bluuebunny/crossref_metadata_2025 huggingface dataset:
Acoustic characterization for creep behaviors of marine sandy hydrate-bearing sediment
Authors: Li Yanlong , Hu Qiaobo , Wu Nengyou , Wang Hongbin , Sun Xiaofeng , Hu Gaowei , Sun Zhiwen , Jiang Yujing
Published: December 2023

Marine natural gas hydrate (NGH) is a promising substitutive low-carbon energy resource, whereas NGH-production induced geoengineering concerns remain challenging. Advanced forecast of possible geoengineering risks is the fundamental for eco-friendly NGH exploitation. Reservoir creep deformation is an early symptom of the geoengineering risks. However, whether the creep deformation behaviors of the NGH-bearing strata is predictable remains controversial. In this study, a series of multi-step loading creep test are conducted for sandy gas hydrate bearing sediment (GHBS) samples, during which the ultrasonic responses are recorded simultaneously. The acoustic velocity, compression-to-shear velocity ratio, Poission’s ratio, main frequency, and main frequency amplitude are used to characterize creep failures of the GHBS for the first time. Combining analyses of the creep behaviors and acoustic responses yield the following conclusions. Firstly, the long-term strength derived from creeping test is 0.45–0.60 times of the shear strength derived from triaxial shearing. Ignoring the creep effect might underestimate the scale and intensity of possible geoengineering risks during long-term NGH exploitation. Secondly, the acoustic velocity increases gently and then decreases continuously during creeping. Once the accelerated creep appears, the acoustic velocity plummets significantly, together with a sudden decrease in the compression-to-shear velocity ratio, and fluctuations in the main frequency and its amplitude. Furthermore, the main frequency and its amplitude shall fluctuate abruptly prior to the emergence of the accelerated creep. Therefore, we anticipate that the combination of abnormal fluctuations of main frequency and its amplitude can be used as early-warning indicators for possible creep failure of the GHBS. The results might have great significance for in-situ detection and prediction of possible reservoir failure during long-term NGH exploitation.
Structural definition of babesial RAP-1 proteins identifies a novel protein superfamily across Apicomplexa
Authors: Hötzel Isidro , Suarez Carlos E.
Published: December 2023

Apicomplexan protozoa are intracellular parasites of medical and economic importance. These parasites contain specialized apical complex organelles, including rhoptries, that participate in the process of host cell invasion. Conserved antigens expressed in the rhoptries are rational vaccine targets, but whether conservation of protein structure is a functional requirement for invasion remains unknown. Novel protein structural modeling enables identification of structurally conserved protein families that are not evident by sequence analysis alone. Here we show by AlphaFold2 structural modeling that the rhoptry-associated protein 1 superfamily of the Piroplasmida hemoparasites Babesia and Theileria (pRAP-1) is structurally conserved, with the core conserved region being composed of a globin-like and a 4-helix bundle subdomain. Search for structurally related members of this protein family in other apicomplexan parasites revealed structural homologues of pRAP-1 in several species of Plasmodium, Toxoplasma gondii and other members of the Sarcocystidae family. Based on these structural findings, pRAP-1 is a conserved apical complex protein, but whether these proteins share functional features in different species remains unknown. Identification of widely conserved elements involved in infection in these parasites will enhance our knowledge of invasion mechanisms, and facilitate the design of methods for controlling diseases that affect humans and animals globally.
Digitalization enhancement in the pharmaceutical supply network using a supply chain risk management approach
Authors: Wong Wai Peng , Saw Pui San , Jomthanachai Suriyan , Wang Leong Seng , Ong Huey Fang , Lim Chee Peng
Published: December 2023

One major issue in pharmaceutical supply chain management is the supply shortage, and determining the root causes of medicine shortages necessitates an in-depth investigation. The concept of risk management is proposed in this study to identify significant risk factors in the pharmaceutical supply chain. Fuzzy failure mode and effect analysis and data envelopment analysis were used to evaluate the risks of the pharmaceutical supply chain. Based on a case study on the Malaysian pharmaceutical supply chain, it reveals that the pharmacy node is the riskiest link. The unavailability of medicine due to unexpected demand, as well as the scarcity of specialty or substitute drugs, pose the most significant risk factors. These risks could be mitigated by digital technology. We propose an appropriate digital technology platform consisting of big data analytics and blockchain technologies to undertake these challenges of supply shortage. By addressing risk factors through the implementation of a digitalized supply chain, organizations can fortify their supply networks, fostering resilience and efficiency, and thereby playing a pivotal role in advancing the Pharma 4.0 era.
Myeloid deletion of talin-1 reduces mucosal macrophages and protects mice from colonic inflammation
Authors: Latour Yvonne L. , McNamara Kara M. , Allaman Margaret M. , Barry Daniel P. , Smith Thaddeus M. , Asim Mohammad , Williams Kamery J. , Hawkins Caroline V. , Jacobse Justin , Goettel Jeremy A. , Delgado Alberto G. , Piazuelo M. Blanca , Washington M. Kay , Gobert Alain P. , Wilson Keith T.
Published: December 2023

The intestinal immune response is crucial in maintaining a healthy gut, but the enhanced migration of macrophages in response to pathogens is a major contributor to disease pathogenesis. Integrins are ubiquitously expressed cellular receptors that are highly involved in immune cell adhesion to endothelial cells while in the circulation and help facilitate extravasation into tissues. Here we show that specific deletion of the Tln1 gene encoding the protein talin-1, an integrin-activating scaffold protein, from cells of the myeloid lineage using the Lyz2-cre driver mouse reduces epithelial damage, attenuates colitis, downregulates the expression of macrophage markers, decreases the number of differentiated colonic mucosal macrophages, and diminishes the presence of CD68-positive cells in the colonic mucosa of mice infected with the enteric pathogen Citrobacter rodentium. Bone marrow-derived macrophages lacking expression of Tln1 did not exhibit a cell-autonomous phenotype; there was no impaired proinflammatory gene expression, nitric oxide production, phagocytic ability, or surface expression of CD11b, CD86, or major histocompatibility complex II in response to C. rodentium. Thus, we demonstrate that talin-1 plays a role in the manifestation of infectious colitis by increasing mucosal macrophages, with an effect that is independent of macrophage activation.
The impact of wind energy on plant biomass production in China
Authors: Gao Li , Wu Qingyang , Qiu Jixiang , Mei Yingdan , Yao Yiran , Meng Lina , Liu Pengfei
Published: December 2023

Global wind power expansion raises concerns about its potential impact on plant biomass production (PBP). Using a high-dimensional fixed effects model, this study reveals significant PBP reduction due to wind farm construction based on 2404 wind farms, 108,361 wind turbines, and 7,904,352 PBP observations during 2000–2022 in China. Within a 1–10 km buffer, the normalized differential vegetation and enhanced vegetation indices decrease from 0.0097 to 0.0045 and 0.0075 to 0.0028, respectively. Similarly, absorbed photosynthetically active radiation and gross primary productivity decline from 0.0094 to 0.0034% and 0.0003–0.0002 g*C/m2 within a 1–7 km buffer. Adverse effects last over three years, magnified in summer and autumn, and are more pronounced at lower altitudes and in plains. Forest carbon sinks decrease by 12,034 tons within a 0–20 km radius, causing an average economic loss of $1.81 million per wind farm. Our findings underscore the balanced mitigation strategies for renewable energy transition when transiting from fossil fuels.
Numerical study on the hydrodynamic performance and internal flow of an axial-flow pump with various inlet flow angles
Authors: Son Yong-Jin , Kim Yong-In , Yang Hyeon-Mo , Lee Kyoung-Yong , Yoon Joon Yong , Choi Young-Seok
Published: December 2023

In this study, numerical simulation was employed to predict the performance and internal flow characteristics of the inlet of an axial-flow pump by assigning an absolute flow angle to the inlet guide vane (IGV) trailing-edge flow. Further, the finite volume method based on the three-dimensional Reynolds-averaged Navier–Stokes equations was employed to discretize the governing equations. The shear stress transport model was used as the turbulence model, and an appropriate number of nodes were selected for the hexahedral grid system through a grid-dependency test. The performance curve and changes in the internal flow field were investigated based on the variation in the flow angle at the inlet of the axial-flow pump. These results can be used to establish an efficient operational plan by adjusting the IGV angle of IGV when installing a variable IGV for an axial-flow pump.
Increased habitat segregation at the dawn of the Phanerozoic revealed by correspondence analysis of bioturbation
Authors: Meek Dean M. , Buatois Luis A. , Mángano M. Gabriela , Eglington Bruce M.
Published: December 2023

The Agronomic Revolution of the early Cambrian refers to the most significant re-structuration of the benthic marine ecosystem in life history. Using a global compilation of trace-fossil records across the Ediacaran-Cambrian transition, this paper investigates the relationship between the benthos and depositional environments prior to, during, and after the Agronomic Revolution to shed light on habitat segregation via correspondence analysis. The results of this analysis characterize Ediacaran mobile benthic bilaterians as facies-crossing and opportunistic, with low levels of habitat specialization. In contrast, the Terreneuvian and Cambrian Series 2 reveal progressive habitat segregation, parallel to matground environmental restriction. This event was conducive to the establishment of distinct endobenthic communities along the marine depositional profile, showing that the increase in styles of animal-substrate interactions was expressed by both alpha and beta ichnodiversity. Habitat segregation at the dawn of the Phanerozoic may illustrate an early extension of the trophic group amensalism at community scale.
Sustained participation in a Payments for Ecosystem Services program reduces deforestation in a Mexican agricultural frontier
Authors: Charoud Hugo , Costedoat Sebastien , Izquierdo-Tort Santiago , Moros Lina , Villamayor-Tomás Sergio , Castillo-Santiago Miguel Ángel , Wunder Sven , Corbera Esteve
Published: December 2023

Payments for Ecosystem Services (PES) provide conditional incentives for forest conservation. PES short-term effects on deforestation are well-documented, but we know less about program effectiveness when participation is sustained over time. Here, we assess the impact of consecutive renewals of PES contracts on deforestation and forest degradation in three municipalities of the Selva Lacandona (Chiapas, Mexico). PES reduced deforestation both after a single 5-year contract and after two consecutive contracts, but the impacts are only detectable in higher deforestation-risk parcels. Enrollment duration increases PES impact in these parcels, which suggests a positive cumulative effect over time. These findings suggest that improved spatial targeting and longer-term enrollment are key enabling factors to improve forest conservation outcomes in agricultural frontiers.
CuO nanoparticles mixed with activated BC extracted from algae as promising material for supercapacitor electrodes
Authors: Ahmed Alsharif Marwah , Alatawi Aishah , Hamdalla Taymour A. , Alfadhli S. , Darwish A. A. A.
Published: December 2023

The present analysis aims to use existing resources to lower the cost of electrodes and reduce environmental pollution by utilizing waste materials like green algae. In the present research, the hydrothermal carbonization technique was utilized to synthesize a nano sized CuO mixed with activated biochar (CuO@BC) extracted from red sea algae (Chlorophyta). The CuO@BC sample was extensively examined using several advanced physical techniques, such as UV/Visible spectroscopy, FTIR, XED, HRTEM, SEM, EDX, BET, and TGA. The HRTEM indicated that the size of the particles is 32 nm with a larger surface area and without aggregations. The BET analysis of CuO@BC indicates that the material contains pores of a relatively large size and with a pore diameter of about 42.56 A°. The electrochemical analysis of CuO@BC modified glassy carbon electrode CuO@BC/GCE has been investigated using CV, GCD, and EIS techniques. This CuO@BC/GCE shows excellent electrochemical features that are significant for energy storage applications. The CuO@BC/GCE showed a specific capacitance of approximately 353 Fg−1 which is higher compared to individual materials. Overall, the research outcomes suggest that the CuO@BC/GCE shows potential for use in high-performance supercapacitors as energy storage systems that are eco-friendly and sustainable.
Acceptance sampling plan based on difference in difference estimator with application
Authors: Azam Muhammad , Khan Maira Ahsan , Arshad Asma , Saleem Muhammad , Aslam Muhammad
Published: December 2023

An acceptance sampling plan has been designed in this study based on the Difference-in-Difference estimator. This plan is designed for the inspection of those product units whose life follows the normal distribution. The operating characteristic function is discussed for the two respective cases of the standard deviation known and unknown. The parameters of the proposed plan are determined by minimizing the sample size and followed by the satisfying optimization rule. The results are computed and tabulated for various parametric combinations of acceptable quality levels and limiting quality levels. The computations are performed by using R statistical programming software for all respective cases. The real-life application of the proposed sampling plan has been discussed and elaborated in detail.
CT texture features and lung shunt fraction measured using 99mTc-macroaggregated albumin SPECT/CT before trans-arterial radioembolization for hepatocellular carcinoma patients
Authors: Lee Jae Hwan , Lee Chong-ho , Kim Minuk , Song Yoo Sung , Yoon Chang Jin , Lee Won Woo
Published: December 2023

The aim of this study is to determine whether contrast-enhanced computed tomography (CECT)-based texture parameters can predict high (> 30 Gy) expected lung dose (ELD) calculated using 99mTc macroaggregated albumin single-photon emission computed tomography/computed tomography (SPECT/CT) for pre-trans-arterial radioembolization (TARE) dosimetry. 35 patients were analyzed, with a treatable planned dose of ≥ 200 Gy for unresectable hepatocellular carcinoma (HCC). Lung shunt fraction (LSF) was obtained from planar and SPECT/CT scans. Texture features of the tumor lesion on CECT before TARE were analyzed. Univariate and multivariate linear regression analyses were performed to determine potential ELD > 30 Gy predictors. Among the 35 patients, nine (25.7%) had ELD > 30 Gy, and had a higher LSF than the ELD ≤ 30 Gy group using the planar (20.7 ± 8.0% vs. 6.3 ± 3.3%; P < 0.001) and SPECT/CT (12.4 ± 5.1% vs. 3.5 ± 2.0%; P < 0.001) scans. The tumor integral total (HU × L) value was a predictor for high LSF using SPECT/CT, with an area under the curve, sensitivity, and specificity of 0.983 (95% confidence interval: 0.869–1.000, P < 0.001), 100%, and 88.5%, respectively. The tumor integral total value is an imaging marker for predicting ELD > 30 Gy. Applying CECT texture analysis may assist in reducing time and cost in patient selection and modifying TARE treatment plans.
Evolution of the Araliaceae family involved rapid diversification of the Asian Palmate group and Hydrocotyle specific mutational pressure
Authors: Kang Jong-Soo , Giang Vo Ngoc Linh , Park Hyun-Seung , Park Young Sang , Cho Woohyeon , Nguyen Van Binh , Shim Hyeonah , Waminal Nomar Espinosa , Park Jee Young , Kim Hyun Hee , Yang Tae-Jin
Published: December 2023

The Araliaceae contain many valuable species in medicinal and industrial aspects. We performed intensive phylogenomics using the plastid genome (plastome) and 45S nuclear ribosomal DNA sequences. A total of 66 plastome sequences were used, 13 of which were newly assembled in this study, 12 from new sequences, and one from existing data. While Araliaceae plastomes showed conserved genome structure, phylogenetic reconstructions based on four different plastome datasets revealed phylogenetic discordance within the Asian Palmate group. The divergence time estimation revealed that splits in two Araliaceae subfamilies and the clades exhibiting phylogenetic discordances in the Asian Palmate group occurred at two climatic optima, suggesting that global warming events triggered species divergence, particularly the rapid diversification of the Asian Palmate group during the Middle Miocene. Nucleotide substitution analyses indicated that the Hydrocotyloideae plastomes have undergone accelerated AT-biased mutations (C-to-T transitions) compared with the Aralioideae plastomes, and the acceleration may occur in their mitochondrial and nuclear genomes as well. This implies that members of the genus Hydrocotyle, the only aquatic plants in the Araliaceae, have experienced a distinct evolutionary history from the other species. We also discussed the intercontinental disjunction in the genus Panax and proposed a hypothesis to complement the previously proposed hypothesis. Our results provide the evolutionary trajectory of Araliaceae and advance our current understanding of the evolution of Araliaceae species.
β-endorphin suppresses ultraviolet B irradiation-induced epidermal barrier damage by regulating inflammation-dependent mTORC1 signaling
Authors: Kim Hyung-Su , Kim Hyoung-June , Hong Yong-Deog , Son Eui Dong , Cho Si-Young
Published: December 2023

Solar ultraviolet B (UVB) radiation triggers excessive inflammation, disrupting the epidermal barrier, and can eventually cause skin cancer. A previous study reported that under UVB irradiation, epidermal keratinocytes synthesize the proopiomelanocortin-derived peptide β-endorphin, which is known for its analgesic effect. However, little is known about the role of β-endorphin in UVB-exposed skin. Therefore, in this study, we aimed to explore the protective role of β-endorphin against UVB irradiation-induced damage to the skin barrier in normal human keratinocytes (NHKs) and on a human skin equivalent model. Treatment with β-endorphin reduced inflammatory responses in UVB-irradiated NHKs by inactivating the NF-κB signaling pathway. Additionally, we found that β-endorphin treatment reversed UVB-induced abnormal epidermal proliferation and differentiation in NHKs and, thus, repaired the skin barrier in UVB-treated skin equivalents. The observed effects of β-endorphin on UVB-irradiated NHKs were mediated via blockade of the Akt/mTOR signaling pathway. These results reveal that β-endorphin might be useful against UVB-induced skin injury, including the disruption of the skin barrier function.
Enhanced far infrared emissivity, UV protection and near-infrared shielding of polypropylene composites via incorporation of natural mineral for functional fabric development
Authors: He Pengfei , Low Rayland Jun Yan , Burns Stephen Francis , Lipik Vitali , Tok Alfred Iing Yoong
Published: December 2023

Far infrared radiation in the range of 4–20 µm has been showed to have biological and health benefits to the human body. Therefore, incorporating far-infrared emissivity additives into polymers and/or fabrics hold promise for the development of functional textiles. In this study, we incorporated nine types of natural minerals into polypropylene (PP) film and examined their properties to identify potential candidates for functional textiles and apparels. The addition of 2% mineral powders into PP film increased the far-infrared emissivity (5–14 µm) by 7.65%-14.48%. The improvement in far-infrared emissivity within the range of 5–14 µm, which overlaps with the peak range of human skin radiation at 8–14 µm, results in increased absorption efficiency, and have the potential to enhance thermal and biological effects. Moreover, the incorporation of mineral powders in PP films exhibited favorable ultraviolet (UV) protection and near-infrared (NIR) shielding properties. Two films, specifically those containing red ochre and hematite, demonstrated excellent UV protection with a UPF rating of 50+ and blocked 99.92% and 98.73% of UV radiation, respectively. Additionally, they showed 95.2% and 93.2% NIR shielding properties, compared to 54.1% NIR shielding properties of PP blank films. The UV protection and NIR shielding properties offered additional advantages for the utilization of polymer composite with additives in the development of sportswear and other outdoor garments. The incorporation of minerals could absorb near-IR radiation and re-emit them at longer wavelength in the mid-IR region. Furthermore, the incorporation of minerals significantly improved the heat retention of PP films under same heat radiation treatment. Notably, films with red ochre and hematite exhibited a dramatic temperature increase, reaching 2.5 and 3.2 times the temperature increase of PP films under same heat radiation treatment, respectively (46.8 °C and 59.9 °C higher than the temperature increase of 20.9 °C in the PP film). Films with additives also demonstrated lower thermal effusivity than PP blank films, indicating superior heat insulation properties. Therefore, polypropylene films with mineral additives, particularly those containing red ochre and hematite, showed remarkable heat capacity, UV-protection, NIR-shielding properties and enhanced far infrared emissivity, making them promising candidates for the development of functional textiles.
SHP2 inhibitors maintain TGFβ signalling through SMURF2 inhibition
Authors: Lai Xianning , Lui Sarah Kit Leng , Lam Hiu Yan , Adachi Yuta , Sim Wen Jing , Vasilevski Natali , Armstrong Nicola J. , Bridgeman Stephanie Claire , Main Nathan Michael , Tan Tuan Zea , Tirnitz-Parker Janina E. E. , Thiery Jean Paul , Ebi Hiromichi , Kumar Alan Prem , Eichhorn Pieter Johan Adam
Published: December 2023

Despite the promising antitumor activity of SHP2 inhibitors in RAS-dependent tumours, overall responses have been limited by their narrow therapeutic window. Like with all MAPK pathway inhibitors, this is likely the result of compensatory pathway activation mechanisms. However, the underlying mechanisms of resistance to SHP2 inhibition remain unknown. The E3 ligase SMURF2 limits TGFβ activity by ubiquitinating and targeting the TGFβ receptor for proteosome degradation. Using a functional RNAi screen targeting all known phosphatases, we identify that the tyrosine phosphatase SHP2 is a critical regulator of TGFβ activity. Specifically, SHP2 dephosphorylates two key residues on SMURF2, resulting in activation of the enzyme. Conversely, SHP2 depletion maintains SMURF2 in an inactive state, resulting in the maintenance of TGFβ activity. Furthermore, we demonstrate that depleting SHP2 has significant implications on TGFβ-mediated migration, senescence, and cell survival. These effects can be overcome through the use of TGFβ-targeted therapies. Consequently, our findings provide a rationale for combining SHP2 and TGFβ inhibitors to enhance tumour responses leading to improved patient outcomes.
Challenges and prospects of visual contactless physiological monitoring in clinical study
Authors: Huang Bin , Hu Shen , Liu Zimeng , Lin Chun-Liang , Su Junfeng , Zhao Changchen , Wang Li , Wang Wenjin
Published: December 2023

The monitoring of physiological parameters is a crucial topic in promoting human health and an indispensable approach for assessing physiological status and diagnosing diseases. Particularly, it holds significant value for patients who require long-term monitoring or with underlying cardiovascular disease. To this end, Visual Contactless Physiological Monitoring (VCPM) is capable of using videos recorded by a consumer camera to monitor blood volume pulse (BVP) signal, heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2) and blood pressure (BP). Recently, deep learning-based pipelines have attracted numerous scholars and achieved unprecedented development. Although VCPM is still an emerging digital medical technology and presents many challenges and opportunities, it has the potential to revolutionize clinical medicine, digital health, telemedicine as well as other areas. The VCPM technology presents a viable solution that can be integrated into these systems for measuring vital parameters during video consultation, owing to its merits of contactless measurement, cost-effectiveness, user-friendly passive monitoring and the sole requirement of an off-the-shelf camera. In fact, the studies of VCPM technologies have been rocketing recently, particularly AI-based approaches, but few are employed in clinical settings. Here we provide a comprehensive overview of the applications, challenges, and prospects of VCPM from the perspective of clinical settings and AI technologies for the first time. The thorough exploration and analysis of clinical scenarios will provide profound guidance for the research and development of VCPM technologies in clinical settings.
A sociotechnical framework to assess patient-facing eHealth tools: results of a modified Delphi process
Authors: Jacob Christine , Lindeque Johan , Müller Roman , Klein Alexander , Metcalfe Thomas , Connolly Samantha L. , Koerber Florian , Maguire Roma , Denis Fabrice , Heuss Sabina C. , Peter Marc K.
Published: December 2023

Among the thousands of eHealth tools available, the vast majority do not get past pilot phases because they cannot prove value, and only a few have been systematically assessed. Although multiple eHealth assessment frameworks have been developed, these efforts face multiple challenges. This study aimed to address some of these challenges by validating and refining an initial list of 55 assessment criteria based on previous frameworks through a two-round modified Delphi process with in-between rounds of interviews. The expert panel (n = 57) included participants from 18 countries and 9 concerned parties. A consensus was reached on 46 criteria that were classified into foundational and contextual criteria. The 36 foundational criteria focus on evaluating the eHealth tool itself and were grouped into nine clusters: technical aspects, clinical utility and safety, usability and human centricity, functionality, content, data management, endorsement, maintenance, and developer. The 10 contextual criteria focus on evaluating the factors that vary depending on the context the tool is being evaluated for and were grouped into seven clusters: data-protection compliance, safety regulatory compliance, interoperability and data integration, cultural requirements, affordability, cost-benefit, and implementability. The classification of criteria into foundational and contextual helps us assess not only the quality of an isolated tool, but also its potential fit in a specific setting. Criteria subscales may be particularly relevant when determining the strengths and weaknesses of the tool being evaluated. This granularity enables different concerned parties to make informed decisions about which tools to consider according to their specific needs and priorities.
Irrigation intensification impacts sustainability of streamflow in the Western United States
Authors: Ketchum David , Hoylman Zachary H. , Huntington Justin , Brinkerhoff Douglas , Jencso Kelsey G.
Published: December 2023

Quantifying the interconnected impacts of climate change and irrigation on surface water flows is critical for the proactive management of our water resources and the ecosystem services they provide. Changes in streamflow across the Western U.S. have generally been attributed to an aridifying climate, but in many basins flows can also be highly impacted by irrigation. We developed a 35-year dataset consisting of streamflow, climate, irrigated area, and crop water use to quantify the effects of both climate change and irrigation water use on streamflow across 221 basins in the Colorado, Columbia, and Missouri River systems. We demonstrate that flows have been altered beyond observed climate-related changes and that many of these changes are attributable to irrigation. Further, our results indicate that increases in irrigation water use have occurred over much of the study area, a finding that contradicts government-reported irrigation statistics. Increases in crop consumption have enhanced fall and winter flows in some portions of the Upper Missouri and northern Columbia River basins, and have exacerbated climate change-induced flow declines in parts of the Colorado basin. We classify each basin’s water resources sustainability in terms of flow and irrigation trends and link irrigation-induced flow changes to irrigation infrastructure modernization and differences in basin physiographic setting. These results provide a basis for determining where modern irrigation systems benefit basin water supply, and where less efficient systems contribute to return flows and relieve ecological stress.
Virtual Screening of Milk Proteins of Risperidone for Taste Improvement; Experimental Validation of Sodium Caseinate Binding by Fluorometry and Taste Assessment by Palatability
Authors: Chatale Bandoo C. , Ananthanarayan Laxmi , Degani Mariam S.
Published: December 2023

Risperidone (RIS), a widely used antipsychotic drug has patient’s non-compliance because of bitter taste. Taste improvement on the basis of milk proteins which seems likely to be effective due to their bio-compatibility, biodegradability, and also has several health benefits. The current research work encompasses the study of the binding interactions of RIS with milk protein employing molecular modelling and fluorometry. Molecular docking was performed for screening various milk proteins for their interactions of RIS with β-Lactoglobulin (β-LG), α-lactalbumin, lactoferrin, and casein which structure has not yet been elucidated by the X-ray crystallography or NMR spectroscopy so homology model of casein was constructed and validated using Ramachandran plot. RIS docked on these milk proteins and casein was found to be an effective mode of binding with RIS. induced fit docking, the Molecular Mechanics‐Generalized Born Surface Area were conducted for prediction of binding mode, along with binding affinity of RIS with casein and it was found effective mode of binding with RIS with casein. The fluorometry was used to study stability of the complex of RIS with NaCAS (sodium salt of casein). Bitter taste improvement potential of NaCAS with RIS was confirmed in-vivo using previously reported single bottle-test rat model. The NaCAS reduced RIS bitter perception, which could directly relate to its binding capacity. Thus Complex formation RIS with NaCAS is a promising approach for taste improvement of RIS.
In-Silico Evaluation of Phytochemicals as Potential Antiepileptic Drugs
Authors: Anand Harshini , Sushmitha B. , Dey Ritrick , Akhilan M. , Shiva S , Mahesh AR.
Published: December 2023

Numerous phytochemical substances have been used by traditional medicinal systems to treat epileptic conditions. The antiepileptic properties of isolated phytochemicals from various natural medicinal sources are well documented. The underlying mechanisms behind how these isolated elements exhibit their anticonvulsant effects is particularly unknown. The goal of the current investigation is to suggest potential receptors for these phytoconstituents’ binding and predict their mechanisms of action, pharmacokinetic and toxicological properties. Molecular interactions were investigated utilizing in-silico molecular docking research with verified docking techniques to determine their potential binding mechanisms. Phytochemicals with favourable docking scores were further sent for in-silico ADME/T (Absorption Distribution Metabolism Excretion Toxicity) studies, so as to determine their pharmacokinetic and toxicological properties. The hit compound obtained from the study was validated using Molecular Dynamics simulations. Amentoflavone, a biflavone present in Rhus pyroides, emerged as the hit compound. It exhibited good binding affinity with majority of the target proteins, which indicates that it might act through multiple targeted mechanisms. It also exhibits high absorption and clearance rates, with low toxicity. Validation of the hit compound Amentoflavone with GABA B (Gamma Amino Butyric Acid receptor type B) was performed through molecular dynamics studies in order to gain deeper insights into their binding interactions. Amentoflavone was identified as the hit compound upon performing molecular docking, ADME/T and molecular dynamics studies. Additionally, validation of the identified hit molecule by pharmacological evaluation would prove its effectiveness as a potential antiepileptic agent.
Screening of Placental Proteins Against Proteases for their Potential Use in Osteoarthritis: A Computational Approach
Authors: James Jithu Jerin , Pavadai Parasuraman , Sandhya K V
Published: December 2023

Osteoarthritis is a chronic joint condition owing to increasing articular cartilage weakening and deterioration. Novel agents targeting articular cartilage molecular mechanisms seem to be most promising. The placental tissues are biocompatible, immunoprivileged and rich in bio factors such as growth factors, cytokines, extracellular matrix and proteins. Placental proteins might reduce cartilage degradation through suppressing the expression of matrix metalloproteases. This study focuses on screening placental proteins against proteases using protein-protein docking and dynamic studies. Protein-protein docking was performed on twenty-six ligand proteins present in placental tissue against matrix metalloproteinase 13 by ZDOCK server and visualized through Biovia Discovery studio. Molecular dynamic study was carried out by DESMOND. Most of the placental proteins were found to have better binding to matrix metalloproteinase 13. Protein-protein docking study showed scores ranging from 1046.272 to 2229.332. Among all the proteins, metalloproteinase inhibitor 3 and plasminogen activator inhibitor 1 scores were found to be 2229.332 and 2131.215 respectively. These ligand proteins bound tightly with the target protein, indicated by greater number of hydrogen bond interactions on the surfaces. Molecular dynamic studies were carried out for the two complexes, complex was found to be stable during molecular dynamic simulation. From the results, metalloproteinase inhibitor 3 and plasminogen activator inhibitor 1 of placenta are found to be a promising candidate for the treatment of osteoarthritis. Based on these findings placental protein can be explored for its anti-arthritis property.
Toxicity and Breast Cancer Risk Prediction Studies for Carbamates: Bioinformatics Approach
Authors: Thathapudi Daveedu , Dumala Naresh , Yendluri Raja Jayarao , Vadela Manohar , Bandaru Nagaraju
Published: December 2023

Pesticides like carbamates are a group of insecticides, widely used in the agricultural sector. Owing to their excessive use in agricultural, domestic, and industrial arenas most of the carbamates are being released into the environment involuntarily. Unintentional or occupational exposure of humans and non-target species to these pesticides may trigger the undesired hazardous consequences. Breast cancer may be one of such consequences and is one of the major life-threatening diseases across the world. However, the ability of these carbamates to induce breast cancer was not well studied and remained elusive. This study was designed to predict the possibility for occurrence of breast cancer upon exposure to the carbamates by interacting with BRCA1 gene using in silico tools. Results of the present investigation revealed that carbamates (propoxur, triallate, carbaryl, allethrin, mobam, butacarb, fenoxycarb and diallate) studied can interact with BRCA1 gene and interfere with the key pathways that are connected with the breast cancer. Furthermore, the findings indicated that the far-reaching impact of their toxicity on human health than their already known effects. These effects need to be validated by in vitro and in vivo methods. This study provides a preliminary yet invaluable information on the carbamates and their possible carcinogenic effect.
Pharmacokinetic Profile of Novel Curcumin-Metformin Conjugate in Rats by LC-MS/MS
Authors: Perumalsamy Vijaybhanu , Kumar D R Harish , Suresh Sarasija
Published: December 2023

Curcumin is known to possess diverse biological activities. But still it has not been introduced as an effective therapeutic agent due to its poor oral bioavailability and stability in gastrointestinal tract. Curcumin-metformin conjugate synthesized by molecular hybridization approach may overcome these limitations. The objective of the study was to develop liquid chromatography-tandem mass spectrometric (LC-MS/MS) method to quantify curcumin in rat plasma and explore the pharmacokinetic profile of novel curcumin-metformin conjugate in comparison with that of free curcumin. Free curcumin and curcumin-metformin conjugate suspensions were administered by oral route to two groups of Sprague-Dawley rats (n=3) at a dose of 130 mg/rat and 40 mg/rat respectively. Blood samples were collected from retro-orbital plexus at regular time intervals and the plasma was analysed for curcumin by LC-MS/MS. Various pharmacokinetic parameters like peak plasma concentration, time taken to reach maximum concentration, area under the curve and half-life were determined. It was observed that curcumin-metformin conjugate increased the bioavailability of curcumin by 6 times of free curcumin on comparing the AUC0-ꝏ values. The results indicated that conjugation of curcumin with metformin enhanced the bioavailability of curcumin. This strategy of conjugation of curcumin with drugs can be used to increase the bioavailability of curcumin thereby potentiating its numerous pharmacological activities.
A Novel Fourier Transform Infrared Spectrophotometric Method for Quantitative Analysis of Irbesartan and Hydrochlorthiazide in Fixed Dose Formulations
Authors: Raghavendra Babu N. , Narender Malothu , Padmavathi Y. , Narmada A. , Ravi Kumar P.
Published: December 2023

The development of reliable Fourier transform infrared (FTIR) instrumentation has made IR spectroscopy a more widely used technique for quantitative analysis. Qualitative organic compound identification has always been its strength. IRB and HTZ were estimated simultaneously in pharmaceutical dosage forms using a new FTIR spectroscopic approach. The approach involves KBr pelletization of IRB and HTZ and direct measurement with a reduced path length cell. In absorbance mode, the instrument gathered infrared spectra with 8cm-1 resolution. IR peaks changed after baseline adjustment. The strong, unambiguous, and proportionate carbonyl (C=O) and amine (N-H) functional groups of IRB and HTZ at 1733cm-1 and 3361cm-1 were chosen for quantitative measurement. IRB concentrations from 60-300μg/mg and HTZ concentrations from 5-25μg/mg followed Beer Lambert’s law. ICH guidelines validated the methodology. A statistical t-test was used to compare the results of the new FTIR method to the outcomes of the current UV method, and the results showed no statistically significant difference between the two ways at p=0.05. From the current study’s findings, it can be inferred that the simultaneous estimation method for IRB and HTZ is simple, accurate, and cost-effective. The proposed method can be successfully used to estimate IRB and HTZ simultaneously in pure and pharmaceutical dosage forms.
Design, Development and Characterization of Eberconazole Proniosomes
Authors: Arvapalli Swarupa , Areti Anka Rao
Published: December 2023

Eberconazole (EBZ) is a BCS class II drug that has poor solubility and high permeability. Aim of the present research work is to prepare and evaluate Eberconazole Proniosomes. Proniosomes were prepared by thin-film hydration method ratios of nonionic surfactant with cholesterol and keeping drug and DCP constant. Multilamellar Proniosome were prepared by the thin-film hydration method. Accurately weighed quantities of drug, surfactant (Span), and CHOL were dissolved in chloroform in a round-bottom flask. DCP were added to each formulation as a negative charge-inducing agent. The chloroform was evaporated at 60oC under reduced pressure using a rotary flash evaporator at various RPM. After chloroform evaporation, the flask was kept under vacuum overnight in a nitrogen atmosphere to remove residual solvent. The thin films were hydrated with 6 ml of phosphate buffered saline (PBS), pH 5.5 and the formulations were Sonicated 3 times at 50 Hz in a bath- sonicator for 15 min with 5 min interval between successive times. Vesicle suspensions were also Sonicated for 5 min. The Proniosomes were prepared by simple hydration and further evaluated for entrapment efficiency, particle size and shape analysis by optical microscopy, in-vitro drug release study, kinetic data analysis and model fitting. The formulation F6, which showed entrapment efficiency of 97.78% and in-vitro release over the period of 12h 97.35%, was found to be best formulation. The proniosomes follows Peppas release kinetics mechanism.
Development and Optimization of Niosomes for Brain Targeting Using Response Surface Methodology
Authors: Veenadevi A. , Srinivasa Babu P. , Kurra Pallavi
Published: December 2023

The current research work deals with the combination of surfactants for vesicular drug delivery of potent chemotherapeutic drugs like capecitabine with advantages of controlled release as well as brain specific targeting. Niosomes formulation was optimized by employing a surface response method in which central composite designed was selected for getting a less number of formulations with better results using Design Expert software version V 11. The niosomes were formulated by using combination of span-80 and brij-78 as non-ionic surfactant by thin film hydration technique in which cholesterol and diacetyl phosphate in constant ratio as per design. Optimized formulation was evaluated for the following parameters like microscopic examination, vesicular size, zeta potential, drug entrapment efficiency, drug content, In-vitro drug release, kinetic studies, and stability studies. Results revealed that the combination of surfactant concentration on the response parameters from statistical optimization method employing various 3D plots and some contour plots for achieving significant results for exhibited a higher retention of Capecitabine inside the vesicles. In-vitro drug release rate was slower at period of 12 hours about 57.01% for optimized formulation. Kinetic evaluation of optimized F10 formulation reported first order drug release with R2 value of 0.9803. The Korsmeyer Peppas model was represented by the release exponent (n) value of 0.0564 indicates that the optimized Niosomal formulation follows a non-Fickian type of drug transport or anomalous diffusion process.
Optimization of Vanillin Crosslinked Chitosan/Polycarbophil Superporous Hydrogel Hybrids Containing Tablets for Regulated Drug Delivery
Authors: Shwetha K , Basavaraj B.V
Published: December 2023

Polysaccharides are most sustainable building blocks with improved characteristics for formulation of superporous hydrogels (SPH). Present research work emphasis on development and optimization of tablets comprising vanillin crosslinked chitosan/polycarbophil (CVP) SPH hybrids for regulated drug delivery. The formulation of CVP SPH hybrids were prepared using microwave irradiation with different concentrations of chitosan (polymer), vanillin (crosslinking agent) and polycarbophil (hybrid agent). Resultant formulation was subjected to FTIR, DSC, TGA, SEM and NMR characterization. Prepared CVP hybrids were powdered and blended with other excipients to formulate CVP tablets using wet granulation technique. These tablets were formulated and systematically optimized using Box Behnken design (BBD). Optimized CVP tablets were assessed for its pre-and post-compression parameters. FTIR, DSC, TGA and NMR studies showed formation of newer bonds due to interactions between the chitosan, vanillin and polycarbophil. SEM images revealed highly interconnected porous structure. BBD successfully provided the significant value for the quadratic model and second order polynomial equation was plotted. Optimized CVP tablets complied with pharmacopeial specifications for hardness, friability and weight variation. Optimized CVP tablets also revealed potential swelling characteristics with chitosan promoting swelling at pH 1 to 4 and polycarbophil at pH 4 to 8 with overall swelling ratio of 17.6531±0.1134 and 21.7031± 0.0791 respectively. Overall, the current study signifies that the optimized CVP tablets can be successfully formulated by BBD and employed for regulated delivery of drugs to the GI tract, buccal cavity, colon, vaginal, and rectal region for both local and systemic action.
Ophthalmic Quercetin Films Preparation and Evaluation Using Euphorbia Hirta
Authors: Srikala K. , Male CH K V L S N Anjana , Jyothi G. Nirmala , Snehitha K. , Asha P. Mary , Anusha N.
Published: December 2023

Cataracts cause the lens to become cloudy, which blurs the image. The arrangement of the protein and water in the lens keeps it clear and allows light to pass through. Age-related protein clumping may cause a cataract, which lowers the amount of light reaching the retina, by blocking a small part of the lens. Cataract can be cured without surgery using quercetin films. Quercetin occular films were produced by using a solvent evaporation method using glycerine as a lubricant and were assessed for physical and chemical characteristics, in-vitro drug release experiments, and in vivo release studies. Each polymer’s formulations were assessed for number of factors, including thickness, surface pH, moisture absorption rate, moisture loss rate, and quercetin drug release, in vitro dissolution studies. All the formulations were tested with formulation release rate by using dissolution process, therapeutic action was tested by using preclinical studies on Wister albino rats for the parameters like decrease in opacity index, when compared to the naphthalene control and standard drug isotine drops were used for measuring the therapeutic parameters. Among all six formulations, F4 formulation drug release rate is high, with 78.9%, at 200 mg concentration. Rats pre-treated with naphthalene for 28 days shows profound decrease in opacity index. Hence may be ophthalmic quercetin films are promising options for the treatment of cataract in upcoming days.