Growth of Size-Tunable Ag2O Polyhedra and Revelation of Their Bulk and Surface Lattices.

By primarily adjusting the reagent amounts, particularly the volume of AgNO3 solution introduced, Ag2O cubes with decreasing sizes from 440 to 79 nm, octahedra from 714 to 106 nm, and rhombic dodecahedra from 644 to 168 nm are synthesized. 733 nm cuboctahedra are also prepared for structural analysis. With in-house X-ray diffraction (XRD) peak calibration, shape-related peak shifts are recognizable. Synchrotron XRD measurements at 100 K reveal the presence of bulk and surface layer lattices. Bulk cell constants also deviate slightly. They show a negative thermal expansion behavior with shrinking cell constants at higher temperatures. The Ag2O crystals exhibit size- and facet-dependent optical properties. Bandgaps red-shift continuously with increasing particle sizes. Optical facet effect is also observable. Moreover, synchrotron XRD peaks of a mixture of Cu2O rhombicuboctahedra and edge- and corner-truncated cubes exposing all three crystal faces can be deconvoluted into three components with the bulk and the [111] microstrain phase as the major component. Interestingly, while the unheated Cu2O sample shows clear diffraction peak asymmetry, annealing the sample to 450 K yields nearly symmetric peaks even when returning the sample to room temperature, meaning even moderately high temperatures can permanently change the crystal lattice.

Automated Generation of hiPSC-Derived Hepatic Progeny by Cost-Efficient Compounds.

Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells (HLCs) hold great promise for liver disease modeling, drug discovery, and drug toxicity screens. Yet, several hurdles still need to be overcome, including among others decrease in the cost of goods to generate HLCs and automation of the differentiation process. We here describe that the use of an automated liquid handling system results in highly reproducible HLC differentiation from hPSCs. This enabled us to screen 92 chemicals to replace expensive growth factors at each step of the differentiation protocol to reduce the cost of goods of the differentiation protocol by approximately 79%. In addition, we also evaluated several recombinant extracellular matrices to replace Matrigel. We demonstrated that differentiation of hPSCs on Laminin-521 using an optimized small molecule combination resulted in HLCs that were transcriptionally identical to HLCs generated using the growth factor combinations. In addition, the HLCs created using the optimized small molecule combination secreted similar amounts of albumin and urea, and relatively low concentrations of alfa-fetoprotein, displayed similar CYP3A4 functionality, and a similar drug toxicity susceptibility as HLCs generated with growth factor cocktails. The broad applicability of the new differentiation protocol was demonstrated for 4 different hPSC lines. This allowed the creation of a scalable, xeno-free, and cost-efficient hPSC-derived HLC culture, suitable for high throughput disease modeling and drug screenings, or even for the creation of HLCs for regenerative therapies.

Selection of reference genes for normalizing gene expression data across seasons in spermatozoa of water buffalo (Bubalus bubalis).

Selection of the most stably expressed reference genes is key to monitoring accurate target gene expression across any tissue or cell type. The mRNA in spermatozoa stores valuable information related to changes in spermatogenesis due to variations in environmental conditions, especially during heat stress, which affects various sperm functions. Semen quality in buffalo bulls is significantly influenced by the seasons. In the study, a panel of nine genes was evaluated to identify the most stably expressed internal control gene (ICG) for the normalization of real-time gene expression data generated across various seasons for Murrah buffalo bulls' spermatozoa. Sperm cells were purified from the semen samples collected during different seasons, with temperature-humidity index (THI) ranging from 80.80 ± 1.47 (hot summer) to 55.88 ± 1.98 (winter), using the BoviPure™ gradient purification method. The RNA isolated from the purified spermatozoa fraction was quality checked prior to reverse transcription and subjected to qPCR (quantitative real-time PCR) based expression analysis. An automated 'endoGene' pipeline was employed to apply the geNorm, NormFinder, and BestKeeper algorithms for data analysis. The result indicated that GAPDH and PP1A were the most stably expressed among the gene panel, whereas ATPSF1 and ACTB were the two least stable expressed reference genes. Further, the most suitable ICGs identified were validated by normalization of real time expression data of heat stress and sperm quality genes, HSFY2 and AKAP4, respectively. The genes identified would help in generating the most reliable results for the expression profiling of the genes dictating sperm quality and heat stress cope-up mechanism in buffalo spermatozoa, collected during different seasons.

Targeting epidermal growth factor receptor and its downstream signaling pathways by natural products: A mechanistic insight.

The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase (RTK) that maintains normal tissues and cell signaling pathways. EGFR is overactivated and overexpressed in many malignancies, including breast, lung, pancreatic, and kidney. Further, the EGFR gene mutations and protein overexpression activate downstream signaling pathways in cancerous cells, stimulating the growth, survival, resistance to apoptosis, and progression of tumors. Anti-EGFR therapy is the potential approach for treating malignancies and has demonstrated clinical success in treating specific cancers. The recent report suggests most of the clinically used EGFR tyrosine kinase inhibitors developed resistance to the cancer cells. This perspective provides a brief overview of EGFR and its implications in cancer. We have summarized natural products-derived anticancer compounds with the mechanistic basis of tumor inhibition via the EGFR pathway. We propose that developing natural lead molecules into new anticancer agents has a bright future after clinical investigation.

Biaryl carboxamide-based peptidomimetics analogs as potential pancreatic lipase inhibitors for treating obesity.

A series of 1,1'-biphenyl-3-carboxamide and furan-phenyl-carboxamide analogs were synthesized using an optimized scheme and confirmed by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry techniques. The synthesized peptidomimetics analogs were screened in vitro to understand the inhibitory potential of pancreatic lipase (PL). Analogs were assessed for the PL inhibitory activity based on interactions, geometric complementarity, and docking score. Among the synthesized analogs, 9, 29, and 24 were found to have the most potent PL inhibitory activity with IC50 values of 3.87, 4.95, and 5.34 µM, respectively, compared to that of the standard drug, that is, orlistat, which inhibits PL with an IC50 value of 0.99 µM. The most potent analog, 9, exhibited a competitive-type inhibition with an inhibition constant (Ki) of 2.72 µM. In silico molecular docking of analog 9 with the PL (PDB ID:1LPB) showed a docking score of -11.00 kcal/mol. Analog 9 formed crucial hydrogen bond interaction with Ser152, His263, π-cation interaction with Asp79, Arg256, and π-π stacking with Phe77, Tyr114 at the protein's active site. The molecular dynamic simulation confirmed that analog 9 forms stable interactions with PL at the end of 200 ns with root mean square deviation values of 2.5 and 6 Å. No toxicity was observed for analog 9 (concentration range of 1-20 µM) when tested by MTT assay in RAW 264.7 cells.

Natural products acting against S. aureus through membrane and cell wall disruption.

Covering: 2015 to 2022Staphylococcus aureus (S. aureus) is responsible for several community and hospital-acquired infections with life-threatening complications such as bacteraemia, endocarditis, meningitis, liver abscess, and spinal cord epidural abscess. In recent decades, the abuse and misuse of antibiotics in humans, animals, plants, and fungi and the treatment of nonmicrobial diseases have led to the rapid emergence of multidrug-resistant pathogens. The bacterial wall is a complex structure consisting of the cell membrane, peptidoglycan cell wall, and various associated polymers. The enzymes involved in bacterial cell wall synthesis are established antibiotic targets and continue to be a central focus for antibiotic development. Natural products play a vital role in drug discovery and development. Importantly, natural products provide a starting point for active/lead compounds that sometimes need modification based on structural and biological properties to meet the drug criteria. Notably, microorganisms and plant metabolites have contributed as antibiotics for noninfectious diseases. In this study, we have summarized the recent advances in understanding the activity of the drugs or agents of natural origin that directly inhibit the bacterial membrane, membrane components, and membrane biosynthetic enzymes by targeting membrane-embedded proteins. We also discussed the unique aspects of the active mechanisms of established antibiotics or new agents.

Shape-Tunable BaTiO3 Crystals Presenting Facet-Dependent Optical and Piezoelectric Properties.

BaTiO3 octahedra, edge-, and corner-truncated cubes, and cubes with four tunable sizes from 132 to 438 nm are synthesized by a solvothermal growth approach. Acetic acid treatment can cleanly remove BaCO3 impurity. Rietveld refinement of X-ray diffraction patterns and Raman spectra help to confirm the particles have a tetragonal crystal structure. The crystals also exhibit size- and facet-dependent bandgap shifts. BaTiO3 octahedra show larger piezoelectric, ferroelectric, and pyroelectric effects than truncated cubes and cubes. The measured dielectric constant differences should be associated with their various facet-dependent behaviors. Piezoelectric nanogenerators fabricated from BaTiO3 octahedra consistently show the best performance than those containing truncated cubes and cubes. In particular, a nanogenerator with 30 wt.%-incorporated octahedra displays an open-circuit voltage of 23 V and short-circuit current of 324 nA. The device performance is also highly stable. The maximum output power reaches 3.9 µW at 60 MΩ. The fabricated nanogenerator can provide sufficient electricity to power light-emitting diodes. This work further demonstrates that various physical properties of semiconductor crystals show surface dependence.

Experimental Revelation of Surface and Bulk Lattices in Faceted Cu2 O Crystals.

Semiconductor crystals have generally shown facet-dependent electrical, photocatalytic, and optical properties. These phenomena have been proposed to result from the presence of a surface layer with bond-level deviations. To provide experimental evidence of this structural feature, synchrotron X-ray sources are used to obtain X-ray diffraction (XRD) patterns of polyhedral cuprous oxide crystals. Cu2 O rhombic dodecahedra display two distinct cell constants from peak splitting. Peak disappearance during slow Cu2 O reduction to Cu with ammonia borane differentiates bulk and surface layer lattices. Cubes and octahedra also show two peak components, while diffraction peaks of cuboctahedra are comprised of three components. Temperature-varying lattice changes in the bulk and surface regions also show shape dependence. From transmission electron microscopy (TEM) images, slight plane spacing deviations in surface and inner crystal regions are measured. Image processing provides visualization of the surface layer with depths of about 1.5-4 nm giving dashed lattice points instead of dots from atomic position deviations. Close TEM examination reveals considerable variation in lattice spot size and shape for different particle morphologies, explaining why facet-dependent properties are emerged. Raman spectrum reflects the large bulk and surface lattice difference in rhombic dodecahedra. Surface lattice difference can change the particle bandgap.

Mechanical thrombectomy versus catheter directed thrombolysis in patients with pulmonary embolism: A multicenter experience.

OBJECTIVES: Compare in-hospital outcomes of patients treated with either mechanical thrombectomy (MT) or catheter directed lysis (CDL) in treatment of acute pulmonary embolism (PE). METHODS: This is a multicenter, retrospective cohort study of patients undergoing MT or CDL for acute PE between 2014 and 2021. The primary outcome was the composite of in-hospital death, significant bleed, vascular complication, or need for mechanical support post-procedure. Secondary outcomes included the individual components of the composite outcome in addition to blood transfusions, invasive hemodynamics, echocardiographic data, and intensive care unit (ICU) utilization. RESULTS: 458 patients were treated for PE with 266 patients in the CDL arm and 192 patients in the MT arm. The primary composite endpoint was not significantly different between the two groups with CDL 12% versus MT 11% (p = 0.5). There was a significant difference in total length of ICU time required with more in the CDL group versus MT (3.8 ± 2.0 vs. 2.8 ± 3.0 days, p = 0.009). All other secondary end points showed no significant difference between the groups. CONCLUSIONS: In patients undergoing catheter directed treatment of PE, there was no difference between MT and CDL in terms of in-hospital mortality, bleeds, catheter-related complications, and hemodynamics.

In-Catalyzed Transfer Hydrogenation and Regioselective Hydrogen-Deuterium Addition to the Olefins.

A unique and valuable methodology is developed for the hydrogenation of aromatic as well as aliphatic 1,1-di- and trisubstituted alkenes. In the presence of catalytic InBr3, readily available 1,3-benzodioxole and residual H2O present in the reaction mixture are utilized as a hydrogen gas surrogate and proved to be a practical source of deuterium incorporation into the olefins on either side by varying the source of the starting deuterated 1,3-benzodioxole or D2O. Experimental studies show the transfer of hydride from 1,3-benzodioxole to the carbocationic intermediate generated from the protonation of alkenes by the H2O-InBr3 adduct remains the critical step.

Plant growth promoting rhizobacterium Bacillus sp. BSE01 alleviates salt toxicity in chickpea (Cicer arietinum L.) by conserving ionic, osmotic, redox and hormonal homeostasis.

Soil salinity leading to sodium toxicity is developing into a massive challenge for agricultural productivity globally, inducing osmotic, ionic, and redox imbalances in plants. Considering the predicted increase in salinization risk with the ongoing climate change, applying plant growth-promoting rhizobacteria (PGPR) is an environmentally safe method for augmenting plant salinity tolerance. The present study examined the role of halotolerant Bacillus sp. BSE01 as a promising biostimulant for improving salt stress endurance in chickpea. Application of PGPR significantly increased the plant height, relative water content, and chlorophyll content of chickpea under both non-stressed and salt stress conditions. The PGPR-mediated tolerance towards salt stress was accomplished by the modulation of hormonal signaling and conservation of cellular ionic, osmotic, redox homeostasis. With salinity stress, the PGPR-treated plants significantly increased the indole-3-acetic acid and gibberellic acid contents more than the non-treated plants. Furthermore, the PGPR-inoculated plants maintained lower 1-aminocyclopropane-1-carboxylic acid and abscisic acid contents under salt treatment. The PGPR-inoculated chickpea plants also exhibited a decreased NADPH oxidase activity with reduced production of reactive oxygen species compared to the non-inoculated plants. Additionally, PGPR treatment led to increased antioxidant enzyme activities in chickpea under saline conditions, facilitating the reactive nitrogen and oxygen species detoxification, thereby limiting the nitro-oxidative damage. Following salinity stress, enhanced K+ /Na+ ratio and proline content were noted in the PGPR-inoculated chickpea plants. Therefore, Bacillus sp. BSE01, being an effective PGPR and salinity stress reducer, can further be considered to develop a bioinoculant for sustainable chickpea production under saline environments.

Targeting mycobacterial membranes and membrane proteins: Progress and limitations.

Among the various bacterial infections, tuberculosis continues to hold center stage. Its causative agent, Mycobacterium tuberculosis, possesses robust defense mechanisms against most front-line antibiotic drugs and host responses due to their complex cell membranes with unique lipid molecules. It is now well-established that bacteria change their membrane composition to optimize their environment to survive and elude drug action. Thus targeting membrane or membrane components is a promising avenue for exploiting the chemical space focussed on developing novel membrane-centric anti-bacterial small molecules. These approaches are more effective, non-toxic, and can attenuate resistance phenotype. We present the relevance of targeting the mycobacterial membrane as a practical therapeutic approach. The review highlights the direct and indirect targeting of membrane structure and function. Direct membrane targeting agents cause perturbation in the membrane potential and can cause leakage of the cytoplasmic contents. In contrast, indirect membrane targeting agents disrupt the function of membrane-associated proteins involved in cell wall biosynthesis or energy production. We discuss the chronological chemical improvements in various scaffolds targeting specific membrane-associated protein targets, their clinical evaluation, and up-to-date account of their ''mechanisms of action, potency, selectivity'' and limitations. The sources of anti-TB drugs/inhibitors discussed in this work have emerged from target-based identification, cell-based phenotypic screening, drug repurposing, and natural products. We believe this review will inspire the exploration of uncharted chemical space for informing the development of new scaffolds that can inhibit novel mycobacterial membrane targets.

Tackling multidrug-resistant Staphylococcus aureus by natural products and their analogues acting as NorA efflux pump inhibitors.

Staphylococcus aureus (S. aureus) is a pathogen responsible for various community and hospital-acquired infections with life-threatening complications like bacteraemia, endocarditis, meningitis, liver abscess, and spinal cord epidural abscess. Antibiotics have been used to treat microbial infections since the introduction of penicillin in 1940. In recent decades, the abuse and misuse of antibiotics in humans, animals, plants, and fungi, including the treatment of non-microbial diseases, have led to the rapid emergence of multidrug-resistant pathogens with increased virulence. Bacteria have developed several complementary mechanisms to avoid the effects of antibiotics. These mechanisms include chemical transformations and enzymatic inactivation of antibiotics, modification of antibiotics' target site, and reduction of intracellular antibiotics concentration by changes in membrane permeability or by the overexpression of efflux pumps (EPs). The strategy to check antibiotic resistance includes synthesis of the antibiotic analogues, or antibiotics are given in combination with the adjuvant. The inhibitors of multidrug EPs are considered promising alternative therapeutic options with the potential to revive the effects of antibiotics and reduce bacterial virulence. Natural products played a vital role in drug discovery and significantly contributed to the area of infectious diseases. Also, natural products provide lead compounds that sometimes need modification based on structural and biological properties to meet the drug criteria. This review discusses natural products and their derived compounds as NorA efflux pump inhibitors (EPIs).

Development and validation of most efficient RNA isolation method from buffalo bull spermatozoa.

BACKGROUND: Being highly fragmented and low in concentration, isolation of good quality RNA from sperm cells is a big challenge. Attempts have been made to evaluate various sperm RNA isolation methods from purified buffalo bull sperm cells. METHODS: Both, non-membrane and membrane-based methods have been evaluated for isolating RNA from Murrah buffalo sperms and compared for their respective efficacies. The traditional TRIzol, TRIzol-heat lysed (H-TRIzol) and cocktail of TCEP-RLT lysis buffer (Qiagen RNeasy mini kit)-TRIzol (C-TRIzol) based isopropanol isolation methods have been evaluated. RESULTS: H-TRIzol yielded best results among conventional methods. The combined T-RLT RNA isolation protocol yielded best quality and quantity compared to other membrane-based methods, due to high lytic property of cocktail of lysis reagents, necessary for complete breakdown of sperm membrane and RNA binding membrane for RNA isolation. Combined lysis performed by treatment with RLT-T and T-RLT differing in order of reagents used were also evaluated. T-RLT combination giving better results compared to RLT-T due to high gDNA contamination and membrane clogging in later protocol steps. CONCLUSION: Overall, in terms of total RNA quantity and quality per million spermatozoa, the heat-lysed TRIzol method (H-TRIzol) performs best among RNA separation techniques employed and is also quite easy to perform. This comparative evaluation of sperm RNA isolation protocols can be useful in deciding the best protocol for isolation of good quality and high concentration sperm RNA from buffalo semen, for transcriptome and other downstream studies.

Natural products and their analogues acting against Mycobacterium tuberculosis: A recent update.

Tuberculosis (TB) remains one of the deadliest infectious diseases caused by Mycobacterium tuberculosis (M.tb). It is responsible for significant causes of mortality and morbidity worldwide. M.tb possesses robust defense mechanisms against most antibiotic drugs and host responses due to their complex cell membranes with unique lipid molecules. Thus, the efficacy of existing front-line drugs is diminishing, and new and recurring cases of TB arising from multidrug-resistant M.tb are increasing. TB begs the scientific community to explore novel therapeutic avenues. A precise knowledge of the compounds with their mode of action could aid in developing new anti-TB agents that can kill latent and actively multiplying M.tb. This can help in the shortening of the anti-TB regimen and can improve the outcome of treatment strategies. Natural products have contributed several antibiotics for TB treatment. The sources of anti-TB drugs/inhibitors discussed in this work are target-based identification/cell-based and phenotypic screening from natural products. Some of the recently identified natural products derived leads have reached clinical stages of TB drug development, which include rifapentine, CPZEN-45, spectinamide-1599 and 1810. We believe these anti-TB agents could emerge as superior therapeutic compounds to treat TB over known Food and Drug Administration drugs.

A computational model of dopaminergic modulation of hippocampal Schaffer collateral-CA1 long-term plasticity.

Dopamine plays a critical role in modulating the long-term synaptic plasticity of the hippocampal Schaffer collateral-CA1 pyramidal neuron synapses (SC-CA1), a widely accepted cellular model of learning and memory. Limited results from hippocampal slice experiments over the last four decades have shown that the timing of the activation of dopamine D1/D5 receptors relative to a high/low-frequency stimulation (HFS/LFS) in SC-CA1 synapses regulates the modulation of HFS/LFS-induced long-term potentiation/depression (LTP/LTD) in these synapses. However, the existing literature lacks a complete picture of how various concentrations of D1/D5 agonists and the relative timing between the activation of D1/D5 receptors and LTP/LTD induction by HFS/LFS, affect the spatiotemporal modulation of SC-CA1 synaptic dynamics. In this paper, we have developed a computational model, a first of its kind, to make quantitative predictions of the temporal dose-dependent modulation of the HFS/LFS induced LTP/LTD in SC-CA1 synapses by various D1/D5 agonists. Our model combines the biochemical effects with the electrical effects at the electrophysiological level. We have estimated the model parameters from the published electrophysiological data, available from diverse hippocampal CA1 slice experiments, in a Bayesian framework. Our modeling results demonstrate the capability of our model in making quantitative predictions of the available experimental results under diverse HFS/LFS protocols. The predictions from our model show a strong nonlinear dependency of the modulated LTP/LTD by D1/D5 agonists on the relative timing between the activated D1/D5 receptors and the HFS/LFS protocol and the applied concentration of D1/D5 agonists.

Synthesis of Zinc Blende-Phased CdSe Nanocrystals with Size-Tunable Optical Properties and Adjustable Valence Band Positions.

CdSe nanocrystals with average sizes of 15, 24, and 32 nm have been synthesized from an aqueous solution of Na2SeSO3, HCl, and cadmium nitrate at 15, 45, and 70 °C, respectively, for about 1 h. Mixing aqueous CdCl2, HNO3, and Na2SeSO3 at 22 °C for 4 h yields 44 nm CdSe nanocrystals. X-ray and electron diffraction analyses indicate the possession of a zinc blende crystal structure for all the samples. Despite the large particle dimensions, their absorption band red-shifts significantly from 520 to 570 nm with increasing particle sizes, and band gap values decrease from 2.03 eV for 15 nm particles to 1.68 eV for 44 nm crystals. Although these nanocrystals are not emissive, introduction of the cetyltrimethylammonium chloride surfactant during crystal growth can restore their photoluminescence attributed to the improved crystal quality, and the similarly sized CdSe nanocrystals have an emission band red-shifting from 544 nm for 15 nm particles to 583 nm for 47 nm crystals. A band diagram was constructed for these CdSe nanocrystals using information from Mott-Schottky plots. While they have close conduction band positions, the notable size-related band gap variation means that their valence band energies differ considerably with implications of electrochemical and photocatalytic properties. The 44 nm CdSe particles also show the smallest electrochemical charge-transfer resistance.

Unraveling the contribution of OsSOS2 in conferring salinity and drought tolerance in a high-yielding rice.

Abiotic stresses are emerging as a potential threat to sustainable agriculture worldwide. Soil salinity and drought will be the major limiting factors for rice productivity in years to come. The Salt Overly Sensitive (SOS) pathway plays a key role in salinity tolerance by maintaining the cellular ion homeostasis, with SOS2, a S/T kinase, being a vital component. The present study investigated the role of the OsSOS2, a SOS2 homolog from rice, in improving salinity and drought tolerance. Transgenic plants with either overexpression (OE) or knockdown (KD) of OsSOS2 were raised in one of the high-yielding cultivars of rice-IR64. Using a combined approach based on physiological, biochemical, anatomical, microscopic, molecular, and agronomic assessment, the evidence presented in this study advocates the role of OsSOS2 in improving salinity and drought tolerance in rice. The OE plants were found to have favorable ion and redox homeostasis when grown in the presence of salinity, while the KD plants showed the reverse pattern. Several key stress-responsive genes were found to work in an orchestrated manner to contribute to this phenotype. Notably, the OE plants showed tolerance to stress at both the seedling and the reproductive stages, addressing the two most sensitive stages of the plant. Keeping in mind the importance of developing crops plants with tolerance to multiple stresses, the present study established the potential of OsSOS2 for biotechnological applications to improve salinity and drought stress tolerance in diverse cultivars of rice.

Cationic RGD peptidomimetic nanoconjugates as effective tumor targeting gene delivery vectors with antimicrobial potential.

Gene delivery combined with systemic targeting approach has shown promising potential in cancer gene therapy. Peptides are ideal functional motif for constructing biocompatible non-viral gene delivery vehicles. RGD peptides, in particular, are known to recognize the integrin αVß3, which is expressed specifically on angiogenic blood vessels and, therefore, is considered vital for anti-angiogenesis strategies and cancer treatment. In recent times, several RGD peptide-based non-viral gene delivery vectors have been utilized for targeted gene delivery, however, lack in proteolytic stability. In the current study, we have investigated a series of non-naturally modified RGD peptide mimic (MOH) nanoconjugates with low molecular weight branched polyethylenimine (bPEI 1.8 kDa). The projected peptide mimic, Fmoc-FFARKA (MOH), has already been demonstrated to have high binding efficiency for αVß3 integrins and enhanced cell adhesive ability with high stability compared to the natural RGD counterpart. The polymer-peptide, PEI-MOH (PMOH), nanoconjugate vectors have been designed to enhance the tumor targeting ability, therapeutic proficiency, transfection efficiency and proteolytic stability. The synthesized nanoconjugates showed the ability to protect the bound DNA with low cytotoxicity and their pDNA complexes displayed enhanced transfection efficiency. Furthermore, a competitive study confirmed their selective behavior towards liver cancer cells, HepG2. Lastly, PMOH nanoconjugates also exerted significant antimicrobial effects against drug-resistant pathogens. Altogether, the data suggest that nanosized non-naturally modified RGD peptide mimic-based gene vectors hold great potential as efficient biomaterials for targeted gene delivery and antimicrobial applications.

Physiologic Lesion Assessment to Optimize Multivessel Disease.

PURPOSE OF REVIEW: Multivessel coronary artery disease, defined as significant stenosis in two or more major coronary arteries, is associated with high morbidity and mortality. The diagnosis and treatment of multivessel disease have evolved in the PCI era from solely a visual estimation of ischemic risk to a functional evaluation during angiography. This review summarizes the evidence and discusses the commonly used methods of multivessel coronary artery stenosis physiologic assessment. RECENT FINDINGS: While FFR remains the gold standard in coronary physiologic assessment, several pressure-wire-based non-hyperemic indices of functional stenosis have been developed and validated as well as wire-free angiographically derived quantitative flow ratio. Identifying and treating functionally significant coronary atherosclerotic lesions reduce symptoms and major adverse cardiovascular events. Coronary physiologic assessment in multivessel disease minimizes the observer bias in visual estimates of stenosis, changes clinical management, and improves patient outcomes.