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1.
Nanotechnology ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32422619

##### RESUMO

The triphenylene based discotic liquid crystal (TP) molecules are rich in $\pi$-electrons which facilitate $\pi$-stacking interaction of the molcules leading to formation of one dimensional nanowires. These nanowires can assemble to form nanoribbons due to a lateral cohesive force among the nanowires. The flat nanoribons undergo a morphological transformation due to incorporation of silver nanoparticles (SNP) into the matrix of TP molecules. The presence of SNP induces a chiral twisting to nanoribbons and therefore the flat nanoribbons transform to helical nanoribbon structure. The global chiral structure exhibited by the composition of achiral constituents is due to creation of topological defects like disclination and dislocation. These defects can lead to a geometrical frustration in the nanoribbons which relaxes with the formation of twisted helical nanoribbons. A minor change in morphology of the supramolecular assembly can have a remarkable effect on the physicochemical properties of the nanoribbons. In this article, we demonstrate that even a minor change in the geometry of aliphatic chains on the surface of nanoribbons can be employed for sensing organic solvents viz. acetone and ethanol. The sensing was performed at the room temperature. The relative humidity has no effect on the sensing response.

2.
BMC Public Health ; 20(1): 628, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375727

##### RESUMO

BACKGROUND: Globally, there has been an exponential rise in smartphone use and selfie taking among youth. To make selfies exciting, dangerous selfies are often taken that may lead to catastrophic consequences, including death. This study aims to estimate the prevalence of dangerous selfies and to determine the factors associated with dangerous selfies among medical and nursing students in India. METHODS: The study was conducted at the All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India, in April-August 2018. The inclusion criteria were students enrolled in the Bachelor of Medicine and Bachelor of Surgery (MBBS) and nursing courses of AIIMS, Bhubaneswar. Students who did not use smartphones were excluded from the study. The interview schedule and Selfitis Behaviour Scale (SBS) were used to collect information on sociodemographic variables, smartphone use and variables related to selfies and dangerous selfies. Forward stepwise logistic regression was undertaken with the probability of entry and removal as 0.05 and 0.10, respectively. RESULTS: Of 633 eligible participants, 595 were included in the study. The mean (SD) age of the participants was 21.2 (1.6) years. More than half (56.8%) of the participants were female, 384 (64.5%) were medical students and 211 (35.5%) were nursing students. Nearly two-thirds of the participants (70.6%) preferred to take selfie. One hundred thirty three (40.3%) of the participants posted selfies on social media daily. The prevalence of dangerous selfies was 8.74% (95% CI: 6.73-11.28). Eight injury episodes while taking selfies were reported by seven (1.2%) participants. Being male (AOR 4.96, 95% CI 2.53-9.74), posting selfies on social media daily (AOR 3.33, 95% CI 1.71-6.47) and an SBS score > 75 (AOR 4.97, 95% CI 1.43-17.28) were independent predictors of dangerous selfies. CONCLUSION: Nearly one in ten medical and nursing students reported having taken a dangerous selfie, and one in one hundred reported having been injured while attempting to take a selfie. Being male, posting selfies on social media daily and an SBS score > 75 were independent predictors of dangerous selfies. Further research is required to identify the community burden of dangerous selfies and to develop strategies to prevent selfie-related fatalities among youths.

3.
J Contemp Dent Pract ; 21(1): 97-104, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32381809

##### RESUMO

AIM: The aim of this study is to establish a proportion between the inferior border of mandible and lower edge of the mental foramen and inferior border of mandible to occlusal plane for dentulous subjects and to evaluate the validity of this proportion in orienting the occlusal plane for edentulous subjects. MATERIALS AND METHODS: The occlusal plane was evaluated in the selected 50 dentulous and edentulous subjects for its relation to the mental foramen and inferior border of the mandible. The orthopantograms obtained were traced with the markings and the measurements were tabulated under different headings. After measuring the distances, the proportion between the distances was determined. The mean proportions of dentulous, edentulous, male, and female subjects were evaluated. Then the proportion of male subjects was compared with that of female subjects and dentulous subjects with that of edentulous subjects. Comparison of proportion between the different groups was done by using unpaired t test. The mean and standard deviation (SD) were determined for each group separately and were compared within each group. From the calculated "t" value, "p" the probability for error was found out. RESULTS: In dentulous subjects, the proportion ranged from 1:3.53 to 1:4.40. The mean was 1:3.90. In edentulous subjects, the proportion ranged from 1:3.50 to 1:4.15. The mean was 1:3.84. On comparison, the difference between both the groups was 0.06. The difference was statistically insignificant (p = 0.14). In the comparison of dentulous male and female subjects, the difference obtained was 0.02. The difference was statistically insignificant (p = 0.77). The comparison of edentulous male and female subjects and the difference obtained was 0.03. The difference was statistically insignificant (p = 0.51). CONCLUSION: The derived proportion of 1:4 between the inferior border of mandible and mental foramen and inferior border of mandible and occlusal plane in edentulous patients as measured on an orthopantogram may yield a plane of occlusion similar to that existing in the dentulous state. CLINICAL SIGNIFICANCE: The above-drawn proportion between the inferior border of the mandible to the lower edge of the mental foramen and between the inferior border of the mandible and the occlusal plane in edentulous patients may yield a plane of occlusion which is oriented similar to that existing in the dentulous state. The proportions derived radiographically in this study can serve as a basis for future studies to establish the occlusal plane for edentulous subjects.

##### Assuntos
Oclusão Dentária , Boca Edêntula , Feminino , Humanos , Masculino , Mandíbula , Forame Mentual , Radiografia Panorâmica
4.
Sci Transl Med ; 12(544)2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32434850

##### RESUMO

Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, are the most widely prescribed medications for diseases involving bone, with nearly 200 million prescriptions written annually. Recently, widespread use of N-BPs has been challenged due to the risk of rare but traumatic side effects such as atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ). N-BPs bind to and inhibit farnesyl diphosphate synthase, resulting in defects in protein prenylation. Yet, it remains poorly understood what other cellular factors might allow N-BPs to exert their pharmacological effects. Here, we performed genome-wide studies in cells and patients to identify the poorly characterized gene, ATRAID Loss of ATRAID function results in selective resistance to N-BP-mediated loss of cell viability and the prevention of alendronate-mediated inhibition of prenylation. ATRAID is required for alendronate inhibition of osteoclast function, and ATRAID-deficient mice have impaired therapeutic responses to alendronate in both postmenopausal and senile (old age) osteoporosis models. Last, we performed exome sequencing on patients taking N-BPs that suffered ONJ or an AFF. ATRAID is one of three genes that contain rare nonsynonymous coding variants in patients with ONJ or an AFF that is also differentially expressed in poor outcome groups of patients treated with N-BPs. We functionally validated this patient variation in ATRAID as conferring cellular hypersensitivity to N-BPs. Our work adds key insight into the mechanistic action of N-BPs and the processes that might underlie differential responsiveness to N-BPs in people.

5.
Plant Physiol ; 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32457089

##### RESUMO

Site-directed nucleases (SDNs) used for targeted genome editing are powerful new tools to introduce precise genetic changes into plants. Like traditional approaches, such as conventional crossing and induced mutagenesis, genome editing aims to improve crop yield and nutrition. Next-generation sequencing studies demonstrate that across their genomes, populations of crop species typically carry millions of single nucleotide polymorphisms and many copy number and structural variants. Spontaneous mutations occur at rates of approximately 10-8 to 10-9 per site per generation, while variation induced by chemical treatment or ionizing radiation results in higher mutation rates. In the context of SDNs, an off-target change or edit is an unintended, non-specific mutation occurring at a site with sequence similarity to the targeted edit region. SDN-mediated off-target changes can contribute to a small number of additional genetic variations compared to those that occur naturally in breeding populations or are introduced by induced-mutagenesis methods. Recent studies show that using computational algorithms to design genome editing reagents can mitigate off-target edits in plants. Finally, crops are subject to strong selection to eliminate off-type plants through well-established multigenerational breeding, selection, and commercial variety development practices. Within this context, off-target edits in crops present no new safety concerns compared to other breeding practices. The current generation of genome editing technologies is already proving useful to develop new plant varieties with consumer and farmer benefits. Genome editing will likely undergo improved editing specificity along with new developments in SDN delivery and increasing genomic characterization, further improving reagent design and application.

6.
Sci Rep ; 10(1): 7334, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32355232

##### RESUMO

Prairie cordgrass (PCG) (Spartina pectinata Link) has a high tolerance to soil salinity and waterlogging, therefore, it can thrive on marginal lands. Optimizing the nitrogen (N) input is crucial to achieving desirable biomass production of PCG without negatively impacting the environment. Thus, this study was based on the hypothesis that the use of legumes such as kura clover (Trifolium ambiguum M. Bieb.) (KC) as an intercrop with PCG can provide extra N to the crop reducing the additional N fertilizer and mitigating soil surface greenhouse gas (GHG) emissions. Specific objective of the study was to assess the impact of PCG managed with different N rates [0 kg N ha-1 (PCG-0N), 75 kg N ha-1 (PCG-75N), 150 kg N ha-1 (PCG-150N), and 225 kg N ha-1 (PCG-255N)], and PCG intercropped with KC (PCG-KC) on GHG fluxes and biomass yield. The experimental site was established in 2010 in South Dakota under a marginally yielding cropland. The GHG fluxes were measured from 2014 through 2018 growing seasons using the static chamber. Net global warming potential (GWP) was calculated. Data showed that cumulative CH4 and CO2 fluxes were similar for all the treatments over the study period. However, the PCG-KC, PCG-0N, and PCG-75N recorded lower cumulative N2O fluxes (384, 402, and 499 g N ha-1, respectively) than the PCG-150N (644 g N ha-1) and PCG-255N (697 g N ha-1). The PCG-KC produced 85% and 39% higher yield than the PCG-0N in 2016 and 2017, respectively, and similar yield to the other treatments (PCG-75N, PCG-150N, and PCG-255N) in these years. Net GWP was 52% lower for the PCG-KC (112.38 kg CO2-eq ha-1) compared to the PCG-225N (227.78 kg CO2-eq ha-1), but similar to other treatments. Soil total N was 15%% and 13% higher under PCG-KC (3.7 g kg-1) than that under PCG-0N (3.2 g kg-1) and PCG-75N (3.3 g kg-1), respectively. This study concludes that intercropping prairie cordgrass with kura clover can enhance biomass yield and reduce fertilizer-derived N2O emissions and net global warming potential.

7.
Daru ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32367410

##### RESUMO

INTRODUCTION: Papaya (Carica papaya Linn.) belongs to the family Caricaceae and is well known for its therapeutic and nutritional properties all over the world. The different parts of the papaya plant have been used since ancient times for its therapeutic applications. Herein, we aimed to review the anticancer, anti-inflammatory, antidiabetic and antiviral activities of papaya leaf. METHODS: All information presented in this review article regarding the therapeutic application of Carica papaya leaf extract has been acquired by approaching various electronic databases, including Scopus, Google scholar, Web of science, and PubMed. The keywords Carica papaya, anticancer, anti-inflammatory, immunomodulatory, and phytochemicals were explored until December 2019. RESULTS: The papaya plant, including fruit, leaf, seed, bark, latex, and their ingredients play a major role in the management of disease progression. Carica papaya leaf contains active components such as alkaloids, glycosides, tannins, saponins, and flavonoids, which are responsible for its medicinal activity. Additionally, the leaf juice of papaya increases the platelet counts in people suffering from dengue fever. CONCLUSION: The major findings revealed that papaya leaf extract has strong medicinal properties such as antibacterial, antiviral, antitumor, hypoglycaemic and anti-inflammatory activity. Furthermore, clinical trials are needed to explore the medicative potential of papaya leaf. Graphical abstract Graphical abstract showing the medicinal properties of Carica papaya leaf.

8.
Cancer Res ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32238357

##### RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death with a median survival time of 6-12 months. Most patients present with disseminated disease and the majority are offered palliative chemotherapy. With no approved treatment modalities for patients who progress on chemotherapy, we explored the effects of long-term Gemcitabine on the tumor microenvironment in order to identify potential therapeutic options for chemo-refractory PDAC. Using a combination of mouse models, primary cell line-derived xenografts, and established tumor cell lines, we first evaluated chemotherapy-induced alterations in the tumor secretome and immune surface proteins by high throughput proteomic arrays. In addition to enhancing antigen presentation and immune checkpoint expression, Gemcitabine consistently increased the synthesis of CCL/CXCL chemokines and TGFß-associated signals. These secreted factors altered the composition of the tumor stroma, conferring Gemcitabine resistance to cancer-associated fibroblasts in vitro and further enhancing TGFß1 biosynthesis. Combined Gemcitabine and anti-PD-1 treatment in transgenic models of murine PDAC failed to alter disease course unless mice also underwent genetic or pharmacologic ablation of TGFß signaling. In the setting of TGFß signaling deficiency, Gemcitabine and anti-PD-1 led to a robust CD8+ T-cell response and decrease in tumor burden, markedly enhancing overall survival. These results suggest that Gemcitabine successfully primes PDAC tumors for immune checkpoint inhibition by enhancing antigen presentation only following disruption of the immunosuppressive cytokine barrier. Given the current lack of third-line treatment options, this approach warrants consideration in the clinical management of Gemcitabine-refractory PDAC.

9.
Carbohydr Res ; 492: 108013, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32335391

##### RESUMO

Synthesis of 2'-O,5'-C-bridged-ß-d-homolyxofuranosyl nucleosides U and T have been achieved starting from diacetone-d-glucose in overall yields 55.7 and 57.1%, respectively. Quantitative regioselective monoacetylation of the lone primary hydroxyl group in trihydroxy nucleoside intermediate, i.e. 3'-O-benzyl-ß-d-glucofuranosyl nucleosides mediated by Novozyme®-435 has been utilized as the key step in the synthesis of homolyxofuranosyl nucleosides. The structure of the synthesized 2'-O,5'-C-bridged-ß-d-homolyxofuranosyl uracil and -thymine has been established on the basis of their spectral (IR, 1H, 13C NMR and HRMS) data analysis and the structure of earlier nucleoside was confirmed by its X-rays diffraction analysis which revealed that these 2'-O,5'-C-bridged homo-nucleosides are locked into S-type sugar puckering.

10.
ACS Nano ; 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32343121

##### RESUMO

Atherosclerotic plaques exhibit high deposition of cholesterol and macrophages. These are not only the main components of the plaques but also key inflammation-triggering sources. However, no existing therapeutics can achieve effective removal of both components within the plaques. Here, we report cargo-switching nanoparticles (CSNP) that are physicochemically designed to bind to cholesterol and release anti-inflammatory drug in the plaque microenvironment. CSNP have a core-shell structure with a core composed of an inclusion complex of methyl-ß-cyclodextrin (cyclodextrin) and simvastatin (statin), and a shell of phospholipids. Upon interaction with cholesterol, which has higher affinity to cyclodextrin than statin, CSNP release statin and scavenge cholesterol instead through cargo-switching. CSNP exhibit cholesterol-sensitive multifaceted antiatherogenic functions attributed to statin release and cholesterol depletion in vitro. In mouse models of atherosclerosis, systemically injected CSNP target atherosclerotic plaques and reduce plaque content of cholesterol and macrophages, which synergistically leads to effective prevention of atherogenesis and regression of established plaques. These findings suggest that CSNP provide a therapeutic platform for interfacing with cholesterol-associated inflammatory diseases such as atherosclerosis.

11.
Lupus ; : 961203320918011, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32299281
12.
PLoS One ; 15(4): e0219882, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32243481

##### RESUMO

Microbial community profiles have been associated with a variety of traits, including methane emissions in livestock. These profiles can be difficult and expensive to obtain for thousands of samples (e.g. for accurate association of microbial profiles with traits), therefore the objective of this work was to develop a low-cost, high-throughput approach to capture the diversity of the rumen microbiome. Restriction enzyme reduced representation sequencing (RE-RRS) using ApeKI or PstI, and two bioinformatic pipelines (reference-based and reference-free) were compared to bacterial 16S rRNA gene sequencing using repeated samples collected two weeks apart from 118 sheep that were phenotypically extreme (60 high and 58 low) for methane emitted per kg dry matter intake (n = 236). DNA was extracted from freeze-dried rumen samples using a phenol chloroform and bead-beating protocol prior to RE-RRS. The resulting sequences were used to investigate the repeatability of the rumen microbial community profiles, the effect of laboratory and analytical method, and the relationship with methane production. The results suggested that the best method was PstI RE-RRS analyzed with the reference-free approach, which accounted for 53.3±5.9% of reads, and had repeatabilities of 0.49±0.07 and 0.50±0.07 for the first two principal components (PC1 and PC2), phenotypic correlations with methane yield of 0.43±0.06 and 0.46±0.06 for PC1 and PC2, and explained 41±8% of the variation in methane yield. These results were significantly better than for bacterial 16S rRNA gene sequencing of the same samples (p<0.05) except for the correlation between PC2 and methane yield. A Sensitivity study suggested approximately 2000 samples could be sequenced in a single lane on an Illumina HiSeq 2500, meaning the current work using 118 samples/lane and future proposed 384 samples/lane are well within that threshold. With minor adaptations, our approach could be used to obtain microbial profiles from other metagenomic samples.

13.
Dalton Trans ; 49(13): 4100-4113, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32141470

##### RESUMO

In the current study, four novel mononuclear Cu(ii) complexes with terpyridine (L) and different co-ligands (phen, bipy, and imd) were synthesized and characterized in detail, where L is 4'-(3,4,5-trimethoxyphenyl)-2,2':6',2''-terpyridine. The identity and purity of all complexes were determined by elemental analysis, spectroscopic techniques (UV-vis, FTIR, ESI-MS, and EPR) and CV, including single crystal X-ray determination of three complexes ([Cu(L)(phen)](ClO4)2 (C-I), [Cu(L)2](ClO4)2 (C-II) and [Cu(L)(imd)(ClO4)](ClO4) (C-IV). DNA binding studies were performed using fluorescence assay and the binding constants were calculated using the Stern-Volmer equation and the modified Stern-Volmer equation. The magnitude of Kapp of all complexes was 105 M-1, indicating moderate intercalative binding between CT-DNA and the complexes. Agarose gel electrophoresis clearly reflected their ability to cleave a double stranded pET-28b plasmid in the presence of an external reducing agent (3-mercapto propionic acid). Steady-state fluorescence quenching was performed to understand their interactions with BSA. The studies suggested a mixed quenching mechanism with an initial static process. Furthermore, the antiproliferative activity of the complexes was evaluated against lung cancer A549 cells and primary mice splenocytes. Interestingly, the complexes show 25-200 fold greater toxicity towards the A549 cells than primary splenocytes, indicating their selectivity towards the former. The good binding behavior of all four complexes towards DNA and BSA and their cytotoxicity render these compounds promising potent anticancer drugs.

14.
PLoS One ; 15(3): e0229554, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126106

##### RESUMO

Domesticated lentil has a relatively narrow genetic base globally and most released varieties are susceptible to severe biotic and abiotic stresses. The crop wild relatives could provide new traits of interest for tailoring novel germplasm and cultivated lentil improvement. The primary objective of this study was to evaluate wild lentil accessions for identification of economically viable agro-morphological traits and resistance against major biotic stresses. The study has revealed substantial variations in seed yield and its important component characters. Further, the diversity analysis of wild accessions showed two major clusters which were bifurcated into sub-clusters, thereby suggesting their wider genetic divergence. However, principal component analysis exhibited that seed yield plant-1, number of seeds plant-1, number of pods plant-1, harvest index and biological yield plant-1 contributed significantly to the total genetic variation assessed in wild lentil taxa. Moreover, some of the wild accessions collected from Syria and Turkey regions showed resistance against more than one disease indicating rich diversity of lentil genetic resources. The identification of most promising genotypes carrying resistance against major biotic stresses could be utilized in the cultivated or susceptible varieties of lentil for enhancing genetic gains. The study has also identified some trait specific accessions, which could also be taken into the consideration while planning distant hybridization in lentil.

15.
Drug Dev Ind Pharm ; 46(4): 659-672, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32208984

##### RESUMO

Objective: In vitro, optimization, characterization, and cytotoxic studies of NAR nanoparticles (NPs) to against pancreatic cancer.Method: The sonication tailored Naringenin (NARG)-loaded poly (lactide-co-glycolic acid) (PLGA) NPs was fabricated for potential cytotoxic effect against pancreatic cancer. NARG NPs were prepared by emulsion-diffusion evaporation technique applying BoxBehnken experimental design based on three-level and three-factors. The effect of independent variables surfactant concentration (X1), polymer concentration (X2), and sonication time (X3) were studied on responses particle size (Y1), and drug release % (Y2). NPs characterized for particles size and size distribution, polydispersity index (PDI), zeta potential, transmission electron microscope (TEM), scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimeter (DSC), and X-ray diffraction (XRD) studies. Further, the studies was fitted to various drug release kinetic model and cytotoxicity evaluated in vitro.Results: The nanosized particles were spherical, uniform with an average size of 150.45 ± 12.45 nm, PDI value 0.132 ± 0.026, zeta potential -20.5 ± 2.5 mV, and cumulative percentage release 85.67 ± 6.23%. In vitro release of NARG from nanoparticle evaluated initially burst followed by sustained release behavior. The Higuchi was best fitted model to drug release from NARG NPs. The cytotoxicity study of NARG NPs apparently showed higher cytotoxic effect over free NARG (p < 0.05). The stability study of optimized formulation revealed no significant physico-chemical changes during 3 months.Conclusions: Thus, NARG-loaded NPs gave ameliorated anticancer effect over plain NARG.

16.
Proc Natl Acad Sci U S A ; 117(14): 7961-7970, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32209667

##### RESUMO

Mixed lineage kinase 3 (MLK3), also known as MAP3K11, was initially identified in a megakaryocytic cell line and is an emerging therapeutic target in cancer, yet its role in immune cells is not known. Here, we report that loss or pharmacological inhibition of MLK3 promotes activation and cytotoxicity of T cells. MLK3 is abundantly expressed in T cells, and its loss alters serum chemokines, cytokines, and CD28 protein expression on T cells and its subsets. MLK3 loss or pharmacological inhibition induces activation of T cells in in vitro, ex vivo, and in vivo conditions, irrespective of T cell activating agents. Conversely, overexpression of MLK3 decreases T cell activation. Mechanistically, loss or inhibition of MLK3 down-regulates expression of a prolyl-isomerase, Ppia, which is directly phosphorylated by MLK3 to increase its isomerase activity. Moreover, MLK3 also phosphorylates nuclear factor of activated T cells 1 (NFATc1) and regulates its nuclear translocation via interaction with Ppia, and this regulates T cell effector function. In an immune-competent mouse model of breast cancer, MLK3 inhibitor increases Granzyme B-positive CD8+ T cells and decreases MLK3 and Ppia gene expression in tumor-infiltrating T cells. Likewise, the MLK3 inhibitor in pan T cells, isolated from breast cancer patients, also increases cytotoxic CD8+ T cells. These results collectively demonstrate that MLK3 plays an important role in T cell biology, and targeting MLK3 could serve as a potential therapeutic intervention via increasing T cell cytotoxicity in cancer.

17.
Biomater Sci ; 8(8): 2055-2073, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32129390

##### RESUMO

Non-specific toxicity of chemotherapeutics and evolution of malignant tumors against them are major challenges for existing cancer chemotherapeutic regimens. Engineering of nanomaterials has attempted to minimize the toxicity of anticancer drugs, but systemic delivery of these nanomaterials still imposes many hurdles in their clinical use like burst release of chemotherapeutics and toxicity and immunogenicity associated with excipients of nanomaterials. However, there has been a surge in the development of natural and synthetic nanomaterials to deliver anticancer agents to the diseased (tumor) site as it can minimize the systemic circulation of anticancer drugs and reduce the toxicity-related challenges. Therefore, localized drug delivery is considered as the most effective way to deliver therapeutics but is further challenged by poor biodegradability, high immunogenicity, poor drug entrapment efficacy and inability to maintain sustained release of anticancer agents at the tumor site. This review maps out recent advancements in engineering of low molecular weight hydrogels derived from amino acid, fatty acyl, steroidal lipid and drug conjugated amphiphilic scaffolds. We have summarized the efforts for the development of molecular hydrogels in terms of biocompatibility, therapeutic potential and challenges associated with existing molecular hydrogels for cancer therapy.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32041396

##### RESUMO

Recent research endeavors have established metal-organic frameworks (MOFs) as suitable platforms for the adsorptive removal of various environmental pollutants. In this regard, the sorptive performances of four MOFs (MOF-199, UiO-66, UiO-66-NH2, and Co-CUK-1) were investigated against two gaseous aliphatic ketones (methyl ethyl ketone (MEK) and methyl isobutyl ketone (MiBK)) at a low partial pressure (0.1 Pa). Activated carbon was utilized as a reference commercial sorbent. The 10% breakthrough volume (BTV10) values for MEK decreased in the following order: MOF-199 (4772 L atm g-1) > activated carbon (224 L atm g-1) > UiO-66-NH2 (106 L atm g-1) > UiO-66 (53 L atm g-1) > Co-CUK-1 (16 L atm g-1). In case of MiBK, the relative ordering in BTV10 was consistently maintained while showing noticeable increases in its magnitude: MOF-199 (7659 L atm g-1) > activated carbon (816 L atm g-1) > UiO-66-NH2 (304 L atm g-1) > UiO-66 (150 L atm g-1) > Co-CUK-1 (31 L atm g-1). The superiority of MOF-199 was confirmed toward the adsorptive removal of gaseous aliphatic ketones. For a binary mixture of ketones, the BTV10 values of MOF-199 were reduced considerably for MEK and MiBK (in comparison to single component sorption) such as 1579 and 3969 L atm g-1, respectively, reflecting competitive inhibition of the adsorption process. Theoretical simulations based on density functional theory (DFT) elucidated the involvement of highly favorable coordination between the carbonyl group present in ketone molecules and the uncoordinated Cu(II) sites in the MOF-199 structure (Lewis acidic centers). Interestingly, MOF-199 maintained appreciable performance toward the mixture of ketones up to 5 cycles to support its practical merit.

19.
Proc Natl Acad Sci U S A ; 117(8): 4180-4187, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32034099

##### RESUMO

Endothelial cells play an important role in maintenance of the vascular system and the repair after injury. Under proinflammatory conditions, endothelial cells can acquire a mesenchymal phenotype by a process named endothelial-to-mesenchymal transition (EndMT), which affects the functional properties of endothelial cells. Here, we investigated the epigenetic control of EndMT. We show that the histone demethylase JMJD2B is induced by EndMT-promoting, proinflammatory, and hypoxic conditions. Silencing of JMJD2B reduced TGF-ß2-induced expression of mesenchymal genes, prevented the alterations in endothelial morphology and impaired endothelial barrier function. Endothelial-specific deletion of JMJD2B in vivo confirmed a reduction of EndMT after myocardial infarction. EndMT did not affect global H3K9me3 levels but induced a site-specific reduction of repressive H3K9me3 marks at promoters of mesenchymal genes, such as Calponin (CNN1), and genes involved in TGF-ß signaling, such as AKT Serine/Threonine Kinase 3 (AKT3) and Sulfatase 1 (SULF1). Silencing of JMJD2B prevented the EndMT-induced reduction of H3K9me3 marks at these promotors and further repressed these EndMT-related genes. Our study reveals that endothelial identity and function is critically controlled by the histone demethylase JMJD2B, which is induced by EndMT-promoting, proinflammatory, and hypoxic conditions, and supports the acquirement of a mesenchymal phenotype.

20.
Nanotechnology ; 31(23): 235709, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32084656

##### RESUMO

Nanowires are widely considered to be key elements in future disruptive electronics and photonics. This paper presents the first detailed study of transport mechanisms in single-crystalline InAs nanowires synthesized by a cheap solvothermal wet chemical method. From detailed analyses of temperature-dependent current-voltage characteristics, it was observed that contacted nanowires operate in a linear transport regime at biases below a critical cross-over voltage. For larger biases, the transport changes to space-charge-limited conduction assisted by traps. The characteristic parameters such as free electron concentration, trap concentration and energy distribution, and electron mobility were all calculated. It was demonstrated that the nanowires have key electrical properties comparable to those of InAs nanowires grown by molecular beam epitaxy. Our results might pave the way for cheap disruptive low-dimensional electronics such as resistive switching devices.