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The carboxy-terminus of Hsp70-interacting protein (CHIP) is a ubiquitin ligase and co-chaperone belonging to Ubox family that plays a crucial role in the maintenance of cellular homeostasis by switching the equilibrium of the folding-refolding mechanism towards the proteasomal or lysosomal degradation pathway. It links molecular chaperones viz. HSC70, HSP70 and HSP90 with ubiquitin proteasome system (UPS), acts as a quality control system. CHIP contains charged domain in between N-terminal TPR and C-terminal Ubox domain. TPR domain interacts with the aberrant client proteins via chaperones while Ubox domain facilitates the ubiquitin transfer to the client proteins for ubiquitination. Thus, CHIP is a classic molecule that executes ubiquitination for degradation of client proteins. Further, CHIP has been found to be indulged in cellular differentiation, proliferation, metastasis and tumorigenesis. Additionally, CHIP can play its dual role as a tumor suppressor as well as an oncogene in numerous malignancies, thus acts as a double agent. Here, in this review, we have reported almost all substrates of CHIP established till date and classified them according to the hallmarks of cancer. In addition, we discussed about its architectural alignment, tissue specific expression, sub-cellular localization, folding-refolding mechanisms of client proteins, E4 ligase activity, normal physiological roles, involvement in various diseases and tumor biology. Further, we aim to discuss its importance in HSP90 inhibitors mediated cancer therapy. Thus, this report concludes that CHIP may be a promising and worthy drug target towards pharmaceutical industry for drug development.

Antibiotic and antimicrobial resistance is a continually growing challenge in the treatment of various bacterial infections worldwide. New drugs and new drug targets are necessary to curb the threat of infectious diseases caused by multidrug-resistant pathogens. The tryptophan biosynthesis pathway is essential for bacterial growth but is absent in higher animals and humans. Drugs that can inhibit the bacterial biosynthesis of tryptophan offer a new class of antibiotics. In this work, we combined a structure-based strategy using in silico docking screening and molecular dynamics (MD) simulations to identify compounds targeting the α subunit of tryptophan synthase with experimental methods involving the whole-cell minimum inhibitory concentration (MIC) test, solution state NMR, and crystallography to confirm the inhibition of L-tryptophan biosynthesis. Screening 1800 compounds from the National Cancer Institute Diversity Set I against α subunit revealed 28 compounds for experimental validation; four of the 28 hit compounds showed promising activity in MIC testing. We performed solution state NMR experiments to demonstrate that Compound 1 binds to the α subunit. We also report a crystal structure of Salmonella enterica serotype Typhimurium tryptophan synthase in complex with one successful inhibitor, 3-amino-3-imino-2-phenyldiazenylpropanamide (Compound 1) which revealed a binding site at the αβ interface of the dimeric enzyme. MD simulations were carried out to examine two binding sites for the compound. Our results show that this small molecule inhibitor could be a promising lead for future drug development. This article is protected by copyright. All rights reserved.

Abiotic stresses have a detrimental impact on plant growth and productivity and are a major threat to sustainable crop production in rapidly changing environments. Proline, an important amino acid, plays an important role in maintaining the metabolism and growth of plants under abiotic stress conditions. Many insights indicate a positive relationship between proline accumulation and tolerance of plants to various abiotic stresses. Because of its metal chelator properties, it acts as a molecular chaperone, an antioxidative defence molecule that scavenges reactive oxygen species (ROS), as well as having signalling behaviour to activate specific gene functions that are crucial for plant recovery from stresses. It also acts as an osmoprotectant, a potential source to acquire nitrogen as well as carbon, and plays a significant role in the flowering and development of plants. Overproduction of proline in plant cells contributes to maintaining cellular homeostasis, water uptake, osmotic adjustment and redox balance to restore the cell structures and mitigate oxidative damage. Many reports reveal that transgenic plants, particularly those overexpressing genes tailored for proline accumulation, exhibit better adaptation to abiotic stresses. Therefore, this review aims to provide a comprehensive update on proline biosynthesis and accumulation in plants and its putative regulatory roles in mediating plant defence against abiotic stresses. Additionally, the current and future directions in research concerning manipulation of proline to induce gene functions that appear promising in genetics and genomics approaches to improve plant adaptive responses under changing climate conditions are also highlighted.

A uni-molecular layer of lipids at air-water interface mimicking one of the leaflets of the cellular membrane provides a simple model to understand the interaction of any foreign molecules with the membrane. Here, the interactions of protein Kalata B1 (KB1) of cyclotide family with the phospholipids 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DPPG), and 1,2-distearoyl-sn-glycero-3-ethylphosphocholine chloride salt (DSEPC) have been investigated. The addition of KB1 induces a change in pressure of the lipid monolayers. The characteristic time of the change in pressure is found to be dependent on the electrostatic nature of the lipid. Even though the protein is weakly surface active, it is capable of modifying the phase behavior and elastic properties of lipid monolayers with differences in their strength and nature making the layers more floppy. The KB1-lipid interaction has been quantified by calculating the excess Gibb's free energy of interaction and the 1-anilino-8-naphthalenesulfonate (ANS) binding studies. The interaction with zwitterionic DPPC and negatively charged DPPG lipids are found to be thermodynamically favorable whereas the protein shows a weaker response to positively charged DSEPC lipid. Therefore, the long ranged electrostatic is the initial driving force for the KB1 to recognize and subsequently attach to a cellular membrane. Thereafter, the hydrophobic region of the protein may penetrate into the hydrophobic core of the membrane via specific amino acid residues.

The direct replacement of sp3 C-H bonds with simple amine units (-NH2 ) remains synthetically challenging, although primary aliphatic amines are ubiquitous in medicinal chemistry and natural product synthesis. We report a mild and selective protocol for preparing primary and secondary aliphatic amines in a single pot, based on intermolecular sp3 C-H imination. The first C-H imination of diverse alkanes, this method shows useful site-selectivity within substrates bearing multiple sp3 C-H bonds. Furthermore, this reaction tolerates polar functional groups relevant for complex molecule synthesis, highlighted in the synthesis of amine pharmaceuticals and amination of natural products. We characterize a unique C-H imination mechanism based on radical rebound to an iminyl radical, supported by kinetic isotope effects, stereoablation, resubmission, and computational modeling. This work constitutes a selective method for complex amine synthesis and a new mechanistic platform for C-H amination.

Lead is produced from ores, concentrates and secondaries using pyrometallurgical process routes. Different hydrometallurgical techniques are also employed to recover lead as metal or its compound. In the present study, an attempt was made to recover lead from the anode slime (12.75% Pb and 18.50% Cu as major elements) that is obtained during electrorefining of copper. Before lead extraction, decopperization was carried out using very dilute sulphuric acid leaching, where Cu was completely removed. Lead was extracted using brine solution as the leachant. The maximum leaching efficiency of 80.66% was obtained using 35% brine solution under the conditions of 5% pulp density, 90 °C temperature and 1 h duration. Lead was further recovered from the brine leach solution as lead sulphide using sodium sulphide by precipitation technique. It is found that lead sulphide of high purity can be produced from anode slime.

The article describes a very simple design philosophy of a coating that responds to temperature-rise by changing its behavior from hydrophilic to superhydrophobic in an instantaneous reversible manner. The material developed can be applied to a variety of surfaces simply by brush or roller, making it highly suitable as the basic ingredient of smart paint. Low surface energy fluoro and amino monomers were introduced to prepare the polymer backbone, which was then used as a binder for achieving a nano-micro dual particle morphology based on nano-silica micro-Titania (pre-functionalized with hydrophobic siloxane) by simple physical blending. The final structure was inspired by the so-called lotus effect. The best designed resulting material shows a water contact angle of 152° with a roll off-angle as low as 2° as a coating in response to elevated temperature, changing its hydrophilic nature. This reversible switching is ascribed to the formation and breaking of hydrogen-bond between amine group (secondary or tertiary) in polymer backbone and water. This bond-breaking introduces a critical change in the roughness of the coating, which was observed using atomic force microscopy. We also show that the response temperature can be tuned, which opens up the possibility of designing country-specific self-cleaning exterior paints.

Neutral nitrogen donor (N-donor) ligand-based MOFs, with their enticing features inclusive of facile synthesis, labile metal-ligand bond, framework flexibility, atomic level tunability renders them appealing in molecular recognition-based studies. Intriguingly, the flexibility in such systems (owing to weaker metal-nitrogen bonds) promote maximization of host-analyte interactions, which is critical for the manifestation of a signaling response. Such host-analyte interactions can be tapped by discerning any change in the physical properties associated with the system, such as optical, fluorometric, chemiresistive, magnetic, dielectric constant, mass. This minireview presents a brief discussion on the various types of signal transduction pathways unveiled hitherto using neutral N-donor ligand-based MOFs and the fundamental insight into the signal's origin. Moreover, an elaborate compilation of the recent examples in this field has been presented. Also, the untapped prospects have been highlighted, which may serve as a beacon to drive future research.

Nano-micron size fiber formation of UHMWPE (ultra-high molecular weight polyethylene) can be carried out by a high temperature (130 °C) electrospinning method. In this work, the effect of solution parameters on fiber formation by the electrospinning method is discussed. Two different grades of UHMWPE having a molecular weight (Mw) of 2.21 million g/mole (UM2.21) and 4.43 million g/mole (UM4.43) were chosen for the analysis. The solution properties of UHMWPE were investigated via rheology, which allowed the identification of the entanglement concentration before conducting the electrospinning process. The entanglement concentration (ce) for UM2.21 was 1.5 wt.%, while that for UM4.43 was 0.8 wt.%, respectively. The concentration exponent in semi dilute unentangled, and semi dilute entangled regimes was 1.23 and 2.59 for UM2.21 and 0.45 and 2.57 for UM4.43, respectively, in-line with de-Gennes’s scaling theory. SEM of the electrospun product revealed that defect-free smooth fiber morphology could only be obtained when the concentration of the solution is around 1.5–2.5 times the entanglement concentration.

Fabricating new and efficient materials aimed at containment of water contamination, in particular removing toxic heavy metal based oxo-anions (e. g. CrO4 2- , TcO4 - ) holds paramount importance. In this work, we report two new highly stable imidazolium based ionic porous organic polymers (iPOPs) decorated with multiple interaction sites along with electrostatics driven adsorptive removal of such oxo-anions from water. Both the iPOPs (namely, iPOP-3 and iPOP-4) exhibited rapid sieving kinetics and very high saturation uptake capacity for CrO4 2- anions (170 and 141 mg g-1 for iPOP-3 and iPOP-4 respectively) and ReO4 - (515.5 and 350.3 mg g-1 for iPOP-3 and iPOP-4 respectively), where ReO4 - anions being the non-radioactive surrogative counterpart of radioactive TcO4 - ions. Noticeably, both iPOPs showed exceptional selectivity towards CrO4 2- and ReO4 - even in presence of several other concurrent anions such as Br- , Cl- , SO4 2- , NO3 - etc. The theoretical binding energy calculations via DFT method further confirmed the preferential interaction sites as well as binding energies of both iPOPs towards CrO4 2- and ReO4 - over all other competing anions which corroborates with the experimental high capacity and selectivity of iPOPs toward such oxo-anions.

The emergence of multidrug resistant (MDR) HIV strains severely reduces the effectiveness of antiretroviral therapy. Clinical inhibitor darunavir (1) has picomolar binding affinity for HIV-1 protease (PR), however, drug resistant variants like PR(S17) show poor inhibition by 1, despite the presence of only two mutated residues in the inhibitor-binding site. Antiviral inhibitors that target MDR proteases like PR(S17) would be valuable as therapeutic agents. Inhibitors 2 and 3 derived from 1 through substitutions at P1, P2 and P2ʹ positions exhibit 3.4- to 500-fold better inhibition than clinical inhibitors for PR(S17) with the exception of amprenavir. Crystal structures of PR(S17)/2 and PR(S17)/3 reveal how these inhibitors target the two active site mutations of PR(S17). The substituted methoxy P2 group of 2 forms new interactions with G48V mutation, while the modified bis-fluoro-benzyl P1 group of 3 forms a halogen interaction with V82S mutation, contributing to improved inhibition of PR(S17).

Manganese nodules from ocean bed are potential resources of Cu, Ni, and Co for which land-based deposits are scarce in India. The present work describes a novel approach of using glycerol, a nontoxic biomass-derived reductant, for the reductive acid leaching of manganese nodules. Parameters such as acid concentration, time, temperature, and pulp density were optimized for leaching. The optimal leaching conditions were found to be 10% (w/v) pulp density and 10% (v/v) H2SO4 at 80 °C with 1% (v/v) glycerol yielding >95% of Ni and >98% Cu, Co, and Mn extraction within an hour. Kinetic analysis of the data based on the initial rate method showed that the leaching process was chemical reaction-controlled with an apparent activation energy of 55.47 kJ/mol. Various oxidation intermediates of glycerol formed during leaching were identified using mass spectrometry and Raman spectroscopy, and a probable oxidation pathway of glycerol during the leaching process has been elucidated based on the analysis. Glycerol was oxidized to glyceraldehyde, glyceric acid, tartronic acid, dihydroxyacetone, hydroxy pyruvic acid, glyoxalic acid, oxalic acid, and finally converted to CO2 during leaching. The fast reaction kinetics, near-complete dissolution of manganese, and other associated metals in the nodule can be attributed to the participation of all intermediate products of glycerol oxidation in redox reactions with MnO2, enhancing the overall reduction leaching efficiency.

Soil organic carbon (SOC) is highly sensitive to land use change and helps in maintaining soil quality. Changes in soil fertility status, SOC dynamics, and carbon indices were studied in a four-yea...

Mercury (Hg2+) is remarked as toxic and hazardous element to global environment. Here, carbon quantum dots (CQDs) were synthesized by simple microwave assisted technique for Hg2+ detection in water samples via. fluorescence quenching and FT-IR spectroscopic approach. The morphology and chemical structure of synthesized CQDs was investigated by TEM, FT-IR, 13C-NMR, fluorescence and UV-vis spectroscopic technique. The resultant CQDs bears spherical morphology with an average size of 2–4 nm. The binding parameters, as Stern-Volmer quenching constant (Ksv) and binding constant for CQDs-Hg system was investigated by fluorescence method, whereas UV-vis techniques was employed for determination of thermodynamic parameters, as Gibb’s free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) at three different temperature (295, 298 and 305 K). Moreover, selectivity assay for Hg2+ detection has been studied in presence of other metal ions by FT-IR as well as fluorescence spectroscopy. Analytical assay was also successfully applied for Hg2+ in spiked water samples collected from different areas of Chhattisgarh, with 98–99 recovery %. The detection of Hg2+ has been demonstrated in the range of 0 to 5.0μM with 3.25 nM detection limit. The present method is found to be simple, highly sensitive and selective for sensing of Hg2+ in aquatic environmental samples using CQDs as sensing probe.

Background Viruses cause many life threatening human diseases. Recently, COVID-19 pandemic has challenged the health care systems worldwide. As a disease preventive approach and to bring relief to the severity of the symptoms, a infusion termed as Bhabha Anti-Viral Infusion-23 (‘BhAVI-23’) was conceptualized and formulated which comprised of 23 selected spices and herbals. Objective The present study was conducted to assess the in vitro antiviral potential of the formulation, BhaAVI-23. Material and methods The in-vitro anti-viral potential of BhAVI-23 was assessed through inhibition of HIV1 reverse transcriptase (RT) as well as through a novel P1 (virulent) bacteriphage based screening assay system. Anti-diabetic potential was assessed by non-enzymatic glycosylation of haemoglobin and the bioactive volatile components were detected through headspace gas chromatography followed by molecular docking analysis. Results The infusion displayed prominent anti-viral activity as evident from significant (57%) inhibition of the HIV1-RT as well as through reduction in the infectivity of P1 (virulent) bacteriophage. The infusion also exerted profound protection (∼64%) to non-enzymatic glycosylation of haemoglobin. Headspace gas chromatography and mass spectrometric analysis confirmed the presence of at least 47 major compounds. Docking analysis indicated possible interaction of α-pinene and eugenol with SARS-CoV spike protein. Conclusion This ‘BhAVI-23’ infusion displayed prominent in-vitro anti-viral and anti-diabetic potential in different model systems. These attributes have relevance as diabetic patients are more prone to COVID-19 morbidity. ‘BhAVI-23’ opens the avenue for its potential inclusion as a supportive health care system upon due regulatory approval during the current pandemic.

Inducement of high charge carrier density in organic field-effect transistors (OFETs) is a subject of immense interest due to its fundamental and applied impact on device operation. Here, the high ...

Small molecules that target the spliceosome SF3B complex are potent inhibitors of cancer cell growth. The compounds affect an early stage of spliceosome assembly when U2 snRNP first engages the branch point sequence of an intron. Employing an inactive herboxidiene analog (iHB) as a competitor, we investigated factors that influence inhibitor interactions with SF3B to inhibit pre-mRNA splicing in vitro. Order-of addition experiments show that inhibitor interactions are long lasting and affected by both temperature and the presence of ATP. Our data are also consistent with the idea that not all SF3B conformations observed in structural studies are conducive to productive inhibitor interactions. Notably, SF3B inhibitors do not impact an ATP-dependent rearrangement in U2 snRNP that exposes the branch binding sequence for base pairing. We also report extended structure activity relationship analysis of the splicing inhibitor herboxidiene. We identified features of the tetrahydropyran ring that mediate its interactions with SF3B and its ability to interfere with splicing. Analyzing our data in the context of recent structural models of SF3B interactions with inhibitors, our results lead us to extend the model for early spliceosome assembly and inhibitor mechanism. We postulate that interactions between a carboxylic acid substituent of herboxidiene and positively charged SF3B1 sidechains in the inhibitor binding channel are required to maintain inhibitor occupancy while counteracting the SF3B transition to a closed state that is required for stable U2 snRNP interactions with the intron.

A cellular membrane, primarily a lipid bilayer, surrounds the internal components of a biological cell from the external components. This self-assembled bilayer is known to be perturbed by ionic liquids (ILs) causing malfunctioning of a cellular organism. In the present study, surface-sensitive X-ray scattering techniques have been employed to understand this structural perturbation in a lipid multilayer system formed by a zwitterionic phospholipid, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine. The ammonium and phosphonium-based ILs with methanesulfonate anions are observed to induce phase-separated domains in the plane of a bilayer. The lamellar X-ray diffraction peaks suggest these domains to correlate across the bilayers in a smectic liquid crystalline phase. This induced IL-rich lamellar phase has a very low lamellar repeat distance, suggesting the formation of an interdigitated bilayer. The IL-poor phase closely related to the pristine lipid phase shows a decrement in the in-plane chain lattice parameters with a reduced tilt angle. The ammonium and phosphonium-based ILs with a relatively bulky anion, p-toluenemethanesulfonate, have shown a similar effect.

The ability to perform routine structure-guided drug design for selective BACE inhibitors has been limited because of the lack of robust platform for BACE2 expression, purification, and crystallization. To overcome this limitation, we developed a platform that produces 2–3 mg of pure BACE2 protein per liter of E. coli culture, and we used this protein to design macrocyclic compounds that potently and selectively inhibit BACE1 over BACE2. Compound 2 was found to potently inhibit BACE 1 (K(i) = 5 nM) with a selectivity of 214-fold over BACE2. The X-ray crystal structures of unbound BACE2 (2.2 Å) and BACE2 bound to compound 3 (3.0 Å and K(i) = 7 nM) were determined and compared to the X-ray structures of BACE1 revealing the S1–S3 subsite as a selectivity determinant. This platform should enable a more rapid development of new and selective BACE inhibitors for the treatment of Alzheimer’s disease or type II diabetes.

Clinical and preclinical data reveal that RECQL5 protein overexpression in breast cancer was strongly correlated with poor prognosis, survival, and therapeutic resistance. In the current investigation, we report design, synthesis, and specificity of a small molecule, 4a, which can preferentially kill RECQL5-expressing breast cancers but not RECQL5 knockout. Our stringent analysis showed that compound 4a specifically sensitizes RECQL5-expressing cancers, while it did not have any effect on other members of DNA RECQL-helicases. Integrated approaches of organic synthesis, biochemical, in silico molecular simulation, knockouts, functional mutation, and rescue experiments showed that 4a potently inhibits RECQL5-helicase activity and stabilizes RECQL5-RAD51 physical interaction, leading to impaired HRR and preferential killing of RECQL5-expressing breast cancer. Moreover, 4a treatment led to the efficient sensitization of cisplatin-resistant breast cancers but not normal mammary epithelial cells. Pharmacologically, compound 4a was orally effective in reducing the growth of RECQL5-expressing breast tumors (human xenograft) in NUDE-mice with no appreciable toxicity to the vital organs.

This study explored the interspecies and seasonal variation of polycyclic aromatic hydrocarbons (PAHs) in the extracted lipids of the leaves of seven local plants in an urban environment of Kolkata (22°33′N and 88°20′E), India. Based on the degree of toxicity and carcinogenicity (expressed in terms of their Benzo(a)pyrene equivalent ( BaP eq ) concentrations) the overall foliar-PAH accumulation during the study period (September 2018‒;August 2019) in the various plants showed the following order: Nerium oleander (80.96 ± 30.08 ng . g dw − 1 ) > Mangifera indica (74.15 ± 20.34 ng . g dw − 1 ) > Lantana aculeata (60.13 ± 21.71 ng . g dw − 1 ) > Thevetia peruviana (40.97 ± 12.45 ng . g dw − 1 ) > Ixora coccinea (38.11 ± 9.5 ng . g dw − 1 ) > Murraya paniculata (37.1 ± 7.35 ng . g dw − 1 ) > Polyalthia longifolia (25.72 ± 5.71 ng . g dw − 1 ). The PAHs like phenanthrene, anthracene, fluoranthene, pyrene, benzo(a)anthracene, chrysene, benzo (b+k)fluoranthene, benzo(a)pyrene, benzo [ghi]perylene and indeno [1,2,3-cd]pyrene were predominant during the study period over the PAHs like naphthalene, acynaphthylene, acenaphthene, fluorine and dibenz [a,h]anthracene in the extracted lipids. The temperature-dependent partitioning of the PAHs onto leaf-surface and photo-degradation could have affected the availability of the PAHs. The foliar PAH accumulation varied seasonally as winter (December–February) > postmonsoon (September–November) > premonsoon (March–May) > monsoon (June–August). The leaf epicuticular wax determined the PAH uptake and storage, which in turn was affected by the temperature and solar radiation. In consistence with the idea of “nature-based solutions” for deteriorated air quality remediation in an urban environment, this study could be a promising initiative to build up cost-effective biological filters to combat the airborne pollutants and improve urban air quality.

Colloidal quantum dots (QDs) are promising materials for optoelectronic devices. In this paper, monodispersed and environment stable cobalt (Co)-doped CdS QDs have been synthesized and characterize...

Recent experimental studies engaging isotopically substituted protein (heavy protein) have revealed that many, but not all, enzymatic systems exhibit altered chemical steps in response to an altered mass. The results have been interpreted as femtosecond protein dynamics at the active site being linked (or not) to transition-state barrier crossing. An altered enzyme mass can influence several kinetic parameters (k(cat), K(m), and k(chem)) in amounts of ≤30% relative to light enzymes. An early report on deuterium-labeled Escherichia coli alkaline phosphatase (AP) showed an unusually large enzyme kinetic isotope effect on k(cat). We examined steady-state and chemical step properties of native AP, [(2)H]AP, and [(2)H,(13)C,(15)N]AP to characterize the role of heavy enzyme protein dynamics in reactions catalyzed by AP. Both [(2)H]- and [(2)H,(13)C,(15)N]APs showed unaltered steady-state and single-turnover rate constants. These findings characterize AP as one of the enzymes in which mass-dependent catalytic site dynamics is dominated by reactant-linked atomic motions. Two catalytic site zinc ions activate the oxygen nucleophiles in the catalytic site of AP. The mass of the zinc ions is unchanged in light and heavy APs. They are essentially linked to catalysis and provide a possible explanation for the loss of linkage between catalysis and protein mass in these enzymes.

To develop and validate a one-step, rapid and simple reversed-phase high-performance liquid chromatography (HPLC)-based protocol for the simultaneous measurement of voriconazole (VCZ), posaconazole (POSA), itraconazole (ITC) in serum/plasma. Calibration standards (CS) and quality control samples were prepared in drug-free serum by spiking with the triazoles at different concentrations. HPLC was performed with C18 column, isocratic mobile phase after extraction with cold acetonitrile. The standardized method was tested in 2693 patients’ serum/plasma samples. Linearity of CS for ITC, VCZ and POSA was proportional to the nominal concentration (correlation coefficient > 0.999). Limit of detection (mg/L) for ITC, VCZ and POSA was 0.25, 0.25 and 0.125, respectively. The lower limit of quantification (mg/L) for ITC, VCZ and POSA was 0.5, 0.5 and 0.25, respectively. Precision and accuracy were in acceptable range with 100% average percentage recovery. No interferences from endogenous substances and other antimicrobial compounds were noted. In clinical samples, the therapeutic range achieved for VCZ was 39.9%. Whereas, 61.1% and 44% of samples with ITC and POSA, respectively, were in the sub-therapeutic range. We developed a rapid and simple HPLC method to quantify common triazoles in a single chromatographic run allowing simultaneous measurement of different antifungals in a small volume of serum/plasma. Thus, therapeutic drug monitoring requests can be processed in one run without changing the protocol parameters, column or column conditioning thereby improving turnaround time.

Introduction: Aedes mosquitoes are responsible for transmitting various life-threatening diseases all over the world and created a burden to society. Control of mosquito vectors is the key challenge to avoid disease transmission. In this regard, the present work is focused to utilize the agronomical waste of Solanum lycopersicum leaf extracts and to evaluate the larvicidal activity against Aedes aegypti. Methods: The qualitative and quantitative screening of S. lycopersicum leaf extracts were carried out. The larvicidal activity of different concentrations were assessed against 3rd instar Ae. aegypti and to determine the morphological effects. The chemical constituents were analysed by gas chromatography coupled with mass spectroscopy (GC-MS). Results: The preliminary phytochemical screening of S. lycopersicum leaf extracts revealed the presence of alkaloids, saponins, phenols and flavonoids. The methanol extract exhibited strong larvicidal activity at 48h treatment with an LC50 value of 20.323mg/ml. The morphological changes revealed that abnormal movement and coiling of treated larvae at 24h. Furthermore, severe damage was noticed in the digestive and respiratory tract of Ae. aegypti larvae at 48h, later on complete mortality was observed. The GC-MS analysis of methanol extract showed chemical constituents such as phytol acetate (42.66%), neophytadiene (29.38%) and other minor compounds. Conclusion: Based on the results, it can be concluded that methanolic leaf extract of S. lycopersicum could be an alternative source to control mosquito vectors and further investigation is strongly suggested in order to utilise this source in many disease-endemic areas.

Designing selective sorbent materials to sequestrate toxic oxo-anions having weaker binding tendency, for instance oxo-anions of selenium and arsenic (Se(IV)/Se(VI)/As(V)), is an arduous challenge. Herein, we demonstrate the molecular shape recognition aided synthesis of a chemically stable cationic MOF (iMOF-3C) which exhibits fast, selective removal behavior (∼99% in 5 min) towards toxic oxo-anions of Se(VI)/As(V)/Se(IV) even at ultralow concentrations (∼1000 ppb). The cationic network illustrates superior performance in the presence of interfering ions, viz. CO32− and SO42−, which was further validated by exceptional distribution coefficient values Kd > 106 mL g−1. The maximum uptake capacity stands among the best performing materials reported in the domain of ionic MOFs (iMOFs). Furthermore, iMOF-3C successfully performs in complicated systems such as river water to yield drinking quality water as per the WHO and US EPA standards. The exceptional binding ability was corroborated by DFT calculations (high binding energies) that also aid in visualizing the binding sites for the entrapped oxo-anions.

A new imidazolium functionalized hexapodal polymeric receptor, [PHIm-Br], showed selective and efficient removal (>99%) of perrhenate (ReO4−), from 100% aqueous medium via solid–liquid extraction, which was 13% higher as compared to its monomeric analouge [HIm-Br]. Most importantly, [PHIm-Br] overcomes the drawback of [HIm-Br] in terms of removal of ReO4− at lower anion concentration of ∼100 ppm along with excellent radiation resistivity and reusability within a wide pH range, which implies its potential towards practical applications.

A complexation route mediated synthesis of orthorhombic antimony sulfide nanoparticles is described in this report where uniformly distributed particles within the size range of 2–12 nm are stabilized within the aniline matrix. The organic–inorganic hybrid system was investigated for dielectric capacitance and electric field-induced polarization performances under varying temperature and frequency conditions. The AC-conductivity revealed a correlated barrier hopping conduction mechanism in the hybrid system. A fatigue free polarization was achieved under the electric field of 9 kV mm−1 for the preformed antimony sulfide system with a stable value of 0.18 μC cm−2. The in situ dielectric capacitance and field dependent polarization measurements were also performed for the in situ synthesized antimony sulfide using the antimony–aniline complex as the precursor.

A complexation strategy has been demonstrated for the fabrication of an organic–inorganic hybrid system, where the organic molecule aniline acted as a ligand for the complexation of antimony chloride. By the addition of a sulfide source (sodium sulfide) to the complex medium, an organic–inorganic composite system (aniline stabilized antimony sulfide) was developed. X-ray diffraction analysis confirmed the formation of orthorhombic antimony sulfide and the microscopic images showed the formation of highly dispersed sulfide nanoparticles on the organic matrix. The optical characterization exhibited changes of characteristic vibrational bands in the FTIR spectrum that support complexation and the particle formation process. The as-synthesized product, aniline stabilized antimony sulfide, was applied as an active material of a device to extract the electrical properties under normal laboratory illumination (LED) and UV irradiation conditions. The device exhibited unipolar and bipolar switching behaviours under two different optical conditions with a moderately high ON-to-OFF ratio. The transport mechanism of the aniline stabilized antimony sulfide-based device was followed by Poole–Frenkel, Ohmic and Schottky emission at different conduction states. The device showed a persistent endurance behaviour, and statistical analysis suggested a stable high conduction state (HCS) and low conduction state (LCS) under LED and UV irradiation conditions. Furthermore, the impedance measurement of the device over the frequency range from 100 Hz to 1 MHz under both LED and UV irradiation conditions was performed to find out the device equivalent circuit and AC conductivity behaviour.

A layer-by-layer (L-B-L) bacterial cellulose (BC)-based transdermal patch has been prepared via a Schiff base reaction. The L-B-L assembly consisting of covalently cross-linked ethylene diamine-mod...

Skin fibrosis caused by excessive collagen synthesis and deposition in the dermis affects the quality of daily life of hundreds of thousands of people around the world. The skin quality, including its smoothness in young age and wrinkly during the aging process, depends largely on the levels of extracellular matrix proteins such as collagen in skin. As physiological levels of collagen are desirable for skin homeostasis, beauty, and its flexibility, too much collagen deposition in the skin is associated with tight hard skin, loss of adipose layer, and flexibility, the pathological manifestations of skin fibrosis in fibrotic diseases such as scleroderma. To understand the molecular basis of skin fibrosis and in search of its therapy, different cellular, molecular, epigenetic, and preclinical studies have been undertaken to control abnormal excessive synthesis and accumulation of matrix protein collagen. Over the last two decades, numerous phase 1 through 3 clinical trials have been conducted to test the safety and efficacy of a wide variety of compounds in amelioration of skin fibrosis and other pathologies in scleroderma, yet, no effective therapy for skin fibrosis is available. This article solely focuses on the role of a nuclear receptor and transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR-γ), as an anti-skin fibrotic driving force and the potential therapeutic efficacies of PPAR-γ-specific ligands/agonists including antidiabetic drugs and other natural or semi-synthetic compounds derived from cannabis in amelioration of skin fibrosis in scleroderma. The underlying molecular basis of agonist-activated PPAR-γ-mediated suppression of profibrogenic signaling and skin fibrogenesis is also highlighted.

The synthesis of carbon nitride supported lead oxide nanoparticles (CNLO) has been reported by the pyrolysis of urea under ambient pressure and high-temperature conditions in the presence of lead n...

A complete process flowsheet to recover metal values from Sm2Co17-type magnet scrap was investigated. The magnet scrap was leached in chloride medium at pulp density of 2% (w/v) under the optimum conditions of 15% (v/v) HCl and 5% (v/v) H2O2 at 70 °C for 3 h, which yielded 98.5% Sm and 99% Co extractions. The full factorial Design of Experiment technique was adopted for the optimization of leaching conditions. Sm was selectively separated from the leach liquor as precipitated double salt using Na2SO4. The precipitated double sulfate was later converted to Sm-oxalate, which was subsequently calcined to produce pure Sm2O3. Following Sm separation, Fe was removed through precipitation by raising the pH to 3.0. For Cu and Co recovery, solvent extraction techniques using LIX 84I and Na-CYANEX 272, respectively, were followed. The McCabe–Thiele diagrams for extraction as well as stripping were presented for both Cu and Co.

We describe an enantioselective synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol which is a key subunit of darunavir, a widely used HIV-1 protease inhibitor drug for the treatment of HIV/AIDS patients. The synthesis was achieved in optically pure form utilizing commercially available sugar derivatives as the starting material. The key steps involve a highly stereoselective substrate-controlled hydrogenation, a Lewis acid catalyzed anomeric reduction of a 1,2-O-isopropylidene-protected glycofuranoside, and a Baeyer-Villiger oxidation of a tetrahydrofuranyl-2-aldehyde derivative. This optically active ligand alcohol was converted to darunavir efficiently.

A high-temperature in situ route has been employed for the synthesis of carbon nitride supported manganese sulfide nanoparticles (CNMS). The hybrid material was characterized using different analyt...

Fluoride and nitrate are the most widespread toxic pollutant elements present in groundwaters in large parts of India. The study assessed the groundwater quality and non-carcinogenic health risk du...

A single pot synthesis method of aminobenzene stabilized bismuth iodide particles (ABBI) is reported for the nonvolatile random access memory application. The microscopic and surface property of the as-synthesized organic-inorganic hybrid system has been characterized using different techniques. The current-voltage characteristic of the device, made with ABBI, exhibited O-shaped hysteresis behaviour. For the random access memory application, the device was demonstrated the steady endurance and retention for 103 times and 2×103 sec, respectively. The charge transport property of the device was followed by space charge limited current and trapped assisted tunneling mechanism.

A single pot, wet chemical route has been applied for the synthesis of polymer supported copper azide, CuN3, nanoparticles (CANP). The hybrid system was used as ‘catalyst-cum-reagent’ for the azide-alkyne cyclo-addition reaction to construct triazole molecules using substituted benzyl bromide and terminal alkyne. The electron donating group containing terminal alkyne produced 5-alkynyl 1,4-disubstituded triazole product whereas for alkyne molecule with terminal electron withdrawing group facilitate the formation of 1,4-disubstituted triazole molecule.

A single-pot, wet chemical method has been reported for the synthesis of bismuth fluoride nanoparticles (BF) and functionalized BF within the network of carbon nitride (BFCN). In BFCN, a structural transformation of BF, from cubic to pseudo-cubic (as evidenced by Rietveld refinement analysis), confirmed the contribution of carbon nitride (CN) on functionalization. The effect of functionalization of BF has been investigated through dielectric and field-induced polarization studies under different temperature and frequency conditions. Enhancement of dielectric constant values was noticed in BFCN as compared with BF system, in the order of 2.5 (30 °C) and 8.0 (100 °C) at 100 Hz. Fatigue-free maximum polarization values of 0.041 µC/cm2 and 0.054 µC/cm2, under the electric field of 5 kV/mm, were achieved for BF and BFCN samples, respectively, for 5 × 103 cycles.