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PubMed2026

Age- and sex-adjusted genomic differences between Korean and Beat AML cohorts.

Genomic profiling plays a central role in risk stratification and therapeutic decision-making in acute myeloid leukemia (AML), yet the clinical implications of population-specific genomic architectures remain incompletely defined. We conducted a prospective, multicenter study of 603 adults with newly diagnosed AML in Korea, integrating targeted sequencing of 83 recurrently mutated genes with comprehensive clinical annotation across treatment intensities, including allogeneic hematopoietic stem cell transplantation (allo-HSCT). For contextual comparison, genomic profiles were evaluated against the Beat AML cohort. The overall genomic landscape was broadly conserved, supporting shared core disease biology across populations. However, RUNX1::RUNX1T1, CEBPA, GATA2, KIT, and DDX41 mutations were more frequent in the Korean cohort, whereas FLT3 and NPM1 mutations were less common. These differences translated into a distinct distribution of European LeukemiaNet (ELN) 2022 risk categories, with implications for therapeutic stratification. Notably, most DDX41 alterations were germline (3.2%), highlighting the need for systematic germline evaluation with implications for genetic counseling and donor selection. Although unadjusted overall survival appeared longer in the Korean cohort, this difference was not significant after adjustment for key clinical variables. These findings indicate that population-specific genomic distributions reshape the clinical application of risk stratification and support population-aware precision medicine strategies in AML.

Journal Article↗

PubMed2026

Identification of molecular subtypes in clear cell renal cell carcinoma based on chromatin regulators and tumor immune microenvironment profiling.

In the histological classification of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC) accounts for the highest proportion and is the most common subtype. Despite advances in management, it continues to be associated with considerable incidence and mortality. Although surgery and systemic therapies are available, their efficacy is constrained by pronounced intratumoral heterogeneity and treatment resistance. Identifying robust biomarkers and clarifying the underlying biological mechanisms are therefore essential to improving diagnosis, risk stratification and therapeutic decision-making. In this work, we identified two ccRCC molecular subtypes displaying divergent chromatin regulator (CR) profiles and different clinical prognoses. Using the genes differentially expressed between these subgroups, we constructed a CR-related score (CRS) that effectively stratified patients according to survival. More analysis concluded that the low expression of CR was more linked with the immune-activated tumors, which encompassed the immune pathway enrichment, as well as the elevation of numerous immune cell subtypes. Moreover, elevated CRS was associated with improved immunotherapy responsiveness. Drug-sensitivity analyses nominated several candidate agents, and SMARCD3 knockdown in 786-O cells inhibited proliferation and migration and reduced sensitivity to masitinib. Collectively, these findings support the prognostic and therapeutic relevance of CR-related states in ccRCC and provide a framework for future experimental validation of chromatin-regulated tumor-immune interactions.

Humans↗

PubMed2026

Hippocampal teneurin-4 knockdown promotes depression-like behavioral phenotypes by disrupting oligodendrocyte differentiation in mice.

Depression is one of the most prevalent mental disorders worldwide. The limited clinical efficacy of current antidepressants highlights identifying new therapeutic targets. Emerging evidence suggests that dysfunction of oligodendrocyte lineage cells contributes to the pathophysiology of depression. Teneurin-4 (Tenm4), a transmembrane protein that promotes oligodendrocyte differentiation and myelination, has been implicated in psychiatric disorders in genome-wide association studies; however, its causal role remains unclear. To determine whether Tenm4 contributes to depressive-like behavioral phenotypes, we examined Tenm4 protein expression in mice exposed to repeated forced swimming stress and generated hippocampal Tenm4 knockdown (Tenm4KD) mice. Chronic stress reduced Tenm4 expression levels in the hippocampus. Mice with hippocampus-specific Tenm4KD exhibited depressive-like behaviors, accompanied by reduced hippocampal myelin basic protein. Importantly, administration of clemastine, a myelin formation promoter, inhibited the reduction of myelin and attenuated depression-like behavioral phenotypes. Immunohistochemical analysis showed that Tenm4KD significantly decreased the number of mature oligodendrocyte cells and increased in the number of oligodendrocyte precursor cells, without changes in the total number of oligodendrocyte lineage cells. This study provides the first evidence that hippocampal Tenm4 deficiency induces depression-like behavior phenotypes through impaired oligodendrocyte differentiation and promoting demyelination. Our results identify Tenm4 as a molecular regulator of stress-induced behavioral phenotypes and suggest that it might represent a potential therapeutic target for mood disorders associated with demyelination.

Animals↗

PubMed2026

Patient experiences of diagnostic uncertainty in musculoskeletal care: a systematic review of qualitative studies.

BACKGROUND: Diagnosis plays a central role in musculoskeletal care. However, establishing a clear diagnosis is often challenging, and diagnostic uncertainty is common. OBJECTIVES: To explore patient experiences of diagnostic uncertainty in musculoskeletal care. METHODS: Five databases (CINAHL, Embase, MEDLINE, AMED, Web of Science) were searched from inception to October 2025. Qualitative studies involving semi-structured interviews with adults receiving care for MSK conditions were included. Methodological quality was appraised using the Joanna Briggs Institute Qualitative Checklist. Data were synthesised using thematic synthesis, and confidence in findings was assessed using the Grading of Recommendations Assessment, Development, and Evaluation Confidence in the Evidence from Reviews of Qualitative Research approach (GRADE-CERQual). RESULTS: Twenty-six studies involving 462 participants were included. Critical appraisal identified 23 studies with varying methodological limitations; all studies were included in the synthesis. Nine descriptive themes were synthesised into three analytical themes: (1) patient expectations and perceived meanings of a diagnosis and interpretations of diagnostic uncertainty; (2) the multi-dimensional experience of diagnostic uncertainty; and (3) the role of contextual factors, particularly communication and the therapeutic relationship, in shaping experiences of diagnostic uncertainty. Using GRADE-CERQual, confidence in these themes was rated as low, moderate and very low, respectively. CONCLUSION: Diagnostic uncertainty is a subjective and multi-dimensional experience shaped in part by patients' expectations and the meanings attributed to diagnosis. Its impact spans predominantly cognitive and affective domains and may influence clinical presentation. Patient-centred communication and strong therapeutic relationships may support patients in navigating diagnostic uncertainty in musculoskeletal care.

Adult↗

PubMed2026

A Novel Moisturizer Formulated With Micronized Centella asiatica and Mandelic Acid Improves Mature, Crepey Skin.

BACKGROUND: Dermatoporosis is a condition of fragile, aging skin that manifests as altered pH, wrinkles, laxity, easy bruising, and hyperpigmentation. This study evaluated efficacy, safety, and subject perception after the use of a novel cream, GC (Galderma Laboratories, LP, Fort Worth, TX), on subjects with mature, aging skin. METHODS: A 12-week multicenter, randomized, blinded, in-use study enrolled female and male subjects aged 40 to 60 years of all races, ethnicities, and Fitzpatrick skin types. Subjects were required to have a history of fragile skin and dry, crepey skin on the knees and thighs. GC cream was applied to knee and upper thigh skin twice daily. Assessments included clinical grading, digital photography, bioinstrumentation (skin texture, pH, and heatmap hydration), standard safety assessments, and satisfaction. RESULTS: Use of GC cream for 12 weeks resulted in significant improvements in skin crepiness, photodamage, and firmness, as well as decreased skin pH and early improvements in skin roughness and smoothness from baseline. Corneometer heatmapping documented improved skin hydration over baseline. No adverse events were reported; the GC cream was well tolerated, and subjects reported high satisfaction. CONCLUSION: Twice-daily application of the novel GC skin cream significantly improved the overall skin quality of mature, aging skin, including crepiness, photodamage, firmness, texture, pH, and hydration. GC cream was well tolerated with high subject satisfaction. These data are intended to help guide healthcare providers and patients in choosing an effective moisturizer that was specifically designed for patients with fragile, mature skin.

Humans↗

PubMed2026

PPRC1 is a prognostic biomarker and key regulator of mitochondrial oxidative phosphorylation in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) remains an incurable haematological malignancy, underscoring the need for novel prognostic biomarkers and therapeutic targets. This study aimed to investigate the clinical and biological significance of peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1) in MM. METHODS: Expression and clinical data were obtained from public databases and an independent local cohort. Kaplan-Meier and Cox regression analyses were performed to evaluate prognostic value. Differential expression analysis, pathway enrichment analysis and single-cell RNA-seq data analysis were used to explore biological functions. PPRC1 was silenced in MM cell lines using siRNA to assess its effects on cell survival and oxidative phosphorylation. RESULTS: PPRC1 was significantly upregulated in MM and was associated with advanced disease stage and poor overall survival. Multivariate Cox analysis identified PPRC1 as an independent prognostic factor. A nomogram incorporating PPRC1 and revised-ISS improved survival prediction. Functional analyses revealed that PPRC1 was positively correlated with oxidative phosphorylation and oncogenic signalling pathways. A potential connection between PPRC1 expression and immune cell infiltration was observed. PPRC1 knockdown inhibited cell proliferation, induced cell cycle arrest and apoptosis and impaired oxidative phosphorylation in MM. CONCLUSIONS: PPRC1 acts as a prognostic biomarker and metabolic regulator in MM by sustaining mitochondrial oxidative phosphorylation. These findings highlight PPRC1 as a potential therapeutic target in MM.

Humans↗

PubMed2026

The emerging applications of JAK inhibitors in dermatology - a systematic review.

BACKGROUND: Janus kinase (JAK) inhibitors are established treatments for selected dermatologic conditions, but their off-label use has expanded across refractory skin diseases. METHODS: We systematically searched MEDLINE, Embase, and Web of Science from inception to October 1, 2025, for studies reporting off-label JAK inhibitor use in dermatologic disorders beyond approved or late-phase trial indications. RESULTS: Of 9,182 records screened, 277 studies met the inclusion criteria, comprising 210 case reports, 55 case series, and 12 retrospective studies involving 764 patients. Owing to substantial clinical heterogeneity, findings were narratively synthesized using a structured disease-family framework. Off-label use most commonly involved lichenoid, neutrophilic, and granulomatous dermatoses. Overall, 725/764 (94.88%) patients experienced clinical benefit, including complete or near-complete response in 209/764 (27.35%) and significant or partial improvement in 516/764 (67.53%). Thirty-five patients (4.58%) showed no clinical change, and four (0.52%) experienced disease worsening. A total of 154 adverse events were reported, most commonly with tofacitinib; most were mild to moderate, although six were serious and 25 resulted in treatment discontinuation. CONCLUSION: JAK inhibitors demonstrate promising therapeutic potential across a broad spectrum of refractory dermatological diseases. The predominance of uncontrolled case-based evidence, heterogeneous dosing, and frequent combination therapy limits attribution of efficacy and safety to JAK inhibitor monotherapy. Prospective controlled studies are needed to better define their therapeutic role.

Humans↗

PubMed2026

Integrative modeling of the genome structure and dynamics in fission yeast.

Genome organization in the nucleus is highly structured and dynamic. Recent advances in genomic technology have enabled the measurement of genome-wide architecture and locus-specific motion, yielding contact maps and live-cell trajectories. However, these outcomes are derived from different modalities and are not directly comparable, with their quantitative integration being a key challenge. Here we establish a genome-wide live-cell imaging platform in fission yeast Schizosaccharomyces pombe, tracking 131 chromosomal loci, along with the spindle pole body (SPB) and nucleolus, to construct a quantitative map of locus dynamics. By integrating these dynamics with contact data through polymer modeling of Hi-C data, we build a physics-based "digital twin" of the S. pombe genome consistent with the spatiotemporal dynamics of interphase chromatin. We validate it against genome-wide mobility patterns and known architectural features, including centromere and telomere clustering. The model also identifies distinct dynamical regimes: centromere- and telomere-proximal loci relax within [Formula: see text]150 s, whereas the remaining loci relax within [Formula: see text]70 s. We measure semiperiodic dynamics of SPB motion, including a characteristic peak near 225 s and [Formula: see text] fluctuations. We use the model with SPB-directed forcing to show how these low-frequency components propagate through the genome to drive genome-wide chromatin displacements. Together, this predictive physics-based modeling framework integrates genome structure and dynamics to reveal how nuclear mechanical driving forces shape chromosome motion, linking mechanically driven chromatin responses to genome maintenance and regulation.

Schizosaccharomyces↗

PubMed2026

A Standardized Nursing-Led Protocol Integrated Pain, Sleep, Medication Adherence, and Symptom Management in Postherpetic Neuralgia.

Postherpetic neuralgia (PHN) is a persistent neuropathic pain condition after herpes zoster that frequently coexists with sleep disturbance, medication-related problems, and fluctuating symptoms. This study evaluated whether a standardized nursing-led protocol could improve multidimensional short-term outcomes beyond usual care. In this prospective, parallel-group randomized controlled trial, 128 adults with PHN were allocated 1:1 to usual care or usual care plus an eight-week protocol integrating structured pain assessment, sleep monitoring, medication-adherence support, and rule-based digital symptom monitoring. The primary outcome was the between-group difference in change in Numeric Rating Scale (NRS) pain score from baseline to Week 8. Secondary outcomes included Pittsburgh Sleep Quality Index (PSQI), MMAS-8 medication adherence, symptom burden, pain-related nocturnal awakenings, breakthrough pain, rescue analgesic use, adverse events, rule-based alerts, and nursing satisfaction. Week-8 data were available for 116 participants (57 usual care; 59 protocol). Mean NRS scores decreased from 7.19 ± 1.08 to 4.82 ± 1.53 in the usual-care group and from 7.28 ± 1.05 to 3.24 ± 1.28 in the protocol group. An NRS reduction of at least 2 points occurred in 49.1% and 76.3% of participants, respectively. The protocol group also showed larger improvements in PSQI, MMAS-8, symptom burden, and nocturnal awakenings, with fewer breakthrough-pain episodes and less rescue-analgesic use. These findings support further evaluation of the standardized nursing-led protocol in preregistered multicenter trials with intention-to-treat analyses and longer follow-up.

Humans↗

PubMed2026

Measurable Residual Disease and the Unresolved Biology of Leukemic Stem Cells.

Measurable residual disease (MRD) testing has transformed the management of hematologic cancers by enabling detection of residual malignant cells after therapy. Current approaches rely on qPCR and next-generation sequencing to monitor leukemia-associated somatic mutations, while multiparameter flow cytometry identifies aberrant leukemic immunophenotypes. Although these methods provide valuable prognostic and therapeutic information, MRD negativity remains an imperfect surrogate for cure. Most MRD platforms evaluate CD45+, rapidly dividing leukemic populations and fail to detect quiescent cells that may survive cytotoxic therapies which efficiently target proliferating hematopoietic cells. Relapse frequently occurs despite deep molecular remission, suggesting persistence of rare leukemic stem cells (LSCs) that are intrinsically resistant to chemotherapy and targeted therapies. The paradox of relapse despite molecular remission could be explained by the presence of very small embryonic-like stem cells (VSELs) which are pluripotent, quiescent stem cells sitting at the top of cellular hierarchy in multiple adult tissues including bone marrow. A pluripotent VSEL divides through asymmetrical cell division to give rise to two cells of different sizes and fates, smaller cell is to self-renew while the bigger is lineage-restricted and tissue-committed progenitor which undergoes extensive epigenetic changes, divides rapidly and undergoes clonal expansion before further differentiation. Dysfunctions of VSELs initiate both solid and hematologic cancers. Based on this view, somatic mutations monitored during MRD assessment possibly represent downstream consequences of clonal expansion rather than the initiating drivers of disease persistence. Thus, exclusive monitoring of somatic mutations and CD45 + leukemic populations possibly overlook rare, small-sized, CD45- VSELs that contribute to therapeutic resistance and relapse.

Humans↗

PubMed2026

A machine learning-derived and functionally validated circadian rhythm signature predicts clinical outcomes and in silico drug sensitivity in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) displays considerable heterogeneity in clinical outcomes, highlighting the need for reliable prognostic biomarkers. While the aberrant expression of circadian rhythm-related genes has been implicated in cancer pathogenesis, its comprehensive role in CRC progression and predicted therapeutic vulnerabilities remains inadequately characterized. METHODS: Bulk and single-cell RNA-sequencing data were integrated from multiple CRC cohorts. A circadian rhythm signature (CRS) was developed through machine learning algorithms and validated for prognostic value. Comprehensive analyses of tumor microenvironment, genomic alterations, and drug sensitivity were performed. Furthermore, the biological function of the core gene, BHLHE40, was validated in CRC cell lines through CCK-8, EdU, and wound healing assays. RESULTS: Single-cell analysis demonstrated an elevated expression signature of circadian rhythm-related genes in dendritic cells. The optimized CRS, comprising 14 circadian rhythm-related genes, successfully categorized patients into high- and low-risk groups. Patients with a high CRS showed markedly poorer overall survival and computationally inferred immunosuppressive features, including reduced CD8+ T cell infiltration and increased M2 macrophage polarization. Genomic analysis revealed enhanced mutation burden in TP53 and alterations in RTK-RAS/WNT pathways. Notably, in vitro assays confirmed that BHLHE40 is significantly overexpressed in CRC cells. Knockdown of BHLHE40 markedly inhibited tumor cell proliferation and migration. Drug sensitivity profiling identified bexarotene and SMER-3 as potential therapeutic options for high-CRS patients. A nomogram integrating CRS with clinical parameters demonstrated superior predictive accuracy for 1-, 3-, and 5-year survival. CONCLUSIONS: The CRS represents a promising prognostic biomarker that reflects tumor immune status and genomic features, providing valuable insights for personalized treatment strategies in CRC.

Circadian rhythm↗

PubMed2026

Post-Breakup Instagram Surveillance: Attachment Style, Personality Traits, and Breakup Distress as Predictors.

The end of a romantic relationship is one of the most emotionally challenging life events. Social media platforms such as Instagram enable users to monitor an ex-partner, a behavior known as Interpersonal Electronic Surveillance (IES), which may complicate coping. This study examined associations with retrospectively reported IES on Instagram during the first 3 weeks post-breakup, focusing on attachment, personality, and breakup-related emotional distress. Previous studies suggest that higher anxious attachment and emotional distress are related to increased monitoring behaviors on Facebook. The present research extends this approach to Instagram, a popular platform among Generation Z, and additionally examines personality factors. Data from N = 232 participants (aged 18-27 years; 84 percent women), who had experienced a breakup within the past year and followed their ex-partner on Instagram, were collected using a cross-sectional online questionnaire. The survey included standardized measures and self-constructed items. Hierarchical regression analyses including breakup-related variables, mediation analyses, and independent-samples t-tests were conducted. Due to extremely low internal consistency, Agreeableness was excluded from inferential analyses. The analyses indicated that Extraversion was the only personality trait directly associated with increased IES. Attachment styles showed no direct associations after emotional distress was included in the model. Emotional distress emerged as the most consistent factor associated with IES, showing patterns consistent with indirect associations involving Neuroticism and anxious attachment, suggesting a central role of emotional distress in post-breakup surveillance behavior. These findings highlight digital monitoring as a potentially maladaptive coping strategy and underscore the importance of addressing social media use in post-breakup adjustment.

Humans↗

PubMed2026

Journey Mapping of the Patient Experience from Diagnosis to End of Life in Lung Cancer: A Qualitative Meta-Synthesis.

OBJECTIVES: This study aimed to systematically synthesize the lived experiences and journey narratives of lung cancer patients across disease stages, and identify key tasks and pain points during the disease course through patient journey mapping, providing evidence for comprehensive disease management throughout the patient journey. METHODS: Ten databases, including PubMed, Embase, Web of Science, Scopus, PsycINFO, CINAHL, Cochrane Library, CNKI, Wanfang, and SinoMed, were systematically searched, with a search period from database inception to August 15, 2025. The JBI Critical Appraisal Tool for qualitative studies was used to evaluate the quality of studies, and the results were integrated using a meta-aggregative approach. RESULTS: Thirteen studies were included. Based on the patient journey mapping, the lung cancer patient journey comprises four potential stages: evaluation and diagnosis, initial treatment, maintenance therapy, and end-of-life. A total of 30 themes emerged within three dimensions: tasks, emotions, and pain points. Each dimension of each stage consists of 2-3 themes. CONCLUSION: The journey of lung cancer patients is protracted and complex, characterized by stage-specific needs and challenges. Future management strategies should be tailored to these distinct phases, providing precision supportive care to optimize treatment outcomes and enhance patients' quality of life. IMPLICATIONS FOR NURSING PRACTICE: This Patient Journey Map integrates routine clinical pathways with patients' lived experiences across each stage, revealing stage-specific challenges and providing targets for tailored nursing interventions. The framework promotes multidisciplinary, digitally enabled supportive care and indicates the importance of including patients' social circles to enhance patient-centered outcomes.

Humans↗

PubMed2026

Early infantile developmental and epileptic encephalopathy: clinical spectrum, diagnosis, outcomes, and evolving treatment strategies.

Early infantile developmental and epileptic encephalopathy (EIDEE) is among the most severe epilepsy syndromes, with onset before three months of age and an estimated incidence of approximately 10 per 100,000 live births. The 2022 International League Against Epilepsy classification unified the historically distinct Ohtahara syndrome and early myoclonic encephalopathy under a single diagnostic framework defined by frequent drug-resistant tonic and/or myoclonic seizures, an abnormal neurological examination, and an abnormal interictal electroencephalogram-most characteristically a burst-suppression pattern. This narrative review synthesizes the clinical, electrophysiological, neuroimaging, genetic, and therapeutic literature within the EIDEE framework. The clinical phenotype is characterized by central hypotonia, postnatal microcephaly, cortical visual impairment, and age-dependent syndromic evolution toward infantile epileptic spasms syndrome or Lennox-Gastaut syndrome in the majority of patients. Electroencephalography remains essential for syndromic classification, while systematic metabolic screening and early trio whole-exome or whole-genome sequencing are central to the etiologic workup, achieving diagnostic yields of 60-65%. The most commonly identified genetic causes include STXBP1, KCNQ2, and SCN2A variants. Outcomes are poor overall and strongly etiology-dependent: vitamin-responsive disorders carry a substantially more favorable prognosis, whereas mortality reaches 25% in genetic cohorts. Genotype-guided pharmacotherapy is now applicable to a clinically meaningful subset of patients, with sodium channel blockers, potassium channel openers, and emerging antisense oligonucleotide therapies representing important therapeutic advances. Gene therapy trials are underway but have encountered early safety signals, underscoring the vulnerability of this population. Critical unmet needs include earlier molecular diagnosis, precision therapies targeting developmental outcomes beyond seizure control, and prospective international registries to characterize the long-term natural history of EIDEE.

Humans↗

PubMed2026

GSTT1 promotes stemness and FGFR inhibitor sensitivity in pancreatic cancer through regulation of CD133 (PROM1).

Pancreatic ductal adenocarcinoma (PDA) is among the deadliest malignancies, driven by metastatic progression and profound cellular heterogeneity. We previously identified glutathione S-transferase theta 1 (GSTT1) as a regulator of a slow-cycling, highly metastatic tumor cell population, suggesting that GSTT1High cells may possess stem-like properties. Here, we define the functional and molecular features of this subpopulation in metastatic PDA. Using a mCherry-tagged Gstt1 reporter system in metastatic murine PDAC cells, we enriched for Gstt1High cells and observed increased tumor sphere formation, accompanied by upregulation of stemness-associated genes including PROM1 (CD133) and activation of Wnt and FGF signaling pathways. In human PDA models, CD133HighGSTT1High cells exhibited enhanced tumor sphere initiation and expansion compared to other populations, defining a maximal stem-like state. Notably, sensitivity to FGFR inhibitors was observed only under tumor sphere conditions, highlighting a context-dependent therapeutic vulnerability. Mechanistically, FGFR3 expression correlated with GSTT1 and CD133 levels, and FGF signaling was required to sustain this state. GSTT1 knockdown reduced CD133 protein levels, impaired tumor sphere formation, and altered sensitivity to FGFR inhibition. These findings were largely recapitulated in patient-derived PDA organoids, where GSTT1 and PROM1 co-expression predicted increased tumor sphere formation and enhanced response to the multi-kinase inhibitor Nintedanib. Together, these results identify a GSTT1HighCD133High stem-like subpopulation in metastatic PDA and identify an FGFR-dependent signaling axis that sustains this state, representing a potential therapeutic vulnerability.

AC133 Antigen↗

PubMed2026

Metabolomics and genomics reveal high diversity and concentrations of cyanopeptides during a Microcystis bloom.

Cyanobacterial blooms are an immense global problem that release complex mixtures of poorly characterized biologically active cyanopeptides into freshwater. In this study, metabolomics and genomics were used to assess the diversity and concentrations of cyanopeptides during a dense Microcystis bloom during the late summer of 2023 in Lake Champlain, a large transboundary lake situated between Canada and the United States. Despite the relatively low genetic diversity of the bloom determined by 16S rRNA metabarcoding, 151 cyanopeptides were detected by non-targeted metabolomics. This represents the most recorded cyanopeptides from a single lake plankton bloom event to date. Fifty-two cyanopeptides were previously reported and 99 represent putative new structures. Standards from the microcystin, cyanopeptolin, microginin, and anabaenopeptin groups were used to either quantify or approximate respective cyanopeptide concentrations over the sampling period. Cyanopeptolins were the most diverse (n = 68) cyanopeptides and the second most abundant, reaching 12,892 μg/L. Microginins were the second most diverse (n = 24) and reached the highest concentrations (18,262 μg/L). Anabaenopeptins were the third most diverse (n = 17) cyanopeptides, reaching 4,818 μg/L. Only 8 microcystins were detected, reaching 4,935 μg/L, where MC-LR was the dominant congener. Target cyanopeptide biosynthesis genes for microcystins (mcyE), cyanopeptolins (mcnC), anabaenopeptins (apnD), microviridins (mdnC), and aeruginosins (aerA) were also quantified using digital droplet PCR (ddPCR). The gene copy numbers for mcyE, mcnC, and apnD were highly correlated with their corresponding cyanopeptide concentrations. Overall, the studied Microcystis bloom produced a very diverse cyanopeptide mixture with high cyanopeptide concentrations including non-microcystin groups.

Microcystis↗

PubMed2026

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 < 30 mg/g, n = 25), microalbuminuric (UACR 30-300 mg/g, n = 26), and macroalbuminuric (UACR > 300 mg/g, n = 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↗

PubMed2026

Genomic and Molecular Interaction Analysis of NodD1 in a Novel Bradyrhizobium yuanmingense sp. B64 Isolate for Nodulation and Symbiosis of Legume Plants.

Rhizobial bacteria are known for their ability to fix nitrogen for leguminous plants and their essential function for sustainable agriculture. This study characterizes the taxonomic status and functional potential of the Bradyrhizobium B64 isolate using integrated genomic and molecular approaches. The whole genome of the B64 isolate was sequenced via Illumina paired-end technology. Species delimitation was performed using average nucleotide identity (ANI) and digital DNA-DNA Hybridization (dDDH). The NodD1 protein structure was modeled using AlphaFold3 and validated by Ramachandran plot analysis. Molecular docking was then conducted to evaluate interactions between NodD1 and four signaling flavonoids: Apigenin, Daidzein, Genistein, and Naringenin. Genomic analysis revealed a maximum ANI of 94.4% and dDDH values between 51.4 and 62.4%. Since these values fall below the standard prokaryotic thresholds (ANI < 95%; dDDH < 70%), the B64 isolate is identified as a novel species. Physiological assays confirmed nitrogen fixation (1.97 ppm), IAA production (3.67 ppm), and phosphate solubilization (26.10 ppm). Structural validation showed 100% of NodD1 residues in allowed regions, ensuring high model reliability. Docking simulations demonstrated strong binding affinities across all flavonoids, with binding free energies ranging from - 8.8 to - 9.0 kcal/mol. Daidzein exhibited the highest thermodynamic stability (- 9.0 kcal/mol), whereas apigenin showed the most extensive residue interaction network. The B64 isolate is a novel Bradyrhizobium species with a high symbiotic capacity. The stable NodD1-flavonoid interactions provide a molecular basis for efficient nodulation, positioning B64 as a promising candidate for developing lipo-chitooligosaccharide (LCO)-based biofertilizers.

Bradyrhizobium↗