Evolution in the asymmetric synthesis of biaryl ethers and related atropisomers.

Axially chiral biaryl ethers and related compounds hold valuable potential in natural products, medicinal chemistry, and catalysis; however, their asymmetric syntheses have always been overlooked compared to other biaryl/hetero-biaryl atropisomers. Unlike the later class molecules bearing a single chiral axis, the former category possesses a unique type of atropisomerism bearing two potential axes. Due to their great importance in diverse research domains, catalytic atropselective biaryl ether synthesis has recently witnessed an upsurge. This highlight article provides an elaborated view on the developments of catalytic synthetic methods that have been explored to achieve dual axial chirality in biaryl ethers and related scaffolds.

Evaluation of Surface Water Quality in the Betwa River Basin through the Water Quality Index Model and Multivariate Statistical Techniques.

The Betwa River Basin (BRB), a sub-basin of the River Yamuna, is the oldest flowing water system in Central India. The water quality of the rivers are under stress, hence regular monitoring and appraisal is required to know the health of the rivers. Factor analysis and principal component analysis (FA/PCA) multivariate statistical techniques were used to extract three and four varimax factors that explained 96.408 and 100.00 percent of the total variance in water quality, respectively. Cluster analysis (CA) categorizes observed items into distinct quality categories based on correlations between stations and years. Point industrial/sewage effluents, diffuse pollution as runoff from arable land, erosion, and natural source pollution contribute to the pollution of the BRB. As a result, water quality is threatened or impaired, and conditions often departed from natural or desirable levels at Rajghat, Garrauli, Mohana, and Shahijina stations. According to the Canadian Council of Ministers of the Environment Water Quality Index (CCME-WQI), the surface water quality at the Rajghat and Mohana stations corresponds to fair ecological status. However, the surface water quality of the Garrauli and Shahijina stations has a marginal water quality as per CCME-WQI. From 1985 to 2018, the Shahijina had the most considerable load of nutrients and organic matter, as determined by the CCME-WQI and by comparing the water quality data. A thorough examination had revealed a fluctuating trend in the BRB pollution, particularly at all stations. Results indicate that between 1985 and 2018, the only defense mechanism of the river was the auto purification mechanism, which is strongly influenced by the drought, point pollution source, and extreme meteorological events that probably cause these fluctuations.

Accessing Pyridines via a Nitrene Internalization Process.

Pyridines are valuable pharmacophores, and their access via direct and selective transmutation of carbon atom with desired nitrogen could become crucial in drug discovery processes. However, only scarce examples can be found when it comes C-to-N-transmutation reactions of aromatics that could lead to the facile synthesis of pyridines or other azaarenes. In this context, Levin and co-workers recently disclosed a process leading to pyridines from the corresponding aryl azides via the regioselective nitrene internalization process. Notably, the transformation did not lead to any further modification of the rest of the aromatic skeleton. This innovative work enabled selectively accessing various pyridine derivatives through direct nitrogen scan operations on benzene derivatives, which were otherwise not feasible.

Experimental Investigation and Characterization of Friction Stir Spot-Welded Dissimilar Aluminum Copper Metallic Lap Joints.

Due to their contrasting physical properties, joining materials like copper and aluminum has always proven difficult. The disadvantages of traditional joining methods include additional weight, solidification problems, and energy waste. Friction stir spot-welding (FSSW) was utilized for joining copper and aluminum in order to get around these difficulties. This study illustrates that friction stir spot-welding (FSSW) produces joints between incompatible copper and aluminum alloys with better mechanical and electrical properties. The numerous FSSW parameters play an important role in deciding how well the welded joint performs. Tool rotational speed (TRS), plunge rate (PR), and dwell duration (DT) are the study parameters. During manufacture, a case-hardened H13 tool was used to lap-joint AA 6061 T6 hot-rolled aluminum flat strips with C11000 copper strips while operating at three different levels of TRS, PR and DT. SEM analysis was utilized to investigate the interface region and bimetallic interface of the joints. In order to demonstrate modifications in the grain-related characteristics, the joints were examined for electrical conductivity, mechanical strength (lap shear, bending, and microhardness test), and analysis of the microstructure at the weld zones. The outcome demonstrates that other factors, such as plunge rate, dwell time, and tool rotation speed, had the greatest impact on the joints' electrical conductivity, mechanical strength, and microstructure.

Organocatalytic Asymmetric Synthesis of Carbo- and Oxacyclic Seven-Membered Bridged Biaryls via Nucleophile-Dependent Switchable Domino Processes.

We disclose herein a highly diastereo- and enantioselective divergent synthesis of seven-membered biaryl-bridged carbo- and oxacyclic frameworks by utilizing the catalytic ability of bifunctional hydrogen-bonding squaramide organocatalysts. Starting with the same biaryl substrate bearing two distinct acceptor sites and by choosing soft or hard nucleophiles, we readily accessed the dibenzocycloheptanes or 5,7-dihydrodibenzo[c,e]oxepines bearing multiple elements of chirality via a domino 1,4/1,2-addition or 1,2/oxa-Michael addition sequence, respectively.

Asymmetric Synthesis of Hydrophenanthrenones Bearing Multiple Stereogenic Centers via Squaramide-Catalyzed Domino 1,4-/1,4-Addition Desymmetrization Sequence.

An unprecedented stereoselective route for procuring tetrahydrophenanthren-2(1H)-ones bearing up to five contiguous stereogenic centers has been accomplished. A bifunctional squaramide enables a domino 1,4-/1,4-addition desymmetrization reaction sequence between the newly developed ß-nitrostyrene-tethered 2,5-cyclohexadienones and trisubstituted enolizable nucleophiles to provide direct access to the polyfunctionalized hydrophenanthren-2(1H)-ones in excellent enantio- (up to >99%) and diastereoselectivity (up to >20:1). By using a psedoenantiomeric squaramide, the enantiomers of hydrophenanthrene derivatives were also accessed with excellent stereocontrol.

Obstructive Sleep Apnea and Hearing Loss: Is There Any Correlation?

Abstract Introduction Obstructive sleep apnea (OSA) is a breathing disorder related to sleep that has a negative effect on the behavior and health of people around the globe. Chronic hypoxemia and variations in the concentration of oxygen in the blood noticed in OSA individuals may have adverse effects on the process of auditory transduction and transmission. Objective To assess the effect of OSA on hearing and to find out the parameters that have more influence on hearing recorded during polysomnography of patients with OSA. Methods The present is a hospital-based, observational, analytical, cross-sectional study conducted over a period of one year. After application of the exclusion criteria, the patients were then submitted to the application of the Berlin questionnaire, as well as polysomnography, impedance, and pure tone audiometry (PTA). Results A total of 58 individuals were studied. Age, gender, and height were comparable among cases and controls, while weight, body mass index (BMI), and neck circumference were significantly higher in cases in comparison to controls. The mean PTA was significantly higher at 10 kHz or higher frequencies in cases in comparison to controls. Conclusion We observed that there is evidence that the auditory mechanism is affected in OSA patients. We recommend early auditory screening of OSA patients for timely diagnosis and to raise awareness about its prevention.

Obstructive Sleep Apnea and Hearing Loss: Is There Any Correlation?

Introduction Obstructive sleep apnea (OSA) is a breathing disorder related to sleep that has a negative effect on the behavior and health of people around the globe. Chronic hypoxemia and variations in the concentration of oxygen in the blood noticed in OSA individuals may have adverse effects on the process of auditory transduction and transmission. Objective To assess the effect of OSA on hearing and to find out the parameters that have more influence on hearing recorded during polysomnography of patients with OSA. Methods The present is a hospital-based, observational, analytical, cross-sectional study conducted over a period of one year. After application of the exclusion criteria, the patients were then submitted to the application of the Berlin questionnaire, as well as polysomnography, impedance, and pure tone audiometry (PTA). Results A total of 58 individuals were studied. Age, gender, and height were comparable among cases and controls, while weight, body mass index (BMI), and neck circumference were significantly higher in cases in comparison to controls. The mean PTA was significantly higher at 10 kHz or higher frequencies in cases in comparison to controls. Conclusion We observed that there is evidence that the auditory mechanism is affected in OSA patients. We recommend early auditory screening of OSA patients for timely diagnosis and to raise awareness about its prevention.

Carbene Formation or Reduction of the Diazo Functional Group? An Unexpected Solvent-Dependent Reactivity of Cyclic Diazo Imides.

The control of the reactivity of diazo compounds is commonly achieved by the choice of a suitable catalyst, e.g. via stabilization of singlet carbenes or radical intermediates. Herein, we report on the light-promoted reactivity of cyclic diazo imides with thiols, where the choice of solvent results in two fundamentally different reaction pathways. In dichloromethane (DCM), a carbene is formed initially and engages in a cascade C-H functionalization/thiolation reaction to deliver indane-fused pyrrolidines in good to excellent yields. When switching to acetonitrile solvent, the carbene pathway is shut down and an unusual reduction of the diazo compound occurs under otherwise identical reaction conditions, where the aryl thiol acts as reductant. A combined set of experimental and computational studies was carried out to obtain mechanistic understanding and to support that indane formation proceeds via the insertion of a triplet carbene, while the reduction of diazo imides proceeds via an electron transfer process.

Enhanced osseointegration of drug eluting nanotubular dental implants: An in vitro and in vivo study.

Faster and predictable osseointegration is crucial for the success of dental implants, especially in patients with compromised local or systemic conditions. Despite various surface modifications on the commercially available Titanium (Ti) dental implants, the bioactivity of Ti is still low. Thus, to achieve both biological and therapeutic activity on titanium surfaces, surface modification techniques such as titanium nanotubes have been studied as nanotube surfaces can hold therapeutic drugs and molecules. The main aim of the present research work is to study the early osseointegration around the novel Simvastatin drug eluting nanotubular dental implant. In the present research, the titanium nanotubes were fabricated on the screw-shaped dental implant surface and the Simvastatin drug was loaded into the nanotubes using the ultrasonication dip method. In vitro and In vivo studies were carried out on the modified dental implants. In vitro cell culture study reported enhanced osteogenic activity on the drug-loaded nanotube surface implants. The invivo animal studies were evaluated by micro-CT, histopathology, and reverse torque removal analysis methods. The test results showed faster osseointegration with the strong interface on the Simvastatin drug-loaded implant surface at 4 weeks of healing as compared to the control implants.

Transcriptome data analysis of primary cardiomyopathies reveals perturbations in arachidonic acid metabolism.

Introduction: Cardiomyopathies are complex heart diseases with significant prevalence around the world. Among these, primary forms are the major contributors to heart failure and sudden cardiac death. As a high-energy demanding engine, the heart utilizes fatty acids, glucose, amino acid, lactate and ketone bodies for energy to meet its requirement. However, continuous myocardial stress and cardiomyopathies drive towards metabolic impairment that advances heart failure (HF) pathogenesis. So far, metabolic profile correlation across different cardiomyopathies remains poorly understood. Methods: In this study, we systematically explore metabolic differences amongst primary cardiomyopathies. By assessing the metabolic gene expression of all primary cardiomyopathies, we highlight the significantly shared and distinct metabolic pathways that may represent specialized adaptations to unique cellular demands. We utilized publicly available RNA-seq datasets to profile global changes in the above diseases (|log2FC| ≥ 0.28 and BH adjusted p-val 0.1) and performed gene set analysis (GSA) using the PAGE statistics on KEGG pathways. Results: Our analysis demonstrates that genes in arachidonic acid metabolism (AA) are significantly perturbed across cardiomyopathies. In particular, the arachidonic acid metabolism gene PLA2G2A interacts with fibroblast marker genes and can potentially influence fibrosis during cardiomyopathy. Conclusion: The profound significance of AA metabolism within the cardiovascular system renders it a key player in modulating the phenotypes of cardiomyopathies.

Electro-Oxidative Synthesis of Phenazines.

We disclose herein electro-oxidative synthesis as the general protocol for procuring phenazines under mild reaction conditions. Using aerial oxygen as an oxidant, inexpensive electrolyte, and electrodes, a diverse range of phenazines have been accessed in good yields via the ring contraction of 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepines. In addition, the syntheses of phenazines and diamino phenazines via direct electro-oxidation of dihydrophenazines and electro-dimerization of o-phenylenediamines, respectively, have also been accomplished.

Comparative analysis of discharge and sediment flux from two contiguous glacierized basins of Central Himalaya, India.

In the present study, suspended sediment load (SSL), sediment yield and erosion rates in Pindari Glacier basin (PGB) and Kafni Glacier basin (KGB) have been estimated using daily discharge and suspended sediment concentration (SSC) data for three ablation seasons (2017-2019). For this, one meteorological observatory and two gauging sites have been established at Dwali (confluence point), and water samples have been collected twice in a day for high flow period (July to September) and daily for lean period (May, June and October). An area-velocity method and stage-discharge relationship has been established to convert water level into discharge (m3 s-1). For estimating SSC (mg/l), collected water samples have been filtered, dried, analysed and confirmed with an automatic suspended solid indicator. Further, SSL, sediment yield and erosion rates have been computed using SSC data. The results reveal that mean annual discharge in PGB (35.06 m3 s-1) has been found approximately 1.7 times higher than KGB (20.47 m3 s-1). The average SSC and SSL in PGB have been observed about 396.07 mg/l and 1928.34 tonnes, and in KGB, it is about 359.67 mg/l and 1040.26 tonnes, respectively. The SSC and SSL have followed the pattern of discharge. A significant correlation of SSC and SSL has been found with discharge in both the glacierized basins (p < 0.01). Interestingly, average annual sediment yield in PGB (3196.53 t/km2/yr) and KGB (3087.23 t/km2/yr) have been found almost identical. Likewise, the erosion rates in PGB and KGB have been witnessed about 1.18 and 1.14 mm/yr, respectively. Sediment yield and erosion rates in PGB and KGB have been found in correspondence with other basins of Central Himalaya. These findings will be beneficial for engineers and water resource managers in the management of water resources and hydropower projects in high-altitude areas and in the planning and designing of water structures (dams, reservoirs etc.) in downstream areas.

Computational analysis of the flexibility in the disordered linker region connecting LIM domains in cysteine-glycine-rich protein.

One of the key proteins that are present in the Z-disc of cardiac tissues, CSRP3, has been implicated in dilated and hypertrophic cardiomyopathy leading to heart failure. Although multiple cardiomyopathy-related mutations have been reported to reside on the two LIM domains and the disordered regions connecting the domains in this protein, the exact role of the disordered linker region is not clear. The linker harbors a few post-translational modification sites and is expected to be a regulatory site. We have carried out evolutionary studies on 5614 homologs spanning across taxa. We also performed molecular dynamics simulations of full-length CSRP3 to show that the length variations and conformational flexibility of the disordered linker could provide additional levels of functional modulation. Finally, we show that the CSRP3 homologs with widely different lengths of the linker regions could display diversity in their functional specifications. The present study provides a useful perspective to our understanding of the evolution of the disordered region between CSRP3 LIM domains.

Relay Organophotoredox/N-Heterocyclic Carbene Catalysis-Enabled Asymmetric Synthesis of Dibenzoxazepine-Fused Pyrrolidinones.

An unprecedented highly stereoselective synthesis of pyrrolo[1,2-d][1,4]oxazepin-3(2H)-ones has been accomplished via photoredox/N-heterocyclic carbene (NHC) relay catalysis. A wide range of substituted dibenzoxazepines and aryl/hetereoaryl enals were well accommodated under the organic photoredox catalysis-promoted amine oxidation to generate the imines, followed by a NHC-catalyzed [3 + 2] annulation reaction to achieve excellent diastereo- and enantioselectivities of the dibenzoxazepine-fused pyrrolidinones.

Physicochemical Properties of UV-Irradiated, Biaxially Oriented PLA Tubular Scaffolds.

PLA and its blends are the most extensively used materials for various biomedical applications such as scaffolds, implants, and other medical devices. The most extensively used method for tubular scaffold fabrication is by using the extrusion process. However, PLA scaffolds show limitations such as low mechanical strength as compared to metallic scaffolds and inferior bioactivities, limiting their clinical application. Thus, in order to improve the mechanical properties of tubular scaffolds, they were biaxially expanded, wherein the bioactivity can be improved by surface modifications using UV treatment. However, detailed studies are needed to study the effect of UV irradiation on the surface properties of biaxially expanded scaffolds. In this work, tubular scaffolds were fabricated using a novel single-step biaxial expansion process, and the surface properties of the tubular scaffolds after different durations of UV irradiation were evaluated. The results show that changes in the surface wettability of scaffolds were observed after 2 min of UV exposure, and wettability increased with the increased duration of UV exposure. FTIR and XPS results were in conjunction and showed the formation of oxygen-rich functional groups with the increased UV irradiation of the surface. AFM showed increased surface roughness with the increase in UV duration. However, it was observed that scaffold crystallinity first increased and then decreased with the UV exposure. This study provides a new and detailed insight into the surface modification of the PLA scaffolds using UV exposure.

Asymmetric synthesis of spirocyclic isobenzofuranones via a squaramide-catalysed sulfa-Michael desymmetrisation reaction.

Enantioselective synthesis of spirocyclohexenone isobenzofuranones has been achieved through an organocatalysed sulfa-Michael desymmetrisation reaction. A cinchona-derived squaramide effectively promotes the desymmetrisation of spirocyclic 2,5-cyclohexadienone isobenzofuranones via the controlled addition of various aryl thiols to generate two vicinal stereocenters with perfect diastereoselectivities and up to very good enantioselectivities.

In vitro antidiabetic, antioxidant, antimicrobial, and cytotoxic activity of Murraya koenigii leaf extract intercedes ZnO nanoparticles.

Nanotechnology is an emerging field with tremendous potential and usage of medicinal plants and green preparation of nanoparticles (NPs) is one of the widely explored areas. These have been shown to be effective against different biological activities such as diabetes mellitus, cancer, antioxidant, antimicrobial, etc. The current studies focus on the green synthesis of zinc NPs (ZnO NPs) from aqueous leaf extract of Murraya koenigii (MK). The synthesized Murraya koeingii zinc oxide NPs (MK ZnO NPs) were characterized using UV-visible spectroscopy, dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), energy-dispersive spectrum (EDS) and cyclic voltammetry (CV). The synthesized MK ZnO NPs were evaluated for their in vitro antidiabetic, antioxidant, antimicrobial, and cytotoxic activity. They demonstrated significant antidiabetic and cytotoxic activity, as well as moderate free-radical scavenging and antibacterial activity.

Glomus Tumor of the Pterygopalatine Fossa: A Rare Case Report.

The pterygopalatine fossa (PPF) is a challenging space and pathological processes in this anatomical space are uncommon. This report presents a case of glomus tumor right PPF in a 65 years old female patient who underwent tumor removal by endoscopic transnasal-transmaxillary approach with preoperative selective embolization of the right internal maxillary artery.

Integrative network analysis interweaves the missing links in cardiomyopathy diseasome.

Cardiomyopathies are progressive disease conditions that give rise to an abnormal heart phenotype and are a leading cause of heart failures in the general population. These are complex diseases that show co-morbidity with other diseases. The molecular interaction network in the localised disease neighbourhood is an important step toward deciphering molecular mechanisms underlying these complex conditions. In this pursuit, we employed network medicine techniques to systematically investigate cardiomyopathy's genetic interplay with other diseases and uncover the molecular players underlying these associations. We predicted a set of candidate genes in cardiomyopathy by exploring the DIAMOnD algorithm on the human interactome. We next revealed how these candidate genes form association across different diseases and highlighted the predominant association with brain, cancer and metabolic diseases. Through integrative systems analysis of molecular pathways, heart-specific mouse knockout data and disease tissue-specific transcriptomic data, we screened and ascertained prominent candidates that show abnormal heart phenotype, including NOS3, MMP2 and SIRT1. Our computational analysis broadens the understanding of the genetic associations of cardiomyopathies with other diseases and holds great potential in cardiomyopathy research.