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Bacteria commonly live in a spatially organized biofilm assemblage. The metabolic activity inside the biofilm leads to segmented physiological microenvironments. In nature, bacteria possess several pleomorphic forms to withstand certain ecological alterations. We hypothesized that pleomorphism also exists within the biofilm, which can be considered as the fundamental niche for bacteria. We report a distinct pattern of cell size variation throughout the biofilm of Bacillus subtilis. Cell size heterogeneity was observed in biofilm development, wherein the frequency of long cells is higher in outer regions, whereas lower in inner regions. Moreover, compared to planktonic cells, bacteria in the biofilm mode reduce their geometric ratio from 8.34 to 3.69 and 2.65 in the outer and inner regions, respectively. There were no significant differences observed in nutrient diffusion from the outer to the inner region, and more than 73 % of cells in the inner region were viable. However, the inner and middle regions were more acidic than the outer of the biofilm. Conclusively, growth rate-independent cell size reduction at low pH suggests that the resulting phenotype switching within biofilm was observed due to the pH gradient of neutral to acidic from the outer to the core of the biofilm. This gradient of H + ions concentration may create exploitative stress within the biofilm, which could favor specific pleomorphic cells to thrive in their specialized niches. By understanding the cell size variation in response to the local environment, we propose a model of biofilm formation by pleomorphic cells., 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 © 2024 Elsevier GmbH. All rights reserved.)

Ophthalmic disorders significantly impact global health, affecting millions worldwide. Conventional treatments often face challenges related to poor bioavailability and short residence times on the ocular surface. In recent years, in-situ gels prepared using different natural gums including gellan gum has been investigated as a viable means of improving ocular medication delivery. Gellan gum undergoes ionotropic-gelation in the presence of multivalent cations, making it suitable for ocular formulations. The synthesis and purification of gellan gum involve microbial fermentation processes. Incorporating gellan gum into ophthalmic formulations offers several advantages, including prolonged residence time, enhanced drug retention, and improved bioavailability. Characterisation techniques such as gelling capacity determination, FTIR spectroscopy, TEM, viscosity and rheological studies and ex-vivo or in-vitro release studies are crucial for assessing the structural and functional properties of gellan gum-based in-situ gels. Numerous investigations have exhibited gellan gum's potential in different drug loaded in-situ gels for ophthalmic uses, resulting in extended drug residency on the ocular surface and enhanced therapeutic effects. The current review presents a comprehensive discussion on preparation, characterisation, recent applications and future prospects of gellan gum-based in-situ gels for ocular drug delivery. In addition, it covers molecular structure, synthesis and characterisation of gellan gum., 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 © 2024 Elsevier B.V. All rights reserved.)

Background: High resistant starch (RS) rice with a low glycemic index (GI) is digested more slowly, resulting in a slow increase in the postprandial blood glucose level. People with milled rice as a staple diet, and with sedentary lifestyles, are more prone to acquire type 2 diabetes in the long term. With an increasing population of diabetics worldwide, one possible solution is the development of rice-based, low-GI foods with high RS content rice. In addition to amylose content (AC), linear chains of amylopectin also affect the rate of starch digestibility., Results: The values of GI (52.49-63.0), RS (0.64% to 2.28%), and AC (3.82% to 24.52%) were found to vary widely in 110 rice genotypes. Genotypes IG 23 and IG 40, with contrasting AC (15.65% and 24.52%, respectively), revealed that amylose alone did not affect digestion rate. Starch morphology, bioaccessibility, and pasting properties differed noticeably among genotypes. A starch debranching enzyme pullulanase assay indicated the role of the linear amylopectin chain in crystallized RS formation within the grains of lower AC genotype IG 23., Conclusion: Enhanced activity of the starch-debranching enzyme pullulanase produced linearized amylopectin resulted into reduced starch digestibility in low-amylose rice. This is probably the first report on the natural presence of high RS (crystallized) in rice with lower AC (IG 23). Development of rice-based food with low GI and high RS could be a promising strategy for lowering the prevalence of type 2 diabetes. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Accessible Summary What is known on the subject Health professionals, including nurses, are shown to have stigmatizing attitudes towards mental illness. For nursing students who are in their formative years of professional development, mental illness stigma can severely impact the care they provide. Little research has investigated multi-national comparisons of nursing students' attitudes towards mental illness. What this paper adds to existing knowledge This study shows that between countries, there were substantial differences amongst nursing students in stigmatizing attitudes towards mental illness. Cultural perspectives may explain some of these differences. What are the implications for practice Regardless of location, stigmatizing attitudes are present at varying levels. Each nation can take steps to reduce these by acknowledging the presence of stigmatizing attitudes amongst nurses, educating nurses regarding the negative impacts of stigma on patient outcomes, and decrease stigmatizing attitudes by facilitating opportunities for nurses (particularly student nurses) to have direct contact with people with lived experiences of mental illness., Abstract: INTRODUCTION: Stigmatizing attitudes perpetuated by nursing professionals are a pervasive problem for people experiencing mental health issues. This global issue has detrimental consequences; inhibiting one's life chances and help-seeking behaviours. To date, few studies have compared nursing students' attitudes towards mental illness from a multi-national perspective., Aim: To compare undergraduate nursing students' attitudes towards mental illness across six countries: Australia, India, Jordan, Saudi Arabia, Taiwan and USA., Method: In a cross-sectional design, data were collected from undergraduate nursing students (N = 426) using the Social Distance Scale. A one-way analysis of variance was used to compare differences between countries., Results: Nursing students' attitudes to mental illness differed between countries. Social Distance Scores were highest amongst nursing students from Jordan and Saudi Arabia. Students from Taiwan and India possessed moderate stigma scores. Social Distance Scores from the USA and Australia were lowest., Discussion: Clear differences in stigmatizing attitudes emerged between countries; these are discussed in relation to possible cultural influences., Implications for Practice: It is suggested that educating nurses, combined with direct contact with people with lived experiences of mental illness, can reduce stigmatizing attitudes regardless of country, location or educational institution., (© 2024 The Authors. Journal of Psychiatric and Mental Health Nursing published by John Wiley & Sons Ltd.)

Direct formic acid fuel cells (DFAFCs) stand out for portable electronic devices owing to their ease of handling, abundant fuel availability, and high theoretical open circuit potential. However, the practical application of DFAFCs is hindered by the unsatisfactory performance of electrocatalysts for the sluggish anodic formic acid oxidation reaction (FAOR). Palladium (Pd) based nanomaterials have shown promise for FAOR due to their highly selective reaction mechanism, but maintaining high electrocatalytic durability remains challenging. In this study, a novel Pd-based electrocatalyst (UiO-Pd-E) is reported with exceptional durability and activity for FAOR, which can be attributed to the Pd nanoparticles encapsulated within a carbon framework where concurrent chemical alloying of Pd and Zr occurs. Further, the UiO-Pd-E demonstrates noteworthy multifunctionality in various electrochemical reactions including electrocatalytic ethanol oxidation reaction (EOR) and oxygen reduction reaction (ORR) in addition to the FAOR, highlighting its practical potentials., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Nitric oxide (NO) is an important vasodilator responsible for maintaining vascular tone in the human body. Its production in endothelial cells (ECs) is regulated by the rise of cytoplasmic Ca 2+ concentration and shear stress perceived by blood flow. The increase in cytoplasmic Ca 2+ concentration is mainly activated by adenosine triphosphate (ATP) released from red blood cells (RBCs) and ECs. However, RBCs, which act as NO scavengers, can affect the bioavailability of NO in blood vessels. In this study, we developed a model that incorporates ATP and shear stress-dependent NO production, integrating various biochemical pathways. The model results are qualitatively consistent with the experimental findings. Given that ATP concentration and shear stress vary spatially within blood circulation, influenced by factors such as vessel width, flow strength and RBC concentration, these variations can significantly affect NO bioavailability. Here, we study RBC flow, ATP release from RBCs and ECs, and [Formula: see text] and NO dynamics in a two-dimensional channel using the immersed boundary lattice Boltzmann method. The main findings from the study include: (i) an increase in RBC concentration leads to a rise in ATP and cytoplasmic Ca 2+ concentrations for all variation in channel widths, while NO concentration exhibits a decrease; (ii) NO bioavailability is significantly influenced by RBC distribution, particularly in strongly confined channels; and (iii) two phases of NO bioavailability are observed in different regions of the blood vessels: one with a significant concentration change at low RBC concentration and another with a minimal concentration change at high RBC concentration, across all confinements. The outcomes of this study may provide valuable insights into the mechanisms of NO-dependent vasodilation and the transport of oxygen by RBCs within microvascular networks for future studies.

The Watson-Crick base pairing property of DNA is widely used for fabricating DNA nanostructures with well-defined geometry. Moreover, DNA nanostructures can be easily modified in terms of shape, size and function at the nanoscale level. Therefore, investigation on smaller and stable branched DNA (bDNA) is of critical significance for biomedical applications. In the present communication, we report smaller and stable branched DNA (bDNA) which is of critical significance for biomedical applications. In this study, a novel strategy has been used in identifying stable bDNA nanostructures with a minimum number of Watson-Crick base pairings. The importance of hybridizing regions and helical twists between multiple oligonucleotides has been explored using various biophysical techniques. The electrophoretic analysis demonstrated that hybridizing regions with ≥12 nt nucleotides can form stable bDNA structures. Substantial negative enthalpic contributions determine the significance of base stacking and the length of oligonucleotides in the hybridization process. Finally, thermal melting investigations confirmed the creation of bDNA nanostructures with ≥12 nt long hybridizing regions. In general, our findings indicate that bDNA oligonucleotides do not undergo hybridization if the number of base pairs is lesser for a single helical turn. Furthermore, the yield and stability of smaller bDNA nanostructures in physiological conditions are comparable with the earlier reported higher-order structures. Hence, smaller bDNAs are more stable which may be preferred over conventional bDNA nanostructures for advanced biomedical applications., 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 © 2024 Elsevier B.V. All rights reserved.)

Background: Rice is considered a high estimated glycemic index (eGI) food because of its higher starch digestibility, which leads to type II diabetes and obesity as a result of a sedentary life style. Furthermore, the incresaing diabetes cases in rice-consuming populations worldwide need alternative methods to reduce the glycemic impact of rice, with dietary prescriptions based on the eGI value of food being an attractive and practical concept. Rice is often paired with vegetables, pulses, tubers and roots, a staple food group in Africa, Latin America and Asia, which are rich in fibre and health-promoting compounds., Results: Rice from four categories (high protein, scented, general and pigmented) was analyzed for eGI and resistant starch (RS) content. Among the genotypes, Improved Lalat had the lowest eGI (53.12) with a relatively higher RS content (2.17%), whereas Hue showed the lowest RS (0.19%) with the highest eGI (76.3) value. The addition of tuber crops to rice caused a significant lowering of eGI where the maximum beneficial effect was shown by elephant foot yam (49.37) followed by yam bean (53.07) and taro (54.43)., Conclusion: The present study suggests that combining rice with suitable tuber crops can significantly reduce its eGI value, potentially reducing the burden of diet-associated lifestyle diseases particularly diabetics. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Relapse and metastasis occur in 30-40% of breast cancer patients, even after targeted treatments like trastuzumab for HER2-positive breast cancer. Accurate individual prognosis is essential for determining appropriate adjuvant treatment and early intervention. This study aims to enhance relapse and metastasis prediction using an innovative framework with machine learning (ML) and ensemble learning (EL) techniques. The developed framework is analyzed using The Cancer Genome Atlas (TCGA) data, which has 123 HER2-positive breast cancer patients. Our two-stage experimental approach first applied six basic ML models (support vector machine, logistic regression, decision tree, random forest, adaptive boosting, and extreme gradient boosting) and then ensembled these models using weighted averaging, soft voting, and hard voting techniques. The weighted averaging ensemble approach achieved enhanced performances of 88.46% accuracy, 89.74% precision, 94.59% sensitivity, 73.33% specificity, 92.11% F-Value, 71.07% Mathew's correlation coefficient, and an AUC of 0.903. This framework enables the accurate prediction of relapse and metastasis in HER2-positive breast cancer patients using H&E images and clinical data, thereby assisting in better treatment decision-making.

Nanostructured lipid carriers (NLCs) are lipidic nanocarriers that recover the permanency and capacity of drug payloads. NLCs are well-known as second-generation lipid nanocarriers with an unstructured matrix, presenting potentially advantageous nanocarrier systems with marketable opportunities because of reproducible production methodologies and biocompatible lipidic excipients. These (NLCs) are now recognized as a very promising nanocarrier structure for the efficient delivery of drugs via different administration routes. In recent years, several NLC-based gels have been developed and evaluated for topical delivery of many drugs and other therapeutic agents. This review article presents an overview of NLC-based topical gels investigated to deliver drugs via ocular, dermal, and transdermal routes. In addition, the classification, manufacturing, characterizations, advantages, and disadvantages of NLCs are addressed in this article. We also discussed different evaluations of NLC-based topical gels., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Fungal keratitis (mycotic keratitis) is an eye infection in which the cornea is infected by fungi and such fungal keratitis management can be effectively possible by ocular administration of antifungal drugs., Objective: The main objectives of the present research were to develop and evaluate fluconazoleloaded transfersomal hydrogels for ocular delivery in the effective management of fungal keratitis., Methods: A 23 factorial design-based approach was used for statistical optimization, where (A) the ratio of lipid to edge activators, (B) the amount of hyaluronic acid (% HA), and (C) the ratio of edge activators (sodium deoxycholate to Span 80) were taken as three factors. The average vesicle diameter (Z, nm) of transfersomes was taken as a response. Further, fluconazole-loaded transfersomes (FTO) were incorporated into 1% Carbopol 940-based hydrogel (OF1) and 2% HMPC K4M-based hydrogel (OF2) containing D-panthenol (5% w/w)., Results: The optimal variable setting for the optimized formulations of FTO was (A) = 9.15, (B) = 0.30%, and (C) = 3.00. FTO exhibited 66.39 nm Z, 0.247 polydispersity index, - 33.10 mV zeta potential, and 65.38 ± 1.77 % DEE, and desirable elasticity. TEM image of FTO demonstrated a unilamellar vesicular structure. The ex vivo ocular permeation of fluconazole from transfersomal hydrogels was sustained over 24 h. All the transfersomal hydrogels showed good bioadhesion and excellent antifungal activity with respect to the zone of inhibition against Candida albicans than Aspergillus fumigates, in vitro. HET-CAM study results demonstrated that both the hydrogels were nonirritant and safe for ocular. Short-term physical stability study suggested the stability of the developed formulation., Conclusion: The current research demonstrated a new way to enhance the ocular penetration of fluconazole via transfersomal hydrogel formulations for ocular delivery in the effective management of fungal keratitis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Yield gap analysis is used to characterize the untapped production potential of cropping systems. With emerging large-n agronomic datasets and data science methods, pathways for narrowing yield gaps can be identified that provide actionable insights into where and how cropping systems can be sustainably intensified. Here we characterize the contributing factors to rice yield gaps across seven Indian states, with a case study region used to assess the power of intervention targeting. Primary yield constraints in the case study region were nitrogen and irrigation, but scenario analysis suggests modest average yield gains with universal adoption of higher nitrogen rates. When nitrogen limited fields are targeted for practice change (47% of the sample), yield gains are predicted to double. When nitrogen and irrigation co-limitations are targeted (20% of the sample), yield gains more than tripled. Results suggest that analytics-led strategies for crop intensification can generate transformative advances in productivity, profitability, and environmental outcomes., (© 2024. The Author(s).)

The importance of data charts is self-evident, given their ability to express complex data in a simple format that facilitates quick and easy comparisons, analysis, and consumption. However, the inherent visual nature of the charts creates barriers for people with visual impairments to reap the associated benefts to the same extent as their sighted peers. While extant research has predominantly focused on understanding and addressing these barriers for blind screen reader users, the needs of low-vision screen magnifer users have been largely overlooked. In an interview study, almost all low-vision participants stated that it was challenging to interact with data charts on small screen devices such as smartphones and tablets, even though they could technically "see" the chart content. They ascribed these challenges mainly to the magnifcation-induced loss of visual context that connected data points with each other and also with chart annotations, e.g., axis values. In this paper, we present a method that addresses this problem by automatically transforming charts that are typically non-interactive images into personalizable interactive charts which allow selective viewing of desired data points and preserve visual context as much as possible under screen enlargement. We evaluated our method in a usability study with 26 low-vision participants, who all performed a set of representative chart-related tasks under different study conditions. In the study, we observed that our method signifcantly improved the usability of charts over both the status quo screen magnifer and a state-of-the-art space compaction-based solution.

Reducing methane (CH 4 ) emissions is increasingly recognized as an urgent greenhouse gas mitigation priority for avoiding ecosystem 'tipping points' that will accelerate global warming. Agricultural systems, namely ruminant livestock and rice cultivation are dominant sources of CH 4 emissions. Efforts to reduce methane from rice typically focus on water management strategies that implicitly assume that irrigated rice systems are consistently flooded and that farmers exert a high level of control over the field water balance. In India most rice is cultivated during the monsoon season and hydrologic variability is common, particularly in the Eastern Gangetic Plains (EGP) where high but variable rainfall, shallow groundwater, and subtle differences in topography interact to create complex mosaics of field water conditions. Here, we characterize the hydrologic variability of monsoon season rice fields ( n = 207) in the Indian EGP ('Eastern India') across two contrasting climate years (2021, 2022) and use the D e n itrification D e c omposition (DNDC) model to estimate GHG emissions for the observed hydrologic conditions. Five distinct clusters of field hydrology patterns were evident in each year, but cluster characteristics were not stable across years. In 2021, average GHG emissions (8.14 mt CO 2 -eq ha -1 ) were twice as high as in 2022 (3.81 mt CO 2 -eq ha -1 ). Importantly, intra-annual variability between fields was also high, underlining the need to characterize representative emission distributions across the landscape and across seasons to appropriately target GHG mitigation strategies and generate accurate baseline values. Simulation results were also analyzed to identify main drivers of emissions, with readily identified factors such as flooding period and hydrologic interactions with crop residues and nitrogen management practices emerging as important. These insights provide a foundation for understanding landscape variability in GHG emissions from rice in Eastern India and suggest priorities for mitigation that honor the hydrologic complexity of the region., Competing Interests: The authors declare that they have no conflicts of interest., (© 2024 The Authors.)

Insulin is a peptide hormone that is essential for regulating body homeostasis. Furthermore, it is involved in various neurological functions such as memory, behaviors, and cognition. The ubiquitous distribution of insulin receptors on various brain cells, such as neurons, microglia, astrocytes, and oligodendrocytes, and their differential localization across various brain regions, including the hippocampus, hypothalamus, and olfactory bulb, collectively underscore the crucial involvement of insulin in the modulation of cerebral functions. Along with ageing, in some pathological conditions such as diabetes and brain insulin resistance, the need for exogenous insulin is felt to compensate for insulin deficiency. In these cases, the biggest obstacle to the delivery of insulin to the brain is the blood-brain barrier (a physical barrier consisting of endothelial cells with tight junctions), which prevents the direct entry of most substances possessing high molecular weight, like insulin, into the brain. Therefore, different delivery methods have been proposed by researchers for insulin delivery that directly or indirectly cause the transfer of insulin to the brain. Some of these methods lack high efficiency and cause many side effects for the patient. In this regard, many new technologies have come to the aid of researchers and have introduced more effective delivery strategies, including the use of nanocarriers. Despite the promising outcomes demonstrated in the experimental models, the utilization of these techniques in human studies remains at a nascent stage and necessitates further comprehensive investigation. This review article aims to examine the diverse methods of insulin administration to the brain by gathering extensive information on insulin and its obstacles to brain delivery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Red blood cells (RBCs) exhibit an interesting response to hydrodynamic flow, releasing adenosine triphosphate (ATP). Subsequently, these liberated ATP molecules initiate a crucial interaction with endothelial cells (ECs), thereby setting off a cascade involving the release of calcium ions (Ca 2 + ). Ca 2 + exerts control over a plethora of cellular functions, and acts as a mediator for dilation and contraction of blood vessel walls. This study focuses on the relationship between RBC dynamics and Ca 2 + dynamics, based on numerical simulations under Poiseuille flow within a linear two-dimensional channel. It is found that the concentration of ATP depends upon a variety of factors, including RBC density, channel width, and the vigor of the flow. The results of our investigation reveals several features. Firstly, the peak amplitude of Ca 2 + per EC escalates in direct proportion to the augmentation of RBC concentration. Secondly, increasing the flow strength induces a reduction in the time taken to reach the peak of Ca 2 + concentration, under the condition of a constant channel width. Additionally, when flow strength remains constant, an increase in channel width corresponds to an elevation in calcium peak amplitude, coupled with a decrease in peak time. This implies that Ca 2 + signals should transition from relatively unconstrained channels to more confined pathways within real vascular networks. This notion gains support from our examination of calcium propagation in a linear channel. In this scenario, the localized Ca 2 + release initiates a propagating wave that gradually encompasses the entire channel. Notably, our computed propagation speed agrees with observations., (© 2024. The Author(s).)

Different nanocarriers-based strategies are now extensively being used as an important strategy for improving drug efficacy and responsiveness, reducing toxicity issues related to drugs and harmful side effects, and overcoming the numerous significant difficulties related to absorption and bioavailability. Amongst different nanocarriers, nanovesicles are excellent and versatile systems for effectively delivering biomolecules, drugs, and targeted ligand distribution and location. Nanovesicles are nanosized self-assembling spherical capsules with an aqueous core and one/more lipid(s) layers. Several synthetic nanovesicles have been developed and investigated for their prospective uses in delivering drugs, proteins, peptides, nutrients, etc. Important procedures for nanovesicle manufacturing are thin-film hydration, unshaken method, ethanol injection, ether injection, proliposomes, freeze-drying, hot method, cold method, reverse-phase evaporation, and ultrasonication. Liposomes, liposomes, ethosomes, exosomes, and transferosomes (elastic vesicles) are the nonvesicular candidates extensively investigated to deliver antiviral drugs. This review article comprehensively reviews different nanovesicles, their compositions, manufacturing, and applications as potential carriers for effectively delivering different antiviral drugs to treat viral diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The current study describes the efficacy of B. acutangula fruit extract in wound healing via incorporation within topical gels. B. acutangula fruit extract was produced by solvent extraction method. The bioactive extract was incorporated within Carbopol 940-based topical gels, which were applied topically over the excision and incision wounds. The change in healing process was observed till 20 days. The percentages of closure of excision wound area were 92.89 % and 93.43 %, when treated with topical herbal gels containing B. acutangula fruit extract of 5 % and 10 %, respectively. The tensile strengths of incision area in rats treated with topical herbal gels containing 5 % and 10 % methanol extract of B. acutangula fruits were found to be 25±5.12 g and 30±4.10 g, respectively. The wound healing activity of topical herbal gels containing B. acutangula fruit extract in rats was found to be significant when compared with that of the reference standard and untreated groups. In addition, in silico studies suggested about good skin permeability and binding to the proteins responsible for delaying wound healing. It can be concluded that this topical herbal gels containing B. acutangula fruit extract could be used clinically for the treatment of wounds., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Carboxylesterase enzymes convert a prodrug ramipril into the biologically active metabolite ramiprilat. It is prescribed for controlling ocular hypertension after oral administration. High concentrations of carboxylesterase enzymes in rectal and colon tissue can transform ramipril significantly to ramiprilat. Sustained rectal delivery of ramipril has been developed for intra-ocular pressure lowering effect using a normotensive rabbit model. Rectal suppositories have been formulated using a matrix base of HPMC K100-PEG 400-PEG 6000, incorporating varying amounts of Gelucire by the fusion moulding method. The presence of Gelucire in the suppository exhibited sustained structural relaxation-based release kinetics of RM compared to its absence. Intravenous and oral administration of ramipril has decreased IOP in the treated rabbit up to 90 and 360 min, respectively. Treated rabbits with suppositories have revealed decreased IOP for an extended period compared to the above. Formulation containing GEL 3% reduced intra-ocular pressure to 540 min, with the highest area under the decreased IOP curve. Compared to oral, the pharmacodynamic bioavailability of ramipril has been improved significantly using a sustained-release rectal suppository. A rectal suppository for sustained delivery of ramipril could be used to lower IOP significantly.

In this work, the electromigration dispersion (EMD) due to the charged electrolytes in microchannels is considered without using the thin electrical double layer assumption. The electrokinetic flow and transport of ions are actuated within a rectangular micro-/nanochannel having a negative surface charge density under the influence of an external electric field. Due to the local variation of the conductivity and the nonvalidity of the electroneutrality condition, the local electric field varies as a function of the solute concentration, wall surface charge density, valency, and Debye layer length. The resulting electrokinetic flow due to the external electric field drives the fluid along with the charged species, where the Taylor-Aris dispersion separates the solutes into their different constituents. The local concentration dependence of the electric field leads to the formation of concentration profiles that are slightly asymmetric with respect to the standard Gaussian distribution. Including a finite Debye layer thickness has an effect on the advection of the species as well as the diffusion of the species. It is found that in cases where Debye layers are thicker, the species advects faster within the microchannel. This might give valuable insights into the nature of the EMD. Our model aims to predict the evolution of ionic concentration at all positions within the channel. A study of the higher-order statistics in skewness and kurtosis has also been conducted to obtain a better understanding of the idealized model consisting of a buffer solution., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

An in-silico approach was implemented to develop a multi-epitope subunit vaccine construct against the recent outbreak of the Monkeypox virus. The contribution of 10 different antigenic proteins based on their antigenicity led to the selection of 10 HTL, 9 CTL, and 6 BCL epitopes. The construct was further investigated for its allergenicity, antigenicity, and physio-chemical properties using servers such as AllerTOP and Allergen FP, VaxiJen and ANTIGENPro, and ProtParam respectively. The secondary structure of the vaccine was predicted using the SOPMA server followed by I-TASSER for the 3D structure. After refinement and validation of structural stability of the modelled vaccine, a molecular docking assay was implemented to study the interaction of the known TLR4 receptor with that of the constructed vaccine using the ClusPro server. The docked vaccine and TLR4 receptor were studied using the molecular dynamics (MD) simulation to validate the stability of the complex. After codon optimization the cDNA was constructed and in-silico cloning of the vaccine construct was carried out. The vaccine was also subjected to computational immune assay which predicted a powerful immune response against the Monkeypox virus validating that the developed multi-epitope vaccine construct can be a potent vaccine candidate., Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00220-5., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: HIF-1α, a key player in medical science, holds immense significance in therapeutic approaches. This review delves into its complex dynamics, emphasizing the delicate balance required for its modulation. HIF-1α stands as a cornerstone in medical research, its role extending to therapeutic strategies. This review explores the intricate interplay surrounding HIF-1α, highlighting its critical involvement and the necessity for cautious modulation., Areas Covered: In sickle cell disease (SCD), HIF-1α's potential to augment fetal hemoglobin (HbF) production and mitigate symptoms is underscored. Furthermore, its role in cancer is examined, particularly its influence on survival in hypoxic tumor microenvironments, angiogenesis, and metastasis. The discussion extends to the intricate relationship between HIF-1α modulation and cancer risks in SCD patients, emphasizing the importance of balancing therapeutic benefits and potential hazards., Expert Opinion: Managing HIF-1α modulation in SCD patients requires a nuanced approach, considering therapeutic potential alongside associated risks, especially in exacerbating cancer risks. An evolutionary perspective adds depth, highlighting adaptations in populations adapted to low-oxygen environments and aligning cancer cell metabolism with primitive cells. The role of HIF-1α as a therapeutic target is discussed within the context of complex cancer biology and metabolism, acknowledging varied responses across diverse cancers influenced by intricate evolutionary adaptations.

Abstract: COVID-19 pandemic has increased the amount of plastic burden to environment and complexities of plastic waste management. Change in behavioral pattern with advent of this pandemic led to increased practice of hygiene and increased use of different types of personal protective equipment. Unfortunately, rapid rise in production of the PPEs (like Hazmat suit, gloves, etc.) and single-use plastics used in RT-PCR and other testing are the biggest source for increased non-biodegradable plastic waste leading to amplified burden on plastic waste management. A number of measures like prioritizing the policies directed towards changes at behavioral, social and institutional level need to be started. Also, reduction in plastic waste along with proper plastic waste management policies should be implemented. To prevent the transition from one pandemic to other; improvement in government policies with public private partnership are the need of the hour.

Bifunctional electrocatalysts for the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) are the heart of metal-air batteries, fuel cells, and other energy storage systems. Here, we report a series of a novel class of redox-active viologen-based ionic covalent organic networks (vCONs) which are directly used as metal-free bifunctional electrocatalysts towards ORR and OER applications. These vCONs (named vGC, vGAC, vMEL and vBPDP) were synthesized by the well-known Zincke reaction. The installation of redox-active viologen moieties among the extended covalent organic architectures played a crucial role for exceptional acid/base stability, as well as bifunctional ORR and OER activities, confirmed by the cyclic voltammetry (CV) curves. Among all of them, vBPDP showed high ORR efficiency with a half-wave potential of 0.72 V against a reversible hydrogen electrode (RHE) in 1 M KOH electrolyte. In contrast, vMEL demonstrated high OER activity with an overpotential of 320 mV at a current density of 10 mAcm -2 and a Tafel slope of 109.4 mV dec -1 in 1 M KOH electrolyte solution. This work is exceptional and unique in terms of directly used pristine ionic covalent organic networks that are used as bifunctional (ORR and OER) electrocatalysts without adding any metals or conductive materials.

Strigolactones (SLs) are a new class of plant hormones that play a significant role in regulating various aspects of plant growth promotion, stress tolerance and influence the rhizospheric microbiome. GR24 is a synthetic SL analog used in scientific research to understand the effects of SL on plants and to act as a plant growth promoter. This study aimed to conduct hormonal seed priming at different concentrations of GR24 (0.1, 0.5, 1.0, 5.0 and 10.0 µM with and without arbuscular mycorrhizal fungi (AMF) inoculation in selected aerobic rice varieties (CR Dhan 201, CR Dhan 204, CR Dhan 205, and CR Dhan 207), Kasalath-IC459373 (P-tolerant check), and IR-36 (P-susceptible check) under phosphorus (P)-deficient conditions to understand the enhancement of growth and priming effects in mycorrhization. Our findings showed that seed priming with 5.0 µM SL GR24 enhanced the performance of mycorrhization in CR Dhan 205 (88.91 %), followed by CR Dhan 204 and 207, and AMF sporulation in CR Dhan 201 (31.98 spores / 10 gm soil) and CR Dhan 207 (30.29 spores / 10 g soil), as well as rice growth. The study showed that the highly responsive variety CR Dhan 207 followed by CR Dhan 204, 205, 201, and Kasalath IC459373 showed higher P uptake than the control, and AMF treated with 5.0 µM SL GR24 varieties CR Dhan 205 followed by CR Dhan 207 and 204 showed the best performance in plant growth, chlorophyll content, and soil functional properties, such as acid and alkaline phosphatase activity, soil microbial biomass carbon (MBC), dehydrogenase activity (DHA), and fluorescein diacetate activity (FDA). Overall, AMF intervention with SL GR24 significantly increased plant growth, soil enzyme activity, and uptake of P compared to the control. Under P-deficient conditions, seed priming with 5.0 µM strigolactone GR24 and AMF inoculum significantly increased selected aerobic rice growth, P uptake, and soil enzyme activities. Application of SLs formulations with AMF inoculum in selected aerobic rice varieties, CR Dhan 207, CR Dhan 204, and CR Dhan 205, will play an important role in mycorrhization, growth, and enhancement of P utilization under P- nutrient deficient conditions., 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., (© 2024 The Authors.)

Rice production faces a significant threat from the rice leaffolder, Cnaphalocrocis medinalis . To address this challenge, growing resistant varieties stands out as a sustainable and eco-friendly pest management strategy. This necessitates identifying resistant sources and understanding their inheritance patterns through employing DNA markers for marker-assisted resistance breeding. Our study involves screening for resistant cultivars following the SES of IRRI, assessing genetic diversity among landraces using molecular markers, and identifying genomic regions associated with resistance. Screening indicated that 33.33%, 27.08%, 19.79%, and 19.80% of genotypes were resistant, moderately resistant, susceptible, and admixture, respectively. Landraces were categorized into three clusters, with clusters I and II predominantly containing moderately resistant and resistant cultivars, and cluster III mainly susceptible types. Molecular variance analysis revealed 12% variation among populations and 88% within the population. Simple linear regression identified significant marker-trait associations, with markers RM 162 and RM 284 on chromosomes 6 and 8, respectively, found highly associated with leaffolder resistance. Phenotypic variation in leaffolder damage correlated highly with the allelic effects of these markers. Further confirmation of marker linkage with resistance loci was established through independent assays on highly resistant and susceptible genotypes. The information derived from genetic diversity and marker-trait associations will be useful for future marker-assisted resistance breeding programs, enhancing the sustainability of rice production., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Forensic age assessments are crucial in the evaluation of criminal responsibility and preventing false age claims. Of all the methods available, the Greulich and Pyle (GP) atlas is most commonly used for age estimation purposes. Therefore, the current study sought to analyze the reliability and applicability of the GP standard and, additionally, to determine any possible association between the socioeconomic status (SES), food habits, and estimated skeletal maturity in the North Indian population. The study included 627 (334 males and 293 females) healthy children up to 19 years of age with varying SES and food habits. The skeletal age (SA) was estimated by three different evaluators using the GP atlas. The chronological mean age (CA) and SA were compared in different age cohorts. A paired t-test and a Pearson chi-square test were applied to show the difference between CA and estimated SA and the association of skeletal maturity with SES and food habits. The estimated skeletal age in males was retarded by 0.142 years or 1.72 months (p ≤ 0.05), whereas in females, it was retarded by 0.259 years or 3.12 months (p ≤ 0.05). In males, the GP method has significantly underestimated SA in age cohorts 3-4, 4-5, 6-7, 7-8, 8-9, and 12-13, whereas it overestimated in 10-11 and 18-19 years. However, in females, the SA was significantly underestimated in age groups 10-11, 12-13, and 14-15, respectively. Estimated skeletal maturity had no significant association with SES and food habits. The current study concludes that the GP atlas may not be applicable to North India's population. The observed difference in assessed skeletal maturity may be due to geographical region, genetics, hormonal effects, etc., which require further investigation. Hence, population-specific standards are necessary to determine the bone age of Indian children accurately., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The future of reactive nitrogen (N) for subtropical lowland rice to be characterised under diverse N-management to develop adequate sustainable practices. It is a challenge to increase the efficiency of N use in lowland rice, as N can be lost in various ways, e.g., through nitrous oxide (N 2 O) or dinitrogen (N 2 ) emissions, ammonia (NH 3 ) volatilization and nitrate (NO 3 - ) leaching. A field study was carried out in the subsequent wet (2021) and dry (2022) seasons to assess the impacts of different N management strategies on yield, N use efficiency and different N losses in a double-cropped rice system. Seven different N-management practices including application of chemical fertilisers, liquid organic fertiliser, nitrification inhibitors, organic nutrient management and integrated nutrient management (INM) were studied. The application of soil test-based neem-coated urea (NCU) during the wet season resulted in the highest economic yield, while integrated nutrient management showed the highest economic yield during the dry season. Total N losses by volatilization of NH 3 , N 2 O loss and leaching were 0.06-4.73, 0.32-2.14 and 0.25-1.93 kg ha -1 , corresponding to 0.06-5.84%, 0.11-2.20% and 0.09-1.81% of total applied N, respectively. The total N-uptake in grain and straw was highest in INM (87-89% over control) followed by the soil test-based NCU (77-82% over control). In comparison, recovery efficiency of N was maximum from application of NCU + dicyandiamide during both the seasons. The N footprint of paddy rice ranged 0.46-2.01 kg N-eq. t -1 during both seasons under various N management. Ammonia volatilization was the process responsible for the largest N loss, followed by N 2 O emissions, and NO 3 - leaching in these subtropical lowland rice fields. After ranking the different N management practices on a scale of 1-7, soil test-based NCU was considered the best N management approach in the wet year 2021, while INM scored the best in the dry year 2022., 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 © 2024 Elsevier Ltd. All rights reserved.)

Rice-based integrated farming system improves the productivity and profitability by recycling resources efficiently. In the sub-humid tropics, rice production without sufficient nutrient replenishment often leads to soil health and fertility degradation. There has been very limited research on soil health and fertility after adopting a multi-enterprising rice-based integrated farming system (IFS), notably in the rice-fish-livestock and agroforestry system, when compared to a conventional farming system (CS). Therefore, the present study analyzed the dynamics of soil properties, soil bacterial community structure and their possible interaction mechanisms, as well as their effect on regulating soil quality and production in IFS, IFSw (water stagnant area of IFS) and CS. The results indicated that soil nutrient dynamics, bacterial diversity indices (Shannon index, Simpson index, Chao 1, ACE and Fisher index) and system productivity were higher in IFSw and IFS compared to CS. Moreover, relative operational taxonomic units of dominant bacterial genera (Chloroflexi, Acidobacteria, Verrucomicrobia, Planctomycetes, Cyanobacteria, Crenarchaeota and Gemmatimonadetes) were also higher in IFSw and IFS compared to CS. Mean soil quality index (SQI) was highest in IFSw (0.780 ± 0.201) followed by IFS (0.770 ± 0.080) and CS (0.595 ± 0.244). Moreover, rice equivalent yields (REY) and rice yields were well correlated with the higher levels of soil biological indices (SQI Biol ) in IFS. Overall, our results revealed that rice-based IFS improved the soil health and fertility and ensuing crop productivity through positive interaction with soil bacterial communities and nutrient stoichiometry leading to agroecosystem sustainability., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Antimicrobial resistance (AMR) has been one of the biggest global health threats in recent years, mostly in low- and middle-income countries, which requires urgent research using a multidisciplinary research approach. The use of large quantities of antimicrobial drugs inappropriately for humans, poultry and agriculture has been recognized as a leading cause of antibiotic resistance and the predominance of drug-resistance pathogens in the environment. This protocol aims to describe the use/misuse of antibiotics (ABs) in the community and evaluate clinical samples from healthcare settings to detect genes associated with antimicrobial resistance., Methods: We will conduct a community-level survey in different villages of the Tigiria block to assess knowledge and awareness on ABs and AMR. We will conduct in-depth interviews (IDIs) with doctors, pharmacists, nurses and drug sellers, as well as focus group discussions (FGDs) with ASHA and ANM workers who are involved in antibiotic supplies to the community. Quantitative data from the community survey and qualitative data of IDIs and FGDs will be linked and analyzed using statistical modeling and iterative thematic content analysis. Specimens (stool, urine, blood and wound/pus) will be collected from clinically diagnosed patients of different healthcare centers of Tigiria block. The samples will be cultured for bacterial isolation and antibiotic sensitivity testing. Genomic DNA will be isolated from positive bacterial cultures and sequenced using PCR to evaluate high-threat multi-drug resistance organisms (MDROs), screening of plasmid-mediated quinolone resistance (PMQR) genes, antimicrobial genes responsible for MDR and quinolone resistance-determining regions (QRDRs)., Conclusion: This is the community-based protocol to evaluate the knowledge, attitudes, awareness and practices regarding ABs and AMR. The study protocol establishes a foundation for evaluating population-based prevalence and risk factors for AMR and MDROs in rural areas of the Odisha state, India., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Pattnaik, Nayak, Karna, Rehman, Sahoo, Palo, Kanungo, Kshatri, Parai, Walia, Pati and Bhattacharya.)

Pharmaceutical grade sugars manufactured under Current Good Manufacturing Practice (cGMP) and complied with International Pharmaceutical Excipients Council (IPEC) quality standards, also contain a significant amount of nano-particulate impurities (NPIs). This review will focus on the origin of NPIs, the mechanism of their interference with Dynamic light scattering (DLS) and endotoxin tests, filtration technology to effectively reduce the NPIs, methodologies for analytical quantification of NPIs, guidance for setting the limits of threshold concentration and the overall impact of NPIs on the therapeutic activity, performance, stability of biopharmaceuticals and protein-based formulations. NPIs with an average particle size of 100 to 200 nm are present in sugars and are a combination of various chemicals such as dextrans (with the presence of β-glucans), ash, inorganic metal salts, aromatic colorants, etc. These NPIs primarily originate from raw materials and cannot be removed during the sugar refinement process. While it is commonly believed that filtering the final formulation with a 0.22 μ sterilizing grade filter removes all microbes and particles, it is important to note that NPIs cannot be filtered using this standard sterile filtration technology. Exceeding the threshold limit of NPIs can have detrimental effects on formulations containing proteins, monoclonal Antibodies (mAbs), nucleic acids, and other biopharmaceuticals. NPIs and β-glucans have a critical impact on the functionality and therapeutic activity of biomolecules and if present below the threshold limit of reaction, stability and shelf-life of biologics formulation will be greatly improved and the risk of immunogenic reactions must be significantly decreased., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)