Proteomic Analysis of Idiopathic Nephrotic Syndrome Triggered by Primary Podocytopathies in Adults: Regulatory Mechanisms and Diagnostic Implications.

Idiopathic nephrotic syndrome (NS) is a heterogeneous group of glomerular disorders which includes two major phenotypes: minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). MCD and FSGS are classic types of primary podocytopathies. We aimed to explore the molecular mechanisms in NS triggered by primary podocytopathies and evaluate diagnostic value of the selected proteomic signatures by analyzing blood proteome profiling. Totally, we recruited 90 participants in two cohorts. The first cohort was analyzed using label-free quantitative (LFQ) proteomics to discover differential expressed proteins and identify enriched biological process in NS which were further studied in relation to clinical markers of kidney injury. The second cohort was analyzed using parallel reaction monitoring-based quantitative proteomics to verify the data of LFQ proteomics and assess the diagnostic performance of the selected proteins using receiver-operating characteristic curve analysis. Several biological processes (such as immune response, cell adhesion, and response to hypoxia) were found to be associated with kidney injury during MCD and FSGS. Moreover, three proteins (CSF1, APOC3, and LDLR) had over 90% sensitivity and specificity in detecting adult NS triggered by primary podocytopathies. The identified biological processes may play a crucial role in MCD and FSGS pathogenesis. The three blood protein markers are promising for diagnosing adult NS triggered by primary podocytopathies.

Exploration of the Clinical Effect of Different Autotransfusion Methods on Patients With Femoral Shaft Fracture Surgery.

OBJECTIVE: To explore the clinical effect of predeposit, salvage, and hemodilution autotransfusion on patients with femoral shaft fracture (FSF) surgery. METHODS: Selected patients with FSF were randomly divided into three groups: intraoperative blood salvage autotransfusion, preoperative hemodilution autohemotransfusion, and predeposit autotransfusion. Five days after the operation, the body temperature, heart rate, blood platelet (PLT), and hemoglobin (Hb) of patients were determined. The concentrations of EPO and GM-CSF in the three groups were calculated by ELISA. The content of CD14+ monocytes was calculated by FCM assay. The growth time and condition of the patient's callus were determined at the 30th, 45th, and 60th day after operation. Cox regression analysis was used to analyze the correlation between EPO, GM-CSF, CD14+ mononuclear content, callus growth, and autotransfusion methods. RESULTS: There were no statistically significant differences in body temperature and heart rate between the three groups (p > 0.05). PLT and Hb in the Predeposit group were markedly increased compared with that in the Salvage and Hemodilution groups. The concentrations of EPO and GM-CSF in the Predeposit group were markedly increased compared with that in the Salvage and Hemodilution groups. The content of CD14+ monocytes in the Predeposit group was significantly higher than that in the Salvage and Hemodilution groups. Predeposit autotransfusion promotes callus growth more quickly. CONCLUSION: Predeposit autotransfusion promoted the recovery of patients with FSF after the operation more quickly than salvage autotransfusion and hemodilution autotransfusion.

Effects of Bone Transport Combined with Drug-loaded Calcium Sulfate on Expression of Inflammatory Factors and VEGF in Rats with Infectious Bone Defects.

Background: Infectious bone defect refers to severe bone tissue damage caused by skeletal infection, often resulting in impaired skeletal function and intense inflammatory responses. Treating infectious bone defects is a challenging task, as conventional treatment methods often fail to completely eliminate the infection focus and may easily lead to inflammatory responses in the bone defect area. Objective: To examine the impacts of bone transport (BT) in conjunction with drug-loaded calcium sulfate (DLCS) on the expression of inflammatory factors and vascular endothelial growth factor (VEGF) in rats with infectious bone defects. Methods: A total of 40 rats were randomly allocated to 4 groups-the sham, model, BT, and BT + DLCS groups-with 10 rats in each group. Interleukin 10 (IL-10), tumor necrosis factor (TNF), nuclear factor-κB (NF-κB), insulinlike growth factor 1 (IGF 1), and recombinant human basic fibroblast growth factor (rhbFGF) concentrations in serum were measured using enzyme-linked immunosorbent assay. In bone tissue, histopathological changes in defective bone were assessed through hematoxylin-eosin staining, CD34 expression was examined by immunohistochemistry, and VEGF expression was examined by Western blot. Results: In comparison with the sham group, the model group had significant increases in serum IL-10, TNF, and NF-κB concentrations as well as notable decreases in IGF-1 and rhbFGF serum concentrations and CD34 and VEGF expression in the bone tissue (P < .05). In contrast to the model group, both the BT and BT + DLCS groups had significant reductions in serum concentrations of IL-10, TNF, and NF-κB. Additionally, the BT and BT + DLCS groups had significant increases in serum concentrations of IGF-1 and rhbFGF as well as expression of CD34 and VEGF in the bone tissue (P < .05). The BT + DLCS group had significantly lower serum concentrations of IL-10, TNF, and NF-κB compared with the BT group. Furthermore, the BT + DLCS group had significantly elevated serum concentrations of IGF-1 and rhbFGF as well as increased expression of CD34 and VEGF in the bone tissue compared with the BT group (P < .05). Conclusion: The promotion of infected bone defect healing in rats through the combination of BT and DLCS may be attributed to the suppression of inflammatory responses and the elevation of VEGF expression to facilitate vascular regeneration.

Modulation of high-quality internal multifoci based on modified three-dimensional Fourier transform.

We report an efficient method to generate arbitrary three-dimensional (3D) parallel multifoci inside a material. Taking into account the numerical aperture of the objective lens and the refractive index of the material, the Ewald cap was modified with a longer radius, then the whole 3D intensity distribution inside the material could be calculated using only a single Fourier transform (FT). By introducing the adaptive weight coefficient, the uniformity of the 3D multifoci improves from 81.3% to 98.9%. By adjusting the axial resolution of the Ewald cap, the uniformity of the axial multifoci improves from 85.9% to 99.7%. In the experiment, we have realized one-dimensional (1D), 2D, and 3D structures inside the fused silica, which are in excellent agreement with the simulation results. The experimental results of the "H-U-S-T" structure demonstrate that customized arbitrary intensity distribution inside the material can be realized.

Integration of an LPAR1 Antagonist into Liposomes Enhances Their Internalization and Tumor Accumulation in an Animal Model of Human Metastatic Breast Cancer.

Lysophosphatidic acid receptor 1 (LPAR1) is elevated in breast cancer. The deregulation of LPAR1, including the function and level of expression, is linked to cancer initiation, progression, and metastasis. LPAR1 antagonists, AM095 or Ki16425, may be effective therapeutic molecules, yet their limited water solubility hinders in vivo delivery. In this study, we report on the synthesis of two liposomal formulations incorporating AM095 or Ki16425, embedded within the lipid bilayer, as targeted nanocarriers for metastatic breast cancer (MBC). The data show that the Ki16425 liposomal formulation exhibited a 50% increase in internalization by MBC mouse epithelial cells (4T1) and a 100% increase in tumor accumulation in a mouse model of MBC compared with that of a blank liposomal formulation (control). At the same time, normal mouse epithelial cells (EpH-4Ev) internalized the Ki16425 liposomal formulation 25% lesser than the control formulation. Molecular dynamics simulations show that the integration of AM095 or Ki16425 modified the physical and mechanical properties of the lipid bilayer, making it more flexible in these liposomal formulations compared with liposomes without drug. The incorporation of an LPAR1 antagonist within a liposomal drug delivery system represents a viable therapeutic approach for targeting the LPA-LPAR1 axis, which may hinder the progression of MBC.

Deduction of CDC42EP3 suppress development and progression of osteosarcoma.

BACKGROUND: Osteosarcoma is a disease with high mortality of malignant tumors in children and adolescents. CDC42 effector protein 3 (CDC42EP3) has been reported to be associated with human cancer cell progression. This study aimed to investigate the biological function and preliminary molecular mechanism of CDC42EP3 in osteosarcoma. METHODS: CDC42EP3 expression in osteosarcoma was analyzed by immunohistochemical (IHC) staining. Secondly, the biological effects of CDC42EP3 in osteosarcoma cells was determined by loss/gain-of-function assays in vitro and in vivo. RESULTS: CDC42EP3 expression was higher in osteosarcoma tissue than in noncancerous tissue. The expression of CDC42EP3 was positively correlated with age, pathological stage and grade of patients with osteosarcoma. Furthermore, downregulation of CDC42EP3 suppressed tumor progression by inhibiting proliferation, migration and inducing apoptosis in vivo. Importantly, knockdown of CDC42EP3 reduced the expression of interstitial markers (N-cadherin, Vimentin and Snail) and increased the expression of epithelial markers (E-cadherin). In addition, CDC42EP3 knockdown downregulated PI3K and reduced the phosphorylation levels of AKT and mTOR. The mice xenograft model further confirmed that CDC42EP3 knockdown inhibited osteosarcoma growth in vitro. CONCLUSIONS: In summary, these findings highlighted the significance of CDC42EP3 in tumor progression, which implicated CDC42EP3 as a promising candidate molecular target for osteosarcoma therapy.

An All-Dielectric Polaritonic Metasurface with a Giant Nonlinear Optical Response.

Enhancing the efficiency of second-harmonic generation using all-dielectric metasurfaces to date has mostly focused on electromagnetic engineering of optical modes in the meta-atom. Further advances in nonlinear conversion efficiencies can be gained by engineering the material nonlinearities at the nanoscale, however this cannot be achieved using conventional materials. Semiconductor heterostructures that support resonant nonlinearities using quantum engineered intersubband transitions can provide this new degree of freedom. By simultaneously optimizing the heterostructures and meta-atoms, we experimentally realize an all-dielectric polaritonic metasurface with a maximum second-harmonic generation power conversion factor of 0.5 mW/W2 and power conversion efficiencies of 0.015% at nominal pump intensities of 11 kW/cm2. These conversion efficiencies are higher than the record values reported to date in all-dielectric nonlinear metasurfaces but with 3 orders of magnitude lower pump power. Our results therefore open a new direction for designing efficient nonlinear all-dielectric metasurfaces for new classical and quantum light sources.

Control of second-harmonic generation in all-dielectric intersubband metasurfaces by controlling the polarity of χ(2).

All-dielectric metasurfaces have recently led to a paradigm shift in nonlinear optics as they allow for circumventing the phase matching constraints of bulk crystals and offer high nonlinear conversion efficiencies when normalized by the light-matter interaction volume. Unlike bulk crystals, in all-dielectric metasurfaces nonlinear conversion efficiencies primarily rely on the material nonlinearity, field enhancements, and the modal overlaps, therefore most efforts to date have only focused on utilizing these degrees of freedom. In this work, we demonstrate that for second-harmonic generation in all-dielectric metasurfaces, an additional degree of freedom is the control of the polarity of the nonlinear susceptibility. We demonstrate that semiconductor heterostructures that support resonant nonlinearities based on quantum-engineered intersubband transitions provide this new degree of freedom. We can flip and control the polarity of the nonlinear susceptibility of the dielectric medium along the growth direction and couple it to the Mie-type photonic modes. Here we demonstrate that engineering the χ(2) polarity in the meta-atom enables the control of the second-harmonic radiation pattern and conversion efficiency. Our results therefore open a new direction for engineering and optimizing second-harmonic generation using all-dielectric intersubband nonlinear metasurfaces.

Terahertz difference-frequency-generation quantum cascade lasers on silicon with wire grid current injectors.

We propose the concept and experimentally verify the operation of terahertz quantum cascade laser sources based on intra-cavity Cherenkov difference-frequency generation on a silicon substrate with the current injection layer configured as a metal wire grid. Such a current injector configuration enables high transmission of TM-polarized terahertz radiation into the silicon substrate while simultaneously providing a low-resistivity metal contact for current injection.

Stealth dicing of 1-mm-thick glass with aberration-free axial multi-focus beams.

Laser stealth dicing can realize material separation with negligible surface damage, but severe aberrations in thick materials degrade processing quality. This Letter presents a nonlinear point-to-point transformation method combined with spherical aberration compensation to achieve aberration-free axial multi-focus beams. The focus peak intensity increases 7 times at a depth of 0.5 mm after spherical aberration compensation, and reaches 44 times at 3.5 mm. Spherical aberration compensation experiments showed that the width of the heat-affected zone remains almost unchanged at different depths inside the glass, and stealth dicing experiments for 1-mm-thick glass demonstrated that aberration-free 1-focus, 2-foci, and 3-foci stealth dicing can be successfully realized.

Coordinate-transformation iteration algorithm for phase modulation of arbitrary axial light distribution.

Axial light distribution modulation is widely applied in optical tweezers, hard-brittle material cutting, multilayer laser direct writing, etc. To generate arbitrary axial light distribution, the coordinate-transformation iteration (CTI) algorithm is presented. The CTI algorithm unifies equations in low and high numerical aperture (NA) scenarios, using the same iterative algorithm to produce phase computer-generated holograms. In a low NA scenario, twin-foci, flattop, and sin2 distributions have been achieved. In high NA scenarios, multirings, multifoci, and needle-like distributions have been realized in simulation with specific polarized incident beams. Since the CTI algorithm is inherently an efficient one-dimensional phase retrieval algorithm that is not limited by NA, this method has the potential to become a well-received solution for axial light distribution modulation.

Inhibitory effects of astilbin, neoastilbin and isoastilbin on human cytochrome CYP3A4 and 2D6 activities.

Astilbin, neoastilbin and isoastilbin are three flavonoid isomers from Smilacis glabrae Roxb. (S. glabrae). Several studies have shown that consumption of flavonoids can increase the risk of food/drug-drug interaction by affecting the activities of human cytochrome CYP3A4 and 2D6. In the present study, an ultrahigh-performance liquid chromatography and triple quadrupole mass spectrometry method was developed for the determination of the interaction between three flavonoid isomers and two CYPs. Under the optimized reaction conditions, the Km values were 18.9 and 36.4 µM and the Vmax values were 0.02 and 0.20 µM/min for CYP3A4 and 2D6 in vitro, respectively. Astilbin showed the strongest inhibition on CYP3A4, followed by isoastilbin and neoastilbin with IC50 values of 2.63, 3.03 and 6.51 µM. Neoastilbin showed the strongest inhibition on CYP2D6, followed by isoastilbin and astilbin, with IC50 values of 1.48, 11.87 and 14.16 µM, respectively. The three isomers showed reversible inhibition on both enzymes. Neoastilbin and astilbin were noncompetitive type for CYP3A4 and 2D6, isoastilbin was a mixture and noncompetitive type for CYP3A4 and 2D6, respectively. Our study suggests that the three isomers may increase the risk of food/drug-drug interactions by affecting the activities of CYP3A4 and 2D6.

The role of microbiota in the development of colorectal cancer.

Colorectal cancer is the third largest cancer in worldwide and has been proven to be closely related to the intestinal microbiota. Many reports and clinical studies have shown that intestinal microbial behavior may lead to pathological changes in the host intestines. The changes can be divided into epigenetic changes and carcinogenic changes at the gene level, which ultimately promote the production and development of colorectal cancer. This article reviews the pathways of microbial signaling in the intestinal epithelial barrier, the role of microbiota in inflammatory colorectal tumors, and typical microbial carcinogenesis. Finally, by gaining a deeper understanding of the intestinal microbiota, we hope to achieve the goal of treating colorectal cancer using current microbiota technologies, such as fecal microbiological transplantation.

A Gyroidal MOF with Unprecedented Interpenetrating utc-c Network Exhibiting Exceptional Thermal Stability and Ultrahigh CO2 Affinity.

A zeolite-like gyroidal MOF (denoted as SCNU-1) constructed with Cu ions and 4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol has a featured interpenetrating uninodal utc-c network which is for the first time found in the real structure. Moreover, SCNU-1 exhibits high thermal (>773 K), solvent, and acid/base stabilities; the largest CO2 affinity, 90 kJ/mol, among the MOFs functionalized with an aromatic hydroxyl group; and excellent CO2/N2 selectivity.

Correction to: Arsenic concentration, speciation, and risk assessment in sediments of the Xijiang River basin, China.

In the original paper, there was an error in the communication unit 1. The communication unit was "Liaoning Engineering Research Center for Treatment and Recycling of Industrially Discharged Heavy Metals, Shenyang University of Chemical Technology, Shenyang 110142, People's Republic of China".

Arsenic concentration, speciation, and risk assessment in sediments of the Xijiang River basin, China.

In order to acquire the spatial distribution, speciation, and risk assessment of arsenic (As), 18 sediment samples were collected in the middle and upper reaches (Nanpan River, Beipan River, Hongshui River, Diaojiang River, and Duliu River) of the Xijiang River basin, China. The chemical fractions of As in the collected sediments were mainly dominated by the residual fraction and the Fe (Mn, Al) oxide/oxyhydroxides fractions. The correlation analysis results showed that the chemical fraction of As in sediments had close correlations with Mn, good correlations with Fe and organic matter (OM), while weak correlations with Al and carbonate. In addition, it also showed that Diaojiang River basin was found to have an extremely high As pollution status and suffered from high ecological risk. Duliu River and Nanpan River had moderately polluted levels of As and showed a low ecological risk. The other sample sites of Xijiang River basin were uncontaminated of As. The assessment results from this study indicated that the different types of species present based on the chemical fractionation of As from the Xijiang River basin showed different risks. Graphical abstract.

Controllable multiband terahertz notch filter based on a parallel plate waveguide with a single deep groove.

The influence of the air gap on the response of transmission for a transverse-electric mode parallel plate waveguide with a single deep groove has been experimentally studied. As the air gap is larger than the resonant wavelength of a high-order cavity mode in a single deep grooved waveguide, only the fundamental cavity mode can be excited and the single resonance (band) can be observed in a transmission spectrum. The decrease of the air gap can not only efficiently push the radiation of the fundamental cavity mode into the deep groove but also excite the high-order cavity modes, resulting in multiple resonances (multiband) in the corresponding spectrum. Based on the above observations, a tunable multiband terahertz notch filter has been proposed and the variation of the air gap has turned out to be an effective method to select band number. Experimental data and simulated results verify this band number tunability.

Research on the Inhibitory Effect of Doxorubicin-loaded Liposomes Targeting GFAP for Glioma Cells.

BACKGROUND: Glioma is the most common and devastating brain tumor. In recent years, doxorubicin (DOX) is one of the drugs used in the treatment of gliomas, but it has side effects and poor clinical outcomes. Therefore, the delivery of drugs to the tumor site by targeted transport is a new approach to tumor treatment. OBJECTIVE: This study focuses on the anti-tumor effects of GFAP-modified drug-carrying liposomes loaded with DOX (GFAP-DOX-LPs) on gliomas. METHODS: GFAP-DOX-LPs were prepared by solvent evaporation method. After characterization analysis of GFAP-DOX-LPs, the encapsulation efficiency, the drug loading capacity and in vitro release performance were determined. Then, the MTT method was used to investigate the cytotoxicity and proliferative behavior of U251 and U87 cell lines. After that, flow cytometry was used to investigate the effect of the drug administration group on tumor cell apoptosis. Eventually, the anti-tumor activity was tested in vivo. RESULTS: The average particle size of GFAP-DOX-LPs was determined to be 116.3 ± 6.2 nm, and the average potential was displayed as 22.8 ± 7.2 mv. Besides, the morphology of the particle indicated a spherical shape. The encapsulation rate and drug loading were calculated and determined, which were 91.84 ± 0.41% and 9.27 ± 0.55%. In an acidic medium, the DOX release rate reached about 87%. GFAP-DOX-LPs could target glioma cells with low cytotoxicity and inhibit glioma cell proliferation with high efficiency, resulting in promoting apoptosis. The anti-tumor effect of GFAP-DOX-LPs was significantly enhanced. At the same time, the number of GFAPpositive cells in tumor tissues was significantly lower after treatment. Therefore, the overall survival time could be significantly prolonged. CONCLUSION: The prepared GFAP-DOX-LPs had good targeting and glioma cell inhibition ability. This demonstrated the promising application of the prepared liposomes in tumor targeting, especially in the field of targeted drug delivery for the treatment of brain tumor.

Examining Protein Translocation by ß-Barrel Membrane Proteins Using Reconstituted Proteoliposomes.

ß-barrel membrane proteins populate the outer membrane of Gram-negative bacteria, mitochondria, and chloroplasts, playing significant roles in multiple key cellular pathways. Characterizing the functions of these membrane proteins in vivo is often challenging due to the complex protein network in the periplasm of Gram-negative bacteria (or intermembrane space in mitochondria and chloroplasts) and the presence of other outer membrane proteins. In vitro reconstitution into lipid-bilayer-like environments such as nanodiscs or proteoliposomes provides an excellent method for examining the specific function and mechanism of these membrane proteins in an isolated system. Here, we describe the methodologies employed to investigate Slam, a 14-stranded ß-barrel membrane protein also known as the type XI secretion system that is responsible for translocating proteins across the outer membrane of many bacterial species.

A Network of Circular RNA and MicroRNA Sequencing Provides Insights into Pigment Deposition of Changshun Blue Eggshell Chickens.

Eggshell color plays important biological roles and attracts the attention of both egg retailers and researchers. However, whether non-coding RNAs are involved in pigment deposition among different eggshell colors remains unknown. In this study, RNA sequencing was used to analyse the uterine gland transcriptome (CircRNA and miRNA) of Changshun chicken blue-shell hens producing four different eggshell color eggs including dark blue PK(DB) and light blue (LB), dark brown and greenish (between blue and pink, DP) and pink (p). We found that miR-192-x, targeting SLC16a7, was expressed in DB, DP, and LB groups compared with the PK group, which indicates that miR-192-x may play a role in the blue eggshell color. KEGG and GO analyses showed that the "metabolic pathways" with targeted genes such BLVRA and HMOX1 were detected in dark and light blue color eggshell chickens, which confirms the different ratios of biliverdin and HO-1 involved in the deposition of blue color. As annotated by connectivity analysis, RASGRF1 and RASGRF2, belonging to the RASGRF family, are involved in the Ras signaling pathway, which plays an important role in cell growth, differentiation, metastasis and apoptosis. Our findings enrich the database of circRNA, miRNAs and genes for chicken uterine tissue, which will be useful in accelerating molecular selection for blue eggshell color layers.