Quinazoline-2,4(1 H,3 H)-dione Scaffold for development of a novel PARP-targeting PET probe for tumor imaging.

PURPOSE: Overexpression of Poly (ADP-ribose) polymerase (PARP) is associated with many diseases such as oncological diseases. Several PARP-targeting radiotracers have been developed to detect tumor in recent years. Two 18F labelled probes based on Olaparib and Rucaparib molecular scaffolds have been evaluated in clinical trials, but their slow hepatic clearance hinders their tumor imaging performance. Although a number of positron emission tomography (PET) probes with lower liver uptake have been designed, the tumor to background ratios remains to be low. Therefore, we designed a probe with low lipid-water partition coefficient to solve this problem. METHODS: A pyridine-containing quinazoline-2,4(1 H,3 H)-dione PARP-targeting group was rationally designed and used to conjugate with the chelator 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) to prepare the lead compound named as SMIC-2001 for radiolabeling. In vitro experiments, the lipid-water partition coefficient, stability, binding affinity, and cellular uptake of [68Ga]Ga-SMIC-2001 were determined. In vivo experiments, the U87MG xenograft models were used to evaluate its tumor imaging properties. RESULTS: [68Ga]Ga-SMIC-2001 showed a low Log D7.4 (-3.82 ± 0.06) and high affinity for PARP-1 (48.13 nM). In vivo study revealed that it exhibited a high tumor-to-background contrast in the U87MG xenograft models and mainly renal clearance. And the ratios of tumor to main organs were high except for the kidney (e.g. tumor to liver ratio reached 2.20 ± 0.51) at 60 min p.i. CONCLUSION: In summary, pyridine-containing quinazoline-2,4(1 H,3 H)-dione is a novel PARP-targeting molecular scaffold for imaging probe development, and [68Ga]Ga-SMIC-2001 is a highly promising PET probe capable of imaging tumors with PARP overexpression.

Bimetallic CuSbSe2 : A Potential Anode Material for Sodium and Lithium-Ion Batteries with High-Rate Capability and Long-Term Stability.

Bimetallic transition metal chalcogenides (TMCs) materials have emerged as attractive anodes for lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) because of the high intrinsic electronic conductivity, rich redox sites and unique reaction mechanism. In this work, we report the synthesis and electrochemical properties of a novel bimetallic TMCs material CuSbSe2 . The as-prepared anode delivers a high reversible capacity of 545.6  mA h g-1 for SIBs and 592.6  mA h g-1 for LIBs at a current density of 0.2 A g-1 , and an excellent rate capability of 425.9  mA h g-1 at 20 A g-1 for SIBs and 226.0  mA h g-1 at 10 A g-1 for LIBs without any common-used surface modification or carbonaceous compositing. In addition, ex situ X-ray diffraction (XRD) and High-resolution transmission electron microscopy (HRTEM) reveal a combined conversion-alloying reaction mechanism of LIBs and NIBs. Our findings suggest bimetallic CuSbSe2 could be a potential anode material for both SIBs and LIBs.

Fibroblast Activation Protein Targeting Probe with Gly-Pro Sequence for PET of Glioblastoma.

As an important cancer-associated fibroblast-specific biomarker, fibroblast activation protein (FAP) has become an attractive target for tumor diagnosis and treatment. However, most FAP-based radiotracers showed inadequate uptake and short retention in tumors. In this study, we designed and synthesized a novel FAP ligand (DOTA-GPFAPI-04) through assembling three functional moieties: a quinoline-based FAP inhibitor for specifically targeting FAP, a FAP substrate Gly-Pro as a linker for increasing the FAP protein interaction, and a 2,2',2″,2‴-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) chelator for radiolabeling with different radionuclides. The FAP targeting ability of DOTA-GPFAPI-04 was investigated by molecular docking studies. DOTA-GPFAPI-04 was then radiolabeled with 68Ga to give [68Ga]Ga-DOTA-GPFAPI-04 for positron emission tomography (PET) imaging of glioblastoma. [68Ga]Ga-DOTA-GPFAPI-04 exhibited a purity of >98% and high stability analyzed by radio-HPLC in saline and mouse serum. Cell uptake studies demonstrated the targeting specificity of the probe. Further in vivo pharmacokinetic studies in normal mice demonstrated the quick clearance of the probe. Moreover, compared with the widely studied [68Ga]Ga-FAPI-04, [68Ga]Ga-DOTA-GPFAPI-04 showed much higher U87MG tumor uptake values (4.467 ± 0.379 for [68Ga]Ga-DOTA-GPFAPI-04 and 1.267 ± 0.208% ID/g for [68Ga]Ga-FAPI-04 at 0.5 h post-injection, respectively). The area under the curve based on time-activity curve (TAC) analysis for tumor radioactivity in small animal models was 422.5 for [68Ga]Ga-DOTA-GPFAPI-04 and 98.14 for [68Ga]Ga-FAPI-04, respectively, demonstrating that the former had longer tumor retention time. The tumor-to-muscle (T/M) ratio for [68Ga]Ga-DOTA-GPFAPI-04 reached 9.15 in a U87MG xenograft animal model. PET imaging and blocking assays showed that [68Ga]Ga-DOTA-GPFAPI-04 had specific tumor uptake. In summary, this study demonstrates the successful synthesis and evaluation of a novel FAPI targeting probe, [68Ga]Ga-DOTA-GPFAPI-04, with a Gly-Pro sequence. It shows favorable in vivo glioblastoma imaging properties and relatively long tumor retention, highlighting DOTA-GPFAPI-04 as a promising molecular scaffold for developing FAP targeting tumor theranostic agents.

Accumulation, transportation, and distribution of tetracycline and cadmium in rice.

Co-exposure to heavy metal and antibiotic pollution might result in complexation and synergistic interactions, affecting rice growth and further exacerbating pollutant enrichment. Therefore, our study sought to clarify the influence of different Tetracycline (TC) and Cadmium(Cd) concentration ratios (both alone and combined) on rice growth, pollutant accumulation, and transportation during the tillering stage in hydroponic system. Surprisingly, our findings indicated that the interaction between TC and Cd could alleviate the toxic effects of TC/Cd on aerial rice structures and decrease pollutant burdens during root elongation. In contrast, TC and Cd synergistically promoted the accumulation of TC/Cd in rice roots. However, their interaction increased the accumulation of TC in roots while decreasing the accumulation of Cd when the toxicant doses increased. The strong affinity of rice to Cd promoted its upward transport from the roots, whereas the toxic effects of TC reduced TC transport. Therefore, the combined toxicity of the two pollutants inhibited their upward transport. Additionally, a low concentration of TC promoted the accumulation of Cd in rice mainly in the root tip. Furthermore, a certain dose of TC promoted the upward migration of Cd from the root tip. Laser ablation-inductively coupled plasma mass spectrometry demonstrated that Cd mainly accumulated in the epidermis and stele of the root, whereas Fe mainly accumulated in the epidermis, which inhibited the absorption and accumulation of Cd by the rice roots through the generation of a Fe plaque. Our findings thus provide insights into the effects of TC and Cd co-exposure on rice growth.

Pressure Tuning of Optical Properties and Structures in All-Inorganic Halide Perovskite Rb7Sb3Cl16.

All lead-free inorganic halide perovskites, as efficient solid-state light emission materials, have become ideal green optoelectronic materials to replace lead halide perovskites for diversified lighting and display applications with their excellent stability. Here, we investigated the pressure-derived optical and structural response of a zero-dimensional lead-free perovskite Rb7Sb3Cl16 through applying controllable pressure. A pressure-induced blue shift of the broadband emission was achieved, and it was followed by the emission color transformation from yellow to green, which was ascribed to the electron-phonon coupling weakening and the suppression of structural deformation upon lattice contraction. In parallel, the band gap was narrowed by about 0.5 eV as a result of enhanced metal halide orbital overlap under high pressure. This work provides a fundamental understanding for modulating the optical properties of the low-dimensional metal halide perovskites.

Tetracycline-Induced Release and Oxidation of As(III) Coupled with Concomitant Ferrihydrite Transformation.

Cocontamination with tetracycline (TC) and arsenic (As) is very common in paddy fields. However, the process and underlying mechanism of arsenite (As(III)) transformation on iron mineral surfaces in the presence of antibiotic contaminants remain unclear. In this study, the release and oxidation of As(III) on ferrihydrite (Fh) surfaces and Fh transformation in the presence of TC under both aerobic and anaerobic conditions were investigated. Our results indicated that the TC-induced reductive dissolution of Fh (Fe(II) release) and TC competitive adsorption significantly promote the release of As, especially under anaerobic conditions. The release of As was increased with increasing TC concentration, whereas it decreased with increasing pH. Interestingly, under both aerobic and anaerobic conditions, the addition of TC enhanced the oxidation of As(III) by Fh and induced the partial transformation of Fh to lepidocrocite. Under aerobic conditions, the adsorbed Fe(II) activated the production of reactive oxygen species (·OH and 1O2) from dissolved O2, with Fe(IV) being responsible for As(III) oxidation. Under anaerobic conditions, the abundant oxygen vacancies of Fh affected the oxidation of As(III) during Fh recrystallization. Thus, this study provided new insights into the role of TC on the migration and transformation of As coupled with Fe in soils.

Identification and Characterization of Abiotic Stress-Responsive NF-YB Family Genes in Medicago.

Nuclear factor YB (NF-YB) are plant-specific transcription factors that play a critical regulatory role in plant growth and development as well as in plant resistance against various stresses. In this study, a total of 49 NF-YB genes were identified from the genomes of Medicago truncatula and Medicago sativa. Multiple sequence alignment analysis showed that all of these NF-YB members contain DNA binding domain, NF-YA interaction domain and NF-YC interaction domain. Phylogenetic analysis suggested that these NF-YB proteins could be classified into five distinct clusters. We also analyzed the exon-intron organizations and conserved motifs of these NF-YB genes and their deduced proteins. We also found many stress-related cis-acting elements in their promoter region. In addition, analyses on genechip for M. truncatula and transcriptome data for M. sativa indicated that these NF-YB genes exhibited a distinct expression pattern in various tissues; many of these could be induced by drought and/or salt treatments. In particular, RT-qPCR analysis revealed that the expression levels of gene pairs MsNF-YB27/MtNF-YB15 and MsNF-YB28/MtNF-YB16 were significantly up-regulated under NaCl and mannitol treatments, indicating that they are most likely involved in salt and drought stress response. Taken together, our study on NF-YB family genes in Medicago is valuable for their functional characterization, as well as for the application of NF-YB genes in genetic breeding for high-yield and high-resistance alfalfa.

Emodin-induced autophagic cell death hinders epithelial-mesenchymal transition via regulation of BMP-7/TGF-ß1 in renal fibrosis.

We aim to explore the effects of emodin and its mechanisms on renal fibrosis (RF). We firstly modeled adriamycin-induced rat RF with unilateral nephrectomy. In vivo and in vitro pharmacological experiments were performed in this study. The presence of collagen deposition was detected by Masson staining. To verify whether emodin attenuates RF by monitoring autophagy, the immunohistochemistry staining for autophagy protein LC3B was performed. We conducted western blot to detect the expression of the autophagy-related proteins in EMT in vitro model after treating with emotin and BMP-7. In vivo, we demonstrated that emodin could improve renal dysfunction and decrease pathological damage of the kidney by activation of autophagy and inhibition of EMT. Upregulation of BMP-7 was recorded in the RF rats subjected to emodin treatment. In vitro studies, emodin has the capacity of reversing EMT and activating autophagy, and emodin could regulate the expression of BMP-7. The results revealed that the attenuation of EMT by emodin could be blocked after the inhibition of BMP-7 and suppression of autophagy. Our findings demonstrated that emodin alleviates EMT during RF by actuating autophagy through BMP-7, suggesting a role of BMP-7 in RF treatment and prevention.

miR-96 regulates migration and invasion of bladder cancer through epithelial-mesenchymal transition in response to transforming growth factor-ß1.

Bladder cancer (BC) is one of the most frequent urological malignancies, and its molecular mechanism still remains unclear. Recent studies have revealed that MicroRNA (miRNAs) acted as oncogenes or tumor suppressors in a variety of cancers. MiRNA-96 has been reported to play a significant role in the development and progression of many cancers. In the current study, we found that transforming growth factor (TGF)-ß1 played a significant role in the progression that miR-96 conducted. And TGF-ß1 could also regulate the expression of FOXQ1, which is the target gene of miR-96. Furthermore, miR-96 induced epithelial-mesenchymal transition in BC cells, which is driven by TGF-ß1. In conclusion, our data revealed that miR-96 regulates the progression and epithelial-mesenchymal transition, which is driven by TGF-ß1 in BC cells; it may provide a new thought for the therapy of BC.

Sorafenib Inhibits Renal Fibrosis Induced by Unilateral Ureteral Obstruction via Inhibition of Macrophage Infiltration.

AIMS: Sorafenib, which has been used extensively for the treatment of renal cell cancer and advanced hepatocellular carcinoma (HCC), has also been shown to have antifibrotic effects in liver fibrosis. However, the effects of sorafenib on renal fibrosis are unknown. Therefore, we investigated whether sorafenib inhibited renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO) and further explored the potential mechanism. METHODS: Mice underwent UUO followed by vehicle or sorafenib treatment. The expression of CD68, a macrophage marker, and the pro-inflammatory cytokines, MCP1 and CXCR3, were immunohistochemically analyzed. The involvement of macrophages in the formation of renal fibrosis was studied using confocal microscopy. RESULTS: Renal histopathology improved in the UUO-sorafenib mice. Sorafenib notably suppressed TGF-ß1-mediated renal fibrogenic effects. The mRNA and protein expressions of CD68, MCP1, and CXCR3 in the obstructed kidney were significantly decreased by sorafenib. Immunohistochemistry showed that CD68 and CXCR3 had a similar distribution, whereas MCP1 was observed predominantly in the tubular epithelial cells. Double immunofluorescence demonstrated that CD68-positive macrophages could co-localize with CXCR3. It also revealed that CXCR3 interacted with CXCL11 in the UUO mouse kidneys. Widespread adhesion of macrophages to myofibroblasts was markedly inhibited in UUO-sorafenib mouse kidneys. CONCLUSIONS: Taken together, the results indicated that sorafenib had protective effects against renal fibrosis; its mechanism of action was associated with inhibition of macrophage infiltration via the CXCR3/CXCL11 pathway. These data suggest the clinical potential of sorafenib for treatment of renal fibrosis and illustrate the immunological mechanisms underlying the protective effects of sorafenib.

Holmium-doped fluorotellurite microstructured fibers for 2.1 µm lasing.

Holmium (Ho3+)-doped fluorotellurite microstructured fibers based on TeO2-BaF2-Y2O3 glasses are fabricated by using a rod-in-tube method. By using a 1.992 µm fiber laser as the pump source, lasing at 2.077 µm is obtained from a 27 cm long Ho3+-doped fluorotellurite microstructured fiber. The maximum unsaturated power is about 161 mW and the corresponding slope efficiency is up to 67.4%. The influence of fiber length on lasing at 2.1 µm is also investigated. Our results show that Ho3+-doped fluorotellurite microstructured fibers are promising gain media for 2.1 µm laser applications.

Enhanced near-infrared upconversion luminescence of GdF3:Yb3+, Tm3+ by Li+.

GdF3:0.23Yb3+, 0.005Tm3+, x%Li+ (x = 0-7) NIR to NIR upconversion nanocrystals (UCNPs) were synthesized by a hydrothermal method. Their XRD patterns show that they are all orthorhombic phase despite of different Li+ ion concentrations. The detailed analysis indicates that lithium ions substitute Gd3+ sites at x < 3. As the Li+ content increases, more Li+ ions enter host lattice interstitially. The doped Li+ ions affect the crystal field symmetry around Tm3+ ions, which results in the change of the irradiation transition probabilities between their corresponding transition levels. Compared with GdF3:0.23Yb3+, 0.005Tm3+, the NIR to NIR upconversion emission intensity of GdF3:0.23Yb3+, 0.005Tm3+, 0.03Li+ nanocrystals (excitation at 980 nm, emission at 808 nm) increases 2.2 times.

Upconversion luminescence properties of Yb3+ and Tm3+ codoped amorphous fluoride ZrF4-BaF2-LaF3-AlF3-NaF thin film prepared by pulsed laser deposition.

The Yb3+ and Tm3+ co-doped 55.98ZrF4-28BaF2-2.5LaF3-4AlF3-7NaF-2.5YbF3-0.02TmF3 amorphous fluoride film was prepared by pulsed laser deposition. The spectroscopic properties and energy transfer analysis of this film were studies in detail. Ultraviolet and visible upconversion emissions were observed under the infrared excitation at 980 nm. In comparison with that of its target, the upconversion emissions of the film in the visible and ultraviolet range were greatly enhanced. The possible energy transfer mechanism of the emissions was given to understand the upconversion process. This kind of thin films has potential applications for the integrated optical waveguide amplifier and ultraviolet laser.

Improved ultraviolet upconversion emissions of Ho3+ in hexagonal NaYF4 microcrystals under 980 nm excitation.

Under 980 nm excitation, enhanced ultraviolet (UV) upconversion (UC) emissions at 242.4 nm, 276.1 nm, 289.7 nm, 296.4 nm, 303.6 nm, 357.7 nm and 387.8 nm of Ho3+ ions were observed in beta-NaYF4:20%Yb3+, 1.5%Ho3+ microcrystals (MC) which were synthesized through a hydrothermal method. The results indicated that these UV emissions came from five- and four-photon UC processes. Dynamical analysis on Ho3+ excited states suggests that, for excited Ho3+ ions, the higher the energy level is, the shorter the lifetime is.

Respiratory effort in mechanical ventilation weaning Prediction: An observational, case-control study.

BACKGROUND: The diaphragm is crucial for ventilator weaning, but its specific impact on weaning indicators needs further clarification. This study investigated the variability in weaning outcomes across different diaphragm function populations and the value of respiratory drive and inspiratory effort in weaning. METHODS: This observational case-control study enrolled patients on mechanical ventilation for more than 48 h and completed a 30-minute spontaneous breathing trial (SBT) with pressure-support ventilation for the first time. After the SBT, airway pressure at 100 ms during occlusion (P0.1), inspiratory effort, and diaphragmatic ultrasound were evaluated to predict weaning outcomes. Weaning failure was defined as re-intubation within 48 h of weaning, the need for therapeutic non-invasive ventilation, or death. RESULTS: 68 patients with a mean age of 63.21 ± 15.15 years were included. In patients with diaphragm thickness (DT) ≥ 2 mm, P0.1 (P=0.002), pressure-muscle index (PMI) (P=0.012), and occluded expiratory airway pressure swing (ΔPocc) (P=0.030) were significantly higher in those who failed weaning. Conversely, for patients with DT<2 mm, PMI (P=0.003) and ΔPocc (P=0.002) were lower in the weaning failure group. Additionally, within the DT≥2 mm group, P0.1 demonstrated a higher area under the curve (AUC) for weaning prediction (0.889 vs. 0.739) compared to those with DT<2 mm. CONCLUSIONS: PMI and ΔPocc are predictive of weaning outcomes in patients with diaphragm thickness ≥ 2 mm, where the assessment value of P0.1 is notably higher. Diaphragm function significantly influences the accuracy of weaning predictions based on respiratory drive and inspiratory effort. IMPLICATIONS FOR CLINICAL PRACTICE: Our findings indicate that the effectiveness of respiratory drive and inspiratory effort in predicting successful weaning from mechanical ventilation may vary across different patient populations. Diaphragm function plays a crucial role in weaning assessments, particularly when using P0.1, the pressure-muscle index (PMI), and occluded expiratory airway pressure swing (ΔPocc).

Identification and analysis of flavonoid pathway genes in responsive to drought and salinity stress in Medicago truncatula.

Flavonoid compounds are widely present in various organs and tissues of different plants, playing important roles when plants are exposed to abiotic stresses. Different types of flavonoids are biosynthesized by a series of enzymes that are encoded by a range of gene families. In this study, a total of 63 flavonoid pathway genes were identified from the genome of Medicago truncatula. Gene structure analysis revealed that they all have different gene structure, with most CHS genes containing only one intron. Additionally, analysis of promoter sequences revealed that many cis-acting elements responsive to abiotic stress are located in the promoter region of flavonoid pathway genes. Furthermore, analysis on M. truncatula gene chip data revealed significant changes in expression level of most flavonoid pathway genes under the induction of salt or drought treatment. qRT-PCR further confirmed significant increase in expression level of several flavonoid pathway genes under NaCl and mannitol treatments, with CHS1, CHS9, CHS10, F3'H4 and F3'H5 genes showing significant up-regulation, indicating they are key genes in response to abiotic stress in M. truncatula. In summary, our study identified key flavonoid pathway genes that were involved in salt and drought response, which provides important insights into possible modification of flavonoid pathway genes for molecular breeding of forage grass with improved abiotic resistance.

A multi-modal framework improves prediction of tissue-specific gene expression from a surrogate tissue.

BACKGROUND: Tissue-specific analysis of the transcriptome is critical to elucidating the molecular basis of complex traits, but central tissues are often not accessible. We propose a methodology, Multi-mOdal-based framework to bridge the Transcriptome between PEripheral and Central tissues (MOTPEC). METHODS: Multi-modal regulatory elements in peripheral blood are incorporated as features for gene expression prediction in 48 central tissues. To demonstrate the utility, we apply it to the identification of BMI-associated genes and compare the tissue-specific results with those derived directly from surrogate blood. FINDINGS: MOTPEC models demonstrate superior performance compared with both baseline models in blood and existing models across the 48 central tissues. We identify a set of BMI-associated genes using the central tissue MOTPEC-predicted transcriptome data. The MOTPEC-based differential gene expression (DGE) analysis of BMI in the central tissues (including brain caudate basal ganglia and visceral omentum adipose tissue) identifies 378 genes overlapping the results from a TWAS of BMI, while only 162 overlapping genes are identified using gene expression in blood. Cellular perturbation analysis further supports the utility of MOTPEC for identifying trait-associated gene sets and narrowing the effect size divergence between peripheral blood and central tissues. INTERPRETATION: The MOTPEC framework improves the gene expression prediction accuracy for central tissues and enhances the identification of tissue-specific trait-associated genes. FUNDING: This research is supported by the National Natural Science Foundation of China 82204118 (D.Z.), the seed funding of the Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province (2020E10004), the National Institutes of Health (NIH) Genomic Innovator Award R35HG010718 (E.R.G.), NIH/NHGRI R01HG011138 (E.R.G.), NIH/NIA R56AG068026 (E.R.G.), NIH Office of the Director U24OD035523 (E.R.G.), and NIH/NIGMS R01GM140287 (E.R.G.).

Short-term clinical effects of photodynamic therapy with topical 5-aminolevulinic acid for facial acne conglobata: an open, prospective, parallel-arm trial.

BACKGROUND: Acne conglobata is hardly curable and easily leads to scar formation after treatment using traditional methods. AIM: To develop a novel way to treat acne conglobata. METHODS: Seventy-five patients with facial acne conglobata were included in this clinical study and divided into either a treatment group (n = 35) to receive photodynamic therapy (PDT) with topical 5% 5-aminolevulinic acid and red light once every 10 days for a month or a control group (n = 40) to receive a Chinese herbal medicine mask plus red light once per week for the same duration. Patients in both groups were given oral viaminate capsules, doxycycline, zinc gluconate, and topical metronidazole. Efficacy was evaluated with respect to symptom score, cure rate, and response rate up to 2 weeks following the final treatment, and time points for assessment included baseline (D0 ), the visit before each treatment (D10 and D20 for the treatment group, and D7 , D14 , and D21 for the control group), and 2 weeks after treatment (D34 for the treatment group and D35 for the control group). Safety was assessed by recording adverse effects. RESULTS: Treatment with PDT significantly improved acne lesions and reduced scar formation. The treatment group had a significantly lower symptom score, a higher cure rate, and response rate than the control group. No systemic side effects occurred. CONCLUSION: The treatment of acne conglobata with PDT is associated with a high cure rate, short treatment period, few side effects, and reduced scar formation. To the best of our knowledge, this is the first report on the treatment of acne conglobata with PDT.

Axial compression performance of square concrete filled double skin SHS steel tubular columns confined by CFRP.

This paper focuses on the axial compression performance of 15 concrete-filled double skinned tubes CFDST columns with different CFRP reinforcement schemes. The design of this test used an outer square steel tube with a square steel tube inside, with concrete poured at the sandwich and the inner steel tube kept hollow. The structure is both cost effective and allows the hollow to be used for utility access. However, in recent years damage to CFDST has occurred due to fire, earthquakes, corrosion etc. Therefore, research into the reinforcement and repair of this structure is crucial. Compared to other reinforcement methods, FRP has the advantage of being lighter and more robust and does not significantly alter the original structure. In this study, the mechanical properties of the specimens were further analyzed from the data of load displacement, peak load and ultimate displacement by mainly observing and analyzing the damage mechanism of the specimens through the strengthening effect of different strengthening schemes for different hollow ratios. The results show that when the hollow ratio is not bigger than 0.33, the CFRP reinforcement effect is relatively obvious, especially the three-layer CFRP wrapped CFDST specimens have a substantial increase in bearing capacity and stiffness. Finally, an analytical study was carried out based on previous research and the experimental results agreed well with the calculated results.

EHD2, a novel HIF target gene, is a promising biomarker in clear cell renal cell carcinoma.

OBJECTIVES: The aim of the present study was to determine the clinical value of a novel hypoxia-inducible factor (HIF) target EH domain-containing protein 2 (EHD2) for predicting the outcome of patients with clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: GEPIA public database was searched to determine a possible association between HIF2Α and EHD protein family members, and kidney renal clear cell carcinoma data were used to find the expression profile of EHD proteins in ccRCC samples. A tissue microarray from 70 ccRCC samples was used for immunohistochemical analysis to determine the specific expression pattern of EHD2 in ccRCC samples. In addition, univariate and multivariate analyses were performed to assess the utility of EHD2 as an independent prognostic factor for ccRCC. RESULTS: EHD protein family members were all found to be significantly correlated with HIF2Α expression in ccRCC. However, EHD2 was the only protein that was observed to be overexpressed in ccRCC cancer tissues compared with normal tissues. EHD2 and HIF2Α mRNA expression levels were found to be higher in cancer tissues compared with those in adjacent normal tissue according to reverse transcription-quantitative PCR analysis. Among the 70 patients with ccRCC, EHD2 was overexpressed in 52.8% (37/70). Subsequently, EHD2 was found to be significantly associated with both overall survival (P=0.016) and disease-free survival (P=0.029). Furthermore, by multivariate analysis, EHD2 was an independent prognostic factor for patients with ccRCC. CONCLUSION: EHD2 is a novel HIF target, based on a relatively large sample of EHD2 research in patients with ccRCC. Furthermore, our study provided evidence that EHD2 can serve as a promising biomarker for predicting ccRCC outcome.