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The present paper describes a new and practical approach for the one-pot preparation of O -isopropylidene derivatives and also orthogonally protected S - and O -glycosides from the corresponding unprotected saccharides by employing 2 mol % of a silicomolybdic acid (SMA) cluster as a versatile and biocompatible catalyst. The present protocol is applicable to two-step one-pot tandem transformations, which include the O-isopropylidation, spiroketal functionalization, 4,6- O -arylidene acetalations, and arylidene acetylation processes under relatively mild reaction conditions. One-pot sequential transformations, low catalyst loading, rapid transformation, high to excellent reaction yields, mild reaction conditions, and a nontoxic biocompatible workup procedure are the notable advantages of devised protocol.

Minerals play a vital role, working synergistically with enzymes and other cofactors to regulate physiological functions including tissue healing and regeneration. The bioactive characteristics of mineral-based nanomaterials can be harnessed to facilitate in situ tissue regeneration by attracting endogenous progenitor and stem cells and subsequently directing tissue-specific differentiation. Here, cellular responses of human mesenchymal stem/stromal cells to traditional bioactive mineral-based nanomaterials, such as hydroxyapatite, whitlockite, silicon-dioxide, and the emerging synthetic 2D nanosilicates are investigated. Transcriptome sequencing is utilized to probe the cellular response and determine the significantly affected signaling pathways due to exposure to these inorganic nanomaterials. Transcriptome profiles of stem cells treated with nanosilicates reveals a stabilized skeletal progenitor state suggestive of endochondral differentiation. This observation is bolstered by enhanced deposition of matrix mineralization in nanosilicate treated stem cells compared to control or other treatments. Specifically, use of 2D nanosilicates directs osteogenic differentiation of stem cells via activation of bone morphogenetic proteins and hypoxia-inducible factor 1-alpha signaling pathway. This study provides  insight into impact of nanomaterials on cellular gene expression profile and predicts downstream effects of nanomaterial induction of endochondral differentiation., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Engineered matrices provide a valuable platform to understand the impact of biophysical factors on cellular behavior such as migration, proliferation, differentiation, and tissue remodeling, through mechanotransduction. While recent studies have identified some mechanisms of 3D mechanotransduction, there is still a critical knowledge gap in comprehending the interplay between 3D confinement, ECM properties, and cellular behavior. Specifically, the role of matrix stiffness in directing cellular fate in 3D microenvironment, independent of viscoelasticity, microstructure, and ligand density remains poorly understood. To address this gap, we designed a nanoparticle crosslinker to reinforce collagen-based hydrogels without altering their chemical composition, microstructure, viscoelasticity, and density of cell-adhesion ligand and utilized it to understand cellular dynamics. This crosslinking mechanism utilizes nanoparticles as crosslink epicenter, resulting in 10-fold increase in mechanical stiffness, without other changes. Human mesenchymal stem cells (hMSCs) encapsulated in 3D responded to mechanical stiffness by displaying circular morphology on soft hydrogels (5 kPa) and elongated morphology on stiff hydrogels (30 kPa). Stiff hydrogels facilitated the production and remodeling of nascent extracellular matrix (ECM) and activated mechanotransduction cascade. These changes were driven through intracellular PI3AKT signaling, regulation of epigenetic modifiers and activation of YAP/TAZ signaling. Overall, our study introduces a unique biomaterials platform to understand cell-ECM mechanotransduction in 3D for regenerative medicine as well as disease modelling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Arsenic (As) and silicon (Si) are two structurally competitive natural elements where Si minimises As accumulation in rice plants, and based on this two-year field trial, the study proposes adopting alternating wetting and drying (AWD) irrigation as a sustainable water management strategy allowing greater Si availability. This field-based project is the first report on AWD's impact on As-Si distribution in fluvio-alluvial soils of the entire Ganga valley (24 study sites, six divisions), seasonal variance (pre-monsoon and monsoon), rice plant anatomy and productivity, soil microbial diversity, microbial gene ontology profiling and associated metabolic pathways. Under AWD to flooded and pre-monsoon to monsoon cultivations, respectively, greater Si availability was achieved and As-bioavailability was reduced by 8.7 ± 0.01-9.2 ± 0.02% and 25.7 ± 0.09-26.1 ± 0.01%. In the pre-monsoon and monsoon seasons, the physiological betterment of rice plants led to the high rice grain yield under AWD improved by 8.4 ± 0.07% and 10.0 ± 0.07%, proving the economic profitability. Compared to waterlogging, AWD evidences as an optimal soil condition for supporting soil microbial communities in rice fields, allowing diverse metabolic activities, including As-resistance, and active expression of As-responsive genes and gene products. Greater expressions of gene ontological terms and complex biochemical networking related to As metabolism under AWD proved better cellular, genetic and environmental responsiveness in microbial communities. Finally, by implementing AWD, groundwater usage can be reduced, lowering the cost of pumping and field management and generating an economic profit for farmers. These combined assessments prove the acceptability of AWD for the establishment of multiple sustainable development goals (SDGs)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Two errors appeared in the text of the manuscript titled "Recent Progress on Synthesis of Functionalized 1,5- disubstituted Triazoles", 2024; 21(4) : 513-558 [1]. We regret the errors and apologize to readers. The original article can be found online at: https://www.eurekaselect.com/article/131107., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Over the last two decades, the design and development of fluorescent chemosensors for the targeted detection of Heavy Transition-metal (HTM) ions, anions, and biological analytes, have drawn much interest. Since the introduction of click chemistry in 2001, triazole moieties have become an increasingly prominent theme in chemosensors. Triazoles generated via click reactions are crucial for sensing various ions and biological analytes. Recently, the number of studies in the field of pyrene appendant triazole moieties has risen dramatically, with more sophisticated and reliable triazole-containing chemosensors for various analytes of interest described. This tutorial review provides a general overview of pyrene appendant-triazole-based chemosensors that can detect a variety of metal cations, anions, and neutral analytes by using modular click-derived triazoles., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Click Chemistry, a modular, rapid, and one of the most reliable tool for the regioselective 1,2,3-triazole forming [3+2] reaction of organic azide and terimal alkyne is widely explored in various emerging domains of research ranging from chemical biology to catalysis and medicinal chemistry to material science. This regioselective reaction from a diverse range of azido-alkyne scaffolds has been well performed in both intermolecular as well as intramolecular fashions. In comparison to the intermolecular metal (Cu/Ru/Ni) variant of 'Click Chemistry', the intramolecular click tool is little addressed. The intramolecular click chemistry is exemplified as a mordern tool of cyclization which involves metal-catalyzed (CuAAC/RuAAC) cyclization, organo-catalyzed cyclization, and thermal-induced topochemical reaction. Thus, we report herein the recent approaches on intramolecular azide-alkyne cycloaddition 'Click Chemistry' with their wide-spread emerging applications in the developement of a diverse range of molecules including fused-heterocycles, well-defined peptidomemics, and macrocyclic architectures of various notable features., (© 2023 The Chemical Society of Japan & Wiley-VCH GmbH.)

A novel organocatalyzed [3+2] cycloaddition reaction of nitroolefins with glycosyl azides as well as organic azides has been developed for successful construction of 1,5-disubstituted triazolyl glycoconjugates. This metal-free and acid-free, regioselective synthetic protocol proceeds in the presence of only Schreiner thiourea organocatalysts, which enable the required activation of nitroolefins through double hydrogen bonding. The straightforward, operationally simple, and regioselectivity of this methodology, complementing to the classical RuAAC catalyzed synthesis of 1,5-disubstituted 1,2,3-triazoles. In the presence of catalytic amount of Schreiner thiourea organocatalyst, organic azides react with a broad array of nitroolefins producing a series of diverse 1,5-disubstituted 1,2,3- triazoles in good yields with excellent regioselectivity., (© 2023 Wiley-VCH GmbH.)

A repeat expansion in the C9orf72 (C9) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we investigate single nucleus transcriptomics (snRNA-seq) and epigenomics (snATAC-seq) in postmortem motor and frontal cortices from C9-ALS, C9-FTD, and control donors. C9-ALS donors present pervasive alterations of gene expression with concordant changes in chromatin accessibility and histone modifications. The greatest alterations occur in upper and deep layer excitatory neurons, as well as in astrocytes. In neurons, the changes imply an increase in proteostasis, metabolism, and protein expression pathways, alongside a decrease in neuronal function. In astrocytes, the alterations suggest activation and structural remodeling. Conversely, C9-FTD donors have fewer high-quality neuronal nuclei in the frontal cortex and numerous gene expression changes in glial cells. These findings highlight a context-dependent molecular disruption in C9-ALS and C9-FTD, indicating unique effects across cell types, brain regions, and diseases., (© 2023. Springer Nature Limited.)

To develop a better chemotherapeutically potential candidate for lung cancer treatment and cure with repurposed motifs, quinine has been linked with biocompatible CuAAC-inspired regioselective 1,2,3-triazole linker and a series of ten novel 1,2,3-triazolyl-9-quinine conjugates have been developed by utilizing click conjugation of glycosyl ether alkynes with 9-epi-9-azido-9-deoxy-quinine under standard click conditions. In parallel, the docking study indicated that the resulting conjugates have an overall appreciable interaction with ALK-5 macromolecules. Moreover, the mannose-triazolyl conjugate exhibited the highest binding interactions of -7.6 kcal/mol with H-bond interaction with the targeted macromolecular system and indicate the hope for future trials for anti-lung cancer candidates., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Prematurely born infants are deprived of maternal hormones and cared for in the stressful environment of Neonatal Intensive Care Units (NICUs). They suffer from long-lasting deficits in learning and memory. Here, we show that prematurity and associated neonatal stress disrupt dentate gyrus (DG) development and induce long-term cognitive deficits and that these effects are mediated by insulin growth factor-1 (IGF1). Nonmaternal care of premature rabbits increased the number of granule cells and interneurons and reduced neurogenesis, suggesting accelerated premature maturation of DG. However, the density of glutamatergic synapses, mature dendritic spines, and synaptic transmission were reduced in preterm kits compared with full-term controls, indicating that premature synaptic maturation was abnormal. These findings were consistent with cognitive deficits observed in premature rabbits and appeared to be driven by transcriptomic changes in the granule cells. Preterm kits displayed reduced weight, elevated serum cortisol and growth hormone, and higher IGF1 expression in the liver and DG relative to full-term controls. Importantly, blocking IGF-1 receptor in premature kits restored cognitive deficits, increased the density of glutamatergic puncta, and rescued NR2B and PSD95 levels in the DG. Hence, IGF1 inhibition alleviates prematurity-induced cognitive dysfunction and synaptic changes in the DG through modulation of NR2B and PSD95. The study identifies a novel strategy to potentially rescue DG maldevelopment and cognitive dysfunction in premature infants under stress in NICUs., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In nature, almost all cells are covered with a complex array of glycan chain namely sialic acids or nuraminic acids, a negatively charged nine carbon sugars which is considered for their great therapeutic importance since long back. Owing to its presence at the terminal end of lipid bilayer (commonly known as terminal sugars), the well-defined sialosides or sialoconjugates have served pivotal role on the cell surfaces and thus, the sialic acid-containing glycans can modulate and mediate a number of imperative cellular interactions. Understanding of the sialo-protein interaction and their roles in vertebrates in regard of normal physiology, pathological variance, and evolution has indeed a noteworthy journey in medicine. In this tutorial review, we present a concise overview about the structure, linkages in chemical diversity, biological significance followed by chemical and enzymatic modification/synthesis of sialic acid containing glycans. A more focus is attempted about the recent advances, opportunity, and more over growing impact of sialosides and sialoconjugates in future drug discovery and development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Arsenic (As) contamination in paddy soils and its further translocation to the rice is a serious global issue. Arsenic loading to the rice depends on soil physico-chemical parameters and agronomic practices. To minimize this natural threat, as a natural substance, rice straw was used to produce rice biochar (RBC) and doped with iron oxide (IO) nanoparticles, another eco-friendly composite. In this study, RBC was used at three different concentrations- 0.5%, 1%, and 1.5% alone as well as conjugated with fixed 20 ppm IO nanoparticles. These treatments were compared with the control soil and control plants that had only As in the setup, without any amendments. The application of these treatments was efficient in reducing soil As bioavailability by 43.9%, 60.5%, and 57.3% respectively. Experimental data proved a significant percentage of As was adsorbed onto the RBC + IO conjugate. Further, the 1% RBC + IO conjugate was found to be the best treatment in terms of making soil macro-nutrients bioavailable. Rice seedlings grown under this treatment was more stress tolerant and produced less antioxidant enzymes and stress markers compared to the control plants grown under As-stress only. Rice plants from these different growth setups were observed for internal anatomical integrity and found that the RBC alone and RBC + IO conjugate, both improved the internal vascular structure compared to the control plants. To minimize soil As stress in crops, IO-doped RBC was proven to be the best sustainable amendment for improving soil-crop quality and achieving the proposed motto of Sustainable Development Goals by the United Nations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Acetimidates, a valuable intermediate has been well explored as versatile synthon in a number of organic transformations particularly as suitable donors in glycosylation reactions. Herein, we explored acetimidates to furnish high-to-excellent yield of diverse glycosylated esters under one-pot mild reaction condition. The commercially available trichloroacetonitrile is implemented for the activation of carboxylic acid via in situ generation of trichloroacetimidate, which was subsequently attacked by sugar alcohols to deliver high-to-excellent yields of desired glycosylated esters. The devised method has some notable features such as metal-free condition, one-pot mild reaction condition, easy-handling, high-to-excellent yields, and broad substrate scope., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Low-dose dexmedetomidine may be a suitable alternative to opioids for pediatric ambulatory procedures under general anesthesia (GA). However, the recovery profile remains unclear. Herein, we aimed to evaluate the effects of low-dose dexmedetomidine on the recovery profile of children., Methods: Seventy-two children undergoing ambulatory oral rehabilitation under GA were randomly and equally distributed into two groups (D and F). Group D received an infusion of dexmedetomidine 0.25 µg/kg for 4 min for induction, followed by maintenance of 0.4 µg/kg/h. Group F received an infusion of fentanyl 1 µg/kg over 4 min for induction, followed by maintenance at 1 µg/kg/h. The primary outcome was the extubation time. The secondary outcomes were awakening time, end-tidal sevoflurane (ET-Sevo) requirement, change in hemodynamic parameters, Richmond Agitation-Sedation Scale (RASS), Children's Hospital of Eastern Ontario pain scale (CHEOPS) score, length of PACU stay, and incidence of adverse events., Results: Statistically significant differences were observed in the recovery profile between the groups: the median time for extubation was 3.65 (3.44-6.2) vs. 6.25 (4.21-7) minutes in groups D vs. F (P = 0.001), respectively, while the corresponding awakening times were 19 (18.75-21) and 22.5 (22-24) minutes, respectively (P < 0.001). The mean ET-Sevo was low in group D (1.1 vs. 1.2; P < 0.001). The heart rate was significantly low across all time points in group D, without resulting in bradycardia. The median RASS and CHEOPS scores were also significantly lower in group D. No significant differences were observed in the mean arterial pressure, incidence of adverse events, or length of PACU stay., Conclusion: Low-dose dexmedetomidine was more effective than fentanyl as an opioid substitute at providing a better recovery profile in pediatric ambulatory oral rehabilitation under GA. Dexmedetomidine also significantly reduced sevoflurane consumption without causing adverse events or prolonging hospital stay., Competing Interests: CONFLICTS OF INTEREST: The authors have no potential conflicts of interest (financial or nonfinancial) to declare., (Copyright © 2022 Journal of Dental Anesthesia and Pain Medicine.)

The present study analysed the levels of potentially toxic elements along with physico-chemical properties of agricultural soil samples (n = 59) collected from fields situated along the path of river Ganga in the middle Gangetic floodplain in two districts, Ballia and Ghazipur. Arsenic (As), chromium (Cr), copper (Cu), nickel (Ni), zinc (Zn), lead (Pb), iron (Fe) and manganese (Mn) levels were analysed by Wavelength Dispersive-X-Ray Fluorescence Spectroscopy (WD-XRF) and the associated health risks along with diverse indices were calculated. The mean concentrations of As, Cu, Cr, Pb, Zn and Ni were found to be 15, 42, 85, 18, 87 and 47 mg kg -1 , respectively in Ballia and 13, 31, 73, 22, 77 and 34 mg kg -1 , respectively in Ghazipur. Physico-chemical properties like pH, ORP and organic matter were found to be 7.91, 209 and 1.20, respectively in Ballia and 8.51, 155 and 1.25, respectively in Ghazipur. The calculated health quotient (HQ) for all the elements was observed to be within the threshold value of one, however with few exemptions. Therefore, the present study showcases the contamination of potentially toxic elements in agricultural fields and possible health hazards for people., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background Parental anxiety has been identified as a risk factor affecting the behaviour of children before operative intervention. A preanaesthetic visit is a standard component of preoperative preparation, which may reduce parental anxiety. The use of audiovisual aids to demonstrate the conduct of anaesthesia may help improve parental education and reduce anxiety. Patient and methods We analysed data from a prospective randomised trial conducted at a tertiary care hospital. Parents of children posted for day care dental procedures were enrolled in the study. Children could be of either gender, aged 2-6 years, and categorised as American Society of Anesthesiologists Physical Status (ASA-PS) 1 or 2. Parents' anxiety regarding the surgical and anaesthesia procedure was assessed using the Amsterdam Preoperative Anxiety and Information Scale (APAIS). The first APAIS scoring was recorded on arrival in the preoperative holding area. Thereafter, the participants were randomly allocated into two groups; one group was shown a short video on a smartphone of a dental operating theatre (OT), dental chair and anaesthesia equipment (SPG group), while the other group was verbally explained the dental procedure (conventional management or CM group). The second APAIS scoring was done in the postoperative recovery area one hour after the procedure. Demographic characteristics, socio-economic conditions and history were recorded. Anxiety scores were compared between the two groups, and any change was analysed. Results Seventy parents were included in the study, with 36 randomised to the SPG group and 34 to the CM group. Both groups were comparable in terms of demographic characteristics. There was a statistically significant decrease in anxiety scores in the SPG group, from a mean of 25.47 at the preoperative assessment to 14.92 at the postoperative timepoint (p<0.001). In the CM group, the mean APAIS score decreased from 25.26 to 24.56 (p=0.059). Conclusion There was a significant reduction in anxiety scores in the postoperative period among parents who were shown an operating room video in the preoperative period., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Phaneendra et al.)

Flexible electronics require elastomeric and conductive biointerfaces with native tissue-like mechanical properties. The conventional approaches to engineer such a biointerface often utilize conductive nanomaterials in combination with polymeric hydrogels that are cross-linked using toxic photoinitiators. Moreover, these systems frequently demonstrate poor biocompatibility and face trade-offs between conductivity and mechanical stiffness under physiological conditions. To address these challenges, we developed a class of shear-thinning hydrogels as biomaterial inks for 3D printing flexible bioelectronics. These hydrogels are engineered through a facile vacancy-driven gelation of MoS 2 nanoassemblies with naturally derived polymer-thiolated gelatin. Due to shear-thinning properties, these nanoengineered hydrogels can be printed into complex shapes that can respond to mechanical deformation. The chemically cross-linked nanoengineered hydrogels demonstrate a 20-fold rise in compressive moduli and can withstand up to 80% strain without permanent deformation, meeting human anatomical flexibility. The nanoengineered network exhibits high conductivity, compressive modulus, pseudocapacitance, and biocompatibility. The 3D-printed cross-linked structure demonstrates excellent strain sensitivity and can be used as wearable electronics to detect various motion dynamics. Overall, the results suggest that these nanoengineered hydrogels offer improved mechanical, electronic, and biological characteristics for various emerging biomedical applications including 3D-printed flexible biosensors, actuators, optoelectronics, and therapeutic delivery devices.

2D covalent organic frameworks (COFs) are an emerging class of crystalline porous organic polymers with a wide-range of potential applications. However, poor processability, aqueous instability, and low water dispersibility greatly limit their practical biomedical implementation. Herein, a new class of hydrolytically stable 2D COFs for sustained delivery of drugs to direct stem cell fate is reported. Specifically, a boronate-based COF (COF-5) is stabilized using amphiphilic polymer Pluronic F127 (PLU) to produce COF-PLU nanoparticles with thickness of ≈25 nm and diameter ≈200 nm. These nanoparticles are internalized via clathrin-mediated endocytosis and have high cytocompatibility (half-inhibitory concentration ≈1 mg mL -1 ). Interestingly, the 2D COFs induce osteogenic differentiation in human mesenchymal stem cells, which is unique. In addition, an osteogenic agent-dexamethasone-is able to be loaded within the porous structure of COFs for sustained delivery which further enhances the osteoinductive ability. These results demonstrate for the first time the fabrication of hydrolytically stable 2D COFs for sustained delivery of dexamethasone and demonstrate its osteoinductive characteristics., (© 2022 Wiley-VCH GmbH.)

Background: While schizophrenia differs between males and females in the age of onset, symptomatology, and disease course, the molecular mechanisms underlying these differences remain uncharacterized., Methods: To address questions about the sex-specific effects of schizophrenia, we performed a large-scale transcriptome analysis of RNA sequencing data from 437 controls and 341 cases from two distinct cohorts from the CommonMind Consortium., Results: Analysis across the cohorts identified a reproducible gene expression signature of schizophrenia that was highly concordant with previous work. Differential expression across sex was reproducible across cohorts and identified X- and Y-linked genes, as well as those involved in dosage compensation. Intriguingly, the sex expression signature was also enriched for genes involved in neurexin family protein binding and synaptic organization. Differential expression analysis testing a sex-by-diagnosis interaction effect did not identify any genome-wide signature after multiple testing corrections. Gene coexpression network analysis was performed to reduce dimensionality from thousands of genes to dozens of modules and elucidate interactions among genes. We found enrichment of coexpression modules for sex-by-diagnosis differential expression signatures, which were highly reproducible across the two cohorts and involved a number of diverse pathways, including neural nucleus development, neuron projection morphogenesis, and regulation of neural precursor cell proliferation., Conclusions: Overall, our results indicate that the effect size of sex differences in schizophrenia gene expression signatures is small and underscore the challenge of identifying robust sex-by-diagnosis signatures, which will require future analyses in larger cohorts., (Copyright © 2021 Society of Biological Psychiatry. All rights reserved.)

Glycodendrimers are receiving considerable attention to mimic a number of imperative features of cell surface glycoconjugate and acquired excellent relevance to a wide domain of investigations including medicine, pharmaceutics, catalysis, nanotechnology, carbohydrate-protein interaction, and moreover in drug delivery systems. Toward this end, an expeditious, modular, and regioselective triazole-forming CuAAC click approach along with double stage convergent synthetic method was chosen to develop a variety of novel chlorine-containing cyclen cored glycodendrimers of high sugar tethers at low generation of promising therapeutic potential. We developed a novel chlorine-containing hypercore unit with 12 alkynyl functionality originated from cyclen scaffold which was confirmed by its single crystal X-ray data analysis. Further, the modular CuAAC technique was utilized to produce a variety of novel 12-sugar coated (G 0 ) glycodendrimers 12-15 adorn with β-Glc-, β-Man-, β-Gal-, β-Lac, along with 36-galactose coated (G 1 ) glycodendrimer 18 in good-to-high yield. The structures of the developed glycodendrimer architectures have been well elucidated by extensive spectral analysis including NMR ( 1 H & 13 CNMR), HRMS, MALDI-TOF MS, UV-Vis, IR, and SEC (Size Exclusion Chromatogram) data., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A simple strategy for yielding chiral tertiary α-hydroxy phosphonates that integrates two highly biologically relevant scaffolds namely 3-alkylidene-2-oxindoles and phosphonates has been described. The hydrogen bonding ability of the bifunctional thiourea catalyst allows simultaneous dual activation of a vinylogous oxindole nucleophile and an acylphosphonate electrophile, affording hydroxyphosphonato-3-alkylidene-2-oxindoles as aldol adducts in high yields (up to 92%) with excellent stereocontrol (up to 99% ee).

Copper(I)-catalyzed 1,3-dipolar cycloaddition between organic azides and terminal alkynes, commonly known as CuAAC or click chemistry, has been identified as one of the most successful, versatile, reliable, and modular strategies for the rapid and regioselective construction of 1,4-disubstituted 1,2,3-triazoles as diversely functionalized molecules. Carbohydrates, an integral part of living cells, have several fascinating features, including their structural diversity, biocompatibility, bioavailability, hydrophilicity, and superior ADME properties with minimal toxicity, which support increased demand to explore them as versatile scaffolds for easy access to diverse glycohybrids and well-defined glycoconjugates for complete chemical, biochemical, and pharmacological investigations. This review highlights the successful development of CuAAC or click chemistry in emerging areas of glycoscience, including the synthesis of triazole appended carbohydrate-containing molecular architectures (mainly glycohybrids, glycoconjugates, glycopolymers, glycopeptides, glycoproteins, glycolipids, glycoclusters, and glycodendrimers through regioselective triazole forming modular and bio-orthogonal coupling protocols). It discusses the widespread applications of these glycoproducts as enzyme inhibitors in drug discovery and development, sensing, gelation, chelation, glycosylation, and catalysis. This review also covers the impact of click chemistry and provides future perspectives on its role in various emerging disciplines of science and technology.

Light-responsive biomaterials are an emerging class of materials used for developing noninvasive, noncontact, precise, and controllable biomedical devices. Long-wavelength near-infrared (NIR) radiation is an attractive light source for in situ gelation due to its higher penetration depth and minimum side effects. The conventional approach to obtain crosslinked biomaterials relies heavily on the use of a photoinitiator by generating reactive species when exposed to short-wavelength radiation, which is detrimental to surrounding cells and tissue. Here, a new class of NIR-triggered in situ gelation system based on defect-rich 2D molybdenum disulfide (MoS 2 ) nanoassemblies and thiol-functionalized thermoresponsive polymer in the absence of a photoinitiator is introduced. Exposure to NIR radiation activates the dynamic polymer-nanomaterials interactions by leveraging the photothermal characteristics of MoS 2 and intrinsic phase transition ability of the thermoresponsive polymer. Specifically, upon NIR exposure, MoS 2 acts as a crosslink epicenter by connecting with multiple polymeric chains via defect-driven click chemistry. As a proof-of-concept, the utility of NIR-triggered in situ gelation is demonstrated in vitro and in vivo. Additionally, the crosslinked gel exhibits the potential for NIR light-responsive release of encapsulated therapeutics. These light-responsive biomaterials have strong potential for a range of biomedical applications, including artificial muscle, smart actuators, 3D/4D printing, regenerative medicine, and therapeutic delivery., (© 2021 Wiley-VCH GmbH.)

Alterations to the mechanical properties of the microenvironment are a hallmark of cancer. Elevated mechanical stresses exist in many solid tumors and elicit responses from cancer cells. Uncontrolled growth in confined environments gives rise to elevated solid compressive stress on cancer cells. Recruitment of leaky blood vessels and an absence of functioning lymphatic vessels causes a rise in the interstitial fluid pressure. Here we review the role of the cancer cell cytoskeleton and the nucleus in mediating both the initial and adaptive cancer cell response to these two types of mechanical stresses. We review how these mechanical stresses alter cancer cell functions such as proliferation, apoptosis, and migration., (© 2021 Wiley Periodicals LLC.)

Arsenic (As) assessment in agricultural soils and corresponding crops is necessary from the global health safety perspective. To the best of our knowledge, we are reporting for the first time, As flux determining parametric equations for paddy field with seasonal rice cultivation under conventional flooding and dry-wet irrigation approaches. Rigorous field experiments and measuring quantitative parameters, flushed out or percolated into the deeper soil As flux was assessed. A wintery (boro)-monsoonal (aman) study from 2016 to 2019 has been conducted showing the efficiency of dry-wet irrigation on reduction of soil As bioavailability. The reduction in boro was 52.4% in 2016 to 64.8% in 2019 while in aman, it was 61% in 2016 to 74.9% in 2019. Low bioavailability was correlated to plant's internal vascular structure that was found more rigid and firm in dry-wet field grown plants. Observed soil physico-chemical parameters clearly influenced As bioavailability as well as soil microbial community. Assessment of microbial diversity using metagenomics under altered water regime was done by population analysis, relative abundance, species richness, Krona chart comparison. Dry-wet field was found to be more diverse and enriched in microbial community than that of the flooded soil indicating an affective reduction of As bioavailability under biotic-abiotic factors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Two-dimensional (2D) metal organic frameworks (MOFs), are an emerging class of layered nanomaterials with well-defined structure and modular composition. The unique pore structure, high flexibility, tunability, and ability to introduce desired functionality within the structural framework, have led to potential use of MOFs in biomedical applications. This article critically reviews the application of 2D MOFs for therapeutic delivery, tissue engineering, bioimaging, and biosensing. Further, discussion on the challenges and strategies in next generation of 2D MOFs are also included. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology., (© 2020 Wiley Periodicals LLC.)

Hyperactivity of amygdala is observed in patients with major depressive disorder. Although the role of α1-adrenoceptor in amygdala on fear memory has been well studied, the role of α1-adrenoceptor in amygdala on depression-like behaviors remains unclear. Therefore, we investigated the effect of α1A-adrenoreceptor in amygdala on despair behavior, evaluated by the immobility time during tail suspension test (TST), pharmacological intervention, and immunohistological methods. C57BL6/J mice given a bilateral intra-amygdala injection of artificial cerebrospinal fluid exhibited an increased duration of immobility in the latter half of both trials of TST with a 24-h interval, a phenomenon known as learned despair. Intra-amygdala injection of WB4101 (1.7 nmol/0.1 µl), an α1 adrenoreceptor antagonist, but not propranolol (250 pmol/0.1 µl), a β-adrenoreceptor antagonist, blocked the induction of learned despair during TST. Immunostaining experiments revealed that ~61-75% of α1A-adrenoreceptor-positive neurons were colocalized with GAD65/67 in amygdala, implying that the α1-adrenoceptors in amygdala may enormously regulate the GABA release. Protein kinase C-beta (PKCβ) was predominantly expressed in the α1A-adrenoreceptor-positive neurons in the BLA, whereas protein kinase C-epsilon (PKCε) was highly expressed with the α1A-adrenoreceptor in the Central nucleus of amygdala. Intra-amygdala injection of ruboxistaurin (10 pmol/0.1 µl), a PKCβ inhibitor, blocked the induction of learned despair during TST, whereas neither TAT-εV1-2 (500 ng/0.1 μl), a cell-permeant PKCε inhibitory peptide, nor HBDDE (50 pmol/0.1 µl), an inhibitor of PKCα and -γ, affected the duration of immobility during TST. These data suggest that the α1-adrenoreceptor in amygdala regulates the induction of learned despair via PKCβ., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

1,4-Diazabicyclo[2.2.2]octane (DABCO)-catalyzed [3 + 3] cycloaddition reaction of 3-alkylidene-2-oxindole and β,γ-unsaturated α-keto esters under mild reaction conditions afforded the spirocyclohexene-oxindole with excellent diastereoselectivity. The [3 + 3] annulation is found to proceed through a vinylogous Michael-aldol cascade reaction and it allows rapid access to a diverse set of highly functionalized spirocyclohexene-oxindoles. Also, a bioactivity study of the compounds on mammalian sarcoma cells has reflected cell growth inhibitory/anti-cancer properties.

Two-dimensional (2D) molybdenum disulfide (MoS 2 ) nanomaterials are an emerging class of biomaterials that are photoresponsive at near-infrared wavelengths (NIR). Here, we demonstrate the ability of 2D MoS 2 to modulate cellular functions of human stem cells through photothermal mechanisms. The interaction of MoS 2 and NIR stimulation of MoS 2 with human stem cells is investigated using whole-transcriptome sequencing (RNA-seq). Global gene expression profile of stem cells reveals significant influence of MoS 2 and NIR stimulation of MoS 2 on integrins, cellular migration, and wound healing. The combination of MoS 2 and NIR light may provide new approaches to regulate and direct these cellular functions for the purposes of regenerative medicine as well as cancer therapy., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Bioprinting is an emerging additive manufacturing approach to the fabrication of patient-specific, implantable three-dimensional (3D) constructs for regenerative medicine. However, developing cell-compatible bioinks with high printability, structural stability, biodegradability, and bioactive characteristics is still a primary challenge for translating 3D bioprinting technology to preclinical and clinal models. To overcome this challenge, we developed a nanoengineered ionic covalent entanglement (NICE) bioink formulation for 3D bone bioprinting. The NICE bioinks allow precise control over printability, mechanical properties, and degradation characteristics, enabling custom 3D fabrication of mechanically resilient, cellularized structures. We demonstrate cell-induced remodeling of 3D bioprinted scaffolds over 60 days, demonstrating deposition of nascent extracellular matrix proteins. Interestingly, the bioprinted constructs induce endochondral differentiation of encapsulated human mesenchymal stem cells (hMSCs) in the absence of osteoinducing agent. Using next-generation transcriptome sequencing (RNA-seq) technology, we establish the role of nanosilicates, a bioactive component of NICE bioink, to stimulate endochondral differentiation at the transcriptome level. Overall, the osteoinductive bioink has the ability to induce formation of osteo-related mineralized extracellular matrix by encapsulated hMSCs in growth factor-free conditions. Furthermore, we demonstrate the ability of NICE bioink to fabricate patient-specific, implantable 3D scaffolds for repair of craniomaxillofacial bone defects. We envision development of this NICE bioink technology toward a realistic clinical process for 3D bioprinting patient-specific bone tissue for regenerative medicine.

The study implements a periodical intermittent water cycle during rice cultivation providing insight potential in minimizing soil bio-available arsenic. Soil As concentrations were 34 ± 0.49 and 72.03 ± 0.54 mg kg-1 As respectively in two selected fields with rice cultivars gosai and satabdi, in comparison to 42.26 ± 0.37 and 83.69 ± 0.48 mg kg-1 in continuously flooded field soil, determined through ICP-MS. The study found higher translocation of silicon from soil to rice plant parts under intermittent irrigation having pH range of 7.6-9.4 and greater availability of soil organic content that in turn release more labile silicon from soil to aqueous phase for plant accumulation. This increased uptake of silicon strengthens rice shoots, nodes and leaf xylem-phloem integrity compared to conventional continuously flooded rice cultivation approach, suppressing the arsenic translocation, as observed under FE-SEM real-time imaging. Fresh plants were analysed for bioaccumulation and translocation factors of arsenic and silicon to justify the enhanced silicon uptake under proposed practice. Plant stress regulator enzymes viz. malondialdehyde (MDA), total protein, superoxide dismutase (SOD), guaiacol peroxidase (GPX) and ascorbate peroxidase (APX) from both conditions and found to be better in intermittent method over conventional practice with higher productivity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Bacterial communities are resilient to the environmental changes, yet the effect of long term ecological changes on bacterial communities remain poorly explored. To study the effect of prolonged environmental changes, a 25 m long sediment core was excavated from a paleo beach ridge located on the Cauvery delta, south east coast of India. Geological evidences suggested that the site has experienced multiple marine transgressions and regressions. The three paleosols from Vettaikaraniruppu (VKI) beach ridge, VKI-2 (2.8 m bgl; 3 kybp), VKI-5 (7.2 m bgl; 6 kybp) and VKI-14 (24.5 m bgl; 146 kybp) was chosen for bacterial community analysis based on their formation period. Bacterial community structure of paleosols was reconstructed using V3 hypervariable region of bacterial 16S rDNA targeted Illumina sequencing. The VKI-5 sediment layer which formed under marine environment contained highest bacterial diversity, and the community was a mix up of terrestrial and marine bacterial population. The final community VKI-2 exhibited an approximate structural pattern witnessed in the native bacterial community VKI-14 which formed during marine regression. Furthermore, marine transgression and regression experienced in VKI resulted in the formation of distinct biogeographic patterns., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Proper orchestration of T lymphocyte development is critical, as T cells underlie nearly all responses of the adaptive immune system. Developing thymocytes differentiate in response to environmental cues carried from cell surface receptors to the nucleus, shaping a distinct transcriptional program that defines their developmental outcome. Our recent work has identified a previously undescribed role for the vacuolar ATPase (V-ATPase) in facilitating the development of murine thymocytes progressing toward the CD4 + and CD8 + αβ T cell lineages. Vav1 Cre recombinase-mediated deletion of the a2 isoform of the V-ATPase (a2V) in mouse hematopoietic cells leads to a specific and profound loss of peripheral CD4 + and CD8 + αβ T cells. Utilizing T cell-restricted Lck Cre and CD4 Cre strains, we further traced this deficiency to the thymus and found that a2V plays a cell-intrinsic role throughout intrathymic development. Loss of a2V manifests as a partial obstruction in the double negative stage of T cell development, and later, a near complete failure of positive selection. These data deepen our understanding of the biological mechanisms that orchestrate T cell development and lend credence to the recent focus on V-ATPase as a potential chemotherapeutic target to combat proliferative potential in T cell lymphoblastic leukemias and autoimmune disease.

We introduced a new concept to the control of wetting characteristics by modulating the degree of atomic defects of two-dimensional transition metal dichalcogenide nanoassemblies of molybdenum disulfide. This work shed new light on the role of atomic vacancies on wetting characteristic that can be leveraged to develop a new class of superhydrophobic surfaces for various applications without altering their topography.

Over the past decades, a multitude of experimental drugs have been shown to delay disease progression in preclinical animal models of amyotrophic lateral sclerosis (ALS) but failed to show efficacy in human clinical trials or are still waiting for approval under Phase I-III trials. Riluzole, a glutamatergic neurotransmission inhibitor, is the only drug approved by the USA Food and Drug Administration for ALS treatment with modest benefits on survival. Recently, an antioxidant drug, edaravone, developed by Mitsubishi Tanabe Pharma was found to be effective in halting ALS progression during early stages. The newly approved drug edaravone is a force multiplier for ALS treatment. This short report provides an overview of the two drugs that have been approved for ALS treatment and highlights an update on the timeline of drug development, how clinical trials were done, the outcome of these trials, primary endpoint, mechanism of actions, dosing information, administration, side effects, and storage procedures. Moreover, we also discussed the pressing issues and challenges of ALS clinical trials and drug developments as well as future outlook., (© 2018 Wiley Periodicals, Inc.)

Preterm birth accounts for the majority of neonatal morbidity and mortality in the developed world. A significant proportion of cases of spontaneous preterm labor are attributable to infections within gestational tissues. Surfactant protein A (SP-A), a collectin produced in the fetal lung and other tissues, has been shown previously in mice to suppress preterm delivery due to intrauterine (IU) instillation of sterile proinflammatory substances. Here we report a powerful antilabor effect for SP-A after IU infection with live Escherichia coli. SP-A abolished preterm birth (rate reduced from 100% to 0%) when it was administered into the uterus simultaneously with bacterial infection, reducing it by 75% when administered intravenously at the same time as IU bacterial inoculation, and by 48% when administered intravenously 4 h after IU bacterial infection. This effect on preterm delivery was accompanied by a parallel benefit on fetal survival in utero. SP-A had no effect on bacterial growth but reversed several major consequences of infection, including increased production of inflammatory mediators and a shift in macrophage polarization to the M1 phenotype. These findings suggest that exogenous SP-A has potential use to counteract infection-induced labor by reversing its proinflammatory consequences.

Chronic stress-induced depression is a common hallmark of many psychiatric disorders with high morbidity rate. Stress-induced dysregulation of noradrenergic system has been implicated in the pathogenesis of depression. Lack of monoamine in the brain has been believed to be the main causative factor behind pathophysiology of major depressive disorder (MDD) and several antidepressants functions by increasing the monoamine level at the synapses in the brain. However, it is undetermined whether the noradrenergic receptor stimulation is critical for the therapeutic effect of antidepressant. Contrary to noradrenergic receptor stimulation, it has been suggested that the desensitization of β-adrenoceptor is involved in the therapeutic effect of antidepressant. In addition, enhanced noradrenaline (NA) release is central response to stress and thought to be a risk factor for the development of MDD. Moreover, fast acting antidepressant suppresses the hyperactivation of noradrenergic neurons in locus coeruleus (LC). However, it is unclear how they alter the firing activity of LC neurons. These inconsistent reports about antidepressant effect of NA-reuptake inhibitors (NRIs) and enhanced release of NA as a stress response complicate our understanding about the pathophysiology of MDD. In this review, we will discuss the role of NA in pathophysiology of stress and the mechanism of therapeutic effect of NA in MDD. We will also discuss the possible contributions of each subtype of noradrenergic receptors on LC neurons, hypothalamic-pituitary-adrenal axis (HPA-axis) and brain derived neurotrophic factor-induced hippocampal neurogenesis during stress and therapeutic effect of NRIs in MDD., 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

Nanoparticle shape has emerged as a key regulator of nanoparticle transport across physiological barriers, intracellular uptake, and biodistribution. We report a facile approach to synthesize ellipsoidal nanoparticles through self-assembly of poly(glycerol sebacate)-co-poly(ethylene glycol) (PGS-co-PEG). The PGS-PEG nanoparticle system is highly tunable, and the semiaxis length of the nanoparticles can be modulated by changing PGS-PEG molar ratio and incorporating therapeutics. As both PGS and PEG are highly biocompatible, the PGS-co-PEG nanoparticles show high hemo-, immuno-, and cytocompatibility. Our data suggest that PGS-co-PEG nanoparticles have the potential for use in a wide range of biomedical applications including regenerative medicine, stem cell engineering, immune modulation, and cancer therapeutics. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2048-2058, 2018., (© 2018 Wiley Periodicals, Inc.)

Two-dimensional nanomaterials, an ultrathin class of materials such as graphene, nanoclays, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs), have emerged as a new generation of materials due to their unique properties relative to macroscale counterparts. However, little is known about the transcriptome dynamics following exposure to these nanomaterials. Here, we investigate the interactions of 2D nanosilicates, a layered clay, with human mesenchymal stem cells (hMSCs) at the whole-transcriptome level by high-throughput sequencing (RNA-seq). Analysis of cell-nanosilicate interactions by monitoring changes in transcriptome profile uncovered key biophysical and biochemical cellular pathways triggered by nanosilicates. A widespread alteration of genes was observed due to nanosilicate exposure as more than 4,000 genes were differentially expressed. The change in mRNA expression levels revealed clathrin-mediated endocytosis of nanosilicates. Nanosilicate attachment to the cell membrane and subsequent cellular internalization activated stress-responsive pathways such as mitogen-activated protein kinase (MAPK), which subsequently directed hMSC differentiation toward osteogenic and chondrogenic lineages. This study provides transcriptomic insight on the role of surface-mediated cellular signaling triggered by nanomaterials and enables development of nanomaterials-based therapeutics for regenerative medicine. This approach in understanding nanomaterial-cell interactions illustrates how change in transcriptomic profile can predict downstream effects following nanomaterial treatment., Competing Interests: Conflict of interest statement: J.K.C. and A.K.G. are coauthors on US Patent Application No. WO2017112802 A1 published on June 29, 2017 (US Provisional Patent Application No. 62/270,403 filed on December 21, 2015)., (Copyright © 2018 the Author(s). Published by PNAS.)

Preterm birth is widespread and causes 35% of all neonatal deaths. Infants who survive face potential long-term complications. A major contributing factor of preterm birth is infection. We investigated the role of interleukin 22 (IL22) as a potential clinically relevant cytokine during gestational infection. IL22 is an effector molecule secreted by immune cells. While the expression of IL22 was reported in normal nonpregnant endometrium and early pregnancy decidua, little is known about uterine IL22 expression during mid or late gestational stages of pregnancy. Since IL22 has been shown to be an essential mediator in epithelial regeneration and wound repair, we investigated the potential role of IL22 during defense against an inflammatory response at the maternal-fetal interface. We used a well-established model to study infection and infection-associated inflammation during preterm birth in the mouse. We have shown that IL22 is upregulated to respond to an intrauterine lipopolysaccharide administration and plays an important role in controlling the risk of inflammation-induced preterm birth. This paper proposes IL22 as a treatment method to combat infection and prevent preterm birth in susceptible patients.

Quick and easy recovery without the loss of the photocatalytic activity of the catalysing agent is an effective way to meet the challenges associated with the high cost of hazard-free hydrogen production. A '2D/0D' covalently conjugated nanocomposite of MoS 2 /Fe 3 O 4 has shown efficient catalyzing ability for five cycles of dye-sensitized H 2 evolution.

"Smart" hydrogels are an emerging class of biomaterials that respond to external stimuli and have been investigated for a range of biomedical applications, including therapeutic delivery and regenerative engineering. Stimuli-responsive nanogels constructed of thermoresponsive polymers such as poly(N-isopropylacrylamide-co-acrylamide) (poly(NIPAM-co-AM)) and magnetic nanoparticles (MNPs) have been developed as "smart carriers" for on-demand delivery of therapeutic biomolecules via magneto-thermal activation. However, due to their small size and systemic introduction, these poly(NIPAM-co-AM)/MNP nanogels result in limited control over long-term, localized therapeutic delivery. Here, we developed an injectable nanoengineered hydrogel loaded with poly(NIPAM-co-AM)/MNPs for localized, on-demand delivery of therapeutics (doxorubicin (DOX)). We have engineered shear-thinning and self-recoverable hydrogels by modulating the crosslinking density of a gelatin methacrylate (GelMA) network. Poly(NIPAM-co-AM)/MNP nanogels loaded with DOX were entrapped within a GelMA pre-polymer solution prior to crosslinking. The temperature and magnetic field dependent release of loaded DOX was observed from the nanoengineered hydrogels (GelMA/(poly(NIPAM-co-AM)/MNPs)). Finally, the in vitro efficacy of DOX released from injectable nanoengineered hydrogels was investigated using preosteoblast and osteosarcoma cells. Overall, these results demonstrated that the injectable nanoengineered hydrogels could be used for on-demand and localized therapeutic delivery for biomedical applications.

A new approach of vacancy-driven gelation to obtain chemically crosslinked hydrogels from defect-rich 2D molybdenum disulfide (MoS 2 ) nanoassemblies and polymeric binder is reported. This approach utilizes the planar and edge atomic defects available on the surface of the 2D MoS 2 nanoassemblies to form mechanically resilient and elastomeric nanocomposite hydrogels. The atomic defects present on the lattice plane of 2D MoS 2 nanoassemblies are due to atomic vacancies and can act as an active center for vacancy-driven gelation with a thiol-activated terminal such as four-arm poly(ethylene glycol)-thiol (PEG-SH) via chemisorption. By modulating the number of vacancies on the 2D MoS 2 nanoassemblies, the physical and chemical properties of the hydrogel network can be controlled. This vacancy-driven gelation process does not require external stimuli such as UV exposure, chemical initiator, or thermal agitation for crosslinking and thus provides a nontoxic and facile approach to encapsulate cells and proteins. 2D MoS 2 nanoassemblies are cytocompatible, and encapsulated cells in the nanocomposite hydrogels show high viability. Overall, the nanoengineered hydrogel obtained from vacancy-driven gelation is mechanically resilient and can be used for a range of biomedical applications including tissue engineering, regenerative medicine, and cell and therapeutic delivery., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Our current understanding of the mechanical properties of nanostructured biomaterials is rather limited to invasive/destructive and low-throughput techniques such as atomic force microscopy, optical tweezers, and shear rheology. In this report, we demonstrate the capabilities of recently developed dual Brillouin/Raman spectroscopy to interrogate the mechanical and chemical properties of nanostructured hydrogel networks. The results obtained from Brillouin spectroscopy show an excellent correlation with the conventional uniaxial and shear mechanical testing. Moreover, it is confirmed that, unlike the macroscopic conventional mechanical measurement techniques, Brillouin spectroscopy can provide the elasticity characteristic of biomaterials at a mesoscale length, which is remarkably important for understanding complex cell-biomaterial interactions. The proposed technique experimentally demonstrated the capability of studying biomaterials in their natural environment and may facilitate future fabrication and inspection of biomaterials for various biomedical and biotechnological applications.

Magnetic liposome-mediated combined chemotherapy and hyperthermia is gaining importance as an effective therapeutic modality for cancer. However, control and maintenance of optimum hyperthermia are major challenges in clinical settings due to the overheating of tissues. To overcome this problem, we developed a novel magnetic liposomes formulation co-entrapping a dextran coated biphasic suspension of La 0.75 Sr 0.25 MnO 3 (LSMO) and iron oxide (Fe 3 O 4 ) nanoparticles for self-controlled hyperthermia and chemotherapy. However, the general apprehension about biocompatibility and safety of the newly developed formulation needs to be addressed. In this work, in vitro and in vivo biocompatibility and therapeutic evaluation studies of the novel magnetic liposomes are reported. Biocompatibility study of the magnetic liposomes formulation was carried out to evaluate the signs of preliminary systemic toxicity, if any, following intravenous administration of the magnetic liposomes in Swiss mice. Therapeutic efficacy of the magnetic liposomes formulation was evaluated in the fibrosarcoma tumour bearing mouse model. Fibrosarcoma tumour-bearing mice were subjected to hyperthermia following intratumoral injection of single or double doses of the magnetic liposomes with or without chemotherapeutic drug paclitaxel. Hyperthermia (three spurts, each at 3 days interval) with drug loaded magnetic liposomes following single dose administration reduced the growth of tumours by 2.5 fold (mean tumour volume 2356 ± 550 mm 3 ) whereas the double dose treatment reduced the tumour growth by 3.6 fold (mean tumour volume 1045 ± 440 mm 3 ) compared to their corresponding control (mean tumour volume 3782 ± 515 mm 3 ). At the end of the tumour efficacy studies, the presence of MNPs was studied in the remnant tumour tissues and vital organs of the mice. No significant leaching or drainage of the magnetic liposomes during the study was observed from the tumour site to the other vital organs of the body, suggesting again the potential of the novel magnetic liposomes formulation for possibility of developing as an effective modality for treatment of drug resistant or physiologically vulnerable cancer.

Amyotrophic lateral sclerosis (ALS) and motor neuron diseases (MNDs) are progressive neurodegenerative diseases that affect nerve cells in the brain affecting upper and lower motor neurons (UMNs/LMNs), brain stem and spinal cord. The clinical phenotype is characterized by loss of motor neurons (MNs), muscular weakness and atrophy eventually leading to paralysis and death due to respiratory failure within 3-5 years after disease onset. No effective treatment or cure is currently available that halts or reverses ALS and MND except FDA approved drug riluzole that only modestly slows the progression of ALS in some patients. Recent advances in human derived induced pluripotent stem cells have made it possible for the first time to obtain substantial amounts of human cells to recapitulate in vitro " disease in dish " and test some of the underlying pathogenetic mechanisms involved in ALS and MNDs. In this review, I discussed the opportunities and challenges of induced pluropotent stem cells-derived motor neurons for treatment of ALS and MND patients with special emphasis on their implications in finding a cure for ALS and MNDs., Competing Interests: Conflicts of interest: None of the authors has any conflict of interest to disclose. The views expressed in this article are those of the author and do not reflect the official policy or position of the NYSPI/Department of Psychiatry, Columbia University Medical center.