A 3D-Printed helmet for precise and repeatable neuromodulation targeting in awake non-human primates.

The application of non-invasive brain stimulation (NIBS) in non-human primates (NHPs) is critical for advancing understanding of brain networks and developing treatments for neurological diseases. Improving the precision of targeting can significantly enhance the efficacy of these interventions. Here, we introduce a 3D-printed helmet designed to achieve repeatable and precise neuromodulation targeting in awake rhesus monkeys, eliminating the need of head fixation. Imaging studies confirmed that the helmet consistently targets the primary motor cortex (M1) with a margin of error less than 1 mm. Evaluations of stimulation efficacy revealed high resolution and stability. Additionally, physiological evaluations under propofol anesthesia showed that the helmet effectively facilitated the generation of recruitment curves for motor area, confirming successful neuromodulation. Collectively, our findings present a straightforward and effective method for achieving consistent and precise NIBS targeting in awake NHPs, potentially advancing both basic neuroscience research and the development of clinical neuromodulation therapies.

Paired box proteins as diagnostic biomarkers for endocervical adenocarcinoma.

In this editorial, we commented on the article by Akers et al published in the recent issue of the World Journal of Clinical Cases. We focused specifically on the role of the transcription factor paired box protein 8 (PAX8) belonging to the family PAX in the carcinogenesis of a gynecologic tumor, endocervical adenocarcinoma, arising from the tissue of mesonephric origin, and the potential diagnostic value for the same type of neoplasms. The global vaccination program of human papillomavirus (HPV) has dramatically reduced the incidence of cervical cancer, including cases of adenocarcinoma. The type of adenoid epithelial origin has a lower frequency of HPV detection but tends to be more aggressive and fatal. Cases of endocervical adenocarcinoma occurring in females of menopause age have been described in the 2023 volume of the World Journal of Clinical Cases and in our study recently published in Oncol Lett. The histopathological findings and immunohistochemical assays showed that the lesions had glandular morphology, and the specimens in these two reports were immunohistochemically positive for the transcription factor PAX8, albeit that they had opposing expression profiles of tumor suppressor p16 and estrogen receptor and the presence of the HPV genome. The presence of a mucin protein, MUC 5AC, as revealed in both studies suggested target molecules for the diagnosis of mucinous adenoid type of uterine tumor and other histological origins. The clinical outcome was unfavorable due to metastasis and recurrence. This prompted the improvement of the antitumor modality, with the introduction of precise targeting therapy. Mucin has now been reported to be the therapeutic target for adenocarcinomas.

Endocytosis-Inspired Zwitterionic Gel Tape for High-Efficient and Sustainable Underoil Adhesion.

Marine oil exploration is important yet greatly increases the risk of oil leakage, which will result in severe environment pollution and economic losses. It is an urgent need to develop effective underoil adhesives. However, realizing underoil adhesion is even harder than those underwater, due to the stubborn attachment of a highly viscous oil layer on target surface. Here, inspired by endocytosis, a tough gel tape composed of zwitterionic polymer network and zwitterionic surfactants is developed. The amphiphilic surfactants can form micelle to capture the oil droplets and transport them from the interface to gel via electrostatic attraction of polymer backbone, mimicking the endocytosis and achieving robust underoil adhesion. Benefiting from the oil-resistance of polymer backbone, the gel further realizes a combination of i) long-term adhesion with high durability, ii) repeated adhesion in oil, and iii) renewable adhesion efficiency after exhausted use. The tape exhibits an ultra-high adhesive toughness of 2446.86 J m-2 to stainless steel in silicone oil after 30 days' oil-exposure; such value of adhesive toughness surpasses many of those achieved in underwater adhesion and is greater than underoil adhesion performance of commercial tape. The strategy illustrated here will motivate the design of sustainable and efficient adhesives for wet environments.

Impaired Sensitivity to Thyroid Hormones is Associated with Central Obesity in Euthyroid Type 2 Diabetes Mellitus Patients with Overweight and Obesity.

Background: Thyroid hormone levels are associated with the distribution of body components in humans. Objective: This study aimed to investigate the associations between thyroid hormone (TH) levels, central sensitivity to THs, and body composition in overweight and obese patients with euthyroid type 2 diabetes mellitus (T2DM). Methods: This cross-sectional study included 1215 euthyroid T2DM patients (721 men and 494 women) aged 20-80 years. The thyroid hormone sensitivity indices included the thyroid feedback quartile-based index (TFQI), thyrotroph T3 resistance index (TT3RI), thyrotroph T4 resistance index (TT4RI), and thyroid-stimulating hormone index (TSHI). The appendicular fat ratio, trunk fat ratio, android fat ratio, gynoid fat ratio, and appendicular skeletal muscle mass (ASM) were measured via dual-energy X-ray absorptiometry. Results: The data revealed a greater proportion of subjects with impaired central sensitivity to THs in the obese group. TFQIFT4 and TFQIFT3 levels were positively correlated with the upper limb fat ratio, lower limb fat ratio, gynoid fat ratio, and total fat ratio. TSHI was positively correlated with body mass index (BMI), upper limb fat ratio, lower limb fat ratio, trunk fat ratio, android fat ratio, gynoid fat ratio, total fat ratio, and appendicular skeletal muscle mass index (ASMI) in women. In men, TSHI was only positively correlated with upper limb fat ratio, lower limb fat ratio, and total fat ratio. Logistic regression analysis indicated that TT3RI and TFQIFT3 were independently and positively associated with central obesity and low muscle mass in overweight and obese men. No significant differences were found among the women. Conclusion: THs central sensitivity is related to the body composition of euthyroid T2DM patients. Specifically, high levels of TT3RI and TFQIFT3 are associated with central obesity and low muscle mass in T2DM men with overweight and obesity.

Neuregulin-1 immunoreactivity in peripheral plasma is associated with rs6982890 polymorphism-mediated psychotic symptoms in schizophrenia.

OBJECTIVES: Neuregulin 1 (NRG1) is a risk gene for schizophrenia and involved in neurodevelopment and synaptic plasticity. Polymorphisms in NRG1 may affect psychotic symptoms in schizophrenia. This study investigated the effects of the single nucleotide polymorphism (SNP) rs6982890 on peripheral plasma NRG1 immunoreactivity, clinical symptoms and cognitive functions in schizophrenia patients. MATERIAL AND METHODS: We recruited subjects from the Han population of northern China from 2010 to 2022. We first genotyped and analyzed 6 NRG1 SNPS in 1304 patients with schizophrenia and 871 healthy controls. Then, 91 patients with schizophrenia and 40 healthy controls were selected to detect the peripheral plasma NRG1 immunoreactivity by ELISA. Among them, 84 patients were divided into rs6982890 genotypes to analyze the correlation between NRG1 immunoreactivity and clinical symptoms. RESULTS: Rs6982890 allelic frequencies were statistically significant between patients and controls. Baseline peripheral plasma NRG1 immunoreactivity in patients were significantly lower than controls. NRG1 immunoreactivity in patients were significantly increased after 8 weeks of antipsychotic treatment and significantly correlated with clinical symptoms and cognitive function. Genotyping of patients with SNP rs6982890 indicated NRG1 immunoreactivity in CC genotype increased significantly after treatment, while CT genotype had no significant change. Baseline NRG1 immunoreactivity with the CT genotype were significantly higher than CC genotype. CONCLUSIONS: NRG1 SNP rs6982890 is significantly associated with schizophrenia in the Han population of northern China, and it may affect the effect of antipsychotic drug treatment by regulating the peripheral plasma NRG1 immunoreactivity.

Thermodynamics and explainable machine learning assist in interpreting biodegradability of dissolved organic matter in sludge anaerobic digestion with thermal hydrolysis.

Dissolved organic matter (DOM) is essential in biological treatment, yet its specific roles remain incompletely understood. This study introduces a machine learning (ML) framework to interpret DOM biodegradability in the anaerobic digestion (AD) of sludge, incorporating a thermodynamic indicator (λ). Ensemble models such as Xgboost and LightGBM achieved high accuracy (training: 0.90-0.98; testing: 0.75-0.85). The explainability of the ML models revealed that the features λ, measured m/z, nitrogen to carbon ratio (N/C), hydrogen to carbon ratio (H/C), and nominal oxidation state of carbon (NOSC) were significant formula features determining biodegradability. Shapley values further indicated that the biodegradable DOM were mostly formulas with λ lower than 0.03, measured m/z value higher than 600 Da, and N/C ratios higher than 0.2. This study suggests that a strategy based on ML and its explainability, considering formula features, particularly thermodynamic indicators, provides a novel approach for understanding and estimating the biodegradation of DOM.

Elevated plasma matrix metalloproteinase 9 in schizophrenia patients associated with poor antipsychotic treatment response and white matter density deficits.

Oxidative stress and neuroinflammation contribute to schizophrenia (SCZ) pathology and may influence treatment efficacy. Matrix metalloproteinase 9 (MMP9) is a critical molecular node mediating the interaction between oxidative stress and inflammation, and so may influence treatment efficacy. Here we examined the associations of plasma MMP9 concentration with antipsychotic drug responses, clinical symptoms, and brain structure. A total of 129 healthy controls and 124 patients with SCZ were included in this study. Patients were monitored clinically during 8 weeks of antipsychotic treatment and classified as poor responders (n = 49) or good responders (n = 75). We then compared plasma MMP9 concentrations in healthy controls at baseline and both SCZ responder groups at baseline and after the 8-week antipsychotic treatment regimen. Cognitive function was also examined using the MATRICS Consensus Cognitive Battery. In addition, we extracted regional white matter density from magnetic resonance images of patients. Compared to healthy controls, plasma MMP9 levels were significantly elevated in poor responders at baseline and negatively correlated with both white matter density in the right superior temporal gyrus and the change in cognitive symptoms after treatment. Conversely, there was no significant difference in plasma MMP9 between good responders and healthy controls, and no associations of plasma MMP9 with cognitive symptoms or regional white matter density among good responders. Elevated plasma MMP9 is associated with poor antipsychotic drug efficacy and white matter deficits in SCZ patients, and so may be a useful biomarker to guide personalized treatment.

Apelin-13 alleviates intrauterine adhesion by inhibiting epithelial-mesenchymal transition of endometrial epithelial cells and promoting angiogenesis.

Intrauterine adhesion (IUA) is a common complication of surgical manipulation of the uterine cavity such as abortion. The pathology of IUA is characterized by fibrosis, but the pathogenesis is not fully understood. The function of Apelin-13 in IUA and related mechanisms were investigated in this study. The IUA rat model was established. The pathological changes and fibrosis degree of rat uterine tissues were detected by HE and Masson staining after intraperitoneal injection of Apelin-13. Epithelial-mesenchymal transition (EMT) of endometrial epithelial cells and endothelial-mesenchymal transition (EnMT) of vein endothelial cells were induced by TGF-ß1. Tube-forming assay using HUVEC was implemented to detect the effect of Apelin-13 upon angiogenesis. IHC staining, immunofluorescence staining, and Western blot were conducted to detect the expression levels of EMT markers, angiogenesis, and key proteins of the TGF-ß1/Smad signaling. Apelin-13 significantly alleviated IUA and fibrosis, and increased endometrial thickness and gland number in IUA rats. In addition, Apelin-13 significantly reversed EMT and EnMT induced by IUA modeling and TGF-ß1, promoted the tube-forming ability of HUVEC, and up-regulated the expression of angiogenesis-related proteins. Mechanistically, Apelin-13 significantly suppressed smad2/3 phosphorylation and inhibited the TGF-ß1/Smad signaling via its receptor APJ. Apelin-13 might alleviate IUA via repressing the TGF-ß1/Smad pathway and is expected to be a potent therapeutic option for the clinical treatment of IUA.

Contribution of Tregs to the promotion of constructive remodeling after decellularized extracellular matrix material implantation.

Host remodeling of decellularized extracellular matrix (dECM) material through the appropriate involvement of immune cells is essential for achieving functional organ/tissue regeneration. As many studies have focused on the role of macrophages, only few have evaluated the role of regulatory T cells (Tregs) in dECM remodeling. In this study, we used a mouse model of traumatic muscle injury to determine the role of Tregs in the constructive remodeling of vascular-derived dECM. According to the results, a certain number of Tregs could be recruited after dECM implantation. Notably, using anti-CD25 to reduce the number of Tregs recruited by the dECM was significantly detrimental to material remodeling based on a significant reduction in the number of M2 macrophages. In addition, collagen and elastic fibers, which maintain the integrity and mechanical properties of the material, rapidly degraded during the early stages of implantation. In contrast, the use of CD28-SA antibodies to increase the number of Tregs recruited by dECM promoted constructive remodeling, resulting in a decreased inflammatory response at the material edge, thinning of the surrounding fibrous connective tissue, uniform infiltration of host cells, and significantly improved tissue remodeling scores. The number of M2 macrophages increased whereas that of M1 macrophages decreased. Moreover, Treg-conditioned medium further enhanced material-induced M2 macrophage polarization in vitro. Overall, Treg is an important cell type that influences constructive remodeling of the dECM. Such findings contribute to the design of next-generation biomaterials to optimize the remodeling and regeneration of dECM materials.

Navigating the landscape of enzyme design: from molecular simulations to machine learning.

Global environmental issues and sustainable development call for new technologies for fine chemical synthesis and waste valorization. Biocatalysis has attracted great attention as the alternative to the traditional organic synthesis. However, it is challenging to navigate the vast sequence space to identify those proteins with admirable biocatalytic functions. The recent development of deep-learning based structure prediction methods such as AlphaFold2 reinforced by different computational simulations or multiscale calculations has largely expanded the 3D structure databases and enabled structure-based design. While structure-based approaches shed light on site-specific enzyme engineering, they are not suitable for large-scale screening of potential biocatalysts. Effective utilization of big data using machine learning techniques opens up a new era for accelerated predictions. Here, we review the approaches and applications of structure-based and machine-learning guided enzyme design. We also provide our view on the challenges and perspectives on effectively employing enzyme design approaches integrating traditional molecular simulations and machine learning, and the importance of database construction and algorithm development in attaining predictive ML models to explore the sequence fitness landscape for the design of admirable biocatalysts.

PEG 300 Promotes Mesodermal Differentiation in iPSC-Derived Embryoid Body Formation In Vitro.

Embryoid bodies (EB) are sensitive to changes in the culture conditions. Recent studies show that the addition of PEG 300 to culture medium affects cell growth and differentiation; however, its effect on the embryoid body is unclear. This study aims to understand the role of PEG 300 in the process of EB formation and germ layer differentiation. EBs formed more efficiently and differentiated toward the mesoderm when cultured in a medium supplemented with appropriate concentrations of PEG 300. The expression of T/Bry, a marker of mesodermal differentiation, increases in EBs in the PEG group, and the expression of TUBB3 generally decreases, showing a quantitative relationship with PEG. Furthermore, further differentiation of PEG-pretreated EB into vascular smooth muscle cells (VSMCs) by directional induction shows that PEG 300-pretreated induced VSMCs have higher expression of phenotypic markers and greater secretory and contractile functions. This study highlights the role of PEG 300 in the culture medium during EB differentiation, which can significantly enhance mesodermal gene expression and the efficiency of subsequent differentiation into smooth muscle cells and other target cells.

Investigating the mechanism of Fuling-Banxia-Dafupi in the treatment of diabetic kidney disease using network pharmacology and molecular docking.

Go deeply into the molecular mechanism of Fuling-Banxia-Dafupi in the treatment of diabetic kidney disease (DKD) by network pharmacology and molecular docking. Fuling-Banxia-Dafupi is a pair of traditional Chinese medicine for diabetic kidney disease, which can slow down the development of diabetic kidney disease. Screening active components and targets of Fuling-Banxia-Dafupi using the TCMSP database. The Uniprot database was also used to identify effective drug targets. DKD-related Targets were retrieved from the Gene Cards database, and the overlap between these targets and Fuling-Banxia-Dafupi was obtained. GO and KEGG pathway concentration analyses were showed using Metascape, and the results were presented by the microcredit platform. A total of 616 active ingredients and targets were confrimed and intersected with 3,951 diabetic neuropathy-related targets, resulting in 306 common targets. Baicalein and cerevisterol are the core components of Fuling-Banxia-Dafupi, and the key targets are TP53, SRC, and STAT 3. PI3K-Akt signalling pathway is an important pathway. The molecular docking indicated that its main active components and target proteins have good binding activity.

Enzyme/ROS dual-sensitive nanoplatform with on-demand Celastrol release capacity for enhanced ulcerative colitis therapy by ROS scavenging, microbiota rebalancing, inflammation alleviating.

BACKGROUND: The oral administration of drugs for treating ulcerative colitis (UC) is hindered by several factors, including inadequate gastrointestinal stability, insufficient accumulation in colonic lesions, and uncontrolled drug release. METHODS: A multiple sensitive nano-delivery system comprising ß-cyclodextrin (CD) and 4-(hydroxymethyl)phenylboronic acid (PAPE) with enzyme/reactive oxygen species (ROS) sensitivity was developed to load celastrol (Cel) as a comprehensive treatment for UC. RESULTS: Owing to the positive charge in the site of inflamed colonic mucosa, the negatively charged nanomedicine (Cel/NPs) could efficiently accumulate. Expectedly, Cel/NPs showed excellent localization ability to colon in vitro and in vivo tests. The elevated concentration of ROS and intestinal enzymes in the colon microenvironment quickly break the CD, resulting in Cel release partially to rebalance microbiota and recover the intestinal barrier. The accompanying cellular internalization of residual Cel/NPs, along with the high concentration of cellular ROS to trigger Cel burst release, could decrease the expression of inflammatory cytokines, inhibit colonic cell apoptosis, promote the macrophage polarization, scavenge ROS, and regulate the TLR4/NF-κB signaling pathway, which certified that Cel/NPs possessed a notably anti-UC therapy outcome. CONCLUSIONS: We provide a promising strategy for addressing UC symptoms via an enzyme/ROS-sensitive oral platform capable of releasing drugs on demand.

Mendelian Randomization Analysis of Systemic Iron Status and Risk of Different Types of Kidney Disease.

With rapid increases in incidence, diverse subtypes, and complicated etiologies, kidney disease remains a global public health problem. Iron, as an essential trace element, has pleiotropic effects on renal function and the progression of kidney diseases. A two-sample Mendelian randomization (MR) analysis was implemented to determine the potential causal effects between systemic iron status on different kidney diseases. Systemic iron status was represented by four iron-related biomarkers: serum iron, ferritin, transferrin saturation (TfSat), and total iron binding capacity (TIBC). For systemic iron status, 163,511, 246,139, 131,471, and 135,430 individuals were included in the genome-wide association study (GWAS) of serum iron, ferritin, TfSat, and TIBC, respectively. For kidney diseases, 653,143 individuals (15,658 cases and 637,485 controls), 657,076 individuals (8160 cases and 648,916 controls), and 659,320 individuals (10,404 cases and 648,916 controls) were included for immunoglobulin A nephropathy (IgAN), acute kidney disease (AKD), and chronic kidney disease (CKD), respectively. Our MR results showed that increased serum iron [odds ratio (OR): 1.10; 95% confidence interval (95% CI): 1.04, 1.16; p < 0.0042], ferritin (OR: 1.30; 95% CI: 1.14, 1.48; p < 0.0042), and TfSat (OR: 1.07; 95% CI: 1.04, 1.11; p < 0.0042)] and decreased TIBC (OR: 0.92; 95% CI: 0.88, 0.97; p < 0.0042) were associated with elevated IgAN risk. However, no significant associations were found between systemic iron status and AKD or CKD. In our MR study, the genetic evidence supports elevated systemic iron status as a causal effect on IgAN, which suggests a potential protective effect of iron chelation on IgAN patients.

Characterization of Gut Microbiota in Rats and Rhesus Monkeys After Methamphetamine Self-administration.

Methamphetamine (MA) is one of the most abused drugs globally, but the mechanism of its addiction remains unclear. Several animal studies have shown that the gut microbiota (GM) influences addictive behaviors, but the pattern of GM changes during addiction in animals of different species remains unclear. The aim of this study was to explore the association between dynamic changes in GM and MA self-administration acquisition among two classical mammals, rhesus monkeys (Macaca mulatta) and rats, MA self-administration models. Male Sprague-Dawley rats and male rhesus monkeys were subjected to classical MA self-administration training, and fecal samples were collected before and after MA self-administration training, respectively. 16S rRNA sequencing was used for GM analyses. We found that GM changes were more pronounced in rats than in rhesus monkeys, as evidenced by more GM taxa producing significant differences before and after MA self-administration training in rats than in monkeys. We also found that the expression of the genus Clostridia_vadinBB60_group significantly decreased after MA self-administration training in both rats and rhesus monkeys. Lactobacillus changes were significantly negatively correlated with total MA uptake in rats (Pearson R = - 0.666, p = 0.035; Spearman R = - 0.721, p = 0.023), whereas its change was also highly negatively correlated with total MA uptake in rhesus monkeys (Pearson R = - 0.882, p = 0.118; Spearman R = - 1.000, p = 0.083), although this was not significant. These findings suggest that MA causes significant alterations in GM in both rhesus monkeys and rats and that the genus Lactobacillus might be a common therapeutic target for MA uptake prevention across the species.

Clinical review and literature analysis of hepatic epithelioid angiomyolipoma in alcoholic cirrhosis: A case report.

BACKGROUND: Hepatic epithelioid angiomyolipoma (HEA) has a low incidence and both clinical manifestations and imaging lack specificity. Thus, it is easy to misdiagnose HEA as other tumors of the liver, especially in the presence of liver diseases such as hepatitis cirrhosis. This article reviewed the diagnosis and treatment of a patient with HEA and alcoholic cirrhosis, and analyzed the literature, in order to improve the understanding of this disease. CASE SUMMARY: A 67-year-old male patient with a history of alcoholic cirrhosis was admitted due to the discovery of a space-occupying lesion in the liver. Based on the patient's history, laboratory examinations, and imaging examinations, a malignant liver tumor was considered and laparoscopic partial hepatectomy was performed. Postoperative pathology showed HEA. During outpatient follow-up, the patient showed no sign of recurrence. CONCLUSION: HEA is difficult to make a definite diagnosis before surgery. HEA has the potential for malignant degeneration. If conditions permit, surgical treatment is recommended.

Burdock miR8175 in diet improves insulin resistance induced by obesity in mice through food absorption.

The incidence of type 2 diabetes mellitus (T2DM) induced by obesity is rapidly increasing. Although there are many synthetic drugs for treating T2DM, they have various side effects. Here, we report that miR8175, a plant miRNA from burdock root, has effective antidiabetic activity. After administration of burdock decoction or synthetic miR8175 by gavage, both burdock decoction and miR8175 can significantly improve the impaired glucose metabolism of diabetic mice induced by a high-fat diet (HFD). Our results demonstrate that burdock decoction and miR8175 enhance the insulin sensitivity of the hepatic insulin signaling pathway by targeting Ptprf and Ptp1b, which may be the reason for the improvement in metabolism. This study provides a theoretical basis for the main active component and molecular mechanism of burdock to improve insulin resistance. And the study also suggests that plant miRNA may be an indispensable nutrient for maintaining human health.

Preparation and Anti-Icing Properties of Zirconia Superhydrophobic Coating.

Zirconia (ZrO2) is a ceramic material with high-temperature resistance and good insulating properties. Herein, for the first time, the surface of ZrO2 was modified with docosanoic acid (DCA) to improve its self-cleaning and hydrophobic properties. This surface modification transformed the surface of ZrO2 from hydrophilic to superhydrophobic. A two-step spraying method was used to prepare the superhydrophobic surface of ZrO2 by sequentially applying a primer and a topcoat. The primer was a solution configured using an epoxy resin as the adhesive and polyamide as the curing agent, while the topcoat was a modified ZrO2 solution. The superhydrophobic surface of ZrO2 exhibited a contact angle of 154° and a sliding angle of 4°. Scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, thermogravimetric analysis, and other analytical techniques were used to characterize the prepared zirconia particles and their surfaces. Moreover, results from surface self-cleaning and droplet freezing tests showed that DCA-modified ZrO2 can be well combined, and its coatings show good self-cleaning and anti-icing properties on TA2 bases.

Development of TSHR-CAR NK-92 cells for Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC) is the predominant type of thyroid cancer, with some patients experiencing relapse, distant metastases, or refractoriness, revealing limited treatment options. Chimeric antigen receptor (CAR)-modified Natural Killer (NK) cells are revolutionary therapeutic agents effective against various resistant cancers. Thyroid-stimulating hormone receptor (TSHR) expression in DTC provides a unique tumor-specific target for CAR therapy. Here, we developed an innovative strategy for treating DTC using modified NK-92 cells armed with a TSHR-targeted CAR. The modified cells showed enhanced cytotoxicity against TSHR-positive DTC cell lines and exhibited elevated degranulation and cytokine release. After undergoing irradiation, the cells effectively halted their proliferative capacity while maintaining potent targeted killing ability. Transfer of these irradiation-treated cells into NSG mice with DTC tumors resulted in profound tumor suppression. NK-92 cells modified with TSHR-CAR offer a promising, off-the-shelf option for advancing DTC immunotherapy.

A Novel Laryngopharyngeal Reflux Disease Model for Bama Pigs.

OBJECTIVE: To develop a novel Laryngopharyngeal Reflux Disease (LPRD) model in Bama pigs through endoscopic cricopharyngeal myotomy. METHODS: A total of eight 8-month-old Bama pigs were randomly assigned to either the control or surgery group. Prior to intervention, upper esophageal sphincter (UES) manometry and laryngopharyngeal Dx-pH monitoring were conducted to establish baseline physiological parameters for each pig. Subsequently, the surgery group underwent endoscopic cricopharyngeal myotomy, while the control group did not. Two weeks postintervention, these procedures were repeated to evaluate changes in UES contractility and the occurrence of reflux events. At week eight postsurgery, mucosal tissues from both groups were harvested for histological analysis. Hematoxylin and eosin (H&E) staining was used to assess inflammation, while transmission electron microscopy (TEM) examined alterations in intercellular spaces and desmosomes. RESULTS: The mean UES pressures in the control and surgery groups were 59 ± 9 mmHg and 68 ± 12 mmHg, respectively. In the surgery group, there was a significant decrease in UES pressure 2weeks after the operation compared to preoperative values (P = 0.005), whereas no significant change was observed in the control group (P = 0.488). Laryngopharyngeal reflux (LPR) was successfully induced in the surgery group as evidenced by reflux events with pH <5.0, which were not detected in the control group. HE staining revealed marked inflammatory cell infiltration and submucosal gland expansion in throat tissues of the surgery group Bama pigs. TEM further showed enlarged intercellular spaces and reduced desmosome numbers in the laryngopharyngeal epithelium compared to controls. CONCLUSION: Given analogous throat epithelial structures to humans, Bama pigs are an appropriate species for an LPRD animal model. Endoscopic cricopharyngeal myotomy effectively induces LPR and observable pathological changes in Bama pigs, providing a valuable platform for further research into LPRD pathophysiology.