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• Pure, Cu2+doped CdS-Zn 3 (PO 4) 2 composites are prepared by hydrothermal route. • XRD pattern exhibit both hexagonal phase of CdS, monoclinic β-phase Zn 3 (PO 4) 2. • With effect of Cu2+, SEM images show hexagonal spheres on rectangular flakes. • At higher Cu2+doping concentration there is a small increase in the band gap. • PL spectra show red shifting and strong luminescence in UV-Visible region. Pure and CuO (0.3, 0.6 and 0.9 mol%) doped CdS-Zn 3 (PO 4) 2 semiconducting nanophosphors were synthesized by hydrothermal technique under mild reaction temperatures. The prepared samples were systematically investigated by Powder X-ray diffraction [XRD], Fourier Transform infra-red spectroscopy [FT-IR], Scanning electron microscopy [SEM] with EDAX, UV–Vis diffuse reflectance spectrometer [DRS] and Photoluminescence [PL] techniques. X-ray diffraction pattern shows hexagonal phase of CdS and monoclinic β-phase of Zn 3 (PO 4) 2 with good crystalline nature. The average crystallite size of nanocomposites are in the range 13 to 25 nm and found to decrease from 18 nm to 13 nm with increasing dopant concentration. FT-IR spectra indicate that the prepared samples are high in purity. The surface morphology of the samples has shown a hetero structure type morphology in which hexagonal CdS spheres network bonding accumulated on rectangular flakes. The obtained chemical composition of all the samples are identified by EDAX is in agreement with the calculated stoichiometry. The optical band gap values are determined by diffuse reflectance spectra and are found to be in the range 2.49 eV to 2.39 eV. The room temperature Photoluminescence spectra of pure CdS-Zn 3 (PO 4) 2 lattice shown a broad strong green emission peak at ~ 518 nm, while upon incorporation CuO ions in host lattice, a sharp luminescence peak around 393 nm has been observed in all the doped samples along with other peaks at 494 nm, 594 nm, 684 nm which are in the violet, blue-green-red fluorescence of UV-Visible region makes them suitable for optoelectronic device applications. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Here we report the development of unprecedented silver-catalyzed intramolecular annulations of N -acrolyl-2-(3-indolyl) benzimidazoles with alkyl carboxylic acids to construct complex fused-pentacyclic alkaloid scaffolds. Divergent reactivities are noticed with altered groups at C2-indole of the substrate. The reaction proceeds through decarboxylative alkylation, followed by dearomative annulation in a domino manner with excellent diastereoselectivity. Owing to the reactivity of the tert -OH group, these aza-enriched scaffolds can be further functionalized.

Food fortification with micronutrients is one of the cost-effective and sustainable methods to prevent micronutrient deficiencies at community level. The rice fortified with iron, folic acid, and vitamin B12 is being supplied through various social welfare schemes in India in a phased manner and planned to cover the entire country by March 2024. We have conducted a situational analysis to assess the rollout of fortified rice supplied through the Public Distribution System (PDS) and to evaluate the accessibility, availability, acceptability, and utilization of fortified rice by the beneficiaries of the PDS. This was a mixed-method, sequential exploratory study conducted in six districts from six different states of India that had begun distribution of fortified rice through PDS in pilot mode during 2020-2021. In each district, the district supply officer of the PDS, Food Corporation of India (FCI) or State Food Corporation (SFC) warehouse supervisor, and four Fair Price Shop (FPS) dealers were interviewed. Under each FPS, a minimum of seven beneficiary households were randomly selected and interviewed using a structured questionnaire. The in-depth interviews were conducted with different stakeholders using theme guides. All the interviewed stakeholders were aware about their roles and responsibilities and purpose to distribute fortified rice. There was a continuous supply of fortified rice (across all visited districts) to beneficiaries through a well-established system. Acceptability and compliance to intake of fortified rice was good with no reported gastrointestinal adverse outcomes following fortified rice intake. There was an efficient roll-out of fortified rice though PDS with a good compliance to intake of fortified rice. It is feasible to design and conduct a study to assess the impact of fortified rice on anemia and iron storage at the community level., Competing Interests: The authors have declared that no competing interest exist., (Copyright: © 2024 Nandeep et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Caffeic acid phenethyl ester (CAPE) is a phenolic natural product with a wide range of biological activities, including anticancer activity; however, the ester group of CAPE is metabolically labile. The corresponding amide, CAPA, has improved metabolic stability but limited anticancer activity relative to CAPE. We report the synthesis using flow and on-water Wittig reaction approaches of five previously reported and five novel CAPA analogues. All of these analogues lack the reactive catechol functionality of CAPA and CAPE. Cytotoxicity studies of CAPE, CAPA, and these CAPA analogues in HeLa and BE(2)-C cells were carried out. Surprisingly, we found that CAPA is cytotoxic against the neuroblastoma BE(2)-C cell line (IC 50 = 12 µM), in contrast to the weak activity of CAPA against HeLa cells (IC 50 = 112 µM), and the literature reports of the absence of activity for CAPA against a variety of other cancer cell lines. One novel CAPA analogue, 3f , was identified as having cytotoxic activity similar to CAPE in HeLa cells (IC 50 = 63 µM for 3f vs. 32 µM for CAPE), albeit with lower activity against BE(2)-C cells (IC 50 = 91 µM) than CAPA. A different CAPA analogue, 3g , was found to have similar effects against BE(2)-C cells (IC 50 = 92 µM). These results show that CAPA is uniquely active against neuroblastoma cells and that specific CAPA analogues that are predicted to be more metabolically stable than CAPE can reproduce CAPA's activity against neuroblastoma cells and CAPE's activity against HeLa cells.

The first sequential acid-catalyzed propargylation/base-mediated aza -cycloisomerization between indolyl-benzimidazoles and propargylic alcohols is described. This protocol enables the one-pot construction of N -fused benzimidazo-β-carbolines in good yields. The synthetic utility of this approach is demonstrated by the assembly of an aza -helicene and also by a gram-scale reaction.

A metal-free oxidative intramolecular dearomative spirocyclization of indole-3-formyl-2-carboxamides has been developed for the first time, affording spiropseudoindoxyls in good yields. This domino process proceeds through sequential oxidation, decarboxylation and ipso -arylation. The unique feature of this approach includes the compatibility of N -protected-indole-2-carboxamides. Further, a hitherto unknown rearrangement of spiropseudoindoxyls to indoloquinolones has been achieved. The synthetic utility of this strategy has also been showcased by the construction of a natural alkaloid, isocryptolepine.

Cancer is a major global health concern, and the constant search for novel, selective anticancer compounds with low toxicity is never ending. Nitrogen heterocyclic compounds such as pyrimidine and triazole have been identified as potential candidates for cancer treatment. A novel series of 1,2,3-triazole incorporated thiazole-pyrimidine-isoxazole derivatives 10 (a-j ) were designed, synthesized and evaluated for antitumorigenic activities against human breast cancer (MCF-7), human lung cancer (A549) and human prostate (PC3 & DU-145) various cell-lines by employing MTT assay using etoposide as the positive control. The synthesized hybrids yielded decent efficacy, which was further compared with the standard drug. Among all the molecules, 10h revealed the more potent anticancerous activities, having IC 50 values ranging from 0.011 ± 0.0017 µM; 0.063 ± 0.0012 µM; 0.017 ± 0.0094 µM and 0.66 ± 0.072 µM with DU145 , PC3 , A549 , and MCF7 cell-lines, respectively. Tubulin, being a major protein involved with diverse biological actions, also serves, as a crucial target for several clinically practiced anticancer drugs, was utilized for docking analyses to evaluate the binding affinity of ligands. Docking results demonstrates that the selected hybrids 10 (g-j) exhibited good binding affinities with protein. Subsequently, drug likeness studies were carried out on the synthesized compounds to evaluate and analyze their drug like properties such as absorption, distribution, metabolism, excretion, and toxicity (ADMET) for toxicity prediction. Based on these analyses, the selected complexes were further employed for molecular dynamic simulations to analyze stability via an exhaustive cumulative 200 nanoseconds simulation. These results suggest that the selected compounds are stable and might serve as potential inhibitors to tubulin complex. In conclusion, we propose these synthesized compounds 10 (g-j) might provide new insights into cancer treatment and have potential for future development.Communicated by Ramaswamy H. Sarma.

Till date, the ipso -cyclization of propiolamides is limited to provide azaspiro[4,5]decatrienones. Herein, we present the first example of ipso -carbocyclization, leading to azaspiro[5,5]-undecatrienones from N -propiolyl-2-arylbenzimidazoles, involving both the radical-based and electrophilic reactions. This report establishes an access to a wide range of chalcogenated (SCN/SCF 3 /SePh) benzimidazo-fused azaspiro[5,5]undecatrienones in good yields.

The regulatory Indian environment for advertising high fat, salt, and sugar (HFSS) foods and non-alcoholic beverages, on various media was reviewed. Identified national-level policies were categorised as mandatory or self-regulatory based on legal content. For each mandatory regulation, Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis was undertaken to determine how existing policies could be strengthened to safeguard children from unhealthy food advertisements. Thirteen policies (nine mandatory; four self-regulatory) relevant to advertising in India were identified. Of the nine mandatory policies, Guidelines for Prevention of Misleading Advertisements and Endorsements for Misleading Advertisements, 2022, is the only policy that restricts HFSS food advertisements to children across all media. There are key shortfalls, including limited scope of 'child-targeted' advertisements and lack of criteria to define HFSS foods. A robust regulatory framework is needed to protect children from HFSS food marketing, not just what is 'directed' at them, with clear evidence-based food classification criteria., Competing Interests: None., (© 2023 The Author(s).)

Tobacco etch virus Protease (TEVp), a cysteine protease, is renowned for its remarkable specific proteolysis, making it an invaluable tool for removing fusion tags from recombinant proteins. However, TEV protease's inherent insolubility limits its broad application. Fusion constructs like an N-terminal MBP fusion, known for its improved solubility, have been employed for TEVp production to address this issue. In this study, we fused the TEVp with the N-terminal domain of the spider silk protein, specifically utilizing a charge-reversed mutant (D40K/K65D) of the N-terminal domain of major ampullate spidroin-1 protein from Euprosthenops australis , referred to as NT*. This fusion construct contains a TEVp cleavage site, enabling intracellular self-processing and the release of a His 7 -tagged protease. The significant increase in soluble protein expression allowed us to purify approximately 90-100 mg of TEVp from a 1-L E. coli culture, surpassing previous findings by a considerable margin. The enzyme remained stable and catalytically active even after several months of storage in a deep freezer (-80 °C)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

(1) Information Technology (IT) Business Process Outsourcing (BPO), the largest employment sector of India, contributes to rapid economic growth. However, the work of IT employees is sedentary, and the food environments of their worksites expose them to an obesogenic environment. This study aimed to assess their metabolic and lifestyle risk factors. (2) Methods: To examine the health and nutrition status of IT employees, anthropometric, biochemical and clinical assessments were conducted among 183 employees from three IT organizations of varied operational sizes. Their health-, diet- and physical activity-related practices were assessed using a questionnaire. The prevalence of MetS was assessed. Selected biomarker levels were assessed and associated with their self-perceived stress levels. (3) Results: The median age of the employees was 30 years (26-35 years). While 44.02% of employees were overweight, 16.85% of employees were obese. About 3.89% of employees were found to be diabetic, and HDL-C levels were lower than recommended in 64.93% of employees. In all, 29.87% of the study population were considered to have metabolic syndrome since they had metabolic risk scores ≥ 3. Those with metabolic syndrome were significantly older ( p = 0.000), and levels of MDA ( p = 0.003), homocysteine ( p = 0.001), IL-6 ( p = 0.017) and IL-4 ( p = 0.000) were significantly higher among them. Although the prevalence of MetS was significantly lower among those aged >30 years, the lifestyle risk factors were significantly higher among them. (4) Conclusions: The assessed parameters indicate a high risk of developing NCDs among employees in the IT industry in India. This shows the need for the modification of lifestyle and workplace food and physical activity environments.

Cytosolic innate immune sensing is critical for protecting barrier tissues. NOD1 and NOD2 are cytosolic sensors of small peptidoglycan fragments (muropeptides) derived from the bacterial cell wall. These muropeptides enter cells, especially epithelial cells, through unclear mechanisms. We previously implicated SLC46 transporters in muropeptide transport in Drosophila immunity. Here, we focused on Slc46a2, which was highly expressed in mammalian epidermal keratinocytes, and showed that it was critical for the delivery of diaminopimelic acid (DAP)-muropeptides and activation of NOD1 in keratinocytes, whereas the related transporter Slc46a3 was critical for delivering the NOD2 ligand MDP to keratinocytes. In a mouse model, Slc46a2 and Nod1 deficiency strongly suppressed psoriatic inflammation, whereas methotrexate, a commonly used psoriasis therapeutic, inhibited Slc46a2-dependent transport of DAP-muropeptides. Collectively, these studies define SLC46A2 as a transporter of NOD1-activating muropeptides, with critical roles in the skin barrier, and identify this transporter as an important target for anti-inflammatory intervention., Competing Interests: Declaration of interests A provisional patent on targeting SLC46s to inhibit inflammation in psoriasis and other auto-inflammatory diseases has been filed by some of the authors (N.S., R.B., and M.H.O.). T.-D.K. consults for Pfizer., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: In India, where agriculture is the prime occupation among the rural population, farmers are extensively using pesticides in crop production without taking adequate precautions., Objective: The current study aimed to examine pesticide usage patterns, usage of personal protective equipment (PPE), knowledge on pesticide toxicity, and attitude towards occupational safety among farmers diagnosed with leukaemia (n = 60), lymphoma (n = 33), and breast cancer (n = 30) visiting a tertiary cancer care hospital in Hyderabad, India., Methods: Face-to-face interviews were conducted using a pre-tested questionnaire and the data collected were analysed with statistical software SPSS 23., Results: The survey revealed that the participants had an average of 19.6 years of farming experience and women were predominantly involved in the mixing of pesticides and other agricultural work apart from spraying. All of them were not using any PPE and the majority of them did not have any knowledge on the route of exposure, toxicity symbols, and safe handling of pesticides. Statistical analysis showed no significant association between educational status and knowledge, attitude and practices (p > 0.05)., Conclusion: Even though the majority of the farmers were educated, their lack of adequate knowledge on pesticides had enabled them to adopt risky behaviours in handling and storage of pesticides. There is a need for continuous training programs for farmers to promote awareness and minimize the hazards of occupational exposure.

The uprise of digital media has bypassed the language and cultural barriers of communicating about food with peers. Sharing exaggeratively glamourized food visuals with fancy hashtags and folksonomy, generally termed as Foodporn, is "trendy". Exposure to Foodporn affects food choices, directly or indirectly, through psychological, physiological and psychosocial means. Though unhealthy connotation is often attributed to foodporn, this perspective article implores that the plausible potential to alluring food pictures to prompt healthy food choices, be explored. Can foodporn be effectively used for e-priming (electronically priming) healthy food choices by glamourizing and idealizing healthy foods?, (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

An efficient and straightforward synthesis of diversified seleno-azaspiro-2,5-cyclohexadienones from N -(4-methoxy aryl)propiolamides using elemental selenium and boronic acids has been demonstrated. The reaction proceeds through silver-catalyzed oxidative dearomatization in the presence of potassium persulfate (K 2 S 2 O 8 ) as the oxidant. Further, this approach was extended to N -(4-methoxy aryl)propiolates and biaryl ynones to access the corresponding selenylated oxospiro-2,5-cyclohexadienones and spiro[5,5]trienones, respectively. The present three-component method offers the diverse substitutions on selenium involving two C-Se and one C-C bond formations., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Advances in the medical field and healthcare sector during the last few decades have resulted in increased longevity. Increased lifespans have in turn led to a rapid global rise of the elderly population. However, ensuring the health and quality of life, especially in the context of chronic age-related ailments, among the growing geriatric population is a challenge. Ageing is associated with several changes in body composition including a decline in the lean body mass usually accompanied by an increase in body fat content which have a bearing on the nutrient requirements for the elderly. The nutrient requirements currently recommended for Indian adults are primarily computed using a factorial approach, that considers the cumulative loss of nutrients and is adjusted for optimal body weights and bioavailability. It is logical that physiological and metabolic changes associated with ageing influence several of these factors: body weight, lean mass, energy expenditure, nutrient retention and bioavailability and thus alter nutrient requirements compared to the adult population. Acknowledging these age-related changes, some international organizations have suggested nutrient requirements specific to the elderly. Given the contextual differences in physiology, caution needs to be exercised in adopting these guidelines for the Indian elderly. In addition, in the Indian context, there is sparse information on the diet and nutrient intakes vis-à -vis nutritional status and physiology of the elderly. This status paper highlights some of the pertinent issues related to nutritional requirements for the elderly that advocate a need for deriving nutritional requirements for the elderly in India.

Objective: To develop a context-specific methodology to assess the 5 A's of food environment: availability, accessibility, affordability, acceptability, and accommodation., Design: Cross-sectional mixed-methods study. Availability of foods was assessed by on-site observation and interviewing vendors. To assess accessibility, buffer zones around food stores were created using geographic information systems. Affordability was controlled by selecting participants from the middle-income group. Accommodation and acceptability were assessed by interviewing vendors and caregivers., Setting: Villages of Ghatkesar subdistrict (n = 4), Telangana, South India., Participants: Caregivers of children aged 6-10 years (n = 160) and food vendors (n = 68)., Analysis: The quality of the 5 A's was graded on the basis of concurrence between actual and perceived measures., Results: The actual and perceived 5 A's for semiperishable foods matched, and hence the food environment was graded as good across the villages. However, for perishable foods, the food environment was graded as poor with respect to accommodation and acceptability in all villages; and with respect to availability and affordability in at least 2 villages as the actual and perceived measures did not match., Conclusions and Implications: This study demonstrated the use of context-specific methods to assess the 5 key dimensions of the food environment, which can be attempted in other contexts with suitable modifications., (Copyright © 2022 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

The uncontrolled spread of (mis)information, news and propaganda related to COVID 19 created an 'infodemic' leading to panic and unscientific practices among the mass. With the largest number of internet users in the world, India has witnessed a steep rise in the number of people seeking information on social media related to COVID-19, which reached a staggering 22.3 million by March, 2020. This study aimed to evaluate the trend of COVID-19 associated food and nutrition news search by Indian internet users between 27th January 2020 to 30th June 2021 (time period between the first detected COVID-19 case and the end of the second wave in India) and its impact on their perceptions and practices. The association between the change in Relative Search Volume (RSV) on Google Trends (GT) of 34 popularly searched keywords classified by the researchers under 5 different categories-"Immunity", "Eating behavior", "Food safety", "Food scares and concerns" and "Covid scare" showed a steep rise in search for immunity boosters, vitamin supplement brands "ayush kadha (ayurvedic decoction) during the first wave (April- August 2020). With a brief period of decline in the search trend, it again hiked correspondingly with the growing number of positive cases during the second wave in India. An online survey conducted on adult Indian internet users (n = 572) reported high (71.9%) consumption of Vitamin C rich fruits as well as Vitamin C (68.2%) and Zinc (61.4%) supplements to boost immunity. Traditional Indian spices like ginger and garlic were used by 62.9% and 50.9% respondents respectively. Most respondents reported to rely on social media for gathering COVID-19 associated tips for boosting immunity, however those with history of COVID-19 infection reported to rely more on doctors and health professionals for information. This study highlights the need of media and health literacy to advocate for the use of health information cautiously., Competing Interests: No Authors have competing interests.

Background: Bevacizumab (BEV) is a recombinant humanized monoclonal immunoglobulin G1 antibody that binds to vascular endothelial growth factor (VEGF)-A and acts as an antiangiogenic agent. It is approved for treatment of many cancer indications, including metastatic colorectal cancer and nonsquamous non-small cell lung cancer., Research Design and Methods: The analytical similarity of the BEV biosimilar MYL-1402O to reference BEV sourced from the European Union and United States was assessed using physicochemical and functional tests to support the clinical development of MYL-1402O. Assessment of physicochemical and analytical similarity showed that MYL-1402O has the same amino acid sequence and similar posttranslational modification profile as the reference BEV products., Results: The functional and biologic activity of MYL-1402O assessed using inhibition of VEGF-induced cell proliferation in human umbilical vein endothelial cells, inhibition of VEGF-induced VEGF receptor 2 phosphorylation, and fragment antigen and fragment crystallizable receptor binding, was comparable to reference BEV products., Conclusions: The totality of the data assessment confirms the high degree of similarity of MYL-1402O to reference BEV with respect to physicochemical and in vitro functional properties. The product quality data presented here, along with data from phase 1 clinical studies, demonstrate the similarity of MYL-1402O to reference BEV products, supporting further clinical development of this BEV biosimilar.

Background: MYL-1401O; trastuzumab-dkst (Ogivri™; Mylan Inc.) is a biosimilar to the trastuzumab reference product (Herceptin®; Genentech, USA). Assessment of physicochemical stability and biological activity for the non-reconstituted, reconstituted, and infused solution over an extended, clinically relevant duration is critical for ensuring optimal patient outcomes and health resource utilization., Methods: The physicochemical and biological stability of MYL-1401O was assessed in non-reconstituted vials stored at 25 °C ± 2 °C/60% ± 5% relative humidity (RH) for 6 months, reconstituted 21 mg/mL solution in vials stored at 2 °C to 8 °C for 10 days, and diluted in 0.9% saline-containing infusion bags at 0.3 mg/mL and 4.0 mg/mL stored for 77 days at 2 °C to 8 °C, plus an additional 2 days at 25 °C ± 2 °C/60% ± 5% RH., Results: At all storage conditions tested, MYL-1401O was physicochemically and biologically stable for extended duration and under various temperature and humidity conditions., Conclusions: MYL-1401O retained its physicochemical and biological stability under different storage conditions, which supports advanced preparation of MYL-1401O, better efficiency, less wastage, and cost-savings for better patient management.

Background: The work style of employees engaged in the Information Technology (IT) and Business Process Outsourcing (BPO) sectors in India is dominantly sedentary exposing them to detrimental obesogenic environments with unhealthy diets, increasing the risk of non-communicable diseases (NCDs). Workplace health interventions have been reported to have the potential of reducing NCDs and related risk factors among the employees and thus reduce cost of absenteeism and improve productivity., Objective: This formative research study aims to explore the opportunities and barriers of the development and implementation of a Workplace Health Programme (WHP)., Methods: In this study, a mixed method including qualitative and quantitative approaches were used. Focus group discussions (FGDs) were conducted with employees and senior managers in employers of IT/BPO companies of different sizes in Hyderabad, India. The food and physical activity environment in the workplaces were explored using a checklist and ground truthing approach. A knowledge, attitudes and practices (KAP) questionnaire was developed to assess health, nutrition and physical activity of the employees., Results: Through this formative research, the required areas for nutrition, physical activity and health education were identified. The scope of utilising existing facilities for physical activity and modifying the food environment was explored. We noted optimistic bias among the junior employees who did not consider themselves at risk of developing NCDs., Conclusions: The identified opportunities and barriers will help in developing strategic WHPs suitable to individual workplaces. The qualitative methods, ground truthing approach, checklist and KAP tools used here can assess the company environment and employee health and nutrition status.

Highly regio- and stereoselective palladium-catalyzed ortho -vinylation of β-naphthols (2) has been reported using easily accessible CF 3 -allyl carbonates (1). The regioselective nucleophilic γ-attack of the CF 3 -π-allyl-Pd-intermediate is the key to furnish ( Z )-CF 3 -vinylnaphthols (3) in good yields. Furthermore, we achieved a one-pot synthesis of CF 3 -naphtho[2,1- b ]furans (4) through an uninterrupted ortho -vinylation/oxidative radical cyclization reaction sequence.

Aims: Preclinical comparative similarity studies of trastuzumab-dkst, a Herceptin ® biosimilar, are reported. Materials & methods: Primary sequence and higher order structure and pharmacological mechanisms of action were compared using multiple techniques. Pharmacokinetics and repeat-dose toxicity were assessed in cynomolgus monkeys. Results: Primary structures were identical; secondary and tertiary structures were highly similar. Non-significant differences were observed for charge heterogeneity. Twelve of 13 glycan species were highly similar, with slightly higher total mannose levels in trastuzumab-dkst. FcγR and FcRn binding activity was highly similar. Each drug equally inhibited HER2 +  cell proliferation, demonstrating equivalent relative potency in mediating HER2 + cell cytolysis by antibody-dependent cellular cytotoxicity. Pharmacokinetic and toxicological profiles in cynomolgus monkeys were similar. Conclusion: Trastuzumab-dkst, US-licensed trastuzumab and EU-approved trastuzumab demonstrate high structural and functional similarity.

Sequence variants (SV) in protein bio therapeutics can be categorized as unwanted impurities and may raise serious concerns in efficacy and safety of the product. Early detection of specific sequence modifications, that can result in altered physicochemical and or biological properties, is therefore desirable in product manufacturing. Because of their low abundance, and finite resolving power of conventional analytical techniques, they are often overlooked in early drug development. Here, we present a case study where trace amount of a sequence variant is identified in a monoclonal antibody (mAb) based therapeutic protein by LC-MS/MS and the structural and functional features of the SV containing mAb is assessed using appropriate analytical techniques. Further, a very sensitive selected reaction monitoring (SRM) technique is developed to quantify the SV which revealed both prominent and inconspicuous nature of the variant in process chromatography. We present the extensive characterization of a sequence variant in protein biopharmaceutical and first report on control of sequence variants to < 0.05% in final drug product by utilizing SRM based mass spectrometry method during the purification steps.

A domino propargylation/furanylation (intramolecular exo - dig -cyclization)/benzannulation reaction of 2,4-diyn-1-ols with 1,3-dicarbonyl compounds has been developed for the first time. This provides a novel and effective method for the preparation of aryl/heteroaryl-fused benzofurans from easily accessible starting materials in a single step. The methodology was extended to pyrrolyl-benzannulation to obtain aryl/heteroaryl-fused indoles. Further, application of this approach in the synthesis of eustifoline D and dictyodendrin structural frameworks has been demonstrated.

Arylative annulation of 2-carbonyl-3-propargyl indoles with boronic acids under sequential palladium/triflic acid catalysis is described. The present strategy to provide di- and triaryl carbazoles in one pot involves benzannulation through difunctionalization of alkynes. The strategy showed a good substrate scope with respect to boronic acids as well as 2-carbonyl-3-propargyl indoles to afford the corresponding carbazoles in decent yields.

A strategy to functionalized spiro[4.5]trienones, by domino silver-catalyzed decarboxylative acylation or alkylation/ ipso -cyclization of N -arylpropiolamides with α-keto acids/alkyl carboxylic acids, is presented. This transformation offers a wide range of substituted 3-acyl/alkyl-spiro[4.5]trienones in high yields with a broad substrate scope. The approach was further extended to access fused tricyclic frameworks, 6,7-dihydro-3 H -pyrrolo[2,1- j ]quinoline-3,9(5 H )-diones.

Adolescence is a transitional phase of development with the risk of adopting unhealthy behaviours, which is carried on to adulthood. Adolescent athletes tend to resort to unhealthy eating habits resulting in eating disorders and other clinical outcomes. Hence, it forms a crucial age to understand modifiable food habits and provide appropriate counselling. In India, coaches closely monitor the adolescent athletes, even concerning their eating habits due to the lack of multi-disciplinary support staff. Thus, our study aimed to understand the perceptions of coaches towards food, appetite and nutrition of adolescent athletes using In-depth interviews (IDI). Of all 14 coaches at the state-sponsored residential sports centre, 10 consented. The IDI were conducted in a standardized manner and were recorded and transcribed. They were coded manually, using the open and axial coding in the grounded theory approach to determine themes. They considered nutrition as key to performance and consumption of higher animal protein as important. Majority of them considered sprouts, dry fruits, fruits and vegetables as healthy foods, though were unable to define the quantities nor nutrients therein. Coaches considered protein as "important", while fat as "unhealthy". They also observed that athletes were avoiding fruits and vegetables, while consuming more rice. Meal timing, fluid and supplement intake were considered essential for international performance, albeit unaware of the specific requirements. Hygiene practices and peer isolation were considered to affect food intake. This lacunae in the nutrition knowledge and the modifiable nutrition practices explored can be targeted by developing a nutrition education and assessment tool for coaches and junior athletes. Further, a long-term engagement of a nutritionist with every sports academy in India is recommended., (© 2020 Published by Elsevier Ltd.)

A novel strategy for the synthesis of 3-hydroxycarbazoles involving the consecutive propargylation/palladium-catalyzed hydroxylative benzannulation of indole-2-carbonyls with propargylic alcohols has been exploited. This one-pot procedure leads to a wide range of substituted 3-hydroxycarbazoles in high yield with a broad substrate scope. The method was further extended to access furano-carbazole derivatives from dialkynols via tandem annulations.