bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional validation of squalene epoxidase in triterpenes biosynthesis in Poria cocos by molecular docking and CRISPR-Cas9 gene editing
Authors: Liu Xiaoliu , Xie Jing , Xie Zhenni , Zhong Can , Liu Hao , Zhang Shuihan , Jin Jian 
Published: March 2023

Abstract
Background
Squalene epoxidase is one of the rate-limiting enzymes in the biosynthetic pathway of membrane sterols and triterpenoids. The enzyme catalyzes the formation of oxidized squalene, which is a common precursor of sterols and triterpenoids. In recent years, CRISPR/Cas9 gene editing technology has emerged and other functional genes in the Poria cocos triterpene synthesis pathway have been studied; PcSE has not been reported.
Results
In this study, the squalene epoxidase gene (PcSE) was evaluated in Poria cocos. Molecular docking between PcSE and squalene was performed and the active amino acids were identified. sgRNA sequences were designed based on the active site residues. In vivo verification of PcSE function was performed using a PEG-mediated protoplast transformation approach. The effect on triterpene synthesis in P. cocos was consistent with the results from ultra-high-performance liquid chromatography-quadruplex time-of-flight-double mass spectrometry (UHPLC-QTOF-MS/MS) analysis. Which showed that deletion of PcSE inhibited triterpene synthesis.
Conclusions
A gene editing system based on molecular docking was successfully constructed to demonstrate that PcSE functions as a house squalene cyclooxygenase, which provides a basis for further studies on the heterologous biosynthesis of P. cocos secondary metabolites.
Waste to resource: An approach towards end-of-life investigation of defense used boot of Bangladesh for sustainable environment
Authors: Sujan SMA , Sarker Shashanka Shekhar , Mahmud Yead , Tamanna Al , Debnath Akash , Alam Md. Ashraful , Mizan Al , Uddin Md. Tushar 
Published: March 2023

AbstractAfter a certain period or end-of-life (EoL), all the valuable products become waste if they are not properly managed. This study reveals the appropriate and sustainable pathway to manage the various solid wastes coming from used footwear (boots) of the Bangladesh Armed Forces and other Forces. The major parts separated from the collected four pair of used boots include leather, thermoplastic rubber (TPR) materials (e.g., sole, toe puff, stiffener, etc.), laces, metal shank, metal eyelet, etc. Careful observation of the used boots and its separated parts indicated 92-96% damage of the boots after the use of the boots for six months. Based on the properties of different parts of used boots, an integrated 4R’s waste management (reuse, recycle, recovery, and reduce) concept was introduced. It helps to minimize greenhouse gas, smog, heavy metals, dyes, pigments, and other pollutants emission to the atmosphere, thereby reducing the severe health consequences, environmental pollution, and climate change. This paper also discusses the critical aspects of various materials obtained from the post-consumer used boot through different mechanical, thermochemical, and chemical treatment processes.
Cytotoxicity Evaluation of Eucalyptus camaldulensis leaf extract against Cholangiocarcinoma Cell lines (CL-6)
Authors: Amuamuta Asmare , Berihun Birhanu 
Published: March 2023

Abstract
Background

Cholangiocarcinoma(CCA) is an important public health problem in many tropical and subtropical parts of the world. Eucalyptus camaldulensis leaves as well as its essential oil extracts are well known for its traditional use and pharmacological actions including insect repellant/insecticidal activity, antimicrobial, cytotoxic/anticancer activity as well as for many other disorders in different parts of the world including Africa and Southeast Asia.

Materials and Methods

This study was conducted to investigate the cytotoxic activity of E. camaldulensis leaf extract preparations at in vitro against the CCA tumor (CL-6 cell line). E. camaldulensis leaves collected from Ethiopia (Western Gojjam and Southern Gonder area) was used for extract preparation in 95% ethanol using different extraction methods, i.e.,ultrasonication, heating reflux, and maceration (1 day, 3 days and 7 days). The extract and the standard anticancer drug preparation 5-fluorouracil (5-FU) were evaluated in triplicate for their cytotoxic activities against CL-6 cell line and normal human cell line (OUMS) using standard MTT cell proliferation assay at eight serial dilution concentrations (3.8–500µg/mL).

Results

A semi-solid brown black residue with a characteristic odor was obtained after solvent removal and extract concentration was done by using a rotary evaporator at 60oC. The highest (mean ± SD) percent yield (3.73 ± 0.61) was obtained by using maceration technique with the solvent for 7 days, followed by heating reflux (1.73 ± 0.80) and the least was obtained from 1day maceration method (0.90 ± 0.52). The extract was then stored at -20oC until use. The cytotoxic activity (mean ± SD IC50 values) E. camaldulensis extract and 5-FU against CL-6 were 102.29 ± 5.87 and 106.75 ± 3.06 (mean IC50 ± SD) µg/mL, respectively. The extract’s IC50 value observed in normal OUMS cell line was 165.9 ± 10.3.

Conclusion

The extract of E. camaldulensis collected from the study area exhibited in vitro cytotoxic activity against human CCA tumor cell line (CL-6). Further in vitro and in vivo evaluation of the selected herbal extract preparation is recommended in the search for development of safe and promising drug options against CCA and other cancer types.
Virtual flavonoids screening identifies potent compounds against enterovirus A71 and coxsackievirus A16
Authors: Sripattarp Amita , Sanachai Kamonpan , Chavasiri Warinthorn , Wolschann Peter , Langer Thierry , Boonyasuppayakorn Siwaporn , Rungrotmongkol Thanyada 
Published: March 2023

Abstract
Worldwide outbreaks of hand, foot, and mouth disease (HFMD) are caused by enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). Since no anti-HFMD drugs are currently available, it is interesting to study potential viral inhibitors. Rupintrivir is a rhinovirus 3C protease (3Cpro) inhibitor with apparent inhibitory activity against HFMD. This study constructs pharmacophore models of the EV-A71 and CV-A16 3Cpro complexed with rupintrivir using molecular dynamics (MD) simulations. Both models had similar pharmacophore features, including hydrogen bond donors and acceptors and hydrophobic interactions. These pharmacophore models were then used as a template to screen 39 flavonoid compounds as potential novel inhibitors. Diosmin, epigallocatechin gallate (EGCG), and RTH-011 showed high binding affinities for EV-A71 and CV-A16 3Cpro. They formed hydrogen bonds with important surrounding residues in both proteins, including H40, L127, T142, A144, T145, H161, I162, G163, and G164. In addition, their effective concentrations against rhabdomyosarcoma (RD) cell infection by EV-A71 and CV-A16 were determined. EGCG had the highest half maximal effective concentration (EC50) of 12.86 ± 1.30 µM for EV-A71 and 15.54 ± 1.50 µM for CV-A16, while diosmin had EC50 of 21.01 ± 1.57 µM for EV-A71 and 30.68 ± 3.25 µM for CV-A16. Both compounds were non-toxic in RD cells, with 50% cytotoxic concentrations of > 100 µM for EGCG and > 500 µM for diosmin. In addition, MD simulation analysis showed that EGCG had a higher binding affinity than diosmin, supported by its significantly lower solvated binding free energies and greater numbers of contact atoms and key binding residues. Moreover, previous studies reported EGCG’s inhibitory effect on other viruses, such as severe acute respiratory syndrome coronavirus 2. Therefore, our findings suggest that EGCG can effectively inhibit the EV-A71 and CV-A16 3Cpro.
Research on anti-impact performance of steel fiber reinforced concrete based on finite element and machine learning
Authors: Zhao Jingshuo , Yang Xiaolin , Gao Shiwu , Ma Hongwei 
Published: March 2023

Abstract
To predict the impact resistance of steel fiber reinforced concrete (SFRC), 50 specimens with different fiber lengths and different fiber contents were loaded using ABAQUS finite element software to obtain data in this paper. Two machine learning (ML) models, backward propagation-artificial neural network (BP-ANN) and support vector machine (SVM), were used to train the data. The results show that in the prediction of the impact resistance of steel fiber reinforced concrete by this model, the deviation of the predicted values from the real values is small, and the two models are well fitted. To further optimize the model, the parameters of the prediction model were adjusted using the whale optimization algorithm (WOA) in this paper, and the accuracy of the optimized model was significantly improved. After optimization, the WOA-BP-ANN and WOA-SVM models have better generalization ability and higher prediction accuracy than the WOA-SVM model.
The Protective Effect of the Asystasia chelonoides Extracts on Hypertensive
Nephropathy Rats
Authors: Duan Tingting , Li Minyi , Lie Beifeng , Lin Ziyang , Li Mengqiu , Xia Tao , Lin Guixuan , Meng Lanqing , Lu Xiuqing , Li Zhenghai , Yang Junzheng 
Published: March 2023

Background:
Hypertensive nephropathy (HN) is one kind of kidney disorders caused
by long-term uncontrolled hypertension, usually resulting in severe kidney damage, including
inflammation and oxidative stress, no matter in cells or tissues, from patients with nephropathy. In
recent years, nephropathy accompanied by hypertension is becoming one of the main causes for
kidney replacement therapy, but few effective treatments have been reported for HN treatment.
Asystasia chelonoides (AC) is a kind of plant with the effects of anti-inflammation, lowering blood
pressure, and anti-oxidative stress. Still, the therapeutic effect of AC in HN rats is not clear.

Methods:
To establish HN model by feeding high sugar and high fat diet spontaneously hypertensive
rats. Blood measurement, HE staining, PAS staining and biochemical analysis and were used
to assess the therapeutic effects of AC extracts and western blotting analyzed the underlying
mechanisms of AC extracts treatment in the HN rat model.

Results:
AC extracts could significantly lower systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) in HN rats; and reduce the expression of total protein (TP), blood urea nitrogen (BUN), microalbuminuria (MALB), creatinine (Cr), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) concentrations, and also could down-regulate expression of IL-6, MDA and AGEs, up-regulate the expression of SOD in HN rats; HE staining and PAS staining demonstrated that AC extracts could alleviate the histopathological changes in HN rats; western blotting demonstrated that AC extracts could up-regulate the expression of PPARγ and down-regulate the expression of TGFβ1 and NF-кB in HN rats.

Conclusion:
The finding of the article demonstrated that AC extracts had the better therapeutic
effect for HN, and provided the pharmacological evidences for AC extracts treatment for HN.
Pyrazole Scaffolds Having Promising Pharmacological Potential: A Review
Authors: Singh Sucheta , Tehlan Sumit , Kumar Verma Prabhakar 
Published: March 2023

Abstract:
Heterocyclic compounds have diverse structure, which makes them broad and economical
therapeutic agents. Pyrazole is a five-membered aromatic ring that contains two nitrogen atom and is
responsible for the diverse functions of heterocyclic compounds. This implies the need of reviewing
the work that already has been done on the potential of pyrazole scaffolds in the field of medicinal
chemistry for the synthesis of new compounds with more effective antimicrobial, antioxidant, anticancer,
anti-tuberculosis, and anti-inflammatory activities.
Functional Nutrition as Integrated Intervention for In- and Outpatient
with Schizophrenia
Authors: Matrisciano Francesco 
Published: March 2023

Abstract:
Schizophrenia is a chronic and progressive disorder characterized by cognitive, emotional,
and behavioral abnormalities associated with neuronal development and synaptic plasticity alterations.
Genetic and epigenetic abnormalities in cortical parvalbumin-positive GABAergic interneurons and
consequent alterations in glutamate-mediated excitatory neurotransmission during early neurodevelopment
underlie schizophrenia manifestation and progression. Also, epigenetic alterations during
pregnancy or early phases of postnatal life are associated with schizophrenia vulnerability and inflammatory
processes, which are at the basis of brain pathology and a higher risk of comorbidities, including
cardiovascular diseases and metabolic syndrome. In addition, schizophrenia patients adopt an
unhealthy lifestyle and poor nutrition, leading to premature death. Here, I explored the role of functional
nutrition as an integrated intervention for the long-term management of patients with schizophrenia.
Several natural bioactive compounds in plant-based whole foods, including flavonoids, phytonutrients,
vitamins, fatty acids, and minerals, modulate brain functioning by targeting neuroinflammation
and improving cognitive decline. Although further clinical studies are needed, a functional diet
rich in natural bioactive compounds might be effective in synergism with standard treatments to improve
schizophrenia symptoms and reduce the risk of comorbidities.
Recent Discovery of Triazine Derivatives as Protease Inhibitors for the
Treatment of Coronavirus-19 (COVID-19)
Authors: De Surya K. 
Published: March 2023

Abstract:
The present application describes a class of compounds exhibiting a
coronavirus 3CL protease inhibitory effect and pharmaceutically acceptable
salts thereof, and a pharmaceutical composition containing the same. The application
also provides the synthesis of compounds and efficacy from in vitro
and cell- based assays.
Centenary of Insulin Therapy: A Review
Authors: Zargar Abrar Ahmad , Kumar Ranjeet , Kumar Arvind , Gangwar Ruby , Sharma Amit 
Published: March 2023

Abstract:
Insulin is an endocrine hormone produced by the beta cells of islets of Langerhans in the
pancreas. It regulates blood sugar levels and various anabolic activities such as glycogenesis and
lipid synthesis. Despite the fact that insulin therapy has been around for 100 years, insulin formulations
are continually being improved to lower the risk of hypoglycaemia and other adverse effects,
including weight gain. The development of insulin pens has significantly reduced the consequences
of hypoglycaemia instead of vials and syringes. Both injectable devices were well-received by the
patients. In the population under study, the efficacy and safety profiles of the pen appeared to be
comparable to those of the vial/syringe. However, more patients reported that they would like to
keep using pen devices. This article aimed to summarize the background of insulin, its mechanism,
types, needle size, injection technique, adverse drug reactions and various studies related to insulin.
It has been recommended intensive treatment of type-1 and type-2 diabetes patients to achieve
good metabolic control and avoid chronic complications caused by poor glycaemic control.
Healthcare professionals should address concerns about safe and effective implementation of inpatient
hypoglycaemic control and insulin usage and they should empower patients to self-manage
their diabetes, so they may improve their quality of life as well as avoid potential complications.
Much more progress is expected in the future, at a faster pace, based on the implementation of
well-organized recovery efforts, advancing technologies, and scientific collaboration.
Diverse Approaches toward Application of Dental Pulp Stem Cells from
Human Permanent and Deciduous Teeth in the Treatment of Diabetes
Authors: Kanafi Mohammad Mahboob , Bhonde Ramesh Ramchandra 
Published: March 2023

Background:
Diabetes Mellitus is defined by hyperglycemia, a condition which is the
result of defects in insulin secretion, insulin action, or both. Evidence suggest that islet transplantation
is a promising treatment approach, but the shortage of sources of insulin-producing cells is a
major problem. Ethical concerns and the limited availability of most stem cells have led scientists
to concentrate on mesenchymal stem cells, which are found in stem cells niches of all organs of the
body including dental tissues on which dental pulp stem cells (DPSCs) and stem cells from exfoliated
deciduous teeth (SHED) are the easiest accessible sources.

Highlights:
Generally, SHED show characteristics similar to DPSCs; however, its proliferative
and clonogenic capacities are higher. It has been proved that these two types of dental mesenchymal
stem cells are able to produce islet-like cells capable of insulin secretion. In this review, we
discuss various conducted approaches on the application of DPSCs and SHED in the treatment of
diseases associated with diabetes such as; pancreatic differentiation cocktails, 2D and 3D culture
techniques, factors that affect pancreatic differentiation, in vivo studies (direct administration of
DPSCs and SHED, administration of their secretome and encapsulation of their-derived insulin
producing cells), clinical trials and future perspectives of these approaches.

Conclusion:
Dental stem cell-based therapy has been considered as a promising therapeutic procedure
for treatment of diabetes. Major advances in research on the derivation of insulin producing
cells from DPSCs and SHED have enhanced our chance of re-establishing glucose-responsive insulin
secretion in patients with diabetes.
Evaluating Diagnostic Efficiency of Thyroid Imaging Reporting and Data
Systems proposed by the American College of Radiology in Surgically Resected
Thyroid Nodules
Authors: Ahmadinejad Izadmehr , Mardasi Kimia Ghanbari , Ahmadinejad Yasmina , Kahrizi Mohammad Saeed , Soltanian Ali , Merdasi Pooriya Ghanbari , Ahmadinejad Mojtaba 
Published: March 2023

Aim:
Thyroid nodules are one of the most common clinical findings, with a prevalence of 68% in adults. Thyroid cancer is the fifth most common cancer in women.

Introduction:
The purpose of this study is to evaluate the diagnostic efficacy of Thyroid Imaging Reporting and Data Systems proposed by the American College of Radiology (ACR-TIRADS) for the diagnosis of malignancy in surgically resected thyroid nodules

Methods:
In this retrospective study, patients who underwent thyroid nodules resected surgically from 2018-2020 were included. Before resection, an ultrasound was performed for TIRADS scores, and after resection histopathology, thyroid mass was obtained. The outcomes of the two systems were statistically compared.

Results:
The mean age of the 146 included patients was 47.6 ± 14.08 years, of which 109 (74.7%) were female. Based on TIRADS, 47 patients (32.2%) were in TI-RADS TR3, 36 patients (24.7%) were in TIRADS TR2, 34 (23.3%) in TIRADS 4, 24 (16.4%) in TIRADS TR5 and 5 patients (3.4%) were in TIRADS TR1. The overall sensitivity was 79.9% when ACR-TIRADS TR4 was set as a diagnostic cutoff value. Considering the total of TIRADS TR4 and TIRADS TR5 as predictors of thyroid malignancy, the sensitivity was 74.5% and the specificity was 76.8%. The positive and negative predictive value was 60.3% and 76.8%.

Conclusion:
ACR-TIRADS 4 and 5 can be considered good predictors of malignancy in thyroid nodules. More studies, including larger samples, are required to obtain a better conclusion.
Application of Transabdominal Ultrasonography in the Diagnosis of Absent
Contractility - A Case Report
Authors: Hu Mingyang , Liu Dong 
Published: March 2023

Introduction:
Absent contractility is a kind of esophageal motility disorder. Patients are often diagnosed by endoscopic ultrasonography or high-resolution
manometry (HRM). In this paper, we report two cases of absent esophageal contractility first discovered by transabdominal ultrasonography.

Case Presentation:
The main symptom of both cases was acid reflux, and the main diagnosis was absent esophageal contractility. They were all discovered by
transabdominal ultrasonography. After the treatment of surgery or drugs, the symptoms relieved during follow-up, without any other discomforts.

Conclusion:
Transabdominal ultrasound as a primary screening method for absent contractility is proposed in this paper, which is non-invasive, real-time, and
fast. Ultrasound is expected to improve the diagnostic efficiency of peristalsis and patient experience in combination with the above invasive
examinations. The use of sonography in the diagnosis of absent contractility has seldom been studied. Further investigation is required to determine
whether this technique may better assess absent contractility.
Risk Factors for Prolonged Intensive Care Unit Stay in Patients with
Hypercapnic Respiratory Failure
Authors: Naurzvai Nurgul , Mammadova Ayshan , Gursel Gul 
Published: March 2023

Introduction:
Hypercapnic respiratory failure (HRF) is one of the most frequent reasons for intensive care unit (ICU) admissions. In this study, we aimed to investigate the risk factors for prolonged ICU stay in HRF patients for longer than 7, 10, and 15 days.

Methods:
Impact of demographics, vitals at the admission, comorbid disease severity, respiratory parameters, admission diagnosis, noninvasive mechanical ventilation (NIV) application time and settings, arterial blood gas, and blood biochemistry results were analyzed in patients with HRF to investigate risk factors for longer ICU stay.

Results:
A total of 210 patients who were admitted to ICU with HRF (PaCO2 values of 45 mmHg and higher) were included in this retrospective cohort study. The mean age of the patients was 69±12 years, and the mean ICU duration was 9±7 days. Forty-five percent of the patients stayed in the ICU for more than one week and %10 of them stayed for more than 15 days. Risk factors for a prolonged stay in ICU for more than 7 days were high SOFA score, acute renal failure (ARF) at admission, low PaO2/FiO2 on the 2nd day of admission, and high TSH level. Low FEV1 and FEV1/FVC ratio, ARF at admission, and low PaO2/FiO2 ratio on the 2nd day of admission were found to be risk factors for prolonged stay in ICU for longer than 10 days. Significant risk factors prolonging the ICU duration for more than 15 days were high SOFA score, low FEV1, low FEV1/FVC ratio (P = 0.008), and hypothyroidism (P = 0.037). FEV1% predicted less than 25.5% and FEV1/FVC% less than 46.5 % were significantly associated with ICU stay longer than 10 days.

Conclusion:
Earlier diagnosis and treatment of patients with hypothyroidism and severe airflow obstruction could shorten the length of ICU stay of hypercapnic patients.