Crystal-Plane-Engineered TiO2-Anchored Vanadium Single Atoms and Clusters for Boosting Ultradeep Aerobic Oxidative Desulfurization of Diesel.

The crystal plane effect has gained extensive attention in heterogeneous catalysis reactions; however, it is far from being systematically probed in titanium dioxide (TiO2)-supported vanadium catalysts. Herein, a series of vanadium (V) single atoms and clusters anchored on TiO2 with different crystal planes was fabricated by an improved "top-down" protocol. The dispersion state, electronic structure, and redox properties of the V single-atom and VOx cluster-supported catalysts were systematically analyzed by a series of characterization methods, including X-ray absorption near edge structure (XANES) and density functional theory (DFT) calculations, and their catalytic performances were examined for aerobic oxidative desulfurization (AODS) of 4,6-dimethyl-dibenzothiophen (4,6-DMDBT) with O2 as the oxidant. The results unveiled that the synergistic effect between the V single atom and the VOx cluster perceptibly promoted the catalytic performances of VOx/TiO2 samples. Therein, VOx/TiO2-(001) shows the lowest apparent activation energy (Ea) value of 46.3 kJ/mol and the optimal AODS performance with complete 4,6-DMDBT conversion to 4,6-dimethyldibenzothiophene sulfone (4,6-DMDBTO2) within 60 min at 120 °C as compared with VOx/TiO2-(101) (81.9 kJ/mol and 180 min) and VOx/TiO2-(100) (68.0 kJ/mol and 240 min), which should be attributed to its higher V5+/V4+ ratio, the optimal redox behavior of the V species, the moderate adsorption energy between 4,6-DMDBT and VOx active centers, and the synthetic effect of V single atoms and VOx clusters. Moreover, VOx/TiO2-(001) exhibits robust durability in seven cycles of reuse, showcasing the potential for practical applications in the future.

3D Printing Technique Fortifies the Ultradeep Hydrodesulfurization Process of Diesel: A Journey of NiMo/Al2O3-MMT.

In this contribution, we rationally designed and controllably fabricated a NiMo/Al2O3-montmorillonite (3D-NiMo/Al2O3-MMT) monolithic catalyst via a 3D printing strategy with economical montmorillonite (MMT) as a binder. The catalytic performance of the resulting NiMo/Al2O3-MMT for 4,6-dimethyldibenzothiophene (4,6-DMDBT) hydrodesulfurization (HDS) was evaluated. The experimental results unveil that the 3D-NiMo/Al2O3-MMT monolithic catalyst exhibits robust stability and exceptional HDS activity with 99.2% 4,6-DMDBT conversion (residual 4 ppm of S), which is remarkably superior to that of conventional NiMo/Al2O3 (61.5%), NiMo/MMT (63.2%), and even NiMo/Al2O3-MMT (76.5%) prepared by the mechanical-mixing method. This should be ascribed to the synthetic effect between the MMT binder and the Al2O3 substrate, which effectively weakens the interaction between the Mo species and the Lewis acids on the original Al2O3 surface, thereby significantly increasing the content of reducible Mo species and considerably facilitating the formation of more highly active NiMoS phase (Type II) with optimal average stacking layers and thereafter remarkably enhancing the ultradeep HDS activity of the 3D-NiMo/Al2O3-MMT monolithic catalyst.

Risk Factors for Cefoperazone/Sulbactam-Induced Coagulation Disorder.

Purpose: Cefoperazone/sulbactam is a ß-lactam/ß-lactamase inhibitor combination effective against intra-abdominal, urinary tract, and respiratory infections. Although some studies have suggested that cefoperazone/sulbactam is associated with coagulation disorders, it remains debatable whether the combination of cefoperazone/sulbactam with tigecycline or valproic acid increases the risk of bleeding, as both drugs can lead to coagulation disorders. This study aimed to explore the risk factors of cefoperazone/sulbactam-induced coagulopathy. Patients and Methods: This was a single-center, retrospective, nested case-control study. The sample groups were derived from individuals registered at the Department of Neurosurgery, Shanxi Provincial People's Hospital. Propensity score matching (PSM) was used to adjust for demographic data. Conditional logistic regression was used to estimate the matched odds ratios representing the odds of cefoperazone/sulbactam-induced coagulopathy (CIC), and a receiver operating characteristic curve was used to determine the optimal cut-off conditions. Results: After PSM, 155 and 56 patients were included in the control and case groups, respectively. Multivariate analysis revealed that advanced age, treatment duration, and total dose were independent risk factors of cefoperazone/sulbactam-induced coagulation disorders. Concomitant use of vitamin K was an independent protective factor against CIC. The optimal cut-off for the length of treatment was 5 d, and the cut-off for the total dose was 48 g. Conclusion: Tigecycline and valproic acid were not associated with CIC. Advanced age and long treatment duration are risk factors for CIC. Supplementation with vitamin K during cefoperazone/sulbactam treatment was associated with a reduced risk.

One-Pot Three-Dimensional Printing of a Hierarchical NiMo/Al2O3 Monolithic Catalyst for 4,6-Dimethyldibenzothiophene Hydrodesulfurization.

The development of a competitive-cost and high-efficiency NiMo/Al2O3 hydrodesulfurization (HDS) catalyst remains challenging in the field of petrochemical industry. Herein, a highly efficient NiMo/Al2O3 monolithic HDS catalyst was elaborately designed and successfully fabricated via a one-pot three-dimensional (3D) printing strategy, and its HDS activity was examined for 4,6-dimethyldibenzothiophene conversion. The results unveil that the NiMo/Al2O3 monolithic catalyst prepared by the 3D printing strategy (3D-NiMo/Al2O3) exhibits hierarchical structure due to the combustion of hydroxymethyl cellulose serving as adhesive, which endows the weaker metal-support-interaction between Mo oxides and Al2O3, remarkably promoting sulfidation of both Mo and Ni species and the formation of "Type II" NiMoS active phase, thereby reducing the apparent activation energy (Ea = 109.2 kJ·mol-1) and increasing the catalytic activity (TOF = 4.0 h-1) and thereafter dramatically boosting the HDS performance of 3D-NiMo/Al2O3 compared with that of NiMo/Al2O3 (Ea = 150.6 kJ·mol-1 and TOF = 2.1 h-1) counterpart synthesized by conventional method with P123 serving as the mesoporous template. Therefore, this study offers a facile and straightforward strategy to fabricate an efficient HDS catalyst with hierarchical structures.

HNRNPK/CLCN3 axis facilitates the progression of LUAD through CAF-tumor interaction.

Background: Chloride channel 3 (CLCN3) is regulated by transcription-coactivator, however, it is unclear which core transcription factor regulates CLCN3. The role of CLCN3 in lung adenocarcinoma (LUAD) is unexplored and the relationship between CLCN3 and tumor microenvironment is unknown. Methods: A 5'-biotin-labeled promoter probe of CLCN3 was used to pull down the promoter-binding transcription factor. Further study was investigated using LUAD samples, cell lines, and xenograft mice models, and the mechanism was explored. Results: CLCN3 was upregulated in human LUAD, and CLCN3 knockdown inhibited tumor proliferation and migration in vitro. Next, heterogeneous nuclear ribonucleoprotein K (HNRNPK) was first validated as a CLCN3 promoter-binding transcription factor. Mechanistically, HNRNPK knockdown suppressed the promoter activity of CLCN3, thus regulating CLCN3 expression at the transcriptional level, and the binding motif 'GCGAGG' and binding site '-538/-248 bp' were identified. Subsequently, the RNA-seq data illustrated that the primary functions of HNRNPK were similar to those of CLCN3. The results from in vitro and in vivo trials indicated that the expression and function of CLCN3 were regulated by HNRNPK. By isolating primary cancer-associated fibroblasts (CAFs) from human LUAD, we confirmed that decreased extracellular CLCN3 secretion induced by HNRNPK knockdown inhibited CAFs activation and TGF-ß1 production, thus suppressing nuclear HNRNPK expression and LUAD progression in a feedback way. Furthermore, this phenomenon was rescued after the addition of TGF-ß1, revealing that the HNRNPK/CLCN3 axis facilitated LUAD progression through intercellular interactions. Finally, we identified that CLCN3 and HNRNPK were upregulated and correlated with poor prognosis in LUAD patients. Conclusions: HNRNPK/CLCN3 axis facilitates the progression of LUAD through CAF-tumor interaction.

Internationalization of Multinational Companies and Cognitive Differences Across Cultures: A Neuroeconomic Perspective.

From a classical perspective, multinational companies (MNCs) operate based on market determinants, but recent economic discussions emphasize the central role of the human cognitive system in the decision-making process, thereby giving birth to interdisciplinary fields such as behavioral economics and neuroeconomics. While neuroeconomics is still considered an emerging field, hitherto scant studies have investigated the reflection of cultural experiences on the nervous system. Moreover, the interpretation of cultural diversity in the decision-making process, especially from a neuroeconomic perspective, has not been explored. In response, this study, aperspective research in nature, endeavors to research the neural responses to cultural diversity by contextualizing the neuroeconomic discussion within an MNC framework as one of the best multicultural settings. This study demonstrates that the internationalization process of MNCs is established on the cultural identity and integration of the executive. Through a neuroscientific lens, our findings prove that culture is a fundamental determinant of the cognitive makeup; therefore, cultural diversity in MNCs influences their decision-making process. Moreover, the performance of MNCs is driven by cultural harmonization at the executive level. Finally, the study reveals that the novel field of neuroeconomics is instrumental in identifying cultural intuitions on brain cells and the implications on economic decisions even at a corporate level. The main contribution of this study is the initiation of a multidisciplinary merge of the sociocultural and economic as well as neuroscientific fields, as a research center for MNCs' decision-making processes.

Music in the Wound Care Center: Effects on Anxiety Levels and Blood Pressure Measurements in Patients Receiving Standard Care.

BACKGROUND: Chronic wounds require frequent assessment, minor procedures, and dressing changes. Discomfort, anxiety, and stress are commonly reported during treatment procedures. PURPOSE: To examine the effect of music during treatment on post-wound care treatment anxiety levels and blood pressure measurements in patients with chronic wounds. METHODS: This randomized controlled trial was conducted in a wound care center within a nonprofit academic medical center with a before-and-after intervention measurement. A total of 222 consecutive patients were randomly allocated to either an intervention group (n = 112; classical music was played during treatment) or a control group (n = 110; no music was played during treatment) at their scheduled routine outpatient visits. The State-Trait Anxiety Inventory (STAI) was administered and blood pressure measurements were obtained automatically by machine before and after the intervention. Pretreatment and posttreatment scores were compared using the paired t-test in SPSS 25. RESULTS: Patient age and sex did not differ between the intervention and control groups and pretreatment and posttreatment STAI scores; blood pressure measurements were almost identitical in the control group. In the intervention group, statistically significant differences between the pretreatment and posttreatment STAI scores (M = 45.94 and 40.83), systolic blood pressure measurements (M = 141.94 and 135.72), and diastolic blood pressure measurements (M = 70.93 and 66.23) were observed (P < .001). CONCLUSION: In this study, playing classical music in the treatment room during wound care interventions resulted in a significant decrease in patient anxiety scores and blood pressure measurements.

Intra-specific kin recognition contributes to inter-specific allelopathy: A case study of allelopathic rice interference with paddy weeds.

Species interactions and mechanisms affect plant coexistence and community assembly. Despite increasing knowledge of kin recognition and allelopathy in regulating inter-specific and intra-specific interactions among plants, little is known about whether kin recognition mediates allelopathic interference. We used allelopathic rice cultivars with the ability for kin recognition grown in kin versus non-kin mixtures to determine their impacts on paddy weeds in field trials and a series of controlled experiments. We experimentally tested potential mechanisms of the interaction via altered root behaviour, allelochemical production and resource partitioning in the dominant weed competitor, as well as soil microbial communities. We consistently found that the establishment and growth of paddy weeds were more inhibited by kin mixtures compared to non-kin mixtures. The effect was driven by kin recognition that induced changes in root placement, altered weed carbon and nitrogen partitioning, but was associated with similar soil microbial communities. Importantly, genetic relatedness enhanced the production of intrusive roots towards weeds and reduced the production of rice allelochemicals. These findings suggest that relatedness allows allelopathic plants to discriminate their neighbouring collaborators (kin) or competitors and adjust their growth, competitiveness and chemical defense accordingly.

Green synthesis of mesoporous MnNbOx oxide by a liquid induced self-assembly strategy for low-temperature removal of NOx.

Herein, we present a facile, sustainable, and highly efficient ionic liquid induced self-assembly protocol to construct a highly porous MnNbOx oxide with exceptionally high catalytic activity for NOx removal at low temperatures and excellent tolerance to H2O and SO2 poisoning.

Trigonal columnar self-assembly of bent phasmid mesogens.

Three compounds with a bent rod-like aromatic core and with three alkoxy chains at each end were synthesised by click reaction. The compounds form a columnar liquid crystal phase with non-centrosymmetric trigonal p31m symmetry, the columns having a 3-arm star-like cross-section.

Telomerase, Autophagy and Acute Kidney Injury.

In humans, aging is associated with telomere shortening and increased susceptibility to acute kidney injury. Telomerase is essential to maintain telomere length. The fourth generation mice with telomerase deletion have progressive shortening of telomeres. Those mice delayed recovery from ischemia-reperfusion injury, due to an increase in tubule cell senescence and impairment of autophagy, the latter of which may be mediated in part by increased mTOR signaling. © 2016 S. Karger AG, Basel.

[Assessment of Antimalarial Activity of Choline Derivatives against Plasmodium falciparum Growth in vitro by SYBR Green I Method].

OBJECTIVE: To investigate the antimalarial activity of four choline derivatives against Plasmodium falciparum 3D7 strain growth in vitro. METHODS: Four choline derivatives MD [N-dodecyl-N-(2-hydroxyethyl)-N,N- dimethyl ammonium bromide], ED [N-dodecyl-N-(2-hydroxyethyl)-N,N-diethyl ammonium bromide], MT [N-tetradecyl-N- (2-hydroxyethyl)-N,N-dimethyl ammonium bromide], and ET [N-tetradecyl-N-(2-hydroxyethyl)-N,N-diethyl ammonium bromide] were dissolved separately in DMSO at serial concentrations (1-10(5) µmol/L). The solutions were diluted by 1,000-fold with RPMI 1640 medium. 20 µl drug-containing medium and 80 µl P. falciparum-infected erythrocyte suspension (2% final hematocrit and 0.3%-0.5% parasitemia) were added to each well of microtiter plates. Drug effect on the in vitro growth of P. falciparum was measured by SYBR Green I method. The half maximal inhibitory concentration (IC50) was calculated from dose-response curves. Artemisinine served as positive control. RESULTS: Artemisinine, MD, ED, MT, and ET showed different degrees of dose-dependent inhibition on P. falciparum growth. When the MD concentration was above 10 nmol/L, the inhibition rate increased significantly. Both ED and ET showed significant inhibitory effects at high concentrations, with inhibition rate of > 95% when their doses were > 10(4) nmol/L. The IC50 values of MD, ED, MT, and ET were 1 620, 33.9, 116, and 68.9 nmol/L, respectively, all significantly higher than that of artemisinine (5.7 nmol/L) (P < 0.05). CONCLUSION: The four choline derivatives show certain antimalarial activity, which is lower than that of artemisinine. Among the four derivatives, ED has the strongest antimalarial activity against P. falciparum 3D7 strain.

Telomerase deficiency delays renal recovery in mice after ischemia-reperfusion injury by impairing autophagy.

The aged population suffers increased morbidity and higher mortality in response to episodes of acute kidney injury (AKI). Aging is associated with telomere shortening, and both telomerase reverse transcriptase (TerT) and RNA (TerC) are essential to maintain telomere length. To define a role of telomerase deficiency in susceptibility to AKI, we used ischemia/reperfusion injury in wild-type mice or mice with either TerC or TerT deletion. Injury induced similar renal impairment at day 1 in each genotype, as assessed by azotemia, proteinuria, acute tubular injury score, and apoptotic tubular epithelial cell index. However, either TerC or TerT knockout significantly delayed recovery compared with wild-type mice. Electron microscopy showed increased autophagosome formation in renal tubular epithelial cells in wild-type mice but a significant delay of their development in TerC and TerT knockout mice. There were also impeded increases in the expression of the autophagosome marker LC3 II, prolonged accumulation of the autophagosome protein P62, an increase of the cell cycle regulator p16, and greater activation of the mammalian target of rapamycin (mTOR) pathway. The mTORC1 inhibitor, rapamycin, partially restored the ischemia/reperfusion-induced autophagy response, without a significant effect on either p16 induction or tubule epithelial cell proliferation. Thus, muting the maintenance of normal telomere length in mice impaired recovery from AKI, owing to an increase in tubule cell senescence and impairment of mTOR-mediated autophagy.

Renal endothelial dysfunction in diabetic nephropathy.

Endothelial dysfunction has been posited to play an important role in the pathogenesis of diabetic nephropathy (DN). Due to the heterogeneity of endothelial cells (ECs), it is difficult to generalize about endothelial responses to diabetic stimuli. At present, there are limited techniques fordirectly measuring EC function in vivo, so diagnosis of endothelial disorders still largely depends on indirect assessment of mediators arising from EC injury. In the kidney microcirculation, both afferent and efferent arteries, arterioles and glomerular endothelial cells (GEnC) have all been implicated as targets of diabetic injury. Both hyperglycemia per se, as well as the metabolic consequences of glucose dysregulation, are thought to lead to endothelial cell dysfunction. In this regard, endothelial nitric oxide synthase (eNOS) plays a central role in EC dysfunction. Impaired eNOS activity can occur at numerous levels, including enzyme uncoupling, post-translational modifications, internalization and decreased expression. Reduced nitric oxide (NO) bioavailability exacerbates oxidative stress, further promoting endothelial dysfunction and injury. The injured ECs may then function as active signal transducers of metabolic, hemodynamic and inflammatory factors that modify the function and morphology of the vessel wall and interact with adjacent cells, which may activate a cascade of inflammatory and proliferative and profibrotic responses in progressive DN. Both pharmacological approaches and potential regenerative therapies hold promise for restoration of impaired endothelial cells in diabetic nephropathy.

Low nitric oxide bioavailability upregulates renal heparin binding EGF-like growth factor expression.

Decreased nitric oxide bioavailability has an important role in the initiation and progression of diabetic nephropathy, but the underlying mechanisms remain unclear. Here, we found that heparin-binding epidermal growth factor-like growth factor (HB-EGF) expression levels increased in the kidneys of both endothelial nitric oxide synthase (eNOS)-knockout and eNOS-knockout diabetic (Lepr(db/db)) mice as early as at 8 weeks of age. Further increases in expression were only seen in eNOS-knockout diabetic mice and paralleled the progression of glomerulopathy. HB-EGF expression increased in endothelium, podocytes, and tubular epithelial cells. In cultured glomerular endothelial cells, the nitric oxide synthase inhibitors NG-nitro-L-arginine methyl ester (L-NAME) or L-N5-(1-iminoethyl) ornithine increased HB-EGF protein expression. Administration of L-NAME dramatically increased renal HB-EGF expression and urinary HB-EGF excretion in diabetic mice. On the other hand, replenishing nitric oxide with sodium nitrate in eNOS-knockout diabetic mice reduced urinary HB-EGF excretion and inhibited the progression of diabetic nephropathy. Furthermore, specific deletion of HB-EGF expression in the endothelium attenuated renal injury in diabetic eNOS-knockout mice. Thus, our results suggest that decreased nitric oxide bioavailability leads to increased HB-EGF expression, which may be an important mediator of the resulting progressive diabetic nephropathy in eNOS-knockout diabetic mice.

Improvement of endothelial nitric oxide synthase activity retards the progression of diabetic nephropathy in db/db mice.

Impaired endothelial nitric oxide synthase (eNOS) activity may be involved in the pathogenesis of diabetic nephropathy. To test this, we used the type 2 diabetic db/db mouse (BKS background) model and found impaired eNOS dimerization and phosphorylation along with moderate glomerular mesangial expansion and increased glomerular basement membrane (GBM) thickness at 34 weeks of age. Cultured murine glomerular endothelial cells exposed to high glucose had similar alterations in eNOS dimerization and phosphorylation. Treatment with sepiapterin, a stable precursor of the eNOS cofactor tetrahydrobiopterin, or the nitric oxide precursor L-arginine corrected changes in eNOS dimerization and phosphorylation, corrected permeability defects, and reduced apoptosis. Sepiapterin or L-arginine, administered to db/db mice from weeks 26 to 34, did not significantly alter hyperfiltration or affect mesangial expansion, but reduced albuminuria and GBM thickness, and decreased urinary isoprostane and nitrotyrosine excretion (markers of oxidative stress). Although there was no change in glomerular eNOS monomer expression, both sepiapterin and L-arginine partially reversed the defect in eNOS dimerization and phosphorylation. Hence, our results support an important role for eNOS dysfunction in diabetes and suggest that sepiapterin supplementation might have therapeutic potential in diabetic nephropathy.

Integrin α1/Akita double-knockout mice on a Balb/c background develop advanced features of human diabetic nephropathy.

Animal models that mimic human diabetic nephropathy are useful to identify key factors in pathogenesis of this disease, as well as the development of new therapies. Several mouse models of diabetes have features of human diabetic nephropathy, yet none of these completely fulfill the Animal Models of Diabetes Complications Consortium criteria and completely reproduce pathological and functional features of the human disease. The Akita mouse carries a mutation in the insulin-2 gene and, to date, only survives as heterozygotes that develop spontaneous type 1 diabetes. Here we show that Akita mice with mutation of both insulin-2 alleles (Akita knockout (KO)) survive if crossed onto the Balb/c background. These mice develop hyperglycemia, more severe albuminuria, and mesangial sclerosis compared with heterozygous mice on the same genetic background. Interestingly, crossing these AkitaKO mice with integrin α1KO mice, a model of exacerbated glomerulosclerosis after injury and also on the Balb/c background, resulted in a 16-fold increase in albuminuria, significant mesangial matrix expansion, nodular and diffuse glomerulosclerosis, and a 2-fold increase in glomerular basement membrane thickening when compared with nondiabetic mice. Moreover, a significant decline in glomerular filtration was evident in the α1KOAkitaKO mice at 6 months of age. Thus, the integrin α1KOAkitaKO Balb/c mouse represents a promising model presenting with most features of human diabetic nephropathy.

Podocyte COX-2 exacerbates diabetic nephropathy by increasing podocyte (pro)renin receptor expression.

Diabetic nephropathy (DN) increases podocyte cyclooxygenase-2 (COX-2) expression, and COX-2 inhibition reduces proteinuria and glomerular injury in animal models of diabetes. To investigate the role of podocyte COX-2 in development of diabetic nephropathy, we employed a streptozotocin model of diabetic mellitus in wild-type and transgenic mice expressing COX-2 selectively in podocytes. Progressive albuminuria developed only in diabetic COX-2 transgenic mice despite hyperglycemia, BP, and GFR being similar to those in wild-type mice. Transgenic mice also manifested significant foot-process effacement, moderate mesangial expansion, and segmental thickening of the glomerular basement membrane. In cultured podocytes overexpressing COX-2, high glucose induced cell injury and increased both expression of the pro(renin) receptor and activation of the renin-angiotensin system. Downregulation of the (pro)renin receptor attenuated the injury induced by high glucose. In vivo, podocyte pro(renin) receptor expression increased in diabetic COX-2-transgenic mice, and treatment with a COX-2 inhibitor abrogated the upregulation of (pro)renin receptor and reduced albuminuria, foot-process effacement, and mesangial matrix expansion. In summary, these results demonstrate that increased expression of podocyte COX-2 predisposes to diabetic glomerular injury and that the (pro)renin receptor may be one mediator for this increased susceptibility to injury.

The glomerulus--a view from the outside--the podocyte.

In the past decade, podocyte research has been greatly aided by the development of powerful new molecular, cellular and animal tools, leading to elucidation of an increasing number of proteins involved in podocyte function and identification of mutated genes in hereditary glomerulopathies. Accumulating evidence indicates that podocyte disorders may not only underlie these hereditary glomerulopathies but also play crucial role in a broad spectrum of acquired glomerular diseases. Genetic susceptibility, environmental influence and systemic responses are all involved in the mediation of the pathogenesis of podocytopathies. Injured podocytes may predisopose to further injury of other podocytes and other adjacent/distant renal cells in a vicious cycle, leading to inexorable progression of glomerular injury. The classic view is that podocytes have a limited ability to proliferate in the normal mature kidney. However, recent research in rodents has provided suggestive evidence for podocyte regeneration resulting from differentiation of progenitor cells within Bowman's capsule.

Distinct roles for basal and induced COX-2 in podocyte injury.

Transgenic mice that overexpress cyclooxygenase-2 (COX-2) selectively in podocytes are more susceptible to glomerular injury by adriamycin and puromycin (PAN). To investigate the potential roles of COX-2 metabolites, we studied mice with selective deletion of prostanoid receptors and generated conditionally immortalized podocyte lines from mice with either COX-2 deletion or overexpression. Podocytes that overexpressed COX-2 were virtually indistinguishable from wild-type podocytes but were significantly more sensitive to PAN-induced injury, produced more prostaglandin E(2) and thromboxane B(2), and had greater expression of prostaglandin E(2) receptor subtype 4 (EP(4)) and thromboxane receptor (TP). Treatment of COX-2-overexpressing podocytes with a TP antagonist reduced apoptosis, but treatment with an EP(4) antagonist did not. In contrast, podocytes from COX-2-knockout mice exhibited increased apoptosis, markedly decreased cell adhesion, and prominent stress fibers. In vivo, selective deletion of podocyte EP(4) did not alter the increased sensitivity to adriamycin-induced injury observed in mice overexpressing podocyte COX-2. In contrast, genetic deletion of TP in these mice prevented adriamycin-induced injury, with attenuated albuminuria and foot process effacement. These results suggest that basal COX-2 may be important for podocyte survival, but overexpression of podocyte COX-2 increases susceptibility to podocyte injury, which is mediated, in part, by activation of the thromboxane receptor.