Diverse Pathways Research Articles

Pathways of Indian Students Transition Through Higher Education: Why do they differ?

Differential pathways followed by the students deserve more attention due to the development of school education in general and higher education in particular during the last two decades in India. Due to the consistent efforts by the Indian government at the school education level, students arriving at the doors of higher education institutions are no longer homogeneous. As a result, the diversity of students in higher education institutions leads towards diversification of pathways followed by the heterogeneous segments of students. There is a real shortage of studies which have researched the students’ differential pathways through higher education in general and specifically in the Indian context from the micro perspective. This study examines the decision-making process and differential trajectories followed by the students during the transition from secondary to higher education. The methodology of the present study involves a mixed-method approach and data was collected from a sample of 900 senior secondary students. A Self-structured questionnaire and semi-structured interviews were used for the collection of data. The findings reveal that the decision-making process of transition through higher education is complex and involves different stakeholders and timelines in the Indian context.

The Expression and Epigenetic Characteristics of the HSF2 Gene in Cattle-Yak and the Correlation with Its Male Sterility.

Aberrant expression of the heat shock proteins and factors was revealed to be closely associated with male reproduction. Heat shock factor 2 (HSF2) is a transcription factor that is involved in the regulation of diverse developmental pathways. However, the role and the corresponding molecular mechanism of HSF2 in male cattle-yak sterility are still poorly understood. Therefore, the aim of this study was to obtain the sequence and the biological information of the cattle-yak HSF2 gene and to investigate the spatiotemporal expression profiles of the locus during the development of cattle-yak testes. Additionally, the differential expression was analyzed between the cattle-yak and the yak, and the methylation of corresponding promoter regions was compared. Our results showed an additional 54 bp fragment and a missense mutation (lysine to glutamic acid) were presented in the cattle-yak HSF2 gene, which correlated with enriched expression in testicular tissue. In addition, the expression of the HSF2 gene showed dynamic changes during the growth of the testes, reaching a peak in adulthood. The IHC indicated that HSF2 protein was primarily located in spermatocytes (PS), spermatogonia (SP), and Sertoli cells (SC) in cattle-yak testes, compared with the corresponding cells of cattle and the yak. Furthermore, bisulfite-sequencing PCR (BSP) revealed that the methylated CpG sites in the promoter region of the cattle-yak HSF2 were more numerous than in the yak counterpart, which suggests hypermethylation of this region in the cattle-yak. Taken together, the low expression abundance and hypermethylation of HSF2 may underpin the obstruction of spermatogenesis, which leads to male cattle-yak infertility. Our study provided a basic guideline for the HSF2 gene in male reproduction and a new insight into the mechanisms of male cattle-yak sterility.

Understanding pathways from implementation to sustainment: a longitudinal, mixed methods analysis of promising practices implemented in the Veterans Health Administration

BackgroundThe Veterans Health Administration (VHA) is the United States largest learning health system. The Diffusion of Excellence (DoE) program is a large-scale model of diffusion that identifies and diffuses evidence-informed practices across VHA. During the period of 2016-2021, 57 evidence-informed practices were implemented across 82 VHA facilities. This setting provides a unique opportunity to understand sustainment determinants and pathways. Our objective was to characterize the longitudinal pathways of practices as they transition from initial implementation to long-term sustainment at each facility.MethodsA longitudinal, mixed-methods evaluation of 82 VHA facilities. Eighty-two facility representatives, chosen by leadership as points-of-contact for 57 DoE practices, were eligible for post-implementation interviews and annual sustainment surveys. Primary outcomes (implementation, sustainment), and secondary outcomes (institutionalization, effectiveness, anticipated sustainment) at four time-points were collected. We performed descriptive statistics and directed content analysis using Hailemariam et al.’s factors influencing sustainment.ResultsAfter approximately five years post-implementation (e.g., 2021 sustainment outcomes), of the 82 facilities, about one-third fully sustained their practice compared to one-third that did not fully sustain their practice because it was in a “liminal” stage (neither sustained nor discontinued) or permanently discontinued. The remaining one-third of facilities had missing 2021 sustainment outcomes. A higher percentage of facilities (70%) had inconsistent primary outcomes (changing over time) compared to facilities (30%) with consistent primary outcomes (same over time). Thirty-four percent of facilities with sustained practices reported resilience since they overcame implementation and sustainment barriers. Facilities with sustained practices reported more positive secondary outcomes compared to those that did not sustain their practice. Key factors facilitating practice sustainment included: demonstrating practice effectiveness/benefit, sufficient organizational leadership, sufficient workforce, and adaptation/alignment with local context. Key factors hindering practice sustainment included: insufficient workforce, not able to maintain practice fidelity/integrity, critical incidents related to the COVID-19 pandemic, organizational leadership did not support sustainment of practice, and no ongoing support.ConclusionsWe identified diverse pathways from implementation to sustainment, and our data underscore that initial implementation outcomes may not determine long-term sustainment outcomes. This longitudinal evaluation contributes to understanding impacts of the DoE program, including return on investment, achieving learning health system goals, and insights into achieving high-quality healthcare in VHA.

Lung adenocarcinomas without driver genes converge to common adaptive strategies through diverse genetic, epigenetic, and niche construction evolutionary pathways

Somatic evolution selects cancer cell phenotypes that maximize survival and proliferation in dynamic environments. Although cancer cells are molecularly heterogeneous, we hypothesized convergent adaptive strategies to common host selection forces can be inferred from patterns of epigenetic and genetic evolutionary selection in similar tumors. We systematically investigated gene mutations and expression changes in lung adenocarcinomas with no common driver genes (n = 313). Although 13,461 genes were mutated in at least one sample, only 376 non-synonymous mutations evidenced positive evolutionary selection with conservation of 224 genes, while 1736 and 2430 genes exhibited ≥ two-fold increased and ≥ 50% decreased expression, respectively. Mutations under positive selection are more frequent in genes with significantly altered expression suggesting they often “hardwire” pre-existing epigenetically driven adaptations. Conserved genes averaged 16-fold higher expression in normal lung tissue compared to those with selected mutations demonstrating pathways necessary for both normal cell function and optimal cancer cell fitness. The convergent LUAD phenotype exhibits loss of differentiated functions and cell–cell interactions governing tissue organization. Conservation with increased expression is found in genes associated with cell cycle, DNA repair, p53 pathway, epigenetic modifiers, and glucose metabolism. No canonical driver gene pathways exhibit strong positive selection, but extensive down-regulation of membrane ion channels suggests decreased transmembrane potential may generate persistent proliferative signals. NCD LUADs perform niche construction generating a stiff, immunosuppressive microenvironment through selection of specific collagens and proteases. NCD LUADs evolve to a convergent phenotype through a network of interconnected genetic, epigenetic, and ecological pathways.

Sirt5 improves cardiomyocytes fatty acid metabolism and ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via CPT2 de-succinylation

RationaleThe disruption of the balance between fatty acid (FA) uptake and oxidation (FAO) leads to cardiac lipotoxicity, serving as the driving force behind diabetic cardiomyopathy (DbCM). Sirtuin 5 (Sirt5), a lysine de-succinylase, could impact diverse metabolic pathways, including FA metabolism. Nevertheless, the precise roles of Sirt5 in cardiac lipotoxicity and DbCM remain unknown. ObjectiveThis study aims to elucidate the role and underlying mechanism of Sirt5 in the context of cardiac lipotoxicity and DbCM. Methods and resultsThe expression of myocardial Sirt5 was found to be modestly elevated in diabetic heart failure patients and mice. Cardiac dysfunction, hypertrophy and lipotoxicity were exacerbated by ablation of Sirt5 but improved by forced expression of Sirt5 in diabetic mice. Notably, Sirt5 deficiency impaired FAO without affecting the capacity of FA uptake in the diabetic heart, leading to accumulation of FA intermediate metabolites, which mainly included medium- and long-chain fatty acyl-carnitines. Mechanistically, succinylomics analyses identified carnitine palmitoyltransferase 2 (CPT2), a crucial enzyme involved in the reconversion of fatty acyl-carnitines to fatty acyl-CoA and facilitating FAO, as the functional succinylated substrate mediator of Sirt5. Succinylation of Lys424 in CPT2 was significantly increased by Sirt5 deficiency, leading to the inactivation of its enzymatic activity and the subsequent accumulation of fatty acyl-carnitines. CPT2 K424R mutation, which mitigated succinylation modification, counteracted the reduction of enzymatic activity in CPT2 mediated by Sirt5 deficiency, thereby attenuating Sirt5 knockout-induced FAO impairment and lipid deposition. ConclusionsSirt5 deficiency impairs FAO, leading to cardiac lipotoxicity in the diabetic heart through the succinylation of Lys424 in CPT2. This underscores the potential roles of Sirt5 and CPT2 as therapeutic targets for addressing DbCM.

Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma

BackgroundIntrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood.MethodsTo address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue.ResultsThrough the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs.ConclusionsThis study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression.

Climate Change and Mental Health (A Global Analysis)

Climate change and its corresponding consequences have been recognized as one of the dominating issues of global concern. Many governments of various nations are currently making efforts to mitigate the undesirable consequences of climate change. The essay is focused on carrying out an analysis of the effect of climate change on mental health in the United Kingdom. The paper presented a methodological framework for the diverse and multiple channels by which climate change impacts on a person’s mental health. In connection with this, this methodological analysis led to the conceptualization of the variables that link or mediate the effect of climate change on human mental health and corresponding well-being. There was an exploration of evidence-based analysis of climate change modifies the variables that impact mental health; this will take care of the expression of the diverse pathways of effect. The essay recognizes that despite the mental health dangers and risks associated with climate change, adopting a strategic climate action can also be a window of opportunity to harness its impact and engage in proactive and preventable measures.

Relevance of Cardiovascular Exercise in Cancer and Cancer Therapy-Related Cardiac Dysfunction.

Cancer therapy-related cardiac dysfunction (CTRCD) has been identified as a threat to overall and cancer-related survival. Although aerobic exercise training (AET) has been shown to improve cardiorespiratory fitness (CRF), the relationship between specific exercise regimens and cancer survival, heart failure development, and reduction of CTRCD is unclear. In this review, we discuss the impact of AET on molecular pathways and the current literature of sports in the field of cardio-oncology. Cardio-oncological exercise trials have focused on variations of AET intensity by using moderate continuous and high intensity interval training, which are applicable, safe, and effective approaches to improve CRF. AET increases CRF, reduces cardiovascular morbidity and heart failure hospitalization and should thus be implemented as an adjunct to standard cancer therapy, although its long-term effect on CTRCD remains unknown. Despite modulating diverse molecular pathways, it remains unknown which exercise regimen, including variations of AET duration and frequency, is most suited to facilitate peripheral and central adaptations to exercise and improve survival in cancer patients.

Bioassay of Root Exudates, their Impact in Susceptible Species and their Degradation in Hydroponics: A Review

Plants grown in hydroponics exhibit superior characters and yield compared to those grown in soil. However, root exudates accumulated particularly in renewed nutrient solution (RNS) hinders development of crops in hydroponics. These exudates are secondary metabolites released by the roots as a result of physiological processes, exhibiting autotoxic effects in plants. They are allelochemicals encompassing various chemical groups such as phenolic compounds, terpenoids, alkaloids, benzoxazinoids or other organic acids. The quantity and type of allelochemical released by plants varies depending on multiple factors such as temperature, light, nutrient deficiency, stress, physiological status of plant, pH and environment. The combined effect of more than one allelochemical is often additive or synergistic thus elevating the impact caused by individual allelochemical. These phytotoxic exudates are known to have inhibited the growth and development of plants by diverse pathways unique to their characteristic. There are several methods developed for degradation of exudates including AC (Activated Charcoal), O3/H2O2 treatment or other. This review discusses the bioassay of secondary metabolites causing autotoxicity, mechanism, impact in horticultural and ornamental crops, factors affecting their release and methods for elimination in hydroponics.

Removal of Exogenous Stimuli Reveals a Canalization of Circadian Physiology in a Vertically Migrating Copepod.

Diel rhythms are observed across taxa and are important for maintaining synchrony between the environment and organismal physiology. A striking example of this is the diel vertical migration undertaken by zooplankton, some of which, such as the 5 mm-long copepod Pleuromamma xiphias (P. xiphias), migrate hundreds of meters daily between the surface ocean and deeper waters. Some of the molecular pathways that underlie the expressed phenotype at different stages of this migration are entrained by environmental variables (e.g., day length and food availability), while others are regulated by internal clocks. We identified a series of proteomic biomarkers that vary across ocean DVM and applied them to copepods incubated in 24 h of darkness to assess circadian control. The dark-incubated copepods shared some proteomic similarities to the ocean-caught copepods (i.e., increased abundance of carbohydrate metabolism proteins at night). Shipboard-incubated copepods demonstrated a clearer distinction between night and day proteomic profiles, and more proteins were differentially abundant than in the in situ copepods, even in the absence of the photoperiod and other environmental cues. This pattern suggests that there is a canalization of rhythmic diel physiology in P. xiphias that reflects likely circadian clock control over diverse molecular pathways.

Applications of Quantitative Microbial Risk Assessment to Respiratory Pathogens and Implications for Uptake in Policy: A State-of-the-Science Review.

Respiratory tract infections are major contributors to the global disease burden. Quantitative microbial risk assessment (QMRA) holds potential as a rapidly deployable framework to understand respiratory pathogen transmission and inform policy on infection control. The goal of this paper was to evaluate, motivate, and inform further development of the use of QMRA as a rapid tool to understand the transmission of respiratory pathogens and improve the evidence base for infection control policies. We conducted a literature review to identify peer-reviewed studies of complete QMRA frameworks on aerosol inhalation or contact transmission of respiratory pathogens. From each of the identified studies, we extracted and summarized information on the applied exposure model approaches, dose-response models, and parameter values, including risk characterization. Finally, we reviewed linkages between model outcomes and policy. We identified 93 studies conducted in 16 different countries with complete QMRA frameworks for diverse respiratory pathogens, including SARS-CoV-2, Legionella spp., Staphylococcus aureus, influenza, and Bacillus anthracis. Six distinct exposure models were identified across diverse and complex transmission pathways. In 57 studies, exposure model frameworks were informed by their ability to model the efficacy of potential interventions. Among interventions, masking, ventilation, social distancing, and other environmental source controls were commonly assessed. Pathogen concentration, aerosol concentration, and partitioning coefficient were influential exposure parameters as identified by sensitivity analysis. Most (84%, ) studies presented policy-relevant content including a) determining disease burden to call for policy intervention, b) determining risk-based threshold values for regulations, c) informing intervention and control strategies, and d) making recommendations and suggestions for QMRA application in policy. We identified needs to further the development of QMRA frameworks for respiratory pathogens that prioritize appropriate aerosol exposure modeling approaches, consider trade-offs between model validity and complexity, and incorporate research that strengthens confidence in QMRA results. https://doi.org/10.1289/EHP12695.

Donor and recipient genetics: Implications for the development of posttransplant diabetes mellitus

Posttransplant diabetes mellitus (PTDM) is a prevalent complication of liver transplantation and is associated with cardiometabolic complications. We studied the consequences of genetic effects of liver donors and recipients on PTDM outcomes, focusing on the diverse genetic pathways related to insulin that play a role in the development of PTDM. One thousand one hundred fifteen liver transplant recipients without a pretransplant diagnosis of type 2 diabetes mellitus (T2D) and their paired donors recruited from 2 transplant centers had polygenic risk scores (PRS) for T2D, insulin secretion, and insulin sensitivity calculated. Among recipients in the highest T2D-PRS quintile, donor T2D-PRS did not contribute significantly to PTDM. However, in recipients with the lowest T2D genetic risk, donor livers with the highest T2D-PRS contributed to the development of PTDM (OR [95% CI] = 3.79 [1.10-13.1], P = .035). Recipient risk was linked to factors associated with insulin secretion (OR [95% CI] = 0.85 [0.74-0.98], P = .02), while donor livers contributed to PTDM via gene pathways involved in insulin sensitivity (OR [95% CI] = 0.86 [0.75-0.99], P = .03). Recipient and donor PRS independently and collectively serve as predictors of PTDM onset. The genetically influenced biological pathways in recipients primarily pertain to insulin secretion, whereas the genetic makeup of donors exerts an influence on insulin sensitivity.

Unraveling genetic underpinnings of purine content in pork

The significance of purine base content as an important nutrition indicator in foods arises from its potential to trigger hyperuricemia or gout via high-purine diet. Livestock meats, including pork, generally contain moderate to high total purine content (TP). Recent research revealed substantial variations within and across pig breeds, implying genetic factors influencing this trait. Thus, this study aimed to unravel the genetic underpinnings governing purine base content in pork. The heritability estimates (h2) for the four purine traits ranged from 0.14 to 0.35. A total of 14, 36, 19 and 25 quantitative trait loci (QTLs) were identified for guanine, adenine, hypoxanthine, and TP, respectively. Our comprehensive gene set enrichment analysis and gene network analysis revealed 15 promising candidate genes intricately interwoven within diverse purine metabolism pathways, such as purine ribonucleotide metabolic process, purine nucleotide metabolism and transport, and purine salvage pathways, all contributing to TP. Strikingly, most genetic variants significantly associated with TP displayed analogous effects on multiple purine bases. Two distinct and highly significant QTLs (P < 10-12) emerged on Sus Scrofa chromosome (SSC) 12: one impacting guanine content and the other concurrently influencing adenine and hypoxanthine levels. The peak of the guanine QTL on SSC12 resided 1.1 kb downstream of the transmembrane protein 238 like (TMEM238L) gene and is encapsulated within a genomic segment characterized by the histone modification H3K27me3. Focused fine-mapping for the SSC12 QTL associated with adenine and hypoxanthine levels narrowed its scope to around 172 kb, encompassing the growth arrest specific 7 (GAS7) and myosin heavy chain 13 (MYH13) genes. However, the observed QTL effect was not attributed to any missense mutations within the two genes. This pioneering study unveils the genetic variations and candidate genes associated with purine content in livestock, laying a robust foundation for the selective breeding of pig lines with reduced purine base content.

Life cycle assessment of hydrogen production, storage, and utilization toward sustainability

AbstractIn the pursuit of sustainable energy solutions, hydrogen emerges as a promising candidate for decarbonization. The United States has the potential to sell wind energy at a record‐low price of 2.5 cents/kWh, making hydrogen production electricity up to four times cheaper than natural gas. Hydrogen's appeal stems from its highly exothermic reaction with oxygen, producing only water as a byproduct. With an energy content equivalent to 2.4 kg of methane or 2.8 kg of gasoline per kilogram, hydrogen boasts a superior energy‐to‐weight ratio compared to fossil fuels. However, its energy‐to‐volume ratio, exemplified by liquid hydrogen's 8.5 MJ.L−1 versus gasoline's 32.6 MJ.L−1, presents a challenge, requiring a larger volume for equivalent energy. In addition, this review employs life cycle assessment (LCA) to evaluate hydrogen's full life cycle, including production, storage, and utilization. Through an examination of LCA methodologies and principles, the review underscores its importance in measuring hydrogen's environmental sustainability and energy consumption. Key findings reveal diverse hydrogen production pathways, such as blue, green, and purple hydrogen, offering a nuanced understanding of their life cycle inventories. The impact assessment of hydrogen production is explored, supported by case studies illustrating environmental implications. Comparative LCA analysis across different pathways provides crucial insights for decision‐making, shaping environmental and sustainability considerations. Ultimately, the review emphasizes LCA's pivotal role in guiding the hydrogen economy toward a low‐carbon future, positioning hydrogen as a versatile energy carrier with significant potential.This article is categorized under: Emerging Technologies &gt; Hydrogen and Fuel Cells

Transcriptional repression of GTL1 under water-deficit stress promotes anthocyanin biosynthesis to enhance drought tolerance.

The transcription factor GT2-LIKE 1 (GTL1) has been implicated in orchestrating a transcriptional network of diverse physiological, biochemical, and developmental processes. In response to water-limiting conditions, GTL1 is a negative regulator of stomatal development, but its potential rolein other water-deficit responses is unknown. We hypothesized that GTL1 regulates transcriptome changes associated with drought tolerance over leaf developmental stages. To test the hypothesis, gene expression was profiled by RNA-seq analysis in emerging and expanding leaves of wild-type and a drought-tolerant gtl1-4 knockout mutant under well-watered and water-deficit conditions. Our comparative analysis of genotype-treatment combinations within leaf developmental age identified 459 and 1073 differentially expressed genes in emerging and expanding leaves, respectively, as water-deficit responsive GTL1-regulated genes. Transcriptional profiling identified a potential role of GTL1 in two important pathways previously linked to drought tolerance: flavonoid and polyamine biosynthesis. In expanding leaves, negative regulation of GTL1 under water-deficit conditions promotes biosynthesis of flavonoids and anthocyanins that may contribute to drought tolerance. Quantification of polyamines did not support a role for GTL1 in these drought-responsive pathways, but this is likely due to the complex nature of polyamine synthesis and turnover. Our global transcriptome analysis suggests that transcriptional repression of GTL1 by water deficit allows plants to activate diverse pathways that collectively contribute to drought tolerance.

Study of individual domains contributing to MALT1 dimerization in BCL10-independent and dependent assembly

The CARMA-BCL10-MALT1 (CBM) signalosome functions as a pivotal supramolecular module, integrating diverse receptor-induced signaling pathways to regulate BCL10-dependent NF-kB activation in innate and adaptive immunity. Conversely, the API2-MALT1 fusion protein in t(11; 18)(q21; q21) MALT lymphoma constitutively induces BCL10-independent NF-kB activation. MALT1 dimer formation is indispensable for the requisite proteolytic activity and is critical for NF-kB activation regulation in both scenarios. However, the molecular assembly of MALT1 individual domains in CBM activation remains elusive. Here we report the crystal structure of the MALT1 death domain (DD) at a resolution of 2.1 Å, incorporating reconstructed residues in previously disordered loops 1 and 2. Additionally, we observe a conformational regulation element (CRE) regulating stem-helix formation in NLRPs pyrin (PYD) within the MALT1 DD structure. The structure reveals a stem-helix-mediated dimer further corroborated in solution. To elucidate how the BCL10 filament facilitates MALT1 dimerization, we reconstitute a BCL10-CARD-MALT1-DD-IG1-IG2 complex model. We propose a N+7 rule for BCL10-dependent MALT1 dimerization via the IG1-IG2 domain and for MALT1-dependent cleavage in trans. Biochemical data further indicates concentration-dependent dimerization of the MALT1 IG1-IG2 domain, facilitating MALT1 dimerization in BCL10-independent manner. Our findings provide a structural and biochemical foundation for understanding MALT1 dimeric mechanisms, shedding light on potential BCL10-independent MALT1 dimer formation and high-order BCL10-MALT1 assembly.

Validation of biomarkers and immunotherapy in head and neck squamous cell carcinoma using bioinformatics and Mendelian randomization

Background To promote carcinogenesis through diverse molecular pathways involving dysregulation of gene expression and abnormalities. Methods We employed Mendelian randomization (MR) to uncover causal relationships between genetic factors and HNSCC. We used the Inverse Variance Weighted (IVW) method as the primary MR analysis, and validated the results through complementary approaches like MR-Egger regression, weighted median, and mode analyses. Results Our analysis identified 2210 genes that are differentially expressed in head and neck cancer (HNSCC) compared to normal tissues. Within the protein interaction network, the genes IL1B, CXCL8, CXCL1, and CCL2 stood out as central hubs. Further investigation revealed that these key genes are involved in important biological processes like skin development, wound healing, and fat metabolism. Notably, our Mendelian randomization analysis provided evidence for a causal relationship between the expression of the IL1B gene and the development of HNSCC. Conclusions Our analysis identified 5 key genes - IL1B, CXCL8, CXCL1, CCL2, and IL1B - that show significant changes in expression in head and neck cancer. These genes could serve as important new biomarkers to help diagnose this disease and track how it progresses over time. Importantly, these genes are involved in regulating the immune system, suggesting that the body’s immune response plays a critical role in head and neck cancer. This provides new avenues for future research to better understand the complex gene expression patterns underlying this type of cancer. Further investigation of these key genes and their regulatory networks could lead to important insights and potential new treatment approaches.

Timescale correlation of shallow trap states increases electrochemiluminescence efficiency in carbon nitrides

Highly efficient interconversion of different types of energy plays a crucial role in both science and technology. Among them, electrochemiluminescence, an emission of light excited by electrochemical reactions, has drawn attention as a powerful tool for bioassays. Nonetheless, the large differences in timescale among diverse charge-transfer pathways from picoseconds to seconds significantly limit the electrochemiluminescence efficiency and hamper their broad applications. Here, we report a timescale coordination strategy to improve the electrochemiluminescence efficiency of carbon nitrides by engineering shallow electron trap states via Au-N bond functionalization. Quantitative electrochemiluminescence kinetics measurements and theoretic calculations jointly disclose that Au-N bonds endow shallow electron trap states, which coordinate the timescale of the fast electron transfer in the bulk emitter and the slow redox reaction of co-reagent at diffusion layers. The shallow electron trap states ultimately accelerate the rate and kinetics of emissive electron-hole recombination, setting a new cathodic electrochemiluminescence efficiency record of carbon nitrides, and empowering a visual electrochemiluminescence sensor for nitrite ion, a typical environmental contaminant, with superior detection range and limit.

Toxic Effects of Rare Earth Elements on Human Health: A Review.

Rare earth elements (REEs) are a new type of material resource which have attracted significant attention in recent years. REEs have emerged as essential metals in modern-day technology due to their unique functions. The long-term, large-scale mining and utilization of rare earths has caused serious environmental pollution and constitutes a global health issue, which has raised concerns regarding the safety of human health. However, the toxicity profile of suspended particulate matter in REEs in the environment, which interacts with the human body, remains largely unknown. Studies have shown that REEs can enter the human body through a variety of pathways, leading to a variety of organ and system dysfunctions through changes in genetics, epigenetics, and signaling pathways. Through an extensive literature search and critical analysis, we provide a comprehensive overview of the available evidence, identify knowledge gaps, and make recommendations for future research directions.

Direct Observation of Particle-To-Particle Variability in Ambient Aerosol pH Using a Novel Analytical Approach Based on Surface-Enhanced Raman Spectroscopy.

The pH of atmospheric aerosols is a key characteristic that profoundly influences their impacts on climate change, human health, and ecosystems. Despite widely performed aerosol pH research, determining the pH levels of individual atmospheric aerosol particles has been a challenge. This study presents a novel analytical technique that utilizes surface-enhanced Raman spectroscopy to assess the pH of individual ambient PM2.5-10 aerosol particles in conjunction with examining their hygroscopic behavior, morphology, and elemental compositions. The results revealed a substantial pH variation among simultaneously collected aerosol particles, ranging from 3.3 to 5.7. This variability is likely related to each particle's unique reaction and aging states. The extensive particle-to-particle pH variability suggests that atmospheric aerosols present at the same time and location can exhibit diverse reactivities, reaction pathways, phase equilibria, and phase separation properties. This pioneering study paves the way for in-depth investigations into particle-to-particle variability, size dependency, and detailed spatial and temporal variations of aerosol pH, thus deepening our understanding of atmospheric chemistry and its environmental implications.