CRISPR single base-editing: in silico predictions to variant clonal cell lines.

Engineering single base edits using CRISPR technology including specific deaminases and single-guide RNA (sgRNA) is a rapidly evolving field. Different types of base edits can be constructed, with cytidine base editors (CBEs) facilitating transition of C-to-T variants, adenine base editors (ABEs) enabling transition of A-to-G variants, C-to-G transversion base editors (CGBEs) and recently adenine transversion editors (AYBE) that create A-to-C and A-to-T variants. The base-editing machine learning algorithm BE-Hive predicts which sgRNA and base editor combinations have the strongest likelihood of achieving desired base edits. We have used BE-Hive and TP53 mutation data from The Cancer Genome Atlas (TCGA) ovarian cancer cohort to predict which mutations can be engineered, or reverted to wild-type (WT) sequence, using CBEs, ABEs or CGBEs. We have developed and automated a ranking system to assist in selecting optimally designed sgRNA that considers the presence of a suitable protospacer adjacent motif (PAM), the frequency of predicted bystander edits, editing efficiency and target base change. We have generated single constructs containing ABE or CBE editing machinery, an sgRNA cloning backbone and an enhanced green fluorescent protein tag (EGFP), removing the need for co-transfection of multiple plasmids. We have tested our ranking system and new plasmid constructs to engineer the p53 mutants Y220C, R282W and R248Q into WT p53 cells and shown that these mutants cannot activate four p53 target genes, mimicking the behaviour of endogenous p53 mutations. This field will continue to rapidly progress, requiring new strategies such as we propose to ensure desired base-editing outcomes.

MAC-ErrorReads: machine learning-assisted classifier for filtering erroneous NGS reads.

BACKGROUND: The rapid advancement of next-generation sequencing (NGS) machines in terms of speed and affordability has led to the generation of a massive amount of biological data at the expense of data quality as errors become more prevalent. This introduces the need to utilize different approaches to detect and filtrate errors, and data quality assurance is moved from the hardware space to the software preprocessing stages. RESULTS: We introduce MAC-ErrorReads, a novel Machine learning-Assisted Classifier designed for filtering Erroneous NGS Reads. MAC-ErrorReads transforms the erroneous NGS read filtration process into a robust binary classification task, employing five supervised machine learning algorithms. These models are trained on features extracted through the computation of Term Frequency-Inverse Document Frequency (TF_IDF) values from various datasets such as E. coli, GAGE S. aureus, H. Chr14, Arabidopsis thaliana Chr1 and Metriaclima zebra. Notably, Naive Bayes demonstrated robust performance across various datasets, displaying high accuracy, precision, recall, F1-score, MCC, and ROC values. The MAC-ErrorReads NB model accurately classified S. aureus reads, surpassing most error correction tools with a 38.69% alignment rate. For H. Chr14, tools like Lighter, Karect, CARE, Pollux, and MAC-ErrorReads showed rates above 99%. BFC and RECKONER exceeded 98%, while Fiona had 95.78%. For the Arabidopsis thaliana Chr1, Pollux, Karect, RECKONER, and MAC-ErrorReads demonstrated good alignment rates of 92.62%, 91.80%, 91.78%, and 90.87%, respectively. For the Metriaclima zebra, Pollux achieved a high alignment rate of 91.23%, despite having the lowest number of mapped reads. MAC-ErrorReads, Karect, and RECKONER demonstrated good alignment rates of 83.76%, 83.71%, and 83.67%, respectively, while also producing reasonable numbers of mapped reads to the reference genome. CONCLUSIONS: This study demonstrates that machine learning approaches for filtering NGS reads effectively identify and retain the most accurate reads, significantly enhancing assembly quality and genomic coverage. The integration of genomics and artificial intelligence through machine learning algorithms holds promise for enhancing NGS data quality, advancing downstream data analysis accuracy, and opening new opportunities in genetics, genomics, and personalized medicine research.

IL-33 Expression Is Lower in Current Smokers at both Transcriptomic and Protein Levels.

Rationale: IL-33 is a proinflammatory cytokine thought to play a role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). A recent clinical trial using an anti-IL-33 antibody showed a reduction in exacerbation and improved lung function in ex-smokers but not current smokers with COPD. Objectives: This study aimed to understand the effects of smoking status on IL-33. Methods: We investigated the association of smoking status with the level of gene expression of IL-33 in the airways in eight independent transcriptomic studies of lung airways. Additionally, we performed Western blot analysis and immunohistochemistry for IL-33 in lung tissue to assess protein levels. Measurements and Main Results: Across the bulk RNA-sequencing datasets, IL-33 gene expression and its signaling pathway were significantly lower in current versus former or never-smokers and increased upon smoking cessation (P < 0.05). Single-cell sequencing showed that IL-33 is predominantly expressed in resting basal epithelial cells and decreases during the differentiation process triggered by smoke exposure. We also found a higher transitioning of this cellular subpopulation into a more differentiated cell type during chronic smoking, potentially driving the reduction of IL-33. Protein analysis demonstrated lower IL-33 levels in lung tissue from current versus former smokers with COPD and a lower proportion of IL-33-positive basal cells in current versus ex-smoking controls. Conclusions: We provide strong evidence that cigarette smoke leads to an overall reduction in IL-33 expression in transcriptomic and protein level, and this may be due to the decrease in resting basal cells. Together, these findings may explain the clinical observation that a recent antibody-based anti-IL-33 treatment is more effective in former than current smokers with COPD.

The effect of SiO2 crystallization in enhancing the luminescence of Dy3+-Sm3+ co-doped glass ceramics for cool white light application.

The present work investigates the structural and luminescence behaviour of Dy3+-Sm3+ co-doped glass ceramics obtained through heat treatment of precursor glasses. The growth of SiO2 polycrystalline particles and evolution of these crystallites in the glass domain are witnessed via XRD and FESEM study. The presence of network vibrational bands, hydroxyl groups and the increased quantity of bridging oxygens (BOs) in glass ceramics are analysed through FTIR spectroscopy study. The absorption study (UV-Visible-NIR) showed the possible electronic transitions of Dy3+ and Sm3+ ions. The red shift in the absorption band edges and the lower bandgap values are obtained as a result of improved heat treatment in glass ceramics. Emission studies show the enhanced luminescence intensity of glass ceramics under 350 and 402 nm excitations. Decay measurement of glass ceramics showed the improved lifetimes of Dy3+ and Sm3+ ions to have appeared in microseconds (×10-6 s). The colour characteristics of glass ceramics analysed using CIE colour chromaticity diagram and correlated colour temperature (CCT) values suggest the neutral to cool white light emissions. Therefore, prepared glass ceramics with SiO2 polycrystalline phase are considered to be suitable materials in cool white LEDs applications.

Increased SARS-CoV-2 Infection, Protease, and Inflammatory Responses in Chronic Obstructive Pulmonary Disease Primary Bronchial Epithelial Cells Defined with Single-Cell RNA Sequencing.

Rationale: Patients with chronic obstructive pulmonary disease (COPD) develop more severe coronavirus disease (COVID-19); however, it is unclear whether they are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and what mechanisms are responsible for severe disease. Objectives: To determine whether SARS-CoV-2 inoculated primary bronchial epithelial cells (pBECs) from patients with COPD support greater infection and elucidate the effects and mechanisms involved. Methods: We performed single-cell RNA sequencing analysis on differentiated pBECs from healthy subjects and patients with COPD 7 days after SARS-CoV-2 inoculation. We correlated changes with viral titers, proinflammatory responses, and IFN production. Measurements and Main Results: Single-cell RNA sequencing revealed that COPD pBECs had 24-fold greater infection than healthy cells, which was supported by plaque assays. Club/goblet and basal cells were the predominant populations infected and expressed mRNAs involved in viral replication. Proteases involved in SARS-CoV-2 entry/infection (TMPRSS2 and CTSB) were increased, and protease inhibitors (serpins) were downregulated more so in COPD. Inflammatory cytokines linked to COPD exacerbations and severe COVID-19 were increased, whereas IFN responses were blunted. Coexpression analysis revealed a prominent population of club/goblet cells with high type 1/2 IFN responses that were important drivers of immune responses to infection in both healthy and COPD pBECs. Therapeutic inhibition of proteases and inflammatory imbalances reduced viral titers and cytokine responses, particularly in COPD pBECs. Conclusions: COPD pBECs are more susceptible to SARS-CoV-2 infection because of increases in coreceptor expression and protease imbalances and have greater inflammatory responses. A prominent cluster of IFN-responsive club/goblet cells emerges during infection, which may be important drivers of immunity. Therapeutic interventions suppress SARS-CoV-2 replication and consequent inflammation.

Early transcriptional responses of bronchial epithelial cells to whole cigarette smoke mirror those of in-vivo exposed human bronchial mucosa.

BACKGROUND: Despite the well-known detrimental effects of cigarette smoke (CS), little is known about the complex gene expression dynamics in the early stages after exposure. This study aims to investigate early transcriptomic responses following CS exposure of airway epithelial cells in culture and compare these to those found in human CS exposure studies. METHODS: Primary bronchial epithelial cells (PBEC) were differentiated at the air-liquid interface (ALI) and exposed to whole CS. Bulk RNA-sequencing was performed at 1 h, 4 h, and 24 h hereafter, followed by differential gene expression analysis. Results were additionally compared to data retrieved from human CS studies. RESULTS: ALI-PBEC gene expression in response to CS was most significantly changed at 4 h after exposure. Early transcriptomic changes (1 h, 4 h post CS exposure) were related to oxidative stress, xenobiotic metabolism, higher expression of immediate early genes and pro-inflammatory pathways (i.e., Nrf2, AP-1, AhR). At 24 h, ferroptosis-associated genes were significantly increased, whereas PRKN, involved in removing dysfunctional mitochondria, was downregulated. Importantly, the transcriptome dynamics of the current study mirrored in-vivo human studies of acute CS exposure, chronic smokers, and inversely mirrored smoking cessation. CONCLUSION: These findings show that early after CS exposure xenobiotic metabolism and pro-inflammatory pathways were activated, followed by activation of the ferroptosis-related cell death pathway. Moreover, significant overlap between these transcriptomic responses in the in-vitro model and human in-vivo studies was found, with an early response of ciliated cells. These results provide validation for the use of ALI-PBEC cultures to study the human lung epithelial response to inhaled toxicants.

Deeply Virtual Compton Scattering Cross Section at High Bjorken x_{B}.

We report high-precision measurements of the deeply virtual Compton scattering (DVCS) cross section at high values of the Bjorken variable x_{B}. DVCS is sensitive to the generalized parton distributions of the nucleon, which provide a three-dimensional description of its internal constituents. Using the exact analytic expression of the DVCS cross section for all possible polarization states of the initial and final electron and nucleon, and final state photon, we present the first experimental extraction of all four helicity-conserving Compton form factors (CFFs) of the nucleon as a function of x_{B}, while systematically including helicity flip amplitudes. In particular, the high accuracy of the present data demonstrates sensitivity to some very poorly known CFFs.

Deep Exclusive Electroproduction of π

We report measurements of the exclusive neutral pion electroproduction cross section off protons at large values of x_{B} (0.36, 0.48, and 0.60) and Q^{2} (3.1 to 8.4 GeV^{2}) obtained from Jefferson Lab Hall A experiment E12-06-014. The corresponding structure functions dσ_{T}/dt+εdσ_{L}/dt, dσ_{TT}/dt, dσ_{LT}/dt, and dσ_{LT^{'}}/dt are extracted as a function of the proton momentum transfer t-t_{min}. The results suggest the amplitude for transversely polarized virtual photons continues to dominate the cross section throughout this kinematic range. The data are well described by calculations based on transversity generalized parton distributions coupled to a helicity flip distribution amplitude of the pion, thus providing a unique way to probe the structure of the nucleon.

Influence of solid state fermentation by Trichoderma spp. on solubility, phenolic content, antioxidant, and antimicrobial activities of commercial turmeric.

The influence of solid state fermentation (SSF) by Trichoderma spp. on the solubility, total phenolic content, antioxidant, and antibacterial activities of turmeric was determined and compared with unfermented turmeric. The solubility of turmeric was monitored by increase in its phenolic content. The total phenolic content of turmeric extracted by 80% methanol and water after SSF by six species of Trichoderma spp. increased significantly from 2.5 to 11.3-23.3 and from 0.5 to 13.5-20.4 GAE/g DW, respectively. The antioxidant activities of fermented turmeric were enhanced using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid) (ABTS), and ferric ion-reducing antioxidant power (FRAP) assays. The antibacterial activity of fermented turmeric against human-pathogenic bacteria Escherichia coli, Streptococcus agalactiae, Staphylococcus aureus, Entreococcus faecalis, Methicillin-Resistant S. aureus, Klebsiella pneumonia, and Pseudomonas aeruginosae showed a broad spectrum inhibitory effect. In conclusion, the results indicated the potentials of using fermented turmeric as natural antioxidant and antimicrobial material for food applications.

Neuropsychological functioning among chronic khat users in Jazan region, Saudi Arabia.

BACKGROUND: Khat chewing effects in the central nervous system are attributed to cathinone and cathine, which are structurally related to amphetamine. However, studies on neuropsychological problems arising from khat use in humans are not extensive and have only included observational and single-case studies. The aims of this study were to (1) to examine neuropsychological functions among khat chewers, and (2) to determine factors affecting neuropsychological outcomes among khat chewers. METHODS: A sample of 70 adult male khat chewers and a control group of 72 nonchewers were recruited from the Jazan region in southwest Saudi Arabia. A questionnaire examining socioeconomic background, medical and occupational history, education, and khat chewing behaviors was administered. Neuropsychological performance was assessed using computerized tests from the Behavioral Assessment and Research System (BARS) that assessed learning, episodic and working memory, motor speed/coordination, attention/information processing speed, sustained attention, set-shifting/response inhibition, and perceptual functions; noncomputerized tests, Trail Making A and B, Block Design, and Benton Visual Retention tests were also administered. RESULTS: Khat chewers performed significantly worse on 3 out of 14 neuropsychological subtests compared with the control group, representing learning, motor speed/coordination, and set-shifting/response inhibition functions. Age and educational level were identified as predictors of neuropsychological outcomes of khat chewers. CONCLUSIONS: The chronic chewing of khat leaves is associated with deficits in some neuropsychological functions, which may affect the mental and neurological health of communities in which khat chewing is a common habit.

Fine tuning deep learning models for breast tumor classification.

This paper proposes an approach to enhance the differentiation task between benign and malignant Breast Tumors (BT) using histopathology images from the BreakHis dataset. The main stages involve preprocessing, which encompasses image resizing, data partitioning (training and testing sets), followed by data augmentation techniques. Both feature extraction and classification tasks are employed by a Custom CNN. The experimental results show that the proposed approach using the Custom CNN model exhibits better performance with an accuracy of 84% than applying the same approach using other pretrained models, including MobileNetV3, EfficientNetB0, Vgg16, and ResNet50V2, that present relatively lower accuracies, ranging from 74 to 82%; these four models are used as both feature extractors and classifiers. To increase the accuracy and other performance metrics, Grey Wolf Optimization (GWO), and Modified Gorilla Troops Optimization (MGTO) metaheuristic optimizers are applied to each model separately for hyperparameter tuning. In this case, the experimental results show that the Custom CNN model, refined with MGTO optimization, reaches an exceptional accuracy of 93.13% in just 10 iterations, outperforming the other state-of-the-art methods, and the other four used pretrained models based on the BreakHis dataset.

Divergent Clinical Equivalence Findings from DVH and NTCP Metrics for Alternative OAR Delineations with Increasing Setup Variability in Head-and-Neck Radiotherapy.

PURPOSE: This study quantifies the variation in dose-volume histogram (DVH) and normal tissue complication probability (NTCP) metrics for head-and-neck (HN) cancer patients when alternative organ-at-risk (OAR) delineations are used for treatment planning and for treatment plan evaluation. We particularly focus on the effects of daily patient positioning/setup variations (SV) in relation to treatment technique and delineation variability. MATERIALS AND METHODS: We generated two-arc VMAT, 5-beam IMRT, and 9-beam IMRT treatment plans for a cohort of 209 HN patients. These plans incorporated five different OAR delineation sets, including manual and four automated algorithms. Each treatment plan was assessed under various simulated per-fraction patient setup uncertainties, evaluating the potential clinical impacts through DVH and NTCP metrics. RESULTS: The study demonstrates that increasing setup variability generally reduces differences in DVH metrics between alternative delineations. However, in contrast, differences in NTCP metrics tend to increase with higher setup variability. This pattern is observed consistently across different treatment plans and delineator combinations, illustrating the intricate relationship between SV and delineation accuracy. Additionally, the need for delineation accuracy in treatment planning is shown to be case-specific and dependent on factors beyond geometric variations. CONCLUSIONS: The findings highlight the necessity for comprehensive quality assurance programs in radiotherapy, incorporating both dosimetric impact analysis and geometric variation assessment to ensure optimal delineation quality. The study emphasizes the complex dynamics of treatment planning in radiotherapy, advocating for personalized, case-specific strategies in clinical practice to enhance patient care quality and efficacy in the face of varying SV and delineation accuracies.

Comprehensive study for radiation shielding features for Bi2O3-B2O3-ZnO composite using computational radioanalytical Phy-X/PSD, MCNP5, and SRIM software.

The current study uses zinc oxide doping nanoparticles to investigate the radiation shielding properties of bismuth borate glass. Fourier transform infrared (FTIR) and X-ray diffraction (XRD) examined the structural characteristics of the current samples. In contrast, the optical properties were determined based on the absorption spectrum for current samples. Appraisal studies are carried out depending on the simulation capabilities of Phy-X/PSD software in conjunction with MCNP5 to achieve this goal. In addition, the neutron and charged particle shielding properties were evaluated theoretically. All glasses are amorphous, as confirmed by the XRD data, and the FTIR data showed several vibration bands and functional groups. The density showed rising from 5.981 to 6.433 g/cm3 with adding ZnO. The band gap values reduced from 2.831 to 2.091 eV for direct and 3.024 to 2.218 eV for indirect with adding ZnO. The investigations' findings demonstrate a strong agreement between the theoretical and simulation-derived estimates of the mass attenuation coefficient. The relative difference of MAC results lie in the range 0.106-2.941% for BBZ0, 0.105-4.348% for BBZ1, 0.105-3.398% for BBZ2, and 0.105-2.032% for BBZ3. The study's findings are valuable insights from thoroughly examining these parameters, which can potentially improve the radiation protection abilities of Bi2O3-B2O3-ZnO glasses. This study represents a significant step in developing more efficient and safer materials for gamma radiation shielding applications.

Assessing the awareness, knowledge, and attitudes of adults in the general population in Saudi Arabia towards testicular torsion: A cross-sectional study.

Introduction: Testicular torsion (TT) is a rare but urgent condition; it leads to severe pain and swelling that must be diagnosed and treated immediately, where there is an expectant period of 6-8 h. It is an important prognostic factor in the arrival time to the emergency department. Raising awareness about TT is essential to ensure early diagnosis and timely treatment, which can prevent irreversible damage and loss of fertility. Aim: Our study aimed to measure the awareness, knowledge, and attitude toward testicular torsion (TT) among the general population in Saudi Arabia. Subject and Methods: This is a cross-sectional study conducted among the general population living in Saudi Arabia. A self-administered questionnaire was distributed among the population using an online survey. The questionnaire includes socio-demographic characteristics (i.e., age, gender, region, etc.), a questionnaire to assess the knowledge of testicular torsion, and questionnaires to assess the prevalence, management, and attitude toward testicular torsion. Results: Of the 473 participants, 56% were males, and 61% were aged between 18 to 30 years old. Unfortunately, One quarter of our population has a good knowledge level about testicular torsion. The overall mean knowledge about Testicular Torsion score was below average (3 out of 8 points). Factors associated with increased knowledge include younger age, male gender, living in the Central Region, working in the medical field, having heard of testicular torsion, and having a personal or family history of testicular torsion. Conclusion: In conclusion, there was a lack of testicular torsion knowledge among the general population. Further studies and social campaigns should be done to encourage the general population's understanding and increase their knowledge level.

Impact of carbimazole combined with vitamin E on testicular injury induced by experimental hyperthyroidism in adult albino rats: oxidative/inflammatory/apoptotic pathways.

Thyroid hormones play essential roles in spermatogenesis, but their effects on infertile males remain poorly understood. This study aimed to evaluate the impact of combining carbimazole (CBZ) with vitamin E (VE) on testicular injury induced by experimental hyperthyroidism in adult albino rats, focusing on oxidative, inflammatory, and apoptotic pathways. In this experimental study, 64 adult male albino Wistar rats were divided into eight groups: Group I (control-untreated), Group II (CBZ-control), Group III (VE-control), Group IV (CBZ + VE-control), Group V (levothyroxine-induced testicular injury), Group VI (levothyroxine + CBZ-treated), Group VII (levothyroxine + VE-treated), and Group VIII (levothyroxine + CBZ + VE-treated). The study was conducted in the Faculty of Medicine, Suez Canal University (Ismailia, Egypt). After cervical decapitation, both testes and epididymis were examined histopathologically and immunohistochemically. Significant differences were observed among groups concerning malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT; all P < 0.001). Polymerase chain reaction analysis showed significant differences in tumor necrosis factor-α (TNF- α ), interleukin-10 (IL-10), Bcl-2-associated X protein (BAX), B-cell lymphoma 2 protein (Bcl2), p53, Caspase-3, Caspase-8, Caspase-9, and nuclear factor-kappa B (NF- κ B) mRNA levels (all P < 0.001). Hyperthyroid group treated with CBZ alone (Group VI) exhibited testicular side effects, affecting seminiferous tubules and spermatogenesis. However, the Group VIII showed improved spermatogenesis and a decrease in testicular side effects. The addition of VE to the treatment of hyperthyroid rats with CBZ reduced testicular side effects and seminiferous tubular affection when potentially improving spermatogenesis. Further research is needed to elucidate the underlying mechanisms fully.

Theoretical framework and inference for fitting extreme data through the modified Weibull distribution in a first-failure censored progressive approach.

The importance of biomedical physical data is underscored by its crucial role in advancing our comprehension of human health, unraveling the mechanisms underlying diseases, and facilitating the development of innovative medical treatments and interventions. This data serves as a fundamental resource, empowering researchers, healthcare professionals, and scientists to make informed decisions, pioneer research, and ultimately enhance global healthcare quality and individual well-being. It forms a cornerstone in the ongoing pursuit of medical progress and improved healthcare outcomes. This article aims to tackle challenges in estimating unknown parameters and reliability measures related to the modified Weibull distribution when applied to censored progressive biomedical data from the initial failure occurrence. In this context, the article proposes both classical and Bayesian techniques to derive estimates for unknown parameters, survival, and failure rate functions. Bayesian estimates are computed considering both asymmetric and symmetric loss functions. The Markov chain Monte Carlo method is employed to obtain these Bayesian estimates and their corresponding highest posterior density credible intervals. Due to the inherent complexity of these estimators, which cannot be theoretically compared, a simulation study is conducted to evaluate the performance of various estimation procedures. Additionally, a range of optimization criteria is utilized to identify the most effective progressive control strategies. Lastly, the article presents a medical application to illustrate the effectiveness of the proposed estimators. Numerical findings indicate that Bayesian estimates outperform other estimation methods by achieving minimal root mean square errors and narrower interval lengths.

Anaplastic lymphoma kinase rearrangement-associated renal cell carcinoma: Rare subset case report.

Anaplastic lymphoma kinase rearrangement-associated renal cell carcinoma (ALK-RCC) is a rare subtype of renal cell carcinoma characterized by genetic rearrangements involving the ALK gene. Managing ALK-RCC is challenging due to its rarity and limited treatment options. Targeted therapies directed at the ALK gene have shown promise. ALK-RCC is a rare subtype of renal cell carcinoma with unique clinical and pathological features. ALK inhibitors may hold promise as a targeted therapy for ALK-RCC. Further research is needed to understand the behavior of ALK-RCC and develop effective treatment strategies.

Adapting blockchain's proof-of-work mechanism for multiple traveling salesmen problem optimization.

The blockchain network uses a Proof-of-Work (PoW) mechanism to validate transactions and keep the blockchain growth safe against tampering, but it is hugely energy-consuming with no benefit to the peer-to-peer network participants. In this paper, we proposed a blockchain network for distributing products to different locations based on the use of the Proof of Useful Work mechanism, in which miners use computing resources to optimize the traveling salesman problem (TSP) as an alternative to solving mathematical problems that represent the basis of the traditional PoW mechanism to get a new block. According to this proposed blockchain, it not only receives and securely stores the distribution locations but also improves the paths for salesmen when traveling between different locations during the transportation process. This strategy aims to take advantage of the miners' efforts to minimize the traveled distance by applying the clustering technique and computing the shortest path by Guided Local Search (GLS) for each cluster at the same time. According to the tested results on TSP-LIB instances, the used strategy works efficiently with an average of 0.08 compared to the rest of the meta-heuristics, and the proposed architecture reduced total distances with an average of 0.025%. In addition, the block generation time in the blockchain decreased by 11.11% compared to other works.

Efficacious elimination of crystal violet pollutant via photo-Fenton process based on Gd(2-x)La(x)Zr2O7 nanoparticles.

The photo-Fenton process is an appropriate method of the Advanced Oxidation Process that is used in the photocatalysis of organic dyes like crystal violet (CV). La3+ ion substituted gadolinium zirconium oxide Gd(2-x)La(x)Zr2O7 nanopowders (x = 0.1, 0.2, 0.3, and 0.5) have been successfully prepared by using sol-gel auto-combustion method to be used for the efficient photocatalysis of CV with photo-Fenton process. The well-crystallized defect-fluorite, structured with space group: Fm-3m, was detected using X-ray diffraction analysis. The lattice parameters were found to increase with the evaluated La3+ ion concentration. The grain size of the synthesized powders increased with the increase in La3+ ion content. The SAED patterns depicted fluorite structured fluorite. UV/Vis. spectrophotometer was used for the determination of band gap energy of Gd(2-x)La(x)Zr2O7 nanopowders which increased with increasing La3+ ion content. It was found to enhance from 4 to 3.6 eV. The visible spectrophotometer was used for determining unknown concentrations during the photocatalysis process to assure the effectiveness of the process. Overall, results illustrate that the photo-Fenton reaction on Gd(2-x)La(x)Zr2O7 performed excellently in removing crystal violet (CV). The photo-remediation ratio of CV reached 90% within 1 h.

Development of Novel pH-Sensitive Eudragit Coated Beads Containing Curcumin-Mesalamine Combination for Colon-Specific Drug Delivery.

This research aims to develop a drug delivery system that effectively treats colitis while administering curcumin/mesalamine by coating alginate/chitosan beads with Eudragit® S-100 to target the colon. Beads were tested to determine their physicochemical characteristics. Coating with Eudragit® S-100 prevents drug release at a pH of less than 7; this was demonstrated by in-vitro release conducted in a medium with gradually varying pH to mimic circumstances in various regions of the gastrointestinal tract. This study examined the efficacy of the coated beads in treating acetic acid-induced colitis in rats. Results showed that spherical beads were formed with an average diameter of 1.6-2.8 mm, and the obtained swelling ranged from 409.80% to 890.19%. The calculated entrapment efficiency ranged from 87.49% to 97.89%. The optimized formula F13 (which was composed of mesalamine-curcumin active ingredients, Sodium alginate as a gelling agent, chitosan as a controlled release agent, CaCl2 as a crosslinking agent, and Eudragit S-100 as a pH-sensitive coating agent) demonstrated the best entrapment efficiency (97.89% ± 1.66), swelling (890.19% ± 60.1), and bead size (2.7 ± 0.62 mm). In formulation #13, which was coated with Eudragit S 100, curcumin (6.01 ± 0.04%) and mesalamine (8.64 ± 0.7%), were released after 2 h at pH 1.2; 6.36 ± 0.11% and 10.45 ± 1.52% of curcumin and mesalamine, respectively, were then released after 4 h and at pH 6.8. Meanwhile, at pH 7.4, after 24 h, approximately 85.34 ± 2.3% (curcumin) and 91.5 ± 1.2% (mesalamine) were released. Formula #13 significantly reduced the colitis, and this suggests that the developed hydrogel beads can be used for delivering curcumin-mesalamine combinations to treat ulcerative colitis after adequate research.