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Metabolic dysfunction-associated steatotic liver disease (MASLD) is primarily driven by a Western-style diet and exacerbated with aging, yet underlying mechanisms remain unclear. Given the essential role of thyroid hormone (TH) in MASLD progression, we hypothesized that impaired intrahepatic TH action during aging promotes MASLD progression and severity of MASH with fibrosis. We evaluated hepatic TH metabolism in young (18-24 weeks) and old (108-120 weeks) C57BL/6J mice fed either a normal chow diet (NCD) or a Western diet with fructose (WDF) for 8 weeks. Liver histology, metabolic parameters, inflammatory and fibrotic markers, intrahepatic thyroxine (T4) and triiodothyronine (T3) concentrations, and activities of deiodinase enzymes (Dio1 and Dio3) were measured. Additionally, an in vitro hepatocyte senescence model using AML12 cells was employed to assess age-related alterations in deiodinase expression and the therapeutic efficacy of resmetirom (an FDA-approved thyromimetic). Aging and WDF synergistically exacerbated hepatic inflammation and fibrosis, accompanied by significant reductions in intrahepatic T4 and T3. Aging markedly decreased Dio1 activity, which converts T4 to active T3, whereas WDF partially restored Dio1 in old mice. Conversely, Dio3 activity, responsible for TH inactivation, increased with age but exhibited age-dependent differential responses to WDF, findings mirrored in senescent hepatocytes. Notably, resmetirom significantly reduced senescence markers, inhibited senescence-associated secretory phenotype (SASP) genes, inflammasome activation, endoplasmic reticulum (ER) stress, and activated autophagy. Collectively, our findings demonstrate that aging and stress by a Western-style diet synergistically impair hepatic TH signaling, accelerating MASLD progression. Furthermore, resmetirom improved hepatic senescence, highlighting its potential therapeutic repurposing for aging-associated hepatic pathologies, including MASLD.

Pediatric primary orbital lymphomas are exceptionally rare entities and represent a very small subset of both childhood orbital tumors and extra-nodal non-Hodgkin lymphomas. They often present with non-specific clinical features that can closely mimic inflammatory or other malignant orbital conditions, thereby posing significant diagnostic challenges. We report a rare case of an orbital lymphoma in an infant presenting with rapidly progressive, painless unilateral eyelid swelling. Magnetic resonance imaging demonstrated a well-defined extraconal orbital mass that appeared isointense on T1-weighted images and iso- to hypointense on T2-weighted sequences, with homogeneous post-contrast enhancement. The lesion exhibited marked diffusion restriction with significantly reduced apparent diffusion coefficient (ADC) values, indicative of a highly cellular neoplasm and in this context, most favorable diagnosis of lymphoma was considered. Histopathological evaluation, supported by immunohistochemistry and flow cytometry, confirmed an aggressive B-cell lymphoma, and molecular analysis revealed features consistent with Burkitt lymphoma. Staging fluorodeoxyglucose positron emission tomography demonstrated residual metabolically active disease confined to the orbit without evidence of systemic involvement. The patient was initiated on intensive multi-agent chemotherapy with an early favorable clinical response. A systematic review of the literature was subsequently done, which highlighted the extreme rarity of primary pediatric orbital lymphomas, with a predominance of high-grade B-cell histology, particularly Burkitt lymphoma. This case highlights the critical role of diffusion-weighted imaging and low ADC values in differentiating orbital lymphomas from other pediatric orbital masses, thereby facilitating early diagnosis, accurate lesion characterization, and timely initiation of therapy. Radiological awareness of these characteristic imaging features is essential to avoid diagnostic delay and to improve clinical outcomes in this rare but aggressive disease, given its marked responsiveness to treatment.

Anomalous systemic arterial supply to the basal lung (ASASB) and partial anomalous pulmonary venous connection (PAPVC) are rare congenital anomalies; their coexistence in a patient with lung cancer has not been previously reported. A 68-year-old woman was referred for a right lower lobe mass detected on screening. Contrast-enhanced computed tomography showed an aberrant artery from the abdominal aorta supplying segments 9-10 and drainage of all right upper pulmonary veins into the superior vena cava. Qp/Qs on echocardiography was 1.3. Three-dimensional reconstruction clarified the vascular anatomy and guided thoracoscopic right lower lobectomy. The aberrant artery was doubly ligated at its intrathoracic origin and divided with a vascular stapler. Postoperative recovery was uneventful. Histology revealed papillary-predominant adenocarcinoma (pT2aN0M0). Twelve-month surveillance showed no recurrence or stump aneurysm; Qp/Qs decreased to 1.1. Careful cardiopulmonary evaluation and three-dimensional imaging permitted safe minimally invasive resection in this rare condition. However, the mechanisms underlying postoperative changes in Qp/Qs remain unclear and require cautious interpretation.

The pathogenesis of Duchenne muscular dystrophy (DMD) is driven by a deficiency of functional dystrophin. Although gene therapy is a promising strategy, current approaches face substantial challenges in balancing therapeutic efficacy with toxicity, largely owing to the requirement for high-dose adeno-associated virus (AAV) administration. We employed a low-dose strategy in neonatal mdx mice, using a muscle-targeted MyoAAV 2 A capsid to deliver a rationally designed, codon-optimized micro-utrophin construct (ΔR4-R22/ΔC + H3/H4) at 1 × 10¹² vg/kg via intraperitoneal injection. Four weeks post-injection, micro-utrophin expression and localization, as well as γ- and α-sarcoglycan recruitment, were assessed by western blotting and immunofluorescence. Vector genome distribution was quantified by real-time quantitative PCR. Tissue histology was evaluated using Evans blue dye uptake, H&E staining, and Masson's trichrome staining. Muscle function was measured by grip strength and treadmill exercise tests. Serum biomarkers of cardiac injury, heart failure, and systemic inflammation were detected by ELISA. Robust micro-utrophin expression was detected in skeletal muscles, diaphragm, and myocardium, with minimal off-target expression in the liver. Sarcolemmal localization and functional recruitment of γ- and α-sarcoglycan confirmed restoration of the dystrophin-glycoprotein complex. In treated animals, serum creatine kinase levels, Evans blue dye uptake, and central nucleation in multiple muscles were significantly reduced, accompanied by improvements in relative grip strength, running time, and distance to exhaustion. No cardiac or hepatic toxicity was observed, as indicated by unchanged cTnI, NT-proBNP, ALT, and AST levels. Additionally, serum IL-6 and C5a concentrations were significantly decreased, and fibrosis and inflammation in the diaphragm and myocardium were markedly attenuated. These findings demonstrate that combining a functional micro-utrophin construct with an advanced muscle-tropic MyoAAV 2 A capsid constitutes a promising strategy to overcome the efficacy-toxicity trade-off that has hindered the clinical translation of DMD gene therapies.

Endometrial cancer is a heterogeneous malignancy involving many criteria considered in treatment planning. This study analyzed risk factors associated with postoperative outcomes in 250 women diagnosed with endometrioid-type endometrial adenocarcinoma. The aim of this analysis was to identify the subgroup with the lowest risk of extrauterine metastasis, which could be exempted from comprehensive staging surgery. Criteria for admission to the study were endometrioid histology, grade 1 or 2 tumors, and tumor invasion of half the myometrium based on pathology reports. Extrauterine metastases, such as lymph node, fallopian tube, ovary, and omentum involvement, were evaluated. Of the 250 patients, 178 (71.2%) had grade 1 tumors and 72 (28.8%) grade 2 tumors; 152 (60.8%) had a tumor size of 3&#x2009;cm or less and 98 (39.2%) had a tumor size of more than 3&#x2009;cm. Eighteen patients (7.2%) had extrauterine metastases. Patients with grade 2 tumors had a higher rate of extrauterine metastases compared with those with grade 1 tumors (15.3% vs 3.9%, P&#x2005;=&#x2005;.003). Patients with tumor size >3&#x2009;cm had a higher rate of extrauterine metastases compared with those with tumor size 3&#x2009;cm or less (13.3% vs 3.3%, P&#x2005;=&#x2005;.006). In multivariate analysis, grade 2 (hazard ratio&#x2005;=&#x2005;3.66, 95% confidence interval: 1.33-10.08; P&#x2005;=&#x2005;.012) and tumor size >3&#x2009;cm (hazard ratio&#x2005;=&#x2005;3.83, 95% confidence interval: 1.28-11.39; P&#x2005;=&#x2005;.016) were independent factors associated with extrauterine metastases. According to the findings of this study, among patients with endometrial cancer with <50% myometrial invasion depth, those with grade 1 tumors and tumor diameters smaller than 3&#x2009;cm had the lowest rate of extrauterine metastasis. Tumor size was identified as a potential factor in determining the risk of extrauterine metastasis. These results support avoiding comprehensive staging surgery in the subgroup meeting the criteria of having a tumor smaller than 3&#x2009;cm and a grade 1 endometrioid tumor.

Sacral epidural cavernous hemangioma involving the intervertebral foramen is exceptionally rare and may closely mimic more common benign nerve sheath tumors on magnetic resonance imaging. We report the case of a woman in her mid-50s who presented with a 1-month history of nocturnal left lower-extremity pain and mild weakness. Contrast-enhanced lumbar magnetic resonance imaging revealed a strongly enhancing nodular lesion in the left S2 foraminal region, and schwannoma was considered preoperatively. The patient underwent microsurgical resection through a posterior midline approach. Intraoperatively, the lesion was dark red, soft, and hypervascular, raising suspicion for a vascular malformation rather than schwannoma. Frozen-section analysis suggested hemangioma, and postoperative histopathology confirmed cavernous hemangioma. The patient experienced marked postoperative relief of radicular pain, and follow-up analysis indicated complete symptom resolution without radiological evidence of residual lesion. This case emphasizes that cavernous hemangioma should be included in the differential diagnosis of sacral foraminal masses. Purely epidural cavernous hemangiomas centered in the sacral foramen are particularly rare and frequently misdiagnosed preoperatively as schwannoma; thus, careful preoperative planning, anticipation of intraoperative hypervascularity, and frozen-section histology may help guide safe resection.

This study aimed to develop and validate diagnostic models for distinguishing benign and malignant thyroid nodules. Between January 2020 and June 2024, 735 patients were retrospectively selected for surgery or needle biopsy at our hospital. This cohort was divided into a training cohort (n=514) and a validation cohort (n=221) in a ratio of 7:3. All models were validated 10 times, and a receiver operating characteristic curve (ROC curve) was generated. Furthermore, a nomogram prediction model was constructed using the independent risk factors from Model 3, and its validity was verified through ROC curves, calibration curves, and clinical decision curves. The AUC of Model 1 in the training cohort was 0.889, 0.913, 0.914, 0.914, 0.928, and 0.910, respectively. The AUC of Model 2 in the training cohort was 0.950, 0.957, 0.936, 0.946, 0.963, and 0.921, respectively. The AUC of Model 3 in the training cohort was 0.985, 0.991, 0.969, 0.949, 0.866, and 0.986, respectively. The Model 3, which was constructed based on the optimal classifier LDA, had the highest predictive value. Moreover, the clinical decision curve also indicated that it offers the greatest net benefit to patients. The integration of clinical features with multimodal ultrasound imageomics significantly improved diagnostic accuracy. The combined model showed enhanced sensitivity and specificity, potentially reducing unnecessary invasive procedures. This study developed a non-invasive preoperative diagnostic method for thyroid nodules using multimodal ultrasound histology and clinical models, and its nomogram was also convenient for clinical application.

Coxsackievirus A6 (CVA6) is a nonenveloped, single-stranded RNA virus linked to neurological complications. Emerging evidence suggests neutrophil pyroptosis drives inflammation. However, the role of neutrophil pyroptosis in CVA6 pathogenesis remains unexplored. Ten-day-old wild-type (WT), Caspase-1 KO, and GSDMD KO mice were infected with a lethal dose of CVA6. For in vivo and in vitro studies, we used the caspase-1 inhibitor belnacasan, disulfiram, and anti-Ly6G antibody. We also generated neutrophil-specific PAD4-knockout mice (PAD4 Ne-KO) by deleting Padi4 under the S100A8 promoter. Post-infection, clinical scores, survival, and body weight were monitored. Brain tissues and bone marrow-derived neutrophils (BMDNs) were collected for analysis. Key methods included qPCR, Western blotting, histology/immunofluorescence, flow cytometry, and TEM to assess pyroptosis, inflammation, and immune cell infiltration. Findings were further validated using blood samples from HFMD patients. In this study, we investigated how the Caspase-1/GSDMD pathway mediates neutrophil extracellular trap (NET) release and drives CVA6-induced neuroinflammation. CVA6 infection increased neutrophil numbers in mouse brain and peripheral blood, along with elevated MPO-DNA-a NET marker. In BMDNs, degranulation and NET formation occurred by 24 hpi, accompanied by Caspase-1/GSDMD activation. Caspase-1 knockout prolonged survival and reduced GSDMD-N expression in brain neutrophils; pharmacological Caspase-1 inhibition decreased mature IL-1&#x3b2; and IL-18 in brain tissue and suppressed CVA6 replication in BMDNs. Together, in vitro and in vivo data indicate that Caspase-1/GSDMD activation and NETosis critically contribute to CVA6-induced brain injury. This was confirmed by GSDMD knockout or disulfiram-mediated GSDMD inhibition, both of which markedly reduced NET release and neuropathology. Notably, global neutrophil depletion worsened infection-suggesting a protective role-whereas neutrophil-specific PAD4 knockout improved survival. Clinically, GSDMD expression showed a significant positive correlation with NETosis markers in patient samples from CVA6-infected individuals. These findings enhance understanding of enteroviral pathogenesis, identify GSDMD as a promising therapeutic target, and provide a novel framework for developing precision interventions that reduce excessive inflammation without impairing essential host defenses.

Helicobacter pylori infection is a major risk factor for gastric cancer (GC), but the molecular mechanisms remain incompletely understood. This exploratory in vitro study investigated whether treatment with the flavonoid morin correlates with altered expression of MAPK/Nrf2/STAT-3 pathway proteins in H. pylori-infected human gastric epithelial cells (GES-1). GES-1 cells were infected with H. pylori (ATCC 49503, MOI 100:1) and treated with 40&#x2009;&#xb5;M morin for 24&#x2009;h. Outcomes included cell viability (MTT assay), ROS production (DCFH-DA), oxidative DNA damage (comet assay), glutathione and malondialdehyde levels (biochemical assays), protein expression (Western blot), and gene expression (RT-PCR). Molecular docking predicted binding affinity between morin and pathway proteins. This study used n&#x2009;=&#x2009;3 biological replicates per group and a lenient false discovery rate threshold (Q&#x2009;=&#x2009;0.25) appropriate for hypothesis generation; findings require independent replication. In this exploratory study, morin treatment (40&#x2009;&#xb5;M) was associated with: Higher MTT-detectable viability in H. pylori-infected cultures compared to infected untreated controls (85% vs. 45%; q&#x2009;=&#x2009;0.042) Lower intracellular ROS levels (q&#x2009;=&#x2009;0.021) and reduced oxidative DNA damage (q&#x2009;=&#x2009;0.018) compared to infected untreated controls Higher GSH and lower MDA levels compared to infected untreated controls Lower phosphorylation levels of MAPK family members (ERK, JNK, p38), PI3K/AKT, and STAT3/EGFR proteins compared to infected untreated controls Higher total Nrf2 protein expression and upregulation of HMOX1 and NQO1 mRNA compared to infected untreated controls Molecular docking predicted binding between morin and MAPK, STAT3, and NRF2 pathway proteins, but these computational findings require experimental validation. These correlative findings are consistent with the hypothesis that morin treatment engages MAPK/Nrf2/STAT-3 pathways in H. pylori-infected GES-1 cells. However, this study does not establish causality, Nrf2 activation (nuclear translocation not demonstrated), or therapeutic efficacy (no positive controls). The observed associations should be interpreted as hypothesis-generating and require independent replication, mechanistic validation (including Nrf2 loss-of-function experiments), and comparative studies with standard agents before any translational inference. Under the specific in vitro conditions tested (GES-1 cells, H. pylori ATCC 49503, 40&#x2009;&#xb5;M morin, 24-h exposure, n&#x2009;=&#x2009;3 biological replicates), morin treatment was associated with lower ROS levels, reduced MAPK/STAT3 phosphorylation, and higher Nrf2 protein expression compared to infected untreated controls. These correlative findings are hypothesis-generating and do not establish therapeutic potential, safety, efficacy, or clinical relevance. Independent replication, comprehensive toxicological characterization (including normal cell lines and in vivo models), direct comparison with standard agents (clarithromycin, sulforaphane), and mechanistic validation (including Nrf2 loss-of-function experiments) are required before any consideration of morin for further development. This study provides no evidence to support morin as a therapeutic, adjuvant, or alternative agent.

Most ovarian cancers are detected at advanced stages, with poor outcomes. Ovarian cancer is heterogeneous; the most common subtype, serous ovarian carcinoma, may originate outside of the ovaries. To inform etiologic heterogeneity, prevention, and treatment of ovarian cancer, we conducted the first evaluation of oophorectomy-corrected incidence and mortality trends of ovarian, fallopian tube, and peritoneal cancers. Ovarian cancer incidence, survival, and incidence-based mortality overall and by subtype were analyzed using the U.S. Surveillance, Epidemiology, and End Results (SEER)-22 and SEER17 databases including cases from 2000 to 2019, with oophorectomy correction based on data from the National Health and Nutrition Examination Survey (NHANES). Rates were age adjusted per 100,000 person-years; annual percent changes in rates were calculated. Age-adjusted prevalence of oophorectomy changed minimally between 2000 and 2019 and was highest among Non-Hispanic White women. Oophorectomy-correction increased ovarian cancer incidence rates by 23% on average. Ovarian cancer incidence decreased by 2% between 2000 and 2019, with a stronger reduction observed in recent years. Fallopian tube cancer incidence increased by 7% from 2000 to 2019. Relative 5-year survival was lowest among Non-Hispanic Black women even after accounting for histotype and stage. Ovarian cancer mortality decreased by 1.8% between 2000 and 2019. Serous carcinomas contributed to 68% of ovarian cancer cases, but 83% of all ovarian cancer deaths. The reasons for decreasing ovarian cancer incidence are not understood. There is evidence for some reclassification of primary ovarian to primary fallopian tube cancers. Low survival rates in Non-Hispanic Black women point to disparities along the continuum of care.

Parkinson's disease (PD) is a common neurodegenerative disease. Our previous single-cell sequencing results suggested that Transcription Factor E3 (TFE3) was only differentially expressed in microglia in the MPTP mouse model. However, the functional role of microglial TFE3 in PD pathogenesis remains unclear. First, motor function was assessed in MPTP mice following TFE3 overexpression in substantia nigra microglia. Second, RNA-seq was used to identify the function of TFE3 in microglia, and the molecular mechanism was verified both in vivo and in vitro. Finally, we investigated whether TFE3 nuclear translocation affects its transcriptional activity and subsequently influences microglia in vitro. Overexpression of TFE3 in substantia nigra microglia could alleviate PD-related phenotypes. RNA-seq revealed that TFE3 regulates microglial phagocytosis and inflammation. Mechanistically, TFE3 affects these functions by regulating the expression of Mer receptor tyrosine kinase (Mertk) and lysosomal-associated membrane protein 1 (Lamp1). Finally, Rapamycin could activate the nuclear translocation of TFE3 and enhance phagocytosis and alleviate inflammation of microglia. Our findings demonstrate that Rapamycin activates TFE3, which in turn upregulates the expression of Mertk and Lamp1 in the substantia nigra. This TFE3-mediated pathway plays a critical role in regulating microglial phagocytosis and inflammation in the PD model.

Parathyroid carcinoma (PC) is a rare malignant tumor, accounting for <1% of all cases of primary hyperparathyroidism. It is typically characterized by markedly elevated parathyroid hormone (PTH) levels, severe hypercalcemia, and target organ damage. This study presents a single-center experience in the management of patients with PC and provides a review of the relevant literature. The clinical and laboratory data of 8 patients diagnosed with PC based on pathological examination between September 2008 and February 2024 at the Endocrinology Clinic of Akdeniz University Hospital (Antalya, Turkey) were retrospectively reviewed. Eight patients (3 males) were identified, with a median age of 49 years at diagnosis (range: 46-71 years) and a median follow-up period of 93 months. All patients presented with hypercalcemia, with a median serum calcium level of 13.39&#x2009;mg/dL (range: 11.2-19) and a median PTH level of 690 ng/L (range: 105-1625). Organ involvement related to hyperparathyroidism was common, most frequently affecting the kidneys (n&#x2005;=&#x2005;3) and bones (n&#x2005;=&#x2005;3). All patients underwent en bloc surgical resection, and 2 received adjuvant radiotherapy. Disease recurrence occurred in 3 patients (37.5%) after a median of 24 months following surgery. The cohort size was insufficient to reliably evaluate predictors of recurrence. The 5-year overall survival and disease-specific survival rates were both 87.5%. PC is characterized by a high recurrence rate and limited treatment options beyond complete surgical excision. The diagnosis should be considered in patients presenting with markedly elevated PTH and calcium levels accompanied by a neck mass. En bloc resection remains the mainstay of treatment. The role of adjuvant radiotherapy remains uncertain and warrants further investigation in larger cohorts.

The optimal surgical strategy for early-stage lung adenocarcinoma appearing as part-solid nodules (PSN) versus pure solid nodules (SPN) remains debated. This study directly compares their clinicopathological features, surgical outcomes, and recurrence patterns to inform personalized management based on CT characteristics. This retrospective study analyzed 710 surgical patients with clinical stage IA lung adenocarcinoma. Nodules were categorized as PSN or SPN by the presence of a GGO component on preoperative CT. Interaction-effect analysis assessed CT-attenuation dynamics in solid components. Propensity-score matching balanced intergroup confounders, and Cox regression identified recurrence risk factors for each type. Mean CT-solid value (-13.2 Hu vs. 22.2 Hu, p&#x2009;<&#x2009;0.001) and the trend of change in CT-solid value during follow-up (Interaction effect Index: -0.011078, p&#x2009;<&#x2009;0.001) were significantly different between PSN and SPN. Upon histological examination, PSN had significantly lower incidences of visceral pleural invasion (11.7% vs. 30.4%, p&#x2009;<&#x2009;0.001) and lymph node metastasis (11.2% vs. 20.6%, p&#x2009;=&#x2009;0.008) than SPN. After propensity-score matching, patients with PSN had significantly better recurrence-free survival (86.8% vs. 70.7%, p&#x2009;<&#x2009;0.001) than those with SPN. In Cox regression analysis, sublobar resection and lymph node sampling-only were associated with increased risk of loco-regional recurrence in SPN, but not in PSN. PSN and SPN show distinct clinicopathological features and prognostic profiles, suggesting potentially different biological behaviors. CT features need to be incorporated with clinical tumor stage in deciding surgical strategies on resection extent and lymph node examination for early-stage lung adenocarcinoma.

The clearance of apoptotic cells by phagocytes is crucial for restoring tissue balance after injury. In autoimmune liver diseases like primary sclerosing cholangitis, cell death is thought to result from accumulation of toxic bile acids within parenchymal cells. Whether, in this context, bile acid-loaded dying cells impact the efficiency of phagocytic macrophages in restoring tissue balance remains unknown. Here, we demonstrate that in a murine model of cholangitis, bile acids accumulate in a subpopulation of efferocytic macrophages with pro-inflammatory features. Our in vitro results indicate that, upon their engulfment, apoptotic hepatocytes laden with bile acids can serve as Trojan horses, delivering bile acids into efferocytic macrophages and thereby shaping macrophage function. This contrasts with the characteristics of macrophages that engulf apoptotic parenchymal cells lacking bile acids. Together, our findings delineate a system in which the content of the phagocytosed dying cells, specifically bile acid-laden hepatocytes, drives a pro-inflammatory program in the corresponding efferocytic macrophages, potentially contributing to chronic hepatic inflammation.

Myeloid-derived suppressor cells (MDSCs) are essential immunosuppressive elements found within the tumor microenvironment (TME) and significantly influence the development of breast cancer (BC). Given their critical role in cancer progression, identifying MDSC-related genes is urgently needed to develop more effective treatment strategies for BC patients. The integration of bulk RNA-seq data from the TCGA-BC cohort alongside scRNA-seq data from the GSE176078 dataset was performed for identifying MDSC-related genes through bioinformatic analysis. Subsequently, the potential of the hub gene BASP1 in predicting prognosis and immune infiltration in BC was evaluated. Furthermore, the functional role of BASP1 in BC was investigated both in vitro and in vivo. Notably, BASP1 levels were significantly higher in BC tissues than in adjacent normal tissues, and elevated BASP1 expression was closely associated with adverse clinical outcomes. Additionally, BC patients with increased BASP1 levels exhibited increased infiltration of immunosuppressive cells (M2 macrophages and Tregs) but reduced infiltration of CD8&#x2009;+&#x2009;T cells. Functionally, downregulation of BASP1 was observed to suppress BC cell proliferation and migration in vitro through inactivation of AKT and ERK signalings. Mechanistically, BASP1 in 4T1 cells promoted MDSC migration, at least partially, via upregulating CXCL12 secretion, while BASP1 in MDSCs directly suppressed T cell function. In vivo experiments showed that BASP1 knockdown markedly inhibited tumor growth in mouse models bearing 4T1 tumors, accompanied by decreased MDSCs infiltration and increased Granzyme B&#x2009;+&#x2009;CD8&#x2009;+&#x2009;T cell accumulation in tumor tissues. Collectively, BASP1 may serve as a potential prognostic biomarker and a therapeutic target for BC intervention, functioning both as a pro-tumorigenic gene and as an immunomodulatory molecule that shapes an immunosuppressive microenvironment.

Obesity is increasingly recognized as a condition that directly impairs skeletal muscle structure, metabolism, and endocrine function through complex molecular and cellular mechanisms extending beyond the classical concept of sarcopenic obesity. This narrative review aimed to synthesize current evidence regarding the intracellular signaling pathways, metabolic alterations, and endocrine interactions involved in obesity-induced skeletal muscle dysfunction independent of overt sarcopenia. Relevant literature from experimental, clinical, and review studies was identified through searches of PubMed, Scopus, and Web of Science databases, focusing on obesity-associated alterations in skeletal muscle metabolism, ectopic lipid accumulation, inflammatory signaling, mitochondrial dysfunction, and adipose-muscle crosstalk. Current evidence indicates that obesity per se promotes skeletal muscle dysfunction through ectopic lipid deposition, lipotoxicity, mitochondrial impairment, and chronic low-grade inflammation mediated by dysregulated intracellular signaling pathways. Altered adipomyokine signaling, including interleukin-6 and tumor necrosis factor-&#x3b1;, further contributes to impaired insulin signaling, reduced metabolic flexibility, oxidative stress, and compromised muscle integrity. These molecular and cellular alterations reinforce skeletal muscle as both a target and an active regulator of obesity-associated metabolic inflammation. Collectively, these findings support the concept that obesity intrinsically disrupts skeletal muscle metabolic and endocrine homeostasis independently of sarcopenic obesity and highlight the importance of targeted strategies aimed at preserving skeletal muscle metabolic function and overall metabolic health.

Lobaric and rhizocarpic acids are secondary metabolites isolated from Antarctic lichens. While several biological activities have been described for lobaric acid, the cellular effects of rhizocarpic acid remain poorly characterized. This study investigated the impact of these compounds on proliferation, apoptosis, and cell cycle regulation in human leukemic cell models. Human leukemic K562 and MOLM-6 cells were exposed to lobaric and rhizocarpic acids under defined experimental conditions; cell viability, apoptosis, cell cycle distribution, and protein expression were evaluated using cell proliferation assays, flow cytometry, and western blot analysis. Both metabolites reduced cell growth and promoted caspase-dependent apoptosis in K562 and MOLM-6 cells. At the molecular level, in K562 cells, lobaric acid treatment was associated with increased Bax protein expression, whereas rhizocarpic acid induced upregulation of Bcl-2. In MOLM-6 cells, both compounds decreased STAT5 protein expression. In addition, both metabolites altered cell cycle distribution. Lobaric acid caused a significant increase of K562 cells in the G2/M phase and a transient rise of MOLM-6 cells in G1 phase, whereas rhizocarpic acid increased the proportion of cells in the G1 phase, with a concomitant reduction in S and G2/M populations in both leukemic cell lines. Analysis of cell cycle regulatory protein expression showed modulation of cyclin B1, cyclin D3, CDK4, and CDK6 by rhizocarpic acid, and upregulation of cyclin D3 by lobaric acid in both cell lines. Overall, these findings provide new insights into the molecular mechanisms underlying the bioactivity of lichen-derived metabolites in leukemic cells and identify rhizocarpic acid as a previously uncharacterized modulator of apoptosis- and cell cycle-related pathway progression. Further studies, including comprehensive dose-response analyses and in vivo evaluations, will be necessary to fully define their therapeutic potential.

To analyze the compensatory characteristics and influencing factors of the maxillary arch curvature in the sagittal plane. A total of 537 pre-treatment cases with cone beam computed tomography (CBCT) and digital dental model were included. CBCT images and dental models were registered and fused to obtain landmark coordinates of the integrated models. On the midsagittal plane, maxillary arch was fitted separately on each side using clinical crown center points, indices reflecting maxillary arch morphology were measured. Generalized estimating equations (GEEs) and additional statistical analyses were employed to examine the relationship between maxillary arch curvature and its influencing factors. The gingival-directional intersection angle between the anterior and posterior segments of the maxillary arch in the sagittal plane (AC/PC) was smaller in adolescents (162.42&#xb0; &#xb1; 6.38&#xb0;) than adults (166.09&#xb0; &#xb1; 6.93&#xb0;). Differences were also observed among patients with varying degrees of crowding, overjet, and overbite. In GEE analyses accounting for within-subject clustering, age demonstrated a significant positive association with AC/PC (&#x3b2; = 1.781, P < 0.001), whereas the maxillomandibular plane angle (MP/PP) showed a significant negative association (&#x3b2; = -0.902, P < 0.001). With increasing age, the sagittal curvature of the maxillary arch tends to flatten, whereas greater curvature is associated with a larger maxillomandibular plane angle (MP/PP). Age and vertical skeletal relationships appear to play key roles in shaping sagittal maxillary arch morphology.

Current preclinical models for cervical dysplasia rely on animal systems that poorly mimic human anatomy. To address this and align with emerging initiatives to reduce animal experimentation, we developed a human-sized, 3D in&#xa0;vitro model of high-grade cervical dysplasia. The construct integrates normal human fibroblasts, keratinocytes, and SiHa cancer cells within a gelatin methacrylate (GelMA) hydrogel, engineered with a cervical "os" and asymmetric lesion to replicate native human cervical architecture. We utilized this platform to evaluate the efficacy and safety of ethyl cellulose-ethanol (EC-ethanol), a novel ablation therapy designed to mitigate the off-target leakage associated with traditional ethanol injections. While control injections of pure ethanol resulted in widespread, non-specific necrosis (approximately 99% cell death), EC-ethanol successfully formed a localized gel depot. High-resolution mapping of the ablation zone demonstrated that EC-ethanol significantly concentrated cytotoxicity within the dysplastic lesion while preserving surrounding healthy tissue. Margin analysis revealed a sharp therapeutic gradient, with cell death normalizing to background levels within approximately 2&#x2009;mm of the injection site. These findings validate the translational potential of EC-ethanol as a spatially precise intervention and demonstrate the utility of macro-scale 3D models as powerful, ethical alternatives to animal testing for optimizing local drug delivery.