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Background: The highly homologous T‐box transcription factors TBX2 and TBX3 are critical for embryonic development, and their overexpression in postnatal tissues contributes to a wide range of malignancies, including melanoma and rhabdomyosarcoma. Importantly, when TBX2 and TBX3 are depleted in cancers where they are overexpressed, the malignant phenotype is inhibited, and they have therefore been regarded as druggable targets. However, the time and costs associated with de novo drug development are challenging and result in drugs that are costly, especially for patients in low‐ and middle‐income countries. In the current study, we therefore combined a targeted and drug repurposing approach to identify drugs that are expected to be more efficacious and cost‐effective with significantly reduced side effects. Methods: A high‐throughput cell‐based immunofluorescence screen was performed to identify drugs in the Pharmakon 1600 drug library that can negatively regulate TBX2 and/or TBX3 levels. "Hit" drugs were validated for their effect on TBX2/TBX3 levels and cytotoxicity in TBX2/TBX3‐dependent melanoma and rhabdomyosarcoma cells. To this end, immunofluorescence, western blotting, quantitative real‐time PCR, and MTT cell viability assays were performed. Results: Niclosamide, piroctone olamine, and pyrvinium pamoate, were identified as TBX2 and/or TBX3‐targeting drugs, and they exhibited cytotoxicity in a TBX2/TBX3‐dependent manner. Furthermore, these "Hit" drugs were shown to induce senescence and/or apoptosis. Conclusions: Niclosamide, piroctone olamine, and pyrvinium pamoate are promising, cost‐effective therapeutic agents for the treatment of TBX2/TBX3‐dependent cancers. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) caused by the Mycobacterium tuberculosis (MTB) pathogen is a serious contagious illness that endangers the public's health. However, TB is treatable but due to the result of ineffective and protracted medication, MDR‐MTB and XDR‐MTB were able to develop, making their eradication highly challenging and necessitating potential treatments to be cured. This study aimed to identify the novel inhibitor for the InhA enzyme, a potential target of MTB. Initially, 2721 phytochemicals libraries were screened for ADME/Tox profiling and 49 phytochemicals were filtered out. Moreover, these phytochemicals with reference inhibitor triclosan were docked against InhA (PDB ID: 1BVR)., were showing binding energies ranging from −9.16–−6.3 kcal/mol, whereas triclosan showed −6.90 kcal/mol of binding energy. The docking results reveal that irilone (−9.16 kcal/mol) and aurantio‐obtusin (−8.84 kcal/mol) exhibit promising binding energy and perfectly occupy the binding site of InhA. Furthermore, molecular dynamics simulation (MDS) and MMGBSA studies showed better affinities of selected compounds in terms of stability, compactness, flexibility, and total BFE in complexes with InhA. This study concluded that irilone and aurantio‐obtusin could be promising InhA inhibitors based on their impressive pharmacokinetic profiling, toxicity, binding affinity, and stability. However experimental validation is a subject of further research. [ABSTRACT FROM AUTHOR]

The pathogen‐based diseases are prime concern for modern society. Some oxide‐based nanomaterials have been found to show promising antimicrobial activities. However, the industrial synthesis of these oxide materials are harmful to environment. Zinc oxide nano‐flakes were prepared using corn silk (Zea mays) extract. The material was characterized by spectral and microscopic techniques. XRD data shows rutile structure and nano‐crystal size of 36.15 nm. SEM indicates morphology consisting of nano size particles with porous structure. EDX confirms presence of Zn and O. UV‐Vis data shows band gap of 3.62 eV. On excitation, PL exhibits a variety of emission bands in visible spectrum. Dielectric properties suggest the dielectric constant has a well‐dispersed real and imaginary portion. The ZnO NFs were subjected to antimicrobial activities (in dark and under white light) against various strains like E. coli, K. pneumonia and S. aureus. The light induced antibacterial activity is slightly higher as compared to that in dark. Best part of this study is that minimum concentration of ZnO can be used in presence of light thereby reducing the toxicity to the environment due to these metal oxides. Based on the observed results, this material could be used as multi‐dimensional functional material in day‐to‐day life. [ABSTRACT FROM AUTHOR]

The appropriate host cell immune responses for the progression of several diseases, including gastric or stomach cancer (GC), are significantly influenced by HLA polymorphisms. Our objective was to systematically review the evidence linking HLA polymorphisms with the risk of Helicobacter. pylori related GC. We conducted a comprehensive literature search to identify studies published between 2000 and April 2023 on the association of HLA polymorphisms with H. pylori related GC using databases such as Medline through PubMed, Embase, Web of Science (core collection), The Cochrane Library, and Scopus. Two authors independently screened articles, extracted data, and assessed the risk of bias using the Risk of Bias Assessment tool for Non‐randomized Studies. From 7872 retrieved studies, 19 met inclusion criteria, encompassing 1656 cases and 16,787 controls across four World Health Organization regions, with Japan contributing the most studies. We explored HLA‐A/B/C, HLA‐DRB1/DQA1/DQB1, HLA‐G, and MICA alleles. Of 29 significant HLA polymorphisms identified, 18 showed a positive association with GC, whereas 11 were negatively associated. HLA‐DQB1*06 allele was most frequently associated to susceptibility, as reported in four studies, followed by HLA‐DRB1*04 and HLA‐DQA1*01, each reported in two studies. Conversely, HLA‐G*01, HLA‐DQA1*01, HLA‐DQA1*05, and HLA‐DQB1*03 were identified as protective in two studies each. Additionally, five genotypes and six haplotypes were reported as positive, whereas three genotypes and two haplotypes were negative factors for the disease incidence or mortality. Despite heterogeneity in the study population and types of HLA polymorphisms examined, our analysis indicates certain polymorphisms are associated with H. pylori related GC progression and mortality in specific populations. [ABSTRACT FROM AUTHOR]

This article describes an effective and atom‐economical protocol to access a wide range of synthetically important functionalized indolizine derivatives. This transformation basically takes place through a Cu(II) catalyzed formal [3+2] annulation of 2‐pyridinyl substituted p‐quinone methides with enaminones. This method displayed a good functional group tolerance and, was found to be effective for most of the enaminones and p‐QMs, and the corresponding indolizines were obtained in moderate to good yields. [ABSTRACT FROM AUTHOR]

The rapid development of the Internet has led to a shift in how people communicate, with social media becoming an essential vehicle for communication and information exchange. In this context, social media influencers have emerged. With expertise in a particular field and strong influence, they can change customers' attitudes, perceptions, and behaviors. Although social media influencers have been widely studied in the marketing field, most scholars at this stage mainly study the change in customers' attitudes and purchasing behaviors towards brands, without considering the contingency of consumers' participation in influencer marketing activities in the context of social media. Plus, researchers did not pay sufficient attention to customers' impulsive purchasing behaviors. Thus, this article investigated the factors influencing customers' impulsive buying behavior in social media influencer marketing situations. This study built an elaboration likelihood model (i.e., ELM) to explore the factors and mediating variables contributing to customers' impulsive buying behavior. Questionnaires were used to explore the factors influencing customers' impulsive buying behavior in a social media influencer marketing context. Respondents' attitudes on each dimension were measured using well‐established scales from existing research, and the data were processed to draw conclusions. Findings showed that in the influencer marketing context, consumers' perceived social value and influencer expertise would not directly impact their impulsive buying behavior. Functional and emotional values could lead to impulse buying behavior, while social values would not lead to customer inspiration. Moreover, authenticity and influence both contributed to impulsive buying behaviors. The findings might have important implications for influencer marketing and further studies on impulsive buying. Companies should select authentic and influential influencers; what's more, the influencers should be sincere and enhance their influence to gain consumers' trust. [ABSTRACT FROM AUTHOR]

Introduction: Socioeconomically deprived populations are at greater risk for smoking‐induced diseases and death, such as cancers, and cardiovascular and respiratory illnesses. The initiation of a nurse‐led smoking cessation program in clinical practice is an effective method to enhance smoking cessation among cardiovascular and respiratory patients in Pakistan. This study aimed to evaluate the effectiveness of nurse‐led smoking reduction intervention performed at out‐patient clinics in Karachi, Pakistan. Methods: A single group pre‐and post‐test study was conducted on eligible patients (n = 83) with a typical profile of cardiovascular and respiratory diseases in a tertiary care hospital from December 2020 to July 2021. Intervention: The multi‐modal nurse‐led intervention consisted of two face‐to‐face motivational counseling (30‐min) and free nicotine replacement therapy with telephonic counseling and follow‐ups offered to all eligible patients for 2 months. Results: The nurse‐led intervention resulted in a significant decrease in daily cigarette consumption in most of the patients (75.9%) by 50% and 16.9% of the patients reported smoking abstinence (quitter) at 1‐week follow‐up (p <.001), verified by a CO breath test. Conclusion: A nurse‐managed smoking reduction intervention for even a short duration (2 months) in clinics is an effective approach in enhancing smoking abstinence and reduction among cardiovascular and respiratory patients. [ABSTRACT FROM AUTHOR]

Based on the current UK decarbonization policy, a general outlook on potential routes for the glass industry to achieve net‐zero is discussed and the differentiation during decarbonization is specified. Biomass ash is considered a potential alternative raw material for low‐carbon glass manufacture as it is rich in certain advantageous components, chiefly network modifiers. Simple sieving processes were shown to effectively separate impurities such as S, Cl, and C from some biomass ashes according to particle size distribution. The concentration of undesirable impurities decreased with increasing particle size. Morphologies and X‐ray diffraction patterns of larger washed biomass ash particles indicated liquid/amorphous phase formation during biomass combustion. The washing of ashes was also shown to be a potential route to purification. A washed bracken ash relevant to both modern and ancient glass production was characterized for comparison. Ultraviolet‐visible near‐infrared (UV‐Vis‐near IR) absorption spectra of representative green container glasses produced using biomass ash confirmed that ∼5 wt.% ash in representative glass batches has little impact on the color and redox state of glasses; the redox status of glass produced using >2 mm biomass ash after washing was less reduced than that of glass produced using high levels (>∼9 wt.%) of >2 mm biomass ash after sieving alone, observed via the redox couple Cr3+/Cr6+ by UV‐Vis‐near IR absorption spectroscopy. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study investigated the effect of heat‐moisture treatment (HMT) and pre‐gelatinization (PG) on the physical, mechanical, barrier, and optical features of films based on starch extracted from the Pakistani well‐known variety "Basmati rice." The thermal disintegration of granules was indicated by Scanning Electron Micrographs for HMT film. Findings: The results of the study showed that the solubility of films in water was reduced in the following sequence: Pre‐gelatinized rice starch film (33.66%) > Native rice starch (NRS) film (30.42%) > Heat moisture‐treated rice starch (HMTRS) film (26.90%). The lowest water‐soluble HMTRS film showed increased water transfer resistance and both treatments (HMT and PG) reduced water vapor permeability values of NRS from 2.49 × 10−10 to 1.25 × 10−10 g−1 s−1 Pa−1 and 1.34 × 10−10 g−1 s−1 Pa−1, respectively. Conclusions: HMT induced structural deviations that impact higher changes in color parameters and reduced transparency while both modified films had higher elongation at break than NRS films, but PG films had lower TS as compared to the HMT and NRS films. Significance and Novelty: The lower water vapor permeability of HMT films makes them suitable for packaging moisture‐sensitive food products, while PG films can find use in the packaging of products that are sensitive to light. [ABSTRACT FROM AUTHOR]

Data‐driven techniques are used extensively for hydrologic time‐series prediction. We created various data‐driven models (DDMs) based on machine learning: long short‐term memory (LSTM), support vector regression (SVR), extreme learning machines, and an artificial neural network with backpropagation, to define the optimal approach to predicting streamflow time series in the Carson River (California, USA) and Montmorency (Canada) catchments. The moderate resolution imaging spectroradiometer (MODIS) snow‐coverage dataset was applied to improve the streamflow estimate. In addition to the DDMs, the conceptual snowmelt runoff model was applied to simulate and forecast daily streamflow. The four main predictor variables, namely snow‐coverage (S‐C), precipitation (P), maximum temperature (Tmax), and minimum temperature (Tmin), and their corresponding values for each river basin, were obtained from National Climatic Data Center and National Snow and Ice Data Center to develop the model. The most relevant predictor variable was chosen using the support vector machine‐recursive feature elimination feature selection approach. The results show that incorporating the MODIS snow‐coverage dataset improves the models' prediction accuracies in the snowmelt‐dominated basin. SVR and LSTM exhibited the best performances (root mean square error = 8.63 and 9.80) using monthly and daily snowmelt time series, respectively. In summary, machine learning is a reliable method to forecast runoff as it can be employed in global climate forecasts that require high‐volume data processing. [ABSTRACT FROM AUTHOR]

Heavy metal ions (HMIs), particularly Hg2+, Fe2+, Pb2+, and Cd2+, are toxic to biological systems. These HMIs display a wide distribution in aqueous systems, and due to their bioaccumulation tendency, their prevalence, even at very low concentrations, results in serious health issues in humans. This warrants the availability of easily affordable, reliable, quick, and sensitive approaches for real‐time monitoring of the concentration of HMIs in aqueous environments. Herein, we present the synthesis of a novel hydrazone functionality‐based chromogenic probe that ensures selective and sensitive spectrophotometric sensing of HMIs. More specifically, the synthesis of 3‐(2‐(2,4‐dinitrophenyl) hydrazono) Penta‐1,4‐diene‐1,5‐diyl) diphenol referred to as HZ in the MS through a two‐step approach via the low‐cost precursors viz. Salicaldehyde, acetone, and 2, 4‐dinitrophenyl hydrazine (2, 4‐DNP) is presented. The unique functionality of the as‐synthesized HZ, well‐characterized via spectroscopic approaches, is demonstrated to facilitate the spectrophotometric sensing of Hg2+, Fe2+, Pb2+, and Cd2+ with detection limits as low as 0.74 μM, 1.46 μM, 0.75 μM, and 0.75 nM respectively. Importantly the spectrophotometric response of HZ is demonstrated to be very sensitive to the nature of HMI, which does ensure selective specification of the chosen HMIs. The sensing ability of the HZ is well within concentration ranges that include WHO‐recommended safe and toxic concentrations for these HMIs. [ABSTRACT FROM AUTHOR]

Biologics manufacturing is capital and consumable intensive with need for advanced inventory planning to account for supply chain constraints. Early‐stage process design and technology transfer are often challenging due to limited information on process variability regarding bioreactor titer, process yield, and product quality. Monte Carlo (MC) methods offer a stochastic modeling approach for process optimization where probabilities of occurrence for process inputs are incorporated into a deterministic model to simulate more likely scenarios for process outputs. In this study, we explore MC simulation‐based design of a monoclonal antibody downstream manufacturing process. We demonstrate that this probabilistic approach offers more representative outcomes over the conventional worst‐case approach where the theoretical minimum and maximum values of each process parameter are used without consideration for their probability of occurrence. Our work demonstrates case studies on more practically sizing unit operations to improve consumable utilization, thereby reducing manufacturing costs. We also used MC simulations to minimize process cadence by constraining the number of cycles per unit operation to fit facility preferences. By factoring in process uncertainty, we have implemented MC simulation‐based facility fit analyses to efficiently plan for inventory when accounting for process constraints during technology transfer from lab‐scale to clinical or commercial manufacturing. [ABSTRACT FROM AUTHOR]

The waste effluents of two different dyes including one vat dye Indigo and one sulphur dye (Stay Black) were treated using continuous electrocoagulation (EC) technique at a denim dyeing plant. A coagulator reactor of 3 L capacity was designed to treat 7.9 L/h to 65.4 L/h of the dye wastewater. Process parameters like pH, flow rate, number of electrodes and material of electrodes were optimised to obtain maximum decrease in chemical oxygen demand (COD) and colour of the effluents before discharge. It was found that by controlling process parameters, COD can be reduced up to 79% and 90% for low concentrated Indigo and sulphur Stay Black dyes, respectively, with a reduction of colour value 98% and 70%, respectively, while for higher effluent concentrations EC efficiency was reported for 81% and 72.3% colour and COD removal, respectively, for indigo dye and 89.3% and 77.6% colour and COD removal, respectively, for sulphur dye. Hence results of the proposed study could provide important information to design a scale up large reactor unit to commercially apply on denim dyeing discharge and control pollution limits of sulphur and sulphates during denim dyeing. [ABSTRACT FROM AUTHOR]

The chemical senses of olfaction and taste are well developed in fish and play a vital role in its various activities such as navigation, mate recognition, and food detection. The small teleost fish Astyanax mexicanus consists of interfertile river‐dwelling and cave‐dwelling populations, referred to as "surface fish" and "cavefish" respectively. An important anatomical feature of cavefish is the lack of eyes leading them to be referred to as blind fish and suggesting an enhanced functional role for other senses such as taste. In this study, we characterize the expression of bitter taste receptors (T2Rs or Tas2Rs) in A. mexicanus and investigate their functionality in a heterologous expression system. The genome database of A. mexicanus (ensemble and NCBI) showed 7 Tas2Rs, among these Tas2R1, Tas2R3, Tas2R4, and Tas2R114 are well characterized in humans and mice but not in A. mexicanus. Therefore, the 4 Tas2Rs were selected for further analysis and their expression in A. mexicanus was confirmed by in situ hybridization and RT‐PCR in early developmental stages. These Tas2Rs are expressed in various oral and extraoral organs (liver, fins, jaws, and gills) in A. mexicanus, and Tas2R1 has maximum expression and is localized throughout the fish body. Using the heterologous expression of A. mexicanus T2Rs in HEK293T cells coupled with cell‐based calcium mobilization assays, we show that A. mexicanus T2Rs are activated by commonly used fish food and known bitter agonists, including quinine. This study provides novel insights into the extraoral expression of T2Rs in A. mexicanus and suggests their importance in extraoral food detection. [ABSTRACT FROM AUTHOR]

The performance of desalination plants predominantly depends on the enhancement of membrane productivity through the effective removal of organic foulants from saline water prior to the membrane process. This research evaluates the performance of the ZnO‐immobilized solar nanophotocatalytic process integrated with Fe2+/H2O2 system for the removal of organics from reverse osmosis (RO) feed seawater. Machine‐learning and response surface methodology (RSM) models were used for optimizing the performance of such a hybrid system in terms of five input factors: initial TOC (mg/L), pH, H2O2 dosage (g/L), Fe2+ dosage (mg/L) and solar irradiation time (minutes). Both machine‐learning and RSM regression models were optimized using nondominated sorting genetic algorithm (NSGA‐III) for estimating optimum organic degradation performance in terms of residual Fe2+, total organic carbon (TOC) removal and chemical oxygen demand (COD) removal. The response values obtained from the experimental run conducted at the optimum settings of ANN‐NSGA‐III was found to be TOC removal = 81.4%, COD removal = 77.4% and residual Fe2+ = 1.95 mg/L. The pilot‐scale solar nanophotocatalytic reactor optimized in the present research is worthy of being upscaled for wide application in desalination plants. ZnO catalyst was efficiently immobilized on borosilicate glass tubes, and the morphology was analysed using SEM. Seawater organics was effectively removed using a hybrid solar/ZnO/photo‐Fenton process. Near‐global‐optimal solution is achieved using RSM‐ANN‐NSGA‐III paradigm. [ABSTRACT FROM AUTHOR]

In Pakistan, around 58% of current electricity is generated from fossil fuels and only 2.4% is generated using renewable energy (RE) resources even though country is blessed with enormous RE potential. Among other RE resources, Pakistan's geographical location offers high solar energy potential, which implies that actual potential assessment should be undertaken. This study, as such, undertakes a comprehensive assessment of solar energy potential and prospects of solar photovoltaic (PV) systems for both off‐grid and grid‐connected systems. This study also estimates the future available capacity of rooftop and rural off‐grid solar PV capacity. Three different types of solar PV modules of the same size, that is, thin‐film, premium, and standard were modeled to compare energy outputs. NREL's System Advisor Model (SAM) is used to estimate the geographical and technical potential of solar PV considering updated data and geographical information. SAM results suggest that an average of 4.5 kWh/kWp/day is obtained from an installed capacity of 1 KWp. The logistic modeling equations are further used to forecast the solar PV penetration over a period until 2090. The research investigation concludes that 2.8 × 106 GWh of electricity can be generated annually in Pakistan. The estimated results prove that solar PV has the potential to meet the present as well as future energy needs of Pakistan. [ABSTRACT FROM AUTHOR]

Biodegradable films based on sodium alginate and aloe vera were prepared by casting technique. The resulting films were characterized by swelling behavior, scanning electron microscopy, biodegradation, as well as mechanical and barrier properties. The aloe vera gel exerted a positive influence on mechanical and physico‐chemical properties. Aloe vera gel improved the tensile strength of the films giving maximum value of 21.20 N/mm2 at 20% gel. Water vapor permeability of the composite films was reduced which made the film more effective as a moisture barrier, giving the most efficient result of 1.16 × 10−10 g m−1 s−1 Pa−1 at 50% aloe vera gel. The present study demonstrates the viability of the composite alginate aloe vera films as a biodegradable alternative to synthetic plastic films for the packaging of food materials. [ABSTRACT FROM AUTHOR]

Biopolymers like polysaccharides are being used to develop biodegradable and edible food packaging films. These films are environment friendly but have inferior mechanical strength as compared to conventional plastics. This study seeks to enhance the mechanical properties of alginate aloe vera composite films by the fusion of organic fibers like carboxymethyl cellulose (CMC) and hydroxypropyl methylcellulose (HPMC). CMC and HPMC were added at varying concentrations (2%–14%).Addition of both these cellulose derivatives had a positive effect on the tensile strength and elongation at break of the composite films. The tensile strength increased to a maximum value of 35.08 and 51.96 N/mm2 in CMC and HPMC films, respectively at 4% concentration of both. Increasing the fiber concentration further resulted in a decrease of tensile strength. Similar trend was observed in the flexibility of the films as the elongation at break value was maximum 5.57% and 3.21%, respectively at 4% concentration. The addition of CMC reduced the water solubility of the film. The solubility decreased to 19% at the maximum concentration of CMC. The effect of HPMC on water solubility was opposite to that of CMC. The solubility of the film increased to 86.42% at highest concentration of HPMC. CMC slowed down the biodegradation rate of the films whereas HPMC increased it. [ABSTRACT FROM AUTHOR]

Transition metal oxides have been the materials of interest in modern‐day science and technology. Among these materials, double perovskites have been studied very often. To explore such types of oxides and to provide a better understanding especially about lanthanum manganates, herein, the system of La2NiMnO6 is investigated, which exists in two phases, viz., monoclinic and rhombohedral via density functional theory. So far, the monoclinic phase which usually exists at low temperatures has been probed a lot; however, very little information is available about the rhombohedral phase and thus needs to be investigated. Herein, the rhombohedral phase of the material is simulated and various properties like band structure, electronic distribution of states, and absorption within the material are investigated. The study of the complex dielectric nature of the material and its refractive index with frequency variations of the incident field is also presented. The self‐interactions have been taken care‐off taking the Hubbard parameter into account. The spontaneous polarization for the first time as a berry phase using a quantum mechanical approach has also been calculated. The high dielectric constant at visible frequencies ensures the potential use of this material in the case of storage devices. [ABSTRACT FROM AUTHOR]

Detergent‐mediated virus inactivation (VI) provides a valuable orthogonal strategy for viral clearance in mammalian processes, in particular for next‐generation continuous manufacturing. Furthermore, there exists an industry‐wide need to replace the conventionally employed detergent Triton X‐100 with eco‐friendly alternatives. However, given Triton X‐100 has been the gold standard for VI due its minimal impact on protein stability and high inactivation efficacy, inactivation by other eco‐friendly detergents and its impact on protein stability is not well understood. In this study, the sugar‐based detergent commonly used in membrane protein purification, n‐dodecyl‐β‐ d‐maltoside was found to be a promising alternative for VI. We investigated a panel of detergents to compare the relative VI efficacy, impact on therapeutic quality attributes, and clearance of the VI agent and other impurities through subsequent chromatographic steps. Detergent‐mediated inactivation and protein stability showed comparable trends to low pH inactivation. Using experimental and modeling data, we found detergent‐mediated product aggregation and its kinetics to be driven by extrinsic factors such as detergent and protein concentration. Detergent‐mediated aggregation was also impacted by an initial aggregation level as well as intrinsic factors such as the protein sequence and detergent hydrophobicity, and critical micelle concentration. Knowledge gained here on factors driving product stability and VI provides valuable insight to design, standardize, and optimize conditions (concentration and duration of inactivation) for screening of detergent‐mediated VI. [ABSTRACT FROM AUTHOR]

Virus removal filtration is a critical step in the manufacture of monoclonal antibody products, providing a robust size‐based removal of both enveloped and non‐enveloped viruses. Many monoclonal antibodies show very large reductions in filtrate flux during virus filtration, with the mechanisms governing this behavior and its dependence on the properties of the virus filter and antibody remaining largely unknown. Experiments were performed using the highly asymmetric Viresolve® Pro and the relatively homogeneous Pegasus™ SV4 virus filters using a highly purified monoclonal antibody. The filtrate flux for a 4 g/L antibody solution through the Viresolve® Pro decreased by about 10‐fold when the filter was oriented with the skin side down but by more than 1000‐fold when the asymmetric filter orientation was reversed and used with the skin side up. The very large flux decline observed with the skin side up could be eliminated by placing a large pore size prefilter directly on top of the virus filter; this improvement in filtrate flux was not seen when the prefilter was used inline or as a batch prefiltration step. The increase in flux due to the prefilter was not related to the removal of large protein aggregates or to an alteration in the extent of concentration polarization. Instead, the prefilter appears to transiently disrupt reversible associations of the antibodies caused by strong intermolecular attractions. These results provide important insights into the role of membrane morphology and antibody properties on the filtrate flux during virus filtration. [ABSTRACT FROM AUTHOR]

Summary: We focus on textual analysis of the US Securities and Exchange Commission's accounting and auditing enforcement releases (AAERs). Our research question is: Did the Sarbanes–Oxley Act (SOX) 2002 affect the qualitative linguistic content of the AAERs in the post‐SOX period? To answer this question, we test the null hypotheses that there will be no differences in the qualitative verbiage and sentiment of AAERs in the time periods that we study related to the enactment of SOX: pre‐SOX and post‐SOX. To resolve the research question, we applied several text mining methods and classification machine‐learning methods. We first used two basic text‐mining methods, generating a bag of words and topic modeling, for descriptive analysis of the AAER content before the enactment of SOX and after the enforcement of SOX. We then conducted sentiment analysis using four sentiment dictionaries on the content of the two time periods: before SOX and after SOX. Finally, we developed three different classification models based on well‐known supervised learning algorithms and determined that SOX‐related AAERs could be distinguished from non‐SOX‐related AAERs. Based on the results, we conclude that there were significant linguistic differences in the AAER content of the post‐SOX period compared with the pre‐SOX period. In other words, post‐SOX‐related AAERs are qualitatively different in terms of linguistic contents and sentiment values compared with the non‐SOX‐related AAERs. [ABSTRACT FROM AUTHOR]

Solar energy is the most techno‐economically viable renewable source of energy and can be effectively converted into electrical power by Photovoltaic (PV) systems. As partial shading (PS) may reduce the harvested energy of PV systems, this paper proposes a novel tunicate swarm algorithm (TSA) based MPPT (maximum power point tracking) strategy to tackle the PS issue. More specifically, the simple and effective modeling of TSA with a search and skipping (SAS) scheme is utilized to minimize the tracking time and search area. The SAS scheme can discard the voltage range lacking global maximum power point (GMPP) and significantly reduce computation time. Consequently, power tracking, tracking time, and robustness can be greatly enhanced. The performance of the proposed TSA strategy is comprehensively analyzed against state‐of‐the‐art techniques, including incremental conductance (InC), improved particle swarm optimization (IPSO), grey wolf optimization (GWO), and cuckoo search algorithm (CSA), through detailed case studies, which include standard array configurations, PS conditions, varying irradiance patterns, fast‐changing temperature, and the field atmospheric data. TSA is further validated on a low‐cost hardware setup, confirming its superior performance. The results provide insightful validation of the practicality of the proposed TSA strategy in the real‐world applications. [ABSTRACT FROM AUTHOR]

Design, synthesis, and bioactivity evaluation of novel mannich bases (2a‐2j) and triazole‐chalcone derivatives (7a‐7k) of Eugenol 1 were reported. Among all the derivatives tested for antiproliferative activity, di‐amine manich derivative 2b (32.92 μM), and 4‐methoxy chalcone triazole derivative 7d (33.05 μM) significantly inhibited HepG2 cell lines when compared to the standard doxorubicin (37.29 μM). Whereas most of the compounds such as diethylamine 2a (17.75 μM), (aminomethyl) methane diamine 2b (17.02 μM), and bis (chloromethyl) amine 2c (20.12 μM) showed moderate to better inhibition towards MCF‐7 cell lines. The synthesized analogues were also tested for antidiabetic and antiobesity potentials. Compounds 2f (55.50%), 2c (54.34%), 7g (55.5%), and 2a (55.5%) have shown moderate inhibitory potentials toward intestinal α‐glucosidase enzyme when compared to the standard Acarbose (72.86%). Likewise, compounds 7d (82.95%), 7f (76.19%), 7g (74.81%), 7e (74.81%), and 2g (72.50%) have shown significant to moderate inhibitory potentials toward Pancreatic lipase enzyme when compared to the standard orlistat (91.10%). ROS induces life‐threatening diseases like diabetes, cancer, etc., and antioxidants play a major role in controlling their production. Compounds 2c (99.81%), 2i (99.80%), 2d (99.26%), 2g (98.79%), and 2f (98.42%) have shown significant antioxidant profiles in ABTS assay when compared to the standard Trolox (99.07%). Further, In silico Molecular docking and pharmacokinetic screening of the eugenol derivatives complemented the in vitro results indicating the drug likeness of the obtained active compounds. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus disease 2019 (COVID‐19) pandemic led to a sudden drop in renal transplant numbers across India in the initial months of 2020. Although the transplant numbers increased with easing of lockdown, the outcome of these transplants remains unknown. Methods: This was a retrospective, observational, multi‐center study done across eight different transplant centers in India. All the transplants done from January 30, 2020 to December 31, 2020 were included. The primary outcomes studied were patient and death censored graft survival as well as incidence of COVID‐19 infection and its outcomes. Results: During the study period a total of 297 kidney transplants were done. After a median follow up of 265 days the patient and death censored graft survival was 95.3% and 97.6%, respectively. Forty‐one patients (13.8%) developed COVID‐19 post‐transplant. Majority (58.5%) were asymptomatic to mildly symptomatic and the case fatality ratio was 14.6%. On multivariable logistic regression analysis older age was associated with higher likelihood of COVID‐19 infection (odds ratio 1.038; CI 1.002–1.077). Conclusions: Patient and graft outcome of kidney transplants done during the COVID‐19 pandemic in India was acceptable. The incidence of COVID‐19 was 13.8% with a high case fatality ratio. [ABSTRACT FROM AUTHOR]

Background: Doctors, despite being the public health leaders, are predisposed to the early development of chronic noncommunicable diseases (NCDs). This study was done to determine the prevalence of risk factors of NCDs among doctors. Methods: A cross-sectional study was conducted among the doctors of a course under the Distance Learning Program at BIRDEM General Hospital, Dhaka. It was done from March 2015 to February 2016. Data were collected using a self-administered questionnaire, and physical and biochemical measurements. However, the measured variables were collected by the investigators. WHO STEPS questionnaire V 3.1, with adaptation to the local context, was used. Results: A total of 404 (223 men and 181 women) of 451 registered doctors participated (89.6%) in the study. The prevalence of smoking was 18.8% among men, and there was no woman smoker. Among the respondents, 17% of men and 0.6% of women drank alcohol at least once in their lifetime. Low physical activity (<600 METmin/week) was reported by 44.4% of men and 34.3% of women. Less than a quarter of them (22.3%) consumed five or more servings of fruit and vegetables. Almost 13% had high blood pressure, and 44.8% were overweight or obese. A total of 3.2% were diabetic, and 5.9% had hypercholesterolemia. Conclusion: High prevalence of NCD risk factors among the doctors in this study highlights the need to create awareness among them. [ABSTRACT FROM AUTHOR]

Objective: The aim was to demonstrate that continuous s.c. infusion of a soluble levodopa (LD)/carbidopa (CD) phosphate prodrug combination effectively delivers stable LD exposure via a minimally invasive and convenient mode and has the potential to treat Parkinson's disease (PD) patients who are not well controlled on oral medication. Methods: Foslevodopa and foscarbidopa were prepared and the equilibrium solubility and chemical stability examined in aqueous media with different values of pH. Solutions of foslevodopa/foscarbidopa (ratios ranging from 4:1 to 20:1) were prepared by dissolving pH‐adjusted lyophilized materials in water and infused s.c. in healthy volunteers for ≤72 hours. Frequent blood samples were collected to measure LD and CD exposure, and safety was monitored throughout the study. Results: Foslevodopa/foscarbidopa (ABBV‐951) demonstrates high water solubility and excellent chemical stability near physiological pH, enabling continuous s.c. infusion therapy. After s.c. infusion, a stable LD pharmacokinetic (PK) profile was maintained for ≤72 hours, and the infusion was well tolerated. Interpretation: Preparation of foslevodopa and foscarbidopa enables preclinical and clinical PK, safety, and tolerability studies in support of their advancement for the treatment of PD. In phase 1 clinical trials, foslevodopa/foscarbidopa demonstrates consistent and stable LD plasma exposure, supporting further studies of this treatment as a potentially transformational option for those suffering from PD. ANN NEUROL 2021;90:52–61 [ABSTRACT FROM AUTHOR]

Indanocine, a potent anticancer investigational drug of National Cancer Institute‐USA, has been much discussed in recent years. Present communication aimed at total synthesis of indanocine and its close analogues. Total synthesis was improved by double yields than previously reported yields. Some of the benzylidene and 2‐benzyl derivatives with free rotation at C2 position exhibited potential cytotoxicities against various human cancer cell lines. Five such analogues exhibited potential antiproliferative effect against HCT‐116 and MIA PACA‐2 cell lines. Benzylindanocine 12i induced microtubule destabilization by occupying colchicine binding pocket of β‐tubulin. It also exhibited anti‐inflammatory activity by down‐regulating IL‐6 and TNF‐α. In Ehrlich ascites carcinoma model, 12i reduced 78.4% of EAC tumour in Swiss albino mice at 90 mg/kg (i.p.) dose. Further, in in vivo safety studies, 12i was found to be safe to rodents up to 1,000 mg/kg dose. Concomitant anticancer and anti‐inflammatory activity of benzylindanocine is distinctive, which suggests its further optimization for better efficacy and druggability. [ABSTRACT FROM AUTHOR]

Process analytical technology (PAT) is a fast‐growing field within bioprocessing that enables innovation in biological drug manufacturing. This study demonstrates novel PAT methods for monitoring multiple quality attributes simultaneously during the ultrafiltration and diafiltration (UF/DF) process operation, the final step of monoclonal antibody (mAb) purification. Size exclusion chromatography (SEC) methods were developed to measure excipients arginine, histidine, and high molecular weight (HMW) species using a liquid chromatography (LC) system with autosampler for both on‐line and at‐line PAT modes. The methods were applied in UF/DF studies for the comparison of single‐use tangential flow filtration (TFF) cassettes to standard reusable cassettes to achieve very high concentration mAb drug substance (DS) in the order of 100–200 g/L. These case studies demonstrated that single‐use TFF cassettes are a functionally equivalent, low‐cost alternative to standard reusable cassettes, and that the on‐line PAT measurement of purity and excipient concentration was comparable to orthogonal offline methods. These PAT applications using an on‐line LC system equipped with onboard sample dilution can become a platform system for monitoring of multiple attributes over a wide dynamic range, a potentially valuable tool for biological drug development and manufacturing. [ABSTRACT FROM AUTHOR]

The Ganges‐Brahmaputra‐Meghna (GBM) delta plain within Bangladesh is one of the most vulnerable to relative sea level rise (RSLR) in the world especially under current anthropogenically modified (i.e., embanked) conditions. Tidal river management (TRM) as practiced in coastal regions of Bangladesh may provide an opportunity to combat RSLR by raising the land level through controlled sedimentation inside beels (depression within embanked polders) with re‐opening of polders. To date, TRM has been applied to tide‐dominated coastal regions, but the potential applicability of TRM for the beels within the polders of river‐dominated and mixed flow (MF) regimes remains to be assessed. We apply a calibrated 2D numerical hydromorphodynamic model to quantify sediment deposition in a beel flooded through breaching of the polder dike under conditions of river‐dominated, tide‐dominated and MF regimes for different seasons and applying different regulation schemes for the flow into the beel. Simulation results show considerable seasonality in sediment deposition with largest deposition during the monsoon season. The potential of controlled flooding is highest in the tide‐dominated region, where sediment accumulation can be up to 28 times higher than in the river‐dominated region. Regulating flow into a beel increases trapping efficiency, but results in slightly lower total deposition than without regulation. We conclude that re‐establishing flooding of the beel within the polder without regulating the flow into the beel through breaching of the polder dike is a promising strategy for the mixed and tide‐dominated flow regions in the delta as the sediment accumulation can raise the land surface at a higher rate than RSLR and effective SLR (ESLR). In the more upstream river‐dominated section of the delta, accumulation rates would be much lower, but the pressure of sea level rise on these areas is lower as well. Owing to the abundant availability of sediment, application of controlled flooding like TRM therefore provides an opportunity to counteract the impact of RSLR and ESLR by means of land raising, particularly along the tidal river reaches in the GBM delta. [ABSTRACT FROM AUTHOR]

This study aims to assess the influence of various non‐starch polysaccharides at different concentrations (0.2%, 0.4%, and 0.6%) on the physicochemical, pasting, and gel properties of taro starch. Guar and xanthan gum appear to reduce the swelling power at higher temperatures while CMC improves it. Least gelation studies show that xanthan and guar gums are effective in producing firm gel at 6 and 8% of starch concentration, respectively. All hydrocolloids are found to be effective in decreasing syneresis and increase the stability of starch gel against repeated freeze−thaw (FT) cycles. The pasting properties of taro starch are greatly affected by all hydrocolloids and it is observed that guar and xanthan gums improve its peak viscosity even at the lowest concentration. The initial pasting temperature of taro starch is found to increase with gum arabic concentration while a significant decrease is noted with both guar gum and CMC which is an indication of ease in gelatinization. Xanthan and arabic gums are effective in controlling the set back of taro starch paste. The results indicate that different ratios of taro starch and hydrocolloids mixtures can play an important role as a functional additive in order to improve the quality of various processed food products. [ABSTRACT FROM AUTHOR]

A slow evaporation solution growth technique is used to grow rare earth (Eu3+ and Tb3+) doped lithium sulfate monohydrate (LSMH) single crystals. X‐ray diffraction analysis of these crystals confirms the monoclinic crystal structure with P21 space group. Energy dispersive X‐ray spectroscopy is used to check the incorporation of dopants into the crystal lattice of these LSMH crystals. Dielectric, UV–vis photoluminescence spectroscopy studies are carried out to study the electrical and optical behavior of these crystals. The optical bandgap decreases by doping and the current material follows the direct allowed transition. The dielectric constant and ac conductivity slightly increase with the incorporation of Eu3+ and Tb3+ ions in the crystal matrix. The effect of doping on the functional groups of LSMH crystals is confirmed by Fourier transform infrared spectroscopy. The micro‐Raman spectroscopic technique is carried out on these samples, confirming the stress experienced by the crystal with dopants, and further leading to the degradation of the crystal structure. The photoluminescence emission with a large decay time of the as‐grown crystals is dominated by the 5D0 → 7Fj transitions of Eu3+ and 5D4 → 7Fj transitions of Tb3+ ions, and further provides a possibility of using them as potential optical materials. [ABSTRACT FROM AUTHOR]

Aims: Few investigations have been conducted to identify genetic determinants of common, polygenetic forms of heart failure (HF), and only a limited number of these genetic associations have been validated by multiple groups. Methods and results: We performed a case–control study to further investigate the potential impact of 14 previously reported candidate genes on the risk of HF and specific HF sub‐types. We also performed an exploratory genome‐wide study. We included 799 patients with HF and 1529 controls. After adjusting for age, sex, and genetic ancestry, we found that the C allele of rs2234962 in BAG3 was associated with a decreased risk of idiopathic dilated cardiomyopathy (odds ratio 0.42, 95% confidence interval 0.25–0.68, P = 0.0005), consistent with a previous report. No association for the other primary variants or exploratory genome‐wide study was found. Conclusions: Our findings provide independent replication for the association between a common coding variant (rs2234962) in BAG3 and the risk of idiopathic dilated cardiomyopathy. [ABSTRACT FROM AUTHOR]

Technologies capable of monitoring product quality attributes and process parameters in real time are becoming popular due to the endorsement of regulatory agencies and also to support the agile development of biotherapeutic pipelines. The utility of vibrational spectroscopic techniques such as Fourier transform mid‐infrared (Mid‐IR) and multivariate data analysis (MVDA) models allows the prediction of multiple critical attributes simultaneously in real time. This study reports the use of Mid‐IR and MVDA model sensors for monitoring of multiple attributes (excipients and protein concentrations) in real time (measurement frequency of every 40 s) at ultrafiltration and diafiltration (UF/DF) unit operation of biologics manufacturing. The platform features integration of fiber optic Mid‐IR probe sensors to UF/DF set up at the bulk solution and through a flow cell at the retentate line followed by automated Mid‐IR data piping into a process monitoring software platform with pre‐loaded partial least square regression (PLS) chemometric models. Data visualization infrastructure is also built‐in to the platform so that upon automated PLS prediction of excipients and protein concentrations, the results were projected in a graphical or numerical format in real time. The Mid‐IR predicted concentrations of excipients and protein show excellent correlation with the offline measurements by traditional analytical methods. Absolute percent difference values between Mid‐IR predicted results and offline reference assay results were ≤5% across all the excipients and the protein of interest; which shows a great promise as a reliable process analytical technology tool. [ABSTRACT FROM AUTHOR]

Molecular imprinted polymers (MIPs) are tailor made from synthetic polymers and designed to mimic the recognition properties of natural biological affinity molecules. MIPs incorporate binding motifs complementary to target organic molecule shape and functional groups in order to mimic the complex binding surfaces of natural macromolecules. This confers selectivity and specificity, with the added advantage of artificial MIP polymer stability and ready adaptability to the fabrication and creation of miniaturised affinity interfaces for electrochemical sensing and extra‐laboratory testing. Their generic capability as robust sorbent phases for drug extraction and concentration allows for targeted, interfacial interrogation by the active electrochemical surface. A wide range of electrochemical sensing strategies has also been advanced in recent years, which is covered by this review. The review covers MIP functional principles, examples of MIP preparative routes and final assay outcomes for the measurement of small molecule drugs of biomedical, and also of potential environmental relevance. Some small molecules as examples of toxin and contaminant measurement are also given. A historic background to MIP development is provided, but the review mainly focuses on electrochemical sensor advances in the last five years. [ABSTRACT FROM AUTHOR]

To achieve the high protein concentrations required for subcutaneous administration of biologic therapeutics, numerous manufacturing process challenges are often encountered. From an operational perspective, high protein concentrations result in highly viscous solutions, which can cause pressure increases during ultrafiltration. This can also lead to low flux during ultrafiltration and sterile filtration, resulting in long processing times. In addition, there is a greater risk of product loss from the hold‐up volumes during filtration operations. From a formulation perspective, higher protein concentrations present the risk of higher aggregation rates as the closer proximity of the constituent species results in stronger attractive intermolecular interactions and higher frequency of self‐association events. There are also challenges in achieving pH and excipient concentration targets in the ultrafiltration/diafiltration (UF/DF) step due to volume exclusion and Donnan equilibrium effects, which are exacerbated at higher protein concentrations. This paper highlights strategies to address these challenges, including the use of viscosity‐lowering excipients, appropriate selection of UF/DF cassettes with modified membranes and/or improved flow channel design, and increased understanding of pH and excipient behavior during UF/DF. Additional considerations for high‐concentration drug substance manufacturing, such as appearance attributes, stability, and freezing and handling are also discussed. These strategies can be employed to overcome the manufacturing process challenges and streamline process development efforts for high‐concentration drug substance manufacturing. [ABSTRACT FROM AUTHOR]

Aims: In Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure (ATHENA-HF), high-dose spironolactone (100 mg daily) did not improve efficacy endpoints over usual care [placebo or continued low-dose spironolactone (25 mg daily) in patients already receiving spironolactone] in the treatment of acute heart failure (HF). We hypothesized that low concentrations of the long-acting active metabolites of spironolactone [canrenone and 7α-thiomethylspironolactone (7α-TMS)] in the high-dose group could have contributed to these neutral results.Methods and Results: In patients randomized to high-dose spironolactone not previously treated with spironolactone (high-dose-naïve, n = 112), concentrations of canrenone and 7α-TMS increased at 48 and 96 h compared to baseline, and between 48 and 96 h (all P < 0.005), indicating that steady-state concentrations had not been reached by 48 h. In patients previously on low-dose, high-dose spironolactone (high-dose-previous, n = 37), concentrations of canrenone increased at 48 and 96 h compared to baseline (both P < 0.0005), with a marginal increase between 48 and 96 h (P = 0.0507). At 48 h, both high-dose groups had higher concentrations of both metabolites than the low-dose spironolactone group (P < 0.0001). Moreover, concentrations of both metabolites were higher in high-dose-previous vs. high-dose-naïve patients (P < 0.01), indicating that previous spironolactone use was significant, and that steady-state has not been reached in high-dose-naïve patients at 48 h. We found limited and inconsistent evidence of correlation between metabolite concentrations and endpoints.Conclusions: Lower-than-anticipated concentrations of spironolactone active metabolites were observed for at least 48 h in the high-dose spironolactone group and may have contributed to the absence of pharmacological effects of spironolactone in the ATHENA-HF trial. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Under irremediable endoplasmic reticulum (ER) stress, hyperactivated inositol‐requiring enzyme 1α (IRE1α) triggers the terminal unfolded protein response (T‐UPR), causing crucial cell dysfunction and apoptosis. We hypothesized that nicotinic acetylcholine receptor (nAChR) signaling regulates IRE1α activation to protect β‐cells from the T‐UPR under ER stress. Materials and Methods: The effects of nicotine on IRE1α activation and key T‐UPR markers, thioredoxin‐interacting protein and insulin/proinsulin, were analyzed by real‐time polymerase chain reaction and western blotting in rat INS‐1 and human EndoC‐βH1 β‐cell lines. Doxycycline‐inducible IRE1α overexpression or ER stress agents were used to induce IRE1α activation. An α7 subunit‐specific nAChR agonist (PNU‐282987) and small interfering ribonucleic acid for α7 subunit‐specific nAChR were used to modulate nAChR signaling. Results: Nicotine inhibits the increase in thioredoxin‐interacting protein and the decrease in insulin 1/proinsulin expression levels induced by either forced IRE1α hyperactivation or ER stress agents. Nicotine attenuated X‐box‐binding protein‐1 messenger ribonucleic acid site‐specific splicing and IRE1α autophosphorylation induced by ER stress. Furthermore, PNU‐282987 attenuated T‐UPR induction by either forced IRE1α activation or ER stress agents. The effects of nicotine on attenuating thioredoxin‐interacting protein and preserving insulin 1 expression levels were attenuated by pharmacological and genetic inhibition of α7 nAChR. Finally, nicotine suppressed apoptosis induced by either forced IRE1α activation or ER stress agents. Conclusions: Our findings suggest that nAChR signaling regulates IRE1α activation to protect β‐cells from the T‐UPR and apoptosis under ER stress partly through α7 nAChR. Targeting nAChR signaling to inhibit the T‐UPR cascade may therefore hold therapeutic promise by thwarting β‐cell death in diabetes. [ABSTRACT FROM AUTHOR]

Bi NPs supported Metal‐Organic Framework MIL‐53(Fe) was developed by hydrothermal method. The as synthesized catalyst exhibits efficient visible light response towards the removal of organic pollutants. Studies based on the changing ratios of "Bi" NPs were also investigated and optimized. The samples were characterized by XRD, SEM, EDX, TEM and DRS. Among the synthesized photocatalysts ternary Bi/Bi2WO6/MIL‐53 heterojunction exhibits the best catalytic response towards the degradation of Rhodamine B. The superior photocatalytic response of ternary phase is attributed to the Plasmonic resonance effect of Bi NPs and the synergism between the MIL‐53 and Bi2WO6. Moreover, the photocatalyst also shows excellent stability after cyclic runs. The scavenging experiments reveal that the.−O2 and h+ are the main species involved in the photocatalytic oxidation and reduction process. Based on these results mechanism with involvement of Plasmonic effect was proposed. [ABSTRACT FROM AUTHOR]

Continuous health monitoring for an infant is crucial for detecting and preventing several diseases. Recent advancement in wearable technology has given rise to the development of wearable infant health monitoring systems (WIHMSs). These systems provide an edge over conventional infant health monitoring systems which are not only bulky and uncomfortable for the infants but are also limited to the clinical settings. This study reviews some state‐of‐the‐art WIHMS, mentions the advantages, limitations and the challenges faced by such systems. This study, for the first time, contributes an appraisal of research prototypes and commercially available systems for WIHMS, which is the need of the day. [ABSTRACT FROM AUTHOR]

Prostate cancer is fourth most abundant cancer type around the globe. Brevifoliol, a rearranged taxoid from Taxus walllichiana needles has been derivatized as C5 esters using Steglich esterification reaction. Seventeen diverse analogues were evaluated against a panel of human cancer cell lines by MTT assay. Among these, two of the semi‐synthetic analogues, that is, 13 and 16 exhibited potent cytotoxicity, selectively against PC‐3, prostate cancer cell lines. In cell cycle analysis, analogue 13 induced S and G2/M phase arrest and induced apoptosis by activating caspase‐3. Compound 13 showed moderate efficacy in in‐vivo Ehrlich ascites carcinoma in Swiss albino mice. Further, compound 13 was found to be safe in Swiss albino mice up to 1,000 mg/kg dose in acute oral toxicity. Brevifoliol ester 13 may further be optimized for better efficacy. [ABSTRACT FROM AUTHOR]