搜索结果：Science and engineering ethics

Engineering ethics education has undergone significant development across institutions worldwide over the last three decades. While earlier analyses have examined aspects of this development, few integrated accounts have traced the evolution of a leading institution's approach to engineering ethics education across this period. This paper addresses this gap. It presents an integrative review of engineering ethics education at Delft University of Technology (TU Delft), one of Europe's most influential institutions in this field. Drawing on peer-reviewed articles, books, book chapters, conference papers, and institutional documents published by TU Delft scholars over three decades, we trace the historical development of the institution's approach, analyze its core theoretical assumptions and examine its learning goals and evolving pedagogical practices. The review identifies two distinct stages in the institution's development. It reflects a deepening of learning goals and, most notably, a shift toward experiential and non-cognitive pedagogical approaches. These findings offer a reference point for discussing how ethics should be taught to engineers, how to integrate it into technical curricula, and which kinds of normative stances institutions should adopt in their ethics programs.

Soil carbon (C) and nitrogen (N) are the major elements of the global bio-geochemical cycle and have a great impact on environmental quality, soil fertility, ecosystem productivity, sustainable agriculture, and in addressing climate change. The present study focuses on the spatial distribution patterns and the drivers of total soil carbon (SC) and total nitrogen (TN) in the rice paddy cropping system of Western Himalayas, Jammu and Kashmir. Soil samples were collected from three depths (0-10, 10-20, and 20-30 cm) from 165 sampling points across 10 districts for the estimation of SC and TN using a CHNS analyzer. The average SC and TN were 56.3 Mg C ha-1 and 5.3 Mg N ha-1, respectively, in the top 30 cm of soils. Both SC and TN showed a negative trend with increasing soil depth. Principal component analysis (PCA) revealed that among structural attributes, paddy biomass components (paddy density, shoot, and root stock) exhibited a significant positive correlation with both SC and TN. In terms of environmental factors, C:N, EC, NDMI, and SMI showed a significant positive trend, whereas MAP, BD, and elevation had a significant negative association with SC and TN. The PCA accounted for 81.5% and 74.3% of variance for SC and TN, respectively. This study reveals that SC and TN storage are synergistically driven by structural attributes, edaphic, and climatic factors. These findings would be indispensable for long-term planning and monitoring programs to enhance and manage SC and TN storage in rice paddies of temperate croplands under changing climate for carbon crediting.

Diarrheal diseases constitute a major global public health threat, particularly endangering young children, the elderly, and immunocompromised individuals. Three key pathogens-norovirus, rotavirus, and adenovirus 40/41-can induce dehydration, electrolyte imbalances, and severe complications, resulting in tens of thousands of deaths annually. Conventional vaccines have inherent limitations, including relatively long development cycles and high production costs. With the deep integration of bioinformatics and immunology, immunoinformatic techniques driven by high-throughput analysis enable reliable prediction of key epitope properties such as immunogenicity and antigenicity, offering an efficient approach for multivalent vaccine development. This study aims to develop a trivalent multi-epitope mRNA vaccine targeting these three pathogens using immunoinformatic methods, providing a potential innovative strategy for the prevention and control of diarrheal diseases. The amino acid sequences corresponding to the target viral proteins were obtained from the NCBI Virus Database. Epitopes were screened and selected based on key properties including high antigenicity, non-allergenicity, and non-toxicity. Appropriate adjuvant components, along with the chosen T-lymphocyte and B-lymphocyte epitopes, were assembled using linker molecules to computationally construct the vaccine. Structural and related features of the computationally designed vaccine were analyzed using online tools. Molecular docking assays, in conjunction with molecular dynamics simulations, were performed to clarify the interaction modes and structural stability characteristics of ligand-receptor binding. mRNA sequences of the vaccine were designed through codon optimization, and their immunogenicity was ultimately assessed using immune simulations. A total of 16 cytotoxic T-cell epitopes, 5 helper T-cell epitopes, and 17 linear B-cell epitopes were selected to construct the vaccine. After evaluating immunological and physicochemical properties, molecular docking and molecular dynamics simulations were performed, suggesting favorable structural stability and plausible interactions with immune receptors. The computationally designed vaccine in this study was predicted to exhibit favorable structural stability, potential immune activation capability, and promising broad population coverage, providing preliminary insights for the development of vaccines against multiple viral co-infections; however, its immunogenicity and safety remain to be further validated through animal model experiments.

The plastic pollution crisis urges innovative recycling solutions. Promising approaches especially for polyester-containing wastes include enzymatic hydrolysis and microbial upcycling. For efficient enzymatic hydrolysis of polyesters, elevated temperatures (70-80 °C) are required, necessitating thermophilic microbial chassis for consolidated bioprocessing (CBP). In this study, we engineered Geobacillus thermoleovorans through adaptive laboratory evolution (ALE) for robust growth on adipic acid (AA) and 1,4-butanediol (BDO), two relevant monomers for example derived from poly(butylene adipate-co-terephthalate) (PBAT), enabling growth rates of up to 0.10 h-1 on AA and 0.13 h-1 on BDO. Based on a high-quality annotated genome sequence of the wild type, genomic mutations and gene expression levels were characterized in mutants grown on the respective substrates compared to glucose. For BDO, an alcohol dehydrogenase (Gth_001044) and an aldehyde dehydrogenase (Gth_001082) were identified to be likely responsible for its oxidative degradation. AA uptake appears to be mediated by a dicarboxylate transporter (Gth_003270), followed by CoA activation and β-oxidation involving a CoA transferase (Gth_003192) and several upregulated CoA-family dehydrogenases. To demonstrate applicability of these strains in plastic upcycling, they were co-cultivated with PBAT as the sole carbon source in combination with the cutinase HiC for PBAT hydrolysis. This resulted in growth on the released AA and BDO. Given the potential to purify the remaining terephthalate (TA), this approach highlights the feasibility of selective monomer valorization in bioprocesses. Additional ALE enabled co-utilization of AA and BDO by a single strain and improved AA consumption at lower concentrations, underscoring the strains' adaptability and high potential for plastic upcycling applications. KEY POINTS: • G. thermoleovorans evolved for robust growth on adipate and 1,4-butanediol at 60 °C. • Genome and transcriptome analyses revealed underlying pathways and enzymes involved. • Co-cultivation of the evolved strains on PBAT with HiC as the sole carbon source.

Information on childhood cancer burden is crucial for effective cancer policy planning. Unfortunately, observed paediatric cancer data are not available in every country, and previous global burden estimates have not discretely reported several common cancers of childhood. We aimed to inform efforts to address childhood cancer burden globally by analysing results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, which now include nine additional cancer causes compared with previous GBD analyses. GBD 2023 data sources for cancer estimation included population-based cancer registries, vital registration systems, and verbal autopsies. For childhood cancers (defined as those occurring at ages 0-19 years), mortality was estimated using cancer-specific ensemble models and incidence was estimated using mortality estimates and modelled mortality-to-incidence ratios (MIRs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the standard life expectancy at the age of death. Prevalence was estimated using survival estimates modelled from MIRs and multiplied by sequelae-specific disability weights to estimate years lived with disability (YLDs). Disability-adjusted life-years (DALYs) were estimated as the sum of YLLs and YLDs. Estimates are presented globally and by geographical and resource groupings, and all estimates are presented with 95% uncertainty intervals (UIs). Globally, in 2023, there were an estimated 377 000 incident childhood cancer cases (95% UI 288 000-489 000), 144 000 deaths (131 000-162 000), and 11·7 million (10·7-13·2) DALYs due to childhood cancer. Deaths due to childhood cancer decreased by 27·0% (15·5-36·1) globally, from 197 000 (173 000-218 000) in 1990, but increased in the WHO African region by 55·6% (25·5-92·4), from 31 500 (24 900-38 500) to 49 000 (42 600-58 200) between 1990 and 2023. In 2023, age-standardised YLLs due to childhood cancer were inversely correlated with country-level Socio-demographic Index. Childhood cancer was the eighth-leading cause of childhood deaths and the ninth-leading cause of DALYs among all cancers in 2023. The percentage of DALYs due to uncategorised childhood cancers was reduced from 26·5% (26·5-26·5) in GBD 2017 to 10·5% (8·1-13·1) with the addition of the nine new cancer causes. Target cancers for the WHO Global Initiative for Childhood Cancer (GICC) comprised 47·3% (42·2-52·0) of global childhood cancer deaths in 2023. Global childhood cancer burden remains a substantial contributor to global childhood disease and cancer burden and is disproportionately weighted towards resource-limited settings. The estimation of additional cancer types relevant in childhood provides a step towards alignment with WHO GICC targets. Efforts to decrease global childhood cancer burden should focus on addressing the inequities in burden worldwide and support comprehensive improvements along the childhood cancer diagnosis and care continuum. St Jude Children's Research Hospital, Gates Foundation, and St Baldrick's Foundation.

The sympathetic adrenergic nerves (SAN) play a significant role in the malignant transformation of breast cancer cells through the activity of norepinephrine (NE). However, the role of tyrosine hydroxylase (TH), a key enzyme of the NE synthesis, in the interaction between the SAN and triple-negative breast cancer (TNBC) cells has not been sufficiently explored, and whether TH can be a therapeutic target for TNBC has not been reported. TH expression in TNBC was examined by analyzing data from an online database and immunohistochemical analysis of our clinical samples. Cell proliferation and drug sensitivity were assessed upon coculture with fluorescently labeled cells using IncuCyte. Changes in the expression of DNA damage and apoptosis-associated proteins were assessed by western blotting. TH expression and NE synthesis in PC12 cells after their coculture with TNBC cells were measured by RT-qPCR, immunofluorescence, and ELISA. RNA sequencing was conducted on the cells before and after coculture. TH expression was relatively high in TNBC tumor tissues and closely associated with prognosis. SAN promoted TNBC cell proliferation through NE and reduced TNBC cell sensitivity to chemotherapeutic agents. Additionally, tumor cells induced TH expression in PC12 cells through nerve growth factor (NGF) secretion. Knocking down TH and using TH inhibitors effectively reversed the proliferation-promoting and drug sensitivity-reducing effects of SAN in TNBC cells. TH may be a central molecule in the positive feedback loop between TNBC cells and SAN. TH is a potential prognostic biomarker and can also serve as a therapeutic target for TNBC. KEY MESSAGES: The overexpression of the sympathetic nerve biomarker tyrosine hydroxylase (TH) in triple-negative breast cancer (TNBC) is an indicator for clinical staging, prognosis, and targeted therapy. There is a feedback loop where TH in nerves produces NE, worsening TNBC and reducing chemotherapy effectiveness. TNBC cell then increases TH expression, further boosting NE production. Furthermore, blocking the activity of TH could effectively inhibit this phenotype.

Cell therapy for neurodegenerative diseases (NDs) is considered a promising strategy to halt disease progression. Currently, most clinically applied cells are derived from two-dimensional (2D) cultures. However, 2D-cultured mesenchymal stem cells (MSCs) are prone to aging and functional deterioration after multiple passages, and the availability of neural precursor cells for cell replacement therapy remains limited. In contrast, three-dimensional (3D) cell cultures have garnered significant attention due to their unique 3D spatial interactions. The unique spatial architecture of 3D culture not only enhances cell-cell and cell-extracellular matrix (ECM) interactions in MSC spheroids, thereby preserving MSCs properties, but also facilitates developmental processes of brain organoids derived from pluripotent stem cells, including embryogenesis, morphogenesis, and organogenesis. This review highlights the therapeutic ability of 3D-cultured MSC spheroids and brain organoids for NDs and summarizes advanced engineering platforms for their production. Future research should integrate the strengths of both technologies by establishing standardized quality control systems and scalable production processes to harness the microenvironmental modulation capacity of MSC spheroids and the precise cell replacement ability of brain organoids, ultimately advancing personalized therapies for NDs.

The most effective approach for minimizing feed cost and maximizing animal production is the creation of breeding materials with simultaneous increases in growth and feed conversion efficiency (FCE). However, the key genes that regulate FCE are unknown. Here, we artificially selected specific strains of yellow catfish with simultaneous improvements in growth and FCE traits and then conducted a genome-wide association study to screen candidate SNPs and genes associated with these traits. A particular locus in the miR-200 cluster on chromosome 23 was identified, and the causal relationships between miR-200a/200b expression and growth/FCE were further validated. Genetic deletion of miR-200a/200b by CRISPR/Cas9 in yellow catfish significantly underpins phenotypic gains in growth and FCE by regulating genes involved in energy intake and energy metabolism without significantly affecting average feed intake or the expression of appetite-regulating genes. Several critical target genes of miR-200a/200b, such as stat5b and fasn, were identified via RNA-RNA pulldown and RNA-seq analyses, and stat5b-transgenic yellow catfish exhibited significantly increased growth and FCE. These findings highlight the pivotal role of the miR-200a/200b-stat5b signaling axis in controlling growth, metabolism, and FCE in yellow catfish, thus providing a strategy toward achieving more effective and sustainable animal agriculture by gene editing.

The increasing demand for irrigation water, together with declining freshwater availability, has intensified interest in wastewater reuse in agriculture. Although wastewater may enhance plant growth because of its nutrient and mineral content, it can also contain salts and heavy metals that may alter plant biochemical quality and raise safety concerns. This study evaluated the morphological, physiological, phytochemical, and antioxidant responses of three aromatic plants-Mentha arvensis, Coriandrum sativum, and Trigonella foenum-graecum-to two irrigation treatments under pot conditions: T0 (distilled water, control) and T1 (100% untreated wastewater). Plant height, selected morphological traits, chlorophyll content, qualitative phytochemical characteristics, antioxidant activity (DPPH assay), and wastewater chemical composition were assessed. Wastewater irrigation promoted vegetative growth in all three species. Plant height increased by 51% in C. sativum (43 to 65 cm), 32% in M. arvensis (68 to 90 cm), and 36% in T. foenum-graecum (33 to 45 cm) under T1 compared with T0. Total chlorophyll increased in C. sativum (96.0 to 111.7 mg/g) and M. arvensis (45.2 to 49.9 mg/g), while it remained nearly unchanged in T. foenum-graecum (110.2 to 109.9 mg/g). In contrast, antioxidant activity generally declined under wastewater irrigation, particularly in the leaves of C. sativum (1.30 to 0.76 mg/mL) and T. foenum-graecum (2.90 to 2.10 mg/mL), with a slight reduction in M. arvensis leaves (1.60 to 1.50 mg/mL). Qualitative phytochemical screening also indicated treatment-related changes in the distribution of secondary metabolites across plant organs. Wastewater analysis showed the presence of nutrient-related constituents alongside potentially toxic elements, including Pb, Ni, and Cd. Overall, untreated wastewater improved short-term growth performance, but it was also associated with altered biochemical responses that may affect crop quality. These findings suggest that wastewater reuse in aromatic crop production should be approached cautiously and supported by treatment, monitoring, and long-term assessment of soil and crop safety.

To address the global increase in cancer incidence, improving prevention strategies, early detection and management of bowel and testicular cancer in primary healthcare can improve clinical decisions. Although national efforts are aligned with global health agendas, there is no consolidated evidence to support effective actions. In this context, this study aims to map the existing scientific evidence on the prevention, early detection and management of penile and testicular cancers within the scope of primary healthcare. Scoping review protocol conducted using Joanna Briggs Institute methodology and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist, guided by the review question Prevention, Early Detection and Management of Penile and Testicular Cancer (concept) carried out by Primary Healthcare Professionals (population) in men's healthcare (context). The search for texts will be carried out in six databases (Ovid Medline ALL, Ovid Embase, CINAHL Complete, Web of Science Core Collection, Global Index Medicus and Cochrane Library) and the grey literature, from inception through to May 2025. Two reviewers will select the studies with the help of the blind-on tool of the Covidence. Discrepancies will be resolved by a third reviewer. Data will be extracted according to a specific form and organised in Covidence. Ethics approval is not required, as this study does not involve human subjects or primary data collection. Findings will be disseminated through a peer-reviewed scientific publication and shared with healthcare professionals and stakeholders engaged in men's health.

Aquaporin-4 (AQP4) is crucial for brain fluid regulation and glymphatic system function. Idiopathic normal pressure hydrocephalus (INPH) is characterized by impaired CSF flow and is treated with shunt surgery. This study investigated AQP4 levels in INPH patients to explore its role in pathophysiology and as a potential biomarker for shunt response. CSF samples from 233 INPH patients and 29 controls were analysed. AQP4 levels were compared between preoperative patients and controls, before and after shunt surgery (110 patients), and between shunt responders and non-responders (204 patients). A bead-based assay was used to measure AQP4, and outcomes were assessed by postoperative changes in maximum gait velocity. In unadjusted analyses, preoperative AQP4 levels were lower in INPH patients than in controls; however, this difference did not remain after adjustment for pre-analytical and demographic confounders (p&#x2009;=&#x2009;0.87). Postoperative AQP4 levels were higher (median 1646 AU IQR 1347-1976) than preoperative levels (1166 AU IQR: 976-1345; p&#x2009;<&#x2009;0.001) and the magnitude of increase showed a modest correlation with gait improvement (r&#x209b; = 0.22, p&#x2009;=&#x2009;0.022). Shunt responders had lower preoperative AQP4 levels median 1089 AU, IQR 971-1277) than non-responders (median 1213 AU, IQR 1074-1361; p&#x2009;=&#x2009;0.008). Pre-analytical factors, including storage duration and sample processing, were strong determinants of measured AQP4 levels. CSF AQP4 levels in INPH did not differ from those in controls and were highly sensitive to pre-analytical sample handling. CSF AQP4 levels increased following shunt surgery. A potential prognostic value of CSF AQP4 is suggested but requires further investigation.

Scientists are increasingly expected to not only produce objective science but also to use their science and expertise to support the public good. Prior studies indicate that scientists see both responsibilities as important; however, it is not clear how scientists manage these responsibilities when they are perceived to be in tension. In this study, scientists at land-grant institutions (n&#x2009;=&#x2009;87) were presented with binary choices to identify where tensions may exist and how scientists make decisions between competing responsibilities. We examined nine categories of potential tensions: direct conflicts between objectivity and public impact, engagement in public outreach, communication priorities and approach, political engagement and perceived bias, the media, funding and disclosure, supporting/protecting specific causes, diversity, and ethical decision making. Results indicate that scientists belong to three cultures of ethical thought: arbiters, advocates, and brokers. These cultures roughly align with the scientist roles described by Pielke and suggest different prioritizations of commitment to public service relative to commitment to objective science, though both commitments were valued. There was variation across cultures of thought on whether scientists should openly support policies based on their research. Broad areas of agreement across cultures of thought were also identified. Scientists of all cultures of thought indicated a willingness to see themselves in a public role, communicating openly with non-experts on issues where scientific research intersects with the public good. There was also an expressed need for scientists to receive better training and tools to manage conflicting responsibilities.

The Three-River-Source Region of the Qinghai-Tibet Plateau is a hyperendemic focus for echinococcosis, with Echinococcus granulosus, E. multilocularis, and E. shiquicus circulating between definitive canid hosts (dogs and foxes) and intermediate hosts (livestock and rodents). However, the extent of environmental contamination by Echinococcus eggs remains understudied and poses significant risks to human and animal health. From 2019 to 2021, we collected 631 canid fecal samples (296 from dogs and 335 from foxes) and 398 adjacent soil samples across endemic counties in the Three-River-Source Region of the Qinghai-Tibet Plateau. Multiplex real-time PCR was employed to detect Echinococcus species DNA in feces and soil samples. The overall Echinococcus prevalence in canid feces was 7.13% (45/631), with 3.01% in E. multilocularis (19/631), 2.06% in E. granulosus (13/631), and 2.06% in E. shiquicus (13/631). Foxes presented increased E. multilocularis (3.88%, 13/335) and E. shiquicus (2.69%, 9/335) infections, whereas dogs presented increased E. granulosus prevalence (2.70%, 8/296). Soil contamination with&#xa0;Echinococcus&#xa0;species was detected in 2.51% (10/398) of the samples. The primary contaminants were&#xa0;E. multilocularis&#xa0;and&#xa0;E. shiquicus&#xa0;(1.01% each, 4/398), whereas&#xa0;E. granulosus&#xa0;was less frequent (0.50%, 2/398). Moreover, the soil near fox feces was contaminated with both E. multilocularis and E. shiquicus, whereas the dog-associated soil was contaminated with all three species. This study suggests widespread environmental deposition of Echinococcus eggs on the Qinghai-Tibet Plateau, driven by canid defecation. If these eggs remain viable, their persistence in soil would indicate a potential zoonotic transmission risk, highlighting the need for integrated control strategies targeting both domestic and wild canids.

LGBTQ+ young people in rural Australia face significant health challenges due to stigma, discrimination and structural barriers that hinder effective access to care. The inaccessibility or altogether absence of tailored primary healthcare services exacerbates poor health outcomes. Safer Spaces will use a mixed-methods approach combining participatory systems science with health economics methods to co-design and implement a ''Safer Spaces' Model of Primary Healthcare (SSMPH) targeting LGBTQ+ young people aged 12-25 years in rural Western Victoria. Phase 1 co-design of the SSMPH will be achieved through the establishment of a Queer Health Alliance, engagement in Group Model Building workshops via Deakin's STICKE platform and the administration of a Discrete Choice Experiment to ascertain LGBTQ+ young people's primary health service preferences. Phase 2 will implement strategies co-designed in phase 1 supporting primary healthcare for LGBTQ+ young people that are equitable, accessible and responsive to local needs. Implementation efficacy will be evaluated using participatory qualitative methods, systems-based monitoring (including causal loop diagrams and social network analysis) and stakeholder-led evaluation. Ethical approval for this research project has been granted by Deakin University's Human Research Ethics Committee. Safer Spaces will be developed in collaboration with lived experience researchers and the community. The knowledge translation plan will be integrated and revised throughout the project as partnerships and engagement with LGBTQ+ young people and their allies continue. All findings will be shared with rural health research bodies, policy makers, rural health providers and LGBTQ+ young people in ways that are meaningful to them. This protocol addresses critical gaps in rural health equity for LGBTQ+ young people by generating insights to guide community-informed service reform and building systemic capacity.

Porcine rotavirus (PoRV), porcine epidemic diarrhea virus (PEDV), and porcine deltacoronavirus (PDCoV) are major pathogens responsible for porcine diarrheal diseases, and their accurate identification is critical for disease control in swine production. However, overlapping clinical symptoms and pathological manifestations pose significant challenges for differential diagnosis. We developed a highly sensitive and specific triplex RT-qPCR assay to simultaneously detect and distinguish these three pathogens. Specific primers and probes were designed and screened based on conserved regions of the NSP5 gene of PoRV, the S gene of PEDV, and the S gene of PDCoV. The reaction system was optimized for primer concentrations, probe concentrations and annealing temperature. The assay demonstrated excellent specificity with no cross-reactivity to other common swine pathogens, a detection sensitivity of 10 copies/&#xb5;L, and intra-batch and inter-batch coefficients of variation (CV) below 1%. Additionally, the method exhibited strong tolerance to inhibitors in complex sample. Parallel testing of 124 clinical samples using this triplex assay and singleplex RT-qPCR commercial kits showed complete concordance in detection rates for PoRV, PEDV, and PDCoV. Our study presents a robust triplex RT-qPCR method that provides a rapid, sensitive, and reliable tool for the differential diagnosis of porcine diarrheal pathogens.

Surface PM2.5 mass reconstructed from MERRA-2 (Modern Era-Retrospective analysis for Research and Applications) chemical species is widely used to assess aerosol-climate interactions and human health impacts, globally. However, species-wise validation of MERRA-2 PM2.5 against in-situ measurements remains sparse over India due to limited ground-based aerosol speciation data. This study presents the first species-wise validation of MERRA-2 PM2.5 components (organic carbon (OC), black carbon (BC), sulfate, sea-salt, and dust) using year-long (2019) in-situ measurements of PM2.5 and its chemical constituents at three geographically distinct Indian sites-Bhopal (central India), Mesra (eastern India), and Mysuru (southern India). Across the study sites, with reference to in-situ species, MERRA-2 OC showed variable agreement, ranging from underestimation (-&#x2009;23%) to overestimation (+&#x2009;22%), while sulfate was predominantly underestimated (-&#x2009;31% to&#x2009;-&#x2009;0.36%). Dust and sea-salt were consistently overestimated (+&#x2009;36% to&#x2009;+&#x2009;65% and&#x2009;+&#x2009;33% to&#x2009;+&#x2009;300%, respectively), with poor sea-salt correlations (correlation coefficient&#x2009;<&#x2009;0.2). The annual mean reconstructed MERRA-2 PM2.5 mass (excluding nitrate) underestimated in-situ PM2.5 by 9-27%. Incorporation of estimated nitrate, derived from nitrate-to-sulfate ratios from the&#xa0;CAMS (Copernicus Atmosphere Monitoring Service) reanalysis, reduced the underestimation to 9-17% at Mesra and Mysuru, and resulted in a slight overestimation (2%) at Bhopal. Mann-Kendall trend analysis (1999-2019) of the MERRA-2 species revealed increasing anthropogenic aerosol species (sulfate, OC, and BC), particularly over eastern and central India, likely driven by coal-based power generation and residential biomass burning. These validated, species-wise MERRA-2 PM2.5 products provide a robust supplementary resource for aerosol, air-quality, climate, and health assessments across India.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by motor neuron degeneration, oxidative stress, and neuroinflammation. This study evaluated the neuroprotective potential of caffeic acid phenethyl ester (CAPE) against MTME&#x2009;+&#x2009;5-induced neurotoxicity in an ALS-like pathology model. CAPE (50 and 100&#xa0;mg/kg., p.o.) demonstrated significant therapeutic efficacy by improving motor and cognitive deficits, restoring oxidative balance, and mitigating neuroinflammatory and apoptotic pathways. Behavioral assessments, including the open field, grip strength, forced swim, and Morris water maze, highlighted CAPE's ability to restore neuromuscular coordination and cognitive function in a dose-dependent manner. Cellular and Molecular analyses revealed that MTME+5 exposure significantly disrupted Klotho/SIRT-1/Nrf2/HO-1 antioxidant signaling, increased pro-inflammatory cytokines (TNF-&#x3b1;, IL-1&#x3b2;), and elevated apoptotic markers (Bax, caspase-3) while depleting anti-inflammatory cytokines (IL-10) and neuroprotective proteins. Furthermore, CAPE treatment restored these parameters, reduced oxidative stress, and enhanced antioxidant defenses (SOD, CAT, r-GSH). Furthermore, CAPE normalized neurotransmitter imbalances, including acetylcholine, dopamine, GABA, serotonin, and glutamate, alleviating excitotoxicity. Histopathological and gross morphological analyses confirmed CAPE50 and CAPE100 ability to preserve neuronal and myelin integrity across key brain regions, including the cerebral cortex, hippocampus, striatum, midbrain, and cerebellum. CAPE also reduced methylmercury accumulation in the brain and cerebrospinal fluid, indicating detoxifying effects. Co-administration of vitamin B1 (VTB1(200)) further amplified CAPE's therapeutic efficacy. Complete blood count (CBC) analysis demonstrated MTME+5-induced hematological abnormalities, including reduced RBCs, hemoglobin, WBCs, and platelets, alongside elevated eosinophils and basophils. CAPE treatment normalized these parameters, indicating systemic recovery. These findings establish CAPE as a promising neuroprotective agent for ALS, capable of targeting neurocomplications.

The Jumonji C domain-containing (JMJD) family of histone demethylases constitutes an essential class of epigenetic regulators that dynamically sculpt gene expression programs through the erasure of methyl groups from histone lysine and arginine residues. Dysregulation of these enzymes is increasingly implicated in the pathogenesis of a wide spectrum of human diseases. Yet, a fragmented, disease-specific understanding has thus far hindered a unified view of their functions across different pathological states. In this review, we provide a comprehensive and comparative analysis of the JMJD family, synthesizing their roles and mechanisms across diverse human conditions, including cancer, neurological disorders, inflammatory, autoimmune, cardiovascular, and metabolic diseases. We highlight that individual JMJD proteins can function paradoxically as both promoters and suppressors of pathology, a duality determined by the specific cellular and pathological context. A key novelty of our work is its integrated, cross-disease perspective, which moves beyond conventional silos to illuminate common pathophysiological pathways and unique regulatory networks orchestrated by these epigenetic erasers. Furthermore, we critically assess the associated therapeutic landscape, summarizing advances in the development of small-molecule JMJD inhibitors and discussing innovative strategies to tackle enduring challenges, such as enzymatic redundancy and selectivity. By integrating insights from disparate disease models, this review seeks to forge a holistic understanding of JMJD biology and accelerate the development of novel epigenetic therapeutics directed at this pivotal protein family.

3-Hydroxypropionic acid (3-HP) is a promising C3 platform chemical with wide industrial applications. However, its microbial production remains limited by insufficient intracellular malonyl-CoA availability and metabolic imbalance. In this study, we systematically engineered Escherichia coli for enhanced 3-HP biosynthesis. The malonate assimilation genes (matB, smatPQM) and 3-HP biosynthesis gene (mcr) were chromosomally integrated using CRISPR/Cas9, resulting in a plasmid-free, antibiotic-free strain (WYY04) that produced 21.97 mM 3-HP, 0.51-fold higher than the plasmid-based system. Further improvement was achieved by CRISPRi-mediated repression of fatty acid biosynthesis genes (fabD, fabF), increasing 3-HP titer by 66%. Introduction of a malonyl-CoA-responsive FapR/fapO biosensor enabled dynamic regulation of mcr expression, enhancing 3-HP production by 59%. Through all these above engineering, the 3-HP production of the strain WYY19 increased by 2.29 times compared to that of the plasmid-expressing system. Under optimized fermentation conditions, the final engineered strain WYY19 produced 42.22&#xa0;g/L 3-HP with the specific productivity of 0.69&#xa0;g/g and 0.46&#xa0;g/L/h from glucose and malonate in fed-batch bioreactor. This study demonstrates a robust, genetically stable, and scalable microbial platform for 3-HP biosynthesis.