Limited Effect Research Articles

Glabridin exhibits potent inhibitory effects against Toxoplasma gondii in vitro and in vivo

BackgroundToxoplasma gondii is an obligate protozoan parasite capable of infecting a wide range of warm-blooded animals and humans. Current treatment options, primarily pyrimethamine and sulfadiazine, have limitations, such as high recurrence rates, long treatment durations, and limited effectiveness against T. gondii. There is an unmet need for novel, safe, low-toxicity, and highly effective treatments. This study aimed to evaluate the anti-T. gondii effects of glabridin, a natural compound derived from the roots of a widely used medicinal plant.MethodsThe cytotoxicity of glabridin in Vero cells was assessed using a CCK-8 cell viability assay. Quantitative polymerase chain reaction (qPCR) targeting the Tg-529 gene was developed to quantify T. gondii and assess the inhibitory effects of glabridin on parasite proliferation. Ultrastructural changes in T. gondii after treatment were examined using electron microscopy. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were examined to assess the effects of glabridin on ROS levels and ΔΨm in T. gondii tachyzoites. Additionally, metabolomics and transcriptomics analyses were conducted to investigate the mechanisms underlying glabridin’s anti-T. gondii effects.ResultsGlabridin exhibited low toxicity to host cells and effectively inhibited T. gondii invasion and proliferation in vitro in a time-dependent manner. Glabridin-treated tachyzoites exhibited significant structural alterations, along with increased ROS production and a reduction in ΔΨm. Metabolomic analysis indicated that glabridin significantly affected amino acid metabolism pathways in T. gondii. In vivo, glabridin treatment significantly improved survival rates in T. gondii-infected BALB/c mice at a dosage of 100 mg/kg.ConclusionsThis study demonstrates that glabridin has potent anti-T. gondii effects in vitro and in vivo, likely through disruption of amino acid metabolism in the parasite. These findings highlight glabridin’s potential as a promising therapeutic agent for toxoplasmosis.Graphical abstract

Impact of nighttime human behavior on exposure to malaria vectors and effectiveness of using long-lasting insecticidal nets in the Ethiopian lowlands and highlands

BackgroundEthiopia continues to grapple with a persistent malaria burden, characterized by ongoing transmission and recurrent outbreaks. Human behavior influences both malaria exposure and the effectiveness of vector interventions, complicating malaria control efforts. Implementing tailored strategies that account for the complex interplay between human activities and vector behavior remains a challenge in both high- and low-transmission areas in Ethiopia, particularly for vulnerable highland populations and temporary labor migrants, due to lack of data. The aim of this study was to examine the spatiotemporal patterns of human—mosquito interactions and evaluate the effectiveness and suitability of long-lasting insecticidal nets (LLINs) in settings involving lowland resident populations, seasonal migrant workers and highland communities.MethodsConcurrent human and vector behavior data were collected from high-transmission lowlands (residents and temporary migrant workers) and vulnerable highlands populations. Hourly human behavior observations (HBOs), which examined LLIN use, indoor versus outdoor human presence and sleeping patterns, were paired in a crossover design with mosquito sampling using US Centers for Disease Control light traps (CDC LT) as a proxy for mosquito biting behavior. The study was conducted during the peak (October–December 2022) and minor (March–May 2023) malaria transmission seasons (‘peak’ and ‘minor’) for a total of 368 nights. In the highlands, four villages consisting of eight households per village were selected for surveillance; in the lowlands, four villages consisting of two resident villages and two farm sites with migrant workers, with eight households/structures per village or farm, were used for data collection. CDC LT and HBO data were integrated to evaluate HBO-adjusted human biting rates (HBO-adjusted HBR) of Anopheles mosquitoes.ResultsIn the highland villages, residents predominantly engaged in indoor activities, with their peak activity overlapping with the peak biting hours (1800-2200 hours). A substantial proportion of inhabitants slept indoors without LLINs in the peak and minor seasons (42.8% and 39.2%, respectively). Highland residents were significantly more exposed to malaria vectors indoors (88.4% peak, 88.6% minor) than outdoors during both transmission seasons. In lowland villages, both resident and seasonal migrant worker populations exhibited predominantly outdoor activity, particularly during peak biting hours (1800-2300 hours). Both residents and temporary migrants were significantly more exposed to Anopheles mosquitoes outdoors (resident: 65.0% peak, 67.1% minor; migrant: 70.5% peak, 80.0% minor) than indoors during both transmission seasons. LLIN usage was minimal and offered limited protection, with < 16.63% of person-time spent under nets by resident populations and 10.7% by migrant workers.ConclusionsMalaria control in Ethiopia requires context-specific strategies tailored to diverse ecological settings that consider the impact of human behavior on exposure to Anopheles mosquitoes. Limited LLIN effectiveness, human activities coinciding with peak biting times and minimal LLIN usage create significant protection gaps. Comprehensive control necessitates supplemental tools addressing exposure in all locations and times. In the Ethiopian highlands, where indoor activities predominate, increased LLIN usage combined with targeted indoor residual spraying could reduce transmission. In lowland areas, both residents and seasonal migrant workers face relatively higher outdoor exposure risks, requiring additional measures, such as topical and spatial repellents. We recommend implementing data-driven, hyperlocal approaches based on specific human—vector interactions to enhance malaria control effectiveness across the Ethiopian highlands and lowlands.Graphical

Can a diet rich in Brassicaceae help control Helicobacter pylori infection? A systematic review

IntroductionHelicobacter pylori (Hp) infection is highly prevalent globally and poses a significant public health challenge due to its link with chronic gastritis, peptic ulcers, and gastric malignancies. Hp’s persistence within the gastric environment, particularly in case of infection with virulent strains, triggers chronic inflammatory responses and mucosal damage. Antibiotic therapy is the primary approach for Hp eradication, but antibiotic resistance and adverse effects hinder treatment efficacy. Emerging evidence suggests that Brassicaceae-derived metabolites could serve as adjunctive therapy for Hp infection, offering potential antimicrobial and anti-inflammatory benefits.MethodsA systematic literature review was conducted following PRISMA guidelines to assess the impact of Brassicaceae-rich diets on Hp infection control. Searches were performed in MEDLINE PubMed, Web of Science, and the Cochrane Library until 18 October 2023, without language or date restrictions. Eligible studies meeting PICOS criteria were included, encompassing populations infected with Hp or Hp-infected human cell cultures, interventions involving Brassicaceae consumption or its bioactive molecules, and outcomes related to Hp infection control, antibiotic therapy interactions, reduction of antibiotic side effects, and inflammation mitigation. Animal studies, cell line experiments, reviews unrelated to the research objectives, and studies on Hp-related gastric cancer were excluded.ResultsAvailable evidence indicates that Brassicaceae consumption exhibits the potential to reduce Hp colonization but achieving complete eradication of the pathogen remains challenging. Conflicting results regarding the efficacy of broccoli in Hp treatment emerge, with certain investigations suggesting limited effectiveness. Other studies point to a potential for heightened eradication rates when combined with standard triple therapy. Furthermore, promising outcomes are observed with broccoli extract supplements, indicating their role in mitigating Hp-induced gastric mucosal damage. In fact, it is noteworthy that sulforaphane and its derivatives manifest notable reductions in pro-inflammatory markers, indicative of their anti-inflammatory properties. Adverse events associated with antibiotic therapy seem unaffected by sulforaphane derivatives or probiotics. However, individual responses to these treatments vary, underscoring the unpredictability of their efficacy in ameliorating antibiotic therapy-related side effects.ConclusionOur systematic review highlights the potential of Brassicaceae-rich diets as adjunctive therapy for Hp infection, offering synergistic interactions with antibiotics and possibly mitigating antibiotic side effects and inflammation. Further research, particularly well-designed randomized trials, is warranted to elucidate the therapeutic efficacy and optimal utilization of Brassicaceae-derived metabolites in managing human Hp-related diseases.

THERAPEUTIC REFRACTIVE VITRECTOMY (TRV) FOR THE MANAGEMENT OF VITREOUS FLOATERS AND OPACITIES (VFO) ASSESSED BY THE STANDARDIZED AND KINETIC ANATOMICAL AND FUNCTIONAL TESTING OF VITREOUS FLOATERS AND OPACITIES (SK VFO TEST).

Propose new terminology and evaluate the effectiveness of Therapeutic Refractive Vitrectomy (TRV) for selective removal of vitreous floaters and opacities (VFO) utilizing Standardized Kinetic Anatomical Functional Testing of VFO (SK VFO Test) and new ultra widefield (UWF) OCT imaging techniques. Retrospective analysis. Twenty eyes underwent TRV for symptomatic VFO. Pre-/post-TRV assessments: SK-VFO Test, including straylight measurements (HD Analyzer, Light Disturbance Analyzer, C-Quant) alongside non-contact imaging including a new UWF OCT to evaluate changes in vitreous anatomical and optical properties. Post-TRV evaluations indicated objective changes in vitreous optical properties and subjective measures. Reduced straylight measurements: HDA 22%, LDA 54.4% (p=0.013), and C-Quant 7.8% (p=0.034). Patient reported outcomes statistically significantly improved (p=0.022). Corrected distance visual acuity (CDVA) changes were marginal. New UWF 26 mm with a 12 mm imaging window OCT facilitated detailed vitreous imaging, confirming status of posterior vitreous detachment (PVD) (100%). Post-TRV UWF and OCT imaging demonstrated restoration of vitreous clarity, confirmed presence of residual cortical vitreous and absence of new PVDs. TRV is a significant contribution for therapeutic refractive surgery as a safe and effective approach to enhancing visual quality, correcting refractive and opaque vitreous anomalies. Improvement in CDVA was minimal representing limited effectiveness as a measure of comprehensive visual function. Improvements in objective straylight measures and imaging are in alignment with subjective symptom improvements post-TRV. This underscores the utility and value of new holistic evaluation methods beyond traditional metrics to assess the impact of TRV on visual function and quality of life.

Mild Magnetothermal Immunotherapy for Malignant Pleural Effusion.

Malignant pleural effusion (MPE) is one of the most difficult complications of cancer to cure, usually indicating poor prognosis in late-stage cancer patients. Due to the presence of a large number of tumor-associated immune cells with the tumor promoting phenotype in MPE and pleural tumors, current clinical therapy offers limited effectiveness. Here, a mild magnetothermal regulation strategy is proposed based on a magnetic nanocatlytic nanoplatform ZCMF@PEG-AF (ZCMF-AF)constructed by surface-modifying anti-F4/80 antibody (AF) on ZnCoFe2O4@ZnMnFe2O4 magnetic nanoparticles (ZCMF) to target and polarize tumor-associated macrophages. Under alternating magnetic field-induced hyperthermia (41-42°C), ZCMF-AF exhibits in situ nanocatalytic production of hydroxyl radicals via released iron ions under acidic cellular environment, which induces repolarization from the immunosuppressed M2 phenotype to the M1 phenotype. More importantly, the tumor cell damage induced by M1 macrophages and magnetic hyperthermia promote the maturation of dendritic cells, which subsequently awakens cytotoxic T lymphocytes to combat tumor cells. The integrated innate and adaptive immunity activations based on ZCMF-AF nano-immunomedicine through intrapleural administration elicit substantially regulated immune microenvironment of MPE and pleural tumors. Moreover, the interpleural magnetic nanoparticle-based immunotherapy effectively reduced the MPE volume and inhibited tumor growth in the pleural cavity, significantly prolonging the survival of the MPE-bearing mice.

The role of exfoliative cytology in diagnosis of oral lesions.

The study aimed to evaluate the use of oral exfoliative cytology and highlight its limited effectiveness in diagnosing oral diseases. A total of 1000 consecutive cases of oral cytology were retrieved from the files of an Oral Pathology Service, comprising the period between January 2002 and December 2022. Patient data and clinical details of the lesions were collected, and all slides were reviewed. Categorical data were presented in absolute and relative frequency (%), while numerical data were expressed as the median with minimum and maximum values. The Chi-square (X2) test was employed for frequency comparisons, with a significance level of 5%. Men constituted 64.6% (n = 646) of the cases, with a statistically significant predominance of white individuals (69.4%; n = 694). Of the 1000 evaluated cases, 87.8% (n = 878) were graded using Papanicolaou staining. Regarding provisional diagnoses, most clinicians (79.1%) suspected fungal lesions (n = 817). Analysis of the agreement between provisional and final cytological diagnoses revealed a statistically significant disagreement. This work reinforces the limited use of exfoliative cytology in diagnosing oral lesions. Exfoliative oral cytology should be restricted to specific cases, particularly for diagnosing fungal disease, and occasionally when oral cancer is suspected, but a biopsy cannot be performed at that time.

Radioimmunotherapy: a game-changer for advanced non-small cell lung cancer

Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related deaths, with conventional treatments offering limited effectiveness in advanced stages, due to distant metastases and treatment resistance. Recent advancements in immunotherapy, specifically immune checkpoint inhibitors (ICIs), have shown promise, but their efficacy as standalone therapies are often insufficient. This has led to increased interest in combining ICIs with radiotherapy, known as radioimmunotherapy (iRT), to enhance treatment outcomes. This review explores the mechanisms that underlie the synergy between radiotherapy and immunotherapy. Radiotherapy can induce the “abscopal effect”, eliciting systemic immune responses that reduce tumor burdens outside the treated area. It also increases the expression of major histocompatibility complex class I (MHC-I) on tumor cells, improving immune recognition. Furthermore, radiotherapy can modify the tumor microenvironment by inducing metabolic reprogramming to bolster anti-tumor immunity. We discuss strategies for optimizing iRT, including considerations of radiation doses, fractionation schedules, and treatment site selection, which significantly influence immune responses by enhancing MHC-I expression or promoting T-cell infiltration. Clinical evidence supports the efficacy of iRT in NSCLC and other cancers, though challenges in standardizing treatment protocols and managing side effects persist. Overall, radioimmunotherapy presents a promising approach to improving NSCLC treatment outcomes. Ongoing research into its mechanisms and the refinement of treatment may reshape clinical practice, offering more effective and personalized options for patients with advanced lung cancer. Further studies are essential to validate these findings and optimize therapeutic protocols.

Early introduction of IL-10 weakens BCG revaccination’s protection by suppressing CD4+Th1 cell responses

BackgroundThe Bacillus Calmette-Guérin (BCG) vaccine, currently the sole authorized vaccine against tuberculosis (TB), demonstrates limited effectiveness in safeguarding adolescents and adults from active TB, even when administered as a booster with either BCG itself or heterologous vaccine candidates. To effectively control the persistent epidemic of adult TB, it is imperative to investigate the mechanisms responsible for the suboptimal efficacy of the BCG prime-boosting strategy against primary Mycobacterium tuberculosis (M.tb) infection.MethodsC57BL/6J mice were immunized with the BCG vaccine either once or twice, followed by analysis of lung tissue to assess changes in cytokine levels. Additionally, varying intervals between vaccinations and detection times were examined to study IL-10 expression across different organs. IL-10-expressing cells in the lungs, spleen, and lymph nodes were analyzed through FACS and intracellular cytokine staining (ICS). BCG-revaccinated IL-10−/− mutant mice were compared with wild-type mice to evaluate antigen-specific IgG antibody and T cell responses. Protection against M.tb aerosol challenge was evaluated in BCG-revaccinated mice, either untreated or treated with anti-IL-10R monoclonal antibody.ResultsIL-10 was significantly upregulated in the lungs of BCG-revaccinated mice shortly after the booster immunization. IL-10 expression peaked in the lungs 3–6 weeks post-revaccination and was also detected in lymph nodes and spleen as early as 2 weeks following the booster dose, regardless of the intervals between the prime and booster vaccinations. The primary sources of IL-10 in these tissues were identified as macrophages and dendritic cells. Blocking IL-10 signaling in BCG-revaccinated mice—either by using IL-10−/− mutant mice or administering anti-IL-10R monoclonal antibody increased levels of antigen-specific IFN-γ+ or IL-2+ CD4+ T cells, enhanced central and effector memory CD4+ T cell responses, and provided better protection against aerosol infection with 300 CFUs of M.tb.ConclusionOur findings are crucial for formulating effective immunization strategies related to the BCG vaccine and for developing efficacious adult TB vaccines.Graphical abstract

Effectiveness of Decentralization of Disaster Risk Management in Borana and South-West Shawa Zones, Oromia Region, Ethiopia

AbstractThis study was designed with the aim of assessing the effectiveness of decentralization of disaster risk management in Borana zone and South-West Shawa zone of Oromia region. A mixed research approach was used to collect data from federal, regional, zonal, district (woreda), and ward (kebele) representatives. Focus group discussions and key informant interviews were the qualitative methods used to collect data, while survey questionnaires were distributed to experts to collect quantitative data. The qualitative data were analyzed using content analysis whereas the quantitative data were analyzed using STATA software version 14. The findings of the research have shown that, the actors are aware of Busa Gonofa as a new indigenous self-help institution. The policy on decentralization of disaster risk reduction was better understood at the federal, regional, and zonal levels of the government tiers than at the woreda and kebele levels. Administrative decentralization was found to be more effective than fiscal and political decentralization. The decentralization of Ethiopian disaster risk reduction is incomplete with limited effectiveness. There exists significant difference between Borana and South-West Shawa zones in decentralization of disaster risk management. The implementation of decentralization was constrained by training, technology, collaboration, financial resources, skill and knowledge, institutional arrangement, and local capacity. Hence, there is a need to address these challenges and make continuous efforts to focus on local-level capacity building in terms of empowerment of actors through training, technology, and financial resources for adaptation and mitigation to drought in Borana and flood in South-West Shawa zones respectively.

Electromechanical-coupling modeling and experimental validation of piezoelectric active vibration isolation for truss structures

Truss structures provide support and connection as essential components of spacecrafts. However, they are constantly disturbed and vibrated, which affects the pointing accuracy and operating stability. An active vibration isolation method for truss structures with embedded piezoelectric actuators (EPAs) is proposed in this study to address the challenges of excessive weight, large size, and limited effectiveness in vibration control equipment. Firstly, the EPA with a sandwich structure is designed and strategically embedded in the truss structure. Secondly, a novel modeling method is developed using the transfer matrix method (TMM) to effectively characterize complex beam structures including truss structures. Finally, a prototype is developed and the measurement system is constructed. The accuracy of the modeling is confirmed by vibration response experiments, with measurement results indicating that the discrepancies between theoretical predictions and experimental data remain within 5 %. Further validation of the EPAs for active vibration isolation is achieved through dedicated experiments, revealing a maximum isolation effect of −27.87 dB for longitudinal vibrations and –22.08 dB for bending vibrations. The experimental findings substantiate the promising application of proposed EPAs in enhancing active vibration isolation for truss structures, offering significant potential for improving the precision pointing and operational stability of space structures and spacecraft.

Enhancing Intrusion Detection Systems with Dimensionality Reduction and Multi-Stacking Ensemble Techniques

The deployment of intrusion detection systems (IDSs) is essential for protecting network resources and infrastructure against malicious threats. Despite the wide use of various machine learning methods in IDSs, such systems often struggle to achieve optimal performance. The key challenges include the curse of dimensionality, which significantly impacts IDS efficacy, and the limited effectiveness of singular learning classifiers in handling complex, imbalanced, and multi-categorical traffic datasets. To overcome these limitations, this paper presents an innovative approach that integrates dimensionality reduction and stacking ensemble techniques. We employ the LogitBoost algorithm with XGBRegressor for feature selection, complemented by a Residual Network (ResNet) deep learning model for feature extraction. Furthermore, we introduce multi-stacking ensemble (MSE), a novel ensemble method, to enhance attack prediction capabilities. The evaluation on benchmark datasets such as CICIDS2017 and UNSW-NB15 demonstrates that our IDS surpasses current models across various performance metrics.

Therapists' perspectives on the Maudsley model anorexia nervosa treatment for adolescents and young adults (MANTRa): A qualitative interview study.

A rising incidence of eating disorders in the young population and limited effectiveness of available treatment approaches underscore the need for innovative therapies. This study explores therapists' perspectives regarding a promising new manualized psychotherapeutic treatment (MANTRa) for adolescents and young adults with anorexia nervosa (AN). Semi-structured qualitative interviews were conducted with 10 therapists (nine female) who provided 24-34 sessions of MANTRa per patient. Interview topics included positive and negative experiences with MANTRa in general, with the workbook and other components. Reflexive thematic analysis was used to interpret the data. Furthermore, written notes taken by the therapists after each sessions were analysed. The thematic analysis revealed five overarching themes: (1) Variety of therapeutic tools and content elements included in the workbook; (2) Getting the therapeutic process going; (3) Flexibility in use of the workbook; (4) Impact of the scientific and multidisciplinary framework on quality assurance; (5) Formal design of the workbook. Therapists' case formulation letters to the patients were regarded as powerful tools to strengthen therapeutic alliance and promote recovery. In-depth therapists' training, regular supervision and a multi-professional treatment setting were important factors to ensure high treatment quality. The findings suggest how the MANTRa content (e.g. inclusion of additional therapeutic tools), the therapists' training and the format (e.g. provision of a digital version) can be improved to reach maximum impact. Therapists' formulation letters may be an effective therapeutic tool not only for AN but also across the spectrum of psychiatric disorders in adolescents and young adults.

Synergistic‐like decreases in alcohol intake following combined pharmacotherapy with GLP‐1 and amylin in male rats

Background and PurposeThe limited effectiveness of current pharmacological treatments for alcohol use disorder (AUD) highlights the need for novel therapies. These may involve the glucagon‐like peptide‐1 receptor or the amylin receptor, as treatment with agonists targeting either of these receptors lowers alcohol intake. The complexity of the mechanisms underlying AUD indicates that combining agents could enhance treatment efficacy. While a combination of amylin receptor and GLP‐1 receptor agonists reduced food intake and body weight synergistic‐like, its influence on alcohol intake is unknown.Experimental ApproachEffects of a range of dose‐combinations of GLP‐1 receptor (dulaglutide) and amylin receptor (salmon calcitonin; sCT) agonists on alcohol intake were explored in male and female rats. We used dose combinations that either lowered alcohol intake as monotherapy (0.1 mg·kg−1 + 5 μg·kg−1), or that did not affect alcohol consumption per se (0.075 mg·kg−1 + 2 μg·kg−1).Key ResultsAcute administration of dulaglutide and sCT (0.1 mg·kg−1 + 5 μg·kg−1) reduced alcohol intake in males, but not in females. When higher doses were evaluated in female rats, a decrease in alcohol intake was observed. Furthermore, the low dose combination (0.075 mg·kg−1 + 2 μg·kg−1) decreased, in in a synergistic‐like manner, alcohol intake and prevented abstinence‐induced drinking without affecting kaolin intake in males. However, tolerance developed during sub‐chronic treatment.Conclusion and ImplicationsCollectively, these findings show that the combination of dulaglutide and sCT decreased, in in a synergistic‐like manner, alcohol consumption in male rats. Contrarily, higher doses are required for females.

Polyphasic approach to the selection of Esteya isolates for the control of the pinewood nematode, Bursaphelenchus xylophilus

Pine wilt disease, caused by the pinewood nematode, Bursaphelenchus xylophilus, is a major phytosanitary concern to pine forests worldwide. Managing pine wilt disease involves a complex logistical undertaking, with limited effectiveness and significant ecological repercussions. An increasing demand for biosolutions has sparked an interest in microbial antagonists capable of controlling the nematode. Esteya spp. are promising fungal biocontrol agents of the pinewood nematode. Here, we carry out an integrative characterization of E. vermicola and E. floridanum isolates, through biological, biochemical, and molecular methods, and provide insights into the selection of these isolates for the biological control of the pinewood nematode. Dual culture assays revealed that Esteya spp. can compete with ophiostomatoid fungi (Leptographium terebrantis and Ophiostoma ips) occurring in the pathosystem of pine wilt disease, an often-neglected ecological perspective that could hinder their success as biocontrol agents. Moreover, E. vermicola can metabolize more carbon sources than E. floridanum, which can have implications on their successful establishment in pine trees. Our experimental approach further shows that both Esteya spp. are equally competent in suppressing the pinewood nematode in vitro. Overall, our results suggest that a prophylactic application of Esteya in pine trees may be preferable for optimal bioprotective effects against the pinewood nematode and fungal pathogens.

An Integrated Approach to Develop a Potent Vaccine Candidate Construct Against Prostate Cancer by Utilizing Machine Learning and Bioinformatics.

Prostate cancer is the most common malignancy among males. Prostaglandin G/H synthase (PGHS) is an essential enzyme in the synthesis of prostaglandins, and its activation has been linked to many malignancies, including colorectal cancer. Due to the limited effectiveness and specificity of existing prostate cancer therapies, this study was designed to formulate improved treatment techniques. Several immunoinformatic, reverse vaccinology, and molecular modeling methodologies were used to discover B- and T-cell epitopes for the glioblastoma multiforme tumor PGH2_HUMAN. This research evaluated Prostaglandin G/H synthase 2 protein as a potential vaccine candidate against the malignancy. The multi-epitope vaccine architecture is engineered to activate the immune system, with each epitope docked to its respective HLAs. Further, MD simulations analysis was performed to validate the findings. A multi-epitope subunit vaccine candidate was developed by concatenating the chosen B- and T-cell epitopes. Results yield a codon adaptive index (CAI) of 0.93 and a GC content of 56.77%. Thus, it conforms to a biological requirement for effective protein expression, suggesting competent vaccine efficacy inside the Escherichia coli system. Significant interleukin and cytokine responses were seen, characterized by elevated levels of IL-2 and IFN-γ in the immune system's response to the immunization. Molecular docking demonstrated an efficient binding affinity of -278 kcal/mol, with hydrogen bonding to several residues. Furthermore, the system total root mean square deviation (RMSD) reached 3.23 Å, with a maximum of up to 5.0 Å at the 100 ns time point but remains stable till 400 ns time intervals followed by stable root mean square fluctuation (RMSF) and radius of gyration values. The hydrogen bond cloud residues are the critical sites that significantly influence the binding energies of MMPBSA and MMGBSA via substantial van der Waals interactions. It has been determined that these in silico analyses will further augment the comprehension necessary for advancing the creation of targeted therapies for chemotherapeutic cancer treatments.

Deletion of the phd3 in zebrafish results in increased resistance to Aeromonas hydrophila infection

Aeromonas hydrophila, a gram-negative pathogen prevalent in aquatic environments, is a known inducer of septicemia in aquatic animals, causing considerable losses in aquaculture. The limited effectiveness of conventional drug therapies underscores the need for exploring innovative treatment strategies. Gene knockout technology presents a promising approach for exploring the immune response in zebrafish and developing therapeutic interventions for aquatic organisms diseases. This study focuses on elucidating the mechanism of action of phd3 in zebrafish against Aeromonas hydrophila through the creation of a phd3 knockout model. Our findings reveal a high degree of conservation of phd3 sequences between zebrafish and commercially important fish species, making it a suitable model organism for studying fish inflammation. Knocking out phd3 significantly improved the resistance of zebrafish to Aeromonas hydrophila, reduced tissue damage, increased survival rates, and decreased bacterial burden. Furthermore, the downregulation of phd3 enhanced immune responses, antioxidant levels, endoplasmic reticulum stress, autophagy reactions and apoptosis. This research underscores the crucial role of phd3 in zebrafish innate immunity, offering novel insights into the prevention and management of diseases in aquatic organisms, and potential immunotherapeutic strategies. Our findings have significant implications for the future development of targeted therapeutic strategies against Aeromonas hydrophila and other aquatic pathogens.

Data level fusion of acoustic emission sensors using deep learning

The acoustic emission (AE) technique is commonly utilized for identifying source mechanisms and material damage. In applications requiring numerous sensors and limited detection areas, achieving significant cost savings, weight reduction, and miniaturization of AE sensors is crucial. This prevents excessive weight burdens on structures while minimizing interference with structural integrity. Thin Piezoelectric Wafer Active Sensors (PWAS), compared to conventional commercially available sensors, offer a miniature, lightweight, and affordable alternative. The low signal-to-noise ratio (SNR) of PWAS sensors and their limited effectiveness in monitoring thick structures result in the decreased reliability of a single classical PWAS sensor for damage detection. This research aims to enhance the functionality of PWAS in AE applications by employing multiple thin PWAS and performing a data-level fusion of their outputs. To achieve this, as a first step, the selection of the optimal PWAS is performed and a configuration is designed for multiple sensors. Pencil break lead (PBL) tests were performed to investigate the compatibility between selected PWAS and traditional WSα and R15α sensors. The responses of all sensors from different AE sources were compared in both the time and frequency domains. After that, convolutional neural networks (CNNs) combined with principal component analysis (PCA) are proposed for signal processing and data fusion. The signals generated by the PBL tests were used for network training and evaluation. This approach, developed by the authors, fuses the signals from multiple PWAS and reconstructs the signals obtained from conventional bulky AE sensors for damage detection. Three CNNs with different architectures were built and tested to optimize the network. It is found that the proposed methodology can effectively reconstruct and identify the PBL signals with high precision. The results demonstrate the feasibility of using a deep-learning-based method for AE monitoring using PWAS for real engineering structures.

Modeling microplastic transport through porous media: Challenges arising from dynamic transport behavior

Modelling microplastic transport through porous media, such as soils and aquifers, is an emerging research topic, where existing hydrogeological models for (reactive) solute and colloid transport have shown limited effectiveness thus far. This perspective article draws upon recent literature to provide a brief overview of key microplastic transport processes, with emphases on less well-understood processes, to propose potential research directions for efficiently modeling microplastic transport through the porous environment. Microplastics are particulate matter with distinct physicochemical properties. Biogeochemical processes and physical interactions with the surrounding environment cause microplastic properties such as material density, geometry, chemical composition, and DLVO interaction parameters to change dynamically, through complex webs of interactions and feedbacks that dynamically affect transport behavior. Furthermore, microplastic material densities, which cluster around that of water, distinguish microplastics from other colloids, with impactful consequences that are often underappreciated. For example, (near-)neutral material densities cause microplastic transport behavior to be highly sensitive to spatio-temporally varying environmental conditions. The dynamic nature of microplastic properties implies that at environmentally relevant large spatio-temporal scales, the complex transport behavior may be effectively intractable to direct physical modeling. Therefore, efficient modeling may require integrating reduced-complexity physics-constrained models, with stochastic or statistical analyses, supported by extensive environmental data.

Probiotics and Prebiotics Intervention in Respiratory and Digestive Infections Linked to Covid-19.

Probiotics and prebiotics have been suggested as natural agents against viral infections and dysbiosis and may encourage clinical applications. This review aims to analyze the main and recent advances related to viral infections such as Covid-19 and its gastrointestinal complications, antiviral immunity generated and possible preventive role that probiotics and/or prebiotics can play in controlling and promoting antiviral immunity. The literature search was performed through a critical analysis of relevant publications reported in PubMed and Scopus databases on clinical trials and assays conducted in vitro on colon cells and in vivo on mice. Some studies using probiotics and prebiotics for the prevention of viral infection in different age groups are discussed. Covid-19 patients have been shown to suffer from gastrointestinal complications in addition to respiratory symptoms due to interactions between the respiratory system and the gastrointestinal tract infected with SARS-CoV-2. Unfortunately, therapies used to prevent (or treat) symptoms of Covid-19 have proven to be of limited effectiveness. In addition, the lack of access to coronavirus vaccines around the world and vaccine hesitancy continue to hamper control of Covid-19. It is therefore crucial to find alternative methods that can prevent disease symptoms. Evidence-based efficacy of certain probiotics (Lactobacillus and Bifidobacterium) that may be useful in viral infections was shown with immunomodulatory properties (pro-inflammatory mediators reduction), promoting antiviral immunity (antibodies production, virus titers) and controlling inflammation (anti-inflammatory effect), as well as viral clearance and antimicrobial potential against opportunistic bacteria (anti-dysbiosis effect). But, available data about clinical application of probiotics in Covid-19 context remain limited and relevant scientific investigation is still in its early stages. Also, evidence for prebiotics potential in this field is limited, since the exact mechanism involved in systemic immune modulation by these compounds is till now unknown. Thus, further research is necessary to explore in the viral infection context the mechanism by which gut and lung interact in the presence of probiotics and prebiotics through more animal and clinical experiments.

Surgical Treatment of Synkinetic Eyelid Closure in Marin-amat Syndrome Complicated by Facial Palsy After COVID-19 Vaccination

Background: Marin-Amat syndrome is a rare, irreversible, and hard-to-treat neurological sequalae that has recently been associated with COVID-19 vaccination. Given the rarity of this condition and the absence of curative treatment to date, the authors herein review the literature to date and report the first ever successful surgical treatment of 2 patients who developed Marin-Amat syndrome after ChAdOx1 nCoV-19 vaccination. Materials and Methods: In this case study, the authors treated Marin-Amat syndrome in a 45-year-old woman and a 75-year-old woman with facial palsy that developed 24 days and 4 months after receiving COVID-19 vaccination, respectively. The patients’ clinical histories and physical examination results were reviewed. A literature review was performed using PUBMED for the years 1990 to the present. Results: It is noteworthy that these are the first reported cases of Marin-Amat Syndrome to be successfully treated by surgery. The patient’s neurological symptoms improved after surgical intervention in contrast with the lack of response after botulinum toxin injection and intensive rehabilitation. Conclusion: This study is the first to demonstrate the successful treatment of the extremely rare Marin-Amat syndrome after ChAdOx1 nCoV-19 vaccination through surgery. Selective myectomy and myotomy in situ in combination with levator plication proves to be highly effective and favorable in treating this condition as the surgery overtakes the limited effectiveness of and directly obviates the need for botulinum toxin injections, thereby improving patient satisfaction and quality of life.