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Our patient was a 57-year-old woman with a history of bilateral retropectoral silicone breast augmentation and axillary hyperhidrosis who underwent a bilateral thoracic sympathectomy via video-assisted thoracoscopic surgery by a surgeon at an outside hospital approximately 20 years ago. The left side required an open thoracotomy. Shortly after the surgery, she developed a left-sided Baker 4 capsular contracture and the left implant was noted to be ruptured. Both implants were exchanged. Several years later the patient began to experience progressive fatigue. Work-up revealed a left lung nodule and she underwent a biopsy that confirmed silicone granulomas. It was hypothesised that at the time of her initial thoracotomy the implant was violated resulting in silicone spillage into the thoracic cavity. The patient was referred to our institution for advanced management of her intrathoracic silicosis. The patient underwent bilateral removal of her silicone implants, total capsulectomy and needle-localised removal of her left thoracic silicone masses. She had an uneventful postoperative course with resolution of her fatigue.

Although there are many treatment options available for wound and burns dressings, improvements in technology are still required. Bacterial cellulose is a polymer derived from the microbiological world and has shown some promising properties that recommend it as a wound healing therapeutic. Moreover, bacterial cellulose can be nanosized to form Bacterial Nanocellulose (BNC), enhancing its properties. Most importantly, in addition to its inherent antibacterial properties, BNC can be used to deliver drugs. This article presents a birds-eye view of the preparation method and applications of BNC-based wound dressings.

Background: Circulating high-sensitivity cardiac troponin T (hsTnT) predominantly reflects myocardial injury, and higher levels are associated with a higher risk of worsening heart failure and death in patients with heart failure with reduced ejection fraction. Less is known about the prognostic significance of changes in hsTnT over time, the effects of dapagliflozin on clinical outcomes in relation to baseline hsTnT levels, and the effect of dapagliflozin on hsTnT levels. Methods: DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) was a randomized, double-blind, placebo-controlled trial of dapagliflozin (10 mg daily) in patients with New York Heart Association class II to IV symptoms and left ventricular ejection fraction ≤40% (median follow-up, 18.2 months). hsTnT (Roche Diagnostics) was measured at baseline in 3112 patients and at 1 year in 2506 patients. The primary end point was adjudicated worsening heart failure or cardiovascular death. Clinical end points were analyzed according to baseline hsTnT and change in hsTnT from baseline to 1 year. Comparative treatment effects on clinical end points with dapagliflozin versus placebo were assessed by baseline hsTnT. The effect of dapagliflozin on hsTnT was explored. Results: Median baseline hsTnT concentration was 20.0 (25th–75th percentile, 13.7–30.2) ng/L. Over 1 year, 67.9% of patients had a ≥10% relative increase or decrease in hsTnT concentrations, and 43.5% had a ≥20% relative change. A stepwise gradient of higher risk for the primary end point was observed across increasing quartiles of baseline hsTnT concentration (adjusted hazard ratio Q4 versus Q1, 3.44 [95% CI, 2.46–4.82]). Relative and absolute increases in hsTnT over 1 year were associated with higher subsequent risk of the primary end point. The relative reduction in the primary end point with dapagliflozin was consistent across quartiles of baseline hsTnT ( P -interaction=0.55), but patients in the top quartile tended to have the greatest absolute risk reduction (absolute risk difference, 7.5% [95% CI, 1.0%–14.0%]). Dapagliflozin tended to attenuate the increase in hsTnT over time compared with placebo (relative least squares mean reduction, –3% [–6% to 0%]; P =0.076). Conclusions: Higher baseline hsTnT and greater increase in hsTnT over 1 year are associated with worse clinical outcomes. Dapagliflozin consistently reduced the risk of the primary end point, irrespective of baseline hsTnT levels. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03036124.

Human oral microflora is one of the most complex microbial communities known. A consistent competitive environment in this niche necessitates the generation of bacteriocins or antimicrobial peptides (AMPs), which play a significant impact on niche ecology by inhibiting the growth of closely related inhabitants. In the current study, draft genomes of oral commensal Streptococcus salivarius strains were analyzed using various bioinformatic tools to design novel short antibiofilm peptides. The antimicrobial potency of peptides was predicted by using AMP database and Bactibase. Novel short peptides were designed, synthesized and evaluated against oral oppurtinistic pathogenic microbes. Synthetic short peptides (SSPs) displayed effective inhibition of biofilm formation by specific oral bacterial strains, indicating their potential applicability as targeted antibiofilm agents for variety of dental material surface coating applications.

Lithium-ion and lithium-polymer batteries have become dominant in consumer electronic products because of their energy density and product longevity. Li dry-cell can give significantly to sustainable waste as well as potential pollutants that are harmful to human health due to their small size, high rates of removal from buy item here whatever we are previously owned, as well as a, require of the same rigid plan at inherent discarding. To assess hazard assessment, source reduction capability, and dangerous potential about lithium battery worn inside the digital telephone, we used standardized leaching monitoring, Lifecycle Impact Assessment (LCIA), and Hazardous Waste Classification. Diffuse Leon batteries are listed as dangerous by US federal regulations due to their main contents. However, due to high levels of cobalt, copper, and nickel, all lithium batteries tested in California are rated as hazardous. Leached amounts of chromium, lead, and thallium in some of Leon's batteries violated California regulations. However, due to high amounts of cobalt, copper, and nickel, all lithium batteries tested in California are rated as hazardous. Leached amounts of chromium, lead, and thallium in some of Leon's batteries violated California regulations materials.

With growing concerns regarding target residue mutation hovering over established anti-TB pharmacophores, it is imperative to have reserve chemotypes at our disposal to curb unrestrained spread of tuberculosis. In this context, we herein present the synthesis and bio-evaluation of a library of new nitrobenzothiazinone (BTZ) congeners comprising 2-mercapto/amino-benzothiazinone tethered 1,2,3-triazole hybrids as antitubercular agents. In preliminary screening, 10 out of 37 compounds displayed substantial in vitro potency against Mtb H37Rv (MIC 0.5–8 μg mL(−1)). Structural optimization of the initial hit 5o (MIC 0.5 μg mL(−1)) led to identification of linker variants 9a, 9b, 9c, and 9d exhibiting potent anti-TB activity (MIC 0.03–0.12 μg mL(−1)). When tested against Vero cells to determine their selectivity index (SI), these compounds displayed no appreciable cytotoxicity (SI >80). Further studies on activity against drug resistant (DR) Mtb indicated these compounds to be equally potent (MIC 0.03–0.25 μg mL(−1)). The in silico covalent docking study suggested a similar polar interaction to that of PBTZ169 with an additional and contrasting side chain interaction at the active site of Mtb DprE1 target protein. Further, the time kill kinetic study found compounds 9a and 9d to be demonstrating bactericidal efficacy, completely eliminating bacilli in 7 days at 10× MIC. The most promising compound 9d, considering its potent anti-TB activity (MIC 0.06 μg mL(−1) against drug susceptible Mtb and MIC 0.06–0.25 μg mL(−1) against DR Mtb) along with a broad therapeutic index (SI >640) demonstrating a comparable concentration dependent bactericidal efficacy to that of RIF, holds a significant edge to be translated into a potent anti-Mtb agent.

Cellulosic fiber or cellulosic biomass finds major role in the modern scientific era. The cellulosic fibers were well utilized in today’s research due to the unique properties of cellulose such as its biocompatibility, biodegradability, non-toxic etc. Nature is the major sources of cellulose along with some minor sources such as microbial cellulose (fungal, bacterial, algal etc.). One of the major research areas today is to extract cellulose from natural resources abundant with us such as rice husk, wheat husk, maize husk, pine needles, cotton, jute etc. Cellulose can be extract from these available sources by numerous chemicals, mechanical and green techniques. Cellulose extraction can be carried out at nano, micro or macro scale by the processes like alkalization, bleaching, acidic hydrolysis etc. Extracted cellulosic fiber was analyzed by different analysis techniques such as X-Ray Diffraction (XRD), Fourier transform infra-red (FTIR) etc. The present review article represents the importance of the waste biomass to be a useful resource for the extraction of cellulose.

India is emerging as an automobile hub and has adequate production capacity of nitrile to cater to the present demand. However with the passage of time huge waste of nitrile is likely to be created which may become a major problem for its disposal. Nitrile has certain unique properties which are suitable for the road surface viz. resistant to oil, resistant to fuels, resistant to acids, high tensile strength etc. Some research has been carried out using nitrile in bitumen and the results have been encouraging. So far research has only been carried out using Nitrile rubber with different grades of bitumen.Now thermosets namely Bakelite, Furan Resin & Epoxy Resin have been used as a partial replacement of bitumen. In this research a 81 combination of Nitrile Rubber and Thermosets (Bakelite, Furan Resin & Epoxy Resin) shall be replaced with bitumen to prepared a Modified Bituminous Mix, whose properties was studied upon.To determine the optimum bitumen content (OBC) of mixes and to predict different Marshall requirements, the Marshall test is easy, economical, and widely available: Marshall consistency, flow value, air voids, mineral aggregate voids, and bitumen filled voids 5 percent, 5.5 percent, 6 percent, 6.5 percent for each of three styles of moulds were observed under 81 thermoset variations. We observed Indirect Tensile (IDT) Strength and TSR with unconditioned and conditioned would be enhanced after equal distribution of Nitrile Rubber and Thermosets (Bakelite, Furan Resin & Epoxy Resin as filler in modified bituminous . The testresults indicated that addition of Nitrile Rubber and Thermosets (Bakelite, Furan Resin & Epoxy Resin as filler remarkably improves the engineering properties of both mixes considered.

Zinc oxide (ZnO) nanoparticles, because of the reality of their biocompatibility are utilized for biomedical applications. The modern technique-based characterization is needed to find out the pharmacology and biological impact of ZnO nanoparticles. Further, these techniques also help to check the biological and toxic levels of ZnO particles. These nanoparticles to maximize their performance can be folded up in a 3-D structure and also have a different range of shapes. ZnO nanoparticles are utilized in many technical devices like sensor and imaging tool devices. ZnO nanoparticles have various useful activities in human life. ZnO nanoparticles also have the application to help in the healing of a wound. ZnO nanoparticles have healing activity against diabetes and cancer. ZnO particles are formed by various methods, like the sol–gel method, hydrothermal method, and by green method. Zinc oxide nanoparticles are also produced by natural method from plant leaf of Sambucus ebulcus and their physiochemical important findings are further examined for use. The X-ray [radiation mediated] diffraction observation, shown that ZnO nanoparticles are highly crystallized. The dimensions of prepared ZnO nanoparticles are observed differently in different conditions. Further, there are large numbers of techniques for the production of ZnO nanoparticles.

Staphylococcus auerus (S. aureus) biofilms are a frequently associated cause of artificial implant infections and failures. Surface coating of titanium (Ti), a widely used implant biomaterial with antimicrobial agents may appear a promising approach to prevent and reduce the periimplant infections and associated failures. Natural antimicrobial peptides (AMPs) viz laterosporulins (LS) from soil bacteria Brevibacillus spp. were bound on titanium (Ti) substrates using a simple, time and cost effective chemical processing technique. Resistance of the AMP coated Ti substrates against biofilm formation of the bacterium S. aureus was determined by crystal violet staining, in vitro. Further the antibiofilm activity was visualized in replicate experiments on Hydroxyapatite (HA) discs also to simulate enamel surfaces consistently layered by saliva in oral cavity to ascertain the biofilm inhibition assessment. AMP coated Ti substrates showed marked reduction in the biofilm formation by S. aureus, in vitro compared against the control-Ti surfaces. Further, Coated HA discs also substantiated the findings in a similar trend compared with control-Ti substrates. The findings suggested a promising potential for laterosporulins as effective antibiofilm agents for coating titanium surfaces for various applications, including dental implants used in oral cavity.

The natural product specialized metabolites produced by microbes and plants are the backbone of our current drugs. Ironically, we are in a golden age of understanding natural product biosynthesis, biochemistry, and engineering. These advances have the potential to usher in a new era of natural product exploration and development, taking full advantage of the unique and favorable properties of natural product compounds in drug discovery. There is now an increasing realization that these privileged structures represent the optimal starting point for the development of clinically viable assets. Here, we outline the current state-of-the-art in antimicrobial natural product drug discovery, specifically Streptomyces species, with a specific focus on how the emerging field of synthetic biology is delivering the tools and technologies required to unlock the therapeutic potential of natural products. We illustrate how these approaches are circumventing many of the problems that have historically plagued conventional screening programs, enabling the expedient discovery of new molecules with novel functions.

With an estimated failure rate of about 90%, immunotherapies that are intended for the treatment of solid tumors have caused an anomalous rise in the mortality rate over the past decades. It is apparent that resistance towards such therapies primarily occurs due to elevated levels of HIF-1 (Hypoxia-induced factor) in tumor cells, which are caused by disrupted microcirculation and diffusion mechanisms. With the advent of nanotechnology, several innovative advances were brought to the fore; and, one such promising direction is the use of perfluorocarbon nanoparticles in the management of solid tumors. Perfluorocarbon nanoparticles enhance the response of hypoxia-based agents (HBAs) within the tumor cells and have been found to augment the entry of HBAs into the tumor micro-environment. The heightened penetration of HBAs causes chronic hypoxia, thus aiding in the process of cell quiescence. In addition, this technology has also been applied in photodynamic therapy, where oxygen self-enriched photosensitizers loaded perfluorocarbon nanoparticles are employed. The resulting processes initiate a cascade, depleting tumour oxygen and turning it into a reactive oxygen species eventually to destroy the tumour cell. This review elaborates on the multiple applications of nanotechnology based perfluorocarbon formulations that are being currently employed in the treatment of tumour hypoxia.

Antimicrobial resistance (AMR) has been increasing unrelentingly worldwide, thus negatively impacting human health. The discovery and development of novel antibiotics is an urgent unmet need of the hour. However, it has become more challenging, requiring increasingly time-consuming efforts with increased commercial risks. Hence, alternative strategies are urgently needed to potentiate the existing antibiotics. In this context, short cationic peptides or peptide-based antimicrobials that mimic the activity of naturally occurring antimicrobial peptides (AMPs) could overcome the disadvantages of AMPs having evolved as potent antibacterial agents. Besides their potent antibacterial efficacy, short peptide conjugates have also gained attention as potent adjuvants to conventional antibiotics. Such peptide antibiotic combinations have become an increasingly cost-effective therapeutic option to tackle AMR. This Review summarizes the recent progress for peptide-based small molecules as promising antimicrobials and as adjuvants for conventional antibiotics to counter multidrug resistant (MDR) pathogens.

Tissue engineering demands intelligently designed scaffolds that encompass the properties of the target tissues in terms of mechanical and bioactive properties. An ideal scaffold for engineering a cartilage tissue should provide the chondrocytes with a favorable 3D microarchitecture apart from possessing optimal mechanical characteristics such as compressibility, energy dissipation, strain stiffening, etc. Herein, we used a unique design approach to develop a hydrogel having a dynamic interpenetrating network to serve as a framework to support chondrocyte growth and differentiation. An amyloid-inspired peptide amphiphile (1) was self-assembled to furnish kinetically controlled nanofibers and incorporated in a dynamic covalently cross-linked polysaccharide network of carboxymethyl cellulose dialdehyde (CMC-D) and carboxymethyl chitosan (CMCh) using Schiff base chemistry. The dynamic noncovalent interaction played a pivotal role in providing the desired modulation in the structure and mechanical properties of the double-network hydrogels that are imperative for cartilage scaffold design. The adaptable nature supported shear-induced extrusion of the hydrogel and facilitated various cellular functions while maintaining its integrity. The potential of the as-developed hydrogels to support in vitro chondrogenesis was explored using human chondrocytes. Evidence of improved cell growth and cartilage-specific ECM production confirmed the potential of the hydrogel to support cartilage tissue engineering while reaffirming the significance of mimicking the biophysical microenvironment to induce optimal tissue regeneration.

Since ancient times the medicinal plants have been under use as food and potential therapeutic agent for the management of overall health and the use of all plant parts including fruits, seeds, is well reported in the literature. One such plant is Berberis aristata which is rich in vitamins, minerals, and various phytochemicals amongst which Berberine is the principal bioactive compound with a range of reported health benefits, and some of the commercial formulations like Rasaut, Darvyadi Leha are being used for the treatments of jaundice, malaria, typhoid fever, inflammation, eye infection, diarrhea, wound healing, etc. The hepatoprotective, antidiabetic, antitumor, anti-cancerous, properties are the recent additions to its functional importance. Berberine has significant bioactivities in the treatments of different diseases. Besides its remarkable applications, the berberine has low efficacy due to its low solubility in water, poor absorption, and low bioavailability. This problem can be solved by using some techniques like Nanotechnology which has been found to increase its solubility in water, bioavailability, and absorption and hence provide a better delivery system of berberine. This review illuminates the therapeutic applications of the plant Berberis aristata, scientific validation to its traditional uses, role of berberine in the treatment of various diseases through its different bioactivities, major flaws in berberine treatment, and the role of nanotechnology in minimizing those flaws and increasing its overall efficacy. Key teaching pointsPlant Berberis aristata has been used since ancient times for the treatment of various ailments like jaundice, hepatitis, fever, bleeding, inflammation, diarrhea, malaria, skin and eye infections, chronic rheumatism, and urinary disorders.Berberine is the major and most significant phytochemical among numerous phytochemicals present in plant Berberis aristata.Berberine has significantly shown many potent effect against emerging diseases like cancer and diabetes. Besides that, it has also shown antioxidant, anti-inflamation, antimicrobial, hepatoprotective, and anti-gastrointestinal disorder properties.Berberine can be very effective in overcoming the demerits of berberine treatment like poor aqueous solubility, low bioavailability, and poor absorption in the human body in the treatment of various diseases.

Emerging evidence suggests that host glycans influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we reveal that the receptor-binding domain (RBD) of the spike (S) protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (Sia), with preference for monosialylated gangliosides. Gangliosides embedded within an artificial membrane also bind to the RBD. The monomeric affinities (Kd = 100–200 μM) of gangliosides for the RBD are similar to another negatively charged glycan ligand of the RBD proposed as a viral co-receptor, heparan sulfate (HS) dp2–dp6 oligosaccharides. RBD binding and infection of SARS-CoV-2 pseudotyped lentivirus to angiotensin-converting enzyme 2 (ACE2)-expressing cells is decreased following depletion of cell surface Sia levels using three approaches: sialyltransferase (ST) inhibition, genetic knockout of Sia biosynthesis, or neuraminidase treatment. These effects on RBD binding and both pseudotyped and authentic SARS-CoV-2 viral entry are recapitulated with pharmacological or genetic disruption of glycolipid biosynthesis. Together, these results suggest that sialylated glycans, specifically glycolipids, facilitate viral entry of SARS-CoV-2. Mass spectrometric profiling of a glycan library reveals that sialylated glycans, especially sialic acid-containing gangliosides, interact with the RBD of the SARS-CoV-2 spike protein and are involved in ACE2-dependent viral infection.

Alzheimer’s disease (AD) is considered the sixth leading cause of death in elderly patients and is characterized by progressive neuronal degeneration and impairment in memory, language, etc. AD is characterized by the deposition of senile plaque, accumulation of fibrils, and neurofibrillary tangles (NFTs) which are responsible for neuronal degeneration. Amyloid-β (Aβ) plays a key role in the process of neuronal degeneration in the case of AD. It has been reported that Aβ is responsible for the production of reactive oxygen species (ROS), depletion of endogenous antioxidants, increase in intracellular Ca2+ which further increases mitochondria dysfunctions, oxidative stress, release of pro-apoptotic factors, neuronal apoptosis, etc. Thus, oxidative stress plays a key role in the pathogenesis of AD. Antioxidants are compounds that have the ability to counteract the oxidative damage conferred by ROS. Therefore, the antioxidant therapy may provide benefits and halt the progress of AD to advance stages by counteracting neuronal degeneration. However, despite the beneficial effects imposed by the antioxidants, the findings from the clinical studies suggested inconsistent results which might be due to poor study design, selection of the wrong antioxidant, inability of the molecule to cross the blood–brain barrier (BBB), treatment in the advanced state of disease, etc. The present review insights into the neuroprotective effects and limitations of the antioxidant therapy for the treatment of AD by targeting mitochondrial-derived ROS. This particular article will certainly help the researchers to search new avenues for the treatment of AD by utilizing mitochondrial-derived ROS-targeted antioxidant therapies.

A laboratory experiment was conducted at AINP on Pesticide Residues, ICAR Unit - 9, AAU, Anand to study the dissipation behaviour of bifenthrin in water at different pH (4.0, 7.0 and 9.2) at the ra...

The present study investigates the micromechanical properties of ceramic coated WC/Co tools and their influence on wear performance during dry Ti6Al4V turning. Physical and micromechanical characterization have been performed for the evaluation of the PVD coating properties. Higher hardness, elastic modulus, and adhesion strength have been obtained for dual-layer (AlTiN/AlCrN) coated tool than monolayer AlTiN and AlCrN coated tools. Micromechanical properties influence the wear mechanisms in thermally activated and abrasion dominant crater zones. Dual-layer coated tools reduced the flank wear at the corner radius and crater wear by 35–50% and 40%, respectively. Dynamic wear and abrasion-dissolution wear mechanisms have been explored over the tool rake face. Dual-layer coatings have improved wear performance by diminishing delamination, micro-fracturing of WC grains, binder dissolution and fractured interface boundaries.

The ECM of cartilage is composed of proteoglycans (PG) that contain glycosaminoglycan (GAG), aggrecan, hyaluronic acid (HA) and other molecular components which play an important role in regulating chondrocyte functions via cell-matrix interactions, integrin-mediated signalling etc. Implantation of chondrocytes encapsulated in scaffolds that mimic the micro-architecture of proteoglycan, is expected to enhance cartilage repair. With an aim to create a hydrogel having macromolecular structure that resembles the cartilage-specific ECM, we constructed a hierarchal structure that mimic the PG. The bottle brush structure of the aggrecan was obtained using chondroitin sulphate and carboxymethyl cellulose which served as GAG and core protein mimic respectively. A proteoglycan-like structure was obtained by cross-linking it with modified chitosan that served as a HA substitute. The physico-chemical characteristics of the above cross-linked injectable hydrogel supported long term human articular chondrocyte subsistence and excellent post-injection viability. The chondrocytes encapsulated in the PMH expressed significant levels of articular cartilage specific markers like collagen II, aggrecan, GAGs etc., indicating the ability of the hydrogel to support chondrocyte differentiation. The biocompatibility and biodegradability of the hydrogels was confirmed using suitable in vivo studies. The results revealed that the PG-mimetic hydrogel could serve as a promising scaffold for chondrocyte implantation.

F-box protein FBXW8 is known to interact with scaffolding protein Cullin1 and Cullin7 to form SCF (SKP1, Cullin and F-box protein) complex. However, detail understanding about the importance of both Cullins for SCF-FBXW8 complex formation as well as its ubiquitin ligase activity remains elusive. Here, we show that, through in vitro and in vivo studies, Cullin1 and Cullin7 increase each other's binding to FBXW8 synergistically. Interestingly, absence of either Cullin results in abrogation of binding of other Cullin to FBXW8. Binding of SKP1 to FBXW8 also increases in the presence of both the Cullins. Thus, SKP1, Cullin1 and Cullin7 are essential to form Cullin1-SKP1-FBXW8-Cullin7 functional ubiquitin ligase complex. Further, using computational, mutational and biochemical analysis, we found that Cullin1 binds to N-terminus of FBXW8 through SKP1 while Cullin7 associates with C-terminus of FBXW8 to form Cullin1-SKP1-FBXW8-Cullin7 functional complex in a cooperative manner. Results showed that Cullin1-SKP1-FBXW8-Cullin7 complex plays a key role in maintaining the basal level expression of β-TrCP1. Moreover, Cullin1-SKP1-FBXW8-Cullin7 complex promotes cell migration by activating β-catenin via directing proteasomal degradation of β-TrCP1. Overall, our study reveals the intriguing molecular mechanism of assembly of SKP1, Cullin1, Cullin7 and FBXW8 to form Cullin1-SKP1-FBXW8-Cullin7 functional complex that control the function of β-TrCP1.

A series of hydrogen-bonded complexes between N-heterocyclic analogs of Indene and amino acid side-chain mimics have been analyzed employing second-order Moller-Plesset perturbation (MP2) theory and density functional theory with dispersion function (DFT-D) calculations with the aim of gaining greater insight in to the nature of intermolecular interactions in these systems. In this study, the hydrogen bonding ability of N-heterocyclic analogs of Indene towards amino acid side-chain mimics follows the sequence Azaindazole (AIND) > Indazole (IND) > Azaindole (AIN) > Indole (IN) whereas the hydrogen bonding ability of amino acid side-chain mimics towards N-heterocyclic analogs of Indene follows the sequence AcOH > MeNH2 > MeOH > MeSH. Bader’s theory of atoms in molecules (AIM) and natural bond orbitals (NBO) analyses are employed to elucidate the interaction characteristics in the complexes under study. The purpose of conducting these studies is to measure the relative strength of hydrogen bonding interactions such as N-H···O=C, N-H···O, N-H···S, N-H···N, and O-H···N in these complexes and their role in providing stability to the complexes. The AIM theory shows good correlation of the electron density and its Laplacian at the bond critical points (BCP) with the computed stabilization energy for all the complexes under study.

Astrocytes regulate the response of the central nervous system to disease and injury and have been hypothesized to actively kill neurons in neurodegenerative disease1–6. Here we report an approach to isolate one component of the long-sought astrocyte-derived toxic factor5,6. Notably, instead of a protein, saturated lipids contained in APOE and APOJ lipoparticles mediate astrocyte-induced toxicity. Eliminating the formation of long-chain saturated lipids by astrocyte-specific knockout of the saturated lipid synthesis enzyme ELOVL1 mitigates astrocyte-mediated toxicity in vitro as well as in a model of acute axonal injury in vivo. These results suggest a mechanism by which astrocytes kill cells in the central nervous system. Astrocytes can respond to diseases and injuries of the central nervous system by driving the death of neurons and mature oligodendrocytes through the delivery of long-chain saturated fatty acids contained in lipoparticles.

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA) are primary causes of skin and soft tissue infections worldwide. To address the emergency caused due to increasing multidrug-resistant (MDR) bacterial infections, a series of novel fluoro and trifluoromethyl-substituted salicylanilide derivatives were synthesized and their antimicrobial activity was investigated. MIC data reveal that the compounds inhibited S. aureus specifically (MIC 0.25–64 µg/mL). The in vitro cytotoxicity of compounds with MIC