell suppression. This study effectively capitalizes on the versatility of SPIONs and offers a simple yet powerful strategy for developing a new nanosized ferroptosis-inducing agent, ultimately improving the inhibition of bladder cancer cells.

The effect of phase contents on the properties of yttria stabilized zirconia dental materials fabricated by stereolithography-based additive manufacturing.

The aim is to investigate the impact of phase contents on mechanical properties, translucency, and aging stability of additively manufactured yttria partially stabilized zirconia ceramics. For that purpose, we evaluated two PSZ materials. The first type was prepared utilizing commercially available 5 mol% yttria-stabilized zirconia(5Y-PSZ), while the second type, denoted as 3Y+8Y-PSZ ceramics, was fabricated by blending 3 mol% and 8 mol% yttria-stabilized zirconia powders. Compared to 5Y-PSZ (39.90 wt% tetragonal phases and c/a2 = 1.0141), 3Y+8Y-PSZ is characterized by a greater abundance of tetragonal phases (47.68 wt%), which display higher tetragonality (c/a2 = 1.0165) and lower yttrium oxide content (2.25mol%). As a result, the 3Y+8Y-PSZ demonstrates elevated strength (816.52 MPa) and toughness (4.32 MPa m1/2), accompanied by reduced translucency(CR:0.47) and it exhibits greater susceptibility to aging. The phase contents, yttrium oxide content, and lattice parameters in the tetragonal phase play a crucial role in determining the mechanical properties, translucency, and aging stability of PSZ ceramics.

[Application of metagenomic next-generation sequencing of bronchoalveolar lavage fluid in the diagnosis and treatment of refractory pneumonia in children]. / æ”¯æ°”ç®¡è‚ºæ³¡çŒæ´—æ¶²å®åŸºå› ç»„äºŒä»£æµ‹åºåœ¨å„¿ç«¥éš¾æ²»æ€§è‚ºç‚Žè¯Šæ²»ä¸­çš„åº”ç”¨.

OBJECTIVES: To investigate the clinical application of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in the etiological diagnosis and treatment of refractory pneumonia (RTP) in children. METHODS: A retrospective analysis was performed on 160 children with RTP who were admitted to the Department of Pediatric Internal Medicine, Maternal and Child Health Hospital of Inner Mongolia Autonomous Region, from January 2020 to March 2023. According to whether mNGS was performed, they were divided into two groups: mNGS (n=80) and traditional testing (n=80). All children received the tests of inflammatory markers and pathogen tests after admission. Traditional pathogenicity tests included microbial culture (sputum specimen collected by suction tube), nucleic acid detection of respiratory pathogens, and serological test (mycoplasma, tuberculosis, and fungi). For the mNGS group, BALF specimens were collected after bronchoscopy and were sent to the laboratory for mNGS and microbial culture. The two groups were analyzed and compared in terms of the detection of pathogens and treatment. RESULTS: Compared with the traditional testing group, the mNGS group had a significantly higher detection rate of pathogens (92% vs 58%, P<0.05), with more types of pathogens and a higher diagnostic rate of mixed infections. Compared with the traditional testing group, the mNGS group had a significantly higher treatment response rate and a significantly lower incidence rate of complications during hospitalization (P<0.05). Treatment was adjusted for 68 children in the mNGS group according to the results of mNGS, with a treatment response rate of 96% (65/68) after adjustment. CONCLUSIONS: Compared with traditional pathogen tests, BALF mNGS can significantly improve the detection rate of pathogens and find some rare pathogens. In clinical practice, when encountering bottlenecks during the diagnosis and treatment of children with RTP, it is advisable to promptly perform the mNGS to identify the pathogens.

Investigation of mechanical properties and low-temperature degradation of dental 3Y-TZP ceramics fabricated by stereolithography in combination with microwave sintering.

The purpose of this study was to obtain dental ceramic materials with excellent mechanical properties and high resistance to low temperature degradation (LTD) via stereolithography (SLA) in combination with microwave sintering (MWS). The results have shown that the unaged MWS-1425 °C 3Y-TZP ceramics with uniform microstructure have high density up to 99.04% and excellent mechanical properties (Vickers hardness 14.07 GPa, fracture toughness 4.32 MPa m1/2, flexural strength 947.87 MPa). After 50 h of LTD, the m-phase content of MWS 3Y-TZP ceramics accounts for only 10.3%. In addition, the surface roughness increases by only 1.3 nm, the degraded depth is less than 5 µm, and the flexural strength exceeds 900 MPa. This exhibits the high resistance to LTD and excellent mechanical properties of dental 3Y-TZP ceramics can be obtained.

Simulation Investigation on the Influence Mechanism of Toluene and Heptane on the Aggregation of Asphaltene Molecules.

Asphaltenes are a group of compounds that are soluble in benzene and toluene but insoluble in nonpolar small molecule n-alkanes. The asphaltene aggregation in the asphaltene-heptane-toluene system was studied using molecular dynamics (MD) simulation, and the interaction between asphaltene molecules during this process was also revealed from the evolution of the density field, radial distribution function (RDF), and intermolecular distance of asphaltenes. Three main findings were made: (1) more asphaltene precipitates (heptane) were contained, and more asphaltene dimers or trimers were formed during the MD simulation; (2) asphaltene molecules interacted with each other to form aggregates in the form of π-π or H-bond interaction. The stable distance of the π-π interaction was 3.3-3.5 Å, and the stable distance of the H-bond connection was 1.7-1.9 Å. (3) The asphaltene interaction in the heptane-rich system was dominated by π-π interaction between asphaltene molecules. However, the asphaltene interactions in the toluene-rich system were mainly the π-π interaction between asphaltene molecules and toluene and the H-bond interaction between the side chains of asphaltene molecules. The results of this study can aid in understanding how asphaltene molecules aggregate and self-associate and can also offer theoretical support for flow assurance in systems used to produce crude oil.

Kondo scattering in underdoped Nd1-xSrxNiO2 infinite-layer superconducting thin films.

The recent discovery of superconductivity in infinite-layer nickelates generates tremendous research endeavors, but the ground state of their parent compounds is still under debate. Here, we report experimental evidence for the dominant role of Kondo scattering in the underdoped Nd1-xSrxNiO2 thin films. A resistivity minimum associated with logarithmic temperature dependence in both longitudinal and Hall resistivities are observed in the underdoped Nd1-xSrxNiO2 samples before the superconducting transition. At lower temperatures down to 0.04 K, the resistivities become saturated, following the prediction of the Kondo model. A linear scaling behavior [Formula: see text] between anomalous Hall conductivity [Formula: see text] and conductivity [Formula: see text]is revealed, verifying the dominant Kondo scattering at low temperature. The effect of weak (anti-)localization is found to be secondary. Our experiments can help in clarifying the basic physics in the underdoped Nd1-xSrxNiO2 infinite-layer thin films.

Investigating the effect of solid loading on microstructure, mechanical properties, and translucency of highly translucent zirconia ceramics prepared via stereolithography-based additive manufacturing.

A study was conducted to explore the potential of 5 mol% yttria-partially stabilized zirconia (5Y-PSZ) ceramics for dental restorations, using stereolithography (SLA) printing technique. Four different solid loadings were established in the ceramic paste systems to study their effects on microstructure, mechanical properties, and translucency. The study examined the rheological behavior and photopolymerization performance of the ceramic pastes with varying solid loadings. Results showed that, an increase in powder concentration resulted in a decrease in cure depth (Cd) and penetration depth (Dp). A narrower pore size distribution was observed in the green bodies with a high solid loading, facilitating the achievement of final densification. The green and sintered densities were highest at 52 vol%, with values of 3.46 ± 0.01 g/cm3 and 6.01 ± 0.02 g/cm3, respectively. Additionally, all of the green strengths exceeded 30 MPa, with a maximum of 35.09 ± 2.02 MPa obtained at 44 vol%. The maximum flexural strength and minimum contrast ratio (CR) value of 746 ± 75 MPa and 0.40 ± 0.01 were achieved at 52 vol% after sintering. No significant differences were observed in the phase composition and hardness of the as-sintered ceramics. Though significant differences were observed in photopolymerization performance, four materials showed similar structural reliability considering Weibull modulus and characteristic strength.

Poly(ß-amino ester)s-based nanovehicles: Structural regulation and gene delivery.

The first poly(ß-amino) esters (PßAEs) were synthesized more than 40 years ago. Since 2000, PßAEs have been found to have excellent biocompatibility and the capability of ferrying gene molecules. Moreover, the synthesis process of PßAEs is simple, the monomers are readily available, and the polymer structure can be tailored to meet different gene delivery needs by adjusting the monomer type, monomer ratio, reaction time, etc. Therefore, PßAEs are a promising class of non-viral gene vector materials. This review paper presents a comprehensive overview of the synthesis and correlated properties of PßAEs and summarizes the progress of each type of PßAE for gene delivery. The review focuses in particular on the rational design of PßAE structures, thoroughly discusses the correlations between intrinsic structure and effect, and then finishes with the applications and perspectives of PßAEs.

Cationic Polymers as Transfection Reagents for Nucleic Acid Delivery.

Nucleic acid therapy can achieve lasting and even curative effects through gene augmentation, gene suppression, and genome editing. However, it is difficult for naked nucleic acid molecules to enter cells. As a result, the key to nucleic acid therapy is the introduction of nucleic acid molecules into cells. Cationic polymers are non-viral nucleic acid delivery systems with positively charged groups on their molecules that concentrate nucleic acid molecules to form nanoparticles, which help nucleic acids cross barriers to express proteins in cells or inhibit target gene expression. Cationic polymers are easy to synthesize, modify, and structurally control, making them a promising class of nucleic acid delivery systems. In this manuscript, we describe several representative cationic polymers, especially biodegradable cationic polymers, and provide an outlook on cationic polymers as nucleic acid delivery vehicles.

Intracellular Rod Crystals in Chronic Lymphocytic Leukemia.

BACKGROUND: So far, rare cases of B cell lymphoproliferative diseases with rod crystals inclusions had been reported. METHODS: Wright's stain and MPO stain are used for cell and rod crystal staining while the immunophenotype examination, fluorescence in situ hybridization probes, routine G-band cytogenetic analysis and molecular biological tests are used to diagnose the disease which is chronic lymphocytic leukemia. RESULTS: One to six colorless rod-like crystals can be seen in some mature lymphocytes of the peripheral blood smear and also colorless by MPO staining. The immunophenotype examination with flow cytometry shows it is consistent with chronic lymphocytic leuke mia/B small lymphocytic lymphoma. CONCLUSIONS: The discovery of this rare phenomenon of rod-shaped crystallization in the peripheral blood may contribute to the diagnosis of lymphoproliferative diseases in B cells.

The nanoformula of zoledronic acid and calcium carbonate targets osteoclasts and reverses osteoporosis.

Osteoporosis is known as an imbalance in bone catabolism and anabolism. Overactive bone resorption causes bone mass loss and increased incidence of fragility fractures. Antiresorptive drugs are widely used for osteoporosis treatment, and their inhibitory effects on osteoclasts (OCs) have been well established. However, due to the lack of selectivity, their off-target and side effects often bring suffering to patients. Herein, an OCs' microenvironment-responsive nanoplatform HA-MC/CaCO3/ZOL@PBAE-SA (HMCZP) is developed, consisting of succinic anhydride (SA)-modified poly(ß-amino ester) (PBAE) micelle, calcium carbonate shell, minocycline-modified hyaluronic acid (HA-MC) and zoledronic acid (ZOL). Results indicate that HMCZP, as compared with the first-line therapy, could more effectively inhibit the activity of mature OCs and significantly reverse the systemic bone mass loss in ovariectomized mice. In addition, the OCs-targeted capacity of HMCZP makes it therapeutically efficient at sites of severe bone mass loss and allows it to reduce the adverse effects of ZOL, such as acute phase reaction. High-throughput RNA sequencing (RNA-seq) reveals that HMCZP could down-regulate a critical osteoporotic target, tartrate-resistant acid phosphatase (TRAP), as well as other potential therapeutical targets for osteoporosis. These results suggest that an intelligent nanoplatform targeting OCs is a promising strategy for osteoporosis therapy.

Precision Nanomedicines: Targeting Hot Mitochondria in Cancer Cells.

Mitochondrion is a multifunctional organelle in a cell, and it is one of the important targets of antitumor therapy. Conventional mitochondrial targeting strategies can hardly distinguish the mitochondria in cancer cells from those in normal cells, which might raise a concern about the biosafety. Recent studies suggest that a relatively high temperature of mitochondria exists in cancer cells. We named it tumor intrinsic mitochondrial overheating (TIMO). By taking advantage of the difference in mitochondrial temperatures between cancer cells and normal cells, therapeutic agents can be specifically delivered to the mitochondria in cancer cells. Here we will briefly overview the mitochondria-targeted delivery strategies. In addition, the recent discovery of hot mitochondria in cancer cells and the development of mitochondrial temperature-responsive delivery systems for antitumor therapy will be reviewed.

LncRNA B4GALT1-AS1 promotes non-small cell lung cancer cell growth via increasing ZEB1 level by sponging miR-144-3p.

Background: Long noncoding RNAs (lncRNAs) are emerging as key players in the development and progression of cancer. Several malignancies involve dysregulated long noncoding ribonucleic acids (lncRNAs) in non-small cell lung cancer cell growth and their aggressive phenotypes. LncRNA B4GALT1-AS1 is important in the advancement of various malignancies, although its contribution to non-small cell lung cancer (NSCLC) remains unexplored. Methods: LncRNA B4GALT1-AS1 in NSCLC tissues was detected and further validated in a cohort of non-small cell lung cancer tissues. The effects of lncRNA B4GALT1-AS1 on proliferation were determined by in vitro experiments. The B4GALT1-AS1-miR-144-3p-ZEB1 axis was assessed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Furthermore, the mechanism of B4GALT1-AS1 was investigated using loss-of-function assays in vitro. Results: We showed significant upregulation of B4GALT1-AS1 in cell lines and tissues of NSCLC. B4GALT1-AS1 knockdown impeded the in vitro proliferation-related characteristics of the NSCLC cells. The demonstration of the binding capacity of B4GALT1-AS1 and miR-144-3p was predicted by bioinformatics and luciferase reporter activity assay. The B4GALT1-AS1 and miR-144-3p interaction was shown by using rescue experiments. NSCLC has a positive association with its target, zinc finger e-box binding homeobox 1 (ZEB1). Conclusions: In summary, the progression of NSCLC was facilitated by lncRNA B4GALT1-AS1 via interaction with miR-144-3p and positive regulation of ZEB1 expression.

Loratadine-associated cystoid macular edema: A case report.

Purpose: To report the first known case of bilateral cystoid macular edema in a patient undergoing long-term loratadine treatment. Observations: A 49-year-old Chinese woman who had been undergoing treatment with loratadine for the past 6 years presented with decreased visual acuity and bilateral cystoid macular edema (CME). Upon cessation of loratadine, macular edema partially resolved, and visual acuity markedly improved. Fundus autofluorescence (FAF), optical coherence tomography (OCT), and fluorescence fundus angiography (FFA) were used to document the severity of CME and its subsequent resolution after cessation of loratadine therapy. Conclusions and Importance: Long-term use of loratadine might cause CME that partially resolves with discontinuation of the drug. The pathophysiology of drug-induced CME without leakage remains unclear. Dysfunction of histamine receptor1-expressed retinal neurons and the associated signal transduction, toxicity to Müller cells or RPE cells with subsequent intracellular fluid accumulation, and subclinical damage to the blood-retina barrier leading to leakage of extracellular fluid, have been proposed.

Mitochondrial temperature-responsive drug delivery reverses drug resistance in lung cancer.

Reversal of cancer drug resistance remains a critical challenge in chemotherapy. Mitochondria-targeted drug delivery has been suggested to mitigate drug resistance in cancer. To overcome the intrinsic limitations in conventional mitochondrial targeting strategies, we develop mitochondrial temperature-responsive drug delivery to reverse doxorubicin (DOX) resistance in lung cancer. Results demonstrate that the thermoresponsive nanocarrier can prevent DOX efflux and facilitate DOX accumulation and mitochondrial targeting in DOX-resistant tumors. As a consequence, thermoresponsive nanocarrier enhances the cytotoxicity of DOX and reverses the drug resistance in tumor-bearing mice. This work represents the first example of mitochondrial temperature-responsive drug delivery for reversing cancer drug resistance.

Prognostic Value and Immune Infiltration Analysis of Nuclear Factor Erythroid-2 Family Members in Ovarian Cancer.

Ovarian cancer (OC) often presents at an advanced stage and is still one of the most frequent causes of gynecological cancer-related mortality worldwide. The nuclear factor erythroid-2 (NFE2) transcription factors include nuclear factor, erythroid 2 like 1 (NFE2L1), NFE2L2, and NFE2L3. NFE2 members bind to the antioxidant-response element (ARE) region and activate the expression of targeted genes. The distinct functions of NFE2 members in OC remain poorly elucidated. Several online bioinformatics databases were applied to determine gene expression, prognosis, mutations, and immune infiltration correlation in OC patients. NFE2L1 and NFE2L2 were decreased in OC, whereas NFE2L3 was increased. NFE2L2 and NFE2L3 were significantly correlated with the clinical stages of OC. High NFE2L1 level was significantly associated with short progression-free survival (PFS) in patients with OC (HR = 1.18, P = 0.021), while high NFE2L2 expression strongly correlated with long PFS (HR = 0.77, P = 0.00067). High NFE2L3 expression was associated with better overall survival and postprogression survival in OC. Functional analysis showed that NFE2 members mainly focused on transcription coactivator activities. Genetic alterations of NFE2 members were found in 13% of OC patients, and amplification ranked the top. The expression of NFE2 members was significantly correlated with immune infiltration of CD4+ T cells, CD8+ T cells, B cells, macrophages, and neutrophils in OC. Our study provides novel insights into the roles and prognostic potential of NFE2 family members in OC.

The Expansion and Cytotoxicity Detection of Human iNKT Cells.

Invariant natural killer T (iNKT) cell is a type of innate-like T cell subsets with both T and NK cell phenotype and functions. They recognize lipid antigens presented by CD1d molecules and can be specifically activated by alpha-galactosylceramide (α-GalCer) in vitro. After activation, iNKT cells expand efficiently and exert direct killing effects. Based on it, we mainly introduce the protocols of detection of human iNKT cell functions in vitro, including in vitro expansion and their cytotoxicity to tumor cells.