bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of the solubilization of faecal sludge by microwave treatment
Authors: Md Principal , Pocock Jon , Velkushanova Konstantina 
Published: March 2024

Abstract

This study examined the effects of microwave treatment on the physicochemical characteristics of faecal sludge (FS). FS from Ventilated Improved Pit (VIP) latrines were treated in a microwave oven at varying microwave power levels and treatment times. Changes in total solids (TS), volatile solids (VS), total chemical oxygen demand (TCOD), and soluble chemical oxygen demand (sCOD) were measured. A response surface methodology (RSM) was used to optimize organic matter solubilization during microwave treatment. A central composite design was employed, and the observed responses were used to fit a second-order response surface model. Microwave treatment at 14,000kJ/kg.TS reduced FS volume by 58%. The VS/TS ratios remained similar before and after microwave treatment. The solubilization of organic matter (measured by sCOD/TCOD ratio) increased after microwave treatment, showing an initial linear increase with specific energy, followed by a decrease. The highest solubilization was 38%, achieved at microwave power level of 630W for 3 minutes. It was observed that organic matter solubilization was more sensitive to contact time than microwave power. The optimized conditions were determined by RSM to be 617.7W and 2.4 minutes, which were within the experimental design boundaries. These findings align with similar observations from other studies using wastewater sludge. The results suggest that microwave treatment can achieve multiple FS treatment objectives. Optimal operating conditions should be identified if the aim is to solubilize organic matter in FS.
Exploring the Antimicrobial and Anticancer Potential of Pyocyanin Produced by Pseudomonas aeruginosa Strain ONO14782
Authors: Ibrahim Prof. Dr. Mohamed Khaled , El-Zawhry Prof. Dr. Yehia Ahmed , Esmaiel Prof. Dr. Ahmed Abdel Rahman , Askora Prof. Dr. Ahmed Abdel Rahman , Mostafa Mohga Tohamy Afifi 
Published: March 2024

Abstract
Background
Pseudomonas aeruginosa is a clinically and epidemiologically important bacterium that causes both acute and chronic infections. The pathogenesis of P. aeruginosa depends on the virulence factors, The important virulence factors of P. aeruginosa included biofilm formation, pigment (pyocyanin), cytotoxins, phospholipases, elastases, and proteases. Pyocyanin is a chloroform soluble blue-green pigment produced by P. aeruginosa, has an antibacterial activity against a wide range of drug-resistant bacteria and pathogenic bacteria, also it was exhibited antifungal activity against different species of mycotoxigenic fungi. and we can use it as an anticancer agent is advised .
Methods
In this study, 46 out of 66 P. aeruginosa isolates were selected based on their pigmentation on cetrimide agar. Pseudomonas isolates were collected from urinary tract infection (urine), burned skin infection and diabetic foot wound (pus) and respiratory infections (sputum). Pseudomonas Cetrimide Agar was used as selective media. TLC technique was used for purification, while UV-Vis, FTIR and GC-MS techniques analysis were used for characterization properties for P73 (ONO14782) strain. Anticancerous effect has been determined by MTT assay established against HepG2, MCF-7 and HCT-116 cell lines.
Results
46 pigmented isolates were selected from 66 isolates. TLC plates showed a blue color in visible light with Rf = 0.81 for pyocyanin. A P73 (ONO14782) strain was used as an experimental strain to study the role of antimicrobial activity of pure pyocyanin, revealing resistance of Klebsiella pneumoniae and Staphylococcus aureus, with Escherichia coli showing intermediate sensitivity. Additionally, pyocyanin demonstrated antifungal efficacy against various yeast and fungi. Furthermore, pyocyanin showed promising anticancer activity against tested cancer cell lines, with strain P73 (ONO14782) displaying activity against HepG2, MCF-7, HCT-116, and A-549 cell lines.
Conclusions
The objective of this study is extraction and purification of pyocyanin from local clinical isolates and choose high productivity strain of pyocyanin studying characterization properties produced from P73 ONO14782 strain and studying its antimicrobial and anticancerous effect. Pyocyanin showed a very high cytotoxic effect on cancerous cell lines leads to reduction in viability of these cells.
Inflammatory Chemokines as Potential Reversal Agents for Tamoxifen Resistance in Breast Cancer Cells
Authors: Ashfaq Isbah , Munir Ali , Izza Bint E Javed , Shaukat Huzaifa , Pervaiz Asim , Asghar Muqadas , Tayyeb Asima 
Published: March 2024

Abstract
Tamoxifen therapy stands as a cornerstone in the treatment regimen for estrogen receptor positive breast cancer. However, emergence and management of tamoxifen resistance pose significant clinical hurdles. Hence, comprehending intricate molecular mechanisms of tamoxifen resistance becomes imperative. This study endeavors to decipher molecular mechanisms underlying acquired tamoxifen resistance. Integrated meta-analysis approach was employed on available microarray gene expression datasets to identify potential targets implicated in tamoxifen resistance. In silico findings were experimentally validated using MCF-7TamR cells model. Meta-analysis highlighted involvement of inflammatory pathways mainly up-regulation of chemokines in tamoxifen resistant breast cancer cells compared to control. qPCR analysis further confirmed significant up-regulation of chemokine genes, including CCL2, CCL20, CXCL6, CXCL14, CXCL12, CXCR4, CCR5, and CCL3 in MCF-7TamR cells. To delineate specific roles of these chemokines in tamoxifen resistance, MCF-7TamR cells were subjected, to selected inflammatory/chemokine antagonists, separately. The observed attenuation of cellular growth, induction of DNA damage, apoptosis, and cell cycle arrest, coupled with the down-regulation of chemokine gene expression, suggests a reversal of the resistance phenotype in treated cells compared to untreated resistant cells. In conclusion, our findings propose that inflammatory chemokines hold the potential to reverse tamoxifen resistance and augment drug sensitivity, offering a promising avenue for mitigating and overcoming tamoxifen resistance in breast cancer therapy.
Inotodiol Ameliorates Oxidative Stress and Apoptosis by Regulating PI3K/Akt/GSK-3β Signaling Pathways in Diabetic Nephropathy
Authors: Tian Lingling , Duan Qi , Li Rongshan , Li Yafeng 
Published: March 2024

Abstract
Diabetic nephropathy (DN), a kind of microvascular complication, is a primary cause of end-stage kidney disease worldwide. However, therapeutic drugs for DN treatment are still in lack. Inotodiol (INO), a kind of lanostane triterpenoid isolated from INO that has various biological activities. In this study, we employed db/db mice as the spontaneous DN model in vivo, and high glucose treated MPC5 cells in vitro to elucidate the protective effects and underlying mechanisms of INO in DN. Ratio of right kidney weight/body weight was calculated, and levels of FBG, urine albumin/creatinine (UACR), BUN and Scr were measured. The SOD, CAT, GSH-Px and MDA levels in kidney were detected by using commercial kits. The histopathological changes of renal tissues were assessed by HE, PAS and Masson staining. The intracellular ROS was detected by using fluorescence probe DCHF-DA. Cytotoxicity assay was performed using CCK-8 assay kit. The rate of apoptosis was detected by flow cytometry. The expressions of Bax, Bcl-2, Cytc, Cleaved caspase-3, GSK-3β, pSer-GSK-3β, Akt, p-Akt, Synaptopodin, WT-1, Nrf2, NQO1, Keap1, heme HO-1 were measured by western blot. The expressions of Bax, CytC, WT-1, Synaptopodin, Bcl-2, GSK-3β and pSer9-GSK-3β in renal tissues were measured by immunohistochemistry. Our results showed that INO treatment reduced the FBG, BUN, Scr and UACR levels in db/db mice. Moreover, INO increased the expressions of Synaptopodin and WT-1 proteins. Besides, INO treatment also mitigated kidney histopathological changes, reduces kidney oxidative stress as reflected by reduced levels of Keap-1, NOX4 and MDA, but increased levels of kidney antioxidants SOD, CAT, GSH-Px, Nrf2, NQO1 and HO-1. Additionally, kidney apoptosis decreased as reflected by decreased protein levels of Cytc, Bax and Cleaved caspase-3 while its anti-apoptosis Bcl-2 protein levels increased. Mechanistically, INO inhibited GSK-3β activity by activating the PI3K/Akt signaling pathway, increased the level of anti-apoptosis, decreased level of oxidative stress and reduced podocyte injury in vivo and in vitro. Collectively, these results indicated that INO protected against DN through ameliorating oxidative stress and apoptosis via the PI3K/Akt/GSK-3β pathway.
Purification and biochemical characterization of beta-hexosaminidase from freshwater cnidarian Hydra vulgaris Ind-Pune
Authors: Kukkemane Kowshik , Krishnapati Lakshmi Surekha , Vuruputuri Ratna Mahathi , Ranganatha Kavyashree Sakharayapatna , Nadimpalli Siva Kumar 
Published: March 2024

Abstract
Beta-N-acetylhexosaminidase (Hex) is a vital lysosomal hydrolase ubiquitous in living organisms, that plays a crucial role in cellular homeostasis. Dysfunctions in this enzyme are implicated in severe pathological conditions such as Tay-Sachs and Sandhoff diseases in humans. We report the purification and biochemical characterization of hexosaminidase from the soluble extracts obtained from the polyps of Hydra vulgaris Ind Pune. The Hydra Hex was purified by two-step sequential chromatography (hydrophobic interaction and gel filtration). Our results suggested that the enzyme isoform purified from Hydra is HexB, most likely to be a homodimer with a subunit mass of 65 kDa showing characteristic wobbling specificity. The pH optimum was in the range of 5.0 to 6.0 and the temperature optimum in the range of 50 ºC to 60 ºC. pH stability and temperature stability were found to be 5.0 and 40 ºC respectively. The homology modelling studies corroborated the homodimeric nature of Hydra HexB, and indicated its structural resemblance to human HexB. This first study offers significant insights into Hydra HexB, providing a foundational framework for further extensive investigations on this and other different lysosomal hydrolases in Hydra. The purified enzyme then holds promise for applications in glycomics and glycobiology research, offering new avenues for exploring the intricate roles of carbohydrates in biological systems.
Motor Skill Learning Modulates Striatal Extracellular Vesicles’ Content in a Mouse Model of Huntington’s Disease
Authors: Solana-Balaguer Júlia , Garcia-Segura Pol , Campoy-Campos Genís , Chicote-González Almudena , Fernández-Irigoyen Joaquín , Santamaría Enrique , Pérez-Navarro Esther , Masana Mercè , Alberch Jordi , Malagelada Cristina 
Published: March 2024

Abstract

Huntington’s disease (HD) is a neurological disorder caused by a CAG expansion in the Huntingtin gene (HTT). HD pathology mostly affects striatal medium-sized spiny neurons and results in an altered cortico-striatal function. Recent studies report that motor skill learning, and cortico-striatal stimulation attenuate the neuropathology in HD, resulting in an amelioration of some motor and cognitive functions. During physical training, extracellular vesicles (EVs) are released in many tissues, including the brain, as a potential means for inter-tissue communication. To investigate how motor skill learning, involving acute physical training, modulates EVs crosstalk between cells in the striatum, we trained wild-type (WT) and R6/1 mice, the latter with motor and cognitive deficits, on the accelerating rotarod test, and we isolated their striatal EVs. EVs from R6/1 mice presented alterations in the small exosome population when compared to WT. Proteomic analyses revealed that striatal R6/1 EVs recapitulated signaling and energy deficiencies present in HD. Motor skill learning in R6/1 mice restored the amount of EVs and their protein content in comparison to naïve R6/1 mice. Furthermore, motor skill learning modulated crucial pathways in metabolism and neurodegeneration. All these data provide new insights into the pathogenesis of HD and put striatal EVs in the spotlight to understand the signaling and metabolic alterations in neurodegenerative diseases. Moreover, our results suggest that motor learning is a crucial modulator of cell-to-cell communication in the striatum.
Microfluidic-on-a-chip for designing celecoxib-based amorphous solid dispersions: when the process shapes the product
Authors: Figueiredo Joana , Mendes Maria , Pais Alberto , Sousa João J. , Vitorino Carla 
Published: March 2024

Abstract

The fundamental idea underlying the use of amorphous solid dispersions (ASDs) is to make the most of the solubility advantage of the amorphous form of a drug. However, the drug stability becomes compromised due to the higher free energy and disorder of molecular packing in the amorphous phase, leading to crystallization. To overcome the stability concern, polymers are used as a matrix to form a stable homogeneous amorphous system. The present work aims to design ASD-based formulations under the quality umbrella by design principles for improving oral drug bioavailability, using celecoxib (CXB) as a model drug. ASDs were prepared from selected polymers and tested both individually and in combinations, using various manufacturing techniques: high-shear homogenization, high-pressure homogenization, microfluidic-on-a-chip, and spray-drying. The resulting dispersions were further optimized, resorting to a 32 full-factorial design, considering the API:Polymers ratio and the total solid content as variables. The formulated products were evaluated regarding analytical centrifugation and the influence of the different polymers on the intrinsic dissolution rate of the CXBASDs. Microfluidic-on-a-chip led to amorphous status of the formulation. The in vitro evaluation demonstrated a remarkable 26-fold enhancement in the intrinsic dissolution rate, and the translation of this formulation into tablets as the final dosage form is consistent with the observed performance enhancement. These findings are supported by ex vivo assays, which exhibited a two-fold increase in permeability compared to pure CXB. This study tackles the bioavailability hurdles encountered with diverse active compounds, offering insights into the development of more effective drug delivery platforms.
Low-complexity Continuous-Variable Quantum Key Distribution with true local oscillator using pilot-assisted frequency locking
Authors: Ruiz-Chamorro Andres , Garcia-Callejo Aida , Fernandez Veronica 
Published: March 2024

Abstract

In the domain of Continuous Variable Quantum Key Distribution (CV-QKD), a significant challenge arises in achieving precise frequency synchronization, an issue commonly termed as frequency locking. This involves matching the optical frequencies of both the quantum signal laser and the local oscillator laser for accurate symbol demodulation during the exchange of quantum keys. As such, implementations today still grapple with maintaining precise synchronization between sender and receiver frequencies, occasionally hindering the efficiency and reliability of the information exchange. Addressing this challenge, we present and empirically validate a novel approach to CV-QKD by incorporating a pilot tone-assisted frequency locking algorithm to enhance stability when using a locally generated local oscillator (LLO) at the receiver. The proposed design leverages software-based optimization techniques, thereby eliminating the need for high-speed electronic stabilization devices and achieving efficient performance at typical repetition rates. Specifically, the introduction of the pilot tone algorithm allows us to effectively mitigate phase fluctuations and preserve the integrity of the quantum signals during transmission without resorting to time-multiplexed reference pulses or fast-locking electronics in the lasers. Our results suggest the potential for achieving secure key rates of up to 1 Mb/s over a 50 km single-mode fiber when using these techniques, offering promising insights into the feasibility of high-rate, low-complexity CV-QKD implementations under realistic conditions.
Disposition of emergency department patients presenting with angiotensin-converting enzyme inhibitor-induced angioedema
Authors: Briggs Blake , Cline David , Husain Iltifat 
Published: March 2024

Abstract

Background
Angiotensin-converting enzyme inhibitors (ACEI) are the most common cause of drug-induced angioedema in the United States (US). Our primary objective was to provide descriptive evidence regarding ED disposition of ACEI-induced angioedema patients. Our secondary objective was to evaluate unique patterns in those with ACEI-induced angioedema at a tertiary referral center.
Methods
This was a retrospective study evaluating all cases of ACEI-induced angioedema at a large, regional academic medical center. We performed a medical record review to identify patients with ACEI-induced angioedema who presented to the ED from January 1, 2016, to December 31, 2022. A total of 637 unique patient encounters met potential inclusion. After a substantial, standardized review, 94 patients met inclusion.
Results
During the study period, there were 94 patients presenting to the ED who were diagnosed as having angioedema secondary to an ACEI (90 patients) or ARB (4 patients). The only treatment found to have statistical association with disposition was intramuscular (IM) epinephrine. Overall, 53 patients (56.38%) improved during their ED stay, and of those, 32 patients (60.38%) were discharged home. None of the 12 patients that worsened were sent home from the ED. Only thirteen of 43 ED discharged patients (23.64%) had their ACEI/ARB documented in their allergy listings compared to 42 of 51 patients (76.36%) of admitted patients, p < 0.0001, odds ratio of failure to document was 0.0929 (95% CI, 0.0352 to 0.24512). Only one patient out of the total 94 returned to the ED during our study period and was subsequently discharged.
Conclusion
Our results indicate that at a large, tertiary care referral center, carefully selected patients with ACEI-angioedema were safely discharged home with low risk of return visit to the ED within 72 hours. No particular symptom or sign predicted the need for intubation, but those who were discharged from the ED with a median stay of 4 hours had no increased risk of return to the ED versus those who were admitted. Further, among those admitted, patients in our study had a short inpatient stay and were safely discharged with no documented early return visit to the ED.
A novel approach to alleviate acetaminophen-induced hepatotoxicity with hybrid balloon flower root-derived exosome-like nanoparticles (BDEs) with silymarin via inhibition of hepatocyte MAPK pathway and apoptosis
Authors: Kim Jisu , Gao Chao , Guo Pengcheng , Sheng Jianyong , Wang Jianxin 
Published: March 2024

Abstract

Introduction: Balloon flower root-derived exosome-like nanoparticles (BDEs) have recently been proposed as physiologically active molecules with no cytotoxicity. However, the therapeutic effects of drug-induced hepatotoxicity of BDEs have not been elucidated. BDEs contain a large amount of platycodin D, which is widely known to be effective in regulating inflammation and ameliorating systemic toxicity. Thus, the main therapeutic activity of BDEs is attributed to inhibiting the inflammatory response and alleviating toxicity.
Objective: Considering the potential therapeutic effects of BDEs, and the potential to achieve synergistic effects to improve therapeutic outcomes, we constructed hybrid BDEs with a soy lecithin-based liposome loaded with silymarin (SM). Since liposomes can provide higher thermal stability and have greater structural integrity, these might be more resistant to clearance and enzymatic degradation of drug molecules.
Methods: Hybrid BDEs with liposome-loaded SM (BDEs@lipo-SM) were fabricated by thin-film hydration and extrusion. BDEs@lipo-SM were characterized using dynamic light scattering and high-performance liquid chromatography. After confirmation of the physical properties of BDEs@lipo-SM, various therapeutic properties were evaluated.
Results: BDEs@lipo-SM were internalized by hepatocytes and immune cells and significantly decreased mRNA expression of apoptosis and inflammation-relevant cytokines by inhibiting the hepatocyte MAPK pathway. BDEs@lipo-SM significantly induced an increase in glutathione levels and inhibited APAP-induced hepatotoxicity.
Conclusion: BDEs@lipo-SM have therapeutic benefits for acute liver injury and can alleviate cell death or toxicity. BDEs@lipo-SM can accelerate liver recovery in the APAP-induced acute liver injury model, which highlights thathybrid BDEs represent an attractive delivery vehicle for therapeutic applications.
Shape optimisation of a hydrodynamic separator using expensive and constrained multi-objective computational modelling
Authors: Roberts Andrew Philip , Rahat Alma As-Aad Mohammad , Jarman Daniel Stuart , Fieldsend Jonathan Edward , Tabor Gavin Randal 
Published: March 2024

Abstract
The shape of a hydrodynamic particle separator has been optimised using unsteady computational fluid dynamics, coupled with Lagrangian particle tracking, combined with a parallelised and robust formulation of Bayesian optimisation. The noise present in the models of the separator required the use of the minimum probability of improvement infill criterion for optimisation of the geometry. This allowed direct inclusion of the objective noise via homoscedastic Gaussian process models. The wall clock time for the fluid modelling suggested that the Bayesian sampling should be parallelised. An existing parallelisation strategy was modified for the infill criterion being used and customised to favour exploitation in the decision space in order to deal with the cliff-edge type landscape that the infill criterion created. A new strategy was developed for convergence failures using Voronoi penalisation, while the approach for handling hardware failures was by manual restart. The presence of unsteady flow in the separator was addressed by time-resolving the flow fields in an Eulerian-Lagrangian manner. The optimisation generated an approximate Pareto front of solutions, which included novel and unexpected geometric shapes, demonstrating the value of Bayesian optimisation in producing innovative designs, which resulted in the filing of a patent.