Incorporating knowledge of disease-defining hub genes and regulatory network into a machine learning-based model for predicting treatment response in lupus nephritis after the first renal flare.

BACKGROUND: Identifying candidates responsive to treatment is important in lupus nephritis (LN) at the renal flare (RF) because an effective treatment can lower the risk of progression to end-stage kidney disease. However, machine learning (ML)-based models that address this issue are lacking. METHODS: Transcriptomic profiles based on DNA microarray data were extracted from the GSE32591 and GSE112943 datasets. Comprehensive bioinformatics analyses were performed to identify disease-defining genes (DDGs). Peripheral blood samples (GSE81622, GSE99967, and GSE72326) were used to evaluate the effect of DDGs. Single-sample gene set enrichment analysis (ssGSEA) scores of the DDGs were calculated and correlated with specific immunology genes listed in the nCounter panel. GSE60681 and GSE69438 were used to examine the ability of the DDGs to discriminate LN from other renal diseases. K-means clustering was used to obtain the separate gene sets. The clustering results were extended to data derived using the nCounter technique. The least absolute shrinkage and selection operator (LASSO) algorithm was used to identify genes with high predictive value for treatment response after the first RF in each cluster. LASSO models with tenfold validation were built in GSE200306 and assessed by receiver operating characteristic (ROC) analysis with area under curve (AUC). The models were validated by using an independent dataset (GSE113342). RESULTS: Forty-five hub genes specific to LN were identified. Eight optimal disease-defining clusters (DDCs) were identified in this study. Th1 and Th2 cell differentiation pathway was significantly enriched in DDC-6. LCK in DDC-6, whose expression positively correlated with various subsets of T cell infiltrations, was found to be differentially expressed between responders and non-responders and was ranked high in regulatory network analysis. Based on DDC-6, the prediction model had the best performance (AUC: 0.75; 95% confidence interval: 0.44-1 in the testing set) and high precision (0.83), recall (0.71), and F1 score (0.77) in the validation dataset. CONCLUSIONS: Our study demonstrates that incorporating knowledge of biological phenotypes into the ML model is feasible for evaluating treatment response after the first RF in LN. This knowledge-based incorporation improves the model's transparency and performance. In addition, LCK may serve as a biomarker for T-cell infiltration and a therapeutic target in LN.

Tropical and subtropical Asia's valued tree species under threat.

Tree diversity in Asia's tropical and subtropical forests is central to nature-based solutions. Species vulnerability to multiple threats, which affect provision of ecosystem services, is poorly understood. We conducted a region-wide, spatially explicit assessment of the vulnerability of 63 socioeconomically important tree species to overexploitation, fire, overgrazing, habitat conversion, and climate change. Trees were selected for assessment from national priority lists, and selections were validated by an expert network representing 20 countries. We used Maxent suitability modeling to predict species distribution ranges, freely accessible spatial data sets to map threat exposures, and functional traits to estimate threat sensitivities. Species-specific vulnerability maps were created as the product of exposure maps and sensitivity estimates. Based on vulnerability to current threats and climate change, we identified priority areas for conservation and restoration. Overall, 74% of the most important areas for conservation of these trees fell outside protected areas, and all species were severely threatened across an average of 47% of their native ranges. The most imminent threats were overexploitation and habitat conversion; populations were severely threatened by these factors in an average of 24% and 16% of their ranges, respectively. Our model predicted limited overall climate change impacts, although some study species were likely to lose over 15% of their habitat by 2050 due to climate change. We pinpointed specific natural areas in Borneo rain forests as hotspots for in situ conservation of forest genetic resources, more than 82% of which fell outside designated protected areas. We also identified degraded areas in Western Ghats, Indochina dry forests, and Sumatran rain forests as hotspots for restoration, where planting or assisted natural regeneration will help conserve these species, and croplands in southern India and Thailand as potentially important agroforestry options. Our results highlight the need for regionally coordinated action for effective conservation and restoration.

Especies de Árboles Valoradas y Amenazadas de Asia Tropical y Subtropical Resumen La diversidad de árboles en los bosques tropicales y subtropicales de Asia es un eje central para las soluciones basadas en la naturaleza. La vulnerabilidad de las especies ante las múltiples amenazas, las cuales afectan el suministro de servicios ambientales, es un tema poco comprendido. Realizamos una evaluación regional espacialmente explícita de la vulnerabilidad de 63 especies de árboles de importancia socioeconómica ante la sobreexplotación, incendios, sobrepastoreo, conversión del hábitat y cambio climático. Los árboles se seleccionaron para su evaluación a partir de listas nacionales de prioridades, y las selecciones fueron validadas por una red de expertos de 20 países. Usamos el modelado de idoneidad Maxent para predecir el rango de distribución de las especies, conjuntos de datos espaciales de libre acceso para mapear la exposición a las amenazas y rasgos funcionales para estimar la susceptibilidad a las amenazas. Con base en la vulnerabilidad a las amenazas actuales y al cambio climático, identificamos las áreas prioritarias para su conservación y restauración. En general, el 74% de las áreas más importantes para la conservación de estos árboles quedó fuera de las áreas protegidas y todas las especies estaban seriamente amenazadas en promedio en el 47% de su distribución nativa. Las amenazas más inminentes fueron la sobreexplotación y la conversión del hábitat; las poblaciones estuvieron seriamente amenazadas por estos factores en promedio en el 24% y 16% de su distribución, respectivamente. Nuestro modelo predijo un impacto general limitado del cambio climático, aunque algunas especies estudiadas tuvieron la probabilidad de perder más del 15% de su hábitat para el 2050 debido a este factor. Identificamos áreas naturales específicas en las selvas de Borneo como puntos calientes para la conservación in situ de los recursos genéticos forestales, más del 82% de los cuales estaban fuera de las áreas protegidas designadas. También identificamos áreas degradadas en los Ghats Occidentales, los bosques secos de Indochina y las selvas de Sumatra como puntos calientes para la restauración, en donde la siembra o la regeneración natural asistida ayudarán a conservar estas especies. Además, identificamos campos de cultivo al sur de India y Tailandia como potenciales opciones importantes de agrosilvicultura. Nuestros resultados resaltan la necesidad de acciones regionales coordinadas para la conservación y restauración efectivas.

Sensitivity enhancement of magneto-optical Faraday effect immunoassay method based on biofunctionalized γ-Fe2O3@Au core-shell magneto-plasmonic nanoparticles for the blood detection of Alzheimer's disease.

In this work, we conducted a proof-of-concept experiment based on biofunctionalized magneto-plasmonic nanoparticles (MPNs) and magneto-optical Faraday effect for in vitro Alzheimer's disease (AD) assay. The biofunctionalized γ-Fe2O3@Au MPNs of which the surfaces are modified with the antibody of Tau protein (anti-τ). As anti-τ reacts with Tau protein, biofunctionalized MPNs aggregate to form magnetic clusters which will hence induce the change of the reagent's Faraday rotation angle. The result showed that the γ-Fe2O3@Au core-shell MPNs can enhance the Faraday rotation with respect to the raw γ-Fe2O3 nanoparticles. Because of their magneto-optical enhancement effect, biofunctionalized γ-Fe2O3@Au MPNs effectively improve the detection sensitivity. The detection limit of Tau protein as low as 9 pg/mL (9 ppt) was achieved. Furthermore, the measurements of the clinical samples from AD patients agreed with the CDR evaluated by the neurologist. The results suggest that our method has the potential for disease assay applications.

Reservoir NO3- pollution and chemical weathering: by dual isotopes of δ15N-NO3-, δ18O-NO3- and geochemical constraints.

Reservoir dams alter the nutrient composition and biogeochemical cycle. Thus, dual isotopes of δ18O-NO3- and δ15N-NO-3 and geochemical signatures were employed to study the NO3- pollution and chemical weathering in the Three Gorges Reservoir (TGR), China. This study found that the TGR dam alters the δ15N-NO3- composition and is enriched in the recharge period. Values of δ15N-NO3- varied from 4.5 to 12.9‰ with an average of 9.8‰ in the recharge period, while discharge period δ15N-NO3- ranged from 3.2 to 12.5‰, with an average of 9.3‰. δ18O-NO3- varies (1.2-11.3‰) with an average of 6.5‰ and (2.4-12.4‰) with an average of 7.5‰, in the recharge and discharge periods, respectively. Stable isotopic values sharply decreased from upstream to downstream, indicating the damming effects. δ18O-NO3- and δ15N NO3- confirm that sewage effluents, nitrification of soil organic material, and NH4+ fertilizers were the primary sources of NO3- in the reservoir. Carbonate weathering mainly provides ions to the reservoir. HCO3- + SO42- and Ca2+ + Mg2+ represent 90% of major ions in the TGR. Downstream sampling sites showed low solute concentration during the recharge period, indicating the dam effect on solute concentration. Ca-Mg-Cl-, Ca-HCO3- and Ca-Cl- were the main water types in the TGR. The average percentage of solutes contribution revealed the carbonate weathering, evaporites dissolution, silicate weathering, and atmospheric input were 51.9%, 41%, 7.8%, and 1.7% for the recharge period. In contrast, the discharge period contributed 66.4%, 29.2%, 10%, and 4.3%, respectively. TGR water is moderately suitable for irrigation, and hardness is high in drinking water. This study provides new insight into the dual isotopic approach and geochemical signatures to interpret the NO3- cycle and chemical weathering process under dam effects in the TGR. However, this isotopic application has some limitations in source identification, isotope fractionation, and transformation mechanisms of nitrate. Thus, further studies need to be done on these topics for a better undestanding.

Different item characteristics of a mild cognitive impairment screening tool in the community-based Yilan Study: application of the item response theory.

BACKGROUND: This study aimed to use item response theory (IRT) to explore the item-by-item characteristics of a mild cognitive impairment (MCI) screening tool using community-based data. METHODS: The Yilan Study is a community-based study that has been conducted since 2012. Until March 2020, 2230 older adults were interviewed according to the household registration data. IRT was applied to determine the item-by-item distinctive characteristics of the Eight-item Interview to Differentiate Aging and Dementia (AD8). RESULTS: The MCI characteristics in the AD8 items have varying degrees of item response threshold. In all circumstances, item AD8-8, which is related to self-rated memory ability, had a low item response threshold. AD8-5 and AD8-7, which are related to the comparisons of time-oriented functional status, had slightly lower thresholds, especially for those aged 65-79 years or without activity limitations. Conversely, AD8-1, AD8-2, AD8-3, AD8-4, and AD8-6 had similar item response thresholds and discriminative power; these items have more detailed functional descriptions or examples for illustration. CONCLUSIONS: Concise and understandable elements are often expected in community-based screening tools. For community-based health screening and population empowerment in the early detection of MCI, assessment tool items with detailed functional descriptions and examples for illustration have similar validities in most of the population. Items related to self-rated memory ability might be less valid. More examples may be needed for items constructed for comparing time-oriented functional status, especially in extremely old adults and individuals with activity limitations.

Downregulation of AANAT by c-Fos in tubular epithelial cells with membranous nephropathy.

Melatonin is a hormone majorly secreted by the pineal gland and contributes to a various type of physiological functions in mammals. The melatonin production is tightly limited to the AANAT level, yet the most known molecular mechanisms underlying AANAT gene transcription is limited in the pinealocyte. Here, we find that c-Fos and cAMP-response element-binding protein (CREB) decreases and increases the AANAT transcriptional activity in renal tubular epithelial cell, respectively. Notably, c-Fos knockdown significantly upregulates melatonin levels in renal tubular cells. Functional results indicate that AANAT expression is decreased by c-Fos and resulted in enhancement of cell damage in albumin-injury cell model. We further find an inverse correlation between c-Fos and AANAT levels in renal tubular cells from experimental membranous nephropathy (MN) samples and clinical MN specimens. Our finding provides the molecular basis of c-Fos in transcriptionally downregulating expression of AANAT and melatonin, and elucidate the protective role of AANAT in preventing renal tubular cells death in albumin-injury cell model and MN progression.

[Autophagic activity of piperine on small intestine in dementia model mice with Parkinson's disease].

This article is to investigate the effect of piperine on the small intestine of mice with Parkinson's disease with dementia(PDD). Ninety-six C57 BL/6 mice of SPF grade were randomly divided into 8 groups(male, 12 in each group): normal group, model group, autophagy inhibitor group(6-amino-3-methylpurine, 3 MA, 30 mg·kg~(-1)), autophagy activator group(rapamycin, 1 mg·kg~(-1)), low, medium, and high dose piperine groups(10, 20, 40 mg·kg~(-1)), and medopar group(112.5 mg·kg~(-1)). Except for the normal group, mice in each group were injected subcutaneously with reserpine(0.1 mg·kg~(-1)) once every 48 hours for 40 days. In addition, on the 20 th day of administration, except for the normal group, the mice in the other groups were subjected to bilateral common carotid artery occlusion to finally prepare PDD models. At the same time, each group was given the corresponding drug treatment once a day for 40 days. After the last administration, the behavioral changes of mice were observed by autonomic activity experiment and hot plate experiment. The expression levels of α-synuclein(α-syn) and tyrosine hydroxylase(TH) in the small intestine were detected by immunohistochemistry. The expression levels of beclin-1, microtubule-associated protein 1 light chain 3 B(LC3 B) and p62 in the small intestine were detected by immunofluorescence assay. Hematoxylin-eosin staining was used to observe the pathological morphology of small intestine tissues in each group. Enzyme-linked immunosorbent assay was adopted for detection of ß-amyloid precursor protein(APP), p-tau, acetylcholine transferase(ChAT), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in small intestine. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression of α-syn, TH, beclin-1, microtubule-associated protein 1 light chain 3(LC3), and p62 mRNA and mmu-miR-99 a-5 p in the small intestine. The results of this study showed that, as compared with the model group, the number of activities, the expression levels of ChAT, TH, and p62 were significantly increased in the 3 MA group, the various piperine dose groups, and the medopar group(P<0.05), and their first foot licking time was shortened; APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly reduced(P<0.05). However, as compared with the model group, the number of activities, ChAT, TH, and p62 expression levels in the rapamycin group were significantly reduced(P<0.05), and the APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly increased(P<0.05). As compared with the 3 MA group, the number of activities, ChAT, TH, and p62 expression levels were significantly reduced in the low and medium dose piperine groups and rapamycin group(P<0.05); howe-ver, their first foot licking time was significantly prolonged, APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were increased significantly(P<0.05). As compared with the medopar group, the number of activities, ChAT, TH, and p62 expression levels were significantly reduced in low dose piperine group and rapamycin group(P<0.05), but their first foot licking time was significantly extended, and APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly increased(P<0.05). In addition, as compared with the normal group, the small intestinal epithelial cells of the model group and the rapamycin group were shed off a lot, with severe damages of intestinal mucosa as well as edema and shedding of the small intestine villi. After administration of the therapeutic interventions, the small intestinal epithelial cells of the 3 MA group, each dose group of piperine, and the medopa group were slightly damaged and the villi were slightly shed off. In summary, piperine has a protective effect on the small intestine of PDD model mice, showing reduced expression of mmu-miR-99 a-5 p, pro-inflammatory factors and autophagy factors, and the mechanism of slowing PDD pathological symptoms may be related to the inhibition of autophagy.

microRNA-448 inhibits stemness maintenance and self-renewal of hepatocellular carcinoma stem cells through the MAGEA6-mediated AMPK signaling pathway.

Hepatocellular carcinoma (HCC) occurs mainly in patients with chronic liver disease and cirrhosis. Increasing evidence has identified the involvement of microRNAs (miRNAs) acting as essential regulators in the progression of HCC. As predicted by microarray analysis, miR-448 might potentially affect HCC progression by regulating the melanoma-associated antigen (MAGEA). Therefore, the present investigation focused on exploring whether or not miR-448 and MAGEA6 were involved in the self-renewal and stemness maintenance of HCC stem cells. The interaction among miR-448, MAGEA6, and the AMPK signaling pathway was evaluated. It was noted that miR-448 targeted and downregulated MAGEA6, thus activating the AMP-activated protein kinase (AMPK) signaling pathway in HCC. Furthermore, for the purpose of exploring the functional relevance of MAGEA6 and miR-448 on the sphere formation, colony formation, and invasion and migration of HCC stem cells, the CD133+ CD44 + HCC stem cells were sorted and treated with the mimic or inhibitor of miR-448, small interfering RNA (siRNA) against MAGEA6 or an AMPK activator AICAR. MAGEA6 silencing or miR-448 overexpression was demonstrated to inhibit the abilities of sphere formation, colony formation, cell migration, and invasion of HCC cells. Afterwards, a rescue experiment was conducted and revealed that MAGEA6 silencing reversed the effects of miR-448 inhibitor on stemness maintenance and self-renewal of HCC stem cells. Finally, after the in vivo experiment was carried out, miR-448 was observed to restrain the tumor formation and stemness in vivo. Altogether, miR-448 activates the AMPK signaling pathway by downregulating MAGEA6, thus inhibiting the stemness maintenance and self-renewal of HCC stem cells, which identifies miR-448 as a new therapeutic strategy for HCC.

2-(m-Azidobenzoyl)taxol binds differentially to distinct ß-tubulin isotypes.

There are seven ß-tubulin isotypes present in distinct quantities in mammalian cells of different origin. Altered expression of ß-tubulin isotypes has been reported in cancer cell lines resistant to microtubule stabilizing agents (MSAs) and in human tumors resistant to Taxol. To study the relative binding affinities of MSAs, tubulin from different sources, with distinct ß-tubulin isotype content, were specifically photolabeled with a tritium-labeled Taxol analog, 2-(m-azidobenzoyl)taxol, alone or in the presence of MSAs. The inhibitory effects elicited by these MSAs on photolabeling were distinct for ß-tubulin from different sources. To determine the exact amount of drug that binds to different ß-tubulin isotypes, bovine brain tubulin was photolabeled and the isotypes resolved by high-resolution isoelectrofocusing. All bands were analyzed by mass spectrometry following cyanogen bromide digestion, and the identity and relative quantity of each ß-tubulin isotype determined. It was found that compared with other ß-tubulin isotypes, ßIII-tubulin bound the least amount of 2-(m-azidobenzoyl)taxol. Analysis of the sequences of ß-tubulin near the Taxol binding site indicated that, in addition to the M-loop that is known to be involved in drug binding, the leucine cluster region of ßIII-tubulin contains a unique residue, alanine, at 218, compared with other isotypes that contain threonine. Molecular dynamic simulations indicated that the frequency of Taxol-accommodating conformations decreased dramatically in the T218A variant, compared with other ß-tubulins. Our results indicate that the difference in residue 218 in ßIII-tubulin may be responsible for inhibition of drug binding to this isotype, which could influence downstream cellular events.

Color-induced changes in oxygen consumption and swimming performance of juvenile bighead carp (Aristichthys nobilis).

Fish physiology and behavior are affected by exposure to light of varying colors, but little is known about the effects on swimming performance and metabolism. The purpose of this study was to measure the effects of light color on the swimming performance of bighead carp (Aristichthys nobilis), a planktivorous fish species widely used in aquaculture. Stepped velocity testing was conducted in a modified Brett-type swim tunnel respirometer to determine critical swimming speed (Ucrit), oxygen consumption (MO2), and excess post-exercise oxygen consumption (EPOC) for juvenile bighead carp under red, yellow, blue, and green lights at 25 °C. Ucrit was significantly lower for fish swimming under yellow and green lights compared with red and blue light. Cost of transport (COT), a measure of swimming efficiency, also varied with color. The results, obtained under controlled conditions, add to our knowledge on the effects of artificial color light on fish physiology and behavior and inform decisions on the use of artificial color light in aquaculture and fishway design.

Taxol Analogues Exhibit Differential Effects on Photoaffinity Labeling of ß-Tubulin and the Multidrug Resistance Associated P-Glycoprotein.

Several next-generation taxanes have been reported to possess high potency against Taxol-resistant cancer cell lines overexpressing ßIII-tubulin and/or P-glycoprotein (P-gp), both of which are involved in drug resistance. Using a photoaffinity Taxol analogue, 2-( m-azidobenzoyl)taxol, two potent next-generation taxanes, SB-T-1214 and SB-CST-10202, exhibited distinct inhibitory effects on photolabeling of ß-tubulin from different eukaryotic sources that differ in ß-tubulin isotype composition. They also specifically inhibited photolabeling of P-gp, and the inhibitory effect correlated well with the steady-state accumulation of [3H]vinblastine in a multidrug resistant (MDR) cell line, SKVLB1. Several microtubule-stabilizing agents (MSAs)-resistant cell lines from the human ovarian cancer cell line Hey were isolated, and their MDR1 and ßIII-tubulin levels determined. Distinct potencies of the two taxanes against different MSA-resistant cells expressing unique levels of MDR1 and ßIII-tubulin were found. Cytotoxicity assays, done in the presence of verapamil, indicated that SB-T-1214 is a substrate, although not as good as Taxol, for P-gp. The mechanisms involved in drug resistance are multifactorial, and the effectiveness of new Taxol analogues depends on the interaction between the drugs and all possible targets; in this case the two major cellular targets are ß-tubulin and P-gp.

Improved Dose-Response Relationship of (+)-Discodermolide-Taxol Hybrid Congeners.

(+)-Discodermolide is a microtubule-stabilizing agent with potential for the treatment of taxol-refractory malignancies. (+)-Discodermolide congeners containing the C-3'-phenyl side chain of taxol (paclitaxel) were synthesized based on computational docking models predicting this moiety would fill an aromatic pocket of ß-tubulin insufficiently occupied by (+)-discodermolide, thereby conferring improved ligand-target interaction. It was recently demonstrated, however, that the C-3'-phenyl side chain occupied a different space, instead extending toward the M-loop of ß-tubulin, where it induced a helical conformation, hypothesized to improve lateral contacts between adjacent microtubule protofilaments. This insight led us to evaluate the biological activity of hybrid congeners using a panel of genetically diverse cancer cell lines. Hybrid molecules retained the same tubulin-polymerizing profile as (+)-discodermolide. Since (+)-discodermolide is a potent inducer of accelerated senescence, a fate that contributes to drug resistance, congeners were also screened for senescence induction. Flow cytometric and transcriptional analysis revealed that the hybrids largely retained the senescence-inducing properties of (+)-discodermolide. In taxol-sensitive cell models, the congeners had improved dose-response parameters relative to (+)-discodermolide and, in some cases, were superior to taxol. However, in cells susceptible to senescence, EMax increased without concomitant improvements in EC50 such that overall dose-response profiles resembled that of (+)-discodermolide.

Angiotensin II type 2 receptor-interacting protein 3a inhibits ovarian carcinoma metastasis via the extracellular HMGA2-mediated ERK/EMT pathway.

Local migration and long-distance metastasis is the main reason for higher mortality of ovarian cancer. Microtubule-associated tumor suppressor 1/angiotensin II type 2 receptor-interacting protein is associated with tumor initiation and progression and exerts anti-tumor effects. High mobility group AT-hook 2 is overexpressed in majority of metastatic carcinomas, which contributes to carcinomas metastasis through Snail-induced epithelial-to-mesenchymal transition signal pathway. The purpose of this study was to investigate the signal pathway of microtubule-associated tumor suppressor 1/angiotensin II type 2 receptor-interacting protein-mediated anti-tumor effects. Our data observed that ovarian carcinoma cells exhibited lower expression of angiotensin II type 2 receptor-interacting protein 3a and higher expression of high mobility group AT-hook 2 compared to normal ovarian cells. Restoration of angiotensin II type 2 receptor-interacting protein 3a expression in ovarian carcinoma cells inhibited high mobility group AT-hook 2 expression and exhibited anti-proliferative effects. In addition, angiotensin II type 2 receptor-interacting protein 3a treatment suppressed the phosphorylation of epithelial-to-mesenchymal transition and extracellular signal-regulated kinase in ovarian carcinoma cells. We also observed that angiotensin II type 2 receptor-interacting protein 3a restoration downregulated expression of Snail, E-Cadherin, N-Cadherin, and Vimentin in ovarian carcinoma cells, whereas angiotensin II type 2 receptor-interacting protein 3a knockdown enhanced the phosphorylation of extracellular signal-regulated kinase and epithelial-to-mesenchymal transition. In vivo assay indicated that angiotensin II type 2 receptor-interacting protein 3a inhibited ovarian tumor growth and elevated survival of tumor-bearing immunodeficient mice. Tumor histological analysis indicated that Snail, E-Cadherin, N-Cadherin, and Vimentin expression levels were downregulated via decreasing high mobility group AT-hook 2 expression. Furthermore, upregulation of angiotensin II type 2 receptor-interacting protein 3a impaired the phenotype of extracellular signal-regulated kinase and epithelial-to-mesenchymal transition in ovarian carcinoma cells and tumor tissues. Taken together, angiotensin II type 2 receptor-interacting protein 3a presents potential in suppressing the proliferation and aggressiveness of ovarian carcinoma cells through the high mobility group AT-hook 2-mediated extracellular signal-regulated kinase/epithelial-to-mesenchymal transition signal pathway.

Optimal pediatric dosing of anti-platelet agents for pipeline stent embolization -a case report and review of the literature.

BACKGROUND: Various strategies are emerging for dosing antiplatelet therapies in preparation for pipeline stent embolization in adults. Hyper-response is associated with hemorrhagic complications. Hypo-response is associated with thromboembolic events. Dosing of antiplatelet agents is highly variable, with little consensus among experts for adults-and even more so for children. To date, pipeline stents have been deployed in 11 pediatric patients, ages 4-15. A variety of clopidogrel and aspirin dosing regimens have been used, with response tested in only three patients, who were all therapeutic. Thrombotic events occurred in two patients, neither of whom were tested. CASE: We describe here the first case of a hemorrhagic complication in a hyper-responsive pediatric patient undergoing placement of a pipeline stent. DISCUSSION: As the use of endovascular therapies requiring dual anti-platelet agents becomes more established, there is an increasing need to develop titration protocols that minimizes the risk of thrombotic and hemorrhagic events.

Taxol®: The First Microtubule Stabilizing Agent.

Taxol®, an antitumor drug with significant activity, is the first microtubule stabilizing agent described in the literature. This short review of the mechanism of action of Taxol® emphasizes the research done in the Horwitz' laboratory. It discusses the contribution of photoaffinity labeled analogues of Taxol® toward our understanding of the binding site of the drug on the microtubule. The importance of hydrogen/deuterium exchange experiments to further our insights into the stabilization of microtubules by Taxol® is addressed. The development of drug resistance, a major problem that arises in the clinic, is discussed. Studies describing differential drug binding to distinct ß-tubulin isotypes are presented. Looking forward, it is suggested that the ß-tubulin isotype content of a tumor may influence its responses to Taxol®.

Carotid Endarterectomy to Remove Retained Solitaire Stent Retriever inside Carotid Stent after Mechanical Thrombectomy.

BACKGROUND: Tandem occlusions of the internal carotid artery (ICA) and middle cerebral artery (MCA) occur in up to a third of patients with acute ischemic strokes undergoing endovascular mechanical thrombectomy. Understanding open neurosurgical management of associated complications with this procedure is important. CASE REPORT: A 67-year-old man with acute onset of left hemiparesis and a tandem right ICA and MCA occlusion. He underwent carotid stent angioplasty of a stenotic ICA, followed by attempted Solitaire stent retrieval of an MCA clot. On withdrawal, the tines of the Solitaire stent lodged inside the Precise carotid stent. The patient was started on aspirin, Plavix, and heparin infusion, and underwent a carotid endarterectomy (CEA) with safe removal of the stents and primary vessel repair. CONCLUSION: This is the first case reported to date of a Solitaire stent becoming lodged inside a Precise carotid stent, salvaged by CEA with safe removal of the stents and primary vessel repair. We discuss the timing, indication, alternatives, and technical nuances of a CEA in this setting.

Microwave enhanced oxidation treatment of organic fertilizers.

BACKGROUND: Liquid organic fertilizers (LOFs) are relatively easier to degrade than those of solid organic fertilizers, and the nutrients are readily available for plant uptake. Microwave enhanced advanced oxidation treatment (MW/H2 O2 -AOP) was used to convert solid organic fertilizers (insoluble blood meal, bone meal, feather meal, sunflower ash and a mixture) into LOF. RESULTS: After the MW/H2 O2 -AOP treatment, high soluble nitrogen (11-29%), soluble phosphorus (64%) and potassium (92%), as well as low total suspended solids content could be obtained. The resulting LOF would make the nutrients more bioavailable, and would provide some of them for the plant uptake immediately. Temperature and hydrogen peroxide dosage were found to be significant factors affecting nitrogen release from blood meal and feather meal, while temperature and pH were found to be significant factors for solubilizing phosphorus and potassium from bone meal and ash, respectively. CONCLUSION: The MW/H2 O2 -AOP reduced suspended solids, and released nutrients into solution; therefore, it was an effective treatment method to make LOFs. © 2016 Society of Chemical Industry.

Functional Remodeling of Both Atria is Associated with Occurrence of Stroke in Patients with Paroxysmal and Persistent Atrial Fibrillation.

BACKGROUND: It is critical to recognize high risk patients who are prone to develop stroke in the management of atrial fibrillation (AF). The purpose of this study was to identify the determinants of AF related stroke by assessing the anatomical and functional remodeling of cardiac chambers. METHODS: We compared the cardiac structure and function of 28 consecutive patients with paroxysmal and persistent AF-related stroke with 69 patients with AF and 21 controls without stroke using contrast-enhanced 64-slice multi-detector computed tomography during sinus rhythm. RESULTS: The volume of left atrium (LA), LA appendage (LAA) and right atrium (RA) were significantly increased across the groups with sinus rhythm (SR), AF and AF-related stroke (p < 0.001 for each, respectively). The emptying fraction and booster-pump function of LA, LAA and RA were decreased across the groups (p < 0.001 for each). In addition, the left ventricular mass index was increased in AF related stroke (p = 0.003). Using multivariate analysis, increased age (p = 0.003), reduced booster-pump function of LA (p = 0.01), LAA (p < 0.001) and RA (p < 0.001) were shown to be independently associated with the occurrence of stroke. CONCLUSIONS: The dilatation and contractile dysfunction of both atria are related to the development of stroke in patients with paroxysmal and persistent AF. Our results suggested that the use of substrate-based assessment may help improve risk stratification of stroke in patients with AF.