Insights into the LiMn2O4 Cathode Stability in Aqueous Electrolytes.

LiMn2O4 (LMO) cathodes present large stability when cycled in aqueous electrolytes, contrasting with their behavior in conventional organic electrolytes in lithium-ion batteries (LIBs). To elucidate the mechanisms underlying this distinctive behavior, we employ unconventional characterization techniques, including variable energy positron annihilation lifetime spectroscopy (VEPALS), tip-enhanced Raman spectroscopy (TERS), and macro-Raman spectroscopy (with tens of µm-size laser spot). These still rather unexplored techniques in the battery field provide complementary information across different length scales, revealing previously hidden features. VEPALS offers atomic-scale insights, uncovering cationic defects and subnanometer pores that tend to collapse with cycling. TERS, operating in the nanometric range at the surface, captured the presence of Mn3O4 and its dissolution with cycling, elucidating dynamic changes during operation. Additionally, TERS highlights the accumulation of SO4 2- at grain boundaries. Macro-Raman spectroscopy focuses on the micrometer scale, depicting small changes in the cathode's long-range order, suggesting a slow but progressive loss of crystalline quality under operation. Integrating these techniques provides a comprehensive assessment of LMO cathode stability in aqueous electrolytes, offering multifaceted insights into phase and defect evolution that can help to rationalize the origin of such stability when compared with conventional organic electrolytes. Our findings advance the understanding of LMO behavior in aqueous environments and provide guidelines for its development for next-generation LIBs.

Arthrospira platensis nanoparticles dietary supplementation improves growth performance, steroid hormone balance, and reproductive productivity of Nile tilapia (Oreochromis niloticus) broodstock.

This study evaluates the impact of dietary supplementation of the blue-green alga Arthrospira platensis NIOF17/003 nanoparticles (AN) on the growth performance, whole-body biochemical compositions, blood biochemistry, steroid hormonal, and fry production efficiency of Nile tilapia (Oreochromis niloticus) broodstock, during the spawning season. After a 21-day preparation period to equip the females and ensure that their ovaries were filled with eggs, mating between the mature females and males took place in a 3:1 ratio during a 14-day spawning cycle. A total of 384 tilapia broodstock 288 females and 96 males with an initial body weight of 450.53±0.75, were divided into four groups; AN0: a basal diet as a control group with no supplementation of Arthrospira platensis, and the other three groups (AN2, AN4, and AN6) were diets supplemented with nanoparticles of A. platensis at levels of 2, 4, and 6 g kg─1 diet, respectively. The results found that fish-fed group AN6 showed the highest significant differences in weight gain (WG), final weight (FW), feed conversion ratio (FCR), protein efficiency ratio (PER), and feed efficiency ratio (FER). Females fed the AN6 diet showed the highest significant fat content. Compared to the AN0 group, fish fed on the supplemented diets showed significant improvement (p < 0.05) in triglyceride, glucose, and aspartate aminotransferase (AST). A gradual increase in AN inclusion level resulted in a gradual increase in the concentrations of luteinizing hormone (LH), and follicle-stimulating hormone (FSH), testosterone, progesterone, and prolactin. The rates (%) of increase in fry production for females fed supplemented diets were 10.5, 18.6, and 32.2% for AN2, AN4, and AN6, respectively, compared to the control group. This work concluded that the inclusion levels of 6 g kg─1 of A. platensis nanoparticles in the diet of Nile tilapia broodstock significantly improved the growth performances, steroid hormone concentrations, and increased the fry production efficiency by 32.2%, respectively. These findings revealed that A. platensis nanoparticles resulted in a significantly enhanced female' reproductive productivity of Nile tilapia broodstock.

Effects of dietary supplementation with benthic diatom Amphora coffeaeformis on blood biochemistry, steroid hormone levels and seed production efficiency of Nile tilapia Oreochromis niloticus broodstock.

Aquafeed additive quality and quantity remain pivotal factors that constrain the sustainability and progress of aquaculture feed development. This study investigates the impact of incorporating the benthic diatom Amphora coffeaeformis into the diet of Nile tilapia (Oreochromis niloticus) broodstock, on the blood biochemistry, steroid hormone (SH) levels and seed production efficiency. Broodstock females displaying mature ovary indications were initially combined with males at a ratio of three females to one male. A total of 384 adult Nile tilapia (288 females and 96 males) were used, with 32 fish (24 females and eight males) assigned to each of 12 concrete tanks (8 m³; 2 m × 4 m × 1 m), with three replicate tanks for each dietary treatment, throughout a 14-day spawning cycle until egg harvest. Fish were fed one of four different dietary treatments: AM0% (control diet), and AM2%, AM4% and AM6% enriched with the diatom A. coffeaeformis at levels of 20, 40 and 60 g/kg of diet respectively. At the trial's conclusion, total protein, albumin, triglyceride and creatinine), SHs (follicle-stimulating hormone, luteinizing hormone, free testosterone, total testosterone, progesterone and prolactin) and seeds production efficiency of Nile tilapia improved significantly (p < 0.05) in alignment with the increment of A. coffeaeformis supplementation. The findings propose that including A. coffeaeformis at levels ranging from 4% to 6% could be effectively employed as a feed additive during the Nile tilapia broodstock's spawning season.

Comparative Antioxidant Activity and Untargeted Metabolomic Analyses of Sour Cherry Cultivars Based on Ultra-Performance-Time of Flight-Mass Spectrometry.

This study was conducted for the comparative analysis of antioxidant activity and untargeted metabolomics of dark- and light-colored sour cherry cultivars grown in Canada. Based on our previous study, we selected four cultivars-'Heimann R', 'Gorsemska', V70142, and 'Montmorency'-to determine the untargeted metabolites and their role in antioxidant activities. A total of 473 metabolites were identified from four sour cherry genotypes using UPLC-ToF-MS. Untargeted metabolomics revealed the dominant chemical groups present in sour cherries. PCA showed that the diversity in sour cherry metabolites was due to the genotype differences indicating iditol, malic acid, chlorobenzene, 2-mercaptobenzothiazole, and pyroglutamic acid as the predominant contributors. The variable importance in the projection (VIP > 1.0) in partial least-squares-discriminant analysis described 20 biomarker metabolites representing the cherry metabolome profiles. A heatmap of Pearson's correlation analysis between the 20 biomarker metabolites and antioxidant activities identified seven antioxidant determinants that displayed the highest correlations with different types of antioxidant activities. TPC and TAC were evaluated using the Folin-Ciocalteu method. The total antioxidant activity was performed using three different assays (ABTS, FRAP, and DPPH). This study of correlating metabolomics and antioxidant activities elucidated that the higher nutritional value and biological functions of sour cherry genotypes can be useful for the development of nutraceutical and functional foods.

Efficacy of N-acetylcysteine in reducing the risk of postoperative atrial fibrillation in cardiothoracic surgery: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: New-onset postoperative atrial fibrillation (POAF) is a common complication following cardiac surgeries. N-acetylcysteine (NAC) showed a significant reduction in the incidence of POAF. This review aimed to systematically summarize and Meta-analyze data from previously published Randomized Controlled Trials (RCTs). EVIDENCE ACQUISITION: Electronic databases: PubMed, Cochrane, Embase, Scopus, and Web of Science were searched. Data was extracted and the quality of the included studies was assessed. A random-effects DerSimonian Laird model was employed for meta-analysis. EVIDENCE SYNTHESIS: Fifteen RCTs were included in this study (NAC, N.=940; control, N.=935). In the NAC group, 16.38% developed POAF compared with 23.53% in the control group. NAC supplementation was associated with a decreased incidence of POAF in patients undergoing cardiothoracic surgery (RR 0.69; 95% CI 0.52, 0.91; P=0.008). Meta-regression of randomized trial data showed that the incidence of POAF was not related to the NAC dose (P=0.439). A subgroup analysis in terms of the time of NAC administration revealed that preoperative and postoperative NAC administration was the only subgroup that demonstrated a statistically significant difference (RR 0.48, 95% CI 0.32, 0.71; P=0.0003) compared with placebo and showed no heterogeneity. CONCLUSIONS: Atrial fibrillation is a significant postoperative complication, particularly in cardiothoracic surgery. This study highlights the need for further research on optimal NAC dosing and timing, with evidence suggesting that preoperative and postoperative NAC administration may significantly decrease postoperative atrial fibrillation in cardiothoracic surgery patients, although limitations and variability in study designs need to be considered.

Non-coding RNA yREX3 from human extracellular vesicles exerts macrophage-mediated cardioprotection via a novel gene-methylating mechanism.

BACKGROUND AND AIMS: Extracellular vesicles (EVs) secreted by cardiosphere-derived cells exert immunomodulatory effects through the transmission of small non-coding RNAs. METHODS: The mechanism and role of yREX3, a small Y RNA abundant in EVs in myocardial injury, was investigated. RESULTS: yREX3 attenuates cardiac ischaemic injury by selective DNA methylation. Synthetic yREX3 encapsulated in lipid nanoparticles triggers broad transcriptomic changes in macrophages, localizes to the nucleus, and mediates epigenetic silencing of protein interacting with C kinase-1 (Pick1) through methylation of upstream CpG sites. Moreover, yREX3 interacts with polypyrimidine tract binding protein 3 (PTBP3) to methylate the Pick1 gene locus in a DNA methyltransferase-dependent manner. Suppression of Pick1 in macrophages potentiates Smad3 signalling and enhances efferocytosis, minimizing heart necrosis in rats with myocardial infarction. Adoptive transfer of Pick1-deficient macrophages recapitulates the cardioprotective effects of yREX3 in vivo. CONCLUSIONS: These findings highlight the role of a small Y RNA mined from EVs with a novel gene-methylating mechanism.

Miconazole and phenothiazine hinder the quorum sensing regulated virulence in Pseudomonas aeruginosa.

Antibiotic resistance is a major health problem worldwide. Pseudomonas aeruginosa is a Gram-negative pathogen with an arsenal of virulence factors and elevated antimicrobial resistance. It is a leading cause of nosocomial infections with high morbidity and mortality. The significant time and effort required to develop new antibiotics can be circumvented using alternative therapeutic strategies, including anti-virulence targets. This study aimed to investigate the anti-virulence activity of the FDA-approved drugs miconazole and phenothiazine against P. aeruginosa. The phenotypic effect of sub-inhibitory concentrations of miconazole and phenothiazine on biofilm, pyocyanin, protease, rhamnolipid and hemolysin activities in PAO1 strain was examined. qRT-PCR was used to assess the effect of drugs on quorum-sensing genes that regulate virulence. Further, the anti-virulence potential of miconazole and phenothiazine was evaluated in silico and in vivo. Miconazole showed significant inhibition of Pseudomonas virulence by reducing biofilm-formation approximately 45-48%, hemolytic-activity by 59%, pyocyanin-production by 47-49%, rhamnolipid-activity by approximately 42-47% and protease activity by 36-40%. While, phenothiazine showed lower anti-virulence activity, it inhibited biofilm (31-35%), pyocyanin (37-39%), protease (32-40%), rhamnolipid (35-40%) and hemolytic activity (47-56%). Similarly, there was significantly reduced expression of RhlR, PqsR, LasI and LasR following treatment with miconazole, but less so with phenothiazine. In-silico analysis revealed that miconazole had higher binding affinity than phenothiazine to LasR, RhlR, and PqsR QS-proteins. Furthermore, there was 100% survival in mice injected with PAO1 treated with miconazole. In conclusion, miconazole and phenothiazine are promising anti-virulence agents for P. aeruginosa.

Integrating sustainability into higher education challenges and opportunities for universities worldwide.

This paper undertakes a comprehensive investigation into incorporating sustainability within higher education, aligning with the United Nations' Sustainable Development Goals (SDGs). Utilizing quantitative and qualitative research methods, our study delves into the status quo, methodologies, and impacts of sustainability education across a spectrum of international and local settings, with a specific lens on the United Arab Emirates. Our analysis spans various topics, from best practices in sustainability integration and educational frameworks to the influence of global initiatives like the Impact Ranking on promoting SDG-aligned transformations within academic institutions. Highlighting case studies from the UAE, we provide concrete evidence of successful sustainability strategies and interventions. These are juxtaposed with a global overview that uncovers the varying challenges and opportunities present in implementing sustainability education worldwide. Among our key findings is the essential role of interdisciplinary approaches and the critical need for active faculty involvement in fostering sustainability education. Drawing from a rich compilation of data and narratives, the paper presents a set of strategic recommendations designed to enhance the efficacy and reach of sustainability education. These recommendations are informed by the challenges observed and the success stories identified during our investigation. Ultimately, our research underscores the indispensable role that higher education plays in preparing future generations to navigate and address the complexities of sustainability challenges effectively.

Fabrication and characterization of a new eco-friendly sulfonamide-chitosan derivative with enhanced antimicrobial and selective cytotoxicity properties.

Chitosan (CH) exhibits low antimicrobial activity. This study addresses this issue by modifying the chitosan with a sulfonamide derivative, 3-(4-(N,N-dimethylsulfonyl)phenyl)acrylic acid. The structure of the sulfonamide-chitosan derivative (DMS-CH) was confirmed using Fourier transform infrared spectroscopy and Nuclear magnetic resonance. The results of scanning electron microscopy, thermal gravimetric analysis, and X-ray diffraction indicated that the morphology changed to a porous nature, the thermal stability decreased, and the crystallinity increased in the DMS-CH derivative compared to chitosan, respectively. The degree of substitution was calculated from the elemental analysis data and was found to be moderate (42%). The modified chitosan exhibited enhanced antimicrobial properties at low concentrations, with a minimum inhibitory concentration (MIC) of 50 µg/mL observed for B. subtilis and P. aeruginosa, and a value of 25 µg/mL for S. aureus, E. coli, and C. albicans. In the case of native chitosan, the MIC values doubled or more, with 50 µg/mL recorded for E. coli and C. albicans and 100 µg/mL recorded for B. subtilis, S. aureus, and P. aeruginosa. Furthermore, toxicological examinations conducted on MCF-7 (breast adenocarcinoma) cell lines demonstrated that DMS-CH exhibited greater toxicity (IC50 = 225.47 µg/mL) than pure CH, while still maintaining significant safety limits against normal lung fibroblasts (WI-38). Collectively, these results suggest the potential use of the newly modified chitosan in biomedical applications.

Molecular Biomarkers and Signaling Pathways of Cancer Stem Cells in Colorectal Cancer.

Colorectal cancer (CRC) is the third most frequently found cancer in the world, and it is frequently discovered when it is already far along in its development. About 20% of cases of CRC are metastatic and incurable. There is more and more evidence that colorectal cancer stem cells (CCSCs), which are in charge of tumor growth, recurrence, and resistance to treatment, are what make CRC so different. Because we know more about stem cell biology, we quickly learned about the molecular processes and possible cross-talk between signaling pathways that affect the balance of cells in the gut and cancer. Wnt, Notch, TGF-ß, and Hedgehog are examples of signaling pathway members whose genes may change to produce CCSCs. These genes control self-renewal and pluripotency in SCs and then decide the function and phenotype of CCSCs. However, in terms of their ability to create tumors and susceptibility to chemotherapeutic drugs, CSCs differ from normal stem cells and the bulk of tumor cells. This may be the reason for the higher rate of cancer recurrence in patients who underwent both surgery and chemotherapy treatment. Scientists have found that a group of uncontrolled miRNAs related to CCSCs affect stemness properties. These miRNAs control CCSC functions like changing the expression of cell cycle genes, metastasis, and drug resistance mechanisms. CCSC-related miRNAs mostly control signal pathways that are known to be important for CCSC biology. The biomarkers (CD markers and miRNA) for CCSCs and their diagnostic roles are the main topics of this review study.

Multidrug-resistance and extended-spectrum beta-lactamase-producing lactose-fermenting enterobacteriaceae in the human-dairy interface in northwest Ethiopia.

BACKGROUND: Antimicrobial resistance (AMR) is among the top public health concerns in the globe. Estimating the prevalence of multidrug resistance (MDR), MDR index (MDR-I) and extended-spectrum beta-lactamase (ESBL)-producing lactose fermenting Enterobacteriaceae (LFE) is important in designing strategies to combat AMR. Thus, this study was designed to determine the status of MDR, MDR-I and ESBL-producing LFE isolated from the human-dairy interface in the northwestern part of Ethiopia, where such information is lacking. METHODOLOGY: A cross-sectional study was conducted from June 2022 to August 2023 by analyzing 362 samples consisting of raw pooled milk (58), milk container swabs (58), milker's hand swabs (58), farm sewage (57), milker's stool (47), and cow's feces (84). The samples were analyzed using standard bacteriological methods. The antimicrobial susceptibility patterns and ESBL production ability of the LFE isolates were screened using the Kirby-Bauer disk diffusion method, and candidate isolates passing the screening criteria were phenotypically confirmed by using cefotaxime (30 µg) and cefotaxime /clavulanic acid (30 µg/10 µg) combined-disk diffusion test. The isolates were further characterized genotypically using multiplex polymerase chain reaction targeting the three ESBL-encoding- genes namely blaTEM, blaSHV, and blaCTX-M. RESULTS: A total of 375 bacterial isolates were identified and the proportion of MDR and ESBL-producing bacterial isolates were 70.7 and 21.3%, respectively. The MDR-I varied from 0.0 to 0.81 with an average of 0.30. The ESBL production was detected in all sample types. Genotypically, the majority of the isolates (97.5%), which were positive on the phenotypic test, were carrying one or more of the three genes. CONCLUSION: A high proportion of the bacterial isolates were MDR; had high MDR-I and were positive for ESBL production. The findings provide evidence that the human-dairy interface is one of the important reservoirs of AMR traits. Therefore, the implementation of AMR mitigation strategies is highly needed in the area.

Oral bioavailability of a noncoding RNA drug, TY1, that acts on macrophages.

All approved RNA therapeutics require parenteral delivery. Here we demonstrate an orally bioavailable formulation wherein synthetic noncoding (nc) RNA, packaged into lipid nanoparticles, is loaded into casein-chitosan (C2) micelles. We used the C2 formulation to deliver TY1, a 24-nucleotide synthetic ncRNA which targets the DNA damage response pathway in macrophages. C2-formulated TY1 (TY1C2) efficiently packages and protects TY1 against degradative enzymes. In healthy mice, oral TY1C2 was well-tolerated and nontoxic. Oral TY1C2 exhibited disease-modifying bioactivity in 2 models of tissue injury: 1) rat myocardial infarction, where a single oral dose of TY1C2 was cardioprotective, on par with intravenously-delivered TY1; and 2) mouse acute lung injury, where a single dose of TY1C2 attenuated pulmonary inflammation. Mechanistic dissection revealed that TY1C2 is not absorbed into the systemic circulation but is, instead, taken up by intestinal macrophages, namely those of the lamina propria and Peyer's patches. This route of absorption may rationalize why an antisense oligonucleotide against Factor VII, which acts on hepatocytes, is not effective when administered in the C2 formulation. Thus, some (but not all) ncRNA drugs are bioavailable when delivered by mouth. Oral RNA delivery and uptake, relying on uptake via the gastrointestinal immune system, has broad-ranging therapeutic implications.

Techno-economic and environmental analysis for the application of renewable energy sources in seaports.

Ports have an indisputable effect on the decarbonization of urban areas, helping to minimize air and environmental pollution and achieve sustainable development. In this instance, it is crucial to do research that can advance our understanding of how to increase ports' energy independence by utilizing renewable energy sources. The current study aims to study the environmental benefits and techno-economic challenges of converting three Egyptian ports to eco-friendly green ports by using solar panels, offshore wind turbines, and hydrogen fuel cells. The study shows that from a technical point of view, the required green power to be installed at Alexandria, Port Said, and Suez ports is around 13 MW, 5 MW, and 1.5 MW, respectively. Furthermore, the environmental analysis findings demonstrate that integrating green energy will significantly lower emissions in seaports. It is anticipated that the ports of Alexandria, Port Said, and Suez will achieve annual reductions in carbon dioxide emissions of roughly 68,7 k-tons, 25,8 k-tons, and 6,4 k-tons, respectively. From an economic point of view, the ports could be supplied with green energy from wind turbines for a cost of between 0.115 and 0.125 USD/kWh, while solar panels have a cost range of 0.098 to 0.129 USD/kWh. Additionally, hydrogen fuel cell systems cost about 0.102 USD/kWh.

Transcriptome Profiling of a Salt Excluder Hybrid Grapevine Rootstock 'Ruggeri' throughout Salinity.

Salinity is one of the substantial threats to plant productivity and could be escorted by other stresses such as heat and drought. It impairs critical biological processes, such as photosynthesis, energy, and water/nutrient acquisition, ultimately leading to cell death when stress intensity becomes uncured. Therefore, plants deploy several proper processes to overcome such hostile circumstances. Grapevine is one of the most important crops worldwide that is relatively salt-tolerant and preferentially cultivated in hot and semi-arid areas. One of the most applicable strategies for sustainable viticulture is using salt-tolerant rootstock such as Ruggeri (RUG). The rootstock showed efficient capacity of photosynthesis, ROS detoxification, and carbohydrate accumulation under salinity. The current study utilized the transcriptome profiling approach to identify the molecular events of RUG throughout a regime of salt stress followed by a recovery procedure. The data showed progressive changes in the transcriptome profiling throughout salinity, underpinning the involvement of a large number of genes in transcriptional reprogramming during stress. Our results established a considerable enrichment of the biological process GO-terms related to salinity adaptation, such as signaling, hormones, photosynthesis, carbohydrates, and ROS homeostasis. Among the battery of molecular/cellular responses launched upon salinity, ROS homeostasis plays the central role of salt adaptation.

Genome-Wide Association Study of Rice Diversity Panel Reveals New QTLs for Tolerance to Water Deficit Under the Egyptian Conditions.

Drought has a significant impact on rice yield by restricting the crop's ability to grow and develop. Producing rice cultivars adapted to water deficit conditions is still the main interest of rice breeders and geneticists. To address this challenge, a set of 413 highly diverse rice populations were evaluated under normal and water deficit conditions for two growing seasons of 2021 and 2022. High genetic variation was found among genotypes for all studied traits. The heritability estimates ranged from 0.82 (panicle length) to 0.95 (plant height). Sterility percentage (SET%) was the most trait affected by water deficit in two growing seasons. 22 Rice genotypes were classified as drought tolerant in both years. Genome-wide association mapping was performed for all traits in the two growing seasons under both conditions using a total of 700,000 SNPs. The GWAS results revealed important and major SNPs associated with all traits. 26 Significant SNPs with stable allele effects were found to be associated with yield traits under water deficit conditions in both years. The results of this study provided rice genotypes that can be adapted under water deficit conditions and important stable SNP markers that can be used for marker-assisted selection after validation in different genetic backgrounds.

Revisiting Metal-Organic Frameworks Porosimetry by Positron Annihilation: Metal Ion States and Positronium Parameters.

Metal-organic frameworks (MOFs) stand as pivotal porous materials with exceptional surface areas, adaptability, and versatility. Positron Annihilation Lifetime Spectroscopy (PALS) is an indispensable tool for characterizing MOF porosity, especially micro- and mesopores in both open and closed phases. Notably, PALS offers porosity insights independent of probe molecules, which is vital for detailed characterization without structural transformations. This study explores how metal ion states in MOFs affect PALS results. We find significant differences in measured porosity due to paramagnetic or oxidized metal ions compared to simulated values. By analyzing CPO-27(M) (M = Mg, Co, Ni), with identical pore dimensions, we observe distinct PALS data alterations based on metal ions. Paramagnetic Co and Ni ions hinder and quench positronium (Ps) formation, resulting in smaller measured pore volumes and sizes. Mg only quenches Ps, leading to underestimated pore sizes without volume distortion. This underscores the metal ions' pivotal role in PALS outcomes, urging caution in interpreting MOF porosity.

Examining the contribution of Notch signaling to lung disease development.

Notch pathway is a widely observed signaling system that holds pivotal functions in regulating various developmental cellular functions and operations. The Notch signaling mechanism is crucial for lung homeostasis, damage, and restoration. Based on increasing evidence, the Notch pathway has been identified, as critical for fibrosis and subsequently, the development of chronic fibroproliferative conditions in various organs and tissues. Recent research indicates that deregulation of Notch signaling correlates with the pathogenesis of significant pulmonary conditions, particularly chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, asthma, pulmonary arterial hypertension (PAH), lung carcinoma, and pulmonary abnormalities in some hereditary disorders. In various cellular and tissue environments, and across both physiological and pathological conditions, multiple consequences of Notch activation have been observed. Studies have ascertained that the Notch signaling cascade exhibits close associations with various other signaling systems. This study provides an updated overview of Notch signaling's role, especially its link to fibrosis and its potential therapeutic implications. This study sheds light on the latest findings regarding the mechanisms and outcomes of irregular or lacking Notch activity in the onset and development of pulmonary diseases. As our insight into this signaling mechanism suggests that modulating Notch signaling might hold potential as a valuable additional therapeutic approach in upcoming research.

Untargeted metabolomics unveiled the role of butanoate metabolism in the development of Pseudomonas aeruginosa hypoxic biofilm.

Pseudomonas aeruginosa is a versatile opportunistic pathogen which causes a variety of acute and chronic human infections, some of which are associated with the biofilm phenotype of the pathogen. We hypothesize that defining the intracellular metabolome of biofilm cells, compared to that of planktonic cells, will elucidate the metabolic pathways and biomarkers indicative of biofilm inception. Disc-shaped stainless-steel coupons (12.7 mm diameter) were employed as a surface for static biofilm establishment. Each disc was immersed in a well, of a 24-well microtiter plate, containing a 1-mL Lysogeny broth (LB) suspension of P. aeruginosa ATCC 9027, a strain known for its biofilm prolificacy. This setup underwent oxygen-depleted incubation at 37°C for 24 hours to yield hypoxic biofilms and the co-existing static planktonic cells. In parallel, another planktonic phenotype of ATCC 9027 was produced in LB under shaking (200 rpm) incubation at 37°C for 24 hours. Planktonic and biofilm cells were harvested, and the intracellular metabolites were subjected to global untargeted metabolomic analysis using LC-MS technology, where small metabolites (below 1.5 kDa) were selected. Data analysis showed the presence of 324 metabolites that differed (p < 0.05) in abundance between planktonic and biofilm cells, whereas 70 metabolites did not vary between these phenotypes (p > 0.05). Correlation, principal components, and partial least square discriminant analyses proved that the biofilm metabolome is distinctly clustered away from that of the two planktonic phenotypes. Based on the functional enrichment analysis, arginine and proline metabolism were enriched in planktonic cells, but butanoate metabolism was enriched in biofilm cells. Key differential metabolites within the butanoate pathway included acetoacetate, 2,3-butandiol, diacetyl, and acetoin, which were highly upregulated in the biofilm compared to the planktonic cells. Exogenous supplementation of acetoin (2 mM), a critical metabolite in butanoate metabolism, augmented biofilm mass, increased the structural integrity and thickness of the biofilm, and maintained the intracellular redox potential by balancing NADH/NAD+ ratio. In conclusion, P. aeruginosa hypoxic biofilm has a specialized metabolic landscape, and butanoate pathway is a metabolic preference and possibly required for promoting planktonic cells to the biofilm state. The butanoate pathway metabolites, particularly acetoin, could serve as markers for biofilm development.

A novel micropeptide, Slitharin, exerts cardioprotective effects in myocardial infarction.

PURPOSE: Micropeptides are an emerging class of proteins that play critical roles in cell signaling. Here, we describe the discovery of a novel micropeptide, dubbed slitharin (Slt), in conditioned media from Cardiosphere-derived cells (CDCs), a therapeutic cardiac stromal cell type. EXPERIMENTAL DESIGN: We performed mass spectrometry of peptide-enriched fractions from the conditioned media of CDCs and a therapeutically inert cell type (human dermal fibrobasts). We then evaluated the therapeutic capacity of the candidate peptide using an in vitro model of cardiomyocyte injury and a rat model of myocardial infarction. RESULTS: We identified a novel 24-amino acid micropeptide (dubbed Slitharin [Slt]) with a non-canonical leucine start codon, arising from long intergenic non-coding (LINC) RNA 2099. Neonatal rat ventricular myocytes (NRVMs) exposed to Slt were protected from hypoxic injury in vitro compared to a vehicle or scrambled control. Transcriptomic analysis of cardiomyocytes exposed to Slt reveals cytoprotective capacity, putatively through regulation of stress-induced MAPK-ERK. Slt also exerted cardioprotective effects in rats with myocardial infarction as shown by reduced infarct size 48 h post-injury. Conclusions and clinical relavance: Thus, Slt is a non-coding RNA-derived micropeptide, identified in the extracellular space, with a potential cardioprotective function.

Spinal intramedullary schwannoma: Report of two cases with review of the literature.

INTRODUCTION: Spinal tumors comprise 15 % of all central nervous system tumors, with schwannomas accounting for 30 % of primary intraspinal neoplasms. While predominantly extramedullary-intradural, spinal schwannomas rarely manifest intramedullary occurrences (0.3 % of intraspinal tumors). This study sheds light on two rare cases of thoracic intramedullary schwannomas, emphasizing their diagnostic complexities and surgical management, alongside a literature review. CASE PRESENTATION: Case 1 involves a 50-year-old female presenting with worsening back pain, right lower limb weakness, and urinary incontinence. MRI revealed an intradural intramedullary soft tissue mass, diagnosed as a schwannoma with an associated organizing hematoma. Surgical removal led to gradual improvement. Case 2 features a 25-year-old male with back pain, partial foot drop, and weakness in the right knee and hip. MRI demonstrated an intradural intramedullary lesion, later confirmed as an intradural intramedullary schwannoma. Surgery resulted in a smooth recovery without adverse effects. DISCUSSION: This article presents two cases of intradural intramedullary thoracic schwannomas initially misdiagnosed as astrocytomas. Surgical resection confirmed the diagnosis, underscoring challenges in preoperative MRI diagnosis. The review of 174 reported cases reveals an equal distribution between the cervical and thoracic regions, with males affected 1.5 times more frequently than females. The average age of onset is 40, and surgical treatment demonstrates a 90 % improvement rate. The complex pathogenesis encompasses six proposed explanations. Clinical suspicion, considering pain and neurological symptoms, is paramount due to potential misdiagnosis and the imperative for histological confirmation. CONCLUSION: Although rare, intramedullary schwannomas (IMS) have significant clinical implications, necessitating precise treatment. Surgical resection yields favorable outcomes, with subtotal resection considered based on adhesion factors. Pre-surgical diagnosis requires a comprehensive integration of radiological and clinical data, with intraoperative analysis ensuring optimal treatment strategies.