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With the popularization of small incision lenticule extraction(SMILE), a large number of one-piece corneal stromal lenticules are removed during surgery. As an additional product of surgery, the experimental research and clinical reuse of extracted corneal stromal lenticules from SMILE have become a research hotspot in recent years. Corneal stromal lenticules are thin and transparent, rich in sources, low in cost, and have the advantages of low immunogenicity and good tissue compatibility, so they can be used as important source of cells and corneal stroma research, and also can be used as good biomaterials for corneal reinforcement, patch graft, refractive correction, and lacrimal duct embolization in clinical study. This article reviews the clinical application of SMILE-derived lenticule in the treatment of corneal-related diseases, correction of hyperopia and presbyopia, coverage of glaucoma drainage valve to prevent their exposure, and its use in lacrimal duct plug, aiming to fully recognize the reuse of lenticules in clinical practice, expand its surgical indication, and providing new directions for the treatment of other eye diseases and its application in tissues and organs.

Diquat (DQ) is a commonly used bipyridine herbicide known for its toxic properties and adverse effects on individuals. However, the mechanism underlying DQ-induced damage remain elusive. Our research aimed to uncover the regulatory network involved in DQ-induced damage. We analyzed publicly accessible gene expression patterns and performed research using a DQ-induced damage animal model. The GSE153959 dataset from the Gene Expression Omnibus collection and the animal model of DQ-induced kidney injury were used to identify differentially expressed genes (DEGs). Pathways including the regulation of DNA-templated transcription in response to stress, RNA polymerase II transcription regulator complex and transcription coregulatory activity were shown to be enriched in 21 DEGs. We used least absolute shrinkage and selection operator (LASSO) regression analysis to find possible diagnostic biomarkers for DQ-induced damage. Then, we used an HK-2 cell model to confirm these results. Additionally, we confirmed that 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) was the major gene associated with DQ-induced damage using multi-omics screening. The sample validation strongly suggested that HMGCS2 has promise as a diagnostic marker and may provide new targets for therapy in the context of DQ-induced damage.

Summary: Sunitinib, a primary treatment for clear cell renal cell carcinoma (ccRCC), frequently encounters the challenge of resistance development. Metabolic reprogramming, a characteristic change in ccRCC, is likely linked to this resistance. Our research revealed a notable decrease in the expression of the key metabolic gene ABAT in ccRCC, which contributed to diminished sensitivity to sunitinib. Downregulation of ABAT led to an increase in the intracellular level of gamma-aminobutyric acid (GABA), triggering abnormal activation of the G-protein-coupled receptor GABA-B. This activation resulted in increased transactivation of the tyrosine kinase receptors SYK and LYN, thereby reducing the antitumor and antiangiogenic properties of sunitinib. However, the application of SYK and LYN inhibitors successfully inhibited this effect. The transactivation of SYK and LYN caused resistance to the antiangiogenic effects of sunitinib through the upregulation of PGF protein levels. Furthermore, the combined application of an LYN inhibitor with sunitinib has been shown to enhance therapeutic efficacy.

The spatial pattern of leaf stoichiometry is critical in predicting plant palatability and ecosystem productivity and nutrient cycling rates and thus is a major focus of community ecological research. Coastal wetlands as vital blue carbon ecosystems, with high possibility to be vulnerable to plant invasion, studies focused on stoichiometry and its pattern are important to unveil the elements cycling process. However, previous studies have mainly focused on stoichiometry in terrestrial ecosystems, there are few studies conducted on coastal wetland ecosystems, especially the studies that compare leaf stoichiometry between native and non-native plants in coastal wetlands. In this study, we compared the latitudinal patterns of leaf nutrient contents and their stoichiometric ratios between native and non-native plant species across coastal wetland ecosystems and investigated whether leaf stoichiometric patterns were driven by climatic factors. We used a compiled global data set of 954 records to conduct a systematic meta-analysis. The results showed that there were significant differences in latitudinal patterns of leaf carbon (C) and nitrogen (N) contents and C:N ratio between native and non-native species, as well as significant differences in leaf C, N, and phosphorus (P) contents. For native species, we found significant latitudinal patterns in leaf C, N, and P contents and C:N and C:P ratios, whereas for non-native species, we found significant latitudinal patterns in leaf N content and C:P and N:P ratios. Mean annual temperature of the data collection site was a significant predictor of leaf stoichiometry of native plants but only of leaf N content and C:P ratio of non-native plants. Thus, we demonstrated spatial heterogeneity in leaf stoichiometries between native and non-native plants in coastal wetlands, indicating that such differences should be emphasized in future biogeochemical models and plant-herbivore interaction studies owing to the important role of wetland plants in global C, N, and P cycles. Our findings increase understanding of plant-related nutrient and elements cycling in coastal wetlands, as well as improve predictions of plant growth rates and vegetation productivity across large scales under plant invasion scenarios.

Abstract Background Long non-coding RNAs (lncRNAs) have been extensively investigated in the field of cancer, among which, lncRNA ladybird homeobox 2-antisense RNA 1 (LBX2-AS1) has been demonstrated to exert carcinogenic effects on a variety of malignancies. However, the biological functions of LBX2-AS1 in clear cell renal cell carcinoma (ccRCC) have not been explicitly elucidated. Methods Arraystar lncRNA chip and qRT-PCR verify the expression of LncRNA LBX2-AS1 in ccRCC. CCK-8 assay and cell cloning assay were used to assess the proliferative capacity of ccRCC cells. Migration abilities were quantified by scratch assay and transwell assay. Potential molecular signaling pathways were determined by high-throughput whole transcriptomics analysis. WB analysis was performed to validate the relationship between LBX2-AS1 and key molecules of mitophagy pathway. The effect of LBX2-AS1 on mitophagy was observed by laser confocal microscopy. Rescue experiments further validated the role of downstream gene FOXO3A in the LBX2-AS1 signaling pathway. Finally, the authentic effect of LBX2-AS1 was verified in vivo. Results LncRNA LBX2-AS1 was over expressed in ccRCC tissues and could enhance the proliferation and migration of ccRCC cells. Autophagic pathway was identified as a possible mechanism involved in the oncogenic effect of LBX2-AS1. Mitophagy levels were observed in LBX2-AS1 low-expressing cells through laser confocal microscopy. Knockdown of LBX2-AS1 significantly elevated mitophagy levels as observed using laser confocal microscopy and led to FOXOA3 decreasing in and BNIP3L and LC3 enrichment. Meanwhile, LBX2-AS1 knocking down dampened the proliferation of ccRCC cells in vivo.

Abstract Despite concerns over their safety, e-cigarettes (e-cigs) remain a popular tobacco product. Although nicotine and flavors found in e-cig liquids (e-liquids) can cause harm in the airways, whether the delivery vehicles propylene glycol (PG) and vegetable glycerin (VG) are innocuous when inhaled remains unclear. Here, we investigated the effects of e-cig aerosols generated from e-liquid containing only PG/VG on airway inflammation and mucociliary function in primary human bronchial epithelial cells (HBEC) and sheep. Primary HBEC were cultured at the air–liquid interface (ALI) and exposed to e-cig aerosols of 50%/50% v/v PG/VG. Ion channel conductance, ciliary beat frequency, and the expression of inflammatory markers, cell type-specific markers, and the major mucins MUC5AC and MUC5B were evaluated after seven days of exposure. Sheep were exposed to e-cig aerosols of PG/VG for five days and mucus concentration and matrix metalloproteinase-9 (MMP-9) activity were measured from airway secretions. Seven-day exposure of HBEC to e-cig aerosols of PG/VG caused a significant reduction in the activities of apical ion channels important for mucus hydration, including the cystic fibrosis transmembrane conductance regulator (CFTR) and large conductance, Ca2+-activated, and voltage-dependent K+ (BK) channels. PG/VG aerosols significantly increased the mRNA expression of the inflammatory markers interleukin-6 (IL6), IL8, and MMP9, as well as MUC5AC. The increase in MUC5AC mRNA expression correlated with increased immunostaining of MUC5AC protein in PG/VG-exposed HBEC. On the other hand, PG/VG aerosols reduced MUC5B expression leading overall to higher MUC5AC/MUC5B ratios in exposed HBEC. Other cell type-specific markers, including forkhead box protein J1 (FOXJ1), keratin 5 (KRT5), and secretoglobin family 1A member 1 (SCGB1A1) mRNAs, as well as overall ciliation, were significantly reduced by PG/VG exposure. Finally, PG/VG aerosols increased MMP-9 activity and caused mucus hyperconcentration in sheep in vivo. E-cig aerosols of PG/VG induce airway inflammation, increase MUC5AC expression, and cause dysfunction of ion channels important for mucus hydration in HBEC in vitro. Furthermore, PG/VG aerosols increase MMP-9 activity and mucus concentration in sheep in vivo. Collectively, these data show that e-cig aerosols containing PG/VG are likely to be harmful in the airways.

A non-absorbable therapeutic candidate for the treatment of hyperammonemia has been identified and characterized. Conventional approaches to reducing ammonia concentration in the blood and colon include acidifying the colon, inhibiting the bacterial production of ammonia, and activation of the urea cycle. Addressing gaps in the literature around therapeutic ammonia adsorption, this study established assays for ammonia uptake from both NH4OH and NH4Cl solutions as well as interference and selectivity for potassium absorption. Performance was characterized for a large number and variety of materials, spanning zeolites, ion-exchange resins, metallopolymers, metal–organic frameworks (MOFs), and polymeric carboxylic acids. The latter class showed low potassium capacity (poly(acrylic acid): 10 mg/g, poly(maleic-co-acrylic acid): 4 mg/g) and a therapeutically relevant depression of pH in buffered simulated intestinal fluid (SIF) (poly(acrylic acid): −2.01 and poly(maleic-co-acrylic acid): −3.23) compared to lactulose (−3.46), an approved therapeutic for hyperammonemia that works by acidifying the colon. In the polymeric organic acids evaluated, pH depression correlated well with pKa and acid site density. Additionally, this class of candidates should avoid the undesirable side effects of lactulose, such as the potential for hyperglycemia in diabetic patients and incompatible use with galactosemic patients.

A novel method for synthesizing dumbbell-shaped (Gd1−xTbx)2O(CO3)2·H2O (GOC:xTb3+) phosphors using sodium carbonate was investigated. An amount of 1 mmol of stable fluorescent powder can be widely prepared using 3–11 mmol of Na2CO3 at a pH value of 8.5–10.5 in the reaction solution. The optimal reaction conditions for the phosphors were determined to be 7 mmol for the amount of sodium carbonate and a pH of 9.5 in the solution. Mapping analysis of the elements confirmed uniform distribution of Gd3+ and Tb3+ elements in GOC:xTb3+. The analysis of fluorescence intensity shows that an optimal excitation wavelength of 273 nm is observed when the concentration of Tb3+ is between 0.005 and 0.3. The highest emission intensity was observed for GOC:0.05Tb3+ with a 57.5% maximum quantum efficiency. The chromaticity coordinates show that the color of GOC:Tb3+ is stable and suitable for fluorescence recognition. Latent fingerprint visualization reveals distinctive features like whorls, hooks, and bifurcations. Therefore, the sodium carbonate method offers an effective alternative to traditional urea chemical reaction conditions for preparing GOC:Tb3+.

Abstract Hand, foot, and mouth disease (HFMD) is a major public health concern in the Asia–Pacific region. Previous studies have implied that ambient air pollution may affect the incidence of HFMD, but the results among different regions are inconsistent. We aimed to deepen the understanding of the associations between air pollutants and HFMD by conducting a multicity study. Daily data on childhood HFMD counts and meteorological and ambient air pollution (PM2.5, PM10, NO2, CO, O3, and SO2) concentrations in 21 cities in Sichuan Province from 2015 to 2017 were collected. A spatiotemporal Bayesian hierarchical model framework was established, and then a distributed lag nonlinear models (DLNMs) was constructed to reveal exposure-lag-response relationships between air pollutants and HFMD while controlling for spatiotemporal effects. Furthermore, given the differences in the levels and seasonal trends of air pollutants between the basin region and plateau region, we explored whether these associations varied between different areas (basin and plateau). The associations between air pollutants and HFMD were nonlinear, with different lag responses. Low NO2 concentrations and both low and high PM2.5 and PM10 concentrations were associated with a decreased risk of HFMD. No significant associations between CO, O3, and SO2 and HFMD were found. The associations between air pollutant concentrations and HFMD were different between the basin and plateau regions. Our study revealed associations between PM2.5, PM10, and NO2 concentrations and HFMD, deepening the understanding of the relationships between air pollutants and HFMD. These findings provide evidence to support the formulation of relevant prevention measures and the establishment of an early warning system.

Perfluorinated compounds (PFCs) are man-made chemicals used in the manufacture of many products with water and dirt repellent properties. Many diseases have been proved to be related to the exposure of PFCs, including breast fibroadenoma, hepatocellular carcinoma, breast cancer and leydig cell adenoma. However, whether the PFCs promote the progression of prostate cancer remains unclear. In this work, through comprehensive bioinformatics analysis, we discovered the correlation between the prostate cancer and five PFCs using Comparative Toxicogenomics Database (CTD), Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. In addition, further analysis showed that several PFCs-related genes demonstrated strong prognostic value for prostate cancer patients. The survival analysis and receiver operating characteristic (ROC) curves revealed that PFCs-related genes based prognostic model held great predictive value for the prognosis of prostate cancer, which could potentially serve as an independent risk factor in the future. In vitro experiments verified the promotive role of perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) in the growth of prostate cancer cells. This study provided novel insights into understanding the role of PFCs in prostate cancer and brought attention to the environmental association with cancer risks and progression.

The problem of registering point clouds in scenarios with low overlap is explored in this study. Previous methodologies depended on having a sufficient number of repeatable keypoints to extract correspondences, making them less effective in partially overlapping environments. In this paper, a novel learning network is proposed to optimize correspondences in sparse keypoints. Firstly, a multi-layer channel sampling mechanism is suggested to enhance the information in point clouds, and keypoints were filtered and fused at multi-layer resolutions to form patches through feature weight filtering. Moreover, a template matching module is devised, comprising a self-attention mapping convolutional neural network and a cross-attention network. This module aims to match contextual features and refine the correspondence in overlapping areas of patches, ultimately enhancing correspondence accuracy. Experimental results demonstrate the robustness of our model across various datasets, including ModelNet40, 3DMatch, 3DLoMatch, and KITTI. Notably, our method excels in low-overlap scenarios, showcasing superior performance.

Abstract Background Epidemiological studies have investigated the short-term effects of meteorological factors and air pollution on the incidence of hand, foot, and mouth disease (HFMD). Several meteorological indicators, such as relative humidity and the diurnal temperature range (DTR), significantly modify the relationship between short-term exposure to temperature and HFMD incidence. However, it remains unclear whether (and how) long-term air pollution levels modify the short-term relationships of HFMD incidence with meteorological factors and air pollution. Methods We obtained daily data on meteorological factors, air pollutants, and HFMD counts in children from 21 prefecture-level cities in Sichuan Province in Southwest China from 2015 to 2017. First, we constructed a distributed lag nonlinear model (DLNM) at each prefecture-level site to evaluate the short-term impacts of meteorological variables and air pollutants on HFMD incidence. Then, we assessed the pooled effects of the exposures and incorporated long-term city-specific air pollutant indicators as meta-predictors to examine their potential modification effects by performing multivariate meta-regression models. Results We found that long-term SO2 and CO concentrations significantly modified the short-term relationships between climatic variables and HFMD incidence. Specifically, high concentrations of CO (P = 0.027) and SO2 (P = 0.039) reduced the risk of HFMD at low temperatures. The relationship between relative humidity and HFMD incidence was weakened at high SO2 concentrations (P = 0.024), especially when the relative humidity was below the median level. When the minimum relative humidity (32%) was compared to the median relative humidity (77%), the risk ratio (RR) was 0.77 (95% CI: 0.51–1.17) in the 90th percentile of SO2 (19.6 μg/m3) and 0.41 (95% CI: 0.27–0.64) in the 10th percentile of SO2 (10.6 μg/m3). Conclusion Our results indicated that long-term SO2 and CO levels modified the short-term associations between HFMD incidence in children and meteorological variables. These findings may inform health authorities to optimize targeted public health policies including reducing ambient air pollution and reinforcing self-protective actions to weaken the adverse health impacts of environmental factors on HFMD incidence.

After being cured by lime and fly ash and then modified by fiber material, waste iron tailings can obtain good road performance, which can not only reduce the accumulation of iron tailings but also save natural resources and can be used as a new road material with good performance. In this study, polypropylene fiber (0 %, 0.25 %, 0.5 %, 0.75 %, 1 %) was added to lime-fly ash solidified iron tailings (LHT) to produce a new type of road composite fiber modified two-ash iron tailings (LHTF). The mechanical properties of LHTF were analysed by unconfined compressive tests and splitting tensile tests, and the optimal ratio of LHTF was obtained. The internal failure mechanism of LHTF was explored and explained by analysing the transformation of the macroscopic failure mode and the change law of the energy absorption capacity of materials. The results show that with increasing fiber content, the unconfined compressive strength, splitting tensile strength and strength gain ratio first increase and then decrease. When the fiber content is 0.75 %, LHTF can achieve the best tension and compression performance and has the largest peak strain. With the increase in fiber content, the failure mode of LHTF gradually changes from brittle failure to ductile failure, and obviously different types of failure characteristics can be seen at the failure interface. The ductility failure characteristics of LHTF with the best fiber content are the most obvious, and the brittleness index is the lowest. The total strain energy density and elastic strain energy density of LHTF first increased and then decreased, while the change law of dissipated energy proportion showed the opposite situation. This study provides a reference for the recycling and utilization of waste iron tailings as road materials.

Summary: Background: Glibenclamide is a promising agent for treating brain oedema, but whether it improves clinical outcomes in patients with intracerebral haemorrhage (ICH) remains unclear. In this study, we aimed to explore the efficacy and safety of glibenclamide treatment in patients with acute ICH. Methods: The Glibenclamide Advantage in Treating Oedema after Intracerebral Haemorrhage (GATE-ICH) study was a randomised controlled phase 2 clinical trial conducted in 26 hospitals in the northwest of China, recruiting patients with acute ganglia ICH no more than 72 h after onset from Dec 12, 2018 to Sept 23, 2020. During the first 7 days after enrolment, patients randomly assigned to the glibenclamide group were given glibenclamide orally (1.25 mg, 3/day) and standard care, while patients randomly assigned to the control group were given standard care alone. The computer-generated randomisation sequence was prepared by a statistician not involved in the rest of the study. Randomisation was computer-generated with a block size of four. The allocation results were unblinded to participants and investigators. The primary outcome was the percentage of patients with poor outcome (defined as modified Rankin Scale [mRS] score of ≥3) at day 90. The trial was registered at ClinicalTrials.gov (NCT03741530). Findings: 220 participants were randomised and 200 participants (mean [standard deviation] age, 56 [11] years; sex, 128 [64.0%] male and 72 [36.0%] female) were included in the final analysis, with 101 participants randomly assigned to the control group and 99 to the glibenclamide group. The incidence of poor outcome at day 90 was 20/99 (20.2%) in glibenclamide group and 30/101 (29.7%) in control group (absolute difference, 9.5%; 95% confidence interval [CI], -3.2%−21.8%; P = 0.121) with adjusted odds ratios of 0.54 (95% CI, 0.24−1.20; P = 0.129). No significant difference was found in the overall rates of adverse events or serious adverse events between groups. However, the incidence of asymptomatic hypoglycaemia was significantly higher in glibenclamide group than control group (15/99 [15.2%] vs 0/101 [0.0%]; absolute difference, 15.2%; 95% CI, 7.5%−24.1%; P < 0.001). Interpretation: Our study provides no evidence that glibenclamide (1.25 mg, 3/day) significantly reduces the proportion of poor outcome at day 90 after ICH. In addition, glibenclamide could result in higher incidence of hypoglycaemia. Larger trials of glibenclamide with optimised medication regimen are warranted. Funding: Shaanxi Province Key Research and Development Project (2017DCXL-SF-02-02) and Shaanxi Province Special Support Program for Leading Talents in Scientific and Technological Innovation (tzjhjw).

PurposeNephron-sparing surgery (NSS) is a mainstream treatment for localized renal tumors. Segmental renal artery clamping (SRAC) is commonly used in NSS. Automatic and precise segmentations of renal artery trees are required to improve the workflow of SRAC in NSS. In this study, we developed a tridimensional kidney perfusion (TKP) model based on deep learning technique to automatically demonstrate renal artery segmentation, and verified the precision and feasibility during laparoscopic partial nephrectomy (PN).MethodsThe TKP model was established based on convolutional neural network (CNN), and the precision was validated in porcine models. From April 2018 to January 2020, TKP model was applied in laparoscopic PN in 131 patients with T1a tumors. Demographics, perioperative variables, and data from the TKP models were assessed. Indocyanine green (ICG) with near-infrared fluorescence (NIRF) imaging was applied after clamping and dice coefficient was used to evaluate the precision of the model.ResultsThe precision of the TKP model was validated in porcine models with the mean dice coefficient of 0.82. Laparoscopic PN was successfully performed in all cases with segmental renal artery clamping (SRAC) under TKP model’s guidance. The mean operation time was 100.8 min; the median estimated blood loss was 110 ml. The ischemic regions recorded in NIRF imaging were highly consistent with the perfusion regions in the TKP models (mean dice coefficient = 0.81). Multivariate analysis revealed that the feeding lobar artery number was strongly correlated with tumor size and contact surface area; the supplying segmental arteries number correlated with tumor size.ConclusionsUsing the CNN technique, the TKP model is developed to automatically present the renal artery trees and precisely delineate the perfusion regions of different segmental arteries. The guidance of the TKP model is feasible and effective in nephron-sparing surgery.

BackgroundCopper-induced cell death has been widely investigated in human diseases as a form of programmed cell death (PCD). The newly recognized mechanism underlying copper-induced cell death provided us creative insights into the copper-related toxicity in cells, and this form of PCD was termed cuproptosis.MethodsThrough consensus clustering analysis, ccRCC patients from TCGA database were classified into different subgroups with distinct cuproptosis-based molecular patterns. Analyses of clinical significance, long-term survival, and immune features were performed on subgroups accordingly. The cuproptosis-based risk signature and nomogram were constructed and validated relying on the ccRCC cohort as well. The cuproptosis scoring system was generated to better characterize ccRCC patients. Finally, in vitro validation was conducted using ccRCC clinical samples and cell lines.ResultPatients from different subgroups displayed diverse clinicopathological features, survival outcomes, tumor microenvironment (TME) characteristics, immune-related score, and therapeutic responses. The prognostic model and cuproptosis score were well validated and proved to efficiently distinguish the high risk/score and low risk/score patients, which revealed the great predictive value. The cuproptosis score also tended out to be intimately associated with the prognosis and immune features of ccRCC patients. Additionally, the hub cuproptosis-associated gene (CAG) FDX1 presented a dysregulated expression pattern in human ccRCC samples, and it was confirmed to effectively promote the killing effects of copper ionophore elesclomol as a direct target. In vitro functional assays revealed the prominent anti-cancer role of FDX1 in ccRCC.ConclusionCuproptosis played an indispensable role in the regulation of TME features, tumor progression, and long-term prognosis of ccRCC.

Purpose The ongoing coronavirus disease 2019 (COVID-19) epidemic increasingly threatens the public health security worldwide. We aimed to identify high-risk areas of COVID-19 and understand how socioeconomic factors are associated with the spatial distribution of COVID-19 in China, which may help other countries control the epidemic. Methods We analyzed the data of COVID-19 cases from 30 provinces in mainland China (outside of Hubei) from 16 January 2020 to 31 March 2020, considering the data of demographic, economic, health, and transportation factors. Global autocorrelation analysis and Bayesian spatial models were used to present the spatial pattern of COVID-19 and explore the relationship between COVID-19 risk and various factors. Results Global Moran’s I statistics of COVID-19 incidences was 0.31 (PConclusion Our results suggested that COVID-19 risk was positively associated with the level of economic development and population movements. Blocking population movement and reducing local exposures are effective in preventing the local transmission of COVID-19.

Diquat (DQ), a widely used bipyridyl herbicide, is associated with significantly higher rates of kidney injuries compared to other pesticides. However, the underlying molecular mechanisms are largely unknown. In this study, we identified the molecular changes in the early stage of DQ-induced kidney damage in a mouse model through transcriptomic, proteomic and metabolomic analyses. We identified 869 genes, 351 proteins and 96 metabolites that were differentially expressed in the DQ-treated mice relative to the control mice (p < 0.05), and showed significant enrichment in the PPAR signaling pathway and fatty acid metabolism. Hmgcs2, Cyp4a10, Cyp4a14 and Lpl were identified as the major proteins/genes associated with DQ-induced kidney damage. In addition, eicosapentaenoic acid, linoleic acid, palmitic acid and (R)-3-hydroxybutyric acid were the major metabolites related to DQ-induced kidney injury. Overall, the multi-omics analysis showed that DQ-induced kidney damage is associated with dysregulation of the PPAR signaling pathway, and an aberrant increase in Hmgcs2 expression and 3-hydroxybutyric acid levels. Our findings provide new insights into the molecular basis of DQ-induced early kidney damage.

Phosphors with a longer excitation wavelength exhibit higher energy conversion efficiency. Herein, quantum cutting KGd(CO3)2:Tb3+ phosphors excited by middle-wave ultraviolet were synthesized via a hydrothermal method. All the KGd(CO3)2:xTb3+ phosphors remain in monoclinic structures in a large Tb3+ doping range. In the KGd(CO3)2 host, 6D3/2 and 6I17/2 of Gd3+ were employed for quantum cutting in sensitizing levels. The excited state electrons could easily transfer from Gd3+ to Tb3+ with high efficiency. There are three efficient excited bands for quantum cutting. The excited wavelengths of 244, 273, and 283 nm correspond to the transition processes of 8S7/2→6D3/2 (Gd3+), 8S7/2→6I17/2 (Gd3+), and 7F6→5F4 (Tb3+), and the maximum quantum yields of KGd(CO3)2:Tb3+ can reach 163.5, 119, and 143%, respectively. The continuous and efficient excitation band of 273–283 nm can well match the commercial 275 nm LED chip to expand the usage of solid-state light sources. Meanwhile, the phosphor also shows good excitation efficiency at 365 nm in a high Tb3+ doping concentration. Therefore, KGd(CO3)2:Tb3+ is an efficient green-emitting phosphor for ultraviolet-excited solid-state light sources.

BackgroundAntiangiogenic agents that specifically target vascular endothelial growth factor receptor (VEGFR), such as sunitinib, have been utilized as the standard therapy for metastatic clear cell renal cell carcinoma (ccRCC) patients. However, most patients eventually show no responses to the targeted drugs, and the mechanisms for the resistance remain unclear. This study is aimed to identify pivotal molecules and to uncover their potential functions involved in this adverse event in ccRCC treatment.MethodsTwo datasets, GSE64052 and GSE76068, were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using the limma package in R software. The gene set enrichment analysis (GSEA) was conducted using clusterProfiler package. A protein–protein interaction (PPI) network was built using the STRING database and Cytoscape software. Kaplan—Meier survival curves were plotted using R software. qRT-PCR and Western blotting were used to detect the MX2 and pathway expression in RCC cell lines. Sunitinib-resistant cell lines were constructed, and loss-of-function experiments were conducted by knocking down MX2. All statistical analyses were performed using R version 3.6.1 and SPSS 23.0.ResultsA total of 760 DEGs were derived from two datasets in GEO database, and five hub genes were identified, among which high-level MX2 exhibited a pronounced correlation with poor overall survival (OS) in sunitinib-resistant ccRCC patients. Clinical correlation analysis and Gene Set Variation Analysis (GSVA) on MX2 showed that the upregulation of MX2 was significantly related to the malignant phenotype of ccRCC, and it was involved in several pathways and biological processes associated with anticancer drug resistance. qRT-PCR and Western blotting revealed that MX2 was distinctly upregulated in sunitinib-resistant RCC cell lines. Colony formation assay and Cell Counting Kit-8 (CCK8) assay showed that MX2 strongly promoted resistant capability to sunitinib of ccRCC cells.ConclusionMX2 is a potent indicator for sunitinib resistance and a therapeutic target in ccRCC patients.

Summary: The design and synthesis of metal chelators with extraordinary metal affinities is a basic and challenging scientific problem of both fundamental and practical importance. Here, we demonstrate a “conformational stability effect” that can significantly enhance the metal affinity of ligands after conjugation to polymer chains with the ability to spontaneously adopt a specific conformation as an optimal “soft” scaffold to ensure maximum thermodynamic stability of the metal complexes. Using iron chelators as models, we show that simple conjugation of small molecule catechol ligands to a polyallylamine chain resulted in more than 8–9 orders of magnitude enhancement of the iron-binding affinity, which is comparable to that of enterobactin, the strongest iron chelator ever known. This study demonstrates that flexible polymer chelators may realize the highest possible metal affinities of the conjugated ligands owing to their ability to achieve an optimal conformation, which could advance the identification of strong metal chelators. : Polymer Chemistry; Chemical Synthesis; Polymers Subject Areas: Polymer Chemistry, Chemical Synthesis, Polymers

Abstract Background Delayed bowel function recovery and postoperative ileus are relatively serious complications of laparoscopic radical cystectomy (LRC). Our study aimed to determine whether performing pelvic re-peritonealization reduces the incidence of these complications. Methods Clinical data of 78 patients who had undergone LRC with pelvic re-peritonealization from August 2015 to December 2017 were retrospectively collected and compared with those of 92 patients who had undergone LRC alone between January 2013 and July 2015 in our institution. Differences in duration of surgery, estimated blood loss, time to recovery of bowel function, the complications of intestinal and blood vessel injury, and incidence of postoperative ileus between the two groups were analyzed. Results Baseline characteristics such as age, sex and BMI were balanced between the two groups. There were no significant differences in duration of surgery (P = 0.072), estimated blood loss (P = 0.717), or incidence of intestinal obstruction (P = 0.225) between the two groups. Interestingly, patients who had undergone pelvic re-peritonealization recovered bowel function more rapidly than those had not (2.79 d vs. 3.72 d, P = 0.001). Additionally, hospitalization stay was significantly shorter for patients with re-peritonealization than for those without (5.46 d vs. 6.68 d, P = 0.029). Conclusions Compared with LRC alone, LRC with pelvic re-peritonealization as described in the present study had comparable perioperative complications, but was associated with more rapid gastrointestinal recovery and shorter hospitalization stay.

Herein, epoxy resins for composite liquid oxygen (LOX) fuel tanks are modified with phosphorous flame retardant (DOPO) and brominated epoxy resin (EX48). With the incorporation of DOPO and EX48, the processing properties requirements for the hot-melt prepreg are contented with the significantly enhanced viscosity of the modified epoxy resin. At the same time, the tensile performance, flexural performance and fracture toughness of epoxy resin at room temperature and 90 K are improved with the introduction of DOPO and EX48. In addition, the epoxy resin of EP/P7.7/Br40 offers a highest limited oxygen index of 33.5% and a lowest LOX impact sensitivity of 5% with the eliminated LOX incompatible reactions including explosion and combustion. Consideration of the excellent cryogenic mechanical properties and LOX compatibility, combined with ideal viscosity for hot-melt prepreg preparation, the epoxy resin modified with DOPO and EX48 simultaneously is attractive as the polymer matrix for composite LOX fuel tanks.

Using fiber, lime and fly ash to modify iron tailings and apply them to a road base is an effective way to utilize iron tailings as resources. To explore the influence of fiber on lime and fly ash-stabilized iron tailings (EIT) under dry and wet cycles at an early curing age, the static and dynamic characteristics of EIT and fiber-modified lime and fly ash-stabilized iron tailings (FEIT) under dry and wet cycles were studied through an unconfined compressive strength (UCS) test, splitting test and dynamic triaxial test. The results show the following. (1) EIT and FEIT still have high UCS and splitting strength after dry–wet cycles, and the dry–wet cycles can promote the static properties of FEIT. (2) The dry–wet cycle is the main factor affecting the change in the dynamic elastic modulus of EIT and FEIT. The dynamic elastic modulus of EIT first increases and then decreases with the increase in dry–wet cycles, and the dynamic elastic modulus of FEIT first decreases and then increases with the increase in dry–wet cycles. The damping ratio of EIT and FEIT decreases with the increase in dry–wet cycles, and then tends to be stable. (3) After seven dry–wet cycles, the compressive performance, tensile performance, deformation resistance and vibration resistance of FEIT are better than those of EIT. This study can provide a reference for the resource application of iron tailings in road engineering.

The long non-coding RNA (lncRNA) H19 has been demonstrated to play a crucial role in carcinogenesis, including renal cell carcinoma (RCC). However, the impact of genetic variations in H19 gene on RCC has not been investigated before. In the present study, we sought to evaluate whether genetic polymorphisms in H19 are related to the susceptibility and mortality of RCC. We genotyped four widely studied polymorphisms in H19 and assessed their relationship with susceptibility and prognosis of RCC in a case-control study compromising 1,027 cases and 1,094 controls. The functionality of the important polymorphism was further investigated by real-time polymerase chain reaction and luciferase reporter assay. We found that H19 rs2839698 was significantly associated with risk and prognosis of RCC. Compared with the H19 rs2839698 CC genotype, the variant genotypes (CT/TT) were significantly associated with increased risk of RCC (P = 0.023, OR = 1.21; 95% CI = 1.03–1.45). Besides, patients with variant genotypes (CT/TT) were more likely to develop large tumor (P = 0.003, OR = 1.47; 95% CI = 1.16–1.85) and advanced disease (P = 0.010, OR = 1.59; 95% CI = 1.12–2.26); and had a significantly unfavorable overall survival than those with the rs2839698 CC genotype (CT/TT vs. CC: Log-rank P = 0.026, HR = 2.25, 95%CI = 1.07–4.75). Furthermore, the CT/TT genotypes were associated with significantly increased expression of H19 in renal tissue. The luciferase reporter assays revealed the potential effect of rs2839698 variant on the binding of microRNAs to H19. Our results suggest that the H19 rs2839698 variant may be a genetic predictor of susceptibility and mortality of RCC. The risk effects and the functional impact of the variant on H19 still need further validation.

The resource utilization of iron tailings is of great significance for all countries in the world. Considering the particle composition and physicochemical characteristics of iron tailings, fiber and lime were used to modify iron tailings. The fiber content was 0%, 0.25%, 0.5%, 0.75%, and 1%, and the lime content was 0%, 2%, 4%, 8%, and 10%, respectively. Through a direct shear test, the shear stress displacement (τ-δ) curves and shear strength of modified iron tailings, under the action of a 0 freeze-thaw cycle and 1 freeze-thaw cycle, were tested. As statistics have shown that there are uncertainty factors associated with direct shear tests, the shear strength index cohesion c and internal friction angle φ of the modified iron tailings were analyzed using the Monte Carlo method. The results show that the τ-δ curve of the fiber-modified iron tailings is a hardening-type curve and that of the lime-modified iron tailings is a softening-type curve. In the direct shear tests, the main uncertain factors are the specimen diameter, vertical force, and horizontal force. The diameter of the sample obeys a normal distribution, and the vertical and horizontal forces obey a uniform distribution. The results of the Monte Carlo simulation show that both c and φ obey a normal distribution. Under a 95% confidence condition, the effect of fiber on the cohesion on iron tailings is obvious, but the effect on the internal friction angle is not obvious. However, the values of c and φ of the iron tailings are clearly improved by lime. Additionally, the iron tailings modified by a fiber content of 1% and those modified by a lime content of 8% have the best frost resistance.

Seawater quality degradation is caused by diverse, non-linearly interacting factors, knowledge of which is essential for understanding and predicting water quality trends. Currently, most water-quality research has been based on certain assumptions to employ linear approaches for solving simplified problems, such as numerical simulations or cumulative impact assessments. To improve the accuracy and ease of prediction, the random forest method has been increasingly employed as a good alternative to traditional prediction methods. In the present study, the random forest method was adopted to construct a model of the water quality response of Xincun Lagoon to anthropogenic nutrient inputs based on a limited amount of sample data, aiming to (a) identify the critical sources of nutrient inputs that affect the meeting of water quality objectives so as to minimize the socioeconomic impact on secondary stakeholders; and (b) predict the impact of a reduction of anthropogenic nutrient inputs on water quality improvement. It can be seen from the results that the intensity of stressors generated by different human activities presents an obvious non-linear superposition pattern, and the random forest method is one of the feasible solutions to this phenomenon; in addition, the impact on the lagoon ecosystem is not directly related to the intensity of the pressure source, for example, coastal aquaculture is more important than shallow sea cage aquaculture. Therefore, the method established in this paper can be used to identify the key pressure sources during the restoration of the lagoon environment, so as to achieve the unity of economy and effectiveness.

Recent large-scale transcriptome analyses have found large numbers of transcripts, including that of long non-coding RNAs (lncRNAs), which are aberrant in various diseases, especially cancers. However, it is not clear whether lncRNAs are involved specifically in renal cell carcinoma (RCC). We investigated the expression patterns of lncRNAs in five RCC tumor samples (T) relative to those of matched adjacent non-tumor tissues (N) via microarray.A microarray with 33,045 lncRNA probes and 30,215 mRNA probes was used to identify deregulated lncRNAs in five RCC patients. Furthermore, we confirmed the relative expression levels of AK096725 and ENST00000453068 in 70 paired samples by quantitative reverse transcription polymerase chain reaction (qRT-PCR).The lncRNA microarray revealed 27,279 lncRNAs in RCC samples, of which 480 were significantly upregulated (P1.5) and 417 were significantly downregulated (P1.5) compared with the matched non-tumor samples. In addition, 19,995 mRNAs were detected, of which 458 were significantly upregulated (P1.5) and 413 were significantly downregulated (P1.5). The expression level changes of AK096725 (P = 0.043) and ENST00000453068 (P

Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) are members of the insulin-like growth factor (IGF) family that play important roles in carcinogenesis. We hypothesized that the functional polymorphisms in IGF-I and IGFBP-3 may be associated with the risk of prostate cancer (PCa) in the Chinese population. This hospital-based case-control study included 664 PCa patients and 702 cancer-free controls. Nine SNPs in IGF-I and IGFBP-3 were genotyped using the TaqMan assay. The genetic associations between the pathogenesis and progression of PCa were assessed by logistic regression. We found that the genotype and allele frequency distribution of rs6218, rs35767 and rs5742612 were significantly different when comparing PCa cases to controls (P = 0.005, 0.005 and 0.020, respectively). In the combined analysis, individuals with 2-6 risk alleles had an elevated risk of PCa compared to those with 0-1 risk alleles. We also found that the association between the combined risk alleles and the risk of PCa appeared stronger in the following subgroups: individuals older than 71 years of age (OR = 1.41, 95%CI = 1.05-1.91, P = 0.020), nonsmokers (OR = 1.68, 95%CI = 1.21-2.32, P = 0.002), nondrinkers (OR = 1.32, 95%CI = 1.02-1.61, P = 0.002), and those with a negative family history of PCa (OR = 1.28, 95%CI = 1.02-1.71, P = 0.022). Our results indicate that the three SNPs (rs6218, rs35767 and rs5742612) and the joint genotypes with 2-6 risk alleles, may contribute to the susceptibility to PCa, but not the progression, in the Chinese population.

BACKGROUND: Raf-1 kinase inhibitor protein (RKIP) plays a critical role in tumor development by regulating cell functions such as invasion, apoptosis and differentiation. Down-regulation of RKIP expression has been implicated in the development and progression of renal cell carcinoma (RCC). Herein, we hypothesized that genetic polymorphisms in RKIP might be associated with susceptibility and progression of RCC. METHODS: A total of 5 tagging single-nucleotide polymorphisms (tSNPs) in RKIP were selected and genotyped by SNapShot method in a case-control study of 859 RCC patients and 1004 controls. The logistic regression was used to evaluate the genetic association with occurrence and progression of RCC. The functionality of the important SNP was preliminary examined by qRT-PCR. RESULT: We found that the rs17512051 in the promoter region of RKIP was significantly associated with decreased clear cell RCC (ccRCC) risk (TA/AA vs. TT: P = 0.039, OR = 0.78, 95%CI = 0.62-0.99). Another SNP (rs1051470) in the 3'UTR region of RKIP was marginally associated with increased ccRCC risk (TT vs. CC+CT: OR = 1.45, 95%CI = 1.01-2.09). In the stratified analysis, the protective effect of rs17512051 was more predominant in the subgroups of male, non-smokers, non-drinkers as well as subjects without history of diabetes. Furthermore, we observed higher RKIP mRNA levels in the presence of the rs17512051A allele in normal renal tissues. CONCLUSION: Our results suggest that the potentially functional RKIP rs17512051 polymorphism may affect ccRCC susceptibility through altering the endogenous RKIP expression level. Risk effects and the functional impact of this polymorphism need further validation.

The composting industry has been growing rapidly in China because of a boom in the animal industry. Therefore, a rapid and accurate assessment of the quality of commercial organic fertilizers is of the utmost importance. In this study, a novel technique that combines near infrared (NIR) spectroscopy with partial least squares (PLS) analysis is developed for rapidly and accurately assessing commercial organic fertilizers quality. A total of 104 commercial organic fertilizers were collected from full-scale compost factories in Jiangsu Province, east China. In general, the NIR-PLS technique showed accurate predictions of the total organic matter, water soluble organic nitrogen, pH, and germination index; less accurate results of the moisture, total nitrogen, and electrical conductivity; and the least accurate results for water soluble organic carbon. Our results suggested the combined NIR-PLS technique could be applied as a valuable tool to rapidly and accurately assess the quality of commercial organic fertilizers.

BACKGROUND: Glutathione S-transferases (GSTs) are a family of multifunctional enzymes that are involved in the metabolism of many xenobiotics, including a wide range of environmental carcinogens. While the null genotypes in GSTM1 and GSTT1 have been implicated in tumorigenesis, it remains inconsistent and inconclusive. Herein, we aimed to assess the possible associations of the GSTM1 and GSTT1 null genotype in cancer risks. METHODS: A meta-analysis based on 506 case-control studies was performed. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. RESULTS: The null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk in cancer (for GSTM1: OR = 1.17; 95%CI = 1.14-1.21; for GSTT1: OR = 1.16; 95%CI = 1.11-1.21, respectively). When the analysis was performed based on their smoking history, the risk associated of GSTM1 null and GSTT1 null genotypes with cancer is further increased (for GSTM1: OR = 2.66; 95%CI = 2.19-3.24; for GSTT1: OR = 2.46; 95%CI = 1.83-3.32, respectively). CONCLUSIONS: These findings indicate that GSTM1 and GSTT1 polymorphisms may play critical roles in the development of cancer, especially in smokers.

BACKGROUND: The plasminogen activator inhibitor-1 (PAI-1) is expressed in many cancer cell types and allows the modulation of cancer growth, invasion and angiogenesis. To date, studies investigated the association between a functional polymorphism in PAI-1 (4G/5G) and risk of cancer have shown inclusive results. METHODS: A meta-analysis based on 25 case-control studies was performed to address this issue. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with I(2) test. RESULTS: Overall, a significant increased risk of cancer was associated with the PAI-1 4G/4G polymorphism for the allele contrast (4G vs. 5G: OR = 1.10, CI = 1.03-1.18, I(2) = 49.5%), the additive genetic model (4G/4G vs. 5G/5G: OR = 1.21, CI = 1.06-1.39, I(2) = 51.9%), the recessive genetic model (4G/4G vs. 4G/5G+5G/5G: OR = 1.11, CI = 1.04-1.18, I(2) = 20.8%). In the subgroup analysis by ethnicity, the results indicated that individuals with 4G/4G genotype had a significantly higher cancer risk among Caucasians (4G/4G vs. 5G/5G: OR = 1.31, 95%CI = 1.09-1.59, I(2) = 59.6%; 4G/4G vs. 4G/5G: OR = 1.12, 95%CI = 1.04-1.21, I(2) = 3.6%; recessive model: OR = 1.12, 95%CI = 1.05-1.21, I(2) = 25.3%). CONCLUSIONS: The results of the present meta-analysis support an association between the PAI-1 4G/5G polymorphism and increasing cancer risk, especially among Caucasians, and those with 4G allele have a high risk to develop colorectal cancer and endometrial cancer.