Search Results (22,474)

The United States faces a maternal health crisis marked by stark racial disparities. Although doula support has emerged as an evidence-based intervention to improve perinatal outcomes by addressing social determinants of health, its integration into healthcare systems remains limited. This qualitative study, informed by phenomenological principles, examined multi-level experiences, perceived barriers, and perceived facilitators of integrating doula services into perinatal care systems and their intersection with health equity goals. We conducted 17 semi-structured interviews with 20 participants across Nebraska and Tennessee, including doulas, midwives, physicians, Medicaid administrators, and public health professionals, and analyzed data using reflexive thematic analysis guided by the Socio-Ecological Model. Three themes emerged: the integration paradox, an overarching theme capturing tensions between doula independence and healthcare system demands for standardization, including divergent views on practice models, provider dynamics, and certification; sustainable financing as the prevailing barrier, encompassing grant limitations, private pay inequities, absent Medicaid reimbursement, and the need for cost-effectiveness evidence; and cultural concordance as the prevailing facilitator, including cultural matching, addressing social determinants, and lived experience as motivation. Sustainable doula integration requires reconciling system demands for standardization with the relational, culturally responsive characteristics that define effective care, through Medicaid reimbursement pathways and policy reforms developed in partnership with doula communities. Full article

Cardiovascular diseases remain the leading cause of mortality worldwide, and one of the key mechanisms driving the development of heart failure is pathological remodeling of the myocardium. This process involves complex structural, cellular, and metabolic alterations in which the immune system and its interactions with cardiomyocytes and fibroblasts play a central role. The aim of this work was to present the current state of knowledge on immunometabolism in cardiac remodeling and to discuss its pathophysiological relevance and therapeutic potential. This review focuses on the metabolism of cardiac macrophages, highlighting the differences between the pro-inflammatory (M1) and reparative (M2) phenotypes and their impact on inflammation, fibrosis, and myocardial regeneration. The roles of major metabolic pathways, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and glutaminolysis, are discussed, as well as the importance of the NLRP3 inflammasome and efferocytosis in regulating the inflammatory response. Furthermore, the review briefly incorporates recent insights into neutrophil, T cell, and regulatory T cell (Treg) metabolism and their contributions to inflammation, repair, and fibrotic remodeling. Particular attention is also given to cardiac fibroblasts and their metabolic reprogramming during fibrosis, with emphasis on the pivotal role of transforming growth factor-β (TGF-β) signaling. The review further discusses the role of microRNAs as mediators of intercellular communication integrating immunological and metabolic signals. The work is complemented by a discussion of therapeutic perspectives, including modulation of macrophage metabolism, fibrogenic signaling pathways, mitochondrial function, and miRNA-based therapies. Immunometabolism emerges as a promising research field whose further exploration may contribute to the development of novel, more precise strategies for the treatment of cardiovascular diseases. Full article

The inflammatory response possesses a central role in human pathophysiology, regulating the tissue microenvironment and cell signaling. Inflammation occurs either as a symptom of homeostasis disturbance or as a driver for determining cell fate. In this context, cells recruit secreted cytokines, chemokines and intracellular mediators, in cooperation with their surrounding cellular components, to integrate inflammatory stimuli. The extracellular matrix (ECM) acts as a scaffold for shaping tissue structure and simultaneously undergoes continuous remodeling to provide a dynamic network for intercellular communication. Serglycin (SRGN) is the only known intracellular and extracellular proteoglycan, implicated in the formation of secretory vesicles and ECM reorganization. The regulatory roles of SRGN in the bioavailability of secreted factors, as well as SRGN pleiotropic interactions within the ECM, as well as with cell surface receptors, have emerged to beessential for inflammatory diseases and tumor progression. Its overexpression and excessive secretion, alongside its contribution to cell signaling, highlight the potential diagnostic and therapeutic aspects of SRGN in human diseases. Full article

Background: Migraine is a highly prevalent neurological disorder associated with substantial disability and socioeconomic burden. Although pharmacological therapies remain the mainstay of treatment, their effectiveness may be limited by incomplete response and adverse effects. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a non-invasive neuromodulatory technique that may modulate cortical excitability and pain-processing networks involved in migraine pathophysiology. This systematic review aimed to evaluate the current evidence regarding the efficacy and safety of rTMS compared with sham stimulation in individuals with migraine. Methods: A systematic search was conducted in PubMed (MEDLINE), PsycNet, and Ovid (including MEDLINE and Embase) from database inception to December 2025 in accordance with PRISMA 2020 guidelines. Studies investigating rTMS in adults with migraine and including a sham comparator were eligible for inclusion. Data regarding study design, participant characteristics, rTMS parameters, outcomes, and adverse events were extracted using a predefined template. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Results: Seven studies comprising a total of 301 participants were included. Most trials evaluated high-frequency rTMS targeting the dorsolateral prefrontal cortex. Across studies, rTMS was generally associated with reductions in migraine frequency and severity compared with sham stimulation, although results varied depending on stimulation parameters and study design. Treatment was consistently well tolerated, with only mild and transient adverse effects reported. However, considerable heterogeneity was observed in diagnostic criteria, stimulation protocols, outcome measures, and follow-up duration. Conclusions: Preliminary evidence suggests that rTMS may represent a promising and well-tolerated neuromodulatory approach for migraine management. Nevertheless, methodological variability, limited sample sizes, and concerns regarding risk of bias restrict definitive conclusions. Larger randomized controlled trials with standardized protocols and longer follow-up periods are needed to clarify the clinical role of rTMS in migraine treatment. Full article

Although nanomedicine has enabled significant advances in drug delivery, the clinical translation of conventional synthetic nanocarriers is limited by immune clearance, non-specific biodistribution, and gastrointestinal instability. This poses major challenges for therapy targeting the intestines. Cell membrane-coated nanotechnology (CMCT) and membrane vesicle-based systems have emerged as biomimetic platforms integrating synthetic nanomaterials with naturally derived biological interfaces. These biohybrid systems inherit biological functions originating from cells, including immune evasion, prolonged circulation, lesion homing, and microenvironment-responsive interactions, through the direct transfer of intact membrane components. This review summarizes recent advances in CMCT and membrane vesicle-based strategies for intestinal drug delivery. It covers fabrication methodologies, programmable manufacturing approaches, and functional regulation enabled by diverse membrane sources and hybrid engineering designs. Applications in inflammatory bowel disease, colorectal cancer, and intestinal infections are highlighted, emphasizing key therapeutic mechanisms, such as targeting inflammation, neutralizing toxins, modulating the immune system, and regulating the microbiome. We also discuss the major challenges of translation, such as preserving membrane and coating integrity, ensuring oral stability, achieving batch reproducibility, and ensuring biosafety. Overall, this review establishes a conceptual and engineering framework to guide the transition of membrane-based nanocarriers from passive biomimicry to adaptive, clinically translatable intestinal delivery systems. Full article

This article analyses how capacity building programmes interact with structural constraints in mission-oriented climate policy, focusing on the Italian pilot Let’sGOv (GOverning the Transition through Pilot Actions) within the EU Mission “100 Climate-Neutral and Smart Cities by 2030”. Using an iterative, reflexive methodology (document analysis, direct observation, and qualitative analysis of questionnaires, workshop outputs, and online training feedback), it examines how municipal actors experience and reinterpret capacity building across three coupled dimensions: internal organisational capacity, external stakeholder relations, and multilevel governance interfaces. The empirical setting is a network of nine Italian Mission Cities (Bergamo, Bologna, Florence, Milan, Padua, Parma, Prato, Rome, Turin) supported by technical partners. The bench-learning pathway combined barrier diagnosis, an intensive in-person workshop, and a codesigned online curriculum structured around three thematic clusters (engagement, data, climate finance). Findings indicate that persistent barriers—departmental silos, resource and time scarcity, rigid human resources and procurement routines, asymmetric data access, and regulatory instability—are not removed by capacity building; rather, they are progressively articulated, specified, and reframed into actionable organisational and policy demands. Bench-learning strengthens diagnostic and relational capacities and enables modest institutional innovations (templates, protocols, internal task forces, shared policy briefs), while “hard” governance infrastructures largely remain unchanged. The paper argues that networked capacity building contributes to the emergence of nascent, project-dependent multilevel interfaces only when it supports collective negotiation with national actors and translates local experimentation into durable multilevel interfaces, mitigating risks of projectification and downward responsibility shifting. Full article

Higher education institutions (HEIs) play a central role in fostering sustainability competencies to address environmental challenges. Within Education for Sustainable Development (ESD) and Sustainable Development Goal (SDG) 4 frameworks, universities must cultivate not only knowledge but also attitudes and behaviours promoting environmental responsibility. This study examines environmental attitudes as sustainability learning outcomes among undergraduate students, analysing differences by gender, age, and discipline in six Andalusian universities. Sustainable Education is defined as an approach integrating environmental, social, and economic sustainability dimensions into teaching to develop active competencies for sustainable development. A cross-sectional survey (n = 1471) used the validated CASEM questionnaire (see previous validation studies) to assess environmental knowledge, environmental education knowledge, and pro-environmental behaviour. The results show significant differences: women outperformed men across all dimensions, students aged over 25 exhibited stronger profiles, and Education Sciences students outperformed Engineering students. A persistent knowledge–behaviour gap emerged, especially in technical fields. These findings reveal curricular inequalities in sustainability integration. Mandatory, discipline-specific ESD—particularly in engineering—may help bridge these gaps and enhance uniform learning outcomes. By employing a multidimensional instrument and stratified sample, this study offers robust evidence of structural disparities, informing policy for equitable Higher Education for Sustainability. Full article

Passion fruit (Passiflora edulis) quality is defined by integrated sensory and nutritional traits, including sugar–acid balance, volatile organic compounds (VOCs), pigment-related attributes, and bioactive compounds such as ascorbic acid and phenolics. These traits emerge from coordinated regulation of carbon allocation, mineral nutrition, ripening metabolism, and stress- and defense-related signaling pathways, which are strongly modulated by environmental conditions. Sustainable biological inputs are increasingly explored as tools to influence these regulatory networks; however, evidence linking such interventions to reproducible fruit quality outcomes in Passiflora remains fragmented. This review first synthesizes current knowledge on the physiological, biochemical, and molecular mechanisms underlying passion fruit quality formation and maintenance, and then discusses how biofertilizers; microbial inoculants (including plant growth-promoting rhizobacteria—PGPR and arbuscular mycorrhizal fungi—AMF); fungal-derived elicitors such as chitosan and chitooligosaccharides; and complementary postharvest biological strategies may modulate these processes. Emphasis is placed on traits beyond yield, including sugar–acid balance, aroma and VOC profiles, color, nutritional quality, texture, and shelf life. By integrating genomics, transcriptomics, metabolomics, proteomics, and microbiome-based evidence, we examine how environmental modulation and key signaling pathways intersect with metabolic networks underlying fruit quality. Available studies indicate that responses to biological inputs are context-dependent and often non-linear. Key knowledge gaps and priorities for mechanism-informed sustainable management of passion fruit quality are identified. Full article

Mesenchymal stem/stromal cells (MSCs) are widely recognized as potent modulators of inflammation and immune function in bacterial and viral infections. However, their roles in fungal disease remain comparatively under-defined despite the growing clinical burden of invasive and opportunistic mycoses. This Feature Review synthesizes emerging evidence that MSCs influence antifungal outcomes through two complementary axes: (i) host-directed effects, including modulation of immune responses, particularly macrophage responses, and tissue/barrier conditioning; and (ii) fungus-directed effects (direct antifungal activity mediated by contact-dependent mechanisms and secreted antimicrobial factors). We will summarize how MSCs reshape cytokine and chemokine networks and tune innate immune effector functions, with emphasis on macrophage polarization, pattern-recognition receptor signaling, and downstream phagocytic and fungicidal pathways. In parallel, we will review data suggesting that MSCs can interact more directly with fungal pathogens through sensing, physical engagement, and secretion of antimicrobial mediators while highlighting mechanistic uncertainties and model-dependent limitations. A dedicated section will address MSC-derived secretome products (conditioned media, extracellular vesicles) as a cell-free strategy to enhance antifungal immunity. We will critically evaluate conflicting findings across studies, highlighting that outcomes depend on pathogen and host context. Clarifying these context dependencies is essential to rationally develop MSC or secretome-based interventions that are safe, reproducible, and tailored to specific fungal pathogens and patient populations. Full article

In situ coagulation is regarded as the most effective measure in response to the frequent metal spills in China. Excessive coagulant is often used in pursuit of extremely high removal rates of contaminants. Yet the secondary ecological impact of the iron-containing coagulation flocs left on the river sediments after emergency response is still unclear. In the current study, we investigated the impact of flocs derived from three different iron-based coagulants, polymeric ferric sulfate (PFS), polymeric ferric chloride (PFC), and ferric chloride (FeCl₃), on microbial communities in sediment based on microcosm experiments. Metagenomics, quantitative PCR, and determination of ammonia oxidation potential were adopted to elucidate community shifts. The results indicate that the community structure and function of microorganisms in sediments have been affected, especially processes and species related to nitrogen cycling, and the effect was coagulant-specific. Flocs retrieved from FeCl₃ caused a more pronounced decline in diversity, shifts in community composition, and decreased potential ammonia oxidation. Ammonia-oxidizing archaea (AOA) was more sensitive to iron-containing flocs than ammonia-oxidizing bacteria (AOB), while PFS-flocs tended to reduce multiple genes involved in nitrate reduction. This indicates that the pre-polymerization of inorganic coagulants may be the primary factor leading to different microbial ecological effects. Sulfate, on the other hand, may affect specific biogeochemical processes due to its competition for electron donors. Our results confirmed that even without heavy metals as contaminants, coagulant flocs alone could present an effect on nitrogen cycling in sediments. The results will provide a scientific basis for environmental emergency decision-making: in emergency response to metal pollution incidents, the use of coagulants should be limited to only the necessary level. Full article

GDSL esterase/lipase (GELP) proteins constitute an evolutionarily conserved yet functionally diversified hydrolase family in land plants. They participate in cuticle and secondary cell wall biosynthesis, seed lipid remobilization, reproductive development, and hormone-mediated responses to biotic and abiotic stresses. Despite extensive genome-wide and comparative genomic studies that have categorized large GELPs across numerous crops and model species, only a fraction of members have been functionally characterized in plants, and their catalytic mechanisms and regulatory architectures remain poorly understood. Recent population genomics and cross-species orthogroup analyses in 46 angiosperms have uncovered substantial natural variation within GELP coding sequences and regulatory regions, providing a powerful framework to link allelic diversity to evolutionary trajectories and physiological functions. This review synthesizes current knowledge on GELP evolution, biochemical properties, and roles in development and stress adaptation, and critically evaluates how these insights can be translated into biotechnology and molecular breeding strategies. It highlights emerging resources and concepts from orthogroup-based classification and multi-species datasets that enable systematic discovery of GELP alleles affecting agronomic traits. It further outlines research exploiting GELPs in crop improvement, emphasizing the integration of reverse and forward genetics with multi-omics profiling, biochemical and structural characterization, and gene regulatory network reconstruction. Systematic assessment of the phenotypic impacts of single and combinatorial GELP perturbations on yield, quality, and stress resilience is proposed as a key step toward translating basic insights into breeding and engineering strategies. Full article

Background/Objectives: The rapid emergence of antimicrobial resistance (AMR) is driven not only by antibiotic selective pressure but also by bacterial adaptive responses that enhance genetic diversification under stress. The SOS response, regulated by the RecA-LexA axis, plays a central role in coordinating DNA repair, mutagenesis, and phenotypic adaptation. Targeting this pathway represents a promising strategy to limit bacterial adaptability without directly affecting viability. This study aimed to evaluate benzoxaborole-based compounds as potential inhibitors of the LexA regulatory pathway. Methods: A drug repurposing approach was employed to investigate the benzoxaborole scaffold and the clinically approved derivatives tavaborole and crisaborole. Biochemical assays were used to assess LexA autocleavage in a RecA-dependent co-protease system. Molecular docking analyses were performed to evaluate compound binding within the LexA catalytic site. Microbiological assays were conducted to examine the effects on antibiotic-induced filamentation and biofilm formation under different growth conditions. Results: Selected benzoxaboroles inhibited LexA autocleavage, with tavaborole showing the strongest inhibitory profile in the biochemical assay. Docking analyses supported these findings, indicating stable binding within the LexA catalytic site near the catalytic serine residue. At the cellular level, tavaborole and benzoxaborole significantly reduced levofloxacin-induced filamentation at sub-inhibitory concentrations. Both compounds also decreased biofilm formation under nutrient-limited conditions, while no significant effects were observed on preformed biofilms. Crisaborole showed limited cellular activity despite measurable biochemical effects. Conclusions: These findings identify benzoxaboroles as modulators of the LexA-dependent SOS response and support the potential repurposing of clinically approved compounds as adjuvants to limit bacterial adaptive responses associated with antimicrobial resistance. Full article

Capsular contracture (CC) remains the most common long-term complication of implant-based breast reconstruction (IBBR), significantly impacting cosmetic outcomes, patient satisfaction, and reoperation rates. Despite substantial advances in surgical technique, implant technology, and perioperative management, the incidence of clinically significant contracture persists at approximately 3–5% at five years in non-irradiated patients and escalates dramatically—to 20–50%—in those receiving postmastectomy radiation therapy (PMRT). The etiology is multifactorial, involving subclinical biofilm formation, a dysregulated host immune and foreign-body response, and radiation-induced fibrosis. This narrative review synthesizes contemporary evidence on the pathophysiology, clinical assessment, and modifiable risk factors for CC in IBBR, with particular emphasis on implant surface characteristics (smooth, textured, and polyurethane[PU]-coated), placement plane (prepectoral versus subpectoral), the role of acellular dermal matrices (ADMs), reconstruction timing (direct-to-implant versus two-stage), and the complex interplay with radiotherapy—including radiation timing, fractionation, and emerging delivery techniques. We also address ongoing controversies, including the lack of standardized objective diagnostic criteria, the comparative effectiveness of ADM versus PU-coated implants, and the optimal sequencing of radiation relative to reconstruction. By integrating the latest evidence from very recent major meta-analyses and national registries, this review provides an updated synthesis. We further propose an evidence-based clinical decision framework for CC risk mitigation. This review aims to inform individualized surgical decision-making and identify priority areas for future investigation. Full article

Tourism development in the Yucatán Peninsula has long been dominated by coastal mass tourism, resulting in environmental pressure and pronounced spatial imbalances. In response, increasing attention has been directed toward diversification strategies based on inland and nature-based attractions. Among these, cenotes—karst sinkholes connected to regional groundwater systems—have emerged as a distinctive tourism resource. This paper introduces the concept of cenotourism as a form of nature-based and geoculturally embedded tourism centred on cenotes and their associated karst environments. The analysis combines conceptual development with empirical evidence from a large-scale tourism survey conducted in Yucatán (n ≈ 2800). The findings suggest that cenotes constitute a meaningful component of tourists’ activity portfolios, with 24.6% of respondents declaring an intention to visit them. Cenotourism contributes to diversification and appears to support the redistribution of tourist flows toward inland areas, while simultaneously increasing exposure to highly sensitive groundwater systems. These results point to a clear sustainability trade-off, although its magnitude may vary depending on local governance conditions. While cenotourism may strengthen local economies and reduce pressure on coastal destinations, it also introduces risks related to groundwater contamination, cultural commodification, and uneven benefit distribution. Such outcomes depend strongly on governance conditions, including visitor management, environmental monitoring, and community participation. By conceptualizing cenotourism as an integrative framework linking tourism demand, environmental vulnerability, and governance processes, the study contributes to understanding tourism development in groundwater-dependent systems. The findings emphasize the need for context-specific management approaches and situate cenotourism within broader water-sensitive tourism planning. Full article

This study employed a 2 × 2 factorial design to investigate the transcriptomic responses of common carp intestine under the single and combined stress of high temperature and zinc. Results from Illumina RNA-seq, WGCNA, and qPCR showed high-quality sequencing data with good reproducibility. High temperature was the core driver of global transcriptomic reprogramming, inducing numerous DEGs via activating metabolic and stress signaling pathways. Zinc alleviated heat stress by reducing DEGs by 43.2% and activating DNA repair and cell cycle pathways. WGCNA identified core modules for heat response and zinc mitigation, revealing “emergency defense” and “repair adaptation” strategies. This study enriches the teleost stress adaptation theory and provides a scientific basis for healthy carp aquaculture. Full article