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Post-traumatic hemorrhage, which can result from accidents or battlefield injuries, is a significant global concern due to the high prehospital mortality rate. Substantial efforts have been made to develop hemostatic agents that can effectively reduce hemorrhage in the immediate aftermath of a traumatic event. The present study investigated the potential efficacy of Ca 2+ and Zn 2+ supplemented sodium alginate-based dry hemostatic particles (SA-CZ DHP) to manage excessive blood loss or post-traumatic hemorrhage. SA-CZ DHP were developed, followed by their physical and biochemical characterization, cytocompatibility and hemocompatibility testing, and critical evaluation of the hemostatic potential in vitro and in vivo . The safe SA-CZ DHP showed high absorption and accelerated blood clotting kinetics with reduced coagulation time (≈70%, p < 0.0001) in whole human blood, observed with insignificant hemolysis and uninterrupted RBC morphology. SA-CZ DHP significantly reduced the mean blood loss (≈90% in SD rats tail incision), and bleeding time (≈60% in BALB/c mice tail incision) was at par with commercially available Celox hemostatic granules. In conclusion, the biocompatible SA-CZ DHP exhibited rapid and effective management of excessive blood loss. It is also pertinent to note that the developed formulation could be a cost-effective alternative to its commercial counterparts.

Numerous toxic substances are directly and indirectly discharged by humans into water bodies, causing distress to the organisms living on it. 6PPD, an amino antioxidant from tires reacts with ozone to form 6PPD-Q, which has garnered global attention due to its lethal nature to various organisms. This review aims to provide an understanding of the sources, transformation, and fate of 6PPD-Q in water and the current knowledge on its effects on aquatic organisms. Furthermore, we discuss research gaps pertaining to the mechanisms by which 6PPD-Q acts within fish bodies. Previous studies have demonstrated the ubiquitous presence of 6PPD-Q in the environment, including air, water, and soil. Moreover, this compound has shown high lethality to certain fish species while not affecting others. Toxicological studies have revealed its impact on the nervous system, intestinal barrier function, cardiac function, equilibrium loss, and oxidative stress in various fish species. Additionally, exposure to 6PPD-Q has led to organ injury, lipid accumulation, and cytokine production in C. elegans and mice. Despite studies elucidating the lethal dose and effects of 6PPD-Q in fish species, the underlying mechanisms behind these symptoms remain unclear. Future studies should prioritize investigating the mechanisms underlying the lethality of 6PPD-Q in fish species to gain a better understanding of its potential effects on different organisms., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This proposed work reports the development of in-house made conductive ink-based screen-printed electrodes (SPEs) for label-free detection of oral cancer biomarkers. Carbon ink synthesis includes graphite powder, gum arabic, and water. The selectivity test of the fabricated SPE involves immobilizing antibodies specific to biomarkers and challenges with redox-active interference, other serum molecules, and non-target biomarkers. Three different biomarkers, cytokeratin-19 fragment (CYFRA 21-1), interleukin 8 (IL-8), and tumor protein p53 (TP-53), act as target entities for the detection of oral cancer in patients' samples (serum, N = 28, and saliva, N = 16) at an early stage. The standard technique enzyme-linked immunosorbent assay (ELISA) was employed to estimate the concentration of the biomarkers in serum and saliva samples. SPEs contain amine (-NH 2 ) functional groups involved in covalent bonding with the carboxyl (-COOH) groups of antibody molecules. These immunosensors exhibited remarkably lower detection limits of 829.5 pg mL -1 , 0.543 pg mL -1 , and 1.165 pg mL -1 , and excellent sensitivity of 0.935 μA mL pg -1 cm -1 , 0.039 μA mL pg -1 cm -1 , and 0.008 μA mL pg -1 cm -1 for CYFRA 21-1, IL-8, and TP-53 biomarkers, respectively. This sensing platform does not require any functionalization for biomolecule immobilization. Thus, it is a cost-effective, disposable, flexible, miniaturized, and sensitive strip to detect oral cancer biomarkers., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In the present investigation, we reported a label-free and highly effective immunosensor for the first time employing a nanostructured molybdenum disulfide nanosheets@reduced graphene oxide (nMoS 2 NS@rGO) nanohybrid interface for the determination of sperm protein 17 (Sp17), an emerging cancer biomarker. We synthesized the nMoS 2 NS@rGO nanohybrid using a one-step hydrothermal technique and then functionalized it with 3-aminopropyltriethoxysilane (APTES). Furthermore, the anti-Sp17 monoclonal antibodies were covalently attached to the APTES/nMoS 2 NS@rGO/indium tin oxide (ITO) electrode utilizing 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide- N -hydroxy succinimide (EDC-NHS) coupling chemistry. Bovine serum albumin (BSA) was then used to block nonspecific binding regions on the anti-Sp17/APTES/nMoS 2 NS@rGO/ITO bioelectrode. The morphological and structural features of the synthesized nanohybrid and the modified electrodes were studied using transmission electron microscopy, scanning electron microscopy with energy dispersive X-ray (EDX) composition studies, atomic force microscopy, Fourier transform infrared spectroscopy, and Raman spectroscopy. The immunoreaction between the Sp17 antigen and anti-Sp17 antibodies on the surface of the BSA/anti-Sp17/APTES/nMoS 2 NS@rGO/ITO sensing bioelectrode was applied as the basis for the detection technique, which measured the electrocatalytic current and impedimetric response change. The designed BSA/anti-Sp17/APTES/nMoS 2 NS@rGO/ITO bioelectrode showed improved amperometric and impedimetric biosensing performance in the response studies, including remarkable sensitivity (23.2 μA ng -1 mL cm -2 and 0.48 kΩ mL ng -1 cm -2 ), wider linearity (0.05-8 and 1-8 ng mL -1 ), an excellent lower detection limit (0.13 and 0.23 ng mL -1 ), and a rapid response time of 20 min. The biosensor exhibited impressive storage durability lasting 7 weeks and showed remarkable precision in identifying Sp17 in serum samples from cancer patients, as confirmed using the enzyme-linked immunosorbent assay method.

To date, previous studies have reported the adverse effects of microplastics (MPs) and nanoplastics (NPs) on both freshwater and marine organisms. However, the information on MPs' and NPs' effects on shrimp species is scarce. In addition, the factors influencing the distribution of these particles in aquatic systems have been explained, yet the mechanisms behind MPs and NPs distribution and consumption, specifically to crustaceans and shrimp, have not been elucidated in detail. The effects of MPs and NPs as well as plastic-carried contaminants and pathogens on shrimp are critical to shrimp production and subsequent human consumption. Recent findings are required to review and discuss to open up new avenues for emerging Shrimp and crustacean research for sustainability. This review summarizes the distribution and fate of MPs and NPs along with contaminants and pathogens and identifies potential risks to shrimp health. The transport of MPs and NPs is influenced by their plastic properties, hydrodynamics, and water properties. Additionally, the fate of these particles on a plastic surface (plastisphere) is regulated by contaminant properties. Pathogens thriving on plastic surfaces and contaminants adsorbed can reach aquatic organisms directly with plastic particles or indirectly after release to an aquatic environment. MPs and NPs can be absorbed by shrimp through their gills and mouth and accumulate in their internal organs. Innate immunity influenced the degree of survival rate, tissue damage, alteration of gut microbiota, and increased oxidative stress caused by MPs and NPs accumulation. The studies on the effects of MPs and NPs are still not sufficient to understand how these particles are absorbed from various parts of the shrimp body and the fate of these plastics inside the body., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Herein, we report the results of the studies relating to developing a simple, sensitive, cost-effective, and disposable electrochemical-based label-free immunosensor for real-time detection of a new cancer biomarker, sperm protein-17 (SP17), in complex serum samples. An indium tin oxide (ITO) coated glass substrate modified with self-assembled monolayers (SAMs) of 3-glycidoxypropyltrimethoxysilane (GPTMS) was functionalized via covalent immobilization of monoclonal anti-SP17 antibodies using EDC(1-(3-(dimethylamine)-propyl)-3-ethylcarbodiimide hydrochloride) - NHS (N-hydroxy succinimide) chemistry. The developed immunosensor platform (BSA/anti-SP17/GPTMS@SAMs/ITO) was characterized via scanning electron microscopy (SEM), atomic force microscopy (AFM), contact angle (CA), Fourier transform infrared (FT-IR) spectroscopic, and electrochemical techniques such as cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS) techniques. The fabricated BSA/anti-SP17/GPTMS@SAMs/ITO immunoelectrode platform was used to measure changes in the magnitude of the current of the electrodes through an electrochemical CV and DPV technique. A calibration curve between current and SP17 concentrations exhibited a broad linear detection range of (100-6000 & 50-5500 pg mL -1 ), with enhanced sensitivity (0.047 & 0.024 μA pg mL -1  cm -2 ), limit of detection (LOD) and limit of quantification (LOQ) of 47.57 & 142.9 pg mL -1 and 158.58 & 476.3 pg mL -1 , by CV and DPV technique, respectively with a rapid response time of 15 min. It possessed exceptional repeatability, outstanding reproducibility, five-time reusability, and high stability. The biosensor's performance was evaluated in human serum samples, giving satisfactory findings obtained via the commercially available enzyme-linked immunosorbent assay (ELISA) technique, proving the clinical applicability for early diagnosis of cancer patients. Moreover, various in vitro studies in murine fibroblast cell line L929 have been performed to assess the cytotoxicity of GPTMS. The results demonstrated that GPTMS has excellent biocompatibility and can be used for biosensor fabrication., Competing Interests: Declaration of competing interest 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., (Copyright © 2023. Published by Elsevier B.V.)

Förster resonance energy transfer (FRET)-based biosensors are being fabricated for specific detection of biomolecules or changes in the microenvironment. FRET is a non-radiative transfer of energy from an excited donor fluorophore molecule to a nearby acceptor fluorophore molecule. In a FRET-based biosensor, the donor and acceptor molecules are typically fluorescent proteins or fluorescent nanomaterials such as quantum dots (QDs) or small molecules that are engineered to be in close proximity to each other. When the biomolecule of interest is present, it can cause a change in the distance between the donor and acceptor, leading to a change in the efficiency of FRET and a corresponding change in the fluorescence intensity of the acceptor. This change in fluorescence can be used to detect and quantify the biomolecule of interest. FRET-based biosensors have a wide range of applications, including in the fields of biochemistry, cell biology, and drug discovery. This review article provides a substantial approach on the FRET-based biosensor, principle, applications such as point-of-need diagnosis, wearable, single molecular FRET (smFRET), hard water, ions, pH, tissue-based sensors, immunosensors, and aptasensor. Recent advances such as artificial intelligence (AI) and Internet of Things (IoT) are used for this type of sensor and challenges.

Antibacterial properties of copper have been known for ages. With the rise of antimicrobial resistance (AMR), hospital-acquired infections, and the current SARS-CoV-2 pandemic, copper and copper-derived materials are being widely researched for healthcare ranging from therapeutics to advanced wound dressing to medical devices. We cover current research that highlights the potential uses of metallic and ionic copper, copper alloys, copper nanostructures, and copper composites as antibacterial, antifungal, and antiviral agents, including those against the SARS-CoV-2 virus. The applications of copper-enabled engineered materials in medical devices, wound dressings, personal protective equipment, and self-cleaning surfaces are discussed. We emphasize the potential of copper and copper-derived materials in combating AMR and efficiently reducing infections in clinical settings., 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 article. The authors declare no competing financial interests., (© 2022 Elsevier Inc. All rights reserved.)

Due to their bactericidal and fluid repellent capabilities, antimicrobial textiles with hydrophobic properties have aroused a lot of interest in healthcare, hygiene, air purifiers, water purification systems, food packaging, and other domains. Silver and silver-derived compounds have long been employed in antimicrobial coatings; nevertheless, they are costly, limiting their widespread use. In this work, we combined mussel-inspired polydopamine (pDA) coating chemistry with graphene oxide (GO) and antimicrobial copper compounds (Cu(NO 3 ) 2 , CuCl 2 , Cu nanoparticles (CuNPs), and Cu-Carbon nanofibers (Cu-CNF)) to create hydrophobic antimicrobial nanocoatings on cotton fabric. The structural, morphological, wettability, and antibacterial characteristics of the produced coatings were evaluated. The fabric coated with Cu(NO 3 ) 2 and CuNPs had good hydrophobicity, which was stabilized for 30 min following GO integration. The coated fabric with GO and CuNPs showed 100% bacterial inhibition for S. aureus and a 99.995% reduction for P. aeruginosa bacteria. Overall, this bioinspired approach to developing antimicrobial coatings on fabric utilizing Cu(NO 3 ) 2 and CuNPs with GO shows a lot of promise in preventing the transmission of bacterial and viral infections through contaminated garments and has potential in designing clothing for healthcare settings such as PPEs, gowns, aprons, face mask filters, curtains, and so on., Competing Interests: Declaration of Competing Interest Authors declare no conflict of Interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

India experiences a substantial burden of cervical cancer and accounts for nearly one third of cervical cancer deaths worldwide. While human papillomavirus (HPV) vaccines have been introduced subnationally in some states, HPV has not yet been rolled out nationally. Given the target age group, schools are the most common delivery channel for HPV vaccines, but this fails to account for local girls who never attended or no longer attend school. We conducted a qualitative, design-informed, community-based study conducted in Uttar Pradesh, India. We assessed facilitators and barriers among out-of-school girls and proposed program characteristics to inform the design of pro-equity HPV vaccine delivery programs for out-of-school girls. Programs should improve parental knowledge of the risk of cervical cancer, engage vaccinated girls as vaccine champions, utilize varied media options for low-literacy populations, and ensure that HPV vaccine services are accessible and flexible to accommodate out-of-school girls. In areas with poor or irregular school attendance among adolescent girls, HPV vaccine coverage will remain suboptimal until programs can effectively address their needs and reach this priority population. Our findings present a meaningful opportunity for program planners to purposefully design HPV vaccination programs according to these parameters, rather than modifying existing programs to include HPV vaccine. Adolescent girls, their parents, and other community members should be involved in program design to ensure that the program can effectively meet the needs of adolescent girls who are not in school.

Metabolites are the intermediatory products of metabolic processes catalyzed by numerous enzymes found inside the cells. Detecting clinically relevant metabolites is important to understand their physiological and biological functions along with the evolving medical diagnostics. Rapid advances in detecting the tiny metabolites such as biomarkers that signify disease hallmarks have an immense need for high-performance identifying techniques. Low concentrations are found in biological fluids because the metabolites are difficult to dissolve in an aqueous medium. Therefore, the selective and sensitive study of metabolites as biomarkers in biological fluids is problematic. The different non-electrochemical and conventional methods need a long time of analysis, long sampling, high maintenance costs, and costly instrumentation. Hence, employing electrochemical techniques in clinical examination could efficiently meet the requirements of fully automated, inexpensive, specific, and quick means of biomarker detection. The electrochemical methods are broadly utilized in several emerging and established technologies, and electrochemical biosensors are employed to detect different metabolites. This review describes the advancement in electrochemical sensors developed for clinically associated human metabolites, including glucose, lactose, uric acid, urea, cholesterol, etc., and gut metabolites such as TMAO, TMA, and indole derivatives. Different sensing techniques are evaluated for their potential to achieve relevant degrees of multiplexing, specificity, and sensitivity limits. Moreover, we have also focused on the opportunities and remaining challenges for integrating the electrochemical sensor into the point-of-care (POC) devices.

We hypothesize that firework events involving the combustion of charcoal fuel, organic binders, metal salts, and cellulose-based wrapping material could be significant transient sources of aerosol brown carbon (BrC). To test this, we couple high time-resolution (1 min) measurements of black carbon (BC) and BrC absorption from a 7-wavelength aethalometer with time-integrated (12-24 h) measurements of filter extracts, i.e., UV-visible, fluorescence, and Fourier-transformed infrared (FT-IR) signatures of BrC, total and water-soluble organic carbon (OC and WSOC), ionic species, and firework tracer metals during a sampling campaign covering the Diwali fireworks episode in India. In sharp contrast to BC, BrC absorption shows a distinct and considerable rise of 2-4 times during the Diwali period, especially during the hours of peak firework activity, as compared to the background. Fluorescence profiles suggest enrichment of humic-like substances (HULIS) in the firework plume, while the enhancement of BrC absorption in the 400-500 nm range suggests the presence of nitroaromatic compounds (NACs). Considerable contributions of WSOC and secondary organics to OC (44.1% and 31.2%, respectively) and of the water-soluble fraction of BrC to total BrC absorption (71.0%) during the Diwali period point toward an atmospherically processed, polar signature of firework-related BrC, which is further confirmed by FT-IR profiles. This aqueous BrC exerts a short-lived but strong effect on atmospheric forcing (12.0% vis-à-vis BC in the UV spectrum), which could affect tropospheric chemistry via UV attenuation and lead to a stabilization of the post-Diwali atmosphere, resulting in enhanced pollutant build-up and exposure., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

SP17 is a mammalian protein found in the testis and spermatozoa that have been identified as a tumor-associated antigen in a range of human cancers. A unique method for fabricating the first ultrasensitive, selective, and label-free immunosensor for the detection of SP17, a new cancer biomarker in complicated serum samples, is presented in this paper. This immunosensor was also the first biosensor built using a disposable ITO sheet modified with an aminosilane known as APTMS as an immobilization platform for fabricating the SP17 biosensor. The immobilization of chemical and biological species onto the electrode surface was cross-verified by various analytical and morphological techniques. Stepwise modifications done on the immunoelectrodes were also studied using electrochemical techniques. Selective interaction between anti-SP17 and SP17 with varying concentrations (100-5000 pg mL -1 ) was measured with the DPV technique. The immunosensor exhibited low LOD and LOQ of 70.07 and 233.57 pg mL -1 , respectively, with a sensitivity of 0.013 μA mL pg -1 cm -2 . The fabricated immunosensor performance was analyzed by quantifying the SP17 concentrations in patient serum samples. The data obtained from the developed immunosensor demonstrated excellent reproducibility, repeatability, and selectivity among various interferants, including cancer biomarkers. Further, the observed results have been validated via ELISA, which showed good agreement with the electrochemical results. This could establish a new platform for detecting other cancer biomarkers and can be employed for clinical diagnostics applications., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Current advances in constructing functional nanomaterials and elegantly designed nanostructures have opened up new possibilities for the fabrication of viable field biosensors. Two-dimensional materials (2DMs) have fascinated much attention due to their chemical, optical, physicochemical, and electronic properties. They are ultrathin nanomaterials with unique properties such as high surface-to-volume ratio, surface charge, shape, high anisotropy, and adjustable chemical functionality. 2DMs such as graphene-based 2D materials, Silicate clays, layered double hydroxides (LDHs), MXenes, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs) offer intensified physicochemical and biological functionality and have proven to be very promising candidates for biological applications and technologies. 2DMs have a multivalent structure that can easily bind to single-stranded DNA/RNA (aptamers) through covalent, non-covalent, hydrogen bond, and π-stacking interactions, whereas aptamers have a small size, excellent chemical stability, and low immunogenicity with high affinity and specificity. This review discussed the potential of various 2D material-based aptasensor for diagnostic applications, e.g., protein detection, environmental monitoring, pathogens detection, etc., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The β-diketo-modified isoxazole derivative of curcumin (IOC) is well renowned for its anticancer, antioxidant, antimalarial, antiproliferative, and many other biological activities. With the aim of obtaining fundamental knowledge on the photophysics of IOC, the present work was directed toward delineating those at different pH environments and studying the degradation profiles of IOC at five different pH values. Because one of the primary drawbacks of curcumin is its rapid degradation at physiological conditions, the studies showed that the problem could be resolved, as the IOC molecule was extremely stable even in a highly alkaline medium. Further, in order to encounter the problems associated with the low solubility of IOC in aqueous media, β-CD (β-cyclodextrin) was used and calculations of the thermodynamic parameters revealed that the process of development of the host-guest inclusion complex was highly spontaneous in nature. The synthesis of the IOC:β-CD inclusion complex has also been accomplished in the solid state, and the solid formed has been characterized using various physicochemical techniques. Finally, while variations in the pH as well as addition of foreign metal ions in +1 and +2 oxidation states showed minimal effect on the photophysics of the IOC:β-CD inclusion complex, antiproliferative studies performed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays revealed their nontoxic nature on fibroblast L929 normal cell lines and extremely toxic activity on human lung cancer A549 cell lines.

Here, we aimed to fabricate a label-free immunosensing platform for the first time based on molybdenum disulfide nanoparticles (nMoS 2 NPs) deposited on ITO) coated glass substrate for the electrochemical detection of ampicillin (AMP). The stable and high surface area of nMoS 2 NPs were made by a low-temperature one-step hydrothermal route, bestowing the carrying capacity of anti-AMP (antibody against AMP) through an amide linkage. The spectroscopic, morphological, and structural characterization of the proposed electrodes were performed using various analytical and electrochemical techniques. The differential pulse voltammetry technique was utilized to evaluate anti-AMP and AMP interaction on the electrode surface. The developed immunosensor exhibits high sensitivity, a broad detection range having a significant detection limit towards detection of AMP having excellent selectivity, acceptable stability, and reproducibility. Furthermore, the applicability of the proposed immunosensor was tested in spiked milk, water, and orange juice, and the results confirmed the consistency of the immunosensor., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Based on recent research reports, dysbiosis and improper concentrations of microbial metabolites in the gut may result into the carcinogenesis of colorectal cancer. Recent advancement also highlights the involvement of bacteria and their secreted metabolites in the cancer causation. Gut microbial metabolites are functional output of the host-microbiota interactions and produced by anaerobic fermentation of food components in the diet. They contribute to influence variety of biological mechanisms including inflammation, cell signaling, cell-cycle disruption which are majorly disrupted in carcinogenic activities., Purpose: In this review, we intend to discuss recent updates and possible molecular mechanisms to provide the role of bacterial metabolites, gut bacteria and diet in the colorectal carcinogenesis. Recent evidences have proposed the role of bacteria, such as Fusobacterium nucleaturm, Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis and Clostridium septicum, in the carcinogenesis of CRC. Metagenomic study confirmed that these bacteria are in increased abundance in CRC patient as compared to healthy individuals and can cause inflammation and DNA damage which can lead to development of cancer. These bacteria produce metabolites, such as secondary bile salts from primary bile salts, hydrogen sulfide, trimethylamine-N-oxide (TMAO), which are likely to promote inflammation and subsequently cancer development., Conclusion: Recent studies suggest that gut microbiota-derived metabolites have a role in CRC progression and causation and hence, could be implicated in CRC diagnosis, prognosis and therapy., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Among gut microbiota-derived metabolites, trimethylamine-N-oxide (TMAO) is receiving increased attention due to its possible role in the carcinogenesis of colorectal cancer (CRC). In spite of numerous reports implicating TMAO with CRC, there is a lack of empirical mechanistic evidences to concretize the involvement of TMAO in the carcinogenesis of CRC. Possible mechanisms such as inflammation, oxidative stress, DNA damage, and protein misfolding by TMAO have been discussed in this review in the light of the latest advancements in the field. This review is an attempt to discuss the probable correlation between TMAO and CRC but this linkage can be concretized only once we get sufficient empirical evidences from the mechanistic studies. We believe, this review will augment the understanding of linking TMAO with CRC and will motivate researchers to move towards mechanistic study for reinforcing the idea of implicating TMAO with CRC causation. KEY POINTS: • TMAO is a gut bacterial metabolite which has been implicated in CRC in recent years. • The valid mechanistic approach of CRC causation by TMAO is unknown. • The article summarizes the possible mechanisms which need to be explored for validation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The catalyst-directed divergent synthesis, commonly termed as "divergent catalysis", has emerged as a promising technique as it allows chartering of structurally distinct products from common substrates simply by modulating the catalyst system. In this regard, gold complexes emerged as powerful catalysts as they offer unique reactivity profiles as compared to various other transition metal catalysts, primarily due to their salient electronic and geometrical features. Owing to the tunable soft π-acidic nature, gold catalysts not only evolved as superior contenders for catalyzing the reactions of alkynes, alkenes, and allenes but also, more intriguingly, have been found to provide divergent reaction pathways over other π-acid catalysts such as Ag, Pt, Pd, Rh, Cu, In, Sc, Hg, Zn, etc. The recent past has witnessed a renaissance in such examples wherein, by choosing gold catalysts over other transition metal catalysts or by fine-tuning the ligands, counteranions or oxidation states of the gold catalyst itself, a complete reactivity switch was observed. However, reviews documenting such examples are sporadic; as a result, most of the reports of this kind remained scattered in the literature, thereby hampering further development of this burgeoning field. By conceptualizing the idea of "Divergent Gold Catalysis (DGC)", this review aims to consolidate all such reports and provide a unified approach necessary to pave the way for further advancement of this exciting area. Based on the factors governing the divergence in product formation, an explicit classification of DGC has been provided. To gain a fundamental understanding of the divergence in observed reactivities and selectivities, the review is accompanied by mechanistic insights at appropriate places.

We report the first characterization of the aerosol brown carbon (BrC) composition in the Indian context using excitation emission matrix (EEM) fluorescence spectroscopy coupled with parallel factor (PARAFAC) analysis. We find that biomass burning (BB)-dominated wintertime aerosols in the Indo-Gangetic Plain (IGP) outflow are characterized by two humic-like (HULIS) (C1&#95;aq and C2&#95;aq) and one protein-like/fossil fuel-derived (C3&#95;aq) component for aqueous-extractable BrC (BrCaq), and by one humic-like (C1&#95;me) and one protein-like (C2&#95;me) component for methanol-extractable BrC (BrCme). Strong correlations of the BB tracer nss-K+ with C1&#95;aq and C2&#95;aq (r = 0.75-0.84, p < 0.01) and C1&#95;me (r = 0.77, p < 0.01) point towards the BB-dominated IGP outflow as the major source. This is also supported by the analysis of fluorescence indices, which suggest extensive humification of BB emissions during atmospheric transport. The HULIS components correlate significantly with BrC absorption (r = 0.85-0.94, p < 0.01), and contribute substantially to the BrC relative radiative forcing of 13-24% vis-à-vis elemental carbon (EC). There is strong evidence that the abundant BB-derived NOX leads to NO3- formation in the IGP plume and drives the formation of water-soluble nitroaromatics (NACs) that constrain BrCaq light absorption (r = 0.56, p < 0.01) to a considerable degree. Overall, the study uncovers complex atmospheric processing of the IGP outflow in winter, which has important implications for regional climate.

Vitamin D (VD) deficiency is a global health concern due to its serious health impacts, and at present, the monitoring of VD status is expensive. Here, a novel immunosensor for sensitive and label-free detection of 25-hydroxy vitamin D 3 (25VD 3 ) is reported. Nanostructured cerium(IV) oxide (nCeO 2 ) was anchored onto carbon cloth (CC) via electrophoretic deposition to fabricate a nanoplatform (nCeO 2 /CC). Subsequently, bioactive molecules (anti-25VD 3 and BSA) were introduced to fabricate the nanobioplatform BSA/anti-25VD 3 /nCeO 2 /CC as an immunosensor. The analytical performance of the developed immunosensor was studied towards 25VD 3 detection. The immunosensor provides a broad linear range of 1-200 ng mL -1 , high sensitivity of 2.08 μA ng -1  mL cm -2 , a detection limit of 4.63 ng mL -1 , and a response time of 15 min, which is better than that of previous reports. The biosensor exhibited high selectivity, good reproducibility, and excellent stability for about 45 days. The potential application of the proposed immunosensor was observed for real serum samples towards 25VD 3 detection that demonstrated a high correlation with the conventional enzyme-linked immunosorbent assay. Graphical abstract.

The understanding of mechanistic insights in environmental remediation and mitigation systems is attracting larger attention, in recent days. Here in, aluminium substituted copper ferrite impregnated rGO hybrid (CAF-rGO) is verified to understand the adsorption/electrosorption mechanism of arsenic in aqueous systems. Near-surface study (XPS: As 3d, Cu 2p, Fe 2p, Al 2p, O 1s, C 1s) proposes redox, and ligand exchange reactions between contaminant, and CAF-rGO. Adsorption capacities are observed around 128.8 mg g -1 [As(III)], 153.5 mg g -1 [As(V)] with Freundlich model isotherms. Kinetics study follows the PSO model with influence of solar light (> 420 nm). Cyclic voltammetry (CV) analysis in different molarity conditions observed with signals around +0.1 and -0.6 V confirm the redox abilities, and N 2 /O 2 purged environments understood that electrosorption occurred through both reduction and sorption. Electrosorption study with pH variation shows the effect of protonation on the redox activity of individual arsenic species. Consistent signal around -0.6 ± 0.05 V in all the CV plots (i.e., Molarity, Environment, pH) recommends the usage of CAF-rGO for arsenic mitigation. Possible influence of photo-current (∼40 μA/cm 2 at ∼ 0 V) towards As(III/V) decontamination is understood though photoelectrochemical analysis. Impedance plot shows low-resistance and better diffusion of arsenic oxy-anions during light irradiation. Synergistic nature of CAF-rGO generates reactive oxygen species (i.e., ● OH/ ● O 2 - / 1 O 2 ) in mitigating highly toxic As(III) species is also detailed in the present work., Competing Interests: Declaration of competing interest 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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Trimethylamine N-oxide (TMAO), a microbiota-derived metabolite has been implicated in human health and disease. Its early detection in body fluids has been presumed to be significant in understanding the pathogenesis and treatment of many diseases. Hence, the development of reliable and rapid technologies for TMAO detection may augment our understanding of pathogenesis and diagnosis of diseases that TMAO has implicated. The present work is the first report on the development of a molecularly imprinted polymer (MIP) based electrochemical sensor for sensitive and selective detection of TMAO in body fluids. The MIP developed was based on the polypyrrole (PPy), which was synthesized via chemical oxidation polymerization method, with and without the presence of TMAO. The MIP, NIP and the non-sonicated polymer (PPy-TMAO) were separately deposited electrophoretically onto the hydrolyzed indium tin oxide (ITO) coated glasses. The chemical, morphological, and electrochemical behavior of MIP, non-imprinted polymer (NIP), and PPy-TMAO were characterized using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and electrochemical techniques. The detection response was recorded using differential pulse voltammetry (DPV), which revealed a decrease in the peak current with the increase in concentration of TMAO. The MIP sensor showed a dynamic detection range of 1-15 ppm with a sensitivity of 2.47 µA mL ppm -1  cm -2 . The developed sensor is easy to construct and operate and is also highly selective to detect TMAO in body fluids such as urine. The present research provides a basis for innovative strategies to develop sensors based on MIP to detect other metabolites derived from gut microbiota that are implicated in human health and diseases.

Iron overload in water is a problem in many areas of the world, which could exert toxic effects on fish. To achieve maximum growth and overall fitness, iron induced toxicity must be alleviated. Therefore, this research was undertaken to investigate the potential mitigation of iron toxicity by dietary vitamin C supplementation in channel catfish (Ictalurus punctatus). Two doses of vitamin C (143 and 573 mg/kg diet) were tested against high environmental iron (HEI, 9.5 mg/L representing 25% of 96 h LC 50 ). Fish were randomly divided into six groups with four replicated tanks. The groups were Control (vitamin C deficient feed), LVc (143 mg vitamin C supplemented per kg diet), HVc (573 mg vitamin C supplemented per kg diet), Con + Fe (control exposed to HEI), LVc + Fe (LVc exposed to HEI) and HVc + Fe (HVc exposed to HEI). Following an 8 week trial, there was a significant reduction in weight gain (WG%) in Con + Fe compared to the control, indicating a toxic effect of HEI on fish growth performance. Interestingly, WG% in both LVc + Fe and HVc + Fe groups were significantly higher than Cont + Fe, signifying that HEI inhibited growth, but this was alleviated by vitamin C. Both hemoglobin content and hematocrit were higher in LVc + Fe compared to the control and Con + Fe. In addition, exposure to HEI (Con + Fe) incited hepatic oxidative stress based on an over-accumulation of malondialdehyde (MDA) along with a significant inhibition in superoxide dismutase (SOD) and catalase (CAT) activities; whereas in LVc + Fe and HVc + Fe, the MDA content restored to basal level. A series of histopathological alterations were observed in the liver and gills, with the most severe lesions in Con + Fe, which was also complemented with a remarkable increase in hepatic iron accumulation. Vitamin C supplementations reduced the augmented concentrations of iron accumulation to that of the control. No effect, regardless of the treatments, was noted for fatty acid composition of muscle. Overall, our findings suggest that the vitamin C supplementation can be an effective therapeutic approach for boosting growth as well as alleviating iron toxicity in catfish., (Published by Elsevier Inc.)

To develop diagnostics and detection methods, current research is focussed on targeting the detection of coronavirus based on its RNA. Besides the RNA target, research reports are coming to develop diagnostics by targeting structure and other parts of coronavirus. PCR based detection system is widely used and various improvements in the PCR based detection system can be seen in the recent research reports. This review will discuss multiple detection methods for coronavirus for developing appropriate, reliable, and fast alternative techniques. Considering the current scenario of COVID-19 diagnostics around the world and an urgent need for the development of reliable and cheap diagnostic, various techniques based on CRISPR technology, antibody, MIP, LAMP, microarray, etc. should be discussed and tried., (Copyright © 2020. Published by Elsevier Masson SAS.)

Herein, we disclose the gold-catalyzed 1,2-diarylation of alkenes through the interplay of ligand-enabled Au I /Au III catalysis with the idiosyncratic π-activation mode of gold complexes. Unlike the classical migratory-insertion-based approach to 1,2-diarylation, the present approach not only circumvents the formation of direct Ar-Ar' coupling and Heck-type side products but more intriguingly demonstrates reactivity and selectivity complementary to those of previously known metal catalysis (Pd, Ni, or Cu). Detailed investigations to underpin the mechanistic scenario revealed oxidative addition of aryl iodides to an Au I complex to be the rate-limiting step owing to the non-innocent nature of the aryl alkene., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Here, non-invasive and label-free detection of trace-level of norfloxacin (NF) in human urine samples has been reported using the electrochemical technique. Nanostructured yttrium oxide (nY 2 O 3 ) was synthesized at low-temperature using a one-step hydrothermal process. These nY 2 O 3 were characterized by various methods including XRD, FT-IR, Raman spectroscopy, and TEM. A biosensing platform based on nY 2 O 3 modified with chitosan (CH) was fabricated for the detection of NF. The nanocomposite film (CH-Y 2 O 3 /ITO) was characterized by FE-SEM, contact angle measurements, and electrochemical techniques. Further, fluoroquinolones antibodies (anti-FQ) were used to modify the CH-Y 2 O 3 /ITO electrode via covalent interaction. Non-specific sites were blocked by bovine serum albumin (BSA), those present on the anti-FQ/CH-Y 2 O 3 /ITO electrode surface. The response study of BSA/anti-FQ/CH-Y 2 O 3 /ITO bioelectrode towards NF detection revealed a wide range (1 pM-10 μM) with a lower detection limit of 3.87 pM using differential pulse voltammetry (DPV). The sensitivity obtained is as high as 10.14 μA μM -1  cm 2 with a fast response time of ~10 min. Moreover, the diagnostic performance of the fabricated sensor was evaluated to detect NF in urine spiked sample. The recovery of NF from the spiked sample was observed from 90.5 to 101.1%, with a maximum relative standard deviation of 7.04. The obtained results of the fabricated bioelectrode (BSA/anti-FQ/CH-Y 2 O 3 /ITO) was validated with ELISA. The results were found better when compared with earlier described biosensors and commercially existing ELISA in terms of sensitivity and lower detection limit., Competing Interests: Declaration of competing interest 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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Competing Interests: There are no conflicts of interest.

Background: Natural defence of plants against insect pests involves protease inhibitors (PIs) that interfere with insect digestive proteases. Pin-II type plant PIs are wound inducible upon insect damage and possess multiple inhibitory repeat domains that can inhibit trypsin and chymotrypsin-like proteases in the insect midgut. Yet, their agricultural ex-vivo application is limited due to large molecular size and environmental instability, which could be overcome by small peptides., Methods: Bicyclic peptides were designed by grafting Pin-II PIs derived reactive center loop (RCL) on synthetic tris(bromomethyl)benzene scaffold. In vitro binding with trypsin-like proteases was evaluated by biochemical and biophysical assays, followed by molecular dynamics simulations. In vivo effects on two major lepidopteran insect pests, Helicoverpa armigera and Spodoptera litura were studied upon feeding with peptide treated leaves. Affinity based pull down assays were used to identify target proteins in insect gut., Results: Bicyclic RCLs showed ten-fold enhanced protease inhibition compared to their linear counterparts. They exhibited feeding deterrence and growth reduction of lepidopteran insects. Bicyclic peptides predominantly interact with midgut serine proteases. Possible binding modes involve simultaneous interaction with the active site and specificity-determining residues of insect gut trypsin., Conclusion: Bicyclic peptides are potent inhibitors of serine proteases in the insect midgut. They cause feeding aversion and larval growth retardation. Bi-domain cyclic peptides interact with two sites on trypsin, leading to enhanced efficacy over linear RCL peptides., General Significance: Bicyclic peptides mimic natural PIs by inhibiting insect proteases leading to growth reduction, thus, could be used as pest control molecules in agriculture., (Copyright © 2019. Published by Elsevier B.V.)

Proteomics by mass spectrometry (MS) allows the large-scale identification and quantitation of the cellular proteins in a given biological context. Systems biology studies from proteomics data are largely limited by the accuracy and coverage of quantitative proteomics along with missing values. Toward this end, statistically robust biological observations are required, comprising multiple replicates, preferably with little technical variations. Multiplexed labeling techniques in proteomics allow quantitative comparisons of several biological samples or conditions. In this focused Review, we discuss an emerging technique called higher order multiplexing or enhanced multiplexing, a unique combination of traditional MS 1 - and MS 2 -based quantitative proteomics methods that allows for expanding the multiplexing capability of MS methods to save valuable instrument time, achieve statistical robustness, enhance coverage and quantitation accuracy, and reduce the run-to-run variability. We discuss the various innovative studies and experimental designs that exploit the power of this technique and its variants to provide an overview of a rapidly growing area and also to highlight the advantages and challenges that lie ahead in the widespread adoption of this technique.

Waterborne ammonia is an environmental pollutant that is toxic to all aquatic animals. However, ammonia induced toxicity as well as compensatory mechanisms to defend against high environmental ammonia (HEA) are not well documented at present for largemouth bass (Micropterus salmoides), a high value fish for culture and sport fisheries in the United States. To provide primary information on the sensitivity of this species to ammonia toxicity, a 96 h-LC 50 test was conducted. Thereafter, responses at physiological, ion-regulatory and transcript levels were determined to get insights into the underlying adaptive strategies to ammonia toxicity. For this purpose, fish were progressively exposed to HEA (8.31 mg/L representing 25% of 96 h-LC 50 ) for 3, 7, 14, 21 and 28 days. Temporal effects of HEA on oxygen consumption rate (MO 2 ), ammonia and urea dynamics, plasma ions (Na + , Cl - and K + ), branchial Na + /K + -ATPase (NKA) and H + -ATPase activity, muscle water content (MWC), energy store (glycogen, lipid and protein) as well as branchial mRNA expression of Rhesus (Rh) glycoproteins were assessed. Probit analysis showed that 96 h-LC 50 of (total) ammonia (as NH 4 HCO 3 ) at 25 °C and pH 7.8 was 33.24 mg/L. Results from sub-lethal end-points shows that ammonia excretion rate (J amm ) was strongly inhibited after 7 days of HEA, but was unaffected at 3, 14 and 21 days. At 28 days fish were able to increase J amm efficiently and concurrently, plasma ammonia re-established to the basal level. Urea production was increased as evidenced by a considerable elevation of plasma urea, but urea excretion rate remained unaltered. Expression of Rhcg isoform (Rhcg2) mRNA was up-regulated in parallel with restored or increased J amm , suggesting its ammonia excreting role in largemouth bass. Exposure to HEA also displayed pronounced augmentations in NKA activity, exemplified by a rise in plasma [Na + ]. Furthermore, [K + ], [Cl - ] and MWC homeostasis were disrupted followed by recovery to the control levels. H + -ATPase activity was elevated but NKA did not appear to function preferentially as a Na + /NH 4 + -ATPase. From 14 days onwards MO 2 was depressed, potentially an attempt towards minimizing catabolism. Glycogen content in liver and muscle were temporarily depleted, whereas a remarkable increment in protein was evident at the last exposure period. Overall, these data suggest that ammonia induced toxicity can disturb several biological processes in largemouth bass, however, it can adapt to the long-term sub-lethal ammonia concentrations by activating various components of ammonia excretory, ion-regulatory and metabolic pathways., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Arginine-rich cell penetrating peptides are powerful tools for in vitro as well as in vivo delivery of a wide plethora of biomolecules. However, presence of consecutive arginine residues leads to enhanced amenability for proteolytic degradation as well as steric hindrances for membrane interactions which compromise its bioavailability. In order to overcome these limitations we previously reported a safe and stable octaarginine based oligomer, i.e., (r-x-r)4-carbamate, where the backbone amide linkages were replaced by carbamate linkages and 6-aminohexanoic acid based spacer moieties were incorporated for better flexibility, hydrophobicity, optimal spacing of guanidinium groups, and protection against proteolytic cleavage; resulting in improved transfection efficiency over its amide counterpart. In the present work we have investigated the mechanism behind this enhanced transfection efficiency and, based on our observations, demonstrate how the synergistic effect of rationalized oligomer designing, complex characteristics, and cell type contributes to overall effective intracellular delivery. Our results indicate that the (r-x-r)4-carbamate-plasmid DNA complexes primarily utilize lipid raft dependent pathway of cellular entry more than other pathways, and this possibly facilitates their increased entry in the lipid raft rich milieu of skin cells. We also emphasize the utility of oligomer (r-x-r)4-carbamate as an efficient carrier for topical delivery of nucleic acids in skin tissue. This carrier can be utilized for safe, efficient, and noninvasive delivery of therapeutically relevant macromolecular hydrophilic cargo like nucleic acids to skin.

Aim: Enteric duplication cysts are rare and uncommon congenital malformations formed during the embryonic period of the development of human digestive system and are mainly encountered during infancy or early childhood, but seldom in adults. The clinical presentation is extremely variable depending upon its size, location and type. We present six cases of enteric duplication cysts with diverse clinico-pathological features., Materials and Methods: This study was carried out in the Department of Pathology and Department of Paediatric Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India for a period of 2 years (January 2013 - December 2014). We retrospectively analyzed six patients of enteric duplication cysts based on data obtained, which consisted of patient's age, sex, clinical presentation, radiological features, operative findings and histopathology report. The data collected was analyzed by descriptive statistics., Results: Six children between age range of 3 days to 10 years had enteric duplication cysts. Two had ileal and one each were of pyloroduodenal, colonic and rectal duplication cyst. In one patient a presumptive diagnosis of enteric duplication cyst was made. Radiology played an important contributory role in diagnosis of these cysts in all the patients but histopathology proved to be gold standard for its confirmation. All these patients were managed by surgical excision. The postoperative and follow up period in all the cases was uneventful., Conclusion: It is important to be aware and make a definitive diagnosis of this rare congenital anomaly as they can present in various clinical forms and can cause significant morbidity and even mortality if left untreated by causing life threatening complications.

The syntheses of novel N-aminoalkyl proline-derived spacers (X') in polycationic (R-X'-R)-motif cell-penetrating α-ω-α-peptides are described as improved molecular transporters and their structural features studied by CD. FACS analysis shows enhanced cellular uptake and confocal microscopy indicates predominantly cytoplasmic localization. The oligomers are efficient at transporting pDNA into cells. The chirality together with the hydrophobicity and flexibility derived from the spacer chain are found to have marked influence on the cell-penetrating and cargo delivery properties of the cell-penetrating peptides (CPPs). The peptides containing N-(3-aminopropyl)-D-proline spacers are found to be the best at cell penetration and cargo delivery in the present study., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Chlorine (Cl(2)) gas exposure poses an environmental and occupational hazard that frequently results in acute lung injury. There is no effective treatment. We assessed the efficacy of antioxidants, administered after exposure, in decreasing mortality and lung injury in C57BL/6 mice exposed to 600 ppm of Cl(2) for 45 minutes and returned to room air. Ascorbate and deferoxamine were administered intramuscularly every 12 hours and by nose-only inhalation every 24 hours for 3 days starting after 1 hour after exposure. Control mice were exposed to Cl(2) and treated with vehicle (saline or water). Mortality was reduced fourfold in the treatment group compared with the control group (22 versus 78%; P = 0.007). Surviving animals in the treatment group had significantly lower protein concentrations, cell counts, and epithelial cells in their bronchoalveolar lavage (BAL). Lung tissue ascorbate correlated inversely with BAL protein as well as with the number of neutrophils and epithelial cells. In addition, lipid peroxidation was reduced threefold in the BAL of mice treated with ascorbate and deferoxamine when compared with the control group. Administration of ascorbate and deferoxamine reduces mortality and decreases lung injury through reduction of alveolar-capillary permeability, inflammation, and epithelial sloughing and lipid peroxidation.

Exposure to chlorine (Cl(2)) damages airway and alveolar epithelia, resulting in acute lung injury and reactive airway dysfunction syndrome. We evaluated the efficacy and mechanisms by which arformoterol, a long-term β(2)-agonist, administered after exposure, mitigated the extent of this injury. Exposure of C57BL/6 mice to 400 ppm Cl(2) for 30 minutes increased respiratory system resistance and airway responsiveness to aerosolized methacholine (assessed by FlexiVent) up to 6 days after exposure, and decreased Na(+)-dependent alveolar fluid clearance (AFC). Inducible Nitric Oxide Synthase (iNOS) knockout mice developed similar degrees of airway hyperreactivity as wild-type controls after Cl(2) exposure, indicating that reactive intermediates from iNOS do not contribute to Cl(2)-induced airway dysfunction in our model. Intranasal administration of arformoterol mitigated the Cl(2) effects on airway reactivity and AFC, presumably by increasing lung cyclic AMP level. Arformoterol did not modify the inflammatory responses, as evidenced by the number of inflammatory cells and concentrations of IL-6 and TNF-α in the bronchoalveolar lavage. NF-κB activity (assessed by p65 Western blots and electrophoretic mobility shift assay) remained at control levels up to 24 hours after Cl(2) exposure. Our results provide mechanistic insight into the effectiveness of long-term β(2)-agonists in reversing Cl(2)-induced reactive airway dysfunction syndrome and injury to distal lung epithelial cells.

Nitrite (NO(2)(-)) has been shown to limit injury to the heart, liver, and kidneys in various models of ischemia-reperfusion injury. Potential protective effects of systemic NO(2)(-) in limiting lung injury or enhancing repair have not been documented. We assessed the efficacy and mechanisms by which postexposure intraperitoneal injections of NO(2)(-) mitigate chlorine (Cl(2))-induced lung injury in rats. Rats were exposed to Cl(2) (400 ppm) for 30 min and returned to room air. NO(2)(-) (1 mg/kg) or saline was administered intraperitoneally at 10 min and 2, 4, and 6 h after exposure. Rats were killed at 6 or 24 h. Injury to airway and alveolar epithelia was assessed by quantitative morphology, protein concentrations, number of cells in bronchoalveolar lavage (BAL), and wet-to-dry lung weight ratio. Lipid peroxidation was assessed by measurement of lung F(2)-isoprostanes. Rats developed severe, but transient, hypoxemia. A significant increase of protein concentration, neutrophil numbers, airway epithelia in the BAL, and lung wet-to-dry weight ratio was evident at 6 h after Cl(2) exposure. Quantitative morphology revealed extensive lung injury in the upper airways. Airway epithelial cells stained positive for terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL), but not caspase-3. Administration of NO(2)(-) resulted in lower BAL protein levels, significant reduction in the intensity of the TUNEL-positive cells, and normal lung wet-to-dry weight ratios. F(2)-isoprostane levels increased at 6 and 24 h after Cl(2) exposure in NO(2)(-)- and saline-injected rats. This is the first demonstration that systemic NO(2)(-) administration mitigates airway and epithelial injury.

Context: Hemoglobin (Hb) Q variant is a group of hemoglobinopathies prevalent in south, south-east and western Asia. The primary structure of all of these molecules is well known. However, very little is known about the secondary and tertiary structures of these molecules. Therefore, a study of their secondary and tertiary structures is needed., Aim: The study was aimed at investigating the secondary and tertiary structures of common Hb Q variants using bioinformatics tool., Settings and Design: The secondary and tertiary structures of common Hb Q variants were evaluated using NNPREDICT server and CPHmodels 2.0 server, respectively., Materials and Methods: Amino acid sequence of alpha globin chain was searched using ExPASY and was used for further mutation to Hb Q variants. The derived sequences were further analyzed using NNPREDICT server and CPHmodels 2.0 server to calculate their secondary and tertiary structures, respectively. These were then compared and any differences noted., Results: It was observed that there is no difference between the predicted secondary structures of normal alpha globin and Hb Q-India. Hb Q-Iran carries an extra helix while Hb Q-Thailand carries two extra helices. The results of tertiary structure prediction also support these findings., Conclusions: Differences in secondary and tertiary structure of various Hb Q variants have been observed in the present study. The study provides valuable data for better understanding of these uncommon hemoglobinopathies.

Chlorine (Cl(2)) is a reactive oxidant gas used extensively in industrial processes. Exposure of both humans and animals to high concentrations of Cl(2) results in acute lung injury, which may resolve spontaneously or progress to acute respiratory failure. Injury to airway and alveolar epithelium may result from chemical reactions of Cl(2), from HOCl (the hydrolysis product of Cl(2)), and/or from the various reaction products, such as chloramines, that are formed from the reactions of these chlorinating species with biological molecules. Subsequent reactions may initiate self-propagating reactions and induce the production of inflammatory mediators compounding injury to pulmonary surfactant, ion channels, and components of lung epithelial and airway cells. Low-molecular-weight antioxidants, such as ascorbate, glutathione, and urate, present in the lung epithelial lining fluid and tissue, remove Cl(2) and HOCl and thus decrease injury to critical target biological targets. However, levels of lung antioxidants of animals exposed to Cl(2) in concentrations likely to be encountered in the vicinity of industrial accidents decrease rapidly and irreversibly. Our measurements show that prophylactic administration of a mixture containing ascorbate and desferal N-acetyl-cysteine, a precursor of reduced glutathione, prevents Cl(2)-induced injury to the alveolar epithelium of rats exposed to Cl(2). The clinical challenge is to deliver sufficient quantities of antioxidants noninvasively, after Cl(2) exposure, to decrease morbidity and mortality.