PSO-XnB: a proposed model for predicting hospital stay of CAD patients.

Coronary artery disease poses a significant challenge in decision-making when predicting the length of stay for a hospitalized patient. This study presents a predictive model-a Particle Swarm Optimized-Enhanced NeuroBoost-that combines the deep autoencoder with an eXtreme gradient boosting model optimized using particle swarm optimization. The model uses a fuzzy set of rules to categorize the length of stay into four distinct classes, followed by data preparation and preprocessing. In this study, the dimensionality of the data is reduced using deep neural autoencoders. The reconstructed data obtained from autoencoders is given as input to an eXtreme gradient boosting model. Finally, the model is tuned with particle swarm optimization to obtain optimal hyperparameters. With the proposed technique, the model achieved superior performance with an overall accuracy of 98.8% compared to traditional ensemble models and past research works. The model also scored highest in other metrics such as precision, recall, and particularly F1 scores for all categories of hospital stay. These scores validate the suitability of our proposed model in medical healthcare applications.

Design, synthesis and biological evaluation of novel pyrimidine derivatives as bone anabolic agents promoting osteogenesis via the BMP2/SMAD1 signaling pathway.

Anti-resorptive inhibitors such as bisphosphonates are widely used but they have limited efficacy and serious side effects. Though subcutaneous injection of teriparatide [PTH (1-34)] is an effective anabolic therapy, long-term repeated subcutaneous administration is not recommended. Henceforth, orally bio-available small-molecule-based novel therapeutics are unmet medical needs to improve the treatment. In this study, we designed, synthesized, and carried out a biological evaluation of 31 pyrimidine derivatives as potent bone anabolic agents. A series of in vitro experiments confirmed N-(5-bromo-4-(4-bromophenyl)-6-(2,4,5-trimethoxyphenyl)pyrimidin-2-yl)hexanamide (18a) as the most efficacious anabolic agent at 1 pM. It promoted osteogenesis by upregulating the expression of osteogenic genes (RUNX2 and type 1 col) via activation of the BMP2/SMAD1 signaling pathway. In vitro osteogenic potential was further validated using an in vivo fracture defect model where compound 18a promoted the bone formation rate at 5 mg kg-1. We also established the structure-activity relationship and pharmacokinetic studies of 18a.

Indole-based aryl sulfides target the cell wall of Staphylococcus aureus without detectable resistance.

Sulfur-containing classes of the scaffold "Arylthioindoles" have been evaluated for antibacterial activity; they demonstrated excellent potency against methicillin-resistant Staphylococcus aureus (MRSA) as well as against vancomycin-resistant strains and a panel of clinical isolates of resistant strains. In this study, we have elucidated the mechanism of action of lead compounds, wherein they target the cell wall of S. aureus. Further, S. aureus failed to develop resistance against two lead compounds tested in a serial passage experiment in the presence of the compounds over a period of 40 days. Both the compounds demonstrated comparable in vivo efficacy with vancomycin in a neutropenic mice thigh infection model. The results of these antibacterial activities emphasize the excellent potential of thioethers for developing novel antibiotics and may fill in as a target for the adjustment of accessible molecules to develop new powerful antibacterial agents with fewer side effects.

Smouldering Myeloma: Chasing a Hyperviscous Sample.

Serum hyperviscosity is a rare laboratory finding. Amongst several causes of serum hyperviscosity, malignant disorders are quite common. Monoclonal gammopathy is a family of disorders in which monoclonal gammopathy of unknown significance (MGUS) and smoldering myeloma are the asymptomatic variants whereas multiple myeloma is the malignant variant showing different signs and symptoms related to bone lesions, renal failure and anemia. Initially during sample preparation, pipetting of a serum sample was found to be cumbersome. This sample during routine analysis in the automated analyser flagged repeated alarms for clot detection indicating a possibility of a hyper viscous sample. Serum was subjected to fibrinogen and D- dimer test. The D-Dimer levels were found to be normal and fibrinogen levels were mildly elevated. Routine biochemistry investigations were normal except grossly reversed A/G ratio. Due to gross reversal of A/G ratio, the possibility of Multiple myeloma was entertained. Physician's were alerted on telephone. Serum was sent for electrophoresis which showeda M spike. Bone marrow aspirate showed 13% plasma cells. Considering the above lab results the diagnosis of monoclonal gammopathy of smoldering type was considered. The sample was traced to a 77 years old male, who presented to Medicine OPD with the chief complaints of generalised weakness for two months without any history of fever. On physical examination pallor was evident but there was no icterus, cyanosis, clubbing, lymphadenopathy or edema. On haematological evaluation patient was found to be anemic. Careful tracking of hyperviscous patient's serum followed up by thorough investigation led us to the final conclusion that the case mentioned is a rare case of Smoldering type of multiple myeloma.

One-pot C-C, C-N, and C-S bond construction for synthesis of 3-sulfenylindoles directly from unactivated anilines involving dual palladium catalysis and mechanistic insights from DFT.

An efficient dual Pd-catalytic system was developed for one-pot synthesis of 3-sulfenylindoles via C-C, C-N and C-S bond construction directly from unactivated 2-iodo(NH)anilines under mild reaction conditions. Furthermore, 3-selenyl/halo/carbon-functionalized indoles were synthesized in good yields and a short reaction time. The synthetic utility of 3-sulfenylindole was also demonstrated. The key role of solvent in palladium catalysis was unravelled by DFT.

Coumarin as a Surrogate for the Protection-group-free Synthesis of o-Hydroxy Stilbenes: Hydrolysis-Decarboxylation-Heck Coupling Reactions in One Pot.

The 2-hydroxystyrylbenzene scaffold is found in various compounds that are widely applicable in medicinal chemistry as well as material chemistry. Here, a successful attempt is made to develop a one-pot protocol for the synthesis of 2-hydroxystilbene derivatives via hydrolysis of natural coumarins followed by in situ decarboxylative Heck coupling with haloarenes. Fine tuning of the reaction conditions allowed exclusive formation of 2-hydroxystyrylbenzenes over other possible side products, i. e., benzofuran/substituted coumarins.

Direct Synthesis of Intermetallic Platinum-Alloy Nanoparticles Highly Loaded on Carbon Supports for Efficient Electrocatalysis.

Compared to nanostructured platinum (Pt) catalysts, ordered Pt-based intermetallic nanoparticles supported on a carbon substrate exhibit much enhanced catalytic performance, especially in fuel cell electrocatalysis. However, direct synthesis of homogeneous intermetallic alloy nanocatalysts on carbonaceous supports with high loading is still challenging. Herein, we report a novel synthetic strategy to directly produce highly dispersed MPt alloy nanoparticles (M = Fe, Co, or Ni) on various carbon supports with high catalyst loading. Importantly, a unique bimetallic compound, composed of [M(bpy)3]2+ cation (bpy = 2,2'-bipyridine) and [PtCl6]2- anion, evenly decomposes on carbon surface and forms uniformly sized intermetallic nanoparticles with a nitrogen-doped carbon protection layer. The excellent oxygen reduction reaction (ORR) activity and stability of the representative reduced graphene oxide (rGO)-supported L10-FePt catalyst (37 wt %-FePt/rGO), exhibiting 18.8 times higher specific activity than commercial Pt/C catalyst without degradation over 20 000 cycles, well demonstrate the effectiveness of our synthetic approach toward uniformly alloyed nanoparticles with high homogeneity.

Reversible and cooperative photoactivation of single-atom Cu/TiO2 photocatalysts.

The reversible and cooperative activation process, which includes electron transfer from surrounding redox mediators, the reversible valence change of cofactors and macroscopic functional/structural change, is one of the most important characteristics of biological enzymes, and has frequently been used in the design of homogeneous catalysts. However, there are virtually no reports on industrially important heterogeneous catalysts with these enzyme-like characteristics. Here, we report on the design and synthesis of highly active TiO2 photocatalysts incorporating site-specific single copper atoms (Cu/TiO2) that exhibit a reversible and cooperative photoactivation process. Our atomic-level design and synthetic strategy provide a platform that facilitates valence control of co-catalyst copper atoms, reversible modulation of the macroscopic optoelectronic properties of TiO2 and enhancement of photocatalytic hydrogen generation activity, extending the boundaries of conventional heterogeneous catalysts.

Synthesis of nanostructured P2-Na2/3MnO2 for high performance sodium-ion batteries.

We report a facile two-step method to synthesize nanostructured P2-Na2/3MnO2via ligand exchange and intercalation of sodium ions into ultrathin manganese oxide nanoplates. Sodium storage performance of the synthesized material shows a high capacity (170 mA h g-1) and an excellent rate performance.

Synergistic Dual Role of [hmim]Br-ArSO2Cl in Cascade Sulfenylation-Halogenation of Indole: Mechanistic Insight into Regioselective C-S and C-S/C-X (X = Cl and Br) Bond Formation in One Pot.

Bifunctionalized indoles are an important class of biologically active heterocyclic compounds and potential drug candidates. Because of the lack of efficient synthetic methods, one pot cascade synthesis of these compounds is rare and remains a challenge. To expand this field, we herein disclose a step-economical and temperature tunable strategy wherein the synergistic effect between [hmim]Br-ArSO2Cl leads exclusively to the formation of 3-arylthio indole via sulfenylation of indole at room temperature, while heating the reaction mixture at 50 °C provided an unexpected 2-halo-3-arylthio indole with construction of C-S and C-S/C-X (X = Cl and Br) bonds without addition of any external halogenating agent via cascade sulfenylation-halogenation reactions under metal-oxidant-base-free conditions. Further, insight into the reaction mechanism provides an unprecedented observation wherein the synergistic interaction between [hmim]Br-ArSO2X in the presence of a catalytic amount of water generates arylsulfonic anhydride (ArSO2)2O in situ as a new sulfur source along with the formation of [hmim]PTS as probed by NMR, ESI-MS, DART-MS, and HPLC studies. Notably, the mixture of bifunctionalized 2-halo(Br/Cl)-3-arylthio indole was smoothly diversified with privileged heterocycle triazole to provide 2-(1 H-triazole-1-yl)-3-arylthio indole, which is an analogue of the potent indole-based anticancer agent.

Styryl-cinnamate hybrid inhibits glioma by alleviating translation, bioenergetics and other key cellular responses leading to apoptosis.

Gliomas are lethal and aggressive form of brain tumors with resistance to conventional radiation and cytotoxic chemotherapies; inviting continuous efforts for drug discovery and drug delivery. Interestingly, small molecule hybrids are one such pharmacophore that continues to capture interest owing to their pluripotent medicinal effects. Accordingly, we earlier reported synthesis of potent Styryl-cinnamate hybrids (analogues of Salvianolic acid F) along with its plausible mode of action (MOA). We explored iTRAQ-LC/MS-MS technique to deduce differentially expressed landscape of native & phospho-proteins in treated glioma cells. Based on this, Protein-Protein Interactome (PPI) was looked into by employing computational tools and further validated in vitro. We hereby report that the Styryl-cinnamate hybrid, an analogue of natural Salvianolic acid F, alters key regulatory proteins involved in translation, cytoskeleton development, bioenergetics, DNA repair, angiogenesis and ubiquitination. Cell cycle analysis dictates arrest at G0/G1 stage along with reduced levels of cyclin D; involved in G1 progression. We discovered that Styryl-cinnamate hybrid targets glioma by intrinsically triggering metabolite-mediated stress. Various oncological circuits alleviated by the potential drug candidate strongly supports the role of such pharmacophores as anticancer drugs. Although, further analysis of SC hybrid in treating xenografts or solid tumors is yet to be explored but their candidature has gained huge impetus through this study. This study equips us better in understanding the shift in proteomic landscape after treating glioma cells with SC hybrid. It also allows us to elicit molecular targets of this potential drug before progressing to preclinical studies.

Biocatalytic synthesis of diaryl disulphides and their bio-evaluation as potent inhibitors of drug-resistant Staphylococcus aureus.

Staphylococcus aureus is a WHO Priority II pathogen for its capability to cause acute to chronic infections and to resist antibiotics, thus severely impacting healthcare systems worldwide. In this context, it is urgently desired to discover novel molecules to thwart the continuing emergence of antimicrobial resistance. Disulphide containing small molecules has gained prominence as antibacterials. As their conventional synthesis requires tedious synthetic procedure and sometimes toxic reagents, a green and environmentally benign protocol for their synthesis has been developed through which a series of molecules were obtained and evaluated for antibacterial activity against ESKAPE pathogen panel. The hit compound was tested for cytotoxicity against Vero cells to determine its selectivity index and time-kill kinetics was determined. The activity of hit was determined against a panel of S. aureus multi-drug resistant clinical isolates. Also, its ability to synergize with FDA approved drugs was tested as was its ability to reduce biofilm. We identified bis(2-bromophenyl) disulphide (2t) as possessing equipotent antimicrobial activity against S. aureus including MRSA and VRSA strains. Further, 2t exhibited a selectivity index of 25 with concentration-dependent bactericidal activity, synergized with all drugs tested and significantly reduced preformed biofilm. Taken together, 2t exhibits all properties to be positioned as novel scaffold for anti-staphylococcal therapy.

Engineering Titanium Dioxide Nanostructures for Enhanced Lithium-Ion Storage.

Various kinds of nanostructured materials have been extensively investigated as lithium ion battery electrode materials derived from their numerous advantageous features including enhanced energy and power density and cyclability. However, little is known about the microscopic origin of how nanostructures can enhance lithium storage performance. Herein, we identify the microscopic origin of enhanced lithium storage in anatase TiO2 nanostructure and report a reversible and stable route to achieve enhanced lithium storage capacity in anatase TiO2. We designed hollow anatase TiO2 nanostructures composed of interconnected ∼5 nm sized nanocrystals, which can individually reach the theoretical lithium storage limit and maintain a stable capacity during prolonged cycling (i.e., 330 mAh g-1 for the initial cycle and 228 mAh g-1 for the 100th cycle, at 0.1 A g-1). In situ characterization by X-ray diffraction and X-ray absorption spectroscopy shows that enhanced lithium storage into the anatase TiO2 nanocrystal results from the insertion reaction, which expands the crystal lattice during the sequential phase transition (anatase TiO2 → Li0.55TiO2 → LiTiO2). In addition to the pseudocapacitive charge storage of nanostructures, our approach extends the utilization of nanostructured TiO2 for significantly stabilizing excess lithium storage in crystal structures for long-term cycling, which can be readily applied to other lithium storage materials.

Facile synthesis of vanillin-based novel bischalcones identifies one that induces apoptosis and displays synergy with Artemisinin in killing chloroquine resistant Plasmodium falciparum.

The inherent affinity of natural compounds for biological receptors has been comprehensively exploited with great success for the development of many drugs, including antimalarials. Here the natural flavoring compound vanillin has been used as an economical precursor for the synthesis of a series of novel bischalcones whose in vitro antiplasmodial activities have been evaluated against erythrocytic stages of Plasmodium falciparum. Bischalcones 9, 11 and 13 showed promising antiplasmodial activity {Chloroquine (CQ) sensitive Pf3D7 IC50 (µM): 2.0, 1.5 and 2.5 respectively}but only 13 displayed potent activities also against CQ resistant PfDd2 and PfIndo strains exhibiting resistance indices of 1.4 and 1.5 respectively. IC90 (8 µM) of 13 showed killing activity against ring, trophozoite and schizont stages. Further, 13 initiated the cascade of reactions that culminates in programmed cell death of parasites including translocation of phosphatidylserine from inner to outer membrane leaflet, loss of mitochondrial membrane potential, activation of caspase like enzyme, DNA fragmentation and chromatin condensation. The combinations of 13 + Artemisinin (ART) exhibited strong synergy (ΣFIC50:0.46 to 0.58) while 13 + CQ exhibited mild synergy (ΣFIC50: 0.7 to 0.98) to mild antagonism (ΣFIC50: 1.08 to 1.23) against PfIndo. In contrast, both combinations showed marked antagonism against Pf3D7(ΣFIC50: 1.33 to 3.34). These features of apoptosis and strong synergy with Artemisinin suggest that bischalcones possess promising antimalarial drug-like properties and may also act as a good partner drugs for artemisinin based combination therapies (ACTs) against Chloroquine resistant P. falciparum.

Large-Scale Synthesis of Carbon-Shell-Coated FeP Nanoparticles for Robust Hydrogen Evolution Reaction Electrocatalyst.

A highly active and stable non-Pt electrocatalyst for hydrogen production has been pursued for a long time as an inexpensive alternative to Pt-based catalysts. Herein, we report a simple and effective approach to prepare high-performance iron phosphide (FeP) nanoparticle electrocatalysts using iron oxide nanoparticles as a precursor. A single-step heating procedure of polydopamine-coated iron oxide nanoparticles leads to both carbonization of polydopamine coating to the carbon shell and phosphidation of iron oxide to FeP, simultaneously. Carbon-shell-coated FeP nanoparticles show a low overpotential of 71 mV at 10 mA cm-2, which is comparable to that of a commercial Pt catalyst, and remarkable long-term durability under acidic conditions for up to 10 000 cycles with negligible activity loss. The effect of carbon shell protection was investigated both theoretically and experimentally. A density functional theory reveals that deterioration of catalytic activity of FeP is caused by surface oxidation. Extended X-ray absorption fine structure analysis combined with electrochemical test shows that carbon shell coating prevents FeP nanoparticles from oxidation, making them highly stable under hydrogen evolution reaction operation conditions. Furthermore, we demonstrate that our synthetic method is suitable for mass production, which is highly desirable for large-scale hydrogen production.

Sulfur-Modified Graphitic Carbon Nitride Nanostructures as an Efficient Electrocatalyst for Water Oxidation.

There is an urgent need to develop metal-free, low cost, durable, and highly efficient catalysts for industrially important oxygen evolution reactions. Inspired by natural geodes, unique melamine nanogeodes are successfully synthesized using hydrothermal process. Sulfur-modified graphitic carbon nitride (S-modified g-CN x ) electrocatalysts are obtained by annealing these melamine nanogeodes in situ with sulfur. The sulfur modification in the g-CN x structure leads to excellent oxygen evolution reaction activity by lowering the overpotential. Compared with the previously reported nonmetallic systems and well-established metallic catalysts, the S-modified g-CN x nanostructures show superior performance, requiring a lower overpotential (290 mV) to achieve a current density of 10 mA cm-2 and a Tafel slope of 120 mV dec-1 with long-term durability of 91.2% retention for 18 h. These inexpensive, environmentally friendly, and easy-to-synthesize catalysts with extraordinary performance will have a high impact in the field of oxygen evolution reaction electrocatalysis.

Cooperative catalysis by bovine serum albumin-iodine towards cascade oxidative coupling-C(sp(2))-H sulfenylation of indoles/hydroxyaryls with thiophenols on water.

Cooperative cascade catalysis by bovine serum albumin (BSA)-iodine allows for the first time the performance of C(sp(2))-H sulfenylation of indole from readily available thiophenol (-SH bond) via in situ generation/cleavage of disulfide (S-S bond) in air under aqueous conditions, whereas BSA or I2 individually do not permit this two step sequence to occur in the same pot towards C-S bond formation. This green cooperative protocol is extendable to sulfenylation of hydroxyaryls (i.e. 2-naphthol or 4-hydroxycoumarin) with diverse thiols (aryl/heteroaryl) without using any toxic metal catalysts, bases or oxidants, thus rendering the process environmentally and economically reliable. Further, the gram scale synthesis of a COX-2 inhibitor (3-(pyridin-2-ylthio)-1H-indole), regioselectivity and recyclability (up to four cycles) are the additional merits of this cooperative cascade bio-chemocatalytic (BSA-I2) protocol. Moreover, HPLC and ESI-MS provide powerful insights into the mechanistic aspects of the above cascade sulfenylation reaction.

Metal nanoparticles triggered persistent negative photoconductivity in silk protein hydrogels.

Silk protein is a natural biopolymer with intriguing properties, which are attractive for next generation bio-integrated electronic and photonic devices. Here, we demonstrate the negative photoconductive response of Bombyx mori silk protein fibroin hydrogels, triggered by Au nanoparticles. The room temperature electrical conductivity of Au-silk hydrogels is found to be enhanced with the incorporation of Au nanoparticles over the control sample, due to the increased charge transporting networks within the hydrogel. Au-silk lateral photoconductor devices show a unique negative photoconductive response under an illumination of 325 nm, with excitation energy higher than the characteristic metal plasmon resonance band. The enhanced photoconductance yield in the hydrogels over the silk protein is attributed to the photo-oxidation of amino groups in the ß-pleated sheets of the silk around the Au nanoparticles followed by the breaking of charge transport networks. The Au-silk nanocomposite does not show any photoresponse under visible illumination because of the localization of excited charges in Au nanoparticles. The negative photoconductive response of hybrid Au-silk under UV illumination may pave the way towards the utilization of silk for future bio-photonic devices using metal nanoparticle platforms.

Thiol-ene "click" reaction triggered by neutral ionic liquid: the "ambiphilic" character of [hmim]Br in the regioselective nucleophilic hydrothiolation.

Thiol-ene "click" chemistry has emerged as a powerful strategy to construct carbon-heteroatom (C-S) bonds, which generally results in the formation of two regioisomers. To this end, the neutral ionic liquid [hmim]Br has been explored as a solvent cum catalyst for the synthesis of linear thioethers from activated and inactivated styrene derivatives or secondary benzyl alcohols and thiols without the requirement of using a metal complex, base, or free radical initiator. Furthermore, detailed mechanistic investigations using (1)H NMR spectroscopy and quadrupole time-of-flight electrospray ionization mass spectrometry (Q-TOF ESI-MS) revealed that the "ambiphilic" character of the ionic liquid promotes the nucleophilic addition of thiol to styrene through an anti-Markovnikov pathway. The catalyst recyclability and the extension of the methodology for thiol-yne click chemistry are additional benefits. A competitive study among thiophenol, styrene, and phenyl acetylene revealed that the rate of reaction is in the order of thiol-yne>thiol-ene>dimerization of thiol in [hmim]Br.

Solid-state transformation of single precursor vanadium complex nanostructures to V2O5 and VO2: catalytic activity of V2O5 for oxidative coupling of 2-naphthol.

A vanadium complex, [(C5H5N)2V2O3·H2O], of different morphologies has been obtained via a modified hydrothermal procedure using pyridine and VOSO4 salt as the starting material. The evolved [(C5H5N)2V2O3·H2O] nanobelts are of 50-200 nm in width and of a length up to several millimeters. At higher temperatures (600 °C), the solid [(C5H5N)2V2O3·H2O] nanostructures are converted to vanadium pentoxide (V2O5) and vanadium dioxide (VO2) when heated in air and nitrogen atmosphere, respectively. During growth, the mechanism of the evolution of octahedra, truncated octahedra, and hollow truncated octahedra of [(C5H5N)2V2O3·H2O] are reported for the first time. These types of well-structured morphology are also isolated while V2O5 and VO2 are evolved. The as-grown belt-like and octahedral morphologies of [(C5H5N)2V2O3·H2O] are retained during the solid-state transformation, suggesting a route to evolve crystalline nanomaterials. Again, the morphological evolution of the [(C5H5N)2V2O3·H2O] nanostructures has been examined to be pyridine and precursor vanadyl sulfate (VS) concentration dependent. Thus, we are able to isolate truncated octahedra as an intermediate during the formation of [(C5H5N)2V2O3·H2O] nanobelts and nanoflowers with a high pyridine (Py) concentration. Interestingly, longer reaction times successively featured the transformation of truncated octahedra into nanobelts. Nanobelt evolution is not observed at low pyridine concentrations. However, the formation of octahedral morphology takes place at low pyridine concentration. All of the nanostructures were critically examined and characterized thoroughly by various physical techniques to ascertain their purity, structure and composition. An interesting, thermodynamically stable, single crystalline product from DMF soluble [(C5H5N)2V2O3·H2O] has been characterized, which indirectly supports the composition of [(C5H5N)2V2O3·H2O]. Selectively, vanadium pentoxide nanobelts have been found to be an efficient catalyst for the oxidative coupling of 2-naphthol to binaphthols under a molecular oxygen atmosphere.