Search Results (928)

Senescence-associated follicular helper T (SA-Tfh) cells contribute to tertiary lymphoid structure (TLS) formation in autoimmune diseases, yet the mechanisms guiding their localization to glandular niches remain unclear. In the Nishiura (NI) Sjögren’s disease (SjD) mouse model, we demonstrated that mouse SA-Tfh (mSA-Tfh; CD4⁺/PD-1⁺/CD153⁺) cells form TLSs specifically within the submandibular gland niche. We identified integrin α7 (ITGα7) expression in mSA-Tfh cells and examined its functional role. Adhesion of mSA-Tfh cells to laminin (LAM) α2/α3/α4 was inhibited by anti-ITGα7 IgG (E-2), and ITGα7-deficient mSA-Tfh cells had reduced adhesion to LAMα1/α2 compared with LAMα3/α4/α5. Osteopontin production by mSA-Tfh cells, either alone or via interactions with mB220⁺/PD-1⁺ cells, was suppressed by E-2, anti-LAMα4 IgG, and ITGα7 deficiency. In female NI mice, E-2 administration at 24 weeks reduced Greenspan grade 4 TLSs at 28 weeks by decreasing ITGα7⁺/CD153⁺ cell accumulation. mSA-Tfh infiltration into aged C57BL/6 mice was similarly diminished by ITGα7 or LAMα4 deficiency. In human SjD cohorts, ITGα7 expression positively correlated with CD153 expression (R² = 0.41) in peripheral lymphocytes and with LAMα4 expression (R² = 0.35) in salivary gland vasculature and ducts. These findings suggest that circulating ITGα7⁺ SA-Tfh cells adhere to the LAMα4⁺ glandular niche to promote TLS formation in SjD. Full article

The FMD is an endangered species under first-class national protection in China. Comparative genomic investigation of microsatellite (SSR) in CDS may provide insights into adaptive evolutionary mechanisms and may inform conservation management strategies for captive populations. Here, we analyzed the FMD genome alongside five closely related ruminants: cattle (Bos taurus), red deer (Cervus elaphus), white-tailed deer (Odocoileus virginianus), sheep (Ovis aries), and goat (Capra hircus). Through genome-wide bioinformatic identification, we systematically compared the abundance, density, structural categories, repeat motifs, chromosomal distribution, and pathway enrichment analysis of SSR-containing genes in CDS. Furthermore, we performed synteny analysis and evaluated population genetic diversity. A total of 2509 SSRs in CDS were identified in the FMD, with a relative density of 62.61 loci/Mb. Trinucleotide SSRs were overwhelmingly dominant (88.46%) in the FMD. Notably, the FMD exhibited the highest relative abundances of both tetranucleotide and pentanucleotide repeats among the six species (2.37 and 2.18 loci/Mb, respectively), with pentanucleotide abundance approximately 5.6- to 9.1-fold higher than that of the other species. Chromosomal mapping revealed the highest SSR density in CDS regions on chromosome 27, while SSR-containing genes exhibited a heterogeneous pattern characterized by localized clustering. Synteny analysis demonstrated relatively conserved syntenic relationships between the FMD and goat, sheep, and cattle, with moderate conservation also observed with red deer and white-tailed deer, suggesting that SSR-containing genes in ruminants may remain highly conserved during chromosomal rearrangements. GO and KEGG analyses indicated that SSR-containing genes across all species were predominantly enriched in transcriptional regulation, RNA processing, and signal transduction pathways. Specifically, the FMD showed enrichment patterns associated with hypoxia response, mRNA processing, and epigenetic regulation, which may reflect lineage-specific transcriptional patterns, though the functional involvement of these SSRs remains to be experimentally validated. In addition, the five primer pairs screened in this study exhibited high polymorphism, with a mean polymorphism information content (PIC) of 0.93. The observed heterozygosity (Ho) was significantly lower than the expected heterozygosity (He), and the mean inbreeding coefficient (FIS) was 0.57, indicating heterozygote deficiency and an elevated risk of inbreeding in this captive FMD population. Collectively, our findings provide preliminary insights into the conserved patterns of microsatellite evolution and lineage-specific divergence in ruminants, offering a reference framework for comparative genomics and adaptive evolution research, as well as practical molecular markers for genetic management of captive populations. Full article

Background/Objectives: Individuals with attention-deficit/hyperactivity disorder (ADHD) often experience communication difficulties (CDs), including challenges with language development, pragmatic communication, and speech processing. While these difficulties are typically associated with cognitive and behavioral symptoms; emerging research suggests that biological and nutritional factors may also contribute. This narrative review aims to explore how diet patterns, gut microbiome changes and oxidative stress might be associated with communication difficulties in ADHD. Methods: This review was performed using the SANRA (Scale for the Assessment of Narrative Review Articles) framework. A structured/comprehensive literature search was performed across major databases including PubMed, Scopus and Web of Science. Google Scholar has been utilized as a complementary database to support emerging studies that have not yet been registered in these databases. The search focused on studies that investigated the connections between nutrition, microbiome dysregulation, oxidative stress, ADHD and communication-related outcomes. Results: Current research indicates that unbalanced diets, micronutrient deficiencies, and changes in the gut microbiome can lead to neuroinflammation and oxidative stress. All these biological processes may disrupt neurotransmission and neural connectivity, which can potentially affect brain regions and networks that are highly important for attention and language processing, including both cortical and subcortical structures. Therefore, communication difficulties in ADHD may, in part, stem from these interconnected neurobiological mechanisms. However, direct clinical evidence linking nutritional factors, gut microbiome alterations, or oxidative stress with communication-specific outcomes in ADHD remains very limited, as most available studies have focused on core ADHD symptoms, attention, executive functioning, or biological markers. Conclusions: Dietary factors, alterations in the gut microbiome, and oxidative stress may collectively contribute to the complex underlying causes of communication disorders in ADHD. This review proposes an integrative framework that links nutrition-related mechanisms to communication outcomes, emphasizing the potential impact of modifiable lifestyle factors. Further longitudinal studies are needed to establish causal relationships and determine the clinical effectiveness of targeted nutritional interventions for communication difficulties in ADHD. Full article

Background/Objectives: Micronutrient deficiencies are common in inflammatory bowel disease (IBD) and contribute to anemia, impaired wound healing, neurologic injury, and adverse disease outcomes. Major societies, including ESPEN, ACG, and ECCO, recommend nutritional and micronutrient assessment in patients with IBD, yet few studies describe how comprehensively these recommendations are applied during hospitalization. This study aimed to characterize inpatient testing practices for vitamins B1, B6, B12, and zinc in hospitalized IBD patients, quantify deficiency frequency among those tested, and identify gaps between guideline-recommended and actual micronutrient assessment. Methods: A retrospective chart review was performed on adults with Crohn’s disease (CD) or ulcerative colitis (UC) hospitalized for an IBD flare at a tertiary care center. Demographics, comorbidities, and deficiency-associated clinical features were recorded. Yield was defined as the proportion of tested patients meeting institutional deficiency thresholds. Yield for each non-B12 micronutrient was compared with B12 as an internal benchmark. Results: Among 356 patients (285 CD, 71 UC), inpatient micronutrient testing was markedly imbalanced: B12 was tested in 97.2%, whereas B6, B1, and zinc were tested in only 34.8%, 30.6%, and 18.8%, respectively. Among those tested, deficiencies were common: B6 40.3%, zinc 32.8%, B1 22.9%, and B12 9.0%. Each non-B12 micronutrient yielded deficiency significantly more often per test than B12 (all p < 0.001), a testing-yield mismatch interpreted cautiously given selective testing of non-B12 nutrients. Deficiency frequencies did not differ significantly between CD and UC. Clinical contexts included tachycardia and edema (B1); elevated inflammatory markers and thromboembolism history (B6); anemia and neuropathy (B12); and diarrhea and hypoalbuminemia (zinc). Conclusions: Inpatient micronutrient assessment in IBD is heavily skewed toward B12, with B1, B6, and zinc under-tested despite a substantially higher yield of identified deficiency per test. This testing-yield mismatch represents a measurable implementation gap between guideline-recommended comprehensive assessment and actual inpatient practice; whether systematic panel-based assessment improves clinical outcomes warrants prospective evaluation. Full article

Chlorophyll content is a key determinant of photosynthetic efficiency and grain yield in rice (Oryza sativa L.), while premature chlorophyll degradation during the reproductive stage can markedly reduce crop productivity. However, the genetic basis underlying chlorophyll degradation and its environmental responsiveness remains incompletely understood. In this study, an F₂ population derived from a cross between the japonica cultivar Shennong0530-9 and the indica cultivar Habataki was used to identify quantitative trait loci (QTLs) associated with chlorophyll content at different developmental stages. A total of 22 QTLs were detected; among these, qCD2 consistently showed a major and stable effect on chlorophyll degradation after heading. Fine mapping using residual heterozygous lines delimited qCD2 to a 54.0 kb genomic interval on the short arm of chromosome 2 containing nine predicted genes. Near-isogenic lines (NIL-qCD2) carrying the qCD2 allele exhibited accelerated chlorophyll loss after heading, accompanied by disrupted chloroplast ultrastructure, reduced photosynthetic capacity, and significant decreases in grain yield and grain quality compared with the recurrent parent. Furthermore, the chlorophyll-deficient phenotype became progressively more severe under elevated temperature conditions, indicating that the phenotypic effect associated with qCD2 is temperature sensitive. Consistent with these physiological changes, the expression patterns of genes involved in chloroplast development, photosynthesis, and leaf senescence were significantly altered in NIL-qCD2. Collectively, these results identify qCD2 as a stable QTL associated with chlorophyll degradation during the reproductive stage and provide a foundation for future identification of the causal gene, providing valuable genetic resources for the molecular breeding of rice with improved photosynthetic efficiency, grain yield, and grain quality. Full article

Heavy metal wastewater, characterized by high toxicity, poor biodegradability, and strong bioaccumulation potential, poses a serious threat to the ecological environment and human health. Conventional chemical treatment methods are costly and prone to secondary pollution. In contrast, using solid waste to prepare environmental functional materials for “waste control by waste” has emerged as a research hotspot in the field of synergistic water pollution control and resource recovery. This review systematically consolidates the sources, physicochemical properties, and compositional characteristics of typical industrial solid wastes—including red mud, electroplating sludge, fly ash, copper slag, and blast furnace slag—and elucidates how compositional variations constrain the selection of functionalization pathways. On this basis, key preparation techniques, namely hydrothermal synthesis, surface modification/impregnation, thermal treatment, geopolymerization, and sol–gel/polymerization, are critically reviewed and compared in terms of product structural regulation, process complexity, and engineering scale-up potential. Subsequently, the adsorption performance of the resultant materials toward heavy metals such as Pb²⁺, Cu²⁺, Cr(VI), As(VI), Cd²⁺, Ni^2+, and Zn²⁺ is discussed, with particular emphasis on the pronounced effects of pH, temperature, initial concentration, coexisting ions, and adsorbent dosage on adsorption capacity. Notably, Pb²⁺ exhibits the highest adsorption capacity, whereas the removal of Cr(VI) and As(V) is strongly governed by the positive charge density and reduction efficiency of the material surface. In quinary heavy metal competitive systems, marked differences in the affinity of adsorption sites toward distinct metal ions have been observed. Mechanistic analysis identifies ion exchange, surface complexation, electrostatic attraction, and redox reactions as the predominant removal pathways. This review further incorporates engineering-oriented assessments, including multi-component competitive adsorption, fixed-bed column operation, and regeneration stability, and identifies the critical bottlenecks currently impeding the transition from laboratory-scale research to practical implementation—namely, performance instability arising from feedstock variability, attenuation of adsorption capacity during prolonged operation (with a 10–40% decline over 5–10 cycles), underdeveloped regeneration and recovery routes, and a systemic deficiency in techno-economic analysis and life-cycle assessment data. Finally, future research directions are proposed, emphasizing the development of low-carbon and energy-efficient preparation technologies, the promotion of synergistic valorization of multiple solid wastes alongside critical metal recovery, and the advancement of this field toward engineering applications through artificial intelligence-assisted design and life-cycle assessment, thereby furnishing theoretical references and technical support for the integrated management of industrial solid waste resource utilization and heavy metal wastewater treatment. Full article

Mycobacterium abscessus (Mab) is an opportunistic pathogen that causes severe infections, especially in immunocompromised individuals. The role of human mast cells (hMCs) during Mab infection remains poorly characterised. This study examines early interactions between Mab and hMCs, evaluating MC viability, degranulation, reactive oxygen species (ROS) production, cytokine secretion, and receptor expression following Mab exposure. MCs interacted with both smooth (ATCC 19977) and rough (clinical isolate) Mab morphotypes. Infection did not induce MC degranulation. Instead, Mab primarily stimulated intracellular ROS generation, Granzyme B, and IL-1β production. CD18 and CD46 were necessary for hMC-Mab interactions, and CD18 deficiency significantly impacted ROS production. hMC cytokine priming with IL-33 or IFN-γ did not significantly affect CD18 expression, nor did it impact ROS production upon Mab infection. These findings demonstrate that MCs mount a rapid, receptor-dependent intracellular response to Mab, highlighting an early and previously underappreciated role of MCs in Mab infection. Full article

Oxidative stress is a central driver of atherosclerosis progression, promoting lipid peroxidation, vascular inflammation, and hepatic metabolic dysfunction. Forchlorfenuron (KT-30), a cytokinin-like plant growth regulator widely used on fruits such as kiwifruit, grapes, and watermelon, has been reported to elevate serum cholesterol levels, suggesting potential atherogenic effects. However, whether KT-30 induces oxidative stress and accelerates atherosclerosis remains unknown. Here, apolipoprotein E-deficient (apoE^−/−) mice were orally administered KT-30 (5 mg/kg/day) for four weeks. KT-30 significantly accelerated atherosclerotic lesion formation, elevated plasma cholesterol levels, upregulated scavenger receptors SR-A and CD36, and downregulated ABCA1 and LXRα, indicating impaired reverse cholesterol transport and enhanced foam cell formation. KT-30 also increased pro-inflammatory cytokines (IL-1β, IL-6, MIP-2) and aortic expression of F4/80 and VCAM-1. Critically, KT-30 exposure was associated with elevated oxidative stress markers, as evidenced by elevated plasma MDA levels, increased aortic 4-HNE immunostaining, and upregulation of NOX-1/4. In the liver, KT-30 induced lipid accumulation, characterized by elevated cholesterol and free fatty acids, accompanied by SREBP-1/2-driven de novo lipogenesis and impaired lipoprotein uptake. Proteomic analysis revealed significant alterations in mitochondrial oxidative phosphorylation- and sirtuin signaling-related protein expression. Taken together, KT-30-associated oxidative stress, accompanied by upregulation of NOX-1/4 and alterations in mitochondrial pathway-related protein expression, may represent an important mechanistic link between lipid homeostasis disruption and accelerated atherosclerosis in apoE^−/− mice, highlighting the potential pro-atherogenic effects of KT-30 in a susceptible experimental model and providing mechanistic evidence that warrants further investigation of its possible cardiovascular implications. Full article

Amino acid metabolic disorders (AAMs) are a group of inherited metabolic diseases caused by defects in enzymes or transporters involved in amino acid metabolism. This systematic review and meta-analysis aimed to evaluate the incidence, disease spectrum, and regional distribution of AAMs in China. A comprehensive search of PubMed, Embase, Web of Science, and major Chinese databases identified studies published between January 2002 and December 2025. After rigorous screening and quality assessment, 65 studies were included, encompassing 16,757,850 newborns and 2928 confirmed AAM cases. The most prevalent subtypes included hyperphenylalaninemia (HPA), hypermethioninemia (MET), citrin deficiency (CD), citrullinemia type 1 (CTLN1), maple syrup urine disease (MSUD), ornithine transcarbamylase deficiency (OTCD), and tyrosinemia (HT). The pooled incidence of AAMs was estimated at 184.0 (95% confidence interval 155.0–218.0) per million newborns. Significant regional differences were observed in the overall incidence of AAMs, with a higher incidence in northern China than southern China (287.0 vs. 126.0 per million, p < 0.0001). This difference was largely attributable to the substantially higher prevalence of HPA in northern China, whereas other major AAM subtypes showed no significant north–south differences. In contrast, no significant north–south differences were identified for other major subtypes. Additionally, the proportion of tetrahydrobiopterin deficiency (BH4D) among HPA cases was significantly higher in southern China (p < 0.001). These findings provide comprehensive epidemiological evidence on AAMs in China and highlight the importance of region-specific newborn screening strategies. Full article

Citrin deficiency (CD) is an autosomal recessive disorder and represents one of the urea cycle disorders. This study aims to analyze the detection rate, clinical features, and genetic mutation characteristics of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in the Hefei region of China. We conducted NICCD screening using tandem mass spectrometry (MS/MS) for infants born in Hefei City between January 2016 and December 2025. Screen-positive cases were subjected to genetic testing via next-generation sequencing (NGS), with subsequent validation by Sanger sequencing. Clinical manifestations, biochemical parameters, and genetic mutation profiles of confirmed cases were systematically analyzed. A total of 924,676 newborns underwent screening, identifying 17 cases of NICCD, yielding a detection rate of 1/54,393, with two false-negative cases identified. The most prevalent mutation site is c.852_855del (p.M285Pfs*2). Following diagnosis, health education, dietary guidance, and symptomatic treatment were administered, resulting in favorable outcomes in the majority of cases. However, one infant exhibited significant growth retardation despite early therapeutic intervention that normalized biochemical parameters. Furthermore, an infant was found to have gallstones at birth and subsequently diagnosed with a liver hemangioma at one year of age. Some patients may experience missed screenings due to delayed elevations in citrulline levels. Therefore, even for newborns with negative screening results, timely assessments of liver function, MS/MS, and genetic testing are recommended for infants experiencing prolonged jaundice. This approach enables early identification and intervention. The combination of MS/MS with genetic screening may serve as a reliable strategy to reduce false-negative results in NICCD screening. Full article

Classical Major Histocompatibility Complex Class I (MHC-I) molecules are traditionally viewed as stable peptide-presenting structures expressed on the surface of all nucleated cells. Their expression by professional antigen-presenting dendritic cells (DCs) enables CD8+ T-cell activation, differentiation, and immune surveillance. However, accumulating evidence indicates that cell-surface MHC-I molecules exist in three major conformational states: (1) β2m-associated, peptide-loaded conformers that originate in the endoplasmic reticulum and pass through the Golgi apparatus after binding proteasome-generated cytosolic peptides (hereafter referred to as closed conformers); (2) β2m-free, peptide-empty conformers that arise following β2m dissociation from closed conformers either at the plasma membrane or after internalization and recycling (hereafter referred to as open conformers); and (3) β2m-associated, peptide-empty conformers that represent an intermediate state between closed and open conformers. Here, we propose a conceptual framework, supported by computational predictors of intrinsically disordered regions, in which transitions between closed and open MHC-I conformers are coupled to intracellular regulatory processes, including post-translational modifications of conserved motifs, intracellular trafficking, and signaling. Although direct experimental evidence linking these processes remains limited, we integrate independent observations into a working model that may guide future investigations into MHC-I-mediated cell–cell communication in both immune and non-immune contexts, in health and disease. For clarity, in this article we define “open conformers” as structurally competent, β2m-free, and peptide-deficient MHC-I molecules. Full article

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder driven by epidermal barrier defects and dysregulated Th2 cell responses. While therapies primarily address adaptive immunity, the role of Natural Killer (NK) cells remains underappreciated. This review analyzes NK cell dysfunctions in AD pathogenesis, evaluating their contributions to compromised skin immunity, microbial dysbiosis, and secondary infections. Accumulating evidence reveals a systemic deficiency of mature, cytotoxic CD56^dim and NKp80+ NK cell subsets in peripheral blood, correlating with disease severity. Within the cutaneous microenvironment, Staphylococcus aureus subverts defenses by utilizing leukocidins to lyse mature NK cells, while superantigens drive an aberrant, pro-inflammatory CD57⁻NKG2+ phenotype, exacerbating inflammation. Furthermore, localized exhaustion of functional NK cells and failure to produce interferon-gamma directly explains AD patients’ unique susceptibility to severe viral complications like eczema herpeticum. Importantly, treatments such as dupilumab and gut microbiota transplantations demonstrate that these NK cell aberrations are reversible, shifting immunity toward a normalized regulatory state. In conclusion, the NK cell compartment represents a vital regulatory axis bridging innate and adaptive immunity. Targeting this axis, particularly through IL-15 superagonists, offers a promising therapeutic frontier to suppress type 2 inflammation and restore antimicrobial defenses. Full article

Background/Objectives: High-grade serous ovarian carcinoma (HGSC) is the most aggressive subtype of epithelial ovarian cancer and is characterized by marked heterogeneity of the tumor immune microenvironment. SET morphology has been associated with homologous recombination deficiency and BRCA1/2 mutations; however, its relationship with the immune microenvironment and progression-free survival (PFS) remains insufficiently understood. This study investigated the association between SET morphology, immune microenvironment characteristics, and PFS in patients with advanced-stage HGSC. Methods: A retrospective cohort of 305 patients with FIGO stage III–IV HGSC treated with primary surgery between 1996 and 2021 was analyzed. Histopathological assessment included evaluation of SET morphology, stromal and intraepithelial tumor-infiltrating lymphocytes (sTILs and itTILs), tumor immune phenotype, and lymphoid aggregates. Immunohistochemical analyses included CD8 and PD-L1 expression. Associations between SET morphology and immune parameters were evaluated using χ² and logistic regression analyses. PFS was assessed using Kaplan–Meier analysis, log-rank testing, and Cox proportional hazards regression. Results: SET morphology was significantly associated with higher sTIL and itTIL levels, increased stromal and intraepithelial CD8⁺ T-cell infiltration, higher PD-L1 TPS and CPS, more frequent primary and secondary lymphoid aggregates, and a predominance of the inflamed immune phenotype (all p < 0.05). Despite these features of an immune-active tumor microenvironment, SET morphology, CD8⁺ T-cell density, PD-L1 expression, lymphoid aggregates, and immune phenotype were not independently associated with prolonged PFS. In contrast, age remained an independent prognostic factor, with patients older than 55 years having a 50% higher risk of disease progression than younger patients (HR = 1.5, 95% CI: 1.1–2.1; p = 0.012). Higher intraepithelial TIL levels (>10%) were independently associated with improved PFS (HR = 2.1, 95% CI: 1.0–4.4; p = 0.045). Conclusions: SET morphology identifies an immune-active subtype of HGSC characterized by increased immune infiltration and PD-L1 expression but does not independently predict prolonged PFS. The dissociation between immune cell abundance and clinical outcome suggests that immune cell functionality, rather than immune infiltration alone, may determine prognosis. Routine histopathological assessment of SET morphology may facilitate biological characterization of HGSC and provide a practical surrogate marker for future biomarker-driven studies evaluating immunotherapy and targeted treatment strategies. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become increasingly common, a trend driven by obesity, excess nutritional intake, and dysfunctional adipose tissue. While continuous dietary stress triggers adipose-tissue-derived lipotoxicity and disrupts hepatic metabolic homeostasis and provokes inflammation, the transcriptional scaffolds that mitigate this lipotoxicity remain incompletely understood. We investigated the role of zinc finger protein 90 (ZFP90) in defending against diet-induced metabolic stress and MASLD pathogenesis. Methods: Wild-type and ZFP90-knockout mice were subjected to a high-fat diet (HFD) to model nutrient-overload-induced MASLD. Hepatic phenotypes were characterized using metabolic profiling and RNA sequencing. Mechanistic dynamics were evaluated through protein interaction assays, and clinical relevance was validated using human MASLD liver biopsies. Results: ZFP90 deficiency significantly accelerated HFD-induced steatosis, systemic insulin resistance, and inflammatory infiltration. Crucially, ZFP90 depletion drove severe white adipose tissue (WAT) dysfunction, characterized by impaired lipogenic capacity, exacerbated lipolysis, and diminished local insulin signaling. This was accompanied by a pro-inflammatory secretory shift in WAT, evident from decreased Adipoq and increased Cd68/Ccl3 expression. In the liver, transcriptomic analysis revealed a profound induction of pathways related to fatty acid uptake and cytokine signaling. Mechanistically, ZFP90 forms a repressive complex with TRIM28, acting as a crucial molecular brake on NF-kB signaling. Loss of ZFP90 unleashes p65-mediated hyper-inflammation. Clinically, hepatic ZFP90 expression is significantly upregulated in patients with MASLD. Conclusions: ZFP90 is a novel regulator of immunometabolic homeostasis under dietary stress. By forming of complex with Trim28 to inhibit the nuclear translocation of NF-κB, ZFP90 suppresses pro-inflammatory responses and protects the liver from obesity-associated systemic lipotoxicity. These findings provide critical insights into the adipo-hepatic axis and highlight ZFP90 as a promising therapeutic target to mitigate the progression to metabolic dysfunction-associated steatohepatitis (MASH). Full article

Background/Objectives: Celiac disease (CD) is an immune-mediated enteropathy with gastrointestinal and extraintestinal manifestations. In primary care, recognition can be delayed when psychiatric symptoms, arthralgia, thyroid dysfunction, alcohol exposure, and liver-test abnormalities coexist. This case report describes a confounder-aware diagnostic approach to histologically confirmed CD in a patient with a multifactorial primary-care presentation. Methods: We report a single-patient, de-identified reflective case from routine family medicine practice, organized according to CARE case-report principles. Results: A woman in her early sixties with hypothyroidism and glaucoma presented with new low mood, anhedonia, somnolence, generalized anxiety, increased alcohol intake, poor appetite, weight loss, abdominal bloating, diarrhea, flatulence, and polyarthralgia. Initial investigations, including celiac serology obtained before gluten-free diet advice, showed mild anemia, marked hyperferritinemia, severe cholestatic and hepatocellular liver-test abnormalities, uncontrolled hypothyroidism, and strongly positive tissue transglutaminase IgA (>250 kIU/L; reference 0.0–14.9). Radiographs showed mild osteoarthritis and osteopenia without erosive arthropathy. Computed tomography excluded malignancy but showed severe diffuse hepatic steatosis and mild pancreatic atrophy. Mirtazapine was started at the index visit; after the initial laboratory results, gluten-free diet advice, alcohol-reduction counseling, and levothyroxine adjustment were undertaken. During the diagnostic episode, small-bowel biopsy demonstrated moderate-to-severe crypt hyperplastic villous atrophy with increased intraepithelial lymphocytes, and gastric biopsies showed no significant pathology; the histology was consistent with CD. Symptoms improved substantially. Longer-term objective follow-up showed persistent but improved celiac serology (tTG-IgA 49.4 kIU/L), normalization of thyroid-stimulating hormone, partial improvement in gamma-glutamyl transferase, which remained elevated, and a later iron-deficiency pattern with persistent anemia. Conclusions: This case supports targeted CD testing when anxiety or depressive symptoms occur alongside gastrointestinal symptoms, weight loss, arthralgia, hypothyroidism or documented thyroid autoimmunity, anemia, osteopenia, or liver-test abnormalities. Histology and repeat serology confirmed the diagnosis, but the psychiatric and hepatic manifestations still require cautious interpretation because hypothyroidism, alcohol exposure, steatotic liver disease, and simultaneous treatments also shaped the clinical course. Full article