bluuebunny/crossref_metadata_2025 huggingface dataset:
A Ground-based Platform for Reliable Estimates of Fruit Number, Size, and Color in Stone Fruit Orchards
Authors: Islam Muhammad S. , Scalisi Alessio , O’Connell Mark Glenn , Morton Peter , Scheding Steve , Underwood James , Goodwin Ian
Published: October 2022

Automatic in-field fruit recognition techniques can be used to estimate fruit number, fruit size, fruit skin color, and yield in fruit crops. Fruit color and size represent two of the most important fruit quality parameters in stone fruit (Prunus sp.). This study aimed to evaluate the reliability of a commercial mobile platform, sensors, and artificial intelligence software system for fast estimates of fruit number, fruit size, and fruit skin color in peach (Prunus persica), nectarine (P. persica var. nucipersica), plum (Prunus salicina), and apricot (Prunus armeniaca), and to assess their spatial and temporal variability. An initial calibration was needed to obtain estimates of absolute fruit number per tree and a forecasted yield. However, the technology can also be used to produce fast relative density maps in stone fruit orchards. Fruit number prediction accuracy was ≥90% in all the crops and training systems under study. Overall, predictions of fruit number in two-dimensional training systems were slightly more accurate. Estimates of fruit diameter (FD) and color did not need an initial calibration. The FD predictions had percent standard errors <10% and root mean square error <5 mm under different training systems, row spacing, crops, and fruit position within the canopy. Hue angle, a color attribute previously associated with fruit maturity in peach and nectarine, was the color attribute that was best predicted by the mobile platform. A new color parameter—color development index (CDI), ranging from 0 to 1—was derived from hue angle. The adoption of CDI, which represents the color progression or distance from green, improved the interpretation of color measurements by end-users as opposed to hue angle and generated more robust color estimations in fruit that turn purple when ripe, such as dark plum. Spatial maps of fruit number, FD, and CDI obtained with the mobile platform can be used to inform orchard decisions such as thinning, pruning, spraying, and harvest timing. The importance and application of crop yield and fruit quality real-time assessments and forecasts are discussed.
Experimental investigation of trace element partitioning between amphibole and alkali basaltic melt: Toward a more general partitioning model with implications for amphibole fractionation at deep crustal levels
Authors: Bonechi Barbara , Fabbrizio Alessandro , Perinelli Cristina , Gaeta Mario , Petrelli Maurizio
Published: October 2022

Time-series experiments were carried out in a piston-cylinder apparatus at 0.8 GPa and 1030–1080 °C using a hydrous K-basalt melt as the starting material to determine the element partition coefficients between amphibole and silicate glass. Major, minor, and trace element compositions of amphibole and glass were determined with a combination of electron microprobe and laser ablation inductively coupled plasma mass spectrometry. Results show that the main mineral phase is calcic amphibole, and the coexisting glass compositions range from basaltic trachyandesite to andesite. We estimated the ideal radius, the maximum partition coefficient and the apparent Young’s modulus of the A, M1-M2-M3, and M4-M4′ sites of amphibole. The influence of melt and amphibole composition, temperature, and pressure on the partition coefficients between amphiboles and glasses has also been investigated by comparing our data with a literature data set spanning a wide range of pressures (0.6–2.5 GPa), temperatures (780–1100 °C), and compositions (from basanite to rhyolite). Finally, we modeled a deep fractional crystallization process using the amphibole-melt partition coefficients determined in this study, observing that significant amounts of amphibole crystallization (>30 wt%) well reproduce the composition of an andesitic melt similar to that of the calc-alkaline volcanic products found in Parete and Castelvolturno boreholes (NW of Campi Flegrei, Italy).
An evolutionary system of mineralogy, Part VII: The evolution of the igneous minerals (>2500 Ma)
Authors: Hazen Robert M. , Morrison Shaunna M. , Prabhu Anirudh , Walter Michael J. , Williams Jason R.
Published: October 2022

Part VII of the evolutionary system of mineralogy catalogs, analyzes, and visualizes relationships among 919 natural kinds of primary igneous minerals, corresponding to 1665 mineral species approved by the International Mineralogical Association—minerals that are associated with the wide range of igneous rock types through 4.566 billion years of Earth history. A systematic survey of the mineral modes of 1850 varied igneous rocks from around the world reveals that 115 of these mineral kinds are frequent major and/or accessory phases. Of these most common primary igneous minerals, 69 are silicates, 19 are oxides, 13 are carbonates, and 6 are sulfides. Collectively, these 115 minerals incorporate at least 33 different essential chemical elements.

Patterns of coexistence among these minerals, revealed by network, Louvain community detection, and agglomerative hierarchical clustering analyses, point to four major communities of igneous primary phases, corresponding in large part to different compositional regimes: (1) silica-saturated, quartz- and/or alkali feldspar-dominant rocks, including rare-element granite pegmatites; (2) mafic/ultramafic rock series with major calcic plagioclase and/or mafic minerals; (3) silica-undersaturated rocks with major feldspathoids and/or analcime, including agpaitic rocks and their distinctive rare-element pegmatites; and (4) carbonatites and related carbonate-bearing rocks.

Igneous rocks display characteristics of an evolving chemical system, with significant increases in their minerals’ diversity and chemical complexity over the first two billion years of Earth history. Earth’s earliest igneous rocks (>4.56 Ga) were ultramafic in composition with 122 different minerals, followed closely by mafic rocks that were generated in large measure by decompression melting of those ultramafic lithologies (4.56 Ga). Quartz-normative granitic rocks and their extrusive equivalents (>4.4 Ga), formed primarily by partial melting of wet basalt, were added to the mineral inventory, which reached 246 different mineral kinds. Subsequently, four groups of igneous rocks with diagnostic concentrations of rare element minerals—layered igneous intrusions, complex granite pegmatites, alkaline igneous complexes, and carbonatites—all first appeared ~3 billion years ago. These more recent varied kinds of igneous rocks hold more than 700 different minerals, 500 of which are unique to these lithologies.

Network representations and heatmaps of primary igneous minerals illustrate Bowen’s reaction series of igneous mineral evolution, as well as his concepts of mineral associations and antipathies. Furthermore, phase relationships and reaction series associated with the minerals of a dozen major elements (H, Na, K, Mg, Ca, Fe, Al, Si, Ti, C, O, and S), as well as minor elements (notably Li, Be, Sr, Ba, Mn, B, Cr, Y, REE, Ti, Zr, Nb, Ta, P, and F), are embedded in these multi-dimensional visualizations.
Petrogenesis of Chang’E-5 mare basalts: Clues from the trace elements in plagioclase
Authors: Tian Heng-Ci , Yang Wei , Zhang Di , Zhang Huijuan , Jia Lihui , Wu Shitou , Lin Yangting , Li Xianhua , Wu Fuyuan
Published: October 2022

This study focuses on using the chemical compositions of plagioclase to further investigate the petrogenesis of Chang’E-5 young mare basalts and constrain its parental melt composition. Together with previously published data, our results show that the plagioclase in mare basalts overall displays large variations in major and trace element concentrations. Inversion of the plagioclase data indicates that the melt compositions parental to Chang’E-5 basalts have high rare earth elements (REE) concentrations similar to the high-K KREEP rocks (potassium, rare earth elements, and phosphorus). Such a signature is unlikely to result from the assimilation of KREEP components, because the estimated melt Sr shows positive correlations with other trace elements (e.g., Ba, La), which are far from the KREEP end-member. Instead, the nearly parallel REE distributions and a high degree of trace element enrichment in plagioclase indicate an extensive fractional crystallization process. Furthermore, the estimated melt REE concentrations from plagioclase are slightly higher than those from clinopyroxene, consistent with its relatively later crystallization. Using the Ti partition coefficient between plagioclase and melt, we estimated the parental melt TiO2 content from the earliest crystallized plagioclase to be ~3.3 ± 0.4 wt%, thus providing robust evidence for a low-Ti and non-KREEP origin for the Chang’E-5 young basalts in the Procellarum KREEP terrane.
Dynamic relationship between equity, bond, commodity, forex and foreign institutional investments: Evidence from India
Authors: Matha Rajeev , E. Geetha , Kumar Satish , Raghavendra
Published: October 2022

The interrelationship between equity, bond, commodity and forex movements can provide investors with abundant trading opportunities regardless of whether one market is trending upward or downward. Hence, to understand the interlinkage between markets, this study examines the long-run and causal linkage between forex, G-sec bonds, oil prices, gold rates, foreign institutional investment (FII) flows, and equity market and sectoral index returns. Daily time-series data from August 2012 to August 2021 were considered for empirical analysis. Johansen’s cointegration test revealed that foreign exchanges like USD, Euro, GBP and Yen, oil and gold rates, G-bond returns and FII flows were significantly cointegrated with the stock market and sectoral indices in the long run. Further, Granger causality found a uni-directional relationship between forex rates (i.e., USD, Euro, Yen) and the market, as well as sectoral indices, except Nifty 50 and Nifty IT indices. Oil price movements were found to effectively predict future price changes of Nifty consumer durables, auto, IT indices. Gold prices are useful to predict Nifty-Auto, Bank, Financial Services, Oil & Gas and PSU. The study also found a bi-directional relationship from FII inflows to the stock market and sectoral indices. The findings suggest that forex rates, oil prices and FII flows significantly affect India’s stock market and sectoral performance. The study contributes to the existing literature by comprehensively examining the interlinkage between commodities such as oil and gold, foreign exchanges like USD, Euro, GBP and Yen, G-bond, FII flows and the stock market, and fourteen sectoral indices in the Indian context.
ROOM-TEMPERATURE PPB-LEVEL ANILINE VAPOR SENSOR FUNCTIONALIZED WITH UIO-66-SO3H
Authors: Cai Jun , Wang Luyu , Wu Yunling
Published: October 2022

Aniline vapor must be immediately detected at low concentrations since it is a hazardous gaseous chemical. Here, ppb level aniline vapor is detected using the metal-organic framework of UIO-66-SO3H. Utilizing a quartz crystal microbalance (QCM) sensing platform, the aniline adsorption-induced mass change of UIO-66-SO3H is converted to a signal of frequency shift. The sensor can detect a concentration of 20 ppb of aniline vapor and has good sensitivity for this purpose. Additionally, the sensor’s repeatability and stability are satisfactory. Notably, the sensor’s selectivity is prominent. Its response to aniline is much higher than that of ten interfering gases and BTEX vapor. And even in conditions with varying levels of humidity, this sensor maintains response stability.
Influence of reservoir impoundment on rainfall erosivity in the Three Gorges Reservoir region of China
Authors: Jiang Guangyi , Lv Jiaorong , He Xiubin , Bao Yuhai
Published: October 2022

New dammed reservoirs are expected to have a significant effect on the regional hydrocycle, but the detailed patterns may not be well understood. Regional climate change is likely to cause soil erosion uncertainty by affecting rainfall erosivity. In the present study, local precipitation and rainfall erosivity were investigated to determine the impounding influence of the Three Gorges Reservoir. Daily erosive precipitation, from 1980 to 2020, was categorized into four intensity levels (light, moderate, heavy, and very heavy), as well as extreme rainfall, to understand their contribution to erosivity. It was found that the impoundment significantly affected local precipitation, with both heavy precipitation and the relative erosivity showing a substantial declining trend (Sen's slope = 2.141, p < 0.05). The Mann–Kendall test indicated an abrupt change point around the year 2002, evidencing the effect of the reservoir impoundment (since 2003). Reservoir impoundment redistributed the intensity levels of erosive precipitation, leading to a 24.3% decrease in the erosivity of heavy precipitation and an 8.2% increase in the moderate category. The unimodal distribution of monthly precipitation was altered to a bimodal distribution with peaks in July and September, resulting in a longer but lower-risky erosion period of high concern. The fluctuations of Rx1day and Rx5day were obviously flattened after impoundment, with a 54.2% peak reduction in relative erosivity on average. Results indicated that heavy rainfall (including extreme rainfall) was reduced, and annual precipitation and erosivity both had a more even seasonal distribution following reservoir impoundment.
Development of evaluation framework for the selection of run-of-river hydropower potential sites to be included in the Zambian Hydropower Atlas
Authors: Mudenda Frank , van Dijk Marco , Bekker Anja
Published: October 2022

Hydropower is a source of renewable energy, which provides clean electricity around the world with lower greenhouse gas emissions than other sources of energy. Zambia's electricity deficit has been increasing in recent years. As of 2019, over 1.9 million households (57.6%) had no access to electricity and over 96% of the rural population are still without electricity. This calls for attention and sustainable solutions to electrification as reinforced by goal number 7 of the sustainable development goals. Such solutions include the development of a Zambian Hydropower Atlas that can showcase the country's hydropower potential including small-scale technologies, which can boost Zambia's electrification by providing green electricity. The aim of this study was to develop a run-of-river evaluation framework for the selection of hydropower potential sites to be included in the Zambian Hydropower Atlas. The data and formulas required to evaluate hydropower potential were identified and evaluated to develop the evaluation process in the Zambian context. The developed evaluation framework was applied to an existing run-of-river hydropower site located in Zambia to show its application, and it estimated the hydropower potential at the site within a deviation of 14%. The developed evaluation framework can give a first-order evaluation of hydropower potential.
4-picoline adsorption from aqueous solution by using baggage fly ash (BFA): Parametric, kinetic and thermodynamic aspects
Authors: Pangarkar Bhausaheb L. , Shrimal Preena , Daware Gaurav B. , Dabhade Ganesh B.
Published: October 2022

Numerous harmful characteristics of wastewater containing pyridine chemical have a significant negative impact on human health. Therefore, it is preferred to remove it from effluent. The derivatives of pyridine are 2- and 4-picoline. In this work, an adsorption technique was used to remove 4-picoline from the effluent. Wastewater was treated to remove 4-picoline using the natural adsorbent baggage fly ash (BFA). 4-picoline adsorption rate of 82% was reported at pH 6.22, BFA adsorbent dosage of 4 g/L, and contact time of 6 h. The current investigation found that 85.83% of 4-picoline could be removed at its maximum with BFA at a temperature of 333 K. Investigations were also carried out into how the starting concentration and temperature affected the elimination of 4-picoline. According to the kinetic analysis, the process uses pseudo-second-order rate kinetics. The thermodynamics study also demonstrated that all temperatures could be predicted using the Freundlich and Langmuir equilibrium adsorption isotherm models. It further demonstrated that 4-picoline adsorption on BFA is an endothermic process.
Urban surface water quality and the potential of phytoremediation to improve water quality in peri-urban and urban areas in sub-Saharan Africa – a review
Authors: Schnabel Bastian , Wright Sam , Miller Rees , Bryant Lee D. , Kjeldsen Thomas R. , Maconachie Roy , Gbanie Solomon P. , Bangura Kabba S. , Kamara Anthony J.
Published: October 2022

In 2017, 400 million people in sub-Saharan Africa (SSA) were still using unimproved drinking water sources, 80 million of whom relied on untreated surface water. Urban areas are vastly expanding all over the continent and many larger cities in SSA struggle to provide safely managed drinking water. Phytoremediation implemented in constructed wetlands (CWs) is a low-cost and sustainable alternative to highly costly and energy-consuming wastewater treatment plants. In addition, CWs offer the potential to be integrated into farming and aqua-culture systems and can therefore improve food quality and production. The most prominent pollutants in urban SSA surface waters and the pollutant removal efficiencies for microbial and chemical contaminations of different plant species were identified from the literature and the accumulation rates for Pb, Cr, and Cd were compared with each other. A strong focus was given to studies conducted in SSA or other (sub)tropical regions. This review identified a range of potential phytoremediators to treat contaminated surface water and highlights the need for further in situ studies in SSA. Plant species such as Lemna minor, Ipomoea aquatica, Spirodela polyrhiza and Brachiaria mutica show a high potential to phytoremediate the heavy metals Pb, Cr and Cd from surface water.
Exploring the role of potassium ferrate and straw fiber in enhancing the strength of cement-based solidified municipal sludge
Authors: Yang Yahong , Xu Weixin , Yang Qiyong , Sun Li , Dai Yuxuan , Liu Zhen , Zeng Ming , Yang Wenjie , Zhou Caihua
Published: October 2022

The effect of potassium ferrate (PF) and straw fiber (SF) on the strength of cement-based solidified municipal sludge, including the influence of reducing the organic matter in the sludge on the efficiency of the hydration of the cement, was studied. Single-factor tests, orthogonal tests, and linear weighted optimization methods were used to obtain suitable ratios to meet practical requirements, and then SEM and XRD analyses were used to explore the solidification mechanism. The results showed that PF and SF had significant influence on the strength, with SF having the greatest influence and the strength increasing with the amount of both admixtures, and cement had no significant influence on the strength. After linear weighting optimization, the ideal dosage was found to be 20% cement, 20% PF, and 5% SF, which produced a solidified sludge that had an strength of 126.87 kPa, far higher than the 50 kPa required to qualify for disposal in landfills. Analysis of the mineral content and microstructure showed that PF and SF could promote cement hydration and produce more hydration products, and the density of the optimized sample was much higher than that of the raw sludge and a sludge sample mixed with 20% cement alone.
FN1 Promotes Thyroid Carcinoma Cell Proliferation and Metastasis by
Activating the NF-Κb Pathway
Authors: Shen Zhijun , Chen Chen
Published: October 2022

Background:

Thyroid cancer (THCA) is a common endocrine tumor. This study aims to
identify the THCA-related key gene Fibronectin 1 (FN1) by bioinformatics methods and explore its
function and regulatory mechanism.

Methods:

Gene Expression Omnibus database (GSE3678, GSE33630, and GSE53157 datasets) was
searched for the analysis of differentially expressed genes (DEGs) in THCA tissues v.s. (normal
tissues). The enrichment of DEGs was investigated by Gene Ontology and Kyoto Encyclopedia of
Genes and Genomes pathways using the DAVID database. Screening the hub gene was performed with
the STRING database and Cytoscape software. The expression and survival analyses of these hub
genes in THCA were studied with the Gene Expression Profiling Interactive Analysis database.
LinkedOmics database was searched for the related signaling pathways regulated by FN1 in THCA.
Real-time quantitative reverse transcriptase polymerase chain reaction was adopted to detect the
mRNA expression of Fibromodulin, microfibril-associated protein 4, Osteoglycin, and FN1. The cell
viability, growth, migration and aggressiveness were examined by Cell counting kit-8, 5-Ethynyl-2 ′-
deoxyuridine assay, scratch assay, and Transwell assay. The expression levels of NF-κB signaling
pathway-related proteins (p-IκB-α, p-IKK-β, NF-κB p65) were detected by Western blot.

Results:

FN1 mRNA was up-regulated in THCA tissues and cell lines (MDA-T85 and MDA-T41).
The high expression of FN1 is relevant to larger tumor diameters and lymph node metastasis in
sufferers with THCA. Functional experiments showed that overexpression of FN1 in the MDA-T85
cell line promoted growth, migration and aggressiveness; knockdown of FN1 in MDA-T41 cells
inhibited these malignant behaviors. In mechanism, FN1 promoted the expression levels of proteins
related with NF-κB signaling pathway and activated NF-κB signaling pathway.

Conclusions:

FN1 is up-regulated in THCA and facilitates cell growth, migration and invasion by
activating the NF-κB signaling pathway. FN1 will be a promising biomarker of THCA and may
become a molecular target for THCA treatment.
Local Drug Delivery and Tissue Engineering Regulate Vascular Injury
Authors: Edelman Blazer R. , Nugent Helen M.
Published: October 2022

It has become apparent that mechanical interventions designed to alleviate atherosclerotic vascular disease are beset by accelerated vascular diseases of their own. A multitude of agents have been directed against one or more of the cellular events thought to be involved in this process known as restenosis. Most of these agents suppress smooth muscle cell growth in tissue culture and in animal models, and yet no drug to date
has shown any demonstrable benefit against human disease. This may be due to the suboptimal manner in which these drugs were administered. It has been demonstrated that far more beneficial effects are observed if one matches the delivery of a drug to the natural release of endogenous growth regulators. Controlled release of heparin from polymeric matrices inhibited smooth muscle cell proliferation following injury to vascular endothelium in a manner more efficient than in systemic administration. Moreover, the biologic control achieved by the endothelium is not due to one or several compounds, but rather to the concomitant presence and complimentary activity of all the cell-based products. Perivascular implantation of tissue engineered endothelial cell implants around injured arteries reduced intimal hyperplasia far better than isolated administration of heparin. Thus the coupling of polymer based drug delivery technology and tissue engineering with the science of molecular and cell biology provides a means to understanding the paradox of restenosis and even potential therapies.
Endothelin Converting Enzyme Inhibitors
Authors: Jeng Arco Y. , De Lombaert Stephane
Published: October 2022

Endothelins (ETs) are a family of potent, peptidic vasoconstrictors and are implicated in the involvement of a variety of cardiovascular, renal, and central nervous system diseases. The final step of post-translational processing of these peptides is catalyzed by endothelin converting enzyme (ECE), a zinc metalloprotease. Inhibitors of this enzyme are expected to suppress the biosynthesis of ETs and provide an alternate approach to the ETA/ETB receptor antagonism. The biochemical characteristics of ECE are briefly reviewedin this article. The main focus is on the design and pharmacological properties of various classes of ECE inhibitors, including peptides, natural products, and low molecular weight molecules featuring a phosphorus-containirrg functionality, a sulfhydryl, a hydroxamic acid, or a carboxylic acid as the zinc-binding group. Compounds such as phosphoramidon, CGS 26303, and SCH 54470 have been shown to be efficacious in experimental models of hypertension, chronic heart failure, cerebral vasospasm following subarachnoid hemorrhage, and renal failure. Thus, ECE inhibitors may represent a new class of agents for the treatment of diseases where an overproduction of ETs plays a pathogenic role.
Characterization, Antifungal Evaluation against Candida spp. Strains and
Application of Nystatin: β-cyclodextrin Inclusion Complexes
Authors: Urban Amanda Migliorini , Morikava Francine Sumie , Schoeffel Amanda Cristina , Novatski Andressa , Moraes Gustavo Simão , Cachoeira Victoria Schlumberger , Matioli Graciette , Sanches Ito Carmen Antonia , Ferrari Priscileila Colerato , Neppelenbroek Karin Hermana , Urban Vanessa Migliorini , Farago Paulo Vitor
Published: October 2022

Background:

Nystatin (Nys) is a fungicidal drug commonly prescribed for candidiasis disease in several administration routes. However, Nys is a class IV drug according to the Biopharmaceutical Classification System, that possesses limited bioavailability, and is used for local activity.

Objective:

This study developed and characterized nystatin:β-cyclodextrin (Nys:βCD) inclusion complexes and evaluated their activity against Candida spp.

Methods:

Complexes were characterized by physicochemical techniques and drug dissolution profiles. The susceptibility of C. albicans, C. krusei, C. parapsilosis, C. glabrata, C. guilliermondii, C. tropicalis, and C. auris was assessed using the broth microdilution method. The applicability of Nys:βCD inclusion complex was evaluated by incorporating it into a temporary soft material for denture stomatitis treatment

Results:

Nys was better complexed in a 1:1 molar ratio by freeze-drying and spray-drying methods. The inclusion complexes show bi-exponential release, an initial burst release followed by a sustained manner, presenting higher dissolution efficiency than raw Nys. The 1:1 freeze-drying Nys:βCD complex presents antifungal activity against all evaluated Candida strains, showing the maintenance of the drug effectiveness. The inclusion complex incorporated into a tissue conditioner material for denture stomatitis treatment effectively inhibited more than 90% of C. albicans biofilm growth during 7 and 14 days, in a half dose compared to raw Nys.

Conclusion:

This work represents a significant contribution to treating a wide variety of diseases caused by the Candida species, optimizing the drug bioavailability and compliance to the treatment due to improved drug solubility, dissolution, and sustained delivery.
Early Memory Impairment is Accompanied by Changes in GluA1/
p-GluA1 in APP/PS1 Mice
Authors: Zhao Ya-Bo , Hou Xue-Fei , Li Xin , Zhu Li-Su , zhu Jing , Ma Guo-Rui , Liu Yu-Xuan , Miao Yu-Can , Zhou Qian-Yu , Xu Lin , Zhou Qi-Xin
Published: October 2022

Aims:

Exploring the neurobiological mechanisms of early AD damage.

Background:

The early diagnosis of Alzheimer's disease (AD) has a very important impact on the
prognosis of AD. However, the early symptoms of AD are not obvious and difficult to diagnose. Existing
studies have rarely explored the mechanism of early AD. AMPARs are early important learning
memory-related receptors. However, it is not clear how the expression levels of AMPARs change in
early AD.

Objective:

We explored learning memory abilities and AMPAR expression changes in APP/PS1 mice
at 4 months, 8 months, and 12 months.

Method:

We used the classic Morris water maze to explore the learning and memory impairment of
APP/PS1 mice and used western blotting to explore the changes in AMPARs in APP/PS1 mice.

Result:

We found that memory impairment occurred in APP/PS1 mice as early as 4 months of age,
and the impairment of learning and memory gradually became serious with age. The changes in GluA1
and p-GluA1 were most pronounced in the early stages of AD in APP/PS1 mice.

Conclusion:

Our study found that memory impairment in APP/PS1 mice could be detected as early as
4 months of age, and this early injury may be related to GluA1.
Hesperidin: A Potential Therapeutic Agent against COVID-19
Authors: Dhingra Ashwani K. , Chopra Bhawna , Rathi Vaibhav , Sapra Sameer
Published: October 2022

COVID-19, aka Coronavirus Disease 2019, triggered by new severe acute respiratory syndrome
coronavirus-2 or SARS-CoV-2, is now a public health emergency due to its rapid spread, high
transmission efficiency, and severe viral pandemic that is significantly increasing the number of
patients and associated deaths. Currently, no specific treatment is available for this highly contagious
virus. The unavailability of effective and specific treatments and the severity of this epidemic situation
potentiate medicinal chemists’ in supporting new prophylactic or therapeutic interventions against
COVID-19. This study discusses the therapeutic potential of hesperidin, a traditionally used herbal
medicine with an exceptional safety profile. Recent studies on hesperidin advocate its promising potential
in the prevention and management of COVID 19. This paper also discusses the recent clinical
studies based on the previously documented antiviral activity of hesperidin. Herein, we propose the
detailed preclinical and clinical manifestations of hesperidin based on its multifaceted bioactivities to
develop a novel anti-COVID-19 lead.
Review on the Discovery of New Benzimidazole Derivatives as Anticancer
Agents: Synthesis and Structure-activity Relationship (2010-2022)
Authors: Shabana Km , Salahuddin  , Mazumder Avijit , Kumar Rajnish , Datt Vimal , Tyagi Sonakshi , Yar Mohammad Shahar , Ahsan Mohamed Jawed , Sarafroz Mohammad
Published: October 2022

Background:

Benzimidazole (Benz-fused bicyclic ring system) is the most versatile class of
heterocyclic compounds due to its numerous applications in industrial and synthetic organic chemistry
because of its many biological actions. Benzimidazole analogs have been used to discover various medical
problems, such as cancer, bacterial infections, fungi infections, etc. Researchers are studying nitrogencontaining
hybrid heterocyclic compounds because they provide a broad range of therapeutic potential
and have minimal side effects.

Objective:

The current literature review emphasizes recent developments in the design of new benzimidazole
derivatives as possible anticancer agents with their relationship between structure and activity,
which will give insight into the future design of more active benzimidazole molecules.

Results:

The present review consists of synthetic protocols for the synthesis of benzimidazole derivatives
along with their pharmacological potentials and structure-activity relationship in correlation with synthetic
molecules to provide a depth view of the work done on benzimidazole.

Conclusion:

It would be significant for further research in developing better drug molecules representing
a potent derivative of medicinal agents.
Natural Products as a Major Source of Candidates for Potential Senolytic
Compounds obtained by in silico Screening
Authors: Barrera-Vázquez Oscar S. , Magos-Guerrero Gil A. , Escobar-Ramírez Juan L. , Gomez-Verjan Juan C.
Published: October 2022

Background:

Preclinical studies suggest that senolytic compounds such as quercetin (a
natural product) and dasatinib (a synthetic product) decrease senescent cells, reduce inflammation,
and alleviate human frailty. This evidence has opened a new field of research for studying the effect
of these compounds on age-related dysfunction and diseases.

Objective:

The present study performed in silico and we identified new potential senolytic candidates
from an extensive database that contains natural products (NPs) and semi-synthetic products (SMSs).

Methods:

Computer programs Chemminer and rcdk packages, which compared the fingerprints of
numerous molecules (40,383) with reference senolytics, and the creation of a pharmacological network
built with signaling pathways and targets involved in senescence processes were used to identify
compounds with a potential activity.

Results:

Six drug-like candidates (3,4'-dihydroxypropiophenone, baicalein, α, β-dehydrocurvularin,
lovastatin, luteolin, and phloretin) were identified.

Conclusion:

To our knowledge, this is the first time that these six natural molecules have been proposed
to have senolytic activity. To validate the methodology employed in the identification of new
drug-like senolytics, experimental evidence is needed with models that evaluate senolytic activity.
Assessment of Knowledge and Awareness Among the Stakeholders of Clinical Research at the Site: A Collaborative, Electronic-Survey Approach to Identify the Indicators of Quality
Authors: Pal Chandana , Rengan Aravind Kumar , Moodahadu Latha , Swaminathan Jayanthi , Nagalla Balakrishna
Published: October 2022

Background:

There has been a concern in the quality of clinical trials conducted in terms of data integrity, accuracy or ethical conduct. This study aimed to assess the tangible gap existing in knowledge and application of rules and guidelines among Researcher, Research staff (RS) and Eth-ics Committee (EC) members - the three research stakeholders at the study sites.

Method:

A validated e-questionnaire with details for demography, role, years of experience, affilia-tion and questions on knowledge and understanding about their clinical research functions based on the New Drugs and Clinical Trials (NDCT) Rules 2019, including: ‘Role and responsibility, Regula-tions, Reporting timelines, Documentation, Conflict of interest and Miscellaneous’ was circulated among the seven research sites of one organization with their fourteen Institutional ECs as part of the planned annual survey. Responses with >60% correct answers were arbitrarily considered to rep-resent adequate knowledge

Results:

Of 201participants, there were 27.4% Researchers, 50.2% were from the EC and 22.4% RS. A greater proportion of Researchers had >5 years (43.6%) of experience. The mean ±SD of correct an-swers obtained was 66.9±14.77 and was statistically significant (p<0.05) among the groups, highest for EC members (71.4±11.51), those with 2-5 years of experience (68.4±14.40), and least for the RS (56.8±11.93). Researchers (> 90%) were aware of their role in the clinical trial agreement and importance of the trial registration in Clinical Trials Registry-India. There were gaps in the Informed Consent (IC) process and post-trial access. Awareness regarding the IC process was adequate among the RS (84%). Awareness that the re-sponsibility of all delegation at site finally lies with the Researchers was adequate (60%) but 20% wrongly believed that the sponsor can have access to subject identification details. Deficiencies were noted regarding documentation, NDCT rules -2019 and serious adverse event (SAE) reporting process. Five percent answered that Data Clarification Forms were generated after reviewing the case report forms. The awareness that NDCT rules-2019 was not for medical devices, student pro-jects or Investigator Initiated Studies was inadequate (56%). The EC members’ awareness in roles and responsibilities was adequate (≥ 90%). Knowledge gaps were noted in EC monitoring of the ongoing trials (32%), and SAE reporting on SUGAM portal (8.8%), where stakeholders can access the regulator's web services using a single window interface for clinical trial related activities.

Conclusion:

There are gaps in the knowledge of the 3 stakeholders at site. Identifying and rectifying the gray areas will have the site better placed in performance. There is a need for regular training and assess-ments.
LncRNA TCTN2 Promotes the Malignant Development of Hepatocellular
Carcinoma via Regulating mIR-1285-3p/ARF6 Axis
Authors: Liu Qian , Zhu Chunfu , Dong Yanfen
Published: October 2022

Background:

Hepatocellular carcinoma (HCC) is one of the most life-threatening malignant
diseases. TCTN2 protein participates in tumorigenesis and development. However, whether
lncRNA TCTN2 is associated with HCC pathogenesis remains unclear.

Methods:

The expression of lncRNA, TCTN2, miR-1285-3p, and ARF6 in HCC tissues and cells was detected by a quantitative Real-Time PCR (qRT-PCR) assay. lncRNA TCTN2 specific shRNA was transfected into HCC cells and a functional investigation was performed. The direct interactions between lncRNA TCTN2 and miR-1285-3p and ARF6 were verified by dual-luciferase reporter gene assay. A rescue experiment was performed to confirm the role of miR-1285-3p/ARF6 in association with lncRNA TCTN2.

Results:

LncRNA TCTN2 exhibited a high expression in HCC tumor tissues and cell lines. Knockdown of lncRNA TCTN2 suppressed cell proliferation, and induced cell cycle arrest, and apoptosis through regulating Cyclin D1/p21 and Bax/Bcl-2 signals. Meanwhile, the Knockdown of lncRNA TCTN2 inhibited HCC cell migration and invasion through upregulating MMP2/MMP9. Mechanistic investigation revealed that lncRNA TCTN2 upregulated the expression of ARF6 via sponging miR-1285-3p. Rescue experiments indicated that miR-1285-3p inhibitor reversed the antitumor effects of lncRNA TCTN2 and ARF6 knockdown inhibited the progression of HCC.

Conclusion:

Our results suggested that the knockdown of lncRNA TCTN2 inhibited HCC development by regulating the miR-1285-3p/ARF6 axis, implying that the lncRNA TCTN2 is upregulated in HCC and may serve as a useful patent of diagnosis biomarker in HCC and may demonstrate an important value for the clinical treatment of patients with HCC.
New Era: Mavacamten for Obstructive Hypertrophic Cardiomyopathy
Authors: Al-Horani Rami A. , Woodland Ma’Lik
Published: October 2022

Obstructive hypertrophic cardiomyopathy results from asymmetric septal hypertrophy,
which eventually obstructs the outflow of the left ventricle. Obstructive hypertrophic cardiomyopathy
is linked to mutations in genes that encode for sarcomere proteins, including actin, β-myosin
heavy chain, titin, and troponin. The mutations lead to structural abnormalities in myocytes and
myofibrils, causing conduction irregularities and abnormal force generation. Obstructive hypertrophic
cardiomyopathy is a chronic disease that worsens over time, and patients become at higher
risk of developing atrial fibrillation, heart failure, and stroke. Up until recently, there were no disease-
specific medications for obstructive hypertrophic cardiomyopathy. Nevertheless, the US Food
and Drug Administration approved mavacamten on April 28, 2022, for the treatment of symptomatic
obstructive hypertrophic cardiomyopathy (New York Heart Association class II to III) in
adults to improve functional capacity and symptoms. Its approval was based on data from EXPLORER-
HCM and EXPLORER-LTE (NCT03723655). Mavacamten is a novel, first-in-class,
orally active, allosteric inhibitor of cardiac myosin ATPase, which decreases the formation of actin-
myosin cross-bridges, and thus, it reduces myocardial contractility, and it improves myocardial
energetics. It represents a paradigm-shifting pharmacological treatment of obstructive hypertrophic
cardiomyopathy. In this review, we describe its chemical and mechanistic aspects as well as its
pharmacokinetics, adverse effects and warnings, potential drug-drug interactions, and contraindications.
Healthy Diet, Grape Phytochemicals, and Vitamin D: Preventing Chronic
Inflammation and Keeping Good Microbiota
Authors: Santa Kazuki
Published: October 2022

Background:

Since the discovery of penicillin, natural antibiotics have protected humans
from malicious microbes. A breakthrough, however, is needed to tackle problems like antimicrobial
resistance (AMR). This review introduces one of the new approaches for the prevention of several
diseases through a healthy diet, grape phytochemicals, and vitamin D, which nurture the growth of
beneficial bacteria, including gut microbiota, suppressing chronic inflammation and up-regulating
immunity. Antibiotics provide protection against infectious diseases by preventing the growth of
pathogenic microbes. However, inappropriate use of antibiotics increases antimicrobial resistance to
bacteria and limits the benefits of antibiotics. In addition, it is well known that antibiotics kill not
only pathogenic microbes but also beneficial ones that reside in healthy individuals. As a result, the
excess use of antibiotics increases the threat of diseases caused by antibiotic-resistant bacteria. We
can reduce the risk of several diseases, including infectious diseases, in the future by nurturing the
good microbes that live in the human body, thereby preventing chronic inflammation induced by the
proinflammatory cytokine TNF-α, improving predisposition, and up-regulating immunity. Along
with human evolution, residing bacteria in the skin, digestive system, and other areas have changed.
They defend their hosts from malicious microbes in the surrounding environment. With the progress
of medicine, science, and technology, the quality of life and environmental public health have improved
over the years. Under these circumstances, it is necessary to reduce the risk of illness and
keep ourselves healthy by nurturing the good resident microbiota in our bodies and preventing
chronic inflammation through the diet and the intake of phytochemicals and vitamin D. This new
approach is important, along with the traditional method for preventing emerging infectious diseases
in the future.
Interleukin-6 Blockers Improve Inflammation-Induced Lipid Metabolism
Impairments but Induce Liver Fibrosis in Collagen-Induced Arthritis
Authors: Denga Tshimangadzo M. , Gunter Sulè , Fourie Serena , Roux Regina le , Manilall Ashmeetha , Millen Aletta M.E. , Mokotedi Lebogang
Published: October 2022

Background:

Interleukin-6 (IL-6) receptor blockers improve systemic inflammation,
however, their inconsistent effects on lipid metabolism and drug-induced liver injuries warrant
further investigation. This study aimed to determine the effects of IL-6 receptor blocker therapy
on lipid metabolism and liver morphology in collagen-induced arthritis.

Methods:

Sixty-three Sprague-Dawley rats were divided into control (n = 24), inflammation (n =
24), and IL-6 blocker (n = 15) groups. Inflammation was induced in the inflammation and IL-6-
blocker groups using Bovine type-II collagen and incomplete Freund’s adjuvant. At first signs of
arthritis, the IL-6 blocker group received an IL-6 blocker, tocilizumab for six weeks. Serum
concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein
cholesterol (HDL-C) and ATP-binding cassette transporter-A1 (ABCA1) were measured. Liver
fibrosis was determined by histological stains and liver enzymes were measured using the
colorimetric-chemistry analyzer.

Results:

In the inflammation group, HDL-C and ABCA1 were reduced compared to control (p <
0.0001 and p = 0.04, respectively) and IL-6 blocker (p = 0.0003 and p < 0.0001, respectively)
groups. LDL-C was increased in the inflammation compared to control (p = 0.02). Markers of
liver fibrosis were increased in the IL-6 blocker group compared to control and inflammation
groups (picrosirius red collagen area fraction: p < 0.0001 and p = 0.0008, respectively; Masson’s
trichrome collagen area fraction: p = 0.0002 and p = 0.01, respectively). Alkaline phosphatase
concentrations were increased in the IL-6 blocker group compared to the control (p < 0.0001) and
inflammation (p = 0.002) groups.

Conclusion:

IL-6 blockers ameliorated inflammation-induced lipid metabolism impairments,
however they induced liver fibrosis. Although IL-6 blockers may reduce inflammation-induced
metabolic impairments in chronic inflammatory disorders, routine monitoring of liver function is
warranted while on treatment.
Design Optimization and Evaluation of Solid Lipid Nanoparticles of
Azelnidipine for the Treatment of Hypertension
Authors: Dugad Tejas , Kanugo Abhishek
Published: October 2022

Background:

Solid lipid nanoparticles (SLN) are the most promising lipid-based drug delivery utilized for enhancing the solubility, bioavailability, and therapeutic efficacy of poorly water-soluble molecules. Azelnidipine (AZN) is a calcium channel blocker widely recommended for the treatment of high blood pressure but its activity is restricted due to high lipophilicity and poor solubility in the GIT. The current research focused on the development of the SLN of AZN and thereby improving the absorption, bioavailability, and therapeutic efficacy in hypertension which is a leading cause of death worldwide. Recent patents on SLN was available as U.S. Patent,10,973,798B2, U.S. Patent 10,251,960B2, U.S. Patent 2021/0069121A1, U.S. Patent 2022/0151945A1.

Methods:

SLN was developed by hot melt emulsification and ultrasonication method using glyceryl monostearate (GMS) as solid lipid and Poloxamer 188 as a surfactant for the stabilization of colloidal dispersion.

Results:

Box-Behnken model was utilized which predicted 13 batches in which concentration of GMS (X1), Poloxamer 188 (X2) and sonication time (X3) were considered as independent parameters. The particle size (Y1) and entrapment efficiency (Y2) were dependable parameters and optimized batch F2 showed a particle size of 166.4 nm, polydispersity index of 0.40 and zeta potential of -13.7 mV. The entrapment efficiency was observed at 86.21 %. FTIR spectra confirm the identity and compatibility with the formulation components. The differential scanning calorimetry (DSC) confirmed the absence of melting point and interpreted that AZN was entirely incorporated in the lipid matrix and transformed from crystalline to amorphous form. The ANOVA for the particle size (p-value: 0.0203), % EE (p-value: 0.0271) was found significant. The in-vitro drug release showed a sustained release pattern for about 12 h. The AZN-loaded SLN was lyophilized and intended for oral delivery.

Conclusion:

AZN-loaded SLN was developed by the hot melt emulsification method which accelerated the solubility and bioavailability and released in a sustained manner for treating hypertension.
Experimental Pharmacology for COVID-19 Treatment: A Geoanalytical
Bibliometric Analysis
Authors: Aguado Cesar , Castaño Victor M.
Published: October 2022

Objective:

The objective of this study is to produce a geo-referenced map of the status
of R&D in COVID-related studies in the world.

Methods::

Spatial mapping of bibliometric data of Cortellis Drug Discovery Intelligence through an spatial bibliometric model with the aid of a GIS (Geographic Information System) called ArcGIS and the software.

Results:

We show the countries that have the most studies related to COV ID-19 and their degree
of collaboration. No drug discovery-related activity was found in South America and Africa. A
geo-referenced map of the most active countries in COVID research was constructed as well as
conceptual maps of the 11 most representative drugs employed for COVID treatment.

Conclusion:

The georeferenced conceptual maps produced in the present report allow not only to
better understand the leading institutions in R&D in COVID-19 related drugs but also to visualize
their interactions and research relationships. This could offer, in addition to a coherent, organized
multinational effort, the possibility of searching for other drugs that have been employed for other
diseases and that, in terms of their conceptual relations, could represent some possibilities for treating
the coronavirus SARS-2.