bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repurposing of Antidiarrheal Loperamide for Treating Melanoma by
Inducing Cell Apoptosis and Cell Metastasis Suppression In vitro and
In vivo
Authors: Yang Shuping , Li Zhi , Pan Mingyue , Ma Jing , Pan Zeyu , Zhang Peng , Cao Weiling 
Published: February 2024

Background:
Melanoma is the most common skin tumor worldwide and still lacks effective therapeutic agents in clinical practice. Repurposing of existing drugs for clinical tumor
treatment is an attractive and effective strategy. Loperamide is a commonly used anti-diarrheal
drug with excellent safety profiles. However, the affection and mechanism of loperamide in melanoma remain unknown. Herein, the potential anti-melanoma effects and mechanism of loperamide were investigated in vitro and in vivo.

Methods:
In the present study, we demonstrated that loperamide possessed a strong inhibition in
cell viability and proliferation in melanoma using MTT, colony formation and EUD incorporation
assays. Meanwhile, xenograft tumor models were established to investigate the anti-melanoma activity of loperamide in vivo. Moreover, the effects of loperamide on apoptosis in melanoma cells
and potential mechanisms were explored by Annexin V-FITC apoptosis detection, cell cycle, mitochondrial membrane potential assay, reactive oxygen species level detection, and apoptosis-correlation proteins analysis. Furthermore, loperamide-suppressed melanoma metastasis was studied by
migration and invasion assays. What’s more, immunohistochemical and immunofluorescence
staining assays were applied to demonstrate the mechanism of loperamide against melanoma in vivo. Finally, we performed the analysis of routine blood and blood biochemical, as well as hematoxylin-eosin (H&E) staining, in order to investigate the safety properties of loperamide.

Results:
Loperamide could observably inhibit melanoma cell proliferation in vitro and in vivo.
Meanwhile, loperamide induced melanoma cell apoptosis by accumulation of the sub-G1 cells
population, enhancement of reactive oxygen species level, depletion of mitochondrial membrane
potential, and apoptosis-related protein activation in vitro. Of note, apoptosis-inducing effects
were also observed in vivo. Subsequently, loperamide markedly restrained melanoma cell migration and invasion in vitro and in vivo. Ultimately, loperamide was witnessed to have an amicable
safety profile.

Conclusion:
These findings suggested that repurposing of loperamide might have great potential
as a novel and safe alternative strategy to cure melanoma via inhibiting proliferation, inducing
apoptosis and cell cycle arrest, and suppressing migration and invasion.
Mild and Efficient Synthesis of Para-Substituted 2-Hydroxymethyl
Piperazine
Authors: Liang Zijian , Guo Liyuan , Li Qian , Liu Chunyan , Liu Chao , Wu Shi 
Published: February 2024

Abstract:
2-Hydroxymethyl piperazine is a crucial structural unit and essential intermediate in the
drug development process. However, there are few reported methods for synthesizing 2-
hydroxymethyl piperazine substituted at position 5. Herein, the 2-hydroxymethyl piperazines are synthesized
from serine methyl ester hydrochloride and N-Boc-L-amino acids through a four-step reaction
of condensation, deprotection, cyclisation, and reduction. This synthetic route has several advantages,
including mild reaction conditions, availability of reagents, non-racemic composition, and
the potential for gram-scale synthesis. In this study, we present a mild and effective synthetic method
for preparing para-substituted 2-hydroxymethyl piperazine.
Hyperoside Inhibits RNF8-mediated Nuclear Translocation of β-catenin to Repress
PD-L1 Expression and Prostate Cancer
Authors: Chen Jie , Zhao Yi , Wang Xiaoli , Zang Long , Yin Dengke , Tan Song 
Published: February 2024

Background:
Hyperoside is a flavonol glycoside isolated from Hypericum perforatum L. that has
inhibitory effects on cancer cells; however, its effects on prostate cancer (PCa) remain unclear. Therefore, we
studied the anti-PCa effects of hyperoside and its underlying mechanisms in vitro and in vivo.

Aim:
This study aimed to explore the mechanism of hyperoside in anti-PCa.

Methods:
3-(4,5-Dimethyl-2-Thiazolyl)-2,5-Diphenyl Tetrazolium Bromide (MTT), transwell, and flow cytometry
assays were used to detect PCa cell growth, invasion, and cell apoptosis. Immunoblot analysis, immunofluorescence,
immunoprecipitation, and quantitative real-time PCR (qRT-PCR) were used to analyze the antitumor
mechanism of hyperoside.

Results:
Hyperoside inhibited PCa cell growth, invasion, and cell cycle and induced cell apoptosis. Furthermore,
RING finger protein 8 (RNF8), an E3 ligase that assembles K63 polyubiquitination chains, was predicted to be a
direct target of hyperoside and was downregulated by hyperoside. Downregulation of RNF8 by hyperoside impeded
the nuclear translocation of β-catenin and disrupted the Wnt/β-catenin pathway, which reduced the expression
of the target genes c-myc, cyclin D1, and programmed death ligand 1 (PD-L1). Decreased PD-L1 levels
contributed to induced immunity in Jurkat cells in vitro. Finally, in vivo studies demonstrated that hyperoside
significantly reduced tumor size, inhibited PD-L1 and RNF8 expression, and induced apoptosis in tumor tissues
of a subcutaneous mouse model.

Conclusion:
Hyperoside exerts its anti-PCa effect by reducing RNF8 protein, inhibiting nuclear translocation of
β-catenin, and disrupting the Wnt/β-catenin pathway, in turn reducing the expression of PD-L1 and improving
Jurkat cell immunity.
A Comprehensive Review on Potential Molecular Drug Targets for the
Management of Alzheimer's Disease
Authors: Sharma Chanchal , Mazumder Avijit 
Published: February 2024

Abstract:
Alzheimer's disease (AD) is an onset and incurable neurodegenerative disorder that has
been linked to various genetic, environmental, and lifestyle factors. Recent research has revealed
several potential targets for drug development, such as the prevention of Aβ production and removal,
prevention of tau hyperphosphorylation, and keeping neurons alive. Drugs that target numerous ADrelated
variables have been developed, and early results are encouraging. This review provides a
concise map of the different receptor signaling pathways associated with Alzheimer's Disease, as
well as insight into drug design based on these pathways. It discusses the molecular mechanisms of
AD pathogenesis, such as oxidative stress, aging, Aβ turnover, thiol groups, and mitochondrial activities,
and their role in the disease. It also reviews the potential drug targets, in vivo active agents, and
docking studies done in AD and provides prospects for future drug development. This review intends
to provide more clarity on the molecular processes that occur in Alzheimer's patient's brains, which
can be of use in diagnosing and preventing the condition.
Effect of Flavonoids against Parkinson’s Disease
Authors: Varshney Himanshi , Siddique Yasir Hasan 
Published: February 2024

Abstract:
Parkinson's disease (PD) is the second most common neurodegenerative disorder. It
is characterized by the depletion of striatal dopamine content and aggregation of alphasynuclein
in the substantia nigra (SN). It is possible to treat the symptoms of PD with a variety
of medications, but they often result in complications and are not able to cure or stop the progression
of the disease. Flavonoids (the phytocomponents present in almost all fruits and vegetables)
are the class of secondary metabolites that have generated a peak of interest because of
their medicinal properties, including a reduction in the risk of PD. Several flavonoids such as
quercetin, kaempferol, hesperitin, anthocyanin and many more have been reported for their anti-
Parkinson’s effect. This review deals with the neuroprotective benefits of different classes of
flavonoids against PD
Molecular Pathway, Epidemiological Data and Treatment Strategies of
Fungal Infection (Mycoses): A Comprehensive Review
Authors: Singh Namrata , Kumari Vibha , Agrawal Karan , Kulshreshtha Mayank 
Published: February 2024

Abstract:
The recent increase in fungal infections is a health crisis. This surge is directly tied
to the increase in immunocompromised people caused by changes in medical practice, such as
the use of harsh chemotherapy and immunosuppressive medicines. Immunosuppressive disorders
such as HIV have exacerbated the situation dramatically. Subcutaneous or superficial fungal
infections can harm the skin, keratinous tissues, and mucous membranes. This category includes
some of the most common skin disorders that impact millions of people worldwide. Despite
the fact that they are seldom fatal, they can have a catastrophic impact on a person's quality
of life and, in rare situations, spread to other people or become obtrusive. The majority of
fungal infections under the skin and on the surface are simply and quickly cured. An opportunistic
organism that preys on a weak host or a natural intruder can both result in systemic fungal
infections. Furthermore, it might be exceedingly lethal and dangerous to one's life. Dimorphic
fungi may pose a hazard to healthy populations that are not exposed to endemic fungi. Increased
surveillance, the availability of quick, noninvasive diagnostic tests, monitoring the
emergence of antifungal medication resistance, and research on the pathophysiology, prevention,
and management of fungal infections are just a few potential solutions to these new health
problems. The goal of this review is to summarize the data available for fungal infections and
the different therapies which are involved in their treatment. Additionally, it also summarizes
the molecular and scientific data of the plants which contain anti-fungal activity. Data are acquired
using Google, PubMed, Scholar, and other online sources.
Machine Learning Based Secure Routing Protocol with Uav-assisted for
Autonomous Vehicles
Authors: Sree A Divya , Sharma Kapil 
Published: February 2024

Aims and Background:
The topology and communication links of vehicular adhoc
networks, or VANETs, are always changing due to the transient nature of automobiles. VANETs
are a subset of MANETs that have applications in the transportation sector, specifically in Intelligent
Transportation Systems (ITS). Routing in these networks is challenging due to frequent
link detachments, rapid topological changes, and high vehicle mobility.

Methods:
As a result, there are many obstacles and constraints in the way of creating an effective
routing protocol that satisfies latency restrictions with minimal overhead. Malicious vehicle detection
is also a crucial role in VANETs. Unmanned-Aerial-Vehicles(UAVs) can be useful for
overcoming these constraints. This study examines the utilize of UAVs operating in an adhoc
form and cooperating via cars VANETs to aid in the routing and detection of hostile vehicles.
VANET is a routing protocol. The proposed UAV-assisted routing protocol (VRU) incorporates
two separate protocols for routing data: (1) a protocol called VRU_vu for delivering data packets
amid vehicles with the assist of UAVs, and (2) a protocol called VRU_u for routing data packets
amid UAVs.

Results:
To estimate the efficacy of VRU routing objects in a metropolitan setting, we run the
NS-2.35 simulator under Linux Ubuntu 12.04. Vehicle and UAV motions can also be generated
with the help of the mobility generator VanetMobiSim and the mobility simulation software MobiSim.

Conclusion:
According to the results of the performance analysis, the VRU-protocol is able to
outperform the other evaluated routing protocols in terms of packet-delivery-ratio (by 17 percent)
&detection-ratio (9 percent). The VRU protocol cuts overhead near 41% and reduces end-to-enddelay
in mean of 15%.
Delay and Fairness Analysis of C-RAN for Single and Multi Scheduling
Domain Strategies
Authors: Dubey Prasanna , Upadhyay Raksha , Bhatt Uma Rathore , Bhat Vijay 
Published: February 2024

Background:
Centralized Radio Access Network (C-RAN) is the most promising network
architecture for next-generation communication networks. It meets the need for flexibility on
fronthaul as well as large bandwidth on backhaul of the network. All along, scheduling is very important
for the transmission of information in an organized manner. C-RAN has not been studied
with the scheduling domain strategies yet in the literature.

Objective:
In this work, packet transmission duration, overall transmission time, wait time, and
fairness index parameters have been calculated and analysed for C-RAN architecture for two different
scheduling domains. The total transmission cycle time parameter is calculated for the three
upper functional split options of C-RAN. The overall transmission time is a parameter calculated
for the entire uplink channel.

Methods:
To implement the network scenario, extensive scripting is done on MATLAB Editor for
single scheduling domain (SSD) and multi-scheduling domain (MSD) for three higher functional
split options of C-RAN. The data traffic generated in the network is considered random.

Results:
A closer examination of results reveals the advantages and disadvantages of both algorithms,
as well as trade-offs between them.

Conclusion:
For quicker data transmission, SSD should be preferred whereas MSD should be preferred
if multiple users want to access resources simultaneously. Lower functional split options of
C-RAN require less transmission cycle time. The MSD technique is fairer than SSD.
Design, Heat Leakage Analysis and Stirling Cryocooler Option of
Stirling-type Lyophilizer
Authors: Feng Yinglong , Zhang Ankuo 
Published: February 2024

Background:
Based on referring to the relevant patents, it was found that the traditional
lyophilizer refrigeration system has the disadvantages of large volume and high power consumption.
Meanwhile, considering the context of advocating low carbon emission and environmental protection,
the use of energy-saving refrigeration technology and the use of non-fluorine and harmless refrigerants
are the trends of future development.

Objective:
In order to solve the traditional lyophilizer problems and enhance the lyophilizer reliability,
the paper designs a Stirling-type lyophilizer with a working temperature of -70°C.

Methods:
Stirling cooling has the advantages of ultra-low refrigeration temperature and high cooling
speed. Based on the above advantages, combining the characteristics of the lyophilization box, a Stirling-
type lyophilizer with a capacity of 0.120 m3 and a shelf area of 0.4 m2 is designed. The Stirlingtype
lyophilizer refrigeration system structure is analyzed. The flat plate heat pipe to transfer the cold
is used. The rigid polyurethane as the insulation material of the lyophilization box is studied. The heat
leakage calculation method of the lyophilization box is given.

Results:
Stirling cryocooler is selected based on the lyophilization box heat leakage. The experimental
test of the Stirling cryocooler is conducted. The feasibility of the design is verified. The Stirling
cryocooler, with a charging pressure of 2.9 MPa and an operating frequency of 68 Hz, could
achieve -87.057°C within 24 min. The lowest refrigeration temperature could be maintained at -
100.286°C after 97 min. The cooling capacity obtained is 40.0 W at an input power of 99.2 W, and
the COP is 0.403.

Conclusion:
Stirling refrigeration technology is suitable for use in lyophilizer and Stirling refrigeration
technology improves the robustness of the lyophilizer refrigeration system.
Intelligent Control of the Dynamic Voltage Restorer for Fault Ride through Capability Enhancement of a Grid-connected Photovoltaic Power Plant in accordance with Recent Moroccan Grid Code
Authors: Saad Sarih , Zakaria Boulghasoul , Abdelhadi Elbacha , Abdelouahed Tajer , Samira Chabaa 
Published: February 2024

Background:
The recent development of small-scale, decentralized generation from
renewable sources and the fall in the price of the equipment needed for this operation have given a
new role to the distribution networks, which is to collect the energy produced by the smallest generation
plants and deliver it to the end customers. However, the national Grid Codes present technical
requirements in terms of FRT and particularly LVRT and HVRT which are imposed on PV
plants connected to medium voltage distribution networks, to ensure the energy needed by the
loads connected to the network at the time of the failure and especially sensitive ones.

Methods::
In this paper, an intelligent neural network approach is applied to the DVR control circuit
to enable the requirements of the sensitive load connected near the PCC, and the system is
tested in the presence of a non-linear load to demonstrate its efficiency for all situations. The proposed
strategy is based on the implementation of an improved ANFIS and ANN control which are
compared to a tuned PI controller, the approach intends to meet the technical requirement of the
recently approved Grid Code in Morocco. The simulation is performed using MATLAB Simulink.

Results:
The proposed approach brings great improvement to the load side voltage waveforms,
and numerical experiment findings demonstrate that it can successfully guarantee the technical
requirements of the electrical grid code.

Conclusion:
The results obtained show better behavior of the system using ANFIS and ANN control
strategy in the presence of a nonlinear load and a significant improvement of the voltage
THD.
Graph Entropy for Adjacently and Non-Adjacently Configured Pentagonal
Structure of Carbon Nanocones
Authors: Alsinai Ammar , Xavier D. Antony , Baby Annmaria , Varghese Eddith Sarah , Ahmed Hanan 
Published: February 2024

aims:
Carbon nanocones possess exceptional properties compared to other nanomaterials, such as nanotubes, graphene etc. Hence they can be used as an alternative to other nanostructures.
This work helps in determining various properties of the nanocone structure through topological descriptors. In this paper, various degree based topological descriptors along with its entropy measures are evaluated for adjacently and non-adjacently configured pentagonal structure of carbon nanocones.

background:
Carbon nanoparticles are gaining much importance in the contemporary world. Among which carbon nanocones have wide range of acceptance in the field of nanotechnology due to its effective properties and applications. Nanocones, also known as nanohorns are carbon networks which are planar in structure and has majority of hexagonal faces along with some nonhexagonal faces, which are most commonly pentagons. Nanocones which include pentagons in their structure can be referred to as adjacently or non- adjacently configured pentagonal structure of nanocones. Various topological descriptors for few nanocone classes were derived by researchers earlier, but not for the class of nanocones in this paper. Through this work, we try to vanish the research gap in this field.

objective:
: The degree based descriptors and corresponding graph entropies for the adjacently and non-adjacently configured pentagonal structure of nanocones were determined, which further can be applied in quantitative structure – activity – property relationship studies. The concept of graph entropy is to assign a probability function to the edges in the chemical graph using the topological descriptor and it helps to characterise the complexity of graphs.

method:
We have employed the degree counting method and edge partition based on the vertices and edges of the adjacently and non-adjacently configured pentagonal nanocone structures to obtain the edge partitions and then using the corresponding mathematical expression, the degree based descriptors and its corresponding entropies were determined.

result:
Result: The analytically closed formulas to compute the degree based topological descriptors and graph entropies for any generation of the class of nanocone structures were obtained.

conclusion:
In this work, the degree based descriptors and the corresponding graph entropies for the adjacently and non-adjacently configured pentagonal structure of carbon nanocones are determined applying the degree counting method and edge partition based on the vertices and edges. Also a graphical comparative study was also done with the help of obtained results.

other:
end.
The Effectiveness of a Telenutrition Intervention to Improve Dietary Behavior and Physical Activity Among Adolescents With Obesity: Protocol for a Systematic Review
Authors: Ansari Muhammad Ridwan , Kodriati Nurul , Pertiwi Ariani Arista Putri , Dewi Fatwa Sari Tetra 
Published: February 2024

Background
The global obesity pandemic among adolescents is becoming a public health issue throughout the world. Telehealth use has significantly increased during and after the COVID-19 pandemic, including its application in adolescent obesity prevention and treatment.

Objective
This review aims to synthesize the evidence on the effectiveness of telenutrition in improving dietary behavior and physical activity in adolescents with obesity.

Methods
The PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols) guideline will be used to structure this protocol. The focus of the systematic review is guided by the population, intervention, comparator, and outcome (PICO) framework. A systematic search of Science Direct, PubMed, Cochrane, Embase, JMIR, ProQuest, and Google scholar databases will be conducted. Two authors will screen the titles and abstracts of identified studies independently and select studies according to the eligibility criteria. The full-text reading will be done independently by 2 reviewers to assess final eligibility. Any discrepancies will then be discussed and resolved. The Cochrane Collaboration Risk of Bias tool was used to assess the risk of bias; a descriptive analysis will summarize the effectiveness of the telenutrition or any type of telehealth intervention used.

Results
The systematic review is expected to be completed by the end of March 2024. The ongoing screening and review of the articles are currently being conducted.

Conclusions
This systematic review aims to summarize the effectiveness, features, design process, usability, and coherence of a telenutrition intervention using behavior change theory to improve dietary patterns and physical activity among adolescents with obesity. It will identify areas for improvement and best practices, informing the development of more useful and engaging telenutrition interventions for adolescents.

Trial Registration
PROSPERO CRD42023458336; http://tinyurl.com/cp46fjj9

International Registered Report Identifier (IRRID)
DERR1-10.2196/53282