Nano-CuFe2O3-catalyzed green synthesis of novel quinazolinone-tetrazole hybrids as anti-cancer agents.

A novel green protocol has been developed for the synthesis of quinazolinone-tetrazole conjugates (7a-g, 8a-g and 9a-g) using recyclable nano-CuFe2O3 catalyst in water. Initially, 2-mercapto-3-substituted phenethylquinazolin-4(3H)-one (5a-c) was prepared by using nano-CuFe2O3 catalyst in water. Then, compounds (5a-c) were reacted with 1-bromo-3-chloropropane under nano-CuFe2O3 catalyst in water solvent to give S-alkylated quinazolinone core intermediate (6a-c), which was subsequently reacted with 1-substituted-1H-tetrazole-5-thiol (2a-g) by employing the similar reaction conditions to afford the final target compounds. The regioselective formation of C-S bond was unambiguously confirmed by single-crystal X-ray diffraction. The anti-cancer activity of the derivatives on various cancer cell lines such as SIHA, MD-AMB-231 and HepG2 was evaluated. Remarkably, compounds, 7f, 8f, 9a, 9d and 9f, showed potent activity in MD-AMB-231 cancer cell line (IC50: 9.13-10.3 µM), while the same derivatives showed significant potent activity in SiHa and HepG2 cancer cell lines (IC50: 17.46-27.0 µM). Most significantly, compound 7o (IC50: 8.15 µM) showed potent activity, compared to the drug etoposide (IC50: 18.11 µM) against MD-AMB-231 cell line. Flow cytometry analysis revealed that compounds 7f, 8f, 9a, 9d and 9f arrested the cell growth in the G1 phase in MD-AMB-231 cell line.

Preoperative factors associated with patient satisfaction 2 years after elective shoulder surgery.

Background Purpose: Patient satisfaction has become an increasingly important component of quality measures for both hospital reimbursement and quality assessment. Additionally, patient satisfaction influences patient behavior and patient follow-up. The purpose of this study was to identify preoperative factors associated with patient satisfaction 2 years after shoulder surgery. Methods: Electronic surveys were used to collect patient information including demographic, surgical, and social history, as well as outcome data. Satisfaction was measured 2 years after surgery using the Surgical Satisfaction Questionnaire. Results: Multivariable linear regression identified preoperative Patient-Reported Outcomes Measurement Information System Pain Interference, annual income, and American Society of Anesthesiologists score as independent predictors of lower patient satisfaction, while total shoulder arthroplasty was an independent predictor of greater patient satisfaction. The model accounted for 15% of the variance in satisfaction scores (R2 = 0.15). Conclusion: Patient satisfaction 2 years after shoulder surgery is associated with preoperative patient-reported outcome scores. Lower patient satisfaction is independently predicted by greater preoperative PROMIS PI, income less than $70,000, and ASA score >1, while higher patient satisfaction is predicted by total shoulder arthroplasty.

Synthesis of novel tetrazole containing hybrid ciprofloxacin and pipemidic acid analogues and preliminary biological evaluation of their antibacterial and antiproliferative activity.

A series of 1-substituted-1H-tetrazole-5-thiol building blocks were synthesized and introduced to the N-4 piperazinyl group at C-7 position of the quinolone core, and these novel compounds (5a-g and 8a-g) were screened for their antibacterial and antiproliferative activities. Bioactive assay studies manifested that most of new compounds exhibited significant antibacterial activity against the tested strains, including multi-drug-resistant MRSA in comparison with reference drugs ciprofloxacin, streptomycin B and pipemidic acid. Among the synthesized compounds, only ciprofloxacin (5a-g) derivatives displayed significant activity ([Formula: see text]) compared to reference drugs. In addition, these compounds were evaluated for their in vitro inhibition of human cancer cell lines viz human cervical carcinoma cell line (SiHA), breast adenocarcinoma (MDA-MB-235) and human pancreas carcinoma (PANC-1) cell lines by using the SRB assay method. Most of the target compounds showed broad potent growth inhibition activity ([Formula: see text]) against all the tested cancer cell lines compared with reference drug. The most promising active compounds in this series were 5c, 5d, 8c, 8d and 8f endowed with excellent antiproliferative activity. A new class of compounds was designed rationally by introducing tetrazole building block on N-4 piperazinyl group at C-7 position of quinolones core. The titled compounds were evaluated for their preliminary antibacterial and antiproliferative activities.

RiceAtlas, a spatial database of global rice calendars and production.

Knowing where, when, and how much rice is planted and harvested is crucial information for understanding the effects of policy, trade, and global and technological change on food security. We developed RiceAtlas, a spatial database on the seasonal distribution of the world's rice production. It consists of data on rice planting and harvesting dates by growing season and estimates of monthly production for all rice-producing countries. Sources used for planting and harvesting dates include global and regional databases, national publications, online reports, and expert knowledge. Monthly production data were estimated based on annual or seasonal production statistics, and planting and harvesting dates. RiceAtlas has 2,725 spatial units. Compared with available global crop calendars, RiceAtlas is nearly ten times more spatially detailed and has nearly seven times more spatial units, with at least two seasons of calendar data, making RiceAtlas the most comprehensive and detailed spatial database on rice calendar and production.

Synthesis and biological evaluation of novel tamoxifen-1,2,4-triazole conjugates.

A new class of compounds, structurally related to the breast cancer drug tamoxifen, was designed and synthesized. The McMurry coupling reaction was used as the key synthetic step in the preparation of these analogs, and the structural assignments were made on the basis of [Formula: see text] NMR, [Formula: see text] NMR, and HRMS studies. The absolute stereochemistry of E and Z isomers was unambiguously confirmed by a single-crystal X-ray diffraction analysis. Water was found to be an inexpensive nontoxic and effective medium for the C-N bond formation. Utilizing this protocol, various tamoxifen derivatives were synthesized in good yields. Environmental acceptability, low cost, and high yields are the important features of this protocol. These compounds were evaluated for their antiproliferative activity on five human tumor cell lines. Compound 4p ([Formula: see text]) showed improved antiproliferative activity against breast cancer cell line (MDA-MB-231) compared to tamoxifen ([Formula: see text]), while the compound 4o ([Formula: see text]) exhibited similar activity against SiHa compared to the reference drug, tamoxifen ([Formula: see text]). In addition, these analogs were investigated for their antibacterial activity against six bacterial strains. Preliminary results indicate that some of the newly synthesized title compounds exhibited promising antibacterial activity compared with the standard drug, vancomycin. A new class of compounds were designed rationally by the replacement of a ethyl group in tamoxifen with a methylene (1H-1,2,4-triazole) group. The absolute stereochemistry of E and Z isomers were unambiguously confirmed by a single-crystal X-ray diffraction analysis. The title compounds were evaluated for their antiproliferative and antibacterial activities.

DW-F5: A novel formulation against malignant melanoma from Wrightia tinctoria.

Wrightia tinctoria is a constituent of several ayurvedic preparations against skin disorders including psoriasis and herpes, though not yet has been explored for anticancer potential. Herein, for the first time, we report the significant anticancer properties of a semi-purified fraction, DW-F5, from the dichloromethane extract of W. tinctoria leaves against malignant melanoma. DW-F5 exhibited anti-melanoma activities, preventing metastasis and angiogenesis in NOD-SCID mice, while being non-toxic in vivo. The major pathways in melanoma signaling mediated through BRAF, WNT/ß-catenin and Akt-NF-κB converging in MITF-M, the master regulator of melanomagenesis, were inhibited by DW-F5, leading to complete abolition of MITF-M. Purification of DW-F5 led to the isolation of two cytotoxic components, one being tryptanthrin and the other being an unidentified aliphatic fraction. The overall study predicts Wrightia tinctoria as a candidate plant to be further explored for anticancer properties and DW-F5 as a forthcoming drug formulation to be evaluated as a chemotherapeutic agent against malignant melanoma.

Fermentative Production of Pyranone Derivate I from Marine Vibrio sp. SKMARSP9: Isolation, Characterization and Bioactivity Evaluation.

Pyranone derivative I was isolated from fermented broth of isolated marine bacterial strain Vibrio sp. SKMARSP9. The compound I was characterized, and evaluated for its antimicrobial properties. The isolated strain was identified based on 16S rRNA based phylogenetic analysis. The molecular analysis data suggested that this strain is closely related to Vibrio ruber, Vibrio sp. MSSRF10 and Vibrio rhizosphaerae. The best fermentative growth of this isolate was achieved under halophilic conditions and grew efficiently at 30 °C in the presence of 12 % NaCl. The compound I production by this strain is associated with growth. The unpurified extract is hydrophobic in nature, and released only during late growth phase. The extract was purified and characterized by spectral data using NMR, DEPT, and ESI-MS. The purity of I was 97 % which was confirmed by HPLC. The pyranone derivative I exhibited >50 % antioxidant activity and broad spectrum antimicrobial properties against gram negative and gram positive strains. Molecular docking analysis revealed that this pyranone derivative I may be a potential candidate at pharmaceutical sector.

Rice responses to rising temperatures--challenges, perspectives and future directions.

Phenotypic plasticity in overcoming heat stress-induced damage across hot tropical rice-growing regions is predominantly governed by relative humidity. Expression of transpiration cooling, an effective heat-avoiding mechanism, will diminish with the transition from fully flooded paddies to water-saving technologies, such as direct-seeded and aerobic rice cultivation, thus further aggravating stress damage. This change can potentially introduce greater sensitivity to previously unaffected developmental stages such as floral meristem (panicle) initiation and spikelet differentiation, and further intensify vulnerability at the known sensitive gametogenesis and flowering stages. More than the mean temperature rise, increased variability and a more rapid increase in nighttime temperature compared with the daytime maximum present a greater challenge. This review addresses (1) the importance of vapour pressure deficit under fully flooded paddies and increased vulnerability of rice production to heat stress or intermittent occurrence of combined heat and drought stress under emerging water-saving rice technologies; (2) the major disconnect with high night temperature response between field and controlled environments in terms of spikelet sterility; (3) highlights the most important mechanisms that affect key grain quality parameters, such as chalk formation under heat stress; and finally (4), we model and estimate heat stress-induced spikelet sterility taking South Asia as a case study.

p-Tolyl isocyanate derivatization for analysis of CWC-related polar degradation products by mass spectrometry.

Most of the precursors and/or degradation products related to the Chemical Weapons Convention (CWC) are polar. Identification of these molecules in environmental samples provides clues regarding the alleged usage and/or synthesis of the parent toxic chemicals. Such polar compounds need to be derivatized in order to analyze them by gas chromatography-mass spectrometry (GC-MS). In this study, we developed a new derivatizing reagent, para-tolyl isocyanate (PTI), for derivatization of polar CWC-related compounds. The PTI reagent selectively derivatizes the -OH and/or-SH functional groups with high efficiency, but does not react with carboxylic acid (-COOH) or phosphonic acid (-(O)P(OH)2) groups. The PTI derivatives of dialkyl aminoethanols, dialkyl aminoethanol-N-oxides, and 3-quinuclidinol were successfully eluted through GC, and their electron ionization (EI) mass spectra were distinct and provided the structure information by which the isomeric compounds can be easily distinguished. We also calculated the GC-retention index values that can be used for further confirmation of the target compounds. All the studied PTI derivatives can be analyzed by EI-MS with direct insertion probe and/or by direct electrospray ionization mass spectrometry (ESI-MS) together with the MS-MS data; both sets of data provide full structure information. The PTI reagent was found to be better in some respects than the conventional bistrimethylsilyl trifluoroacetamide (BSTFA), a trimethyl silylating reagent. The PTI reagent is commercially available, and the PTI derivatives are highly stable for months and are not sensitive to moisture. The applicability of the PTI derivatization for trace-level determination of the target CWC-related polar compounds in environmental matrices and in human plasma samples is also evaluated.

Serum cystatin C as a marker of renal function in detection of early acute kidney injury.

In patients with acute kidney injury (AKI), serum creatinine level does not increase until moderate to severe reduction in glomerular filtration rate (GFR) occurs. Thus its use for estimating GFR in early AKI delays detection of kidney damage and making important therapeutic decisions. Moreover, serum cystatin C is not affected by gender, age, race, and muscle mass and also does not suffer from lag period for its rise in early AKI. We studied 200 healthy subjects and 130 AKI patients over a period of 2 years at a tertiary care hospital. Serum creatinine and serum cystatin C were studied and analyzed in relevance to early AKI. We found that 56.2% of patients of AKI group had normal levels of serum creatinine in early phase, while all patients had elevated serum cystatin C at same time. Multiple logistic regression analysis revealed cystatin C-based GFR reflecting decline in GFR with worsening AKI in better than creatinine-based GFR. Serum cystatin C is a better marker of renal function in early stages of AKI and is less affected by age, gender, muscle mass, and ethnicity. Its use helps in early therapeutic intervention and possibly favorable outcome.

Mass spectral characterization of the CWC-related isomeric dialkyl alkylphosphonothiolates/alkylphosphonothionates under gas chromatography/mass spectrometry conditions.

RATIONALE: The isomeric dialkyl alkylphosphonothiolates and dialkyl alkylphosphonothionates are listed as scheduled chemicals of the Chemical Weapons Convention (CWC) implemented by the OPCW. The P-S and P-R bond connectivity has to be correctly identified for the verification of the CWC. The present study demonstrates successful identification of the target isomers by selective fragmentation under electron ionization (EI) or chemical ionization (CI) conditions. METHODS: All the studied isomeric compounds (27 in total) were synthesized in our laboratory using established methods, then analyzed by EI and CI gas chromatography/mass spectrometry (GC/MS) using an Agilent 6890 gas chromatograph equipped with a HP-5MS capillary column and interfaced to a 5973 N mass-selective detector. The retention index (RI) values of all the compounds were calculated using Van den Dool's formula. GC/MS/MS and GC/HRMS experiments were also performed using a VG-Autospec (magnetic sector) and JEOL-AccuToF (time-of-flight) mass spectrometer, respectively. RESULTS: The EI mass spectra of all the compounds had an abundant molecular ion at m/z 182, except in the case of a few selected butyl-substituted compounds, where this ion was of low abundance. The EI fragmentation pathways include α-cleavage, McLafferty rearrangement, McLafferty + 1 rearrangement, O/S-alkyl radical loss, and an alkene loss with a hydrogen shift. The characteristic fragment ions and their relative abundances are significant in elucidating the alkyl group attached to the P/S/O-atoms as well as the P-S/P = S bond connectivity. The EI and CI mass spectra together with RI values enable unambiguous identification of all the studied isomeric compounds. CONCLUSIONS: The present study highlights the structural characterization of the isomeric phosphonothiolates and phosphonothionates based on their selective EI fragmentation. The assigned fragmentation pathway helps in the assignment of P-S and P-alkyl connectivity in phosphonothiolates and phosphonothionates, consequently the structure of the unknown compounds. The EI mass spectra (27 compounds) of isomeric compounds are immensely useful in the OPCW official proficiency tests and for off-site analysis.

Mass spectral analysis of N-oxides of Chemical Weapons Convention related aminoethanols under electrospray ionization conditions.

N,N'-Dialkylaminoethanols are the hydrolyzed products or precursors of chemical warfare agents such as V-agents and nitrogen mustards, and they are prone to undergo oxidation in environmental matrices or during decontamination processes. Consequently, screening of the oxidized products of aminoethanols in aqueous samples is an important task in the verification of chemical weapons convention-related chemicals. Here we report the successful characterization of the N-oxides of N,N'-dialkylaminoethanols, alkyl diethanolamines, and triethanolamine using positive ion electrospray ionization mass spectrometry. The collision-induced dissociation (CID) spectra of the [M+H](+) and [M+Na](+) ions show diagnostic product ions that enable the unambiguous identification of the studied N-oxides, including those of isomeric compounds. The proposed fragmentation pathways are supported by high-resolution mass spectrometry data and product/precursor ion spectra. The CID spectra of [M+H](+) ions included [MH-CH(4)O(2)](+) as the key product ion, in addition to a distinctive alkene loss that allowed us to recognize the alkyl group attached to the nitrogen. The [M+Na](+) ions show characteristic product ions due to the loss of groups (R) attached to nitrogen either as a radical (R) or as a molecule [R+H or (R-H)] after hydrogen migration.

Electrospray ionization mass spectral studies of N,N-dialkylaminoethane-2-sulphonic acids.

Oxidative reactions of VX type compounds and N,N-dialkylaminoethane-2-thiols that are precursors for VX compounds produce N,N-dialkylaminoethane-2-sulphonic acids, N(R(1))(R(2))-CH(2)-CH(2)SO(3)H (where R(1) and R(2) = methyl, ethyl, n-propyl and isopropyl, 1-10), as the degradation products, and these degradation products are considered as markers for the detection of chemicals listed in the schedules of Chemical Weapons Convention (CWC) chemicals. Off-site detection of such degradation products in aqueous samples is an important task in the verification of CWC-related chemicals. Here we report a simple method involving the direct analysis of aqueous samples using positive and/or negative ion electrospray ionization (ESI) for the screening, detection and identification of N,N-dialkylaminoethane-2-sulphonic acids, avoiding sample preparation and chromatographic steps. The positive ion ESI mass spectra of all the compounds result in abundant [M+Na](+) ions, and the negative ion spectra show abundant [M-H](-) ions to confirm their molecular weight. The collision-induced dissociation spectra of [M+Na](+) and [M-H](-) give characteristic product ions by which it is easy to detect and identify all the studied N,N-dialkylaminoethane-2-sulphonic acids including those of isomeric compounds. The method is successfully applied to detect the spiked chemical, N,N-diisopropylaminoethane-2-sulphonic acid, present in a water sample received in a proficiency test.

Differential effects of cholesterol and 7-dehydrocholesterol on ligand binding of solubilized hippocampal serotonin1A receptors: implications in SLOS.

The serotonin1A receptor is an important member of the G-protein coupled receptor family, and is involved in the generation and modulation of a variety of cognitive, behavioral, and developmental functions. Solubilization of the hippocampal serotonin1A receptor by 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) is accompanied by loss of membrane cholesterol which results in a reduction in specific agonist binding activity. Replenishment of cholesterol to solubilized membranes restores the cholesterol content of the membrane and significantly enhances specific agonist binding activity. In order to test the stringency of the requirement of cholesterol in this process, we solubilized native hippocampal membranes followed by replenishment with 7-dehydrocholesterol (7-DHC). 7-DHC is an immediate biosynthetic precursor of cholesterol differing only in a double bond at the 7th position in its sterol ring. Our results show, for the first time, that replenishment of solubilized hippocampal membranes with 7-DHC does not restore ligand binding activity of the serotonin1A receptor, in spite of recovery of the overall membrane order. This observation shows that the requirement for restoration of ligand binding activity is more stringent than the requirement for the recovery of overall membrane order. These novel results have potential implications in understanding the interaction of membrane sterols with this important neuronal receptor under pathogenic conditions such as the Smith-Lemli-Opitz syndrome.

Gas chromatographic-mass spectrometric determination of alkylphosphonic acids from aqueous samples by ion-pair solid-phase extraction on activated charcoal and methylation.

In the present paper, we report an improved ion-pair solid-phase extraction (IP-SPE) method for the analysis of alkylphosphonic acids, namely, methyl, ethyl and propylphosphonic acids, present in the aqueous sample. The aqueous sample was mixed with an ion-pair reagent, phenyltrimethylammonium hydroxide (PTMAH) and passed through activated charcoal SPE cartridge. The retained chemicals in the cartridge were extracted with methanol and analysed by gas chromatography-mass spectrometry (GC-MS) under the electron impact ionization (EI) mode. The analytes were converted to their methyl esters by pyrolytic methylation in the hot GC injection port. The recoveries of alkylphosphonic acids were above 95% and the minimum detection limits were as low as 10 ng/mL. The recovery of the test chemicals was tested with solvents, dichloromethane, n-hexane, ethyl acetate, acetone, acetonitrile and methanol. The chemicals could be efficiently extracted by the hydrophilic solvents. The method did not work at the highly acidic pH (when acidified with dilute HCl) but worked well from pH 4.0 to 14.0. The present method was also tested with other tetra-(methyl, ethyl, propyl and n-butyl)ammonium hydroxides. The test chemicals were not converted to their methyl and ethyl esters with tetramethyl and tetraethylammonium hydroxides, whereas they were converted to their corresponding propyl and n-butyl esters with tetrapropyl and tetra(n-butyl)ammonium hydroxides. The method was also applied to two highly cross-linked polymeric sorbents DSC-6S and Oasis HLB. The recovery of the chemicals on these sorbents was observed to be poor. Methylation using phenyltrimethylammonium hydroxide is non-hazardous and advantageous over methylation using diazomethane. The method was applied to the analysis of aqueous samples given in one of the official proficiency tests conducted by the Organization for the Prohibition of Chemical Weapons and all the spiked chemicals were identified as methyl esters.

In situ nucleophilic substitution reaction of N,N-dialkylaminoethyl-2-chlorides monitored by gas chromatography/mass spectrometry.

The detection and identification of degradation products of scheduled chemicals, which are characteristic markers of Chemical Warfare agents (CWAs), plays a key role in verification analysis. Identification of such non-scheduled but specific markers of CWAs helps in deciphering the kind of agent that was present in the sample submitted for off-site analysis. This paper describes the stability of N,N-dialkylaminoethyl-2-chlorides, which are precursors for highly toxic chemicals like VX, in different solvents. These compounds are stable in chloroform, acetonitrile, hexane and dichloromethane but tend to undergo in situ nucleophilic substitution reaction in the presence of alcohols giving the corresponding alkyl ether. The study shows that N,N-dialkylaminoethyl alkyl ethers can be used as markers of N,N-dialkylaminoethyl-2-chlorides. A detailed degradation study of these compounds in the presence of alcohols was carried out and it was found that the reaction follows pseudo-first order kinetics. Electron ionization mass spectral data for the methyl ethers of all the compounds are briefly discussed.

Electrospray ionisation mass spectral studies on hydrolysed products of sulfur mustards.

Off-site detection of the hydrolysed products of sulfur mustards in aqueous samples is an important task in the verification of Chemical Weapons Convention (CWC)-related chemicals. The hydrolysed products of sulfur mustards are studied under positive and negative electrospray ionisation (ESI) conditions using an additive with a view to detecting them at trace levels. In the presence of cations (Li(+), Na(+), K(+) and NH(4) (+)), the positive ion ESI mass spectra of all the compounds include the corresponding cationised species; however, only the [M+NH(4)](+) ions form [M+H](+) ions upon decomposition. The tandem mass (MS/MS) spectra of [M+H](+) ions from all the hydrolysed products of the sulfur mustard homologues were distinct and allowed these compounds to be characterised unambiguously. Similarly, the negative ion ESI mass spectra of all the compounds show prominent adducts with added anions (F(-), Cl(-), Br(-), and I(-)), but the [M-H](-) ion can only be generated by decomposition of an [M+F](-) ion. The MS/MS spectra of the [M-H](-) ions from all the compounds result in a common product ion at m/z 77. A precursor ion scan of m/z 77 is shown to be useful in the rapid screening of these compounds in aqueous samples at trace levels, even in the presence of complex masking agents, without the use of time-consuming sample preparation and chromatography steps. An MS/MS method developed to measure the detection limits of the hydrolysed products of sulfur mustards found these to be in the range of 10-500 ppb.

Environmental regulation, productive efficiency and cost of pollution abatement: a case study of the sugar industry in India.

In this paper the input distance function is estimated for the Indian Sugar industry under alternative assumptions of weak and strong disposability of bad outputs. The estimated distance function is used to make the estimates of environmental efficiency, Malmquist productivity index and shadow prices of pollutants. The technical efficiency measure estimated under the assumption of weak disposability of bad outputs is utilized to test the Porter hypothesis. Marginal costs of pollution abatement functions are estimated for different pollutants of water. Pollutant specific taxes are computed using the tax-standards method.