Novel potential urinary biomarkers for effective diagnosis and prognostic evaluation of high-grade bladder cancer.

Background: High-grade bladder cancer (HGBC) has a higher malignant potential, recurrence and progression rate compared to low-grade phenotype. Its early symptoms are often vague, making non-invasive diagnosis using urinary biomarkers a promising approach. Methods: The gene expression data from urine samples of patients with HGBC was extracted from the GSE68020 dataset. The clinical information and gene expression data in tumor tissues of HGBC patients were obtained from The Cancer Genome Atlas (TCGA) database. Multivariate Cox analysis was used to predict the optimal risk model. The protein-protein interaction (PPI) analysis was performed via the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape. Overall survival (OS) was evaluated in the Gene Expression Profiling Interactive Analysis (GEPIA) online platform. Competing endogenous RNA (ceRNA) network was also visualized using Cytoscape. The expression levels of specific genes were assessed through quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Moreover, co-expressed genes and potential biological functions related to specific genes were explored based on the Cancer Cell Line Encyclopedia (CCLE) database. Results: A total of 560 differentially expressed genes (DEGs) were identified when comparing the urine sediment samples from HGBC patients with the benign ones. Using these urinary DEGs and the clinical information of HGBC patients, we developed an optimal risk model consisting of eight genes to predict the patient outcome. By integrating the node degree values in the PPI network with the expression changes in both urine and tissue samples, eighteen hub genes were selected out. Among them, DKC1 and SNRPG had the most prominent comprehensive values, and EFTUD2, LOR and EBNA1BP2 were relevant to a worse OS in bladder cancer patients. The ceRNA network of hub genes indicated that DKC1 may be directly regulated by miR-150 in HGBC. The upregulation of both SNRPG and DKC1 were detected in HGBC cells, which were also observed in various tumor tissues and malignant cell lines, displaying high correlations with other hub genes. Conclusions: Our study may provide theoretical basis for the development of effective non-invasive detection and treatment strategies, and further research is necessary to explore the clinical applications of these findings.

AKTeO2(CO3) (A = Li, Na): The First Carbonatotellurites Featuring a Zero-Dimensional [Te2C2O10]4- Cluster and a Wide Band Gap.

The first carbonatotellurites, AKTeO2(CO3) (A = Li, Na), have been successfully synthesized by using boric acid as the mineralizer. AKTeO2(CO3) (A = Li, Na) crystallize in the monoclinic space group P21/n (no. 14), and their structures exhibit the novel zero-dimensional (0D) [Te2C2O10]4- clusters, in which two [TeO4]4- groups form a [Te2O6]4- dimer via edge-sharing, with each side of the dimer attached by a [CO3]2- group via a Te-O-C bridge. The alkali metal cations occupy the voids between the 0D clusters and maintain the charge balance. The ultraviolet-visible-near-infrared diffuse reflectance spectra show that the short absorption cut-off edges of LiKTeO2(CO3) (LKTC) and NaKTeO2(CO3) (NKTC) are 248 and 240 nm, respectively, and LKTC exhibits the largest experimental band gap (4.58 eV) among all of the tellurites containing the π-conjugated anionic groups reported. Theoretical calculations revealed that they exhibit moderate birefringences of 0.029 and 0.040@1064 nm, respectively.

Research progress of therapeutic effects and drug resistance of immunotherapy based on PD-1/PD-L1 blockade.

The binding of programmed death-1 (PD-1) on the surface of T cells and PD-1 ligand 1 (PD-L1) on tumor cells can prevent the immune-killing effect of T cells on tumor cells and promote the immune escape of tumor cells. Therefore, immune checkpoint blockade targeting PD-1/PD-L1 is a reliable tumor therapy with remarkable efficacy. However, the main challenges of this therapy are low response rate and acquired resistance, so that the outcomes of this therapy are usually unsatisfactory. This review begins with the description of biological structure of the PD-1/PD-L1 immune checkpoint and its role in a variety of cells. Subsequently, the therapeutic effects of immune checkpoint blockers (PD-1 / PD-L1 inhibitors) in various tumors were introduced and analyzed, and the reasons affecting the function of PD-1/PD-L1 were systematically analyzed. Then, we focused on analyzing, sorting out and introducing the possible underlying mechanisms of primary and acquired resistance to PD-1/PD-L1 blockade including abnormal expression of PD-1/PD-L1 and some factors, immune-related pathways, tumor immune microenvironment, and T cell dysfunction and others. Finally, promising therapeutic strategies to sensitize the resistant patients with PD-1/PD-L1 blockade treatment were described. This review is aimed at providing guidance for the treatment of various tumors, and highlighting the drug resistance mechanisms to offer directions for future tumor treatment and improvement of patient prognosis.

Nitrate Quantification in Fresh Vegetables in Shanghai: Its Dietary Risks and Preventive Measures.

To investigate nitrate and nitrite content in fresh vegetables, 264 samples were randomly collected in the farmers' markets in Shanghai, Southeast China. The results indicate that 25.0% of the fresh vegetables were critically or more contaminated by nitrate [>1440 mg/kg FW (Fresh weight)]. Generally, leafy vegetables were more highly enriched in nitrate than root-tuber and fruit vegetables. About 22.6% of the leafy vegetables had a nitrate content exceeding the limit for edible permission (>3000 mg/kg FW). Nitrite content in the fresh vegetables was all within the safe level (<1 mg/kg FW). It was estimated that the daily nitrate intake through eating vegetables in Shanghai exceeded the WHO/FAO allowable limit. The field experiment indicated that the hyper-accumulation of nitrate and nitrite in the vegetables was mainly attributed to the excessive application of chemical fertilizers. The maxima of nitrate and nitrite in the vegetables were attained one week after applying chemical fertilizer, and thus they cannot be picked for dietary use. Applying organic manure can effectively lower the risk of nitrate and nitrite contamination in vegetables. The old leaves and leaf petioles were more easily enriched in nitrate due to their weaker metabolic activity. Vegetables with high nitrate content had a high risk of nitrite toxicity during storage due to the biological conversion of nitrate into nitrite, which is easily triggered by suitable temperature and mechanical damage processing. Therefore, fresh vegetables should be stored by rapid cooling and in undamaged forms to prevent nitrite accumulation.

NaBa3[M2B7O16(OH)2]F2 (M = Ge, Si): Two Synthetic F Analogues of Garrelsite with [B7O16(OH)2]13- Polyanions and Deep-Ultraviolet Cutoff Edges.

Two new borogermanate/borosilicate fluorides, namely, NaBa3[M2B7O16(OH)2]F2 (M = Ge, Si), have been successfully synthesized through a conventional mild hydrothermal method. They represent the first examples of mixed alkali and alkaline-earth borogermanate/borosilicate fluorides. NaBa3[M2B7O16(OH)2]F2 (M = Ge, Si) crystallize in the space group of C2/c, and their structures feature a unique 3D anionic framework composed of [B7O16(OH)2]13- polyanions corner-sharing with SiO4 or GeO4 tetrahedra, forming 1D 10-membered-ring tunnels along the b axis, which are filled by Na+, Ba2+, and F- ions. UV-vis-near-IR absorption spectra identify the title compounds possessing short deep-ultraviolet absorption edges (below 200 nm), while their birefringences were calculated to be 0.021 and 0.016 at 1064 nm, respectively. Optical property, thermal stability, and theoretical calculations have also been conducted on NaBa3[M2B7O16(OH)2]F2 (M = Ge, Si).

Cd2(IO3)(PO4) and Cd1.62Mg0.38(IO3)(PO4): metal iodate-phosphates with large SHG responses and wide band gaps.

The first NLO-active metal iodate-phosphates, namely, Cd2(IO3)(PO4) and Cd1.62Mg0.38(IO3)(PO4) (1 and 2), with three types of NLO groups, have been reported. 1 and 2 are isostructural and the structure of 1 features a 3D network formed by the Cd4(IO3)8/4(PO4)6/3 groups. 1 and 2 with strong SHG signals of 4 × and 3.5 × KH2PO4 are promising SHG materials in the visible region.

Association of C-reactive Protein with Cardiovascular Outcomes: A Mendelian Randomization Study in the Japanese Population.

OBJECTIVE: Traditional epidemiological studies have shown that C-reactive protein (CRP) is associated with the risk of cardiovascular diseases (CVDs). However, whether this association is causal remains unclear. Therefore, Mendelian randomization (MR) was used to explore the causal relationship of CRP with cardiovascular outcomes including ischemic stroke, atrial fibrillation, arrhythmia and congestive heart failure. METHODS: We performed two-sample MR by using summary-level data obtained from Japanese Encyclopedia of Genetic association by Riken (JENGER), and we selected four single-nucleotide polymorphisms associated with CRP level as instrumental variables. MR estimates were calculated with the inverse-variance weighted (IVW), penalized weighted median and weighted median. MR-Egger regression was used to explore pleiotropy. RESULTS: No significant causal association of genetically determined CRP level with ischemic stroke, atrial fibrillation or arrhythmia was found with all four MR methods (all Ps > 0.05). The IVW method indicated suggestive evidence of a causal association between CRP and congestive heart failure ( OR: 1.337, 95% CI: 1.005-1.780, P = 0.046), whereas the other three methods did not. No clear pleiotropy or heterogeneity were observed. CONCLUSIONS: Suggestive evidence was found only in analysis of congestive heart failure; therefore, further studies are necessary. Furthermore, no causal association was found between CRP and the other three cardiovascular outcomes.

M(B(SeO3)3)H2O (M = Al, Ga): the first boroselenites with a unique sandwich like double-layer structure.

Exploration of new types of borates is important because of their promising applications in diverse fields. Two new boroselenites, namely, M(B(SeO3)3)H2O (M = Al, Ga), which represent the first IIIA metal boroselenite, were synthesized by hydrothermal reactions. M(B(SeO3)3)H2O (M = Al, Ga) possesses a unique sandwich like double-layer structure formed by two 2D [MSe2O8]5- layers interconnected by 1D [BSeO5]3- chains. More interestingly, both compounds display large band gaps (4.86/4.79 eV) and moderate birefringences (Δn = 0.063/0.064 at 1064 nm) based on density functional theory (DFT) calculations.

The characteristics and mixing states of PM2.5 during a winter dust storm in Ningbo of the Yangtze River Delta, China.

Dust particulates play an essential role for the nucleation, hygroscopicity and also contribute to aerosol mass. We investigated the chemical composition, size distribution and mixing states of PM2.5 using a single-particle aerosol mass spectrometer (SPAMS), Monitor for AeRosols and Gases (MARGA), and off-line membrane sampling from 2018.1.24 to 2018.2.20 at a coastal supersite in Ningbo, a port city in Yangtze River Delta, China. During the study campaign, the eastern part of China had experienced a wide range of cooling, sandstorm, and snowfall processes. The entire sampling campaign was categorized into five sub-periods based on the levels of PM2.5 and the ratios of PM2.5/PM10, namely clean (T1), heavy pollution (T2), light pollution (T3), dust (sandstorm) (T4) and cleaning pollution (T5) period. After comparing the average mass spectrum for each period, it shows that the primary ions, such as Ca2+and SiO3-, rarely coexist with each other within a single particle, but secondary ions generally coexist with these primary ions. Furthermore, the coexistence of each two different ions within a particle does not show distinct variation for the whole study periods. All these suggest that the absorption and partitioning of gaseous contaminants into the surface of primary aerosol through heterogeneous reactions are the major pathways of aging and growth of aerosol; and the merging of particles through collisions usually is insignificant. Although the absolute concentrations of nitrate and sulfate all increased with the PM2.5 concentrations, the relative equivalent concentrations of NO3- and SO42- displayed opposite trends; the relative contribution of sulfate decreased and that of nitrate increased as the increase of pollution. During the dust period, the relative equivalent concentrations of calcium and/or potassium ions in PM2.5 are significantly higher. This study provided deep insights about the mixing states and characteristics of particulate after long-range transport and a visualization tool for aerosol study.

Tensor Approach to DOA Estimation of Coherent Signals with Electromagnetic Vector-Sensor Array.

This paper addresses the direction-of-arrival (DOA) estimation problem using a uniform rectangular array with electromagnetic vector-sensors in correlated/coherent signal environments. The polarization information is separated from the steering matrix to decorrelate the signals. By developing a tensorial structured received measurements of the array, we propose a tensor-based eigenvector DOA estimation method. Then we apply the forward-backward averaging to the tensor since it obeys the centro-Hermitian structure. In addition, a tensor-based polarization parameters estimation method is presented. The proposed algorithms are superior to the state-of-the-art algorithms in terms of estimation accuracy of coherent signals while only demand a modest computation burden comparing with the latter ones. Simulation results are given to demonstrate the effectiveness of the proposed methods under different scenarios.