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PubMed2026

Clinical pharmacokinetics of afatinib: A systematic review.

BACKGROUND: Afatinib is commonly used in the treatment of non-small cell lung cancer (NSCLC). This systematic review summarizes clinical pharmacokinetics (PK) evidence focusing on the effect of disease state and drug interactions on afatinib exposure. METHODS: Google Scholar, Science Direct, PubMed, and the Cochrane library were searched for human studies reporting the clinical PK of afatinib. The search yielded 24 articles that met the predefined inclusion criteria. RESULTS: Afatinib exposure increased slightly more than dose proportionally, with higher doses producing greater AUC0-24 and Cmax values. The apparent oral clearance reported after administration of the oral solution was lower than that observed following tablet administration. The Cmax of afatinib increases by 38.5% after coadministration with ritonavir and exposure decreases 34.3% with rifampicin. The Cmax decreases 31.45% when given with pemetrexed. Both the AUC0-24 and Cmax increase in NSCLC and tumor state. The AUC0-24 of afatinib is 2.61 folds higher following multiple oral doses among patients with solid tumors. Afatinib exposure is 22.1 % higher in renal impaired patients than in healthy controls. In grade 2 diarrhea, the AUC0-24 of afatinib is 83.93% higher as than in grade 0-1 diarrhea in solid tumor patients. CONCLUSION: This systematic review provides an updated synthesis of clinical PK evidence on afatinib. Afatinib exposure is influenced by dose, repeated administration, renal impairment, diarrhea associated toxicity, and P-glycoprotein mediated drug interactions. These findings may support individualized dosing, toxicity-guided dose adjustment, and future development of PK models for afatinib.

Humans↗

PubMed2026

Siglec-7 orchestrates mitochondrial dynamics and metabolic reprogramming to restrain human NK cell cytotoxic function.

Natural killer (NK) cells are innate lymphocytes that directly eliminate tumor and virus-infected cells by integrating signals from activating and inhibitory receptors, and their effector functions are tightly coupled to cellular metabolism. Given that the inhibitory receptor PD-1 reprograms T cell metabolism to shape functional fate, the bioenergetic consequences of inhibitory receptor engagement on human NK cells remain largely unexplored, particularly for sialic acid-binding immunoglobulin-like lectin (Siglec-7), a glyco-immune checkpoint receptor. Here, we investigated metabolic programs and effector functions associated with Siglec-7 expression and antibody-mediated Siglec-7 ligation in primary NK cells and NK-92MI cells. Siglec-7POS NK cells exhibited selectively impaired CD107a degranulation under glycolytic and oxidative phosphorylation inhibition, whereas Siglec-7NEG cells remained relatively resistant, indicating distinct energetic wiring between these subsets. Engagement of Siglec-7 by an agonistic antibody induced mitochondrial fission with altered Drp1 phosphorylation, transient mitochondrial depolarization, and broadly suppressed mitochondrial respiration, while concurrently enhancing glycolytic capacity, consistent with a dual metabolic shift upon Siglec-7 ligation. In contrast, sustained Siglec-7 expression in NK-92MI-S cells was associated with globally enhanced mitochondrial respiratory capacity, indicating that sustained Siglec-7 expression and short-term treatment with an agonistic anti-Siglec-7 antibody were associated with distinct metabolic profiles in NK cells. Furthermore, Siglec-7POS NK cells showed increased accumulation of autophagic vacuole, reduced proliferation, and heightened apoptotic susceptibility compared with Siglec-7NEG counterparts. Collectively, these findings support an association between Siglec-7 status, mitochondrial homeostasis, and metabolic fitness in NK cells, with Siglec-7NEG cells retaining a metabolically robust, cytotoxic phenotype.

Journal Article↗

PubMed2026

Shared genetic architecture and cellular convergence between female reproductive disorders and pulmonary function: a genome-wide cross-trait analysis.

Female reproductive disorders (FRDs), including polycystic ovary syndrome, endometriosis, uterine leiomyomata, and infertility, have been epidemiologically associated with impaired pulmonary function. However, it remains unclear whether this cross-organ link reflects shared genetic etiology and, if so, which cellular mechanisms mediate it. We performed a systematic genome-wide cross-trait analysis of three FRDs and lung function traits (FEV₁, FVC, FEV₁/FVC) using GWAS summary statistics from individuals of European ancestry, integrating genetic correlation, bidirectional causal inference, pleiotropy mapping, and single-cell enrichment analyses. We identified significant negative genetic correlations between FRDs and lung volume traits, most prominently for FVC (rg range: - 0.077 to - 0.178). Bidirectional causal analyses indicated that FRDs have a detrimental effect on lung volume, with higher FRD genetic liability associated with reduced lung volume. Cross-trait meta-analysis identified 17 pleiotropic variants across 11 loci, with the 19q13.2 (LTBP4) and 12q13.13 (HOXC6/HOXC9) loci showing strong evidence of shared causal variants. Critically, single-cell analyses revealed that shared genetic risk converged on mesenchymal lineages across organs, specifically alveolar adventitial fibroblasts in the lung and stromal/smooth muscle cells in the endometrium. Transcriptome-wide analyses further nominated the estrogen-responsive gene RERG as a convergent gene linking these conditions with lung function. Our study revealed a shared genetic architecture between female reproductive disorders and lung function traits, providing a basis for further mechanistic investigations and potential clinical evaluation. Furthermore, our findings suggest that shared fibroproliferative and hormone-responsive pathways may offer insights into the biological mechanisms underlying these conditions.

Female↗

PubMed2026

Oxygen-controlled gamma-irradiation and annealing enable terminal processing of collagen-based biomaterials.

Gamma irradiation is a widely adopted method for terminal sterilization of medical devices; however, its application to collagen-based extracellular matrix (ECM) materials remains limited due to radiation-induced degradation of structural integrity and mechanical performance. Here, we present an engineered terminal-processing strategy that combines oxygen controlled gamma irradiation (25-30 kGy) with post-irradiation dry-heat annealing to preserve ECM functionality while achieving effective sterilization. By modulating oxygen availability during irradiation, this approach alters radical reaction pathways, suppresses oxygen-mediated oxidative degradation, and generates a metastable radical-containing intermediate, which is subsequently converted into a structurally stabilized collagen network through thermal annealing. As a result, the treated matrices preserved ECM integrity and recovered clinically relevant mechanical properties. Furthermore, the process achieved cumulative viral reductions exceeding 6 log10 across a representative panel including enveloped and non-enveloped DNA and RNA viruses, demonstrating compatibility with sterility assurance and viral safety requirements for biologically derived medical devices. Notably, preliminary observations indicate that mechanical integrity can be partially preserved even at elevated irradiation doses up to 50 kGy, suggesting potential applicability to sterilization validation frameworks requiring higher assurance levels. Overall, this work establishes a mechanistically grounded terminal-processing paradigm that enables control of radical fate, decouples sterilization efficacy from material degradation, and integrates sterilization, viral safety, and functional preservation into a unified and scalable framework for collagen-based biomaterials. This concept repositions gamma-irradiation from a purely degradative process to a controllable tool for tuning collagen structure and performance.

Gamma Rays↗

PubMed2026

LINE-1 repeats are a defining feature of the Xce.

During early development, female mammals inactivate one X chromosome to balance their X-linked gene dosage with males. While allelic choice is random in inbred mouse populations, choice can be significantly skewed in interstrain hybrids. The genetic basis of skewing has long been attributed to the mysterious "X chromosome controlling element(s)" (Xce) with different strengths among species, subspecies, and strains. When two X-chromosomes with different Xce strengths are inherited by offspring, the X chromosome with the stronger Xce will have a higher probability of remaining active. Here, we provide evidence that L1Tf repeats-a subfamily of long interspersed nuclear elements 1-plays a role in determining Xce strength. L1Tf elements form a condensed core within the inactive X (Xi) territory. Mouse strains with varying Xce strengths differ in the L1Tf copy number on the X chromosome, with the strength of the Xce allele being inversely related to L1Tf copy number. L1Tf expression mediates the Xce effect. However, in contrast to a prior report, L1Tf RNA does not coat the Xi. Rather, L1Tf promotes condensation of the Xi core. Intriguingly, L1Tfs recruit and sequester YY1 from active genes, accelerating XCI in cis. Thus, L1Tf copy number, expression, and binding of YY1 are key defining features of the Xce. We propose a model in which the Xce influences the choice of Xist alleles by promoting YY1 binding to the nucleation site for the initiation of Xist spreading.

Animals↗

PubMed2026

Meaning in Life in Palliative Cancer Care: Psychosocial and Existential Outcomes-A Systematic Review.

BackgroundExistential distress, marked by hopelessness, loss of meaning, and spiritual suffering, is prevalent among patients with advanced illness, and is associated with psychological burden and a wish to hasten death (WTHD).PurposeThis systematic review aimed to synthesize current evidence on meaning in life (MIL) in adult palliative care (PC) populations, focusing on its associations with quality of life (QOL), mental health, existential and spiritual well-being (SWB), and WTHD.MethodsMEDLINE, Web of Science, Scopus, and the Cochrane Library were searched for eligible studies (English, 2016-2024) involving adult cancer patients receiving PC. MIL was examined as a central intervention component or outcome. Risk of bias was assessed: findings were synthesized narratively. The review was registered in PROSPERO.ResultsEight studies (n = 1733 participants) were included: four cross-sectional, two randomized controlled trials, one longitudinal observational study, and one qualitative study. Several studies had small samples and substantial attrition. Risk of bias was high (n = 7), and moderate in one cross-sectional study. MIL was inversely associated with depression, anxiety, demoralization, and WTHD; and positively associated with QOL and SWB. MIL may also mediate psychological outcomes (eg, purpose, coherence, and personal values). However, heterogeneity in MIL conceptualization and measurement, combined with low methodological quality, limited comparability and certainty of findings.ConclusionMIL may be relevant to psychosocial/existential outcomes in PC. Conclusions are constrained by a small and methodologically weak evidence base. Further high-quality, longitudinal research is needed before MIL-centered interventions can be recommended for routine clinical practice.

Humans↗

PubMed2026

ATF4-histone 2-hydroxyisobutyrylation feedback loop drives sepsis-induced inflammation.

BACKGROUND AND PURPOSE: The role and mechanisms of lysine 2-hydroxyisobutyrylation (Khib) in the acute inflammatory phase of sepsis remain unclear. We investigated the function and underlying mechanisms of histone H4 lysine 5 2-hydroxyisobutyrylation (H4K5-hib) in sepsis-induced inflammation in vivo and in vitro. EXPERIMENTAL APPROACH: Acute sepsis was induced by caecal ligation and puncture (CLP) in mice, and inflammatory responses were modelled in lipopolysaccharide (LPS)-stimulated macrophages. CUT&Tag-seq was used to identify genomic targets associated with H4K5-hib and activating transcription factor 4 (ATF4). Immunofluorescence, Western blotting, qPCR, dual-luciferase assays, and ELISA were performed to investigate the underlying mechanisms. KEY RESULTS: H4K5-hib levels were increased in macrophages during the acute inflammatory phase of sepsis. LPS stimulation enhanced H4K5-hib enrichment at the ATF4 promoter, thereby promoting ATF4 transcription. Inhibition of EP300-mediated 2-hydroxyisobutyrylation or mutation of H4K5 abolished ATF4 activation. Increased H4K5-hib activated the ATF4/NLRP3 signalling axis, promoting inflammasome assembly and amplifying inflammatory responses. ATF4 directly bound to the EP300 promoter and enhanced its transcription, forming a positive feedback loop that further increased H4K5-hib levels. In CLP-induced sepsis, pharmacological inhibition of EP300 or ATF4 reduced H4K5-hib levels and suppressed NLRP3 inflammasome activation. CONCLUSION AND IMPLICATIONS: These findings reveal a previously unrecognized epigenetic mechanism underlying sepsis-induced inflammation and identify the EP300/ATF4/H4K5-hib positive feedback loop as a potential therapeutic target for sepsis.

Animals↗

PubMed2026

Perinatal depression, maternal thyroid status and fetus/infant health and development: A systematic review.

BACKGROUND: Thyroid hormones are known to influence both maternal depression and child developmental outcomes, while maternal depression independently affects child outcomes. The potential interaction between thyroid dysfunction and depression in shaping child development remains insufficiently explored. The present study addresses such interplay. METHODS: Following PRISMA 2020 and JBI guidelines, three databases were searched through December 2025 for primary studies on maternal thyroid status, perinatal depression, and child development. Risk of bias (RoB) was assessed using validated tools. Due to clinical and methodological heterogeneity, data were synthesized narratively following SWiM guidelines. RESULTS: Eleven studies were included. Beyond independent risks for preterm birth and behavioral problems, limited evidence supports a synergistic model, while most studies likely reflect the simple co-occurrence of risks. Maternal thyroid peroxidase antibodies (TPO-Ab) were associated with child externalizing problems exclusively in the presence of clinical depression. High depressive symptoms also attenuated the cognitive benefits of prenatal iodine supplementation. Thyroid status appears to function as a risk moderator rather than a mediator. However, 50% of observational studies presented high RoB, primarily due to participant attrition. CONCLUSION: Findings are still scarce to support a synergistic risk model where specific maternal thyroid parameters (i.e. thyroid autoimmunity and iodine status) may moderate the impact of depressive symptoms on child development. Despite the high RoB in half of the studies, results highlight the need for integrated screening protocols. Simultaneously assessing mental health and thyroid status may optimize risk stratification for high-risk mother-infant dyads.

Female↗

PubMed2026

Liquid biopsy-based detection of circulating and exfoliated cholangiocarcinoma tumor cells from blood and bile using heparan sulfate octasaccharides on integrated microfluidic systems.

Early diagnosis of cholangiocarcinoma (CCA) remains challenging because existing diagnostic approaches often lack sufficient sensitivity for reliable detection of early-stage disease. Circulating tumor cells (CTCs) in blood and exfoliated tumor cells (ETCs) in bile represent valuable targets for liquid biopsy-based detection; however, their low abundance and the complexity of clinical sample analysis pose substantial technical challenges for reliable enrichment and identification. Herein, we present a reproducible workflow for isolating and identifying CCA tumor cells from blood for CTCs and bile for ETCs using synthetic cell-surface heparan sulfate (HS) octasaccharide-functionalized magnetic beads (MBs) on integrated microfluidic systems. The method combined sample pre-processing, magnetic bead-based enrichment, controlled low-shear mixing and immunofluorescence-based identification into a unified workflow compatible with distinct clinical sample types. Key operational parameters, including MB concentration, mixing frequency, and pressure settings, were detailed to facilitate consistent performance. Using this workflow, tumor cell capture rates of approximately 70% in bile (for ETCs) and blood (for CTCs) were achieved, with a total processing time of 60-90 min per sample under clinically relevant low-abundance conditions. The platform enables reliable detection of as few as 1 tumor cell per mL of blood or bile. This method provides a practical and adaptable strategy for glycosaminoglycan-mediated liquid biopsy applications and may be extended to other tumor-cell enrichment workflows involving heterogeneous cell-surface interactions.

Humans↗

PubMed2025

UV-based homogeneous disinfection process for removal of antibiotic resistance genes: Efficiency, mechanisms and influencing factors.

The proliferation and dissemination of antibiotic resistance genes (ARGs) in aquatic environments pose a serious threat to global public health. Ultraviolet-driven homogeneous advanced oxidation processes (UV-AOPs) represent a prospective suite of technologies for the efficient removal of ARGs. This review critically assesses recent advances in the application of UV-AOPs, specifically UV/hydrogen peroxide (UV/H2O2), UV/peracetic acid (UV/PAA), UV/persulfate (UV/PS), and UV/chlorine (UV/Cl), for the elimination of extracellular ARGs and intracellular ARGs. The underlying mechanisms involve direct ultraviolet-induced DNA damage, including pyrimidine dimer formation and strand breakage, as well as oxidation mediated by radicals such as hydroxyl radicals, sulfate radicals, carbon-centered radicals, and reactive chlorine species. The relative contribution of radical and non-radical pathways is strongly influenced by water chemistry and process conditions. We further expound on the critical operational and environmental factors governing ARG removal kinetics, including UV wavelength and fluence, oxidant type and dosage, ARG sequence characteristics, pH, ubiquitous anions, and dissolved organic matter, which collectively affect radical generation, quenching, and reaction microenvironments. Notably, for i-ARGs, UV-AOPs facilitate degradation not only through direct radical attack but also by disrupting cellular integrity and permeabilizing membranes, thereby enhancing the exposure of genetic materials to oxidative and photolytic damage. This review synthesizes current understanding to provide a mechanistic basis for the design and optimization of UV-AOP systems, highlighting their potential as effective barriers against the dissemination of antibiotic resistance in water reuse and purification scenarios.

Disinfection↗

PubMed2026

The clinical relevance of regional lymph node microarchitecture in oesophageal cancer patients - Results from the UK MRC OE02 trial.

BACKGROUND: In oesophageal cancer (OeC) patients, neoadjuvant chemotherapy followed by surgery improves survival. Anti-tumour immune responses are mediated by lymph node (LN) microarchitecture. We investigated whether neoadjuvant chemotherapy and/or presence of tumour changes LN microarchitecture, and whether such changes are associated with survival. METHODS: Microarchitectural features (lymphocytes, germinal centres (GermC), histiocytes) were quantified morphometrically in 433 LNs from 333 OE02 trial patients (165 neoadjuvant chemotherapy+surgery (CS), 168 surgery alone (S)). Features were compared between tumour-negative (LNneg) and tumour-positive LN (LNpos) by treatment group. Associations with clinicopathological variables and overall survival (OS) were evaluated. RESULTS: LNneg GermC density was lower in CS patients than in S patients (median: 1% vs 2%; p = 0.0004). No other microarchitectural features differed by treatment group or LN status (LNneg vs LNpos). Low histiocyte content in LNneg and LNpos was associated with improved OS in S patients only (HR:0.67, 95%CI: 0.46-0.97, p = 0.03). Multivariable analysis confirmed the independent prognostic significance of LNneg histiocytes (HR:0.62, 95%CI: 0.42-0.9, p = 0.01). CONCLUSION: These findings suggest that LN microarchitecture may be a biomarker for treatment-related immune modulation and prognosis in patients with resectable OeC. These findings warrant independent validation and further investigation to determine whether LN microarchitectural features could inform personalised therapeutic strategies.

Humans↗

PubMed2026

Overcoming Immunological Barriers in MSC-Derived Insulin-Producing Cells through CRISPR-Based Hypoimmunogenic Engineering and Translational Perspectives for Type 1 Diabetes.

Mesenchymal stromal cell (MSC)-derived insulin-producing cells (IPCs) represent an emerging strategy for β-cell replacement in type 1 diabetes mellitus (T1DM) owing to their differentiation potential, intrinsic immunomodulatory properties, and lower tumorigenic risk compared with pluripotent stem cell-derived platforms. However, accumulating evidence indicates that differentiation-associated immunogenicity, context-dependent immune recognition, and recurrent autoimmune responses may substantially limit long-term graft survival and therapeutic durability following transplantation. This review critically examines the immunological barriers associated with MSC-derived IPCs, including altered MHC expression, susceptibility to alloimmune and autoimmune-mediated rejection, and potential reactivation of autoreactive immune memory. We discuss the application of CRISPR-based hypoimmunogenic engineering strategies targeting antigen presentation pathways, NK-cell activation, and immune checkpoint modulation to generate more immune-evasive MSC-derived IPCs while preserving β-cell functionality. By integrating insights from T1DM immunopathogenesis, MSC biology, genome editing, and translational immunology, we propose a framework linking immune engineering with controlled differentiation, functional maturation, and long-term safety evaluation. In parallel, we comparatively position MSC-derived IPCs alongside clinically advancing iPSC-derived β-cell platforms to highlight their distinct translational niche, including potential advantages related to safety, immunomodulatory capacity, manufacturing accessibility, and scalability, while acknowledging the superior functional maturity and clinical progression currently demonstrated by iPSC-derived systems. Finally, we discuss key translational challenges, including genomic stability, immune-evasion durability, GMP-compliant manufacturing, and the need for rigorous functional and immunological benchmarking prior to clinical application of hypoimmunogenic MSC-derived IPC therapies in T1DM.

Humans↗

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

Identification of CXCL13 as an agonist and CXCL11 as an inverse agonist for the viral G protein-coupled receptor ORF74.

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes latent infection in humans, but under conditions of immune suppression, it may reactivate and contribute to severe diseases, including Kaposi's sarcoma (KS) and B-cell malignancies. The KSHV genome encodes a single G protein-coupled receptor (GPCR), open reading frame 74 (ORF74), which shows homology to human chemokine receptors. Since its identification in 1996, ORF74 has subsequently been shown to interact with a broad range of human CXC chemokines, as well as CCL1 and the viral chemokine vCCL2. Compared with many human chemokine receptors, ORF74 displays high basal activity. These properties allow ORF74 to deregulate host cellular pathways through constitutive and chemokine-modulated signaling. In this study, we evaluated several human chemokines that, to our knowledge, had not previously been tested in ORF74-dependent cellular assays. Whereas CXCL9, CXCL14, CXCL16 and CXCL17 did not interact with ORF74, CXCL13 was identified as an additional ORF74 agonist and CXCL11 as an inverse agonist. CXCL13 dose-dependently induced ORF74-mediated Ca2+ release, β-arrestin1/2 recruitment and chemotaxis, and enhanced basal nuclear factor κB (NF-κB) activity in ORF74-expressing cells. In contrast, CXCL11 showed no detectable ORF74 agonist activity in the calcium mobilization or chemotaxis assay, but antagonized CXCL1-induced responses in both readouts. CXCL11 also elicited inverse agonist-like responses in β-arrestin1/2 recruitment assays and reduced basal NF-κB signaling. Our study thus reveals CXCL13 and CXCL11 as two additional chemokine ligands for ORF74, further expanding the pharmacological profile of this viral GPCR.

Humans↗

PubMed2026

Antennal transcriptome analysis of chemosensory proteins in the raspberry weevil, Aegorhinus superciliosus (Coleoptera: Curculionidae).

Aegorhinus superciliosus (Coleoptera: Curculionidae) is a polyphagous pest of economic importance in southern Chile, the chemical ecology of which remains poorly characterized. Across insect species, chemosensory proteins, including odorant receptors (ORs), gustatory receptors (GRs), ionotropic receptors (IRs), odorant-binding proteins (OBPs), chemosensory proteins (CSPs), and sensory neuron membrane proteins (SNMPs), mediate the detection of chemical cues involved in host selection, reproduction, and other ecologically relevant behaviors. In this study, the antennal transcriptome of adult A. superciliosus was sequenced and analyzed using a de novo RNA-seq approach. Three independent biological replicates per sex were used for RNA-seq, and the same number of independent biological replicates was used for RT-qPCR validation; sequencing yielded 147,409,936 high-quality reads after quality filtering. A total of 112 candidate chemosensory genes were identified, comprising 43 ORs, 34 OBPs, 10 CSPs, 18 IRs, 5 GRs, and 2 SNMPs. Phylogenetic analyses assigned these candidate proteins to established clades, providing a comparative framework for functional inference for ORs and OBPs. Sex- and tissue-biased expression analyses revealed that several ORs, including AsupOR4, AsupOR19, and AsupOBP13, exhibit antennal enrichment and sex-specific expression patterns. Notably, AsupOR19 and AsupOBP13 displayed strong female-biased expression. In addition, transcripts of selected ORs and OBPs were detected in non-antennal tissues, such as the rostrum and legs, suggesting potential functional versatility beyond canonical olfaction. Together, these findings represent the first molecular identification of the chemosensory repertoire of A. superciliosus. This study establishes a foundation for reverse chemical ecology approaches aimed at identifying behaviorally active volatile organic compounds (VOCs) toward environmentally sustainable strategies for integrated pest management.

Animals↗

PubMed2026

Soluble CD163 as a Non-Invasive Biomarker in Autoimmune Nephrological and Rheumatological Diseases.

Autoimmune nephrological and rheumatological diseases involve macrophage-driven inflammation, yet disease activity is often assessed using invasive or non-specific measures. Soluble CD163 (sCD163), released from activated monocytes and macrophages, is emerging as a biomarker of macrophage-mediated inflammation in these conditions. This narrative review summarizes current evidence on the diagnostic, prognostic, and disease-monitoring potential of sCD163 measured in blood, urine, and synovial fluid in autoimmune nephrological and rheumatological diseases. This review is based on a narrative analysis of selected publications investigating the clinical utility of sCD163 in autoimmune kidney and rheumatic diseases, with emphasis on correlations with disease activity, histopathological findings, and clinical outcomes. Urinary sCD163 shows excellent diagnostic accuracy for active lupus nephritis (area under the receiver operating characteristic [AUROC] 0.89-0.998), correlates with histological activity index (but not chronicity), and distinguishes ongoing inflammation from chronic damage during treatment. In IgA nephropathy, it predicts remission failure and greater benefit from corticosteroids. In ANCA-associated vasculitis, it identifies active renal involvement (AUROC 0.95 in multicenter cohorts). In rheumatoid arthritis (RA), serum sCD163 correlates with early disease activity, predicts radiographic progression, and detects subclinical macrophage activation in remission. In spondylarthritis, synovial fluid sCD163 reflects a disease-specific M2-polarized macrophage phenotype distinct from RA. Utility is compartmentalized: urinary levels indicate intrarenal macrophage activation, synovial fluid local joint inflammation, and serum systemic activation. sCD163 is a promising macrophage-specific biomarker across autoimmune diseases, but its compartmentalized nature requires context-specific measurement. Before clinical implementation, assay standardization, multicenter validation, and interventional trials showing the benefit of sCD163-guided management are needed.

Humans↗

PubMed2026

Individual differences in brain dynamics across a social cognition network induced by cortico-cerebellar tDCS in adults with autism spectrum disorder (ASD).

Autism spectrum disorder (ASD) is a neurodevelopmental condition with core diagnostic domains of social communication impairments, restricted interests and repetitive behaviors. Idiosyncratic brain organization is a potential hallmark of ASD. Previous transcranial direct current stimulation (tDCS) studies often targeted dorsolateral prefrontal cortex, with changes oin brain dynamics averaged across the cohort. We utilized a magnetoencephalographic (MEG) array to characterize individual differences in brain dynamics induced by cortico-cerebellar tDCS across nodes of a social cognition network. A randomized, sham-controlled, double-blind, within-subject clinical trial was conducted in a cohort of 24 young adults with ASD or high autistic traits. Two separate sessions of computerized social learning activities were combined with verum/sham tDCS, with anodal electrode over right temporoparietal junction (TPJ) and cathode on right deltoid. Following stimulation, theta- and alpha-band activity were evaluated within nodes of a social cognition network: bilateral TPJ, fusiform, medial prefrontal cortex and Crus I/II of cerebellum. Idiosyncratic participant-specific up- and down-regulation of theta- and alpha-band activity occurred across the network. Activity in right Crus I/II, a region inundated by the stimulation current, strongly correlated with the change of activity summed across all cerebral cortical nodes in theta- but not alpha-band. Intrinsic theta-band activity is believed to mediate input/output relationships in cerebellar cortex and to drive synaptic plasticity. These results suggest that theta-band stimulation of cerebellar cortex might be an effective therapy for individuals on the autism spectrum who present with cerebellar hyperactivity.

Humans↗

PubMed2026

An Integrated Proteomics and Genomics Approach to Identify Essential Protein Kinases During Human Trophoblast Development.

In the developing human placenta, three subtypes of trophoblast cells, cytotrophoblasts (CTBs), extravillous trophoblasts (EVTs), and syncytiotrophoblasts (STBs), mediate critical functions essential for a successful pregnancy. CTBs constitute the stem/progenitor compartment and differentiate into STBs and EVTs within the floating and anchoring villi, respectively. STBs establish the maternal-fetal exchange interface and secrete human chorionic gonadotropin (hCG), a hormone vital for the maintenance of early pregnancy. EVTs anchor the maternal endometrium and invade the uterine tissue to remodel maternal cells, supporting implantation and progression of pregnancy. In this study, we used human trophoblast stem cells (hTSCs) as a model system and performed quantitative, label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) to profile the proteome and phosphoproteome in TSC stem state (analogous to undifferentiated CTBs) and following their differentiation to STBs and EVTs. Through a multiomics approach, we integrated our proteomics data with global gene expression profiles to correlate cell-type specific gene and protein expression during human trophoblast development. We also identified global phosphoproteome and analyzed kinases that are specifically active in hTSC stem state, as well as in differentiated STBs and EVTs. We experimentally validated specific kinases, such as BUB1B, PAK6, PKYMT1, and TNIK, that are essential for maintaining the hTSC stem-state. Additionally, atypical protein kinase C isoforms PKCζ are essential for STB development, whereas PTK2B, SRC, TRIO, and LYN are important for EVT development. Our findings highlight key kinases uniquely required for specific stages of trophoblast development during human placentation and suggest that pharmacological inhibition of these kinases could negatively impact the placentation process during pregnancy.

Humans↗