Gynecological cancer tumor Microenvironment: Unveiling cellular complexity and therapeutic potential.

Gynecological cancers, including ovarian, cervical, endometrial, and vulvar cancers, present significant challenges in diagnosis and treatment globally. The tumor microenvironment (TME) plays a pivotal role in cancer progression and therapy response, necessitating a deeper understanding of its composition and dynamics. This review offers a comprehensive overview of the gynecological cancer tumor microenvironment, emphasizing its cellular complexity and therapeutic potential. The diverse cellular components of the TME, including cancer cells, immune cells, stromal cells, and extracellular matrix elements, are explored, elucidating their interplay in shaping tumor behavior and treatment outcomes. Across various stages of cancer progression, the TME exerts profound effects on tumor heterogeneity, immune modulation, angiogenesis, and metabolic reprogramming. The urgency for novel therapeutic strategies is underscored by understanding immune evasion mechanisms within the TME. Emerging approaches such as immunotherapy, stromal-targeting therapies, anti-angiogenic agents, and metabolic inhibitors are discussed, offering promising avenues for improving patient outcomes. Interdisciplinary collaborations and translational research are emphasized, aiming to advance precision oncology and enhance therapeutic efficacy in gynecological cancers.

Cardiovascular disease and covid-19: A systematic review.

Background: Cardiovascular complications of COVID-19 are numerous and aspects of this phenomenon are not well known. The main objective of this manuscript is a systematic review of the acute and chronic cardiovascular complications secondary to COVID-19. Methods: A systematic review of the literature through Medline via PubMed was conducted (2020-2024). Results: There is a plethora of effects of COVID-19 on the heart in the acute setting. Here we discuss pathophysiology, myocardial infarctions, heart failure, Takotsubo Cardiomyopathy, myocardial injury, myocarditis and arrhythmias that are caused by COVID-19. Additionally, these cardiovascular injuries can linger and may be an underlying cause of some Long COVID symptoms. Conclusions: Cardiovascular complications of COVID-19 are numerous and life-threatening. Long COVID can affect cardiovascular health. Microclotting induced by SARS-CoV-2 infection could be a therapeutic target for some aspects of Long Covid.

Implementation Strategies for Maternal Near-Miss Case Reviews in LICs and LMICs: A scoping review protocol.

Background: Maternal mortality remains a persistent public health concern despite significant strides in reduction over the past few decades, with a global maternal mortality ratio (MMR) of 223 deaths per 100,000 live births in 2020, indicating a 34.3% decline over 20 years, with Low income countries (LICs) and Lower Middle-Income Countries (LMICs) bearing the major burden. Effective implementation of facility-based near-miss case reviews (NMCR), endorsed by the World Health Organization (WHO), faces challenges hindering progress, making exploring implementation strategies through a scoping review essential. This scoping review aims to identify and characterize implementation strategies employed in Low and Lower Middle- Income Countries to facilitate the implementation of facility-based NMCR. Methods: The scoping review will follow Arksey and O'Malley's methodological framework, involving five stages: identifying the research question, selecting relevant studies, selecting data, charting, and summarizing the results. Electronic databases like PubMed, Embase, Web of Science, EBSCOhost - CINAHL Ultimate, and Ovid MEDLINE will be searched, supplemented by citation tracking. Rayyan will be used to screen and remove duplicates, with data charting conducted using Google Sheets. Two independent reviewers will conduct blinded screening, eligibility assessment, and inclusion phases. Reviewers will conduct Systematic data extraction independently using piloted forms, with discrepancies resolved through team discussion and consensus. Results: The review will identify and characterize implementation strategies employed to facilitate the implementation of facility-based near-miss case reviews in LICs and LMICs. Conclusions: The findings of this review will contribute to the understanding of implementing strategies for facility-based NMCR in LICs and LMICs. The review can help in designing interventions/programs to reduce maternal mortality and knowledge products.

Enhancing carboplatin sensitivity in ovarian cancer cells by blocking the mercapturic acid pathway transporter.

RLIP acts as a transporter that responds to stress and provides protection, specifically against glutathione-electrophile conjugates and xenobiotic toxins. Its increased presence in malignant cells, especially in cancer, emphasizes its crucial anti-apoptotic function. This is achieved by selectively regulating the cellular levels of pro-apoptotic oxidized lipid byproducts. Suppressing the progression of tumors in human xenografts can be achieved by effectively inhibiting RLIP, a transporter in the mercapturic acid pathway, without involving chemotherapy. Utilizing ovarian cancer (OC) cell lines (MDAH2774, OVCAR4, and OVCAR8), we observed that agents targeting RLIP, such as RLIP antisense and RLIP antibodies, not only substantially impeded the viability of OC cells but also remarkably increased their sensitivity to carboplatin. To delve further into the cytotoxic synergy between RLIP antisense, RLIP antibodies, and carboplatin, we conducted investigations in both cell culture and xenografts of OC cells. The outcomes revealed that RLIP depletion via phosphorothioate antisense led to rapid and sustained remissions in established subcutaneous human ovary xenografts. Furthermore, RLIP inhibition by RLIP antibodies exhibited comparable efficacy to antisense and enhanced the effectiveness of carboplatin in MDAH2774 OC xenografts. These investigations underscore RLIP as a central carrier crucial for supporting the survival of cancer cells, positioning it as a suitable focus for cancer treatment.

Clinical management of typical and atypical carcinoids/neuroendocrine tumors in ENETS centres of excellence (CoE): Survey from the ENETS lung NET task force.

Lung carcinoid tumours are neuroendocrine neoplasms originating from the bronchopulmonary tract's neuroendocrine cells, accounting for only 1%-3% of all lung cancers but 30% of all neuroendocrine tumours. The incidence of lung carcinoids, both typical and atypical, has been increasing over the years due to improved diagnostic methods and increased awareness among clinicians and pathologists. The most recent WHO classification includes a subgroup of lung carcinoids with atypical morphology and higher mitotic count and/or Ki67 labelling index. Despite appropriate surgery, the 5-year survival rate for atypical carcinoids barely exceeds 50%-70%. The role of adjuvant therapy in lung carcinoids is not well-defined, and clinical decisions are generally based on the presence of high-risk features. Long-term follow-up is essential to monitor for recurrence, although the optimal follow-up protocol remains unclear. To address the lack of consensus in clinical management decisions, the European Neuroendocrine Tumor Society (ENETS) initiated a survey among 20 expert centres. The survey identified varied opinions on approaches to imaging, surgery, use of adjuvant therapy, and follow-up protocols. Notably, the absence of dedicated multidisciplinary lung neuroendocrine tumour boards in some centres was evident. Experts agreed on the need for a prospective adjuvant trial in high-risk patients, emphasizing the feasibility of such a study. In conclusion, the study highlights the need for a more uniform adoption of existing guidelines in the management of lung carcinoid tumours and emphasizes the importance of international collaboration to advance research and patient care. Close collaboration between healthcare providers and patients is vital for effective long-term surveillance and management of these rare tumours.

Stromal cartilage oligomeric matrix protein as a tumorigenic driver in ovarian cancer via Notch3 signaling and epithelial-to-mesenchymal transition.

BACKGROUND: Cartilage oligomeric matrix protein (COMP), an extracellular matrix glycoprotein, is vital in preserving cartilage integrity. Further, its overexpression is associated with the aggressiveness of several types of solid cancers. This study investigated COMP's role in ovarian cancer, exploring clinicopathological links and mechanistic insights. METHODS: To study the association of COMP expression in cancer cells and stroma with clinicopathological features of ovarian tumor patients, we analyzed an epithelial ovarian tumor cohort by immunohistochemical analysis. Subsequently, to study the functional mechanisms played by COMP, an in vivo xenograft mouse model and several molecular biology techniques such as transwell migration and invasion assay, tumorsphere formation assay, proximity ligation assay, and RT-qPCR array were performed. RESULTS: Based on immunohistochemical analysis of epithelial ovarian tumor tissues, COMP expression in the stroma, but not in cancer cells, was linked to worse overall survival (OS) of ovarian cancer patients. A xenograft mouse model showed that carcinoma-associated fibroblasts (CAFs) expressing COMP stimulate the growth and metastasis of ovarian tumors through the secretion of COMP. The expression of COMP was upregulated in CAFs stimulated with TGF-ß. Functionally, secreted COMP by CAFs enhanced the migratory capacity of ovarian cancer cells. Mechanistically, COMP activated the Notch3 receptor by enhancing the Notch3-Jagged1 interaction. The dependency of the COMP effect on Notch was confirmed when the migration and tumorsphere formation of COMP-treated ovarian cancer cells were inhibited upon incubation with Notch inhibitors. Moreover, COMP treatment induced epithelial-to-mesenchymal transition and upregulation of active ß-catenin in ovarian cancer cells. CONCLUSION: This study suggests that COMP secretion by CAFs drives ovarian cancer progression through the induction of the Notch pathway and epithelial-to-mesenchymal transition.

Strong Carbon Layer-Encapsulated Cobalt Tin Sulfide-Based Nanoporous Material as a Bifunctional Electrocatalyst for Zinc-Air Batteries.

Global demands for cost-effective, durable, highly active, and bifunctional catalysts for metal-air batteries are tremendously increasing in scientific research fields. In this work, a strategy for the rational fabrication of carbon layer-encapsulated cobalt tin sulfide nanopores (CoSnOH/S@C NPs) material as a bifunctional electrocatalyst for rechargeable zinc (Zn)-air batteries by a cost-effective and facile two-step hydrothermal method is reported. Moreover, the effect of metal elements on the morphology of CoSnOH nanodisks material via the hydrothermal method is investigated. Owing to its excellent nanostructure, exclusive porous network, and high specific surface area, the optimized CoSnOH/S@C NPs material reveals superior catalytic properties. The as-prepared CoSnOH/S@C NPs electrocatalyst reveals better properties of oxygen reduction reaction (half-wave potential of -0.88 V vs reversible hydrogen electrode) and oxygen evolution reaction (overpotential of 137 mV at 10 mA cm-2) when compared with commercial Pt/C and IrO2 catalyst materials. Most significantly, the CoSnO/S@C NPs-based Zn-air battery exhibits more excellent cycling stability than the Pt/C+IrO2 catalyst-based one. Consequently, the proposed material provides a new route for fabricating more active and stable multifunctional catalyst materials for energy conversion and storage systems.

SIRT1 mediates breast cancer development and tumorigenesis controlled by estrogen-related receptor ß.

Silent mating type information regulation 2 homolog 1 (SIRT1) is a class III histone deacetylase (HDAC) that is NAD + dependent and essential for metabolism, senescence, and cell survival. SIRT1 is overexpressed in several cancers, including breast cancer. SIRT1 is a well-known target gene of the estrogen receptor alpha (ER alpha) and is closely related to ER alpha deacetylation. Transcription factor Estrogen-related receptors (ERRs) share sequence homology with ERs in the DNA-binding domain, therefore, the possibility of sharing target genes between them is high. Our current research aims to gain insight into the function of ERRß in regulating the activity of SIRT1 during the progression of breast cancer. ER-positive (ER + ve) breast cancer cells and tissues had considerably enhanced SIRT1 expression. Six potential ERRE sites were identified by analysis of the 5' upstream region of SIRT1, and both in vitro and in vivo experiments supported their presence. We found SIRT1 to be up-regulated in ERRß overexpressed ER + ve breast cancer cells. Furthermore, our findings suggested that ectopic production of ERR and PCAF would increase SIRT1 activity. Our findings also indicated that ectopic production of ERRß and PCAF increased SIRT1 activity. With sufficient evidence demonstrating the substantial involvement of SIRT1 in cell proliferation, migration, and colony formation capability, we were also able to illustrate the tumorigenic role of SIRT1. Overall, our findings highlight SIRT1's tumorigenic influence on breast cancer and suggest that SIRT1 inhibitors might serve as potential therapeutic drugs for the treatment of breast cancer.

Association between serum osteocalcin and atherosclerosis in Type-2 diabetes mellitus: a cross-sectional study.

BACKGROUND: The past few decades have seen a marked increase in the macrovascular complications of Type-2 diabetes mellitus (T2DM) such as coronary heart disease, peripheral arterial disease, and cerebrovascular disease. This has been predominantly attributed to the increased atherosclerosis in these patients. Atherosclerosis usually remains an asymptomatic condition and this poses a significant challenge in its early diagnosis and timely intervention. Hence, there is an immediate need for exploring novel tools to aid in the early detection of atherosclerosis, especially in T2DM patients. Osteocalcin (OC), synthesized by osteoblasts, is a protein hormone found in the skeletal system. This protein is considered as a marker for bone density and in recent times has been gaining interest due to its protective role in cerebrovascular diseases(CVD). METHODS: We conducted a cross-sectional study and evaluated the association between serum OC levels and atherosclerosis in 113 T2DM patients. Carotid intima-media thickness (CC-IMT) was used as an estimate of atherosclerosis and patients were divided into two groups (CC-IMT < 0.9 and ≥ 0.9). Correlation of serum OC levels and glycemic parameters and lipid profiles were studied and compared between both groups. RESULTS: There is a significant negative correlation between the CC-IMT estimates and serum OC levels. CC-IMT also has a significant association with other biochemical parameters such as fasting blood sugar, glycated hemoglobin and high-density lipoprotein. CONCLUSION: Although the independent association of serum OC could not be established in the T2DM patient population, overall, the results favor low serum OC as a prognostic marker for atherosclerosis.

Tumor cell p38 inhibition to overcome immunotherapy resistance.

Patients with tumors that do not respond to immune-checkpoint inhibition often harbor a non-T cell-inflamed tumor microenvironment, characterized by the absence of IFN-γ-associated CD8+ T cell and dendritic cell activation. Understanding the molecular mechanisms underlying immune exclusion in non-responding patients may enable the development of novel combination therapies. p38 MAPK is a known regulator of dendritic and myeloid cells however a tumor-intrinsic immunomodulatory role has not been previously described. Here we identify tumor cell p38 signaling as a therapeutic target to potentiate anti-tumor immunity and overcome resistance to immune-checkpoint inhibitors (ICI). Molecular analysis of tumor tissues from patients with human papillomavirus-negative head and neck squamous carcinoma reveals a p38-centered network enriched in non-T cell-inflamed tumors. Pan-cancer single-cell RNA analysis suggests that p38 activation may be an immune-exclusion mechanism across multiple tumor types. P38 knockdown in cancer cell lines increases T cell migration, and p38 inhibition plus ICI in preclinical models shows greater efficacy compared to monotherapies. In a clinical trial of patients refractory to PD1/L1 therapy, pexmetinib, a p38 inhibitor, plus nivolumab demonstrated deep and durable clinical responses. Targeting of p38 with anti-PD1 has the potential to induce the T cell-inflamed phenotype and overcome immunotherapy resistance.

Red Blood Cell Conservation and Use in the Cardiovascular Operating Rooms at Ben Taub General Hospital.

OBJECTIVES: A conservative hemoglobin transfusion threshold is noninferior to a liberal threshold in cardiac surgery. However, red blood cell (RBC) transfusion remains common during cardiac surgery. The authors' single-center, retrospective study aimed to decrease RBC transfusions for hemoglobin >7.5 g/dL in nonemergent cardiovascular surgeries utilizing cardiopulmonary bypass (CPB), by educating the anesthesiology and surgical staff on the benefits of a conservative threshold for transfusions, and incorporating the discussion and routine use of blood conservation methods for all nonemergent cardiac surgeries. DESIGN: This was a single-center, retrospective study that included all nonemergent coronary artery bypass grafting and single-valve cases utilizing CPB from January 2018 to December 2021 before and after the intervention in July 2019. SETTING: The data involved a single community hospital. PARTICIPANTS: A total of 417 patients were included in the study. INTERVENTIONS: The authors adopted a conservative threshold for blood transfusion and implemented a collaborative multidisciplinary approach to blood conservation. MEASUREMENTS AND MAIN RESULTS: Baseline patient characteristics were summarized, and the incidence of RBC transfusion before and after the intervention on July 26, 2019, were compared by Wilcoxon rank sum and chi-square tests. Multivariate logistic regression was used. The intervention was significantly associated with reduced RBC transfusion rate after adjusting for confounding variables (p < 0.05). The odds of receiving an RBC transfusion among patients after the intervention was 0.615 times the odds among patients before intervention (95% CI: 0.3913-0.9663). CONCLUSIONS: The authors' goal was to improve patient outcomes and the quality of perioperative care during cardiac surgery. By implementing a protocol and educating anesthesiologists, surgeons, and perfusionists, they successfully decreased the incidence of RBC transfusion above a hemoglobin of 7.5 g/dL.

A novel 3-miRNA network regulates tumour progression in oral squamous cell carcinoma.

BACKGROUND: Late diagnosis is one of the major confounders in oral squamous cell carcinoma (OSCC). Despite recent advances in molecular diagnostics, no disease-specific biomarkers are clinically available for early risk prediction of OSCC. Therefore, it is important to identify robust biomarkers that are detectable using non-invasive liquid biopsy techniques to facilitate the early diagnosis of oral cancer. This study identified potential salivary exosome-derived miRNA biomarkers and crucial miRNA-mRNA networks/underlying mechanisms responsible for OSCC progression. METHODS: Small RNASeq (n = 23) was performed in order to identify potential miRNA biomarkers in both tissue and salivary exosomes derived from OSCC patients. Further, integrated analysis of The Cancer Genome Atlas (TCGA) datasets (n = 114), qPCR validation on larger patient cohorts (n = 70) and statistical analysis with various clinicopathological parameters was conducted to assess the effectiveness of the identified miRNA signature. miRNA-mRNA networks and pathway analysis was conducted by integrating the transcriptome sequencing and TCGA data. The OECM-1 cell line was transfected with the identified miRNA signature in order to observe its effect on various functional mechanisms such as cell proliferation, cell cycle, apoptosis, invasive as well as migratory potential and the downstream signaling pathways regulated by these miRNA-mRNA networks. RESULTS: Small RNASeq and TCGA data identified 12 differentially expressed miRNAs in OSCC patients compared to controls. On validating these findings in a larger cohort of patients, miR-140-5p, miR-143-5p, and miR-145-5p were found to be significantly downregulated. This 3-miRNA signature demonstrated higher efficacy in predicting disease progression and clinically correlated with poor prognosis (p < 0.05). Transcriptome, TCGA, and miRNA-mRNA network analysis identified HIF1a, CDH1, CD44, EGFR, and CCND1 as hub genes regulated by the miRNA signature. Further, transfection-mediated upregulation of the 3-miRNA signature significantly decreased cell proliferation, induced apoptosis, resulted in G2/M phase cell cycle arrest and reduced the invasive and migratory potential by reversing the EMT process in the OECM-1 cell line. CONCLUSIONS: Thus, this study identifies a 3-miRNA signature that can be utilized as a potential biomarker for predicting disease progression of OSCC and uncovers the underlying mechanisms responsible for converting a normal epithelial cell into a malignant phenotype.

Audit of clinical follow-up and complications after acute pulmonary embolism in an Australian Metropolitan Health Service.

We explored post-pulmonary embolism (post-PE) follow-up at a large Australian regional city hospital health service. Over a 12-month period, we identified 195 (49% male) patients with a median age of 62 years. Post-PE follow-up was not organised for 23 patients and delayed for seven patients. Post-PE complication occurred in 21% of all patients reviewed in the clinic after discharge. Follow-up imaging was arranged in 28% of patients. To deliver high-quality care, we recommend implementing a local post-PE follow-up pathway, which balances individual physician preference with available resources and expert recommendations.

Single-night continuous positive airway pressure treatment improves blood fluid properties in individuals recently diagnosed with obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is a prevalent disorder that causes repetitive, temporary collapses of the upper airways during sleep, resulting in intermittent hypoxaemia and sleep fragmentation. Given those with OSA also exhibit decreased blood fluidity, this clinical population is at heightened risk for cardiovascular disease (CVD) development. Continuous positive airway pressure (CPAP) remains a primary therapy in OSA, which improves sleep quality and limits sleep fragmentation. While CPAP effectively ameliorates nocturnal hypoxic events and associated arousals, it remains unclear whether CVD risk factors are positively impacted. The aim of the present study was thus to assess the effects of an acute CPAP therapy on sleep quality and the physical properties of blood that determine blood fluidity. Sixteen participants with suspected OSA were recruited into the current study. Participants attended the sleep laboratory for two visits: an initial diagnostic visit that included confirmation of OSA severity and comprehensive assessments of blood parameters, followed by a subsequent visit where participants were administered an individualised, acute CPAP therapy session and had their blood assessments repeated. Holistic appraisal of blood rheological properties included assessment of blood and plasma viscosity, red blood cell (RBC) aggregation, deformability, and osmotic gradient ektacytometry. Acute CPAP treatment significantly improved sleep quality parameters, which were associated with decreased nocturnal arousals and improved blood oxygen saturation. Whole blood viscosity was significantly decreased following acute CPAP treatment, which might be explained by the improved RBC aggregation during this visit. Although an acute increase in plasma viscosity was observed, it appears that the alterations in RBC properties that mediate cell-cell aggregation, and thus blood viscosity, overcame the increased plasma viscosity. While deformability of RBC was unaltered, CPAP therapy had mild effects on the osmotic tolerance of RBC. Collectively, novel observations demonstrate that a single CPAP treatment session acutely improved sleep quality, which was accompanied by improved rheological properties.

Predicting seizure outcome after epilepsy surgery: Do we need more complex models, larger samples, or better data?

OBJECTIVE: The accurate prediction of seizure freedom after epilepsy surgery remains challenging. We investigated if (1) training more complex models, (2) recruiting larger sample sizes, or (3) using data-driven selection of clinical predictors would improve our ability to predict postoperative seizure outcome using clinical features. We also conducted the first substantial external validation of a machine learning model trained to predict postoperative seizure outcome. METHODS: We performed a retrospective cohort study of 797 children who had undergone resective or disconnective epilepsy surgery at a tertiary center. We extracted patient information from medical records and trained three models-a logistic regression, a multilayer perceptron, and an XGBoost model-to predict 1-year postoperative seizure outcome on our data set. We evaluated the performance of a recently published XGBoost model on the same patients. We further investigated the impact of sample size on model performance, using learning curve analysis to estimate performance at samples up to N = 2000. Finally, we examined the impact of predictor selection on model performance. RESULTS: Our logistic regression achieved an accuracy of 72% (95% confidence interval [CI] = 68%-75%, area under the curve [AUC] = .72), whereas our multilayer perceptron and XGBoost both achieved accuracies of 71% (95% CIMLP = 67%-74%, AUCMLP = .70; 95% CIXGBoost own = 68%-75%, AUCXGBoost own = .70). There was no significant difference in performance between our three models (all p > .4) and they all performed better than the external XGBoost, which achieved an accuracy of 63% (95% CI = 59%-67%, AUC = .62; pLR = .005, pMLP = .01, pXGBoost own = .01) on our data. All models showed improved performance with increasing sample size, but limited improvements beyond our current sample. The best model performance was achieved with data-driven feature selection. SIGNIFICANCE: We show that neither the deployment of complex machine learning models nor the assembly of thousands of patients alone is likely to generate significant improvements in our ability to predict postoperative seizure freedom. We instead propose that improved feature selection alongside collaboration, data standardization, and model sharing is required to advance the field.

Control over Charge Density by Tuning the Polyelectrolyte Type and Monomer Ratio in Saloplastic-Based Ion-Exchange Membranes.

Membranes based on polyelectrolyte complexes (PECs) can now be prepared through several sustainable, organic solvent-free approaches. A recently developed approach allows PECs made by stoichiometric mixing of polyelectrolytes to be hot-pressed into dense saloplastics, which then function as ion-exchange membranes. An important advantage of PECs is that tuning their properties can provide significant control over the properties of the fabricated materials, and thus over their separation properties. This work studies the effects of two key parameters─(a) ratio of mixing and (b) choice of polyelectrolytes─on the mechanical, material, and separation properties of their corresponding hot-pressed saloplastic-based ion-exchange membranes. By varying these two main parameters, charge density─the key property of any IEM─was found to be controllable. While studying several systems, including strong/strong, strong/weak, and weak/weak combinations of polyelectrolytes, it was observed that not all systems could be processed into saloplastic membranes. For the processable systems, expected trends were observed where a higher excess of one polyelectrolyte would lead to a more charged system, resulting in higher water uptake and better permselectivities. An anomaly was the polystyrenesulfonate-polyvinylamine system, which showed an opposite trend with a higher polycation ratio, leading to a more negative charge. Overall, we have found that it is possible to successfully fabricate saloplastic-based anion- and cation-exchange membranes with tunable charge densities through careful choice of polyelectrolyte combination and ratio of mixing.

Divergence of alternative sugar preferences through modulation of the expression and activity of the Gal3 sensor in yeast.

Optimized nutrient utilization is crucial for the progression of microorganisms in competing communities. Here we investigate how different budding yeast species and ecological isolates have established divergent preferences for two alternative sugar substrates: Glucose, which is fermented preferentially by yeast, and galactose, which is alternatively used upon induction of the relevant GAL metabolic genes. We quantified the dose-dependent induction of the GAL1 gene encoding the central galactokinase enzyme and found that a very large diversification exists between different yeast ecotypes and species. The sensitivity of GAL1 induction correlates with the growth performance of the respective yeasts with the alternative sugar. We further define some of the mechanisms, which have established different glucose/galactose consumption strategies in representative yeast strains by modulating the activity of the Gal3 inducer. (1) Optimal galactose consumers, such as Saccharomyces uvarum, contain a hyperactive GAL3 promoter, sustaining highly sensitive GAL1 expression, which is not further improved upon repetitive galactose encounters. (2) Desensitized galactose consumers, such as S. cerevisiae Y12, contain a less sensitive Gal3 sensor, causing a shift of the galactose response towards higher sugar concentrations even in galactose experienced cells. (3) Galactose insensitive sugar consumers, such as S. cerevisiae DBVPG6044, contain an interrupted GAL3 gene, causing extremely reluctant galactose consumption, which is, however, improved upon repeated galactose availability. In summary, different yeast strains and natural isolates have evolved galactose utilization strategies, which cover the whole range of possible sensitivities by modulating the expression and/or activity of the inducible galactose sensor Gal3.

Activated carbon based paste electrodes for the simultaneous and effective detection of divalent cadmium and lead ions in wastewater.

Heavy metals (HM) have gained significant attention in terms of regular monitoring and detection owing to their toxicity, non-biodegradability, and persistence. Current techniques for detecting HM are expensive, cumbersome, and require sophisticated instruments and skilled labour. Hence, developing cheap, rapid, energy-efficient, and accurate sensors is imperative and electrochemical techniques have emerged as promising tools. The current study involves the fabrication of an electrochemical sensor for the concurrent detection of lead (Pb2+) and cadmium (Cd2+) ions using modified carbon paste electrodes (mCPE). Activated carbon (AC) with a BET surface area of 1118 m2 g-1 was obtained by chemical activation and thermal treatment of the waste rubberwood sawdust. AC-Graphite, AC-Reduced Graphene Oxide (RGO), and AC-RGO-Chitosan were the types of mCPEs that were utilised. The electrochemical behaviours and effects of pH, concentration, and scan rate were studied using Cyclic voltammetry (CV). Studies on detection were conducted using CV and linear sweep voltammetry. Although all the 3 mCPEs detected Cd2+ and Pb2+ in the simulated wastewater, the CPE with RGO and AC could detect Cd2+ as low as 10.91 µg L-1 and Pb2+ as low as 14.01 µg L-1. The work explored the possibility of using AC as a potential sustainable substitute for graphite in CPE.