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.

Integrating population-level and cell-based signatures for drug repositioning.

Drug repositioning presents a streamlined and cost-efficient way to expand the range of therapeutic possibilities. Furthermore, drugs with genetic evidence are more likely to progress successfully through clinical trials towards FDA approval. Exploiting these developments, single gene-based drug repositioning methods have been implemented, but approaches leveraging the entire spectrum of molecular signatures are critically underexplored. Most multi-gene-based approaches rely on differential gene expression (DGE) analysis, which is prone to identify the molecular consequence of disease and renders causal inference challenging. We propose a framework TReD (Transcriptome-informed Reversal Distance) that integrates population-level disease signatures robust to reverse causality and cell-based drug-induced transcriptome response profiles. TReD embeds the disease signature and drug profile in a high-dimensional normed space, quantifying the reversal potential of candidate drugs in a disease-related cell screen assay. The robustness is ensured by evaluation in additional cell screens. For an application, we implement the framework to identify potential drugs against COVID-19. Taking transcriptome-wide association study (TWAS) results from four relevant tissues and three DGE results as disease features, we identify 37 drugs showing potential reversal roles in at least four of the seven disease signatures. Notably, over 70% (27/37) of the drugs have been linked to COVID-19 from other studies, and among them, eight drugs are supported by ongoing/completed clinical trials. For example, TReD identifies the well-studied JAK1/JAK2 inhibitor baricitinib, the first FDA-approved immunomodulatory treatment for COVID-19. Novel potential candidates, including enzastaurin, a selective inhibitor of PKC-beta which can be activated by SARS-CoV-2, are also identified. In summary, we propose a comprehensive genetics-anchored framework integrating population-level signatures and cell-based screens that can accelerate the search for new therapeutic strategies.

Two CYP93A enzymes play a dual role in isoflavonoid biosynthesis in Glycine max L.

Glycine max L. is rich in isoflavonoids with diverse biological activities. However, isoflavonoid biosynthetic pathway is not fully elucidated in soybean. In the present study, we investigated characteristics of all the thirteen CYP93 subfamily members, and found GmCYP93A1, GmCYP93A2, and GmCYP93A3 are closely clustered, preferentially expressed in roots, and highly inducible by elicitor. When expressed in yeast, GmCYP93A1 was active towards liquiritigenin, naringenin, and 3,9-dihydroxyptercarpan, GmCYP93A2 towards 3,9-dihydroxyptercarpan with strict substrate specificity, whereas GmCYP93A3 did not show any activity towards all the tested substrates. Both GmCYP93A1 and GmCYP93A2 could catalyze 3,9-dihydroxyptercarpan into daidzein and glycinol, with both hydroxylation and aryl migration activity. Site-directed mutagenesis assays revealed that mutation in Thr446 to Ser446 in heme-binding domain increased the enzyme activity of GmCYP93A1 towards 3,9-dihydroxyptercarpan, which highlights its key amino acid residues as shown with its molecular docking with 3,9-dihydroxyptercarpan and HEM. Overexpression of GmCYP93A1 and GmCYP93A2 in the soybean hairy roots reduced the content of daidzein, whereas knockdown of these two genes increased genistein content, indicating changes in expression level of GmCYP93A1 and GmCYP93A2 altered isoflavonoid flux in soybean. Our studies on the activity of GmCYP93A1 and GmCYP93A2 enriched diverse functions of CYP93 subfamily in soybean isoflavonoid pathway, which is valuable for further understanding and bioengineering of isoflavonoid pathway in soybean.

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.

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.

New dual functional CYP450 gene involves in isoflavone biosynthesis in Glycine max L.

Glycine max L. accumulates a large amount of isoflavonoid compounds, which is beneficial for plant defense, plant-microbe symbiotic interactions, and human health. Several CYP450 subfamily genes are involved in the flavonoid biosynthetic pathway in plants. In the present study, we found 24 CYP82 subfamily genes were differentially expressed in various tissues of soybean, in Phytophthora sojae-infected soybean varieties and in soybean hairy roots treated with cell wall glucan elicitor. Six of them (GmCYP82A2, GmCYP82A3, GmCYP82A4, GmCYP82A23, GmCYP82C20 and GmCYP82D26) were co-expressed with other known isoflavonoid pathway genes in soybean. Their enzymatic activity in yeast feeding assays showed that only GmCYP82D26 was able to convert naringenin to daidzein with both aryl migration and dehydration function. When GmCYP82D26 was over-expressed in soybean hairy roots, the contents of the two major isoflavonoid aglycones in soybean (daidzein and genistein) were reduced, but total flavonoids were not affected. When GmCYP82D26 was suppressed by RNAi in the hairy roots, daidzein content was decreased but genistein content was increased, with unchanged total flavonoid content. GmCYP82D26 was found to be localized in the endoplasmic reticulum at subcellular level when transiently expressed in tobacco leaf epidermis. GmCYP82D26 gene was preferentially expressed in roots, with low expression level in other tissues in soybean. Homology modeling and molecular docking showed that GmCYP82D26 could form hydrogen bond with both HEM and naringenin at C5-OH and C4 carbonyl. All these results indicated that GmCYP82D26 possesses new and dual enzymatic activity, which bridges the two branches (daidzein and genistein branch) of isoflavonoid pathway in soybean.

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.

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.

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.

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.

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.

Mechanistic insights into the environmental fate of tetracycline affected by ferrihydrite: Adsorption versus degradation.

Tetracycline (TC), a widely used antibiotic, is frequently detected in soil environments. It has a strong tendency to form complexes with metals, including iron (oxyhydr)oxide. In this study, ferrihydrite (Fh), a representative iron oxyhydroxide of the iron plaques on the surface of plant roots, was chosen to study the contributions of iron oxyhydroxide on the environmental fate of TC in the rhizosphere environment. Fh adsorption isotherm of TC showed good fitting to the Freundlich model, and the Fh adsorption capacity of TC was found much larger than the other iron oxyhydroxide of high crystallinity. The adsorption mechanisms mainly included electrostatic interaction, H-bonding, and complexation. The results of FTIR and XPS spectra revealed that tricarbonylamide, dimethylamino, and the hydroxyl in the B ring of TC were mainly responsible for the complexation with Fh surface hydroxyl groups. Furthermore, it should be noted that the adsorbed TC on Fh could be degraded and the degradation kinetics of TC better fitted to the pseudo-second-order model. Fh could promote electron transfer from TC to Fe(III) on the Fh surface, which led to the degradation of TC and the formation of Fe(II) ions. The degradation pathways of TC mainly involved three reactions: hydroxylation, dealkylation, and deamination. This study provides mechanistic insights on TC-Fh interaction, which improves the understanding of TC fate in the rhizosphere environment.

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.

Novel VHL substrate targets SFMBT1 and ZHX2 may be important prognostic predictors in patients with ccRCC.

Renal cell carcinoma is one of the most malignant cancers, with limited prognostic prediction system. The present study aimed to determine the prognostic value of novel von Hippel-Lindau (VHL) substrate targets in predicting the outcome of clear cell renal cell carcinoma (ccRCC). A total of 97 patients with ccRCC were enrolled in the present study, and the tissue microarray that was constructed using 97 ccRCC samples was used for immunohistochemical analysis. Univariate and multivariate Cox regression analyses were performed to determine the independent prognostic factors. Reverse transcription-quantitative PCR analysis demonstrated that the mRNA expression levels of scm-like with four malignant brain tumor domains (SFMBT1) and zinc fingers and homeoboxes 2 (ZHX2) were upregulated in cancer tissues compared with adjacent normal tissues. Among the 97 patients with ccRCC, SFMBT1 expression was upregulated in 61.9% (60/97), while ZHX2 expression was upregulated in 52.6% (51/97). Overall survival (OS) and disease-free survival (DFS) analyses indicated that SFMBT1 or ZHX2 alone were of limited predictive value; however, the combined expression of these two targets (high SFMBT1 and high ZHX2 expression, SHZH group) was significantly associated with OS (P=0.0350) and DFS (P=0.0434). In addition, multivariate analysis identified SHZH as an independent prognostic factor in patients with ccRCC. Taken together, these results suggest that SFMBT1 and ZHX2 act as novel substrate targets of VHL and, to the best of our knowledge, the present study was the first to provide insight on the co-expression of these two targets in representing a promising biomarker to predict the outcome of patients with ccRCC.

Epidemiological features and medical care-seeking process of patients with COVID-19 in Wuhan, China.

BACKGROUND: We aimed to investigate the epidemiological and clinical features, and medical care-seeking process of patients with the 2019 coronavirus disease (COVID-19) in Wuhan, China, to provide useful information to contain COVID-19 in other places with similar outbreaks of the virus. METHODS: We collected epidemiological and clinical information of patients with COVID-19 admitted to a makeshift Fangcang hospital between 7 and 26 February, 2020. The waiting time of each step during the medical care-seeking process was also analysed. RESULTS: Of the 205 patients with COVID-19 infection, 31% had presumed transmission from a family member. 10% of patients had hospital-related transmission. It took as long as a median of 6 days from the first medical visit to receive the COVID-19 nucleic acid test and 10 days from the first medical visit to hospital admission, indicating early recognition of COVID-19 was not achieved at the early stage of the outbreak, although these delays were shortened later. After clinical recovery from COVID-19, which took a mean of 21 days from illness onset, there was still a substantial proportion of patients who had persistent SARS-CoV-2 infection. CONCLUSIONS: The diagnostic evaluation process of suspected patients needs to be accelerated at the epicentre of the outbreak and early isolation of infected patients in a healthcare setting rather than at home is urgently required to stop the spread of the virus. Clinical recovery is not an appropriate criterion to release isolated patients and as long as 4 weeks' isolation for patients with COVID-19 is not enough to prevent the spread of the virus.

Noninvasive ventilation failure in patients with hypoxemic respiratory failure: the role of sepsis and septic shock.

BACKGROUND: Sepsis and septic shock are common in noninvasive ventilation (NIV) patients. However, studies on the association between sepsis and NIV failure are lacking. METHODS: A prospective multi-center observational study was performed in 16 Chinese intensive care units (ICUs). Patients who used NIV due to hypoxemic respiratory failure were enrolled. Sepsis and septic shock were diagnosed according to the guideline of sepsis-3. RESULTS: A total of 519 patients were enrolled. Sepsis developed in 365 patients (70%) and septic shock developed in 79 patients (15%). However, 75 patients (14%) had no sepsis. NIV failure was 23%, 38%, and 61% in patients, with no sepsis, sepsis, and septic shock, respectively. Multivariate analysis found that sepsis [odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.06-3.61] and septic shock (OR = 2.47, 95% CI: 1.12-5.45) were independently associated with NIV failure. In sepsis and septic shock population, the NIV failure was 13%, 31%, 37%, 53%, and 67% in patients with sequential organ failure assessment (SOFA) scores of ⩽2, 3-4, 5-6, 7-8, and ⩾9, respectively. Patients with nonpulmonary induced sepsis had similar NIV failure rate compared with those with pulmonary induced sepsis, but had higher proportion of septic shock (37% versus 10%, p ⩽ 0.01) and lower ICU mortality (10% versus 22%, p ⩽ 0.01). CONCLUSIONS: Sepsis was associated with NIV failure in patients with hypoxemic respiratory failure, and the association was stronger in septic shock patients. NIV failure increased with the increase of organ dysfunction caused by sepsis. The reviews of this paper are available via the supplemental material section.

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.

Hydrothermal Synthesis and Multicolor Upconversion Fluorescence of Novel LiLuF4:Yb3+,Tm3+ Microcrystals.

LiLuF4:Yb3+,Tm3+ upconversion luminescence materials were synthesized by a hydrothermal method, in which NaF and NaBF4 were used as fluorine sources (labeled as sample A and B, respectively). Their morphologies, XRD patterns and UC emission properties were compared. The synthesized crystallites consist of regular octahedrons of several micrometers and aggregates. The XRD patterns indicate that they belong to tetragonal crystal system with 141/a space group. These microcrystals emit strong UC violet, visible and near infrared light under the excitation of 980 nm laser diode. The multicolor UC emissions from sample B are much stronger than those from sample A. The strong emission intensity is ascribed to good crystal quality of sample B.