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Background: Probiotics, like Lactobacillus plantarum, show promise in managing obesity, but delivery challenges hinder their effectiveness. This study explores the effects of NCAP microcapsules with L. plantarum on weight, lipids, liver function, and insulin in rats over eight weeks, enhancing the bacteria’s survivability through microencapsulation. Results: NCAP microcapsules (10–15 μm, >79% survival) effectively protected L. plantarum. In rats, a high-fat diet with NCAP microcapsules (HFDC) significantly reduced body weight (176 g vs 179 g, p

Viral vectors are among the main approaches currently used in studies for executing gene delivery to target cells. During the past decades of active studies in gene therapy, including viruses, adenoviruses (Ads), lentiviruses (LVs), and adeno-associated viruses (AAVs), have received the most attention among the biological approaches where potentially successful outcomes are recorded for numerous genetic conditions. The success of delivery methods, however, remains unsatisfactory. Using some additives that can improve transgene expression, transfection efficiency, viral particle production, and transduction efficiency is considered as a solution to overcoming the limitations of gene delivery approaches. These additives include caffeine, histone deacetylase (HDAC) inhibitors like sodium butyrate and valproic acid, and polycationic agents like polybrene and protamine sulfate. In this review article, we present an overview of viral vector-mediated retinal gene therapies and the application of some enhancers used to improve the outcomes of gene delivery. Three routes of administrating viral vectors into ocular compartments are employed for the delivery of target genes into impacted cells, and some additives have shown enhanced efficiency of gene delivery in retinal cells. The current study places a special focus on the viral vectors and enhancers used for gene therapies of inherited retinal diseases.How to cite: Najafi S, Rahimpour A, Ahmadieh H, et al. The significance of chemical transfection/transduction enhancers in promoting the viral vectors-assisted gene delivery approaches: A focus on potentials for inherited retinal diseases. Electron J Biotechnol 2024;72. https://doi.org/10.1016/j.ejbt.2024.07.005.

Abstract Background Adolescence is a unique stage of life accompanied by physiological and psychological modifications, along with stress, confusion, and depression. Materials and methods The present descriptive-analytical cross-sectional research was done on 267 male adolescents who studied at high schools in Zanjan, Iran. Demographic characteristics questionnaires, a 48-item food frequency questionnaire, a short version of the International Physical Activity Questionnaire (IPAQ), the Depression Anxiety Stress Scale (DASS-21), and the Pittsburgh Sleep Quality Index (PSQI) were used to collect data. Results The mean ± standard deviation (SD) of age, weight, height, and sitting time was 15.94 ± 0.91 years, 68.53 ± 15.28 kg, 1.75 ± 0.06 m, and 449.25 ± 322.06 min, respectively. The study results showed that students with poor sleep quality showed a higher rate of depression than those with good sleep quality in the high and low physical activity groups (p

This paper is a call to action. By publishing concurrently across journals like an emergency bulletin, we are not merely making a plea for awareness about climate change. Instead, we are demanding immediate, tangible steps that harness the power of microbiology and the expertise of researchers and policymakers to safeguard the planet for future generations.

Abstract Objective Digital technologies have improved the performance of surveillance systems through early detection of outbreaks and epidemic control. The aim of this study is to introduce an outbreak detection web application called OBDETECTOR (Outbreak Detector), which as a professional web application has the ability to process weekly or daily reported data from disease surveillance systems and facilitates the early detection of disease outbreaks. Results OBDETECTOR generates a histogram that exhibits the trend of infection within a time range selected by the user. The output comprises red triangles and plus signs, where the former denotes outbreak days determined by the algorithm applied to the data, and the latter represents days identified as outbreaks by the researcher. The graph also displays threshold values and its symbols enable researchers to compute evaluation criteria for outbreak detection algorithms, including sensitivity and specificity. OBDETECTOR allows users to modify algorithm parameters based on their research objectives immediately after loading data. The implementation of automatic web applications results in immediate reporting, precise analysis, and prompt alert notification. Moreover, Public Health authorities and other stakeholders of surveillance can benefit from the widespread accessibility and user-friendliness of these tools, enhancing their knowledge and skills for better engagement in surveillance programs.

Abstract Neuroendocrine (NE) transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor prognosis. Up to date, even if patients at high risk of transformation can be identified by the occurrence of Tumor Protein P53 (TP53) and Retinoblastoma Transcriptional Corepressor 1 (RB1) mutations in their tumors, no therapeutic strategies are available to prevent or delay histological transformation. Upregulation of the cell cycle kinase Cell Division Cycle 7 (CDC7) occurred in tumors during the initial steps of NE transformation, already after TP53/RB1 co-inactivation, leading to induced sensitivity to the CDC7 inhibitor simurosertib. CDC7 inhibition suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation by inducing the proteasome-mediated degradation of the MYC Proto-Oncogen (MYC), implicated in stemness and histological transformation. Ectopic overexpression of a degradation-resistant MYC isoform reestablished the NE transformation phenotype observed on targeted therapy, even in the presence of simurosertib. CDC7 inhibition also markedly extended response to standard cytotoxics (cisplatin, irinotecan) in lung and prostate small cell carcinoma models. These results nominate CDC7 inhibition as a therapeutic strategy to constrain lineage plasticity, as well as to effectively treat NE tumors de novo or after transformation. As simurosertib clinical efficacy trials are ongoing, this concept could be readily translated for patients at risk of transformation.

Abstract Background MiRNA-146a and miRNA-223 are key epigenetic regulators of toll-like receptor 4 (TLR4)/tumor necrosis factor-receptor-associated factor 6 (TRAF6)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathway, which is involved in diabetic nephropathy (DN) pathogenesis. The currently available oral anti-diabetic treatments have been insufficient to halt DN development and progression. Therefore, this work aimed to assess the renoprotective effect of the natural compound 6-gingerol (GR) either alone or in combination with metformin (MET) in high-fat diet/streptozotocin-induced DN in rats. The proposed molecular mechanisms were also investigated. Methods Oral gavage of 6-gingerol (100 mg/kg) and metformin (300 mg/kg) were administered to rats daily for eight weeks. MiRNA-146a, miRNA-223, TLR4, TRAF6, nuclear factor-kappa B (NF-κB) (p65), NLRP3, caspase-1, and hypoxia-inducible factor-1 alpha (HIF-1α) mRNA expressions were measured using real-time PCR. ELISA was used to measure TLR4, TRAF6, NLRP3, caspase-1, tumor necrosis factor-alpha (TNF-α), and interleukin-1-beta (IL-1β) renal tissue levels. Renal tissue histopathology and immunohistochemical examination of fibronectin and NF-κB (p65) were performed. Results 6-Gingerol treatment significantly reduced kidney tissue damage and fibrosis. 6-Gingerol up-regulated miRNA-146a and miRNA-223 and reduced TLR4, TRAF6, NF-κB (p65), NLRP3, caspase-1, TNF-α, IL-1β, HIF-1α and fibronectin renal expressions. 6-Gingerol improved lipid profile and renal functions, attenuated renal hypertrophy, increased reduced glutathione, and decreased blood glucose and malondialdehyde levels. 6-Gingerol and metformin combination showed superior renoprotective effects than either alone. Conclusion 6-Gingerol demonstrated a key protective role in DN by induction of miRNA-146a and miRNA-223 expression and inhibition of TLR4/TRAF6/NLRP3 inflammasome signaling. 6-Gingerol, a safe, affordable, and abundant natural compound, holds promise for use as an adjuvant therapy with metformin in diabetic patients to attenuate renal damage and stop the progression of DN.

Abstract Background Using next-generation sequencing technologies, scientists can sequence complex microbial communities directly from the environment. Significant insights into the structure, diversity, and ecology of microbial communities have resulted from the study of metagenomics. The assembly of reads into longer contigs, which are then binned into groups of contigs that correspond to different species in the metagenomic sample, is a crucial step in the analysis of metagenomics. It is necessary to organize these contigs into operational taxonomic units (OTUs) for further taxonomic profiling and functional analysis. For binning, which is synonymous with the clustering of OTUs, the tetra-nucleotide frequency (TNF) is typically utilized as a compositional feature for each OTU. Results In this paper, we present AFIT, a new l-mer statistic vector for each contig, and AFITBin, a novel method for metagenomic binning based on AFIT and a matrix factorization method. To evaluate the performance of the AFIT vector, the t-SNE algorithm is used to compare species clustering based on AFIT and TNF information. In addition, the efficacy of AFITBin is demonstrated on both simulated and real datasets in comparison to state-of-the-art binning methods such as MetaBAT 2, MaxBin 2.0, CONCOT, MetaCon, SolidBin, BusyBee Web, and MetaBinner. To further analyze the performance of the purposed AFIT vector, we compare the barcodes of the AFIT vector and the TNF vector. Conclusion The results demonstrate that AFITBin shows superior performance in taxonomic identification compared to existing methods, leveraging the AFIT vector for improved results in metagenomic binning. This approach holds promise for advancing the analysis of metagenomic data, providing more reliable insights into microbial community composition and function. Availability A python package is available at: https://github.com/SayehSobhani/AFITBin .

A major characteristic of cancer is dysregulated cell division, which results in aberrant growth of cells. Consequently, medicinal targets that prevent cell division would be useful in the fight against cancer. The primary regulator of proliferation is a complex consisting of cyclin and cyclin-dependent kinases (CDKs). The FDA has granted approval for CDK inhibitors (CDKIs) to treat metastatic hormone receptor-positive breast cancer. Specifically, CDK4/6 CDKIs block the enzyme activity of CDK4 and CDK6. Unfortunately, the majority of first-generation CDK inhibitors, also known as pan-CDK inhibitors because they target multiple CDKs, have not been authorized for clinical use owing to their serious side effects and lack of selection. In contrast to this, significant advancements have been created to permit the use of pan-CDK inhibitors in therapeutic settings. Notably, the toxicity and negative consequences of pan-CDK inhibitors have been lessened in recent years thanks to the emergence of combination therapy tactics. Therefore, pan-CDK inhibitors have renewed promise for clinical use when used in a combination regimen. The members of the CDK family have been reviewed and their primary roles in cell cycle regulation were covered in this review. Next, we provided an overview of the state of studies on CDK inhibitors.

Vascularization is crucial for providing nutrients and oxygen to cells while removing waste. Despite advances in 3D-bioprinting, the fabrication of structures with void spaces and channels remains challenging. This study presents a novel approach to create robust yet flexible and permeable small (600–1300 μm) artificial vessels in a single processing step using 3D coaxial extrusion printing of a biomaterial ink, based on tyramine-modified polyethylene glycol (PEG-Tyr). We combined the gelatin biocompatibility/activity, robustness of PEG-Tyr and alginate with the shear-thinning properties of methylcellulose (MC) in a new biomaterial ink for the fabrication of bioinspired vessels. Chemical characterization using NMR and FTIR spectroscopy confirmed the successful modification of PEG with Tyr and rheological characterization indicated that the addition of PEG-Tyr decreased the viscosity of the ink. Enzyme-mediated crosslinking of PEG-Tyr allowed the formation of covalent crosslinks within the hydrogel chains, ensuring its stability. PEG-Tyr units improved the mechanical properties of the material, resulting in stretchable and elastic constructs without compromising cell viability and adhesion. The printed vessel structures displayed uniform wall thickness, shape retention, improved elasticity, permeability, and colonization by endothelial-derived - EA.hy926 cells. The chorioallantoic membrane (CAM) and in vivo assays demonstrated the hydrogel's ability to support neoangiogenesis. The hydrogel material with PEG-Tyr modification holds promise for vascular tissue engineering applications, providing a flexible, biocompatible, and functional platform for the fabrication of vascular structures.

The objective was to assess a range of stress indices to discern wheat genotypes resilient to drought stress, so forty-nine genotypes underwent scrutiny in both drought stress in rainfed conditions and non-stress settings (with supplementary irrigation), employing a 7 × 7 lattice layout with two replicates across years 2019 and 2020. The evaluation incorporated twenty stress indices anchored in yield under water stress (YS) and potential (YP) circumstances. Primary analysis indicated that eight indices (RDI, YSI, YI, K2STI, MRP, REI, RR and SSPI) did not give any new information, so they were eliminated in further analysis. Genotypes G33 (4234 kg ha-1) and G9 (2227 kg ha-1) were the best genotypes based on YP in 2019 and 2020, respectively. A positive association was observed between ATI and YP and between YS with DI and K1STI in the year 2019, while in the second year, such positive associations were not seen. We found some wheat genotypes G6, G9, G10 and G11 demonstrated high performance in both potential and rainfed conditions across two years, showing yield higher than 1,800 and 2,700 kg ha-1 for YS and YP, respectively, across both years. These genotypes were detected as the most tolerant genotypes by mean-based indices (TOL, HM, GMP, and MP) as well as SSI and ATI indices, so it can be concluded that these indices are more useful than other indices for identifying the most tolerant as well as the high yielding genotypes.

Summary: A poor maternal diet during pregnancy predisposes the infant to severe lower respiratory tract infections (sLRIs), which, in turn, increases childhood asthma risk; however, the underlying mechanisms remain poorly understood. Here, we show that the offspring of high-fat diet (HFD)-fed mothers (HFD-reared pups) developed an sLRI following pneumovirus inoculation in early life and subsequent asthma in later life upon allergen exposure. Prior to infection, HFD-reared pups developed microbial dysbiosis and low-grade systemic inflammation (LGSI), characterized by hyperneutropoiesis in the liver and elevated inflammatory cytokine expression, most notably granulocyte-colony stimulating factor (G-CSF), interleukin-17A (IL-17A), IL-6 and soluble IL-6 receptor (sIL-6R) (indicative of IL-6 trans-signaling) in the circulation and multiple organs but most prominently the liver. Inhibition of IL-6 trans-signaling using sgp130Fc transgenic mice or via specific genetic deletion of IL-6Ra on neutrophils conferred protection against both diseases. Taken together, our findings suggest that a maternal HFD induces neonatal LGSI that predisposes to sLRI and subsequent asthma via neutrophil-mediated IL-6 trans-signaling.

The ability of air pollution to induce acute exacerbation of asthma is well documented. However, the ability of ozone (O3), the most reactive gaseous component of air pollution, to function as a modulator during sensitization is not well established. C57BL/6 J male mice were intranasally sensitized to house dust mite (HDM) (40 μg/kg) for 3 weeks on alternate days in parallel with once-a-week O3 exposure (1 ppm). Mice were euthanized 24 h following the last HDM challenge. Lung lavage, histology, lung function (both forced oscillation and forced expiration-based), immune cell profiling, inflammation (pulmonary and systemic), and immunoglobulin production were assessed. Compared to HDM alone, HDM + O3 leads to a significant increase in peribronchial inflammation (p

Broad biochemical complexity and frequent overlapping clinical symptoms of inborn errors of metabolism (IEM), especially in energy-deficient patients, make accurate diagnosis difficult. In recent years, whole exome sequencing (WES), a comprehensive protein coding genetic test, has been used to diagnose patients at the molecular level. This study aims to evaluate the potential of WES in diagnosing energy-deficient IEM patients with limited biochemical findings and to identify common symptoms patterns in reported cases. Articles were identified using a combination of search terms in online databases (Science Direct, PubMed Central and Wiley). English-language case reports citing WES in the diagnosis of energy-deficient IEM patients were reviewed. This systematic review was conducted and reported using the ‘Preferred Reporting Items for Systematic Reviews and Meta-Analyses’ checklist. The quality and risk of bias were assessed using Joanna Briggs Institute critical appraisal tool. A total of 37 studies comprising of 54 case reports were included in this review. The median age of the patients was 0.4 years, with 55.6% being male and 44.4% being female. A total of 33 mutant genes were reported and they related to either metabolism or mitochondrial function. WES was able to identify mutations in 53 of 54 cases reported. The diagnosis of energy-deficient IEM patients is crucial, particularly given the challenging range of diverse clinical symptoms they present. The high accuracy of the WES technique appears to improve the diagnostic process. Further research defining more detailed guidelines is needed to engage with this rare set of genetic diseases.

Background: Colon carcinoma poses a significant health challenge globally, particularly in developed nations where sedentary lifestyles, poor dietary choices, and genetic factors play a crucial role in its prevalence. Chemotherapy, the primary treatment method, carries severe side effects that can jeopardize patients' lives. Herbal extracts such as Ocimum Basillicum extract have shown effectiveness against cancer cells. Additionally, nanoparticles can significantly enhance drug delivery efficacy in these scenarios. Aim: This article aims to investigate the impact of copper nanoparticles coated with Ocimum Bassilicum at chemoradiotherapy of Colon Carcinoma to hopefully create new treatment options with fewer side effects for patients. Methodology: CuO bio-NPs were produced by the addition of 15 mL of extract dropwise to 80 mL of a 5 mM Cu (OAc)2 aqueous solution, which was then refluxed for 2 h at 100 °C. The mixture gradually became darker brown in color as a result of the heating procedure. The production of CuO NPs and the hydrogen-donating activity of antioxidant phenols within the plant are signaled by surface plasmon resonance excitation, which is the cause of this. In the cell culture, LS174t colon cancer cells were treated with OB extract, CuNPs, and OB-coated CuNPs with and without different radiation levels in order to assess cell viability, through the MTT assay, and the pro-apoptotic BAX and anti-apoptotic BCL2 expressions, through qPCR assay. Results: The results demonstrate a decrease in cell viability and the expression of BCL2 and an increase in the expression of BAX especially when treated with OB-coated CuNPs and even furthermore when paired with radiation therapy. Conclusions: After doing the clinical trial studies, the recent nanoparticles can be used for the treatment of Colorectal carcinoma.

Systems biology is an interdisciplinary field that aims to understand complex biological processes at the system level. The data, driven by high-throughput omics technologies, can be used to study the underpinning mechanisms of metabolite production under different conditions to harness this knowledge for the construction of regulatory networks, protein networks, metabolic models, and engineering of strains with enhanced target metabolite production in microalgae. In the current study, we comprehensively reviewed the recent progress in the application of these technologies for the characterization of carotenoid biosynthesis pathways in microalgae. Moreover, harnessing integrated approaches such as network analysis, meta-analysis, and machine learning models for deciphering the complexity of carotenoid biosynthesis pathways were comprehensively discussed.

Abstract Background In the UK National Health Service (NHS), the patient’s vital signs are monitored and summarised into a National Early Warning Score (NEWS) score. A set of computer-aided risk scoring systems (CARSS) was developed and validated for predicting in-hospital mortality and sepsis in unplanned admission to hospital using NEWS and routine blood tests results. We sought to assess the accuracy of these models to predict the risk of COVID-19 in unplanned admissions during the first phase of the pandemic. Methods Adult ( > = 18 years) non-elective admissions discharged (alive/deceased) between 11-March-2020 to 13-June-2020 from two acute hospitals with an index NEWS electronically recorded within ± 24 h of admission. We identified COVID-19 admission based on ICD-10 code ‘U071’ which was determined by COVID-19 swab test results (hospital or community). We assessed the performance of CARSS (CARS_N, CARS_NB, CARM_N, CARM_NB) for predicting the risk of COVID-19 in terms of discrimination (c-statistic) and calibration (graphically). Results The risk of in-hospital mortality following emergency medical admission was 8.4% (500/6444) and 9.6% (620/6444) had a diagnosis of COVID-19. For predicting COVID-19 admissions, the CARS_N model had the highest discrimination 0.73 (0.71 to 0.75) and calibration slope 0.81 (0.72 to 0.89) compared to other CARSS models: CARM_N (discrimination:0.68 (0.66 to 0.70) and calibration slope 0.47 (0.41 to 0.54)), CARM_NB (discrimination:0.68 (0.65 to 0.70) and calibration slope 0.37 (0.31 to 0.43)), and CARS_NB (discrimination:0.68 (0.66 to 0.70) and calibration slope 0.56 (0.47 to 0.64)). Conclusions The CARS_N model is reasonably accurate for predicting the risk of COVID-19. It may be clinically useful as an early warning system at the time of admission especially to triage large numbers of unplanned admissions because it requires no additional data collection and is readily automated.

Non-alcoholic fatty liver disease (NAFLD) is a high-prevalence and progressive disorder. Due to lack of reliable in vitro models to recapitulate the consecutive phases, the exact pathogenesis mechanism of this disease and approved therapeutic medications have not been revealed yet. It has been proven that the interplay between multiple hepatic cell types and liver extracellular matrix (ECM) are critical in NAFLD initiation and progression. Herein, a liver microtissue (LMT) consisting of Huh-7, THP-1, and LX-2 cell lines and human umbilical vein endothelial cells (HUVEC), which could be substituted for the main hepatic cells (hepatocyte, Kupffer, stellate, and sinusoidal endothelium, respectively), encapsulated in liver derived ECM-Alginate composite, was bioengineered. When the microtissues were treated with free fatty acids (FFAs) including Oleic acid (6.6×10−4M) and Palmitic acid (3.3×10−4M), they displayed the key features of NAFLD, including similar pattern of transcripts for genes involved in lipid metabolism, inflammation, insulin-resistance, and fibrosis, as well as pro-inflammatory and pro-fibrotic cytokines’ secretions and intracellular lipid accumulation. Continuing FFAs supplementation, we demonstrated that the NAFLD phenomenon was established on day 3 and progressed to the initial fibrosis stage by day 8. Furthermore, this model was stable until day 12 post FFAs withdrawal on day 3. Moreover, administration of an anti-steatotic drug candidate, Liraglutide (15 μM), on the NAFLD microtissues significantly ameliorated the NAFLD phenomenon. Overall, we bioengineered a drug-responsive, cost-benefit liver microtissues which can simulate the initiation and progression of NAFLD. It is expected that this platform could potentially be used for studying molecular pathogenesis of NAFLD and high-throughput drug screening.

Coronary heart disease (CHD) continues to be the leading cause of morbidity and mortality. There are numerous therapeutic reperfusion methods, including thrombolytic therapy, primary percutaneous coronary intervention, and anti-remodeling drugs like angiotensin-converting enzyme inhibitors and beta-blockers. Despite this, there is no pharmacological treatment that can effectively stop cardiomyocyte death brought on by myocardial ischemia/reperfusion (I/R) injury. For the purpose of regenerating cardiac tissue, mesenchymal stem cell (MSC) therapy has recently gained more attention. The pleiotropic effects of MSCs are instead arbitrated by the secretion of soluble paracrine factors and are unrelated to their capacity for differentiation. One of these paracrine mediators is the extracellular vesicle known as an exosome. Exosomes deliver useful cargo to recipient cells from MSCs, including peptides, proteins, cytokines, lipids, miRNA, and mRNA molecules. Exosomes take part in intercellular communication processes and help tissues and organs that have been injured or are ill heal. Exosomes alone were found to be the cause of MSCs' therapeutic effects in a variety of animal models, according to studies. Here, we have focused on the recent development in the therapeutic capabilities of exosomal MSCs in cardiac diseases.

Abstract Humans receive sensory information from the past, requiring the brain to overcome delays to perform daily motor skills such as standing upright. Because delays vary throughout the body and change over a lifetime, it would be advantageous to generalize learned control policies of balancing with delays across contexts. However, not all forms of learning generalize. Here, we use a robotic simulator to impose delays into human balance. When delays are imposed in one direction of standing, participants are initially unstable but relearn to balance by reducing the variability of their motor actions and transfer balance improvements to untrained directions. Upon returning to normal standing, aftereffects from learning are observed as small oscillations in control, yet they do not destabilize balance. Remarkably, when participants train to balance with delays using their hand, learning transfers to standing with the legs. Our findings establish that humans use experience to broadly update their neural control to balance with delays.

Abstract Background Quantifying gene expression is a critical aspect of applied genomics research across all organisms, and real-time PCR has emerged as a powerful tool for this purpose. However, selecting appropriate internal control genes for data normalization presents specific challenges. This study aimed to identify suitable reference genes for gene expression analysis under various conditions, encompassing salinity, low and high-temperature stresses, and different elicitor treatments. These treatments included titanium dioxide, cold plasma, 24-epibrassinolide, and melatonin, resulting in a total of 13 unique treatments and 148 treatment combinations applied to fenugreek plants. Results As per the analysis performed with the BestKeeper tool, EEF-1α, and GAPDH were recognized as the most stable reference genes under the majority of conditions. Furthermore, the GeNorm and NormFinder tools identified β-tubulin and EEF-1α as the most stable reference genes. The findings of this research demonstrated that, although the stability of three reference genes expression was acceptable in almost all evaluated treatments, fluctuations in their expression were observed under the treatments of cold stress with TiO2 NPs application, cold plasma application with salinity stress, and cold plasma application with high-temperature stress compared to others. Simultaneously, the GeNorm analysis results demonstrated that in the mentioned treatments, relying on only one reference gene is inadequate. To corroborate the results, we examined the expression profile of the SSR gene, a pivotal gene in diosgenin biosynthesis, under all investigated treatments and treatment combinations. The outcomes suggested that employing stable reference genes yielded highly consistent results. Conclusions The varying expression patterns of the target genes emphasize the crucial need for precise optimization of experimental conditions and selecting stable reference genes to achieve accurate results in gene expression studies utilizing real-time PCR. These findings offer valuable insights into the selection of appropriate reference genes for gene expression analysis under diverse conditions using real-time PCR.

Introduction: Globally, one of the major causes of renal dysfunction is diabetes mellitus (DM), and diabetic-induced nephrotoxicity has been linked with anemia. Presently, numerous antidiabetic drugs have been designed for the management of this disorder but they possess their undesirable effects such as anemia and acute kidney injury. Hence, we explore the use of vitamin D with or without exercise for the management of DM-induced renal dysfunction. Methods: Thirty-six (36) Wistar rats were randomly separated into six (6) groups: control (vehicle treated), diabetes untreated (HFD + STZ), diabetes + vitamin D (HFD + STZ + vitamin D), diabetes + exercise (HFD + STZ + exercise), diabetes + vitamin D + exercise (HFD + STZ + vitamin D+ exercise), diabetes + metformin (HFD + STZ + metformin). Results: Vitamin D with or without exercise significantly reduced T2DM-induced hyperglycemia. Also, a decrease in T2DM-induced increase in urea, creatinine, lactate dehydrogenase, lactate, cholesterol, and triglyceride and a rise in DM-associated reduction in high-density lipoprotein. These events were associated with a significant increase in red blood cells, hematocrit value, hemoglobin, erythropoietin, and a decrease in white blood cell count. Furthermore, vitamin D with or without exercise reversed T2DM-induced increase in pro-oxidant and pro-inflammatory markers. This observed oxido-inflammatory response was associated with a significant increase in xanthine oxidase activities and uric acid concentration. Interestingly, better recovery rates from DM-associated hematological imbalance were discovered in rats co-treated with vitamin D and exercise. Conclusion: Our findings revealed that exercise enhanced the hematological effect of vitamin D in HFD + STZ-induced T2DM animals.

Trans-activation response (TAR) RNA-binding protein (TRBP) has emerged as a key player in the RNA interference pathway, wherein it binds to different pre-microRNAs (miRNAs) and small interfering RNAs (siRNAs), each varying in sequence and/or structure. We hypothesize that TRBP displays dynamic adaptability to accommodate heterogeneity in target RNA structures. Thus, it is crucial to ascertain the role of intrinsic and RNA-induced protein dynamics in RNA recognition and binding. We have previously elucidated the role of intrinsic and RNA-induced conformational exchange in the double-stranded RNA-binding domain 1 (dsRBD1) of TRBP in shape-dependent RNA recognition. The current study delves into the intrinsic and RNA-induced conformational dynamics of the TRBP-dsRBD2 and then compares it with the dsRBD1 study carried out previously. Remarkably, the two domains exhibit differential binding affinity to a 12-bp dsRNA owing to the presence of critical residues and structural plasticity. Furthermore, we report that dsRBD2 depicts constrained conformational plasticity when compared to dsRBD1. Although, in the presence of RNA, dsRBD2 undergoes induced conformational exchange within the designated RNA-binding regions and other residues, the amplitude of the motions remains modest when compared to those observed in dsRBD1. We propose a dynamics-driven model of the two tandem domains of TRBP, substantiating their contributions to the versatility of dsRNA recognition and binding.

The Nipah virus (NiV) belongs to the Henipavirus genus is a serious public health concern causing numerous outbreaks with higher fatality rate. Unfortunately, there is no effective medication available for NiV. To investigate possible inhibitors of NiV infection, we used in silico techniques to discover treatment candidates in this work. As there are not any approved treatments for NiV infection, the NiV-enveloped attachment glycoprotein was set as target for our study, which is responsible for binding to and entering host cells. Our in silico drug design approach included molecular docking, post-docking molecular mechanism generalised born surface area (MM-GBSA), absorption, distribution, metabolism, excretion/toxicity (ADME/T), and molecular dynamics (MD) simulations. We retrieved 418 phytochemicals associated with the neem plant ( Azadirachta indica ) from the IMPPAT database, and molecular docking was used to ascertain the compounds’ binding strength. The top 3 phytochemicals with binding affinities of −7.118, –7.074, and −6.894 kcal/mol for CIDs 5280343, 9064, and 5280863, respectively, were selected for additional study based on molecular docking. The post-docking MM-GBSA of those 3 compounds was −47.56, –47.3, and −43.15 kcal/mol, respectively. As evidence of their efficacy and safety, all the chosen drugs had favorable toxicological and pharmacokinetic (Pk) qualities. We also performed MD simulations to confirm the stability of the ligand-protein complex structures and determine whether the selected compounds are stable at the protein binding site. All 3 phytochemicals, Quercetin (CID: 5280343), Cianidanol (CID: 9064), and Kaempferol (CID: 5280863), appeared to have outstanding binding stability to the target protein than control ribavirin, according to the molecular docking, MM-GBSA, and MD simulation outcomes. Overall, this work offers a viable approach to developing novel medications for treating NiV infection.

The result of infection of bone with microorganisms is osteomyelitis and septic arthritis. Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for most of its cases (more than 50%). Since MRSA is resistant to many treatments, it is accompanied by high costs and numerous complications, necessitating more effective new treatments. Recently, development of gelatin nanoparticles have attracted the attention of scientists of biomedicine to itself, and have been utilized as a delivery vehicle for antibiotics because of their biocompatibility, biodegradability, and cost-effectiveness. Promising results have been reported with gelatin modification and combinations with chemical agents. Although these findings have been suggested that gelatin has the potential to be a suitable option for continuous release of antibiotics in osteomyelitis and septic arthritis treatment, they still have not become routine in clinical practices. The most deliver antibiotic using gelatin-derived composites is vancomycin which is showed the good efficacy. To date, a number of pre-clinical studies evaluated the utility of gelatin-based composites in the management of osteomyelitis. Gelatin-based composites were found to have satisfactory performance in the control of infection, as well as the promotion of bone defect repair in chronic osteomyelitis models. This review summarized the available evidence which provides a new insight into gelatin-derived composites with controlled release of antibiotics.

Summary: Noonan syndrome patients harboring causative variants in LZTR1 are particularly at risk to develop severe and early-onset hypertrophic cardiomyopathy. In this study, we investigate the mechanistic consequences of a homozygous variant LZTR1L580P by using patient-specific and CRISPR-Cas9-corrected induced pluripotent stem cell (iPSC) cardiomyocytes. Molecular, cellular, and functional phenotyping in combination with in silico prediction identify an LZTR1L580P-specific disease mechanism provoking cardiac hypertrophy. The variant is predicted to alter the binding affinity of the dimerization domains facilitating the formation of linear LZTR1 polymers. LZTR1 complex dysfunction results in the accumulation of RAS GTPases, thereby provoking global pathological changes of the proteomic landscape ultimately leading to cellular hypertrophy. Furthermore, our data show that cardiomyocyte-specific MRAS degradation is mediated by LZTR1 via non-proteasomal pathways, whereas RIT1 degradation is mediated by both LZTR1-dependent and LZTR1-independent pathways. Uni- or biallelic genetic correction of the LZTR1L580P missense variant rescues the molecular and cellular disease phenotype, providing proof of concept for CRISPR-based therapies.

Further analysis of the effectiveness of integrating project-based learning (PjBL) in Invertebrate Zoology courses to improve students' science process skills and conceptual understanding needs to be carried out. This research was aimed to analyze the integration of PjBL in the Invertebrate Zoology course on scientific process skills and conceptual understanding of student. As for seeing the effect of each indicator from each predictor, a qualitative descriptive analysis was carried out. Respondents in this study were students of the Biology Education Study Program FTTE Universitas Bengkulu. A sample of 30 respondents was taken by random sampling technique. The research instrument is a questionnaire for scientific process skills and tests for understanding concepts. The hypothesis is tested using Analysis of Variance (ANOVA). The integration of PjBL has a significant influence on the scientific skills process of 0.038 with an F value of 4.524 and also has a significant influence on concept understanding at 0.018 with an F value of 0.018. It was concluded that there was an effect of the integration of PjBL on scientific process skills and conceptual understanding of Invertebrate Zoology, with a significance level of 0.05, so that it can be taken into consideration in developing learning in the Invertebrate Zoology course.

The enhancement of associative synaptic plasticity often results in impaired rather than enhanced learning. Previously, we proposed that such learning impairments can result from saturation of the plasticity mechanism (Nguyen-Vu et al., 2017), or, more generally, from a history-dependent change in the threshold for plasticity. This hypothesis was based on experimental results from mice lacking two class I major histocompatibility molecules, MHCI H2-Kb and H2-Db (MHCI KbDb−/−), which have enhanced associative long-term depression at the parallel fiber-Purkinje cell synapses in the cerebellum (PF-Purkinje cell LTD). Here, we extend this work by testing predictions of the threshold metaplasticity hypothesis in a second mouse line with enhanced PF-Purkinje cell LTD, the Fmr1 knockout mouse model of Fragile X syndrome (FXS). Mice lacking Fmr1 gene expression in cerebellar Purkinje cells (L7-Fmr1 KO) were selectively impaired on two oculomotor learning tasks in which PF-Purkinje cell LTD has been implicated, with no impairment on LTD-independent oculomotor learning tasks. Consistent with the threshold metaplasticity hypothesis, behavioral pre-training designed to reverse LTD at the PF-Purkinje cell synapses eliminated the oculomotor learning deficit in the L7-Fmr1 KO mice, as previously reported in MHCI KbDb−/−mice. In addition, diazepam treatment to suppress neural activity and thereby limit the induction of associative LTD during the pre-training period also eliminated the learning deficits in L7-Fmr1 KO mice. These results support the hypothesis that cerebellar LTD-dependent learning is governed by an experience-dependent sliding threshold for plasticity. An increased threshold for LTD in response to elevated neural activity would tend to oppose firing rate stability, but could serve to stabilize synaptic weights and recently acquired memories. The metaplasticity perspective could inform the development of new clinical approaches for addressing learning impairments in autism and other disorders of the nervous system.

Socio-economic disparities were associated with disproportionate viral incidence between neighborhoods of New York City (NYC) during the first wave of SARS-CoV-2. We investigated how these disparities affected the co-circulation of SARS-CoV-2 variants during the second wave in NYC. We tested for correlation between the prevalence, in late 2020/early 2021, of Alpha, Iota, Iota with E484K mutation (Iota-E484K), and B.1-like genomes and pre-existing immunity (seropositivity) in NYC neighborhoods. In the context of varying seroprevalence we described socio-economic profiles of neighborhoods and performed migration and lineage persistence analyses using a Bayesian phylogeographical framework. Seropositivity was greater in areas with high poverty and a larger proportion of Black and Hispanic or Latino residents. Seropositivity was positively correlated with the proportion of Iota-E484K and Iota genomes, and negatively correlated with the proportion of Alpha and B.1-like genomes. The proportion of persisting Alpha lineages declined over time in locations with high seroprevalence, whereas the proportion of persisting Iota-E484K lineages remained the same in high seroprevalence areas. During the second wave, the geographic variation of standing immunity, due to disproportionate disease burden during the first wave of SARS-CoV-2 in NYC, allowed for the immune evasive Iota-E484K variant, but not the more transmissible Alpha variant, to circulate in locations with high pre-existing immunity.

The main purpose of this work is studying the linear Susceptibility in the hybrid nanostructure that composed of a dual quantum dot (DQD) and metal nanoparticle (MNP) hybrid system under a standing-wave field. In our model, we used density matrix equations by taking into our account the interaction between excitons and surface plasmons. The proposed DQD is composed of two QDs. Each QD contains an InAs QD with a disk shape. The interaction between the QD and the wetting layer (WL) is taken into consideration. The application of the standing wave field on DQD-MNP hybrid system was modeled and examined. The susceptibility of thehybridDQD-MNPsystem reduced by the pump field under a standing-wave field. The high susceptibility obtained with a wide MNP radius. An interesting result was shown in the inversion of the grating period with the tunneling component in the conduction band. The smaller size of DQD gave us high susceptibility due to the quantization effect.

Summary: Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers. By profiling histone modifications and DNA methylation, we identified highly recurrent epigenomic reprogramming enriched in sRCC. Furthermore, CRISPRa experiments implicated the transcription factor FOSL1 in activating sRCC-associated gene regulatory programs, and FOSL1 expression was associated with the response to ICIs in RCC in two randomized clinical trials. Finally, we established a blood-based diagnostic approach using detectable sRCC epigenomic signatures in patient plasma, providing a framework for discovering epigenomic correlates of tumor histology via liquid biopsy.

هدف هذا البحث الى امكانية استخدام الطحالب البحرية المخمرة وخلائطها مع التربة الزراعية بنسب (1/2 ، 1/3 ، 1/4 ) على التوالي كوسط زراعي في المشاتل الحراجية بالمقارنة مع وسط الشاهد ( التربة الزراعية )، والمادة النباتية المدروسة الخرنوب Ceratonia siliqua L. ، وأجري هذا البحث خلال العام 2020 -2021 في مركز بوقا النباتي التابع لكلية الزراعة في جامعة تشرين . أظهرت نتائج البحث إلى أن عملية خلط كمبوست الطحالب البحرية مع التربة الزراعية زاد من نسبة الانبات بالمقارنة مع الشاهد ومع وسط الكمبوست منفرداً، وهذا يعني صلاحيّة الأوساط الأساسيّة بمفردها وخلائطها لأن تكون وسطاً جيّداً لانبات بذور الخرنوب. كما أظهرت النتائج إن متوسط طول المجموع الخضري كان الأفضل في معاملات خلط الكمبوست مع التربة الزراعية بالمقارنة مع الشاهد والكمبوست منفرداً، كما حسن خلط الكمبوست مع التربة الزراعية من قيم الوزن الجاف للمجموعين الخضري والجذري بالمقارنة مع الشاهد الكمبوست ومنفرداً، وأن أفضل القيم لـ R / S ( طول ، وزن ) في المعاملتين ( خلط الكمبوست مع التربة الزراعية 1 /3، 1 /4 ).

هدف هذا البحث الى امكانية استخدام الطحالب البحرية المخمرة وخلائطها مع التربة الزراعية بنسب (1/2 ، 1/3 ، 1/4 ) على التوالي كوسط زراعي في المشاتل الحراجية بالمقارنة مع وسط الشاهد ( التربة الزراعية )، والمادة النباتية المدروسة الخرنوب Ceratonia siliqua L. ، وأجري هذا البحث خلال العام 2020 -2021 في مركز بوقا النباتي التابع لكلية الزراعة في جامعة تشرين . أظهرت نتائج البحث إلى أن عملية خلط كمبوست الطحالب البحرية مع التربة الزراعية زاد من نسبة الانبات بالمقارنة مع الشاهد ومع وسط الكمبوست منفرداً، وهذا يعني صلاحيّة الأوساط الأساسيّة بمفردها وخلائطها لأن تكون وسطاً جيّداً لانبات بذور الخرنوب. كما أظهرت النتائج إن متوسط طول المجموع الخضري كان الأفضل في معاملات خلط الكمبوست مع التربة الزراعية بالمقارنة مع الشاهد والكمبوست منفرداً، كما حسن خلط الكمبوست مع التربة الزراعية من قيم الوزن الجاف للمجموعين الخضري والجذري بالمقارنة مع الشاهد الكمبوست ومنفرداً، وأن أفضل القيم لـ R / S ( طول ، وزن ) في المعاملتين ( خلط الكمبوست مع التربة الزراعية 1 /3، 1 /4 ).

Objective: Glioma is one of the most malignant brain tumors, accounting for about half of the gliomas that occur in central nervous system (CNS), originates from the glial tissue of the brain. The aim of the present study was to determine the expression levels of 3 lncRNAs (AGAP2-AS1, LINC01446 and HOTAIRM1) in patients with high grade glioma in comparison with low grade glioma. Methods: Case group consisted of 70 high grade glioma patients control group consisted of 70 patients affected with low grade glioma. RNA extraction was performed using a RNA extraction kit. Result: Our results showed that the expression of AGAP2-AS1 and LINC01446 genes significantly increased with increasing tumor grade (with fold-change ratio of 2.1 and 3.8 respectively). Also the expression of HOTAIRM1 gene increased with increasing tumor grade but this increase was not statistically significant (P value=0.6). Conclusion: We concluded that AGAP2-AS1 and LINC01446 are promising lncRNA markers in prognosis of glioma.

Osteoarthritis (OA) is a degenerative joint disease that occurs with aging. In its late phases, it is determined by the loss of chondrocytes and the breakdown of the extracellular matrix, resulting in pain and functional impairment. Interleukin-1 beta (IL-1β) is increased in the injured joints and contributes to the OA pathobiology by inducing chondrocyte apoptosis and up-regulation of matrix metalloproteinases (MMPs). Here, we aimed to understand whether minocycline could protect chondrocytes against the IL-1β-induced effects. The human C28/I2 chondrocyte cell line was treated with IL-1β or IL-1β plus minocycline. Cell viability/toxicity, cell cycle progression, and apoptosis were assessed with MMT assay and flow cytometry. Expression of apoptotic genes and MMPs were evaluated with qRT-PCR and western blotting. IL-1β showed a significant cytotoxic effect on the C28/I2 chondrocyte cells. The minocycline effective concentration (EC50) significantly protected the C28/I2 cells against the IL-1β-induced cytotoxic effect. Besides, minocycline effectively lowered IL-1β-induced sub-G1 cell population increase, indicating the minocycline anti-apoptotic effect. When assessed by real-time PCR and western blotting, the minocycline treatment group showed an elevated level of Bcl-2 and a significant decrease in the mRNA and protein expression of the apoptotic markers Bax and Caspase-3 and Matrix metalloproteinases (MMPs) such as MMP-3 and MMP-13. In conclusion, IL-1β promotes OA by inducing chondrocyte death and MMPs overexpression. Treatment with minocycline reduces these effects and decreases the production of apoptotic factors as well as the MMP-3 and MMP-13. Minocycline might be considered as an anti-IL-1β therapeutic supplement in the treatment of osteoarthritis.

Abstract Bone tissue engineering necessitates a stem cell source capable of osteoblast differentiation and mineralized matrix production. Dental pulp stem cells (DPSCs), a subtype of mesenchymal stem cells from human teeth, present such potential but face challenges in osteogenic differentiation. This research introduces an innovative approach to bolster DPSCs’ osteogenic potential using niosomal and hyaluronan modified niosomal systems enriched with rosuvastatin. While rosuvastatin fosters bone formation by regulating bone morphogenetic proteins and osteoblasts, its solubility, permeability, and bioavailability constraints hinder its bone regeneration application. Using a Box-Behnken design, optimal formulation parameters were ascertained. Both niosomes were analyzed for size, polydispersity, zeta potential, and other parameters. They displayed average sizes under 275 nm and entrapment efficiencies exceeding 62%. Notably, niosomes boosted DPSCs’ cell viability and osteogenic marker expression, suggesting enhanced differentiation and bone formation. Conclusively, the study underscores the potential of both niosomal systems in ameliorating DPSCs’ osteogenic differentiation, offering a promising avenue for bone tissue engineering and regeneration. Graphical Abstract

Background: Obesity carries great risks related to health, such as the development and progression of chronic inflammation and obvious metabolic disorders. This study aimed to examine the effect of eight weeks of moderate-intensity resistance training with garlic supplementation on the lipid profile in overweight women. Methods: The present research was a semi-experimental study and the participants were 60 overweight women from Gachsaran City with (body mass index: 28/45±6/72) who were randomly divided into four groups (n = 15): supplemental exercise, placebo exercise, garlic supplemental, and placebo. Two training groups performed moderate-intensity resistance training for eight weeks and three sessions per week. One day before the start of training and 48 hours after the last training session, blood samples were collected to measure total cholesterol (TC), triglyceride (TG), LDL-C, and HDL-C variables. Data were analyzed by one-way ANOVA and LSD post-hoc test. Results: Findings showed that there is a significant decrease in the serum levels of TC, TG, and LDL-C and a significant increase in HDL-C (P

Background: CD38 is highly expressed on multiple myeloma (MM) cells and has been successfully targeted by different target therapy methods. This molecule is a critical prognostic marker in both diffuse large B-cell lymphoma and chronic lymphocytic leukemia.Objective: We have designed and generated an anti-CD38 CAR-NK cell applying NK 92 cell line. The approach has potential application as an off-the-shelf strategy for treatment of CD38 positive malignancies.Methods: A second generation of anti-CD38 CAR-NK cell was designed and generated, and their efficacy against CD38-positive cell lines was assessed in vitro. The PE-Annexin V and 7-AAD methods were used to determine the percentage of apoptotic target cells. Flow cytometry was used to measure IFN-γ, Perforin, and Granzyme-B production following intracellular staining. Using in silico analyses, the binding capacity and interaction interface were evaluated.Results: Using Lentivirus, cells were transduced with anti-CD38 construct and were expanded. The expression of anti-CD38 CAR on the surface of NK 92 cells was approximately 25%. As we expected from in silico analysis, our designed CD38-chimeric antigen receptor was bound appropriately to the CD38 protein. NK 92 cells that transduced with the CD38 chimeric antigen receptor, generated significantly more IFN-γ, perforin, and granzyme than Mock cells, and successfully lysed Daudi and Jurkat malignant cells in a CD38-dependent manner.Conclusion: The in vitro findings indicated that the anti-CD38 CAR-NK cells have the potential to be used as an off-the-shelf therapeutic strategy against CD38-positive malignancies. It is recommended that the present engineered NK cells undergo additional preclinical investigations before they can be considered for subsequent clinical trial studies.

This paper describes the detailed design procedure of electric machines using finite element analysis (FEA). The proposed method uses the available findings from the literature and FEA results for the design procedure. In addition to electromagnetic analysis, thermal analysis is executed to examine the capability of the designed machines for handling the load in terms of thermal limits. It allows for considering the normal and overload performance of the electric machines during design. The proposed design procedure is used for designing a 100 kW induction machine (IM) and interior permanent magnet synchronous machine (IPMSM) for a parallel hybrid electric vehicle (HEV). The differences between the performance parameters of the studied machines are discussed, and the advantages and disadvantages of each design are highlighted. The designed machines are compared with commercially available electrical machines in terms of performance and power density. The comparison demonstrates that the developed machines can offer comparable performance to other designs.

The nests of mound-building ants are unexplored reservoirs of fungal diversity. A previous assessment of this diversity in the nests of Formica ulkei suggested that water availability may be a determinant of the composition of this mycota. To investigate this question, we recovered 3594 isolates of filamentous Ascomycota from the nests of Formica obscuripes and adjacent, non-nest sites, employing Dichloran Rose Bengal agar (DRBA), Dichloran Rose Bengal agar containing glycerol (DRBAG), and malt extract agar containing sucrose (MEA20S). Higher numbers of fungi were isolated from the tops of mounds than from within mounds and non-mound sites. Mound nest soils were dominated by members of the family Aspergillaceae, and up to 50% of the colonies isolated on DRBAG belonged to the genus Aspergillus. Pseudogymnoascus pannorum and species of Talaromyces were also present in higher numbers in mound soils. Species of Penicillium were more abundant in non-nest soils, where they accounted for over 66% of isolates on DRBA. All Aspergillaceae assessed for xerotolerance on a medium augmented with glycerol or sucrose were xerophilic. These results, and our observation that the nests of F. obscuripes are low-water environments, indicate that water availability influences the structure of the fungal communities in these animal-modified habitats.

Dangerous emerging water micropollutants like Diclofenac are harming ecosystems all over the planet, and immediate action is needed. The large bandgap photocatalysts conventionally used to degrade them need to be more efficient. Cu2ZnSnS4, a well-known light absorber in photovoltaics with a bandgap of 1.5 eV, can efficiently harvest an abundant portion of the solar spectrum. However, its photocatalytic activity has so far only been reported in relation to the degradation of organic dyes, and it is usually used as a benchmark to assess the activity of a photocatalyst without testing its actual potential on a hazardous water micropollutant conventionally encountered in primary and secondary waters. Here, we report the promising photocatalytic activity of Cu2ZnSnS4 nanoparticles in the degradation of Diclofenac, chosen as a benchmark for dangerous emerging water micropollutants.

Background/Objectives: Acute myocardial infarction (AMI), characterized by irreversible heart muscle damage and impaired cardiac function caused by myocardial ischemia, is a leading cause of global mortality. The damage associated with reperfusion, particularly mitochondrial dysfunction and reactive oxygen species (ROS) formation, has emerged as a crucial factor in the pathogenesis of cardiac diseases, leading to the recognition of mitochondrial proteins as potential markers for myocardial damage. This study aimed to identify differentially expressed proteins based on the type of cardiac injury, in particular those with and without reperfusion. Methods: Male C57Bl/6J mice were either left untreated, sham-operated, received non-reperfused AMI, or reperfused AMI. Twenty-four hours after the procedures, left ventricular (LV) function and morphological changes including infarct size were determined using echocardiography and triphenyl tetrazolium chloride (TTC) staining, respectively. In addition, plasma was isolated and subjected to untargeted mass spectrometry and, further on, the ELISA-based validation of candidate proteins. Results: We identified mitochondrial creatine kinase 2 (Ckmt2) as a differentially regulated protein in plasma of mice with reperfused but not non-reperfused AMI. Elevated levels of Ckmt2 were significantly associated with infarct size and impaired LV function following reperfused AMI, suggesting a specific involvement in reperfusion damage. Conclusions: Our study highlights the potential of plasma Ckmt2 as a biomarker for assessing reperfusion injury and its impact on cardiac function and morphology in the acute phase of MI.

This field study explores construction workers’ perceptions of using a passive shoulder exoskeleton to better understand how to improve its adoption in construction. We provided forty-one construction workers with an exoskeleton to perform their regular work activities for two days. Workers’ feedback of the tool was collected at the end of each day. Two-thirds indicated they would likely or very likely use an exoskeleton if their employer provided it. Participants felt exoskeletons were helpful for specific overhead tasks, such as installing upper tracks, framing and drywalling bulkheads, taping and mudding ceilings, and installing light fixtures. To improve their adoption within the construction industry, exoskeletons should be designed to be compatible with harnesses and toolbelts, be close-fitting to allow working in tight spaces, be easily adjustable (for fit and level of support), be rugged and easy to clean, and should not encumber workers in performing their tasks.

Chronic wounds remain trapped in a pro-inflammatory state, with strategies targeted at inducing re-epithelialization and the proliferative phase of healing desirable. As a member of the lectin family, galectin-3 is implicated in the regulation of macrophage phenotype and epithelial migration. We investigated if local delivery of galectin-3 enhanced skin healing in a full-thickness excisional C57BL/6 mouse model. An electrospun gelatin scaffold loaded with galectin-3 was developed and compared to topical delivery of galectin-3. Electrospun gelatin/galectin-3 scaffolds had an average fiber diameter of 200 nm, with 83% scaffold porosity approximately and an average pore diameter of 1.15 μm. The developed scaffolds supported dermal fibroblast adhesion, matrix deposition, and proliferation in vitro. In vivo treatment of 6 mm full-thickness excisional wounds with gelatin/galectin-3 scaffolds did not influence wound closure, re-epithelialization, or macrophage phenotypes, but increased collagen synthesis. In comparison, topical delivery of galectin-3 [6.7 µg/mL] significantly increased arginase-I cell density at day 7 versus untreated and gelatin/galectin-3 scaffolds (p < 0.05). A preliminary assessment of increasing the concentration of topical galectin-3 demonstrated that at day 7, galectin-3 [12.5 µg/mL] significantly increased both epithelial migration and collagen content in a concentration-dependent manner. In conclusion, local delivery of galectin 3 shows potential efficacy in modulating skin healing in a concentration-dependent manner.

Glioblastoma multiforme (GBM) represents the deadliest form of brain cancer, characterized by complex interactions within its microenvironment. Despite the understanding of GBM biology, GBM remains highly resistant to any therapy. Therefore, defining innovative biomarkers in GBM can provide insights into tumor biology and potential therapeutic targets. In this study, we explored the potential of GPRC5A to serve as a pertinent biomarker for GBM. We utilized the GBM-TCGA dataset and presented the reproducible bioinformatics analysis for our results. We identified that GPRC5A expression was significantly upregulated in GBM compared to normal tissues, with higher levels correlating with poor overall survival (OS) and progression-free interval (PFI). Moreover, it was associated with key genetic mutations, particularly NF1 and PTEN mutations, and strongly correlated with the mesenchymal stem-like phenotype. GPRC5A was also predominantly associated with aggressive GBM features, including hypoxia, high extracellular matrix (ECM) environments, and extensive stromal and immune infiltrations. Its strong correlation with mesenchymal markers and hypoxic regions underscores its potential as a biomarker and therapeutic target in GBM. These findings provide valuable insights into the role of GPRC5A in GBM pathology and its potential impact as a target for GBM stratifications and treatment strategies.

Paraquat (PQ) is an herbicide toxin that induces injury in different organs. The anti-inflammatory and antioxidant effects of carvacrol were reported previously. The effects of carvacrol and pioglitazone (Pio) alone and their combination on inhaled PQ-induced systemic and lung oxidative stress and inflammation as well as behavioral changes were examined in rats. In this study, animals were exposed to saline (control [Ctrl]) or PQ (PQ groups) aerosols. PQ-exposed animals were treated with 0.03 mg/kg/day dexamethasone (Dexa), 20 and 80 mg/kg/day carvacrol (C-L and C-H), 5 mg/kg/day Pio, and Pio+C-L for 16 days. Inhaled PQ markedly enhanced total and differential white blood cell (WBC) counts, nitric oxide (NO), and malondialdehyde (MDA) levels but decreased catalase (CAT) and superoxide dismutase (SOD) activities and thiol levels both in the bronchoalveolar lavage fluid (BALF) and blood and increased interferon-gamma (INF-γ) and interleukin-10 (IL-10) levels in the BALF (p

Mutations in the gene encoding Cu-Zn superoxide dismutase 1 (SOD1) cause a subset of familial amyotrophic lateral sclerosis (fALS) cases. A shared effect of these mutations is that SOD1, which is normally a stable dimer, dissociates into toxic monomers that seed toxic aggregates. Considerable research effort has been devoted to developing compounds that stabilize the dimer of fALS SOD1 variants, but unfortunately, this has not yet resulted in a treatment. We hypothesized that cyclic thiosulfinate cross-linkers, which selectively target a rare, 2 cysteine-containing motif, can stabilize fALS-causing SOD1 variants in vivo. We created a library of chemically diverse cyclic thiosulfinates and determined structure-cross-linking-activity relationships. A pre-lead compound, "S-XL6," was selected based upon its cross-linking rate and drug-like properties. Co-crystallographic structure clearly establishes the binding of S-XL6 at Cys 111 bridging the monomers and stabilizing the SOD1 dimer. Biophysical studies reveal that the degree of stabilization afforded by S-XL6 (up to 24°C) is unprecedented for fALS, and to our knowledge, for any protein target of any kinetic stabilizer. Gene silencing and protein degrading therapeutic approaches require careful dose titration to balance the benefit of diminished fALS SOD1 expression with the toxic loss-of-enzymatic function. We show that S-XL6 does not share this liability because it rescues the activity of fALS SOD1 variants. No pharmacological agent has been proven to bind to SOD1 in vivo. Here, using a fALS mouse model, we demonstrate oral bioavailability; rapid engagement of SOD1G93A by S-XL6 that increases SOD1G93A's in vivo half-life; and that S-XL6 crosses the blood-brain barrier. S-XL6 demonstrated a degree of selectivity by avoiding off-target binding to plasma proteins. Taken together, our results indicate that cyclic thiosulfinate-mediated SOD1 stabilization should receive further attention as a potential therapeutic approach for fALS.

Photosynthetic eukaryotes, such as microalgae and plants, foster fundamentally important relationships with their microbiome based on the reciprocal exchange of chemical currencies. Among these, the dicarboxylate metabolite azelaic acid (Aze) appears to play an important, but heterogeneous, role in modulating these microbiomes, as it is used as a carbon source for some heterotrophs but is toxic to others. However, the ability of Aze to promote or inhibit growth, as well as its uptake and assimilation mechanisms into bacterial cells are mostly unknown. Here, we use transcriptomics, transcriptional factor coexpression networks, uptake experiments, and metabolomics to unravel the uptake, catabolism, and toxicity of Aze on two microalgal-associated bacteria, Phycobacter and Alteromonas, whose growth is promoted or inhibited by Aze, respectively. We identify the first putative Aze transporter in bacteria, a ‘C4-TRAP transporter’, and show that Aze is assimilated through fatty acid degradation, with further catabolism occurring through the glyoxylate and butanoate metabolism pathways when used as a carbon source. Phycobacter took up Aze at an initial uptake rate of 3.8×10–9 nmol/cell/hr and utilized it as a carbon source in concentrations ranging from 10 μM to 1 mM, suggesting a broad range of acclimation to Aze availability. For growth-impeded bacteria, we infer that Aze inhibits the ribosome and/or protein synthesis and that a suite of efflux pumps is utilized to shuttle Aze outside the cytoplasm. We demonstrate that seawater amended with Aze becomes enriched in bacterial families that can catabolize Aze, which appears to be a different mechanism from that in soil, where modulation by the host plant is required. This study enhances our understanding of carbon cycling in the oceans and how microscale chemical interactions can structure marine microbial populations. In addition, our findings unravel the role of a key chemical currency in the modulation of eukaryote-microbiome interactions across diverse ecosystems.

Tracking body parts in behaving animals, extracting fluorescence signals from cells embedded in deforming tissue, and analyzing cell migration patterns during development all require tracking objects with partially correlated motion. As dataset sizes increase, manual tracking of objects becomes prohibitively inefficient and slow, necessitating automated and semi-automated computational tools. Unfortunately, existing methods for multiple object tracking (MOT) are either developed for specific datasets and hence do not generalize well to other datasets, or require large amounts of training data that are not readily available. This is further exacerbated when tracking fluorescent sources in moving and deforming tissues, where the lack of unique features and sparsely populated images create a challenging environment, especially for modern deep learning techniques. By leveraging technology recently developed for spatial transformer networks, we propose ZephIR, an image registration framework for semi-supervised MOT in 2D and 3D videos. ZephIR can generalize to a wide range of biological systems by incorporating adjustable parameters that encode spatial (sparsity, texture, rigidity) and temporal priors of a given data class. We demonstrate the accuracy and versatility of our approach in a variety of applications, including tracking the body parts of a behaving mouse and neurons in the brain of a freely moving C. elegans. We provide an open-source package along with a web-based graphical user interface that allows users to provide small numbers of annotations to interactively improve tracking results.