Alleviation of microplastic toxicity in soybean by arbuscular mycorrhizal fungi: Regulating glyoxalase system and root nodule organic acid.

Microplastic accumulation in the soil-plant system can stress plants and affect products quality. Currently, studies on the effect of microplastics on plants are not consistent and underlying molecular mechanisms are yet unknown. Here for the first time, we performed a study to explore the molecular mechanism underlying the growth of soybean plants in soil contaminated with various types of microplastics (PS and HDPE) and arbuscular mycorrhizal fungi (AMF) (presence/absence). Our results revealed that a dose-dependent decline was observed in plant growth, chlorophyll content, and yield of soybean under MPs stress. The addition of MPs resulted in oxidative stress closely related to hydrogen peroxide generation (H2O2), methylglyoxal (MG) levels, lipid peroxidation (MDA), and lipoxygenase (LOX). In contrast, MPs addition enhanced mycorrhizal colonization and dependency relative to control while the rubisco and root activity declined. All the genes (GmHMA13 and GmHMA19) were downregulated in the presence of MPs except GmHMA18 in roots. AMF inoculation alleviated MPs-induced phytotoxic effects on colonization, rubisco activity, root activity and restored the growth of soybean. Under MPs exposure, AMF inoculation induced plant defense system via improved regulation of antioxidant enzymes, ascorbate, glutathione pool, and glyoxalase system. AMF upregulated the genes responsible for metals uptake in soybean under MPs stress. The antioxidant and glyoxalase systems coordinated regulation expressively inhibited the oxidative and carbonyl stress at both MPs types. Hence, AMF inoculation may be considered an effective approach for minimizing MPs toxicity and its adverse effects on growth of soybean grown on MPs-contaminated soils.

Straw incorporation into microplastic-contaminated soil can reduce greenhouse gas emissions by enhancing soil enzyme activities and microbial community structure.

Microplastic (MP) contamination poses a substantial threat to agroecosystems, disrupting soil properties, nutrient cycles, and microbial communities and ultimately affecting plant growth and ecosystem resilience. The effects of straw addition on the storage of soil organic carbon (SOC) and greenhouse gas emissions have been extensively explored, but these effects have not been examined in the context of MP contamination. To assess the impacts of legume straw and polyethylene microplastics on SOC fractions and carbon dioxide (CO2) and nitrous oxide (N2O) emissions, 7-month soil incubation experiments were performed. The results revealed that the inclusion of legume straw in soil considerably increased microbial SOC compared to the control. However, straw addition to MP-contaminated soil reduced microbial SOC compared to that in soil containing only straw. In contrast, the addition of straw to MP-contaminated soil elevated (+44%) the SOC mineral relative to the sole application of straw. Intriguingly, straw incorporation into MP-contaminated soil reduced microbial biomass carbon and nitrogen relative to soil containing only straw. Straw addition to MP-contaminated soil enhanced the nitrification activity and reduced the relative expression of AOBamoABC gene compared to sole straw-incorporated soil and the control. Greenhouse gas emissions were also modulated; for instance, straw incorporation into MP-contaminated soil reduced CO2 and N2O emissions by -11% and -46%, compared to straw incorporation alone. The urease and phosphatase activities were decreased (-58% and -12%) in the MP-polluted soil with straw incorporation compared with those in the soil in which only straw was applied. However, invertase and catalase activities were upregulated in the straw-incorporated soil contaminated with MPs. Straw addition in the MP-polluted soil considerably enhanced (+2%) the microbial community structure (indicated by PLFA) compared to the sole straw application. These results provide a comprehensive perspective on the role of legume straw incorporation in addressing MP pollution, showcasing its potential for sustainable agricultural practices in the face of evolving environmental challenges.

Mycorrhizosphere bacteria inhibit greenhouse gas emissions from microplastics contaminated soil by regulating soil enzyme activities and microbial community structure.

Microplastics (MPs) accumulation in terrestrial ecosystems can affect greenhouse gases (GHGs) production by altering microbial and soil structure. Presently, research on the MPs effect on plants is not consistent, and underlying molecular mechanisms associated with GHGs are yet unknown. For the first time, we conducted a microcosm study to explore the impact of MPs addition (Raw vs. aged) and Trichoderma longibrachiatum and Bacillus subtilis inoculation (Sole vs. combination) on GHGs emission, soil community structure, physiochemical properties, and enzyme activities. Our results indicated that the addition of aged MPs considerably enhanced the GHGs emissions (N2O (+16%) and CO2 (+21%), respectively), C and N cycling gene expression, microbial biomass carbon, and soil physiochemical properties than raw MPs. However, the soil microbial community structure and enzyme activities were enhanced in raw MPs added treatments, irrespective of the MPs type added to soil. However, microbial inoculation significantly reduced GHGs emission by altering the expression of C and N cycling genes in both types of MPs added treatments. The soil microbial community structure, enzymes activities, physiochemical properties and microbial biomass carbon were enhanced in the presence of microbial inoculation in both type of MPs. Among sole and combined inoculation of Trichoderma and Bacillus subtilis, the co-applied Trichoderma and Bacillus subtilis considerably reduced the GHGs emission (N2O (-64%) and CO2 (-61%), respectively) by altering the expression of C and N cycling genes regardless of MPs type used. The combined inoculation also enhanced soil enzyme activities, microbial community structure, physiochemical properties and microbial biomass carbon in both types of MPs treatment. Our findings provide evidence that polyethylene MPs likely pose a high risk of GHGs emission while combined application of Trichoderma and Bacillus subtilis significantly reduced GHGs emission by altering C and N cycling gene expression, soil microbial community structure, and enzyme activities under MPs pollution in a terrestrial ecosystem.

Delineating Marker-Trait Associations for Fusarium Wilt in Chickpea Using the Axiom® CicerSNP Array.

Fusarium wilt (FW) caused by Fusarium oxysporum f. sp. ciceri is a devastating disease of chickpea (Cicer arietinum). To identify promising resistant genotypes and genomic loci for FW resistance, a core set of 179 genotypes of chickpea was tested for FW reactions at the seedling and reproductive stages under field conditions and controlled conditions in the greenhouse. Our results revealed that at the seedling stage, most of the genotypes were resistant, whereas at the reproductive stage, most of the genotypes were susceptible. Genotyping using a 50K Axiom® CicerSNP Array and trait data of FW together led to the identification of 26 significant (P ≤ E-05) marker-trait associations (MTAs) for FW resistance. Among the 26 MTAs, 12 were identified using trait data recorded in the field (three at the seedling and nine at the reproductive stage), and 14 were identified using trait data recorded under controlled conditions in the greenhouse (six at the seedling and eight at the reproductive stage). The phenotypic variation explained by these MTAs varied from 11.75 to 15.86%, with an average of 13.77%. Five MTAs were classified as major, explaining more than 15% of the phenotypic variation for FW, and two were declared stable, being identified in two environments. One of the promising stable and major MTAs (Affx_123280060) detected in field conditions at the reproductive stage was also detected in greenhouse conditions at the seedling and reproductive stages. The stable and major (>15% PVE) MTAs can be used in chickpea breeding programs.

Transition-Metal-Catalyzed Directing Group Assisted (Hetero)aryl C-H Functionalization: Construction of C-C/C-Heteroatom Bonds.

Transition-metal-catalyzed C-H functionalization is one of the fascinating scientific fronts in organic synthesis for the formation of conjugated arenes and has emerged as a benchmark to revolutionize the synthetic enterprise since past decades. In this realm, chelation-guided functionalization of C-H bonds using an exogenous directing group has received considerable attention recently for the expedient regioselective construction of C-C and C-heteroatom bonds as an efficient and sustainable alternative. This article outlines our contribution towards a wide variety of transformations that have been achieved by the directed C-H functionalization through the fine tuning of catalytic systems.

Identification of differentially expressed genes and pathways in isonuclear kenaf genotypes under salt stress.

Salinity is a potential abiotic stress and globally threatens crop productivity. However, the molecular mechanisms underlying salt stress tolerance with respect to cytoplasmic effect, gene expression, and metabolism pathway under salt stress have not yet been reported in isonuclear kenaf genotypes. To fill this knowledge gap, growth, physiological, biochemical, transcriptome, and cytoplasm changes in kenaf cytoplasmic male sterile (CMS) line (P3A) and its iso-nuclear maintainer line (P3B) under 200 mM sodium chloride (NaCl) stress and control conditions were analyzed. Salt stress significantly reduced leaf soluble protein, soluble sugars, proline, chlorophyll content, antioxidant enzymatic activity, and induced oxidative damage in terms of higher MDA contents in both genotypes. The reduction of these parameters resulted in a reduced plant growth compared with control. However, P3A was relatively more tolerant to salt stress than P3B. This tolerance of P3A was further confirmed by improved physio-biochemical traits under salt stress conditions. Transcriptome analysis showed that 4256 differentially expressed genes (DEGs) between the two genotypes under salt stress were identified. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that photosynthesis, photosynthesis antenna-protein, and plant hormone signal transduction pathways might be associated with the improved NaCl stress tolerance in P3A. Conclusively, P3A cytoplasmic male sterile could be a potential salt-tolerant material for future breeding program of kenaf and can be used for phytoremediation of salt-affected soils. These data provide a valuable resource on the cytoplasmic effect of salt-responsive genes in kenaf and salt stress tolerance in kenaf.

The transition-metal-catalyzed stereoselective ring-expansion of vinylaziridines and vinyloxiranes.

The transition-metal-aided stereoselective construction of sp3-carbon-rich heterocyclic scaffolds using strained-ring systems has received considerable attention in recent years due to the prominent presence of these scaffolds in myriad natural products, bioactive molecules, and pharmaceutical components. In this area, the catalytic ring-enlargement of vinylaziridines and vinyloxiranes plays a predominant role when synthesizing high sp3-content biorelevant heterocyclic compounds. This article aims to portray recent advancements in the ring-expansion of vinylaziridines and vinyloxiranes for accessing densely functionalized stereoselective heterocycles that have been developed over the past five years, with an emphasis on the substrate scopes and mechanistic insights into the key methodologies, and it is arranged based on the transition metals used and the ring sizes of the heterocyclic scaffolds.

Biosynthesis and characterization of titanium dioxide nanoparticles and its effects along with calcium phosphate on physicochemical attributes of wheat under drought stress.

Drought stress is reducing the production of crops globally. This research was designed to evaluate the role of titanium dioxide (TiO2 NPs) nanoparticles and calcium phosphate on wheat facing drought stress. TiO2 NPs were prepared by green synthesis and their characterization (by UV-visible spectroscopy, scanning electron microscopy (SEM), and energy-dispersive X-ray (EDX)) was also done. The results showed that TiO2 NPs worked efficiently and improved plant growth under drought. However, the best results were obtained from combined applications of 40 ppm TiO2 NPs and 40 ppm calcium phosphate on plants. They increased root length (33%), shoot length (53%), fresh weight (48%), and dry weight (44%) of wheat as compared to control. The physiological parameters including chlorophyll content, relative water content, membrane stability index, and osmolyte content (proline and sugar) were also improved. The increase in superoxide dismutase, peroxidase and, catalase activity by the combined application of TiO2 NPs and calcium phosphate was 83% and 78%, 74% and 52%, 81%, and 67% in Pakistan-13 and Zincol-16 respectively, as compared to untreated drought exposed plants. They also enhanced the nutrients uptake (including potassium, phosphorus, and nitrogen) that ultimately improved plant biomass. They also maintained the level of growth hormones in plants. These hormones regulate cellular processes and are responsible for germination, development, and plant reaction in drought stress. The increase in the yield was also significant, hence it is recommended that the 40 ppm concentration of TiO2 NPs along with calcium phosphate improves the productivity of wheat under drought stress.

Lack of trusted diagnostic tools for undetermined male infertility.

Semen analysis is the cornerstone of evaluating male infertility, but it is imperfect and insufficient to diagnose male infertility. As a result, about 20% of infertile males have undetermined infertility, a term encompassing male infertility with an unknown underlying cause. Undetermined male infertility includes two categories: (i) idiopathic male infertility-infertile males with abnormal semen analyses with an unknown cause for that abnormality and (ii) unexplained male infertility-males with "normal" semen analyses who are unable to impregnate due to unknown causes. The treatment of males with undetermined infertility is limited due to a lack of understanding the frequency of general sperm defects (e.g., number, motility, shape, viability). Furthermore, there is a lack of trusted, quantitative, and predictive diagnostic tests that look inside the sperm to quantify defects such as DNA damage, RNA abnormalities, centriole dysfunction, or reactive oxygen species to discover the underlying cause. To better treat undetermined male infertility, further research is needed on the frequency of sperm defects and reliable diagnostic tools that assess intracellular sperm components must be developed. The purpose of this review is to uniquely create a paradigm of thought regarding categories of male infertility based on intracellular and extracellular features of semen and sperm, explore the prevalence of the various categories of male factor infertility, call attention to the lack of standardization and universal application of advanced sperm testing techniques beyond semen analysis, and clarify the limitations of standard semen analysis. We also call attention to the variability in definitions and consider the benefits towards undetermined male infertility if these gaps in research are filled.

Selection and screening of drought tolerant high yielding chickpea genotypes based on physio-biochemical indices and multi-environmental yield trials.

BACKGROUND: Chickpea is one of the major legume crops being cultivated in the arid and semi-arid regions of Pakistan. It is mainly grown on the marginal areas where, terminal drought stress is one of the serious threats to its productivity. For defining the appropriate selection criteria for screening drought tolerant chickpea genotypes, present study was conducted. Distinct chickpea germplasm was collected from different pulses breeding institutes of Pakistan and evaluated for drought tolerance at germination and early seedling stages, furthermore, at late vegetative growth stages physiochemical traits and multi-environment yield performance were also tested. RESULTS: Chickpea genotypes under different environments, were significantly varied for different seedling traits, physio-chemical attributes and seed yield. Genotypes showing drought tolerance by performing better at an early seedling stages were not correspondingly high yielding. Screening for drought tolerance on seed yield basis is the most appropriate trait to develop the drought tolerant as well as high yielding chickpea genotypes. Results confirmed that traits of early growth stages were not reflecting the drought tolerance at terminal growth stages and also did not confer high yielding. NIAB-rain fed environment proved ideal in nature to screen the chickpea genotypes whereas, NIAB-lysimeter and Kalur Kot was least effective for selecting genotypes with high seed yield. Genotypes D0091-10, K010-10, D0085-10, K005-10, D0078-10, 08AG016, 08AG004, D0080-10, 09AG002, K002-10 and D0099-10 were high yielding and drought tolerant based on their performance across multiple hotspot environments. CONCLUSIONS: The selected genotypes are intended for further evaluation for varietal approval to recommend for general cultivation on farmer fields in drought hit areas of Pakistan. Among physio-biochemical traits, higher proline, glycine betain, RWC and CMS were reflecting the higher capability to tolerate the drought stress in chickpea. Drought sensitive genotypes (K0037-10, 2204, K0052-10, 09AG015, K0042-10, CM709/06, K0068-10, K004-10, K0026-10 and K0063-10) were also identified in present study which were resourceful asset for using as contrasting parents in hybridization programs. To our knowledge, this is first report using an integrated approach involving, physio-biochemical indices, and multi-environmental yield trials, for comparison, screening and selection of chickpea genotypes for drought tolerance.

Cp*Co(III)-Catalyzed C-7 C-C Coupling of Indolines with Aziridines: Merging C-H Activation and Ring Opening.

A Cp*Co(III)-catalyzed directing group-assisted C7 C-C coupling of indolines with aziridines has been developed by merging C-H activation and ring opening. The use of cobalt catalyst, detection of a Co(III) intermediate, and late-stage removal of the directing group are important practical features.

Preparation of CTCNFs/Co9S8 hybrid nanofibers with enhanced microwave absorption performance.

A three-step synthesis strategy has been applied to the preparation of Co9S8-loaded tubular carbon nanofibers (CTCNFs/Co9S8 hybrid nanofibers) with excellent microwave absorbing ability. Firstly, tubular polymer nanofibers (TPNFs) are synthesized using the confined self-condensation method that we developed. Afterwards, TPNFs are converted into surface carboxylated tubular carbon nanofibers (CTCNFs) by carbonization and subsequent acidification processes. Finally, a hydrothermal method is used for the controllable growth of Co9S8 nanoparticles on CTCNFs, and a series of CTCNFs/Co9S8 hybrid nanofibers with different Co9S8 loading are obtained. The prepared CTCNFs/Co9S8 hybrid nanofibers possess abundant effective interface and defect dipoles, which will lead to stronger polarization. Using the strategy of enhancing dielectric loss, the microwave dissipation ability of CTCNFs/Co9S8 hybrid nanofibers has been significantly improved, showing an excellent low-frequency absorbing performance with a minimum reflection loss of -46.81 dB@5.3 GHz. In addition, the composition, structure and properties of nanofibers have been systematically characterized. The Co9S8 loading on CTCNFs and the filler content of CTCNFs/Co9S8 hybrid nanofibers in matrix are studied and optimized. The microwave attenuation mechanism is also explained.

Effects of intravenous immunoglobulin therapy and Fc gamma receptor polymorphisms on BK virus nephropathy in kidney transplant recipients.

BACKGROUND: BK virus nephropathy (BKVN) is a major complication in kidney transplant patients. This study aimed to investigate the efficacy of intravenous immunoglobulin (IVIG) therapy against persistent BKVN and to evaluate the association between persistent BKVN and Fc gamma receptor (FcγR) single nucleotide polymorphisms (SNPs). METHODS: A total of 86 patients out of 279 kidney recipients with BKVN were investigated in a single-center retrospective study. The majority of 86 patients were Hispanic and Asian (69.8% and 17.4%). Patients were treated with adjunctive IVIG or standard therapy (controls). Subgroup analysis was performed between IVIG responders and non-responders. BK virus copy number and serum creatinine (SCr) were measured to evaluate the impact of IVIG. We analyzed the association between the response to IVIG and genotype at FcγR3A (rs396991) and FcγR2A (rs1801274) SNPs. RESULTS: Viral load in IVIG non-responders was significantly higher than in responders at the time of diagnosis (219 271.8 vs 29 816.3 copies/mL, P = .015) and after 6 months of IVIG use (12 789.5 vs 1369.5 copies/mL, P < .001). However, analyses SNP of FcγR2A (OR = 0.807, CI = 0.435-1.496 P = .495) and FcγR3A (OR = 0.997, CI = 0.505-1.970, P = .993) SNPs showed no significant differences between the 2 groups. CONCLUSION: IVIG appears to lower BK DNA viral load significantly in patients with persistent BKVN. However, no associations were identified between BKVN and FcγR2A or FcγR3A SNPs.

MRI and MRS of intact perfused cancer cell metabolism, invasion, and stromal cell interactions.

Because of the spatial and temporal heterogeneities of cancers, technologies to investigate cancer cells and the consequences of their interactions with abnormal physiological environments, such as hypoxia and acidic extracellular pH, with stromal cells, and with the extracellular matrix, under controlled conditions, are valuable to gain insights into the functioning of cancers. These insights can lead to an understanding of why cancers invade and metastasize, and identify effective treatment strategies. Here we have provided an overview of the applications of MRI/MRS/MRSI to investigate intact perfused cancer cells, their metabolism and invasion, and their interactions with stromal cells and the extracellular matrix.

Cp*Co(III)-Catalyzed Regioselective C2 Amidation of Indoles Using Acyl Azides.

A cobalt-catalyzed C2-selective amidation of indoles using acyl azides has been accomplished. Isotope experiments suggest that C-H activation is reversible. The use of sustainable Co catalysis, functional group diversity, substrate scope, and regioselectivity are the important practical features.

Molecular causes of elevated phosphoethanolamine in breast and pancreatic cancer cells.

Elevated phosphoethanolamine (PE) is frequently observed in MRS studies of human cancers and xenografts. The role of PE in cell survival and the molecular causes underlying this increase are, however, relatively underexplored. In this study, we investigated the roles of ethanolamine kinases (Etnk-1 and 2) and choline kinases (Chk-α and ß) in contributing to increased PE in human breast and pancreatic cancer cells. We investigated the effect of silencing Etnk-1 and Etnk-2 on cell viability as a potential therapeutic strategy. Both breast and pancreatic cancer cells showed higher PE compared with their nonmalignant counterparts. We identified Etnk-1 as a major cause of the elevated PE levels in these cancer cells, with little or no contribution from Chk-α, Chk-ß, or Etnk-2. The increase of PE observed in pancreatic cancer cells in culture was replicated in the corresponding tumor xenografts. Downregulation of Etnk-1 with siRNA resulted in cell cytotoxicity that correlated with PE levels in breast and pancreatic cancer cells. Etnk-1 may provide a potential therapeutic target in breast and pancreatic cancers.

Omics Approaches for Engineering Wheat Production under Abiotic Stresses.

Abiotic stresses greatly influenced wheat productivity executed by environmental factors such as drought, salt, water submergence and heavy metals. The effective management at the molecular level is mandatory for a thorough understanding of plant response to abiotic stress. Understanding the molecular mechanism of stress tolerance is complex and requires information at the omic level. In the areas of genomics, transcriptomics and proteomics enormous progress has been made in the omics field. The rising field of ionomics is also being utilized for examining abiotic stress resilience in wheat. Omic approaches produce a huge amount of data and sufficient developments in computational tools have been accomplished for efficient analysis. However, the integration of omic-scale information to address complex genetics and physiological questions is still a challenge. Though, the incorporation of omic-scale data to address complex genetic qualities and physiological inquiries is as yet a challenge. In this review, we have reported advances in omic tools in the perspective of conventional and present day approaches being utilized to dismember abiotic stress tolerance in wheat. Attention was given to methodologies, for example, quantitative trait loci (QTL), genome-wide association studies (GWAS) and genomic selection (GS). Comparative genomics and candidate genes methodologies are additionally talked about considering the identification of potential genomic loci, genes and biochemical pathways engaged with stress resilience in wheat. This review additionally gives an extensive list of accessible online omic assets for wheat and its effective use. We have additionally addressed the significance of genomics in the integrated approach and perceived high-throughput multi-dimensional phenotyping as a significant restricting component for the enhancement of abiotic stress resistance in wheat.

Pattern Of Presentation Among Adults Hospitalized With Dengue Disease.

BACKGROUND: Dengue is a mosquito born viral infection that has rapidly spread in the world particularly in Southeast Asia. The aim of this hospital based study was to see the demographic, clinical and laboratory characteristics in adults with dengue infection in Hazara region of Northern Pakistan. METHODS: This is a descriptive study. Clinical, laboratory and demographic information were collected from adult patients with suspected dengue infection (n=100) and then managed in one of medical units of tertiary care hospital in Abbottabad from August to October 2015. RESULTS: Total number of patients was 100, 78 were male and 22 were female. 49 patients were in age group from 21 to 40 years. Most patients were from Mansehra district (69), followed by Haripur (11), Abbottabad (11), Battagram (06) and Kohistan (03). Common clinical features were fever (100%), body aches (95%), headache (94%), chills (87%), and anorexia (86%), haemorrhagic tendencies (12%), rash (05%), and sore throat (03%). Thrombocytopenia was observed in 98%, leucopoenia in 25%, high Aminotransferases (ALT) in 67%, Ns1 antigen positive 66%, negative 18% and unknown 16%. IgM Antibodies against Dengue Virus was positive 67%, negative 19% and were unknown in 14%, IgG antibodies positive in 54%, negative 32% and were unknown in 14%. CONCLUSIONS: We concluded in our study that presentation of dengue infection is same as in other Southeast Asian countries; however, the disease is more prevalent in cities located on plain than hilly areas.

Lymphatic endothelial cells actively regulate prostate cancer cell invasion.

Lymphatic vessels serve as the primary route for metastatic spread to lymph nodes. However, it is not clear how interactions between cancer cells and lymphatic endothelial cells (LECs), especially within hypoxic microenvironments, affect the invasion of cancer cells. Here, using an MR compatible cell perfusion assay, we investigated the role of LEC-prostate cancer (PCa) cell interaction in the invasion and degradation of the extracellular matrix (ECM) by two human PCa cell lines, PC-3 and DU-145, under normoxia and hypoxia, and determined the metabolic changes that occurred under these conditions. We observed a significant increase in the invasion of ECM by invasive PC-3 cells, but not poorly invasive DU-145 cells when human dermal lymphatic microvascular endothelial cells (HMVEC-dlys) were present. Enhanced degradation of ECM by PC-3 cells in the presence of HMVEC-dlys identified interactions between HMVEC-dlys and PCa cells influencing cancer cell invasion. The enhanced ECM degradation was partly attributed to increased MMP-9 enzymatic activity in PC-3 cells when HMVEC-dlys were in close proximity. Significantly higher uPAR and MMP-9 expression levels observed in PC-3 cells compared to DU-145 cells may be one mechanism for increased invasion and degradation of matrigel by these cells irrespective of the presence of HMVEC-dlys. Hypoxia significantly decreased invasion by PC-3 cells, but this decrease was significantly attenuated when HMVEC-dlys were present. Significantly higher phosphocholine was observed in invasive PC-3 cells, while higher glycerophosphocholine was observed in DU-145 cells. These metabolites were not altered in the presence of HMVEC-dlys. Significantly increased lipid levels and lipid droplets were observed in PC-3 and DU-145 cells under hypoxia reflecting an adaptive survival response to oxidative stress. These results suggest that in vivo, invasive cells in or near lymphatic endothelial cells are likely to be more invasive and degrade the ECM to influence the metastatic cascade. Copyright © 2016 John Wiley & Sons, Ltd.

Switching STudy of Kidney TRansplant PAtients with Tremor to LCP-TacrO (STRATO): an open-label, multicenter, prospective phase 3b study.

Tremor is a common side effect of tacrolimus correlated with peak-dose drug concentration. LCPT, a novel, once-daily, extended-release formulation of tacrolimus, has a reduced Cmax with comparable AUC exposure, requiring a ~30% dose reduction vs. immediate-release tacrolimus. In this phase 3b study, kidney transplant recipients (KTR) on a stable dose of tacrolimus and with a reported clinically significant tremor were offered a switch to LCPT. Tremor pre- and seven d post-conversion was evaluated by independent, blinded movement disorder neurologists using the Fahn-Tolosa-Marin (FTM) scale and by an accelerometry device; patients completed the QUEST (quality of life in essential tremor) and the Patient Global Impression of Change. There were 38 patients in the mITT population. A statistically and clinically significant improvement in tremor (FTM score, amplitude as measured by the accelerometry device and QOL [p-values < 0.05]) resulted post-conversion. Change in QUEST was significantly (p = 0.006) correlated (R = 0.44) with change in FTM; 78.9% of patients reported an improvement after switching to LCPT (p < 0.0005). To our knowledge this is the first trial in KTR that utilizes a sophisticated and reproducible measurement of tremor. Results suggest LCPT is associated with clinically meaningful improvement of hand tremor and may be an alternative management approach in lieu of further dose reduction of immediate-release tacrolimus for patients experiencing tremor.