bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic profiling of Early-onset sporadic Alzheimer’s disease patients
Authors: Caldwell Andrew B , Anantharaman Balaji G , Ramachandran Srinivasan , Nguyen Phuong , Liu Qing , Trinh Ivy , Galasko Douglas R , Desplats Paula A , Wagner Steven L , Subramaniam Shankar 
Published: June 2022

Abstract
Alzheimer’s disease (AD) manifested before 65 years of age is commonly referred to as early-onset AD (EOAD) [1]. Significant research on EOAD has focused on autosomal-dominant familial mutations in PSEN1, PSEN2, and APP; however, these mutations only represent 5–10% of EOAD cases. Although EOAD has a higher heritability (92–100%) than sporadic late-onset AD (LOAD, 70%), which is polygenic, EOAD may be due to autosomal recessive inheritance or combinatorial polygenic risk [2, 3]. Even though the endpoint clinicopathological changes, i.e., Aβ plaques, tau tangles, and cognitive decline, are common across EOAD and LOAD, the disease progression is highly heterogeneous [4]. The heterogeneity, leading to temporally distinct age of onset (AOO) and stages of cognitive decline, may be caused by myriad combinations of distinct disease-associated molecular mechanisms. We and others have used transcriptome profiling in AD patient-derived neuron models of autosomal-dominant EOAD and sporadic LOAD to identify disease endotypes [5–7]. Further, analyses of large cohorts of postmortem brains demonstrate that only one-third of AD patients show hallmark disease endotypes like increased inflammation and decreased synaptic signaling [4]. Areas of the brain less affected by AD pathology at early disease stages—such as the primary visual cortex—exhibit similar transcriptomic dysregulation as those regions traditionally affected, and therefore may offer a view into the molecular mechanisms of AD without the associated inflammatory changes and gliosis induced by pathology [8]. To this end, we analyzed AD patient samples from the primary visual cortex (19 EOAD, 20 LOAD), using transcriptomic signatures to identify patient clusters and disease endotypes. Interestingly, although the clusters showed distinct combinations and severity of endotypes, each patient cluster contained both EOAD and LOAD cases, suggesting that AOO may not directly correlate with the identity and severity of AD endotypes.
Bayesian inference of physicochemical quality elements of tropical lagoon Nokoué (Benin)
Authors: HOUNYEME Romuald , LOGEZ Maxime , MAMA Daouda , ARGILLIER Christine 
Published: June 2022

Abstract
In view of the very strong degradation of aquatic ecosystems, it is urgent to set up monitoring systems that are best able to report on the effects of the stresses they undergo. This is particularly true in developing countries, where specific and relevant quality standards and funding for monitoring programs are lacking. The objective of this study was to make a relevant and objective choice of physico-chemical parameters informative of the main stressors occurring on African lakes and to identify their alteration thresholds. Based on statistical analyses of the relationship between several driving forces and the physico-chemical parameters of the Nokoué lagoon, relevant physico-chemical parameters were selected for its monitoring. An innovative method based on Bayesian statistical modeling was used. Eleven physico-chemical parameters were selected for their response to at least one stressor and their threshold quality standards also established: Total Phosphorus (<4.5mg/L) , Orthophosphates (<0.2mg/L), Nitrates (<0.5 mg/L), TKN (<1.85 mg/L), Dry Organic Matter (<5 mg/L) , Dissolved Oxygen (>4 mg/L), BOD (<11.6 mg/L) , Salinity (7.6 ‰) , Water Temperature (<28.7 °C) , pH (>6.2) , and Transparency (>0.9 m) . According to the System for the Evaluation of Coastal Water Quality, these thresholds correspond to "good to medium" suitability classes, except for total phosphorus. One of the original features of this study is the use of the bounds of the credibility interval of the fixed-effect coefficients as local weathering standards for the characterization of the physico-chemical status of this anthropized African ecosystem.
Additive Manufacturing and Printing Approaches for the Development of Pharmaceutical
Dosage Forms with Improved Biopharmaceutical Attributes
Authors: Kawish Syed M. , Sharma Shwetakshi , Almalki Waleed H. , Alghamdi Saad , Afzal Obaid , Kazmi Imran , Altamimi Abdulmalik S.A. , Al-Abbasi Fahad A. , Beg Sarwar , Ahmad Farhan J. 
Published: June 2022

Abstract:
Pharmaceutical industry is moving ahead with the future experiencing an innovation in drug development through the introduction of personalized medicine technologies. Instead of adapting the dose which a patient actually needs, they were adapted to the manufacturer’s dose. Now patient specific or customized method of dosing and dose combinations has superior insistence rather than the standard mass medicines. Printing technology has gained interest during the last years for manufacturing of personalized dosage forms. For manufacturing of personalized drug products three dimensional printing (3DP) has expanded to the pharmaceutical industry. With the approval of first 3DP product an unprecedented opportunity for the discovery of new compounds and technologies has arisen. In this article, we have re-evaluated various printing technology and its utilization in personalized medicines. Further, we also discussed its history, advantages, challenges and various types of printing technologies with advantages and limitations particularly in the area of pharmaceutical research.
Human Colon Cancer HT29 Cell Line Treatment with High-Dose LAscorbic
Acid Results to Reduced Angiogenic Proteins Expression
and Elevated Pro-apoptotic Proteins Expression
Authors: Samie Kosar Abbasi , Dayer Dian , Eshkiki Zahra Shokati 
Published: June 2022

Background:
Some studies have shown anticarcinogenic effects of high dose L-Ascorbic Acid. However, there are controversies around the therapeutic administration of Ascorbic acid as an anticancer medicine.

Objective:
we conducted a case-control study to investigate the role of pharmacologic concentration of Ascorbic acid on viability and angiogenesis of human colon cancer (HT29) cell line.

Methods:
The HT29 cells were cultured in DMEM-HG and treated with 10 mM ascorbic acid for 3h. The culture medium was exchanged, and after incubation at 37 ˚C for 24 h, the cells were collected and utilized to evaluate viability, ROS production, gene expression and protein expression levels. The control group consisted of untreated HT29 cells. The viability of the cells was determined using the MTT method. Moreover, Nitro Blue Tetrazolium (NBT) was used to detect the ROS production capacity. The mRNA transcript’s level and protein expression were evaluated by Real-time PCR and Western blotting, respectively.

Results:
The ascorbic acid-treated group showed a significant increase in ROS production and an obvious reduction in viability compared to the control group. The treated group showed significant increased levels of both early apoptotic markers (Bax, Cyt C, Caspase3, and Caspase 9) and late apoptotic marker (Caspase 8). Bcl2 expression showed significantly decreased levels relative to the control group. Ascorbic acid therapy substantially reduced the expression of bFGF, bFGFR, PDGF, PDGFR and PLC- γ compared to the control group.

Conclusion:
The results confirm that high- dose L-ascorbic acid reduces HT29 cell line viability in vitro.
Facile Synthesis of Three Types of Mesoporous Silica Microspheres as
Drug Delivery Carriers and their Sustained-Release Properties
Authors: Zhu Yameng , Wang Boyao , Chen Jian , He Jun , Qiu Xilong 
Published: June 2022

Background:
Mesoporous silica nanoparticles (MSNs) are one of the most promising carriers for drug delivery. MSNs have been widely used in pharmaceutical research as drug carriers because
of their large pore volume, high surface area, excellent biocompatibility, nontoxicity, ease to functionalize, and sustained release effects. MSNs have attracted much attention during drug delivery because of
their special structure.

Objective:
The present study aimed to synthesize mesoporous silica nanoparticles (MSNs), dendritic
mesoporous silica nanoparticles (DMSN), and hollow mesoporous silica nanoparticles (HMSN) through
facile methods, and to compare the drug release properties of nano-porous silica with different pore
structures as a stroma for PUE drug.

Methods:
MSN, DMSN, and HMSN were characterized by SEM, TEM, FT-IR, nitrogen adsorptiondesorption isotherms, XRD, and zeta potential methods. Subsequently, puerarin (PUE) was used as the
active ingredient and loaded into the three mesoporous materials, respectively. And, the drug delivery
behavior was measured in PBS solution with different pH values. The sustained-release properties of
MSN, DMSN, and HMSN loaded with PUE were investigated. Finally, the biocompatibility and stability of MSN, DMSN, and HMSN were studied by MTT assay and hemolysis assay.

Results:
Our results showed that MSN, DMSN, and HMSN were successfully synthesized and the three
types of mesoporous silica nanoparticles had higher drug loading and encapsulation efficiency. According to the first-order release equation curve and Higuchi equation parameters, the results showed that the
PUE-loaded MSN, DMSN, and HMSN exhibited sustained-release properties. Finally, MTT and hemolysis methods displayed that MSN, DMSN, and HMSN had good biocompatibility and stability.

Conclusion:
In this study, MSN, DMSN, and HMSN were successfully synthesized, and to compare the
drug release properties of nano-porous silica with different pore structures as a stroma for PUE drug, we
provided a theoretical and practical basis for the application of PUE.
Quinic and Digallic acids from Pistacia atlantica Desf. Leaves Extracts as
Potent Dual Effect Inhibitors against main Protease and RNA-dependent
RNA Polymerase of SARS-CoV-2
Authors: Benguechoua Mebarka Imane , Benarous Khedidja , Benahmed Ziyad , Boukhalkhal Sarah , Silva Artur M. S. , Yousfi Mohamed 
Published: June 2022

Background:
Through this study, the Chemical composition realized by UHPLC-DAD-ESI-MSn allowed the detection of different phenolic compounds groups from Pistacia atlantica Desf. leaves extracts. We studied the inhibition of main protease (CL3 Mpro) and RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2 by the identified molecules through molecular docking.

Objective:
The objective of this study is to identify compounds from Pistacia atlantica Desf. leaves extracts, which might have anti-viral effects.

Methods:
Chemical composition realized by UHPLC-DAD-ESI-MSn, the inhibition of main protease (CL3 Mpro) and RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2 is studied using molecular docking with Autodock Vina software. ADMET analysis was carried out.

Results:
The identified compounds are quinic acid, digallic acid, galloylquinic acid, gallic acid, trigallic acid, digalloylquinic acids, trigalloylquinic acids and methyl gallate; digallic and quinic acids are the best inhibitors. Digallic acid had binding affinity energy (BAE) of -8.2 kcal/mol, and Ki of 1µM for the CL3 Mpro, Ki of 0.62 mM for the RdRp. Quinic acid showed Ki of 4.6 mM, recorded for both enzymes. Through ADMET analysis, we have found that the two molecules are good drugs candidate.

Conclusion:
This is the first time that a group of identified compounds from Pistacia atlantica Desf. leaves is studied for their potential activity against the novel virus by inhibiting two key enzymes in its life cycle, and no further studies have been published in this context.
Modeling the Influence of Extraction Parameters on the Recovery of
Antioxidant Compounds of Microwave Extracted Citrus (Citrus reticulata)
Peel by Response Surface Methodology
Authors: Martati Erryana , Utari Dwiyani P. , Wulan Siti N. 
Published: June 2022

Background:
Microwave-assisted extraction (MAE) is a green extraction technology that
saves both in energy and time and that bioactive compounds can be extracted without loss as much as in
traditional extraction methods.

Objectives:
This study aims to optimize the MAE process for maximizing the recovery of antioxidant
compounds of flavonoids and the activity of radical scavenging of DPPH (2,2-diphenyl-1-picrylhydrazyl)
from citrus peels (CP).

Methods:
The modeling used Box-Behnken Design (BBD) experimental design for optimizing three extraction
parameters of time (5, 15, and 25 min), ethanol concentration (50%, 70%, and 90%), and extraction
temperature (55, 65, and 75 °C). UHPLC-MS analysis was performed to identify the qualitative flavonoid
content in the extract.

Results:
Our results showed that the optimum MAE conditions that maximize the total flavonoid content
and antioxidant activity of the CP extract were extraction time of 16.87 min, 50% ethanol, and temperature
at 75°C. The obtained CP extract had a TFC of 14.10 mg QE/g and antioxidant activity of 51.52%,
which was in line with the predicted values. Flavonoids of neohesperidin, naringin, hesperidin, narirutin,
and nobiletin were identified in the extract of CP.

Conclusion:
The ethanolic extract of CP was confirmed to have high flavonoids content with potent antioxidant
activity.
A Highly Sensitive Room-Temperature NO2 Gas Sensor based on Porous
MnO2/rGO Hybrid Composites
Authors: Sun Youyi , Zhang Hui , Ou Kangtai , Guan Ruihua , Cao Yang , Li Xiao 
Published: June 2022

Background:
The NOX (e.g. NO2) is harmful to human health and environmental
quality. It is of great interest to monitor the hazardous NOx with a simple, reliable, and sensitive
sensor. Currently, the commonly used detection methods have disadvantages of complex operation,
unstable cycling performance and low sensitivity.

Objective:
In this paper, rGO coated Ni foam supported MnO2 is synthesized to develop a more
advanced detection method for the rapid analysis of NO2.

Methods:
A three-dimensional nickel foam supported MnO2 and rGO (MnO2/rGO@NF) was
prepared by a hydrothermal method for application in binder-free electrode of NO2 sensor.

Results:
The MnO2/rGO@NF composite displayed significantly better NO2 sensing performance
compared to single MnO2@NF or rGO@NF. The excellent sensing response (5.9%) as well as
high cycling stability were observed in the presence of 50.0 ppm NO2 at room temperature. Furthermore,
the mechanism of the great gas-sensing performance was also investigated by the density
functional theory (DFT).

Conclusion:
These results were very important to further design and prepare new sensitive materials
applied in binder-free electrode of gas NO2 sensors.
Novel Molecular Targets and Mechanisms for Neuroprotective Modulation
in Neurodegenerative Disorders
Authors: Irannejad Hamid , Azari Aala , Goodarzi Amin , Jafarkhani Behrouz , Eghbali Mohammad , Karimi Zohreh , Hosseini Balef Seyed Sajad 
Published: June 2022

Background:
Neuronal death underlies the symptoms of several human neurological
disorders, including Alzheimer's, Parkinson's and Huntington's diseases, and amyotrophic lateral
sclerosis and their precise pathophysiology have not yet been elucidated. According to various
studies, the prohibition is the best therapy with neuroprotective approaches, which are advanced
and safe methods.

Methods:
This review summarizes some of the already-known and newly emerged neuroprotective
targets and strategies and their experimental effects have also been reported. Accordingly, literature
was studied from 2000 to 2021, and appropriate articles were searched in Google Scholar and
Scopus with the keywords given in the keywords section of the current review.

Results:
Lewy bodies are the histopathologic characteristics of neurodegenerative disorders and
are protein-rich intracellular deposits in which Alpha-Synuclein is its major protein. Alpha-
Synuclein’s toxic potential provides a compelling rationale for therapeutic strategies aimed at decreasing
its burden in neuronal cells through numerous pathways, including ubiquitin-proteasome
system and autophagy-lysosome pathway, proteolytic breakdown via cathepsin D, kallikrein-6
(neurosin), calpain-1 or MMP9, heat shock proteins, and proteolysis targeting chimera which consists
of a target protein-ligand and an E3 ubiquitin ligase (E3) followed by target protein ubiquitination
(PROTACs). Other targets that have been noticed recently are the mutant huntingtin, tau
proteins and glycogen synthase kinase 3β; their accumulation proceeds extensive neuronal damage
and up to the minute approach such as Proteolysis Targeting Chimera promotes its degradation in
cells. Various studies demonstrated that Mendelian gene mutations can result in neurodegenerative
diseases. An additional target that has gained much interest is epigenetics, such as mutation, phosphodiesterase,
RNA binding proteins and Nuclear respiratory factor 1.

Conclusion:
The novel molecular targets and new strategies compiled and introduced here can be
used by scientists to design and discover more efficient small molecule drugs against neurodegenerative
diseases. And also, the genes in which their mutations can lead to the α-synuclein aggregation
or accumulation have been discussed and considered a valuable information on epigenetics in
dementia.
Amyloid Beta Peptide-Mediated Alterations in Mitochondrial Dynamics
and its Implications for Alzheimer’s Disease
Authors: Monsalvo-Maraver Luis Ángel , Maya-López Marisol , Rangel-López Edgar , Túnez Isaac , Tinkov Alexey A. , Skalny Anatoly , Ferrer Beatriz , Aschner Michael , Santamaría Abel 
Published: June 2022

Abstract:
Alzheimer’s disease (AD) is considered the most frequent neurodegenerative disorder
worldwide, compromising cognitive function in patients, with an average incidence of 1-3% in the
open population. Protein aggregation into amyloidogenic plaques and neurofibrillary tangles, as well
as neurodegeneration in the hippocampal and cortical areas, represent the neuropathological hallmarks
of this disorder. Mechanisms involved in neurodegeneration include protein misfolding, augmented
apoptosis, disrupted molecular signaling pathways and axonal transport, oxidative stress, inflammation,
and mitochondrial dysfunction, among others. It is precisely through a disrupted energy metabolism
that neural cells trigger toxic mechanisms leading to cell death. In this regard, the study of mitochondrial
dynamics constitutes a relevant topic to decipher the role of mitochondrial dysfunction in
neurological disorders, especially when considering that amyloid-beta peptides can target mitochondria.
Specifically, the amyloid beta (Aβ) peptide, known to accumulate in the brain of AD patients, has
been shown to disrupt overall mitochondrial metabolism by impairing energy production, mitochondrial
redox activity, and calcium homeostasis, thus highlighting its key role in the AD pathogenesis. In
this work, we review and discuss recent evidence supporting the concept that mitochondrial dysfunction
mediated by amyloid peptides contributes to the development of AD.
Multi-temporal Cloud Pixels Reconstruction Method for Optical Remote
Sensing Satellite Images
Authors: Liu Huiqian , Zhong Ruofei , Wang Haiyin , Wu Shiyong , Li Qingyang , Yang Cankun 
Published: June 2022

Bachground:
The existence of cloud pixels reduces the practicability of optical satellite remote sensing data.

Existing problems:
Existing cloud reconstruction methods generally cannot solve the following problems:(1)Large-scale thick cloud cannot be well reconstructed. (2)There are high requirements for reconstructed data. (3)Most data used to reconstructed are single temporal images.

Ways:
In order to overcome these problems, a new multi temporal weighted aggregation method is proposed. Specifically, we adopt a multi-temporal iterative aggregation method for cloud pixels to reconstruct and a multi-temporal weighted aggregation method for cloud shadow pixels to reconstruct.

Result:
Finally, the experiment proves that our method can quickly and accurately complete the cloud reconstruction, and under the effective uniform color strategy, a cloud- free image with accurate geometric position and uniform gray scale can be obtained.

Conclusion:
Experiments prove that the pixel reconstruction method proposed in this paper has achieved good cloud and cloud shadow pixel reconstruction effects in different types of ground objects.
Formulation and Development of Nanostructured Lipid Carriers for a
Poorly Water-Soluble Drug: Furosemide
Authors: Jadhav Abhish B. , Savkare Anand D. , Gaikwad Sachin S. 
Published: June 2022

Aim:
Formulation, development and evaluation of solid lipid nanoparticles.

Background:
It was found that furosemide (FU) was a very potent drug but it fails to produce bioavailability
due to its BCS class IV, so drug- cyclodextrin (CD)- nanostructured lipid carriers
(NLC) will be an alternative to improve solubility and permeability as a result of this overall bioavaibility
will be improved.

Objective:
To improve the solubility of drug by using complexation of cyclodextrin. Coating with
the lipids (NLC) will improve the permeability of the drug.

Methods:
To generate solid Furosemide–cyclodextrin complexes (FU–CD), two distinct CDs and
three different techniques were used. The co-evaporation (COE) Furosemide-β-cyclodextrinloaded
NLC (FU– β-CD-COE-loaded NLC) was obtained by emulsification ultrasonic dispersion
method. The selected batch was suitably characterized for particle size, polydispersity index, zeta
potential, Entrapment efficiency, Drug release study, and permeability study. The crystallization of
the drug in the furosemide cyclodextrin complex (FU–CD complex) and the co-evaporation Furosemide-
β-cyclodextrin-loaded NLC (FU–β-CD-COE-loaded NLC) was investigated by differential
scanning calorimetry (DSC). The in vitro release study was carried out.

Results:
The FU–β-CD-COE-loaded NLC and FU–HP-β-CD-COE-loaded NLC (Hydroxypropyl)
presented a superior physicochemical property and were selected for further study. The in vitro release
study of the above selected batches exhibited a higher dissolution rate in the pH 5.8 phosphate
buffer than Furosemide suspension and FU–NLC. The permeability studies of abovementioned
batches were compared with FU-Suspension.

Conclusion:
The novel formulation considerably enhanced the solubility and permeability of furosemide
for oral delivery, and was successfully developed.