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Ugi-four component reaction (Ugi-4CR) is extremely attractive for diversity-oriented and step economical synthesis as evident from past applications. Here we report the synthesis of fused polycyclic β-carboline derivatives by sequential Pictet-Spengler's and Ugi-4CR multi-component reaction followed by cascade cyclization. The post cyclisation of Ugi product provides conformationally stable heterocyclic molecule that is expected to be suitable for interaction with different biological targets. The methodology provides a simple and facile access to heterocycles embedded in polycyclic framework which otherwise seems difficult to synthesize by conventional methods. Synthesis of fused Polycyclic β-Carboline Derivatives Using Ugi-4CR Followed by Cascade Cyclization., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Several one-dimensional and three-dimensional CdS@CeO 2 nanocomposites were synthesized by a solvothermal route. A nanoflower-shaped CdS@CeO 2 nanocomposite (CdS-NF@CeO 2 ) was selected as the model catalyst after various characterizations. It was, then, employed directly as a luminescent sensor for Cr(VI) detection in an aqueous medium. A good linear quenching was observed in the range of 0-0.5 μM with a detection limit of 0.04 μM. The quantum yield of the catalyst was found to be 73%. Moreover, our catalyst is highly selective toward Cr(VI) and can be applied as an efficient sensor for real water analysis. The efficiency of the catalyst was also tested in controlling the photocatalytic activity for oxidation of benzylamine to N-benzylidenebenzylamine under a domestic LED bulb with molecular O 2 as a sole, green oxidant. Conversion (>99.9%) and selectivity as high as 100% were observed for the CdS-NF@CeO 2 photocatalyst. These results show the potential applications of CdS-NF@CeO 2 nanocomposites as an efficient photocatalyst for organic transformation and environmental remediation., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Electroencephalogram (EEG) is a very promising and widely implemented procedure to study brain signals and activities by amplifying and measuring the post-synaptical potential arising from electrical impulses produced by neurons and detected by specialized electrodes attached to specific points in the scalp. It can be studied for detecting brain abnormalities, headaches, and other conditions. However, there are limited studies performed to establish a smart decision-making model to identify EEG's relation with the mood of the subject. In this experiment, EEG signals of 28 healthy human subjects have been observed with consent and attempts have been made to study and recognise moods. Savitzky-Golay band-pass filtering and Independent Component Analysis have been used for data filtration.Different neural network algorithms have been implemented to analyze and classify the EEG data based on the mood of the subject. The model is further optimised by the usage of Blackman window-based Fourier Transformation and extracting the most significant frequencies for each electrode. Using these techniques, up to 96.01% detection accuracy has been obtained., (© 2023 IOP Publishing Ltd.)

Introduction: Natural carotenoids are well known for their anti-oxidant property and also shown to have antimicrobial and anticancer efficacy. Production of carotenoids from microbial resources mainly from yeast has attracted commercial interest. Breast cancer has the highest incidence among women, and therapy resistance and lack of effective therapeutic strategies are major treatment bottlenecks, particularly for triple-negative subtypes. Yeast carotenoids are recently being evaluated for affordable, non-toxic, natural product-based therapies. In the present study, we have shown an environment-friendly and inexpensive method for carotenoid production from yeasts, utilizing "mandi" wastes, and investigated the biomedical properties of carotenoids, particularly antineoplastic properties., Methods: Vegetable "mandi" waste was used to prepare waste hydrolysate, a culture medium, in which oleaginous red yeast Rhodosporidium sp. was grown. Carotenoid pigments were extracted using the solvent extraction method and analyzed by UV spectroscopy, thin-layer chromatography (TLC), and high-performance liquid chromatography (HPLC). Antimicrobial, antioxidant, and anticancer activities of the extract were evaluated, followed by in silico docking and absorption, distribution, metabolism, and excretion/toxicity (ADME/T) studies., Results: Carotenoid extract was found to be composed of three main pigments-β-carotene, torulene, and torularhodin. Extract exhibited significant antioxidant, antimicrobial, and anti-breast cancer activities in vitro while being biocompatible. Interestingly, carotenoids have shown better efficacy in triple-negative breast cancer (TNBC) cells than ER+PR+ cells. In silico evaluation predicted binding with breast cancer-specific molecular targets, specifically the three components showed good binding energy toward VEGF receptors and good drug likeliness properties, as well as less toxicity., Discussion: This is the first report on anti-breast cancer activities, particularly targeting TNBC cells by red yeast carotenoids (β-carotene, torulene, and torularhodin) produced via a sustainable environment-friendly bioprocess utilizing waste hydrolysate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. One of the handling editors for this special issue is DP, who is also an author of this submitted manuscript. We have therefore suggested name of other handling editor Shashi Kant Bhatia for our manuscript to avoid the conflict., (Copyright © 2023 Sinha, Das, Saha, Paul and Basu.)

Biofilms, ubiquitous in nature, are three-dimensional complex microbial communities sheathed in a self-secreted extracellular polymeric matrix. Infections caused by these communities have sprouted as serious threats to global healthcare systems due to their intrinsic tolerance toward conventional antibiotics. There is a huge demand for alternative "cutting-edge" materials featuring strong antibiofilm abilities to mitigate and/or exterminate pre-matured biofilms. Natural or synthetic macromolecule-based compounds have evolved as one of the most sought-after materials because of their unique stimulus-directed selective targeting efficiency to the bacterial cell, antibiotic-encapsulation ability endowing them with a synergistic effect, and highly dense embedded cationic functionalities that promote accumulation within the biofilm. In this comprehensive review, we aim to highlight the progress made in inhibiting or eradicating bacterial biofilms using various forms of polymeric material including cationic and charge-switchable macromolecules, conjugated polymers, polymeric metal nanocomposites, hydrogels, and supramolecular polymers. We particularly emphasize understanding the underlying antibiofilm mechanisms of each presented example ushered in by state-of-the-art synthetic strategies. Lastly, focusing on bench-to-bedside, the review is concluded by providing some forthcoming aspects and possible future development directions to expand polymer-based antibiofilm research, keeping their clinical translations in mind.

This study proposed a two-step method involving hydrothermal and electrostatic self-assembly processes for synthesising an amine-functionalised magnetic ligand graphene oxide-based nanocomposite (EDTA@Fe 3 O 4 @GO). The amine groups were successfully attached to the surface of iron (II, III) oxide (Fe 3 O 4 ), which were embedded on the surface of graphene oxide (GO) (Fe 3 O 4 @GO). This EDTA@ Fe 3 O 4 @GO nanocomposite was used as a chelating agent to bind the toxic heavy metal ions. EDTA@Fe 3 O 4 @GO demonstrated the synergistic effect between the large surface area and magnetic behaviour of Fe 3 O 4 @GO and the chelating effect of EDTA, and it showed higher efficiency than the individual GO and Fe 3 O 4 . The possible structural and compositional characteristics were proposed based on Fourier transform infrared spectra (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM), Brunauer-Emmett-Teller (BET) and Raman spectroscopy analysis. The outcomes revealed the mechanism behind the excellent As(V) adsorption onto EDTA@Fe 3 O 4 @GO. The adsorption process was studied by fitting the experimental data obtained into various kinetic and isotherm models. The pseudo-second-order (PSO) kinetic model and the Freundlich isotherm model (FIM) were found to be the best fit models for the removal of As(V) by EDTA@Fe 3 O 4 @GO. EDTA@Fe 3 O 4 @GO has the utmost adsorption capacity of 178.4 mg/g. Furthermore, the EDTA@Fe 3 O 4 @GO nanocomposite is reusable, and it showed excellent adsorption capacity up to 5 cycles. This study has provided insight into the potential of EDTA@Fe 3 O 4 @GO and its applications in large-scale wastewater treatment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fixation of atmospheric dinitrogen in plants by [Mo-Fe] cofactor of nitrogenase enzyme takes place efficiently under atmospheric pressure and normal temperature. In search for an alternative methodology for the highly energy intensive Haber-Bosch process, design and synthesis of highly efficient inorganic and organometallic complexes by mimicking the structure and function of [Mo-Fe] cofactor system is highly desirable for ammonia synthesis from dinitrogen. An ideal catalyst for ammonia synthesis should effectively catalyse the reduction of dinitrogen in the presence of a proton source under mild to moderate conditions, and thereby, significantly reducing the cost of ammonia production and increasing the energy efficacy of the process. In the light of current research, it is evident that there is a plenty of scope for the development and enhanced performance of the inorganic and organometallic catalysts for ammonia synthesis under ambient temperature and pressure. The review furnishes a comprehensive outlook of numerous organometallic catalysts used in the synthesis of ammonia from dinitrogen in the past few decades., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Blast injuries from improvised explosive devices (IEDs) are known to cause blast traumatic brain injuries (bTBIs), hemorrhagic shock (HS), organ damage, mitochondrial dysfunction, and subsequent free radical production. A pre-citric acid cycle reagent, pyruvate, is suggested to improve mitochondrial ATP production through the activation of the mitochondrial gatekeeper enzyme "pyruvate dehydrogenase complex (PDH)." Our study aimed to investigate the role of physiologic, metabolic, and mitochondrial effects of hypertonic sodium pyruvate resuscitation in rats with a combined blast and HS injury., Methods: A pre-clinical rat model of combined injury with repetitive 20 PSI blast exposure accompanied with HS and fluid resuscitation (sodium pyruvate as metabolic adjuvant or hypertonic saline as control), followed by transfusion of shed blood was used in this study. Control sham animals (instrumental and time-matched) received anesthesia and cannulation, but neither received any injury nor treatment. The mean arterial pressure and heart rate were recorded throughout the experiment by a computerized program. Blood collected at T0 (baseline), T60 (after HS), and T180 (end) was analyzed for blood chemistry and mitochondrial PDH enzyme activity., Results: Sodium pyruvate resuscitation significantly improved the mean arterial pressure (MAP), heart rate (HR), pulse pressure (PP), hemodynamic stability (Shock index), and autonomic response (Kerdo index) after the HS and/or blast injury. Compared with the baseline values, plasma lactate and lactate/pyruvate ratios were significantly increased. In contrast, base excess BE/( HCO 3 - ) was low and the pH was also acidotic <7.3, indicating the sign of metabolic acidosis after blast and HS in all animal groups. Sodium pyruvate infusion significantly corrected these parameters at the end of the experiment. The PDH activity also improved after the sodium pyruvate infusion., Conclusion: In our rat model of a combined blast and HS injury, hypertonic sodium pyruvate resuscitation was significantly effective in hemodynamic stabilization by correcting the acid-base status and mitochondrial mechanisms via its pyruvate dehydrogenase enzyme., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Saha, Sahu and Sharma.)

Platelets extravasate from the circulation into tumor microenvironment, enable metastasis, and confer resistance to chemotherapy in several cancers. Therefore, arresting tumor-platelet cross-talk with effective and atoxic antiplatelet agents in combination with anticancer drugs may serve as an effective cancer treatment strategy. To test this concept, we create an ovarian tumor microenvironment chip (OTME-Chip) that consists of a platelet-perfused tumor microenvironment and which recapitulates platelet extravasation and its consequences. By including gene-edited tumors and RNA sequencing, this organ-on-chip revealed that platelets and tumors interact through glycoprotein VI (GPVI) and tumor galectin-3 under shear. Last, as proof of principle of a clinical trial, we showed that a GPVI inhibitor, Revacept, impairs metastatic potential and improves chemotherapy. Since GPVI is an antithrombotic target that does not impair hemostasis, it represents a safe cancer therapeutic. We propose that OTME-Chip could be deployed to study other vascular and hematological targets in cancer., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

Aims: COVID-19 has currently emerged as the major global pandemic affecting the lives of people across the globe. It broke out from Wuhan Province of China, first reported to WHO on 31 st December 2019 as "Pneumonia of unknown cause". Over time more people were infected with this virus, and the only tactic to ensure safety was to take precautionary measures due to the lack of any effective treatment or vaccines. As a result of unavailability of desired efficacy for previously repurposed drugs, exploring novel scaffolds against the virus has become the need of the hour., Main Methods: In the present study, 23 new annomontine analogues were designed representing β -Carboline based scaffolds. A hypothesis on its role as an effective ligand was laid for target-specific binding in SARS-CoV-2. These molecules were used for molecular docking analysis against the multiple possible drug targets using the Maestro Interface. To ensure the drug safety of these molecules ADME/Tox analysis was also performed., Key Findings: The molecular docking analysis of the 23 novel molecules indicated the efficiency of these derivates against COVID-19. The efficiency of molecules was computed by the summation of the docking score against each target defined as Lig E Score and compared against Hydroxycholoquine as a standard. Based on the docking score, the majority of the annomontine derivatives were found to have increased binding affinity with targets as compared to hydroxycholoquine., Significance: Due to the lack of efficiency, effectiveness, and failure of already repurposed drugs against the COVID-19, the exploration of the novel scaffold that can act as effective treatment is much needed. The current study hence emphasizes the potential of Annomontine based - β - Carboline derivatives as a potential drug candidate against COVID-19., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

In this work, we have synthesized two new [C, C] cyclometalated Ir(iii)-NHC complexes, [IrCp*(C∧C:NHC)Br](1a,b), [Cp* = pentamethylcyclopentadienyl; NHC = (2-flurobenzyl)-1-(4-methoxyphenyl)-1H-imidazoline-2-ylidene (a); (2-flurobenzyl)-1-(4-formylphenyl)-1H-imidazoline-2-ylidene (b)] via intramolecular C-H bond activation. The molecular structure of complex 1a was determined by X-ray single crystal analysis. The catalytic potentials of the complexes were explored for acceptorless dehydrogenation of alcohols to carboxylic acids with concomitant hydrogen gas evolution. Under similar experimental conditions, complex 1a was found to be slightly more efficient than complex 1b. Using 0.1 mol% of complex 1a, good-to-excellent yields of carboxylic acids/carboxylates have been obtained for a wide range of alcohols, both aliphatic and aromatic, including those involving heterocycles, in a short reaction time with a low loading of catalyst. Remarkably, our method can produce benzoic acid from benzyl alcohol on a gram scale with a catalyst-to-substrate ratio as low as 1 : 5000 and exhibit a TON of 4550. Furthermore, the catalyst could be recycled at least three times without losing its activity. A mechanism has been proposed based on controlled experiments and in situ NMR study.

In ovarian cancer, platelet extravasation into the tumor and resulting metastasis is thought to be regulated mostly by the vascular endothelium. Because it is difficult to dissect complex underlying events in murine models, organ-on-a-chip methodology is applied to model vascular and platelet functions in ovarian cancer. This system (OvCa-Chip) consists of microfluidic chambers that are lined by human ovarian tumor cells interfaced with a 3-dimensional endothelialized lumen. Subsequent perfusion with human platelets within the device's vascular endothelial compartment under microvascular shear conditions for 5 days uncovered organ-to-molecular-level contributions of the endothelium to triggering platelet extravasation into tumors. Further, analysis of effluents available from the device's individual tumor and endothelial chambers revealed temporal dynamics of vascular disintegration caused by cancer cells, a differential increase in cytokine expression, and an alteration of barrier maintenance genes in endothelial cells. These events, when analyzed within the device over time, made the vascular tissue leaky and promoted platelet extravasation. Atorvastatin treatment of the endothelial cells within the OvCa-Chip revealed improved endothelial barrier function, reduction in inflammatory cytokines and, eventually, arrest of platelet extravasation. These data were validated through corresponding observations in patient-derived tumor samples. The OvCa-Chip provides a novel in vitro dissectible platform to model the mechanisms of the cancer-vascular-hematology nexus and the analyses of potential therapeutics., (© 2020 by The American Society of Hematology.)

A general and simple metal-free protocol for expedient C-H functionalization leading to the regioselective generation of C-5 chalcogenated 8-aminoquinoline analogues in up to 90% yield at room temperature (25 °C) has been established. This methodology is an eco-friendly approach to the atom-economical utilization of diaryl/dialkyl chalcogenides for direct access to chalcogenated quinolines and is scalable to the gram scale without considerable decrease in the yield of the product. It represents a practical alternative to the existing metal-catalyzed functionalization of 8-aminoquinoline derivatives with broad functional group tolerance. The controlled experiments suggest that the reaction possibly proceeds through an ionic pathway at room temperature. Furthermore, the potentiality for the functionalization of free amines in chalcogenated-8-aminoquinolines provides an attractive perspective for further elaboration of the amine substituent through chemical manipulations. The applicability of the standardized method has been augmented through late-stage antimalarial drug diversification of primaquine analogues.

Cloud point driven interaction and relaxation dynamics of aqueous solutions of amphiphilic thermoresponsive copolymers were explored through picosecond resolved and steady state fluorescence measurements employing hydrophilic (coumarin 343, C343) and hydrophobic (coumarin 153, C153) solute probes of comparable sizes. These thermoresponsive random copolymers, with tunable cloud point temperatures ( T cp 's) between 298 and 323 K, were rationally designed first and then synthesized via reversible addition-fragmentation chain transfer (RAFT) copolymerization of methyl methacrylate (MMA) and poly(ethylene glycol) monomethyl ether methacrylate (PEGMA). Subsequently, copolymers were characterized by NMR spectroscopy and size exclusion chromatography (SEC). A balance between the hydrophilic (PEGMA) and the hydrophobic (MMA) content dictates the critical aggregation concentration (CAC), with CAC ∼ 2-14 mg/L for these copolymers in aqueous media. No abrupt changes in the steady state spectral features of both C153 and C343 in the aqueous solutions of these polymers near but below the cloud point temperatures were observed. Interestingly, spectral properties of C153 in these solutions show the impact of hydrophobic/hydrophilic interaction balance but not by those of C343. More specifically, C153 reported a blue shift (relative to that in neat water) and heterogeneity in its local environment. This suggested different locations for the hydrophilic (C343) and the hydrophobic (C153) probes. In addition, the excited state fluorescence lifetime (⟨τ life ⟩) of C153 increased with the increase of hydrophobic (MMA) content in these copolymers. However, C343 reported no such variations, although fluorescence anisotropy decays for both solutes were significantly slowed down in these aqueous solutions compared to neat water. Anisotropy decays indicated bimodal time-dependent friction for these solutes in aqueous solutions of these copolymers but monomodal in neat water. A linear dependence of the average rotational relaxation rates (⟨ k rot ⟩ = ⟨τ rot ⟩ -1 ) of the type ⟨ k rot ⟩ ∝ (| T - T cp |/ T cp ) γ with negative values for the exponent γ was observed for both solutes. No slowing down of the solute rotation with temperature approaching the T cp was detected; rather, rotation became faster upon increasing the solution temperature, suggesting domination of the local friction.

Since temperature is one of the most significant physiological parameters that dictate the cellular status of living organisms, accurate intracellular temperature measurement is crucial and a valuable biomarker for the diagnosis and treatment of diseases. Herein, we introduce the foremost example of a non-conjugated polymer as a next generation fluorescent thermometer which is capable of addressing the key shortcomings including toxicity and thermal-induced fluorescence quenching associated with π-π conjugated system-based thermometers developed so far. We revealed, for the first time, the unique photophysical and aggregation-induced emission (AIE) characteristics of well-known thermoresponsive poly( N -vinylcaprolactam) (PNVCL) devoid of any classical fluorophore entity. PNVCL underwent a coil to globular conformational transition in an aqueous medium and appeared to be fluorescent above its lower critical solution temperature (LCST) near body temperature (38 °C). Eventually, this intriguing aspect enabled higher cellular uptake of PNVCL at the LCST boundary. By virtue of the AIE effect, the thermo-induced aggregation phenomenon has been ingeniously utilized to apply PNVCL as a novel fluorescent thermometer for intracellular temperature determination., (This journal is © The Royal Society of Chemistry 2020.)

We explore in this work, after synthesizing and appropriately characterizing an amphiphilic diblock copolymer, its interaction with water molecules and the subsequent aqueous solution dynamics by employing time-resolved fluorescence measurements (TRF) and megahertz-gigahertz dielectric relaxation (DR) experiments. The synthesized amphiphilic diblock copolymer is poly(2-((( tert -butoxycarbonyl)alanyl)oxy)ethyl methacrylate)- b -poly(polyethylene glycol monomethyl ether methacrylate) (P(Boc-l-Ala-HEMA)- b -PPEGMA). Dynamic light scattering measurements of aqueous solutions indicate formation of 14-20 nm particles from a balance between the chain lengths of the hydrophobic (P(Boc-l-Ala-HEMA) and hydrophilic (PPEGMA) segments. Field-emission scanning electron microscopy, on the other hand, suggests a spherical shape for the dried micelles. The critical micelle concentration of the P(Boc-l-Ala-HEMA)- b -PPEGMA block copolymer at different block lengths in aqueous media, determined via steady-state fluorescence measurements, is very low (∼4-8 mg/L), and the resultant micellar size has been found to be insensitive to the polymer concentration. Interfacial and bulk aqueous dynamics have been investigated by tracking the solution frictional resistance on rotational motion of dissolved hydrophobic and hydrophilic dipolar solute probes of comparable sizes. TRF anisotropy measurements reflect the biphasic temporal profile for the frictional resistance. Interestingly, the hydrophobic probe, because of its preferential location at the micellar interface, experiences greater frictional resistance than the hydrophilic counterpart, although the latter reports stronger polymer concentration dependence of the frictional retardation than the former. DR measurements at the highest of the polymer concentrations considered suggest presence of aqueous dynamics slower than that for neat bulk water, although evidence for such "slow" dynamics at lower concentrations has not been detected in the present DR measurements.

Delivery of clinically approved nonfluorescent drugs is facing challenges because it is difficult to monitor the intracellular drug delivery without incorporating any integrated fluorescence moiety into the drug carrier. The present investigation reports the synthesis of a pH-responsive autofluorescent polymeric nanoscaffold for the administration of nonfluorescent aromatic nitrogen mustard chlorambucil (CBL) drug into the cancer cells. Copolymerization of poly(ethylene glycol) (PEG) appended styrene and CBL conjugated N-substituted maleimide monomers enables the formation of well-defined luminescent alternating copolymer. These amphiphilic brush copolymers self-organized in aqueous medium into 25-68 nm nanoparticles, where the CBL drug is enclosed into the core of the self-assembled nanoparticles. In vitro studies revealed ∼70% drug was retained under physiological conditions at pH 7.4 and 37 °C. At endolysosomal pH 5.0, 90% of the CBL was released by the pH-induced cleavage of the aliphatic ester linkages connecting CBL to the maleimide unit. Although the nascent nanoparticle (without drug conjugation) is nontoxic, the drug conjugated nanoparticle showed higher toxicity and superior cell killing capability in cervical cancer (HeLa) cells rather than in normal cells. Interestingly, the copolymer without any conventional chromophore exhibited photoluminescence under UV light irradiation due to the presence of "through-space" π-π interaction between the C═O group of maleimide unit and the adjacent benzene ring of the styrenic monomer. This property helped us intracellular tracking of CBL conjugated autofluorescent nanocarriers through fluorescence microscope imaging. Finally, the 4-(4-nitrobenzyl)pyridine (NBP) colorimetric assay was executed to examine the ability of CBL-based polymeric nanomaterials toward alkylation of DNA.

Background: Aeromedical evacuation to definitive care is standard in current military conflicts. However, there is minimal knowledge on the effects of hypobaria (HYPO) on either the flight crew or patients. The effects of HYPO were investigated using healthy swine., Methods: Anesthetized Yorkshire swine underwent a simulated 4 h "transport" to an altitude of 2,441 m (8,000 feet.; HYPO, N = 6) or at normobaric conditions (NORMO, N = 6). Physiologic and biochemical data were collected. Organ damage was assessed for hemorrhage, inflammation, edema, necrosis, and for lungs only, microatelectasis., Results: All parameters were similar prior to and after "transport" with no significant effects of HYPO on hemodynamic, neurologic, or oxygen transport parameters, nor on blood gas, chemistry, or complete blood count data. However, the overall Lung Injury Score was significantly worse in the HYPO than the NORMO group (10.78 ± 1.22 vs. 2.31 ± 0.71, respectively) with more edema/fibrin/hemorrhage in the subpleural, interlobular and alveolar space, more congestion in alveolar septa, and evidence of microatelectasis (vs. no microatelectasis in the NORMO group). There was also increased severity of pulmonary neutrophilic (1.69 ± 0.20 vs. 0.19 ± 0.13) and histiocytic inflammation (1.83 ± 0.23 vs. 0.47 ± 0.17) for HYPO versus NORMO, respectively. On the other hand, there was increased renal inflammation in NORMO compared with HYPO (1.00 ± 0.13 vs. 0.33 ± 0.17, respectively). There were no histopathological differences in brain (whole or individual regions), liver, pancreas, or adrenals., Conclusion: Hypobaria, itself, may have an adverse effect on the respiratory system, even in healthy individuals, and this may be superimposed on combat casualties where there may be preexisting lung injury. The additional effects of anesthesia and controlled ventilation on these results are unknown, and further studies are indicated using awake models to better characterize the mechanisms for this pathology and the factors that influence its severity.

In the past, significant effort has been made to develop ultrathin membranes exhibiting physiologically relevant mechanical properties, such as thickness and elasticity of native basement membranes. However, most of these fabricated membranes have a relatively high elastic modulus, ∼MPa-GPa, relevant only to retinal and epithelial basement membranes. Vascular basement membranes exhibiting relatively low elastic modulus, ∼kPa, on the contrary, have seldom been mimicked. Membranes demonstrating high compliance, with moduli ranging in ∼kPa along with sub-microscale thicknesses have rarely been reported, and would be ideal to mimic vascular basement membranes in vitro. To address this, we fabricate ultrathin membranes demonstrating the mechanistic features exhibited by their vascular biological counterparts. Salient features of the fabricated ultrathin membranes include free suspension, physiologically relevant thickness ∼sub-micrometers, relatively low modulus ∼kPa, and sufficiently large culture area ∼20 mm 2 . To fabricate such ultrathin membranes, undiluted PDMS Sylgard 527 was utilized as opposed to the conventional diluted polymer-solvent mixture approach. In addition, the necessity to have a sacrificial layer for releasing membranes from the underlying substrates was also eliminated in our approach. The novelty of our work lies in achieving the distinct combination of membranes having thickness in sub-micrometers and the associated elasticity in kilopascal using undiluted polymer, which past approaches with dilution have not been able to accomplish. The ultrathin membranes with average thickness of 972 nm (thick) and 570 nm (thin) were estimated to have an elastic modulus of 45 and 214 kPa, respectively. Contact angle measurements revealed the ultrathin membranes exhibited hybrophobic characteristics in unpeeled state and transformed to hydrophilic behavior when freely suspended. Human umbilical vein endothelial cells were cultured on the polymeric ultrathin membranes, and the temporal cell response to change in local compliance of the membranes was studied by evaluating the cell spread area, density, percentage area coverage, and spread rate. After 24 h, single cells, pairs, and group of three to four cells were noticed on highly compliant thick membranes, having average thickness of 972 nm and modulus of 45 kPa. On the contrary, the cell monolayer was noted on the glass slide acting as a control. For the thin membranes featuring average thickness of 570 nm and modulus of 214 kPa, the cells tend to exhibit response similar to that on control with initiation of monolayer formation. Our results indicate, the local compliance, in turn, the membrane thickness governs the cell behavior and this can have vital implications during disease initiation and progression, wound healing, and cancer cell metastasis.

This study reports adsorptive removal of Cr(VI) by magnetic manganese ferrite and manganese oxide nano-particles (MnF-MO-NPs) composite from aqueous media. The X-ray diffraction pattern of MnF-MO-NPs revealed a polycrystalline nature with nanoscale crystallite size. The prepared adsorbent with high Brunauer-Emmett-Teller specific surface area of 100.62 m 2 /g and saturation magnetization of 30.12 emu/g exhibited maximum Cr(VI) removal at solution pH 2.0 and was easily separated from water under an external magnetic field. Adsorption capacity as much as 91.24 mg/g is reported and electrostatic interaction between positively charged adsorbent surface and anionic metal ion species is the main driving force in this adsorption. Adsorption experimental data followed Langmuir isotherm and second order kinetics. Partial involvement of intra-particle diffusion was also observed due to the mesoporous nature of MnF-MO-NPs. The thermodynamic studies revealed that the process was favorable, spontaneous and exothermic in nature. An artificial neural network model was developed for accurate prediction of Cr(VI) ions removal with minimum mean squared error (MSE) of 15.4 × 10 -4 and maximum R 2 of 0.98. Owing to large surface to volume ratio, advantage of easy magnetic separation, and high adsorption capacity towards Cr(VI), the reported MnF-MO-NPs appear to be a potential candidate in Cr(VI) contaminated wastewater remediation.

Intermolecular energy transfer for the vibrationally excited propylbenzene cation (C 9 H 12 + ) in a helium bath was studied with chemical dynamics simulations. The bond energy bond order relationship and electronic structure calculations were used to develop an intramolecular potential for C 9 H 12 + . Spin component scaled MP2/6-311++G** calculations were used to develop an intermolecular potential for He + C 9 H 12 + . The He + He intermolecular potential was determined from a previous explicitly correlated Gaussian electronic structure calculation. For the simulations, C 9 H 12 + was prepared with a 100.1 kcal/mol excitation energy to compare with experiment. The average energy transfer from C 9 H 12 + , ⟨ΔE c ⟩, decreased as C 9 H 12 + was vibrationally relaxed and for the initial excitation energy ⟨ΔE c ⟩ = 0.64 kcal/mol. This result agrees well with the experimental ⟨ΔE c ⟩ value of 0.51 ± 0.26 kcal/mol for collisions of He with the ethylbenzene cation. The ⟨ΔE c ⟩ value found for He + C 9 H 12 + collisions is compared with reported values of ⟨ΔE c ⟩ for He colliding with other molecules.

A one-dimensional nanostructure with sp 3 -hybridized carbon atoms, namely, poly[5]asterane (PA), is predicted by means of electronic structure calculations and reactive molecular dynamics simulations. Thermochemical analysis based on homodesmotic reactions showed that the formation of poly[5]asterane is more favorable than that of polytriangulane and comparable to that of polytwistane. A plane-wave DFT approach gave a computed Young's modulus of about 0.84 TPa, which is quite promising and comparable to those of other sp 3 -hybridized nanothreads. Simulations of the desorption of hydrogen atoms from PA showed a high activation energy (E a ≈52 kcal mol -1 ), which again indicates substantial chemical stability. Interestingly, PA was shown to exhibit auxetic behavior (negative Poisson's ratio). Thus, PA is advocated as a new mechanically and chemically stable nanothread with exotic auxetic behavior., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Over the past decade, the demand for high-performance wearable sensors has increased because of their capability for interaction with humans. Such sensors have typically been prepared on conventional substrates, such as silicon, PDMS, and copper mesh. In this work, we propose a class of wearable sensors fabricated from reduced graphene oxide (rGO) patterned paper substrates (rGO-paper). These rGO-paper sensors are highly sensitive to various deformations and capable of measuring bending and folding angles as small as 0.2° and 0.1°, respectively. We have demonstrated the applicability of these high-performance rGO-paper sensors by patterning rGO on kirigamis that can detect pulse and the motion of knees, wrists, and fingers. Finally, paper rings lined with rGO sensors were used to control a robotic hand, and an rGO-paper keyboard was used to light LEDs.

Oxygen-carrying perfluorocarbon (PFC) fluids have the potential to increase tissue oxygenation during hypoxic states and to reduce ischemic cell death. Regulatory approval of oxygen therapeutics was halted due to concerns over vasoconstrictive side effects. The goal of this study was to assess the potential vasoactive properties of Perftoran by measuring brain pial arteriolar diameters in a healthy rat model. Perftoran, crystalloid (saline) or colloid (Hextend) solutions were administered as four sequential 30 min intravenous (IV) infusions, thus allowing an evaluation of cumulative dose-dependent effects. There were no overall changes in diameters of small-sized (<50 μm) pial arterioles within the Perftoran group, while both saline and Hextend groups exhibited vasoconstriction. Medium-sized arterioles (50-100 μm) showed minor (~8-9%) vasoconstriction within saline and Hextend groups and only ~5% vasoconstriction within the Perftoran group. For small- and medium-sized pial arterioles, the mean percent change in vessel diameters was not different among the groups. Although there was a tendency for arterial blood pressures to increase with Perftoran, pressures were not different from the other two groups. These data show that Perftoran, when administered to healthy anesthetized rats, does not cause additional vasoconstriction in cerebral pial arterioles or increase systemic blood pressure compared with saline or Hextend., Competing Interests: The authors declare no conflict of interest. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government. Authors are military service members (or an employee of the U.S. Government). This work was prepared as part of their official duties. Title 17 USC §105 provides that “copyright protection under this title is not available for any work of the U.S. Government”. Title 17 USC §101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person’s official duties.

Recently, polymer drug conjugates (PDCs) have attracted considerable attention in the treatment of cancer. In this work, a simple strategy has been developed to make PDCs of an antitumor alkylating agent, chlorambucil, using a biocompatible disulphide linker. Chlorambucil-based chain transfer agent was used to prepare various homopolymers and block copolymers in a controlled fashion via reversible addition-fragmentation chain transfer polymerization. Chlorambucil conjugated block copolymer, poly(polyethylene glycol monomethyl ether methacrylate)-b-poly(methyl methacrylate), formed nanoaggregates in aqueous solutions, which are characterized by dynamic light scattering and field emission-scanning electron microscopy. Finally, the simplicity of the design is exemplified by performing a release study of chlorambucil under reducing condition by using D,L-dithiothreitol., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Hypoxia is a critical secondary injury mechanism in traumatic brain injury (TBI), and early intervention to alleviate post-TBI hypoxia may be beneficial. NVX-108, a dodecafluoropentane perfluorocarbon, was screened for its ability to increase brain tissue oxygen tension (PbtO2) when administered soon after TBI., Methods: Ketamine-acepromazine anesthetized rats ventilated with 40% oxygen underwent moderate controlled cortical impact (CCI)-TBI at time 0 (T0). Rats received either no treatment (NON, n=8) or 0.5 ml/kg intravenous (IV) NVX-108 (NVX, n=9) at T15 (15 min after TBI) and T75., Results: Baseline cortical PbtO2 was 28±3 mm Hg and CCI-TBI resulted in a 46±6% reduction in PbtO2 at T15 (P<0.001). Significant differences in time-group interactions (P=0.013) were found when comparing either absolute or percentage change of PbtO2 to post-injury (mixed-model ANOVA) suggesting that administration of NVX-108 increased PbtO2 above injury levels while it remained depressed in the NON group. Specifically in the NVX group, PbtO2 increased to a peak 143% of T15 (P=0.02) 60 min after completion of NVX-108 injection (T135). Systemic blood pressure was not different between the groups., Conclusion: NVX-108 caused an increase in PbtO2 following CCI-TBI in rats and should be evaluated further as a possible immediate treatment for TBI., (Published by Elsevier B.V.)

In the crystal of the title compound, C26H31N3O2, pairs of N-H⋯O hydrogen bonds link molecules, forming inversion dimers, which enclose an R 2 (2)(20) ring motif. One N atom does not form hydrogen bonds and lies in a hydro-phobic pocket with closest inter-molecular contacts of 4.196 (2) and 4.262 (2) Å.

Substituted 1-azidocyclopentenes and 1-azidocyclohexenes were photolyzed to generate 2,3-bridged 2H-azirines. In the case of bridgehead azirines with a six-membered carbocycle, detection by NMR spectroscopic analysis was possible, whereas even kinetically stabilized bridgehead azirines with a five-membered ring could not be characterized by low-temperature NMR spectroscopic analysis. Thus, a recent report on the latter heterocycles was corrected. Depending on the substitution pattern, irradiation of 1-azidocyclopentenes either led to products that can be explained on the basis of short-lived 2,3-bridged 2H-azirines, or gave secondary products generated from triplet nitrenes. The diverse photoreactivity of 2,3-bridged 2H-azirines was also studied by quantum chemical methods (DFT, CCSD(T), CASSCF(6,6)) with respect to the singlet and triplet energy surfaces. The ring-opening processes leading to the corresponding vinyl nitrenes were identified as key steps for the observed reactivity., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Dipalladium(I) and diruthenium(I) compounds bridged by two [{(5,7-dimethyl-1,8-naphthyridin-2-yl)amino}carbonyl]ferrocene (L) ligands have been synthesized. The X-ray structures of [Pd(2)L(2)][BF(4)](2) (1) and [Ru(2)L(2)(CO)(4)][BF(4)](2) (2) reveal dinuclear structures with short metal-metal distances. In both of these structures, naphthyridine bridges the dimetal unit, and the site trans to the metal-metal bond is occupied by weakly coordinating oxygen from the amido fragment. The catalytic utilities of these bimetallic compounds are evaluated. Compound 1 is an excellent catalyst for phosphine-free, Suzuki cross-coupling reactions of aryl bromides with arylboronic acids and provides high yields in short reaction times. Compound 1 is also found to be catalytically active for aryl chlorides, although the corresponding yields are lower. A bimetallic mechanism is proposed, which involves the oxidative addition of aryl bromide across the Pd-Pd bond and the bimetallic reductive elimination of the product. Compound 1 is also an efficient catalyst for the Heck cross-coupling of aryl bromides with styrenes. The mechanism for aldehyde olefination with ethyl diazoacetate (EDA) and PPh(3), catalyzed by 2, has been fully elucidated. It is demonstrated that 2 catalyzes the formation of phosphorane utilizing EDA and PPh(3), which subsequently reacts with aldehyde to produce a new olefin and phosphine oxide. The efficacy of bimetallic complexes in catalytic organic transformations is illustrated in this work.

High temperature quantum chemical molecular dynamics simulations on the polycyclic aromatic hydrocarbon (PAH) formation during combustion of benzene were performed using the density-functional tight-binding (DFTB) method. Systems with varying H/C of 0.8, 0.6, 0.4, and 0.2 and temperatures of T(n)=2500 K and T(n)=3000 K were employed for the study of the PAH formation and growth mechanism, and trajectories were analyzed by recording average C:H compositions, common elementary reactions and molecular species, ring count, and other characteristic quantities as functions of time. We found that at H/C=0.8 mostly short polyacetylenic hydrocarbons were formed, and no significant PAH growth was found. At lower H/C ratio, longer polyacetylenic chains started to form and new five- and six-membered rings were created due to chain entanglement. Significant PAH growth forming only pericondensed PAHs was observed at lower H/C ratios of 0.4 and 0.2. In addition, smaller hydrocarbon species, such as C(2)H(2), C(2)H, and C(2), are constantly produced by fragmentation of hydrocarbons (unimolecular reactions) and remain common species, although they are simultaneously consumed by the H-abstraction-C(2)H(2)-addition growth mechanism. Hydrogen is found to have a clear inhibitive effect on PAH and carbon cluster growth in general, in agreement with recent experimental observations.

The 1,8-naphthyridine-functionalized N-heterocyclic carbene 1-benzyl-3-(5,7-dimethyl-1,8-naphthyrid-2-yl)imidazol-2-ylidene (BIN) has been successfully coordinated to Pd(II), W(0), Rh(I), and Ir(III), exhibiting its diverse binding modes. Reaction of BIN x HBr with Ag(2)O, followed by transmetalation with PdCl(2)(COD)(2) provides a cis complex PdCl(2)(kappaC(2)-BIN)(2) (1). Treatment of BIN x HBr with W(CO)(4)(piperidine)(2) in acetonitrile affords a chelate complex W(CO)(4)(kappa(2)C(2),N(1)'-BIN) (2). Reaction of {RhCl(COD)}(2) with KO(t)Bu and subsequent treatment with BIN x HBr in 1:2 and 1:1 ratio results in the mono and dinuclear complexes [Rh(COD)Br(kappaC(2)-BIN)] (3) and [{Rh(COD)Br}(2)(kappaN(8)':kappaC(2)-BIN)] (4), respectively. In complex 3, the "Rh(COD)Br" unit is coordinated to the carbene center, whereas an additional "Rh(COD)Br" unit is attached to naphthyridine nitrogen in complex 4 in an anti arrangement. Under identical reaction condition, a novel Ir(III) complex [Ir(kappa(2)C(2),N(1)'-BIN)(kappa(2)C(3)',C(2)-BIN)(H(2)O)Br]Br (5) has been synthesized. Complex 5 is proved to be catalytically active in hydrogen transfer reaction from (i)PrOH. All complexes have been characterized by spectroscopic methods and X-ray crystallography.

A pathogenic vancomycin-resistant Staphylococcus aureus (VRSA) isolate (MIC > or =64 microg ml(-1)) was obtained from a Kolkata hospital in June 2005. Species identification was confirmed by Gram staining, standard biochemical tests and PCR amplification of the nuc gene, which encodes the thermostable nuclease that is highly specific for S. aureus. The VRSA isolate was also resistant to beta-lactams (amoxicillin, ampicillin, cefepime, cefotaxime, cefuroxime, cephalexin and meticillin), chloramphenicol, streptomycin, macrolides (erythromycin and roxithromycin), clindamycin, rifampicin and trimethoprim-sulfamethoxazole. However, the isolate was susceptible to gentamicin (an aminoglycoside) and ciprofloxacin (a fluoroquinolone). The resistance to vancomycin was inducible in vitro, because the MIC of vancomycin increased from 64 microg ml(-1) initially to 1024 microg ml(-1) during culture of this VRSA strain in the presence of vancomycin. The VRSA isolate contained a large plasmid ( approximately 53.4 kb) and four small plasmids of approximately 6, 5.5, 5.1 and 1.5 kb. The large plasmid of approximately 53.4 kb harboured the vancomycin-resistance genes vanHAX, which was confirmed by PCR amplification using the same plasmid as template and, separately, primers specific for the 2.61 kb vanHAX gene cluster, vanH (969 bp), vanA (1032 bp) and vanX (609 bp). The VRSA isolate was also positive for mecA. Vancomycin resistance was successfully transferred from this VRSA donor to a vancomycin-sensitive recipient S. aureus clinical isolate by a broth mating procedure. The MIC of vancomycin for the transconjugant was 32 microg ml(-1), as against 2 microg ml(-1) for the parent strain. Nucleotide sequencing of the PCR product showed partial homology with van genes of an enterococcal transposon Tn1546-like element. This is believed to be the first Indian S. aureus isolate that has been shown to be phenotypically vancomycin-resistant, presumably due to a vanHAX analogue.

Halide or alkoxide free yttrium-salen complexes are excellent catalysts for the ring opening of epoxides mediated by TMSCN and TMSN3. Substrate to catalyst ratios up to 10000 have been realized in these potentially useful reactions, which can be run under solvent-free conditions. Even though the enantioselectivities for the TMSCN-mediated reaction remains modest (best 77% ee), these studies with a highly tunable ligand system may provide further impetus for work in this important area of catalysis. Even though attempts to isolate a Y-cyanide complex, which was detected by in situ IR spectroscopy, failed, a related dimeric hydroxide complex was isolated. A kinetic study using in situ IR spectroscopy did not provide conclusive data to assign an order with respect to Y in this reaction.

The symmetry-adapted cluster-configuration interaction (SAC-CI) method has been used to investigate the optical and geometric properties of the oligomers of poly(para-phenylene vinylene) (PPV) and poly(para-phenylene) (PP). Vertical singlet and triplet absorption spectra and emission spectra have been calculated accurately; the mean average deviation from available experimental results lies within 0.2 eV. The chain length dependence of the transition energies has been improved in comparison to earlier TDDFT and MRSDCI calculations. The present analysis suggests that conventional TDDFT with the B3LYP functional should be used carefully, as it can provide inaccurate estimates of the chain length dependence of the excitation energies of these molecules with long pi conjugation. The T1 state was predicted to be at a lower energy, by 1.0-1.5 eV for PPV and by 0.9-1.7 eV for PP, than the S1 state, which indicates a localized T1 state with large exchange energy. By calculating the SAC-CI electron density difference between the ground and excited states, the geometry relaxations due to excitations can be analyzed in detail using electrostatic force theory. For trans-stilbene, the doubly excited 21Ag state was studied, and the calculated transition energy of 4.99 eV agrees very well with the experimental value of 4.84 eV. In contrast to previous ab initio calculations, we predict this doubly excited 21Ag state to lie above the 11Bu state.

Excited-state geometries and electronic spectra of butadiene, acrolein, and glyoxal have been investigated by the symmetry adapted cluster configuration interaction (SAC-CI) method in their s-trans conformation. Valence and Rydberg states below the ionization threshold have been precisely calculated with sufficiently flexible basis sets. Vertical and adiabatic excitation energies were well reproduced and the detailed assignments were given taking account of the second moments. The deviations of the vertical excitation energies from the experiment were less than 0.3 eV for all cases. The SAC-CI geometry optimization has been applied to some valence and Rydberg excited states of these molecules in the planar structure. The optimized ground- and excited-state geometries agree well with the available experimental values; deviations lie within 0.03 A and 0.7 degrees for the bond lengths and angles, respectively. The force acting on the nuclei caused by the excitations has been discussed in detail by calculating the SAC-CI electron density difference between the ground and excited states; the geometry relaxation was well interpreted with the electrostatic force theory. In Rydberg excitations, geometry changes were also noticed. Doubly excited states (so-called 2 (1)A(g) states) were investigated by the SAC-CI general-R method considering up to quadruple excitations. The characteristic geometrical changes and large energetic relaxations were predicted for these states.

N-Cinnamoyl-L-proline can be used as a template on which beta-substituted phenylalanine and beta-phenylisoserine residues can be synthesized leading to tripeptide derivatives as structural analogues of HIV protease inhibitors.