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The value of international collaborations for supporting neuroanesthesia practice, education, and research in resource-constrained settings.

PURPOSE OF REVIEW: Neuroanesthesia practice in low- and middle-income countries is constrained by workforce shortages, limited infrastructure, and variability in clinical practice. Growing global interest in collaboration makes it timely to evaluate how international partnerships can address these gaps and improve equity in care, education, and research. RECENT FINDINGS: Recent literature highlights substantial variability in neuroanesthesia practice and limited access to context-appropriate guidelines and advanced technologies. International collaborations, including training partnerships, scholarship programs, and research networks, have improved knowledge exchange, workforce development, and the adoption of standardized practices. Evidence suggests that specialized training is associated with improved clinical outcomes. However, persistent inequities in research participation, authorship, and leadership, as well as concerns regarding sustainability and 'parachute research', remain. SUMMARY: International collaboration is a key strategy for advancing neuroanesthesia in resource-constrained settings. Sustainable, equitable partnerships that prioritize local ownership, capacity building, and contextual adaptation are essential to improving clinical practice, strengthening education, and enhancing global research representation.

Humans

Hip Arthroscopy During Female Menstruation: A Retrospective Analysis of Safety and Clinical Outcomes With 24-Month Follow-Up.

OBJECTIVES: To investigate the safety and clinical outcomes of hip arthroscopy performed during menstruation in reproductive-age female patients, and to determine whether surgery during menstruation increases intraoperative risks or adversely affects postoperative recovery. Currently, clear clinical guidelines regarding the timing of elective orthopedic surgeries relative to the menstrual cycle are lacking, often leading to unnecessary surgical rescheduling. Therefore, this study aimed to provide evidence-based guidance for perioperative management and optimal surgical scheduling, thereby addressing a critical clinical need. METHODS: This retrospective cohort study included reproductive-age female patients who underwent hip arthroscopy at the First Medical Center of Chinese PLA General Hospital, the Fourth Medical Center of Chinese PLA General Hospital, and the Department of Sports Medicine at the Second Hospital of Shandong University from December 2018 to September 2023. Patients were categorized into the menstruation group (MP) and the non-menstruation group (NMP) based on whether they were menstruating on the day of surgery. The NMP group consisted of equally sized ovulatory (OP) and luteal (LP) phases. Perioperative outcomes included: intraoperative blood loss, anesthetic dosage, operative time, hemoglobin (Hb) change (within 24&#x2009;h postoperatively), prothrombin time (PT), and activated partial thromboplastin time (APTT). Postoperative outcomes included analgesic consumption, duration of analgesic use, time to first unassisted weight-bearing ambulation, complications, and urinary tract infections. Functional outcomes were assessed at 24-month follow-up using the Visual Analog Scale (VAS), Modified Harris Hip Score (mHHS), International Hip Outcome Tool-12 (iHOT-12), Hip Outcome Score-Activities of Daily Living (HOS-ADL), and Hip Outcome Score-Sports Specific Subscale (HOS-SSS). RESULTS: Of 884 eligible patients, 28 were included in the MP group and 56 matched patients in the NMP group. Operative time, anesthetic use, Hb change, PT, and APTT were comparable between the two groups (all p&#x2009;>&#x2009;0.05). No serious complications or urinary tract infections occurred in either group. At the 24-month follow-up, both groups demonstrated significant improvements in VAS, mHHS, iHOT-12, HOS-ADL, and HOS-SSS (all p&#x2009;<&#x2009;0.001), with no statistically significant differences observed between the groups. CONCLUSIONS: Hip arthroscopy during menstruation does not increase intraoperative bleeding, impair coagulation, or delay functional recovery for female patients. Menstruation should not be considered a contraindication when appropriate perioperative management is applied.

Humans

Identification of elements determining KIR gene demethylation at the CD56-bright stage of NK cell development.

The variegated expression of the KIR family of class I MHC receptors generates specialized natural killer (NK) cells capable of allele-specific HLA recognition. Understanding the mechanism of KIR gene activation will lead to improved methods for the generation of fully functional NK cells. A central RUNX-binding site in the KIR proximal promoter is required for gene activation. RUNX proteins recruit ten-eleven translocation (TET) proteins that generate 5-hydroxymethylcytosine (5hmC) and drive DNA demethylation. Assessment of 5-methylcytosine (5mC) and 5hmC residues at four stages of NK cell development reveals deposition of 5hmC primarily in a CREB site next to the RUNX site at the CD56Bright stage but not the subsequent CD56Dim stage representing fully mature NK cells. KIR promoter demethylation is delayed relative to other lineage-associated genes, indicating a high threshold for KIR gene demethylation in developing NK cells, and a window of opportunity for RUNX/TET-dependent KIR gene activation in CD56Bright NK cells.

6-base sequencing

Control of foreign DNA: emerging roles of xenogeneic silencers.

Bacteria continuously acquire foreign DNA through horizontal gene transfer, yet its successful integration depends on regulatory mechanisms that balance genome protection with evolutionary innovation. Xenogeneic silencers are central to this process: they preferentially bind AT-rich DNA, a common feature of many horizontally acquired genetic elements, and repress its transcription. Recent studies, however, reveal a much broader regulatory repertoire. Beyond transcriptional repression, these proteins contribute to chromosome organization by forming higher-order nucleoprotein complexes and phase-separated condensates that shape bacterial nucleoid architecture. Furthermore, they play roles in regulating bacteriophage infection cycles, including mechanisms by which phages hijack host silencing activities for their own benefit. Their extensive regulatory reach, spanning virulence genes, biofilm formation, specialized metabolite production, and mobile genetic elements (MGEs), underscores their central role in connecting environmental signals, including fluctuations in the second messenger c-di-GMP, with gene expression, and genome organization. The diversification of xenogeneic silencers across bacterial chromosomes, plasmids, phages, and other MGEs highlights their evolutionary significance. Together, these recent findings position xenogeneic silencers as dynamic regulatory modules that shape the fate of foreign DNA across the horizontal gene transfer network.

Gene Transfer, Horizontal

Interventions to improve school attendance: a systematic review and meta-analysis of evidence from randomised controlled trials.

BACKGROUND: Poor school attendance adversely affects youth behaviour and health trajectories. We reviewed and synthesised the evidence from randomised controlled trials (RCTs) on interventions to improve school attendance. METHODS: This systematic review and meta-analysis updates the Education Endowment Foundation (EEF) 2022 review on attendance interventions. We synthesised RCT data to inform recommendations. We searched ERIC (via EBSCOhost), PsycINFO, Web of Science and Google Scholar for publications 1 January 2020-16 October 2024 to identify attendance interventions delivered to students, parents/guardians or school staff. We also extracted and analysed RCTs identified in the EEF review. Two reviewers independently extracted data from published articles and assessed risk of bias and certainty of evidence (Grading of Recommendations Assessment, Development and Evaluation, GRADE assessment). We synthesised and meta-analysed data per our protocol (PROSPERO: CRD42024610037). RESULTS: We screened 9366 titles and abstracts and included 61 articles (2000-2024): 43 articles published 2020-2024 plus 18 articles from the previous review (2000-2020), reporting 57 trials of 54 interventions. Pooled mean difference and 95% CIs for days of school attended was 0.63 (-0.34 to 1.61), I2=64.0%, low certainty, for mentoring interventions and 0.43 (0.10 to 0.76), I2=91.9%, moderate certainty, for parental engagement interventions. Other intervention areas including targeted approaches, behavioural programmes and social-emotional interventions had smaller, heterogeneous evidence bases. Risk of bias was moderate-to-low in most trials. CONCLUSION: A large range of interventions exist to address the diverse causes of school absence. Parental engagement demonstrated a small positive effect on attendance, particularly among younger age groups. Most trials were from the USA; implementation and evaluation in other countries will inform effectiveness.

CHILD

The hidden threat from food-derived carbon dots: Formation, biodistribution, and potential health risks.

Food-derived carbon dots (CDs) are a new class of carbon-based nanoparticles generated during the thermal processing of food matrices. These nanomaterials have been extensively studied for their unique fluorescence, good biocompatibility, and tunable surface chemistry in food detection, intelligent packaging, and biomedical applications. However, their nanoscale size and high surface activity have raised safety concerns regarding biological interactions, in vivo biodistribution, and potential long-term health hazards. Although CDs have traditionally been regarded as low-toxicity materials due to their favorable biocompatibility, the potential hidden risks of CDs have not received sufficient attention. CDs exhibit dose-dependent toxicity, not only accumulating in various tissues and organs but also potentially inducing oxidative stress and interfering with cellular metabolic functions. Therefore, this review summarizes the advances in sources, synthetic strategies, and core properties of CDs, with a special focus on in vivo biological interactions, fates, and potential safety challenges. In addition, it is proposed that the standardized detection and risk assessment system should be established to further explore the long-term health effects of CDs under real dietary exposure, thereby ensuring their safety and sustainable application.

Carbon Quantum Dots

Recent advances in Strongyloides screening, diagnostics, therapeutics, and management.

PURPOSE OF REVIEW: Strongyloidiasis affects an estimated 30-100 million people globally and can have life-threatening consequences in immunocompromised hosts, yet it remains underdiagnosed due to limited access and performance of available diagnostics. Novel assays and anthelmintics may reshape screening, diagnosis, treatment, and prevention for at-risk populations. RECENT FINDINGS: Advances in molecular diagnostics coupled with robust stool extraction methods have supplanted traditional parasitologic methods in settings where nucleic acid amplification is feasible. Transition from standard immunoglobulin G (IgG)-based immunoassays to the new IgG- and IgG4-based rapid diagnostic tests using recombinant Strongyloides stercoralis nematode immunodominant E antigen (NIE) and/or S. stercoralis immunoreactive antigen (SsIR) has facilitated serologic screening at the point of care. The World Health Organization now conditionally recommends community-wide ivermectin mass drug administration in highly endemic settings. Regarding new treatment options, moxidectin is noninferior to ivermectin with 93-94% cure rates and a longer half-life, while emodepside shows 80-90% predicted cure rates in early trials and offers a mechanistically distinct option. Understanding of immunosuppressed populations at risk for hyperinfection has expanded, prompting updated screening recommendations. SUMMARY: Serologic and molecular tools are improving screening and diagnosis, and moxidectin and emodepside may broaden treatment options, but data in severe disease and special populations remain limited. Priorities include harmonized screening algorithms and prospective studies in high-risk groups.

Humans

Genital surgery in children with differences of sex development (DSD): Strengths and concerns across diverging regulations in four European countries.

Differences of Sex Development (DSD) is a collective term for a heterogeneous group of rare congenital conditions characterized by atypical genetic, gonadal, or genital sexual development. The treatment of children with DSD, particularly the indications for and timing of surgical interventions, has been the subject of debate for decades. In recent years, social developments emphasizing children's rights to self-determination and bodily integrity, along with increasing societal acceptance of atypical sex characteristics, have encouraged a more cautious approach toward early genital surgery in children with DSD. In 2019, the European Parliament adopted a resolution urging Member States to enact legislation prohibiting elective genital surgical interventions on intersex infants and children. Since then, several countries have indeed implemented restrictive measures, including legal bans on early surgical procedures. In this paper, we share the experiences and insights gained in recent years as pediatric urologists working in four neighboring countries in multidisciplinary university centers specializing in DSD care and research. We focus on current approaches to the care of children with DSD, the evolution of relevant national policies over time, and the nature and impact of recently introduced restrictive regulations on early surgical interventions. By presenting perspectives from pediatric urologists across these four countries, we aim to contribute to ongoing discussions on the alignment and refinement of surgical treatment practices for children with DSD.

Humans

The mighty microproteins: from versatile cellular regulators to precision medicine therapeutics.

Microproteins, are tiny proteins encoded by small open reading frame (sORF), translation of these non-canonical open reading frames (ncORFs) has been implicated in diverse biological processes and diseases. This review summarizes recent developments in the discovery, biogenesis, and functional characterization of microproteins, and their involvement in various disease, with special focus on their roles in cancer, cardiovascular, metabolic, neurodegenerative and immune-related disorders. We emphasize the regulation of key cellular pathways by microproteins, including mitochondrial homeostasis, apoptosis, metabolic reprogramming, and immune signaling, all of which affect disease initiation and progression. Emerging evidence also supports their potential as disease biomarkers and therapeutic candidates for precision medicine. Finally, the review critically discusses the current challenges including discrepancies in microprotein annotation, the limitations of ribosome profiling and proteogenomic approaches, the gap between computationally predicted and experimentally validated microproteins, and the need for rigorous orthogonal validation by means of CRISPR-based genome editing, ribosome release assays, mutational analysis, high-resolution mass spectrometry, and functional studies. Finally, we review recent development of AI-assisted ORF prediction, single-cell translatomics, spatial proteomics, and integrated multi-omics as emerging technologies reshaping. Microprotein discovery and functional annotation. Finally, we discuss the translational potential of microproteins and highlight the remaining challenges to clinical application, including peptide stability, pharmacokinetics, tissue-specific delivery, immunogenicity, and the need for rigorous preclinical and clinical validation. Together, this review provides an updated and critical overview of the rapidly evolving microprotein field and highlights future research priorities for translating these molecules into clinically useful biomarkers and precision therapeutics.

Microproteins

Venomous Lepidoptera: defensive toxin systems, venom composition, and clinical significance.

Venomous Lepidoptera constitute an underrecognized yet medically significant group of toxin-producing arthropods that employ contact-mediated defensive envenomation through specialized integumentary structures such as setae, spines, and scoli. Unlike actively stinging arthropods, these insects deliver venom passively upon contact, eliciting a diverse spectrum of clinical manifestations collectively termed lepidopterism. Clinical outcomes range from localized pain and dermatitis to severe systemic effects, including hemorrhagic syndromes, complement activation, and chronic inflammatory disorders. Recent advances in proteomic and transcriptomic technologies have transformed our understanding of lepidopteran venoms, revealing unexpectedly complex toxin repertoires comprising serine proteases, phospholipases, pore-forming proteins, disulfide-rich peptides, neuroactive RF-amide peptides, and immune-modulating components. These findings have provided new insights into the molecular basis of toxicity, host-pathogen interactions, and the evolutionary diversification of venom systems within Lepidoptera. This review synthesizes current knowledge on the morphology of venom-delivery structures, venom composition, mechanisms of action, and associated clinical manifestations, while highlighting medically important taxa, particularly species of the genus Lonomia. The successful development of antivenom against Lonomia envenomation underscores the translational relevance of lepidopteran toxin research and its potential for therapeutic innovation. By integrating molecular, clinical, and evolutionary perspectives, this review repositions venomous Lepidoptera as a legitimate and important component of arthropod toxinology. Furthermore, it identifies critical methodological limitations and key knowledge gaps, providing a framework for future investigations aimed at advancing our understanding of toxin biology, immunopathology, and the development of novel biomedical applications.

Animals

Transcriptome analysis of the pectoral fin degeneration in half-smooth tongue sole (Cynoglossus semilaevis).

Appendage degeneration is a notable morphological feature of some teleosts with specialized benthic lifestyles. The half-smooth tongue sole (Cynoglossus semilaevis) undergoes severe pectoral fin regression during metamorphosis. However, the molecular basis underlying rapid pectoral fin degeneration remains unclear. Here, we performed time-series transcriptome sequencing on pectoral fins at pre-metamorphosis, metamorphosis peak and post-metamorphosis to characterize the molecular changes associated with pectoral fin degeneration. Transcriptional dynamics and functional enrichment showed that no significant enrichment of classical apoptosis-related transcriptional pathways was detected during pectoral fin degeneration. Instead, sustained downregulation of twist1b, identified as a transcriptomic candidate, together with significant upregulation of ssh1, coupled with enrichment of lysosome and ubiquitin-proteasome system (UPS) pathways, suggested enhanced tissue remodeling during pectoral fin degeneration. Temporal expression clustering revealed heterochronic misalignment in the developmental gene expression: upstream initiator tbx5 was upregulated at early metamorphosis, while downstream maintenance signal fgf10 decreased synchronously. Distal patterning gene hoxd12a exhibited premature expression and rapid decay, losing sustained late-phase expression. Moreover, transient elevation of gli3 during metamorphosis may contribute to restricted distal fin growth. We conclude that pectoral fin degeneration in C. semilaevis is associated with heterochronic disruption of developmental signaling and extensive tissue remodeling. This study provides transcriptomic insights into pectoral fin degeneration in tongue soles and establishes a basis for future functional studies of appendage reduction in teleosts.

Animals

Comparative analyses of olfactory receptor repertoires in Schizothorax fish based on the chromosome-level genomes: Implications for regulatory roles of dietary differentiation and ploidy variation.

The olfactory receptor (OR) genes constitute the molecular basis of fish olfaction, mediating survival behaviors and environmental adaptation while coevolving with habitat-driven evolution. Schizothorax, a cyprinid genus endemic to the Qinghai-Tibetan Plateau, exhibits remarkable dietary divergence and ploidy variation in response to plateau environmental changes, which presumably facilitates the adaptive evolution of OR genes. However, the evolutionary patterns of OR genes associated with trophic divergence and ploidy variation in this genus remain unclear. In this study, three species were selected: the herbivorous diploid S. macropogon, the carnivorous diploid S. lantsangensis, and the herbivorous tetraploid S. curvilabiatus. S. macropogon possessed 142 OR genes (92.25% functional), primarily located on chromosomes 14 and 24, with the fewest sequence clusters. Such compact gene repertoire and highly overlapping chromosomal clusters indicated specialization for a herbivorous olfactory niche. S. lantsangensis contained 127 OR genes (93.70% functional), concentrated on chromosomes 4 and 5, with fewer sequence clusters and a scattered distribution, reflecting evolution of OR genes under carnivorous feeding habits. The herbivorous tetraploid S. curvilabiatus exhibited striking features: 316 OR genes (94.30% functional), the most subfamilies, unique &#x3b5; and &#x3ba; OR subfamilies, and species-specific motifs. These characteristics revealed that ploidy, rather than herbivory, dominated OR gene evolution. In conclusion, dietary differentiation and ploidy variation together drove olfactory adaptive evolution in Schizothorax, providing new insights into vertebrate OR gene ecological adaptation.

Animals

The Meaning and Significance of Breastfeeding for Biological Mothers of Children with Cleft Lip and/or Palate.

INTRODUCTION: Given the functional, emotional, and symbolic challenges imposed by cleft lip and/or palate (CL/P) on exclusive breastfeeding (EBF), mothers often experience early breastfeeding cessation with impacts on maternal identity and the mother-infant bond. This study aimed to explore the meanings, feelings, and experiences of mothers of children with CL/P regarding breastfeeding in the face of these adversities. METHODS: This qualitative study applied the Clinical-Qualitative Method as proposed by Turato. Six in-depth semistructured interviews were conducted with biological mothers of children with CL/P, recruited from a specialized craniofacial reference center in Brazil. Data were analyzed using a qualitative content analysis approach, grounded in psychodynamic concepts from the Medical Psychology theoretical framework. RESULTS: Based on the analysis of the collected material, three analytical categories were identified and constructed: (1) "Existential conflict regarding the inability to fulfill the ideal maternal role"; (2) "Duality between the need and the fear of caregiving"; and (3) "The anguish experienced between tangible and intangible support during breastfeeding."Conclusions:Although the inability to EBF in children with CL/P generates emotional distress, motherhood is reimagined through adaptive forms of care and bonding, highlighting gaps in institutional support and the need for more humanized, emotionally sensitive health practices.

Humans

Viral replication through phase separation: Cytosolic and nuclear condensates.

Replication of many RNA and DNA viruses occurs within specialized intracellular hubs organized as membraneless biomolecular condensates (BCs) driven by liquid-liquid phase separation. As obligate intracellular parasites, viruses depend on the host cell machinery to complete their replication cycles and therefore actively remodel the intracellular environment to favor viral genome replication, transcription, and assembly. Cytosolic and nuclear phase-separated replication compartments (RC) provide concentrated and dynamic platforms that promote efficient interactions between viral genomes and viral or host proteins essential for infection. The formation of viral replication BCs is typically facilitated by viral proteins enriched in intrinsically disordered regions and low-complexity domains, which enable multivalent interactions with viral nucleic acids and cellular factors. These interactions are mediated by diverse biophysical forces, including hydrophobic and &#x3c0; interactions, hydrogen bonding, molecular crowding, and osmotic effects. Throughout infection, viral BCs remain highly dynamic, allowing continuous exchange of components and functional maturation of replication hubs. Their properties and activities are further regulated by post-translational modifications of viral and host proteins, such as phosphorylation, acetylation, and methylation. In this review, we summarize current evidence supporting liquid-liquid phase separation as a central organizing principle of viral RCs. We focus on representative RNA and DNA viruses that replicate in the cytosol or nucleus, highlighting virus-specific strategies, conserved mechanisms, and the consequences of BC formation for viral replication efficiency, host antiviral responses, and therapeutic intervention.

Phase Separation

The relationship between composite dietary antioxidant index and odds of depression: A systematic review and dose-response meta-analysis of observational studies.

BACKGROUND: Recently, the association between the composite dietary antioxidant index (CDAI) score and depression has received special attention from researchers. However, this possible association has not been comprehensively examined. Thus, the present study aims to comprehensively assess the relationship between CDAI score and depression odds. METHODS: A thorough literature search was performed using Scopus, PubMed, and Web of Science up to November 2025. Observational studies assessing the relationship between CDAI score and depression odds were included. The odds ratios (ORs) and their 95% confidence intervals (CIs) reported in each study were extracted, and a pooled effect size was calculated using a random-effects model with inverse-variance weighting. RESULTS: Four observational studies were included in the current systematic review and meta-analysis. The pooled effect size indicated that a higher CDAI score was associated with lower odds of depression (OR:0.62; 95%CI: 0.51-0.76, I2&#xa0;=&#xa0;48.5%; P-value&#xa0;=&#xa0;0.121). In an exploratory linear dose-response analysis based on two eligible studies, no significant association was observed between a one-unit increase in CDAI score and the odds of depression (OR&#xa0;=&#xa0;0.96; 95% CI: 0.91-1.02; I2&#xa0;=&#xa0;92.2%; P-value<0.001). Given the limited number of studies and substantial heterogeneity, these findings should be interpreted cautiously. CONCLUSIONS: Our findings suggest that higher CDAI scores, reflecting greater adherence to antioxidant-rich dietary patterns, are associated with lower odds of depression.

Humans

Identification and characterization of G protein-coupled receptors in the nocturnal halictid bee Megalopta genalis.

G protein-coupled receptors (GPCRs) are one of the largest families of membrane proteins in insects, regulating vision, neural signal transduction, and various physiological behaviors. Megalopta genalis exhibits a unique facultatively eusocial lifestyle and possesses adaptations for nocturnal activity; however, its GPCR family has not yet been systematically characterized. In this study, we performed genome-wide identification, phylogenetic analysis, and expression profiling of GPCRs in M. genalis by integrating genomic annotation and transcriptomic analysis. The results showed that a total of 99 GPCRs were identified in the genome of M. genalis, which were classified into four major families. Here, we show that M. genalis has undergone lineage-specific GPCR repertoire remodeling, marked by the expansion of novel orphan receptors and the systematic loss of multiple receptor subtypes, such as the neuropeptide receptors MIP-R and NPFR. Moreover, opsins have formed a diverse array of combinations and non-GPCR odorant receptors have undergone significant expansion via tandem duplication. Together, these features may represent part of the molecular repertoire associated with the adaptation of M. genalis to a nocturnal lifestyle. Furthermore, transcriptomic analysis revealed distinct spatiotemporal expression divergence within each of the Mth/Mthl and Fz GPCR families, suggesting functional specialization across development and adult tissues. This study provides the first systematic identification and initial functional characterization of GPCRs in M. genalis, revealing an evolutionary pattern characterized by the coexistence of contraction and expansion within the GPCR family. These findings lay a foundation for further studies aimed at elucidating the roles of these GPCRs in regulating M. genalis physiology and behavior.

Animals

Metabolic depot for nucleated erythrocyte degradation: molecular and structural elucidation of the teleost melanomacrophage center.

The function of melanomacrophage centers (MMCs) has long been controversial. While their foundational function is widely accepted as "metabolic dumps" for waste processing, a widely circulated hypothesis posits that they are primitive germinal centers (GCs) executing adaptive immunity. To elucidate this controversy, this study systematically evaluated the splenic MMCs in a higher teleost ( Micropterus salmoides) by combining transmission electron microscopy (TEM) and high-resolution spatial transcriptomics. Structurally, TEM revealed that the MMC comprises a core with characteristic sparse cellular density, filled with cellular debris and encapsulated by a fibrous layer. Molecularly, under physiological conditions, MMC regions exhibited low transcriptional activity. We did not detect clear enrichment of B cell and T cell lineage genes, and the key GC marker aicda was not observed. Conversely, its predominant molecular signature was characterized by macrophage-driven iron metabolism (e.g., ferritin) and erythrocyte degradation (e.g., hba1). Furthermore, the physicochemical properties of MMCs pigments (e.g., argyrophilia) suggest that traditional histological staining methods warrant cautious interpretation regarding potential non-specific signals. In conclusion, our findings characterize the MMC as a highly specialized metabolic processing and sequestration niche. This study provides new perspectives on the evolution of immune-metabolic homeostasis in poikilothermic vertebrates, advances comparative immunology, and offers a critical scientific reference for the accurate interpretation of MMCs as a biological indicator in pathology and ecotoxicology.

Animals

Normoalbuminuric and albuminuric diabetic kidney disease exhibit divergent renal proteomic characteristics: implications for management.

BACKGROUND: The pathogenesis of diabetic kidney disease (DKD) is complex. Normoalbuminuric diabetic kidney disease (NADKD) is a special subtype of DKD that often progresses insidiously without detectable albuminuria, posing diagnostic and therapeutic challenges. Its pathogenesis remains unclear. Proteomic analysis of renal tissues may offer insights into its pathogenesis and identify biomarkers. METHODS: Clinicopathological data from 295 biopsy-proven DKD patients were collected and classified into normoalbuminuric (UACR&#xa0;<&#xa0;30&#xa0;mg/g, n&#xa0;=&#xa0;25), microalbuminuric (UACR 30-300&#xa0;mg/g, n&#xa0;=&#xa0;26), and macroalbuminuric (UACR&#xa0;>&#xa0;300&#xa0;mg/g, n&#xa0;=&#xa0;244) groups. Laser microdissection combined with mass spectrometry (LMD/MS) was used to analyze glomerular and proximal tubule proteomics in 5 patients per DKD subgroup and 5 control subjects. Associations with clinical features were examined. RESULTS: Glomerular proteomic analysis revealed that oxidative stress and metabolic pathways (UQCRC1) were upregulated in NADKD group, whereas the complement and coagulation cascades (C3, C5, C6, C9, CFH, CFHR1) were significantly upregulated in the microalbuminuric and macroalbuminuric DKD groups. The proximal tubule proteomics analysis showed that oxidative phosphorylation-related proteins (SDHA, CYCS, UQCRQ) were upregulated in NADKD, and collagen I related proteins (COL1A1, COL1A2) were significantly upregulated. CONCLUSION: Oxidative stress and mitochondrial dysfunction are involved in the progression of NADKD, lesions predominantly located in the tubulointerstitium. The complement pathway participates in the pathogenesis and progression of albuminuric DKD (ADKD). These divergent molecular profiles suggest that NADKD and ADKD may reflect different pathophysiological mechanisms and have important implications for therapeutic strategies in diabetes management.

Humans