Multi-regulatory potency of USP1 on inflammasome components promotes pyroptosis in thyroid follicular cells and contributes to the progression of Hashimoto's thyroiditis.

BACKGROUND: Inflammatory diseases are often initiated by the activation of inflammasomes triggered by pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs), which mediate pyroptosis. Although pyroptosis resulting from aberrant inflammasome triggering in thyroid follicular cells (TFCs) has been observed in Hashimoto's thyroiditis (HT) patients, the underlying mechanisms remain largely unknown. Given the extensive involvement of protein ubiquitination and deubiquitination in inflammatory diseases, we aimed to investigate how deubiquitinating enzymes regulate thyroid follicular cell pyroptosis and HT pathogenesis. METHODS: Our study specifically investigated the role of Ubiquitin-specific peptidase 1 (USP1), a deubiquitinase (DUB), in regulating the inflammasome components NLRP3 and AIM2, which are crucial in pyroptosis. We conducted a series of experiments to elucidate the function of USP1 in promoting pyroptosis associated with inflammasomes and the progression of HT. These experiments involved techniques such as USP1 knockdown or inhibition, measurement of key pyroptosis indicators including caspase-1, caspase-1 p20, and GSDMD-N, and examination of the effects of USP1 abrogation on HT using a mouse model. Furthermore, we explored the impact of USP1 on NLRP3 transcription and its potential interaction with p65 nuclear transportation. RESULTS: Our findings provide compelling evidence indicating that USP1 plays a pivotal role in promoting inflammasome-mediated pyroptosis and HT progression by stabilizing NLRP3 and AIM2 through deubiquitination. Furthermore, we discovered that USP1 modulates the transcription of NLRP3 by facilitating p65 nuclear transportation. Knockdown or inhibition of USP1 resulted in weakened cell pyroptosis, as evidenced by reduced levels of caspase-1 p20 and GSDMD-N, which could be restored upon AIM2 overexpression. Remarkably, USP1 abrogation significantly ameliorated HT in the mice model, likely to that treating mice with pyroptosis inhibitors VX-765 and disulfiram. CONCLUSIONS: Our study highlights a regulatory mechanism of USP1 on inflammasome activation and pyroptosis in TFCs during HT pathogenesis. These findings expand our understanding of HT and suggest that inhibiting USP1 may be a potential treatment strategy for managing HT.

A radiomics-boosted deep-learning for risk assessment of synchronous peritoneal metastasis in colorectal cancer.

OBJECTIVES: Synchronous colorectal cancer peritoneal metastasis (CRPM) has a poor prognosis. This study aimed to create a radiomics-boosted deep learning model by PET/CT image for risk assessment of synchronous CRPM. METHODS: A total of 220 colorectal cancer (CRC) cases were enrolled in this study. We mapped the feature maps (Radiomic feature maps (RFMs)) of radiomic features across CT and PET image patches by a 2D sliding kernel. Based on ResNet50, a radiomics-boosted deep learning model was trained using PET/CT image patches and RFMs. Besides that, we explored whether the peritumoral region contributes to the assessment of CRPM. In this study, the performance of each model was evaluated by the area under the curves (AUC). RESULTS: The AUCs of the radiomics-boosted deep learning model in the training, internal, external, and all validation datasets were 0.926 (95% confidence interval (CI): 0.874-0.978), 0.897 (95% CI: 0.801-0.994), 0.885 (95% CI: 0.795-0.975), and 0.889 (95% CI: 0.823-0.954), respectively. This model exhibited consistency in the calibration curve, the Delong test and IDI identified it as the most predictive model. CONCLUSIONS: The radiomics-boosted deep learning model showed superior estimated performance in preoperative prediction of synchronous CRPM from pre-treatment PET/CT, offering potential assistance in the development of more personalized treatment methods and follow-up plans. CRITICAL RELEVANCE STATEMENT: The onset of synchronous colorectal CRPM is insidious, and using a radiomics-boosted deep learning model to assess the risk of CRPM before treatment can help make personalized clinical treatment decisions or choose more sensitive follow-up plans. KEY POINTS: Prognosis for patients with CRPM is bleak, and early detection poses challenges. The synergy between radiomics and deep learning proves advantageous in evaluating CRPM. The radiomics-boosted deep-learning model proves valuable in tailoring treatment approaches for CRC patients.

Differential reinforcement of cGAS-STING pathway-involved immunotherapy by biomineralized bacterial outer membrane-sensitized EBRT and RNT.

Radiotherapy (RT), including external beam radiation therapy (EBRT) and radionuclide therapy (RNT), realizes physical killing of local tumors and activates systemic anti-tumor immunity. However, these effects need to be further strengthened and the difference between EBRT and RNT should be discovered. Herein, bacterial outer membrane (OM) was biomineralized with manganese oxide (MnO2) to obtain OM@MnO2-PEG nanoparticles for enhanced radio-immunotherapy via amplifying EBRT/RNT-induced immunogenic cell death (ICD) and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) activation. OM@MnO2-PEG can react with H2O2 and then gradually produce O2, Mn2+ and OM fragments in the tumor microenvironment. The relieved tumor hypoxia improves the radio-sensitivity of tumor cells, resulting in enhanced ICD and DNA damage. Mn2+ together with the DNA fragments in the cytoplasm activate the cGAS-STING pathway, further exhibiting a positive role in various aspects of innate immunity and adaptive immunity. Besides, OM fragments promote tumor antigen presentation and anti-tumor macrophages polarization. More importantly, our study reveals that OM@MnO2-PEG-mediated RNT triggers much stronger cGAS-STING pathway-involved immunotherapy than that of EBRT, owing to the duration difference of RT. Therefore, this study develops a powerful sensitizer of radio-immunotherapy and uncovers some differences between EBRT and RNT in the activation of cGAS-STING pathway-related anti-tumor immunity.

Controlled Cationic Polymerization of p-Methylstyrene in Ionic Liquid and Its Mechanism.

Ionic liquid (IL) as a green solvent is entirely composed of ions; thus, it may be more than a simple solvent for ionic polymerization. Here, the cationic polymerization of p-methylstyrene (p-MeSt) initiated by 1-chloro-1-(4-methylphenyl)-ethane (p-MeStCl)/tin tetrachloride (SnCl4) was systematically studied in 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([Bmim][NTf2]) IL at -25 °C. The results show that IL did not participate in cationic polymerization, but its ionic environment and high polarity were favorable for the polarization of initiator and monomer and facilitate the controllability. The gel permeation chromatography (GPC) trace of the poly(p-methylstyrene) (poly(p-MeSt)) changes from bimodal in dichloromethane (CH2Cl2) to unimodal in IL, and polydispersities Mw/Mn of the polymer in IL showed narrower (1.40-1.59). The reaction rate and heat release rate were milder in IL. The effects of the initiating system, Lewis acid concentration, and 2,6-di-tert-butylpyridine (DTBP) concentration on the polymerization were investigated. The controlled cationic polymerization initiated by p-MeStCl/SnCl4 was obtained. The polymerization mechanism of p-MeSt in [Bmim][NTf2] was also proposed.

Application of Imaging Indicators Based on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Colorectal Peritoneal Carcinomatosis.

Objective: The imaging features of peritoneal carcinomatosis (PC) with different locations and pathological types of colorectal cancer (CRC) on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) were analyzed and discussed. Methods: The PET/CT data of 132 patients with colorectal peritoneal carcinomatosis (CRPC) who met the inclusion and exclusion criteria between May 30, 2016, and December 31, 2019, were collected and analyzed. Observations included the location and pathological type of CRC, the peritoneal cancer index (PCI), standardized uptake maximum value (SUVmax), and retention index (RI) of the CRPC. Statistical analysis was performed using SPSS 20.0 software, and P < 0.05 was considered statistically significant. Results: (1) The range of the PCI in the 132 patients studied was 2-30, with a mean value of 7.40 ± 8.14. The maximum long diameter of the CRPC lesions ranged from 0.6 to 12.1 cm, with an average of 3.23 ± 1.94 cm. The SUVmax ranged from 1.2 to 31.0, with a mean value of 9.65 ± 6.01. The SUVmax and size correlation coefficient for maximal CRPC lesions was r = 0.47 (P < 0.001). The RI range of the 72 patients who underwent time-lapse scanning was -10.0-112.2%, with RI quartiles of 13.5-48.9%; RI was ≥5% in 65 cases and <5% in seven cases. (2) The patients were grouped by the location of their CRC: the right-sided colon cancer (RCC, n = 37), left-sided colon cancer (LCC, n = 44), and rectal cancer groups (RC, n = 51). There were significant differences in the CRC pathological types (P = 0.009) and PCI scores (P = 0.02) between the RCC and RC groups and the RI between the RCC group and the other two groups (P < 0.001). (3) There were 88 patients organized into three groups by the pathology of their CRC: the moderately well-differentiated adenocarcinoma (group A, n = 57), poorly differentiated adenocarcinoma (group B, n = 16), and mucinous adenocarcinoma groups (group C, n = 15 cases, including one case of signet-ring cell carcinoma). There were significant differences in the CRC position (P = 0.003) and SUVmax (P = 0.03) between groups A and C. Conclusion: The PCI, SUVmax, and RI of peritoneal metastatic carcinoma caused by CRC in different locations and pathological types vary. Mucinous adenocarcinoma and poorly differentiated adenocarcinoma are relatively common in the right colon, and the PCI of peritoneal metastatic carcinoma is fairly high, but the SUVmax and RI are somewhat low.

Distribution Characteristics of Colorectal Peritoneal Carcinomatosis Based on the Positron Emission Tomography/Peritoneal Cancer Index.

Background: Colorectal peritoneal carcinomatosis (CRPC) is a primary cause of death in colorectal cancer (CRC) patients. In the past, computed tomography (CT) has been the primary method used to evaluate the distribution of CRPC. This study uses 18F-FDG positron emission tomography/computed tomography (PET/CT) to investigate the distribution characteristics of CRPC. Materials and Methods: The distribution characteristics of 46 patients with CRC who were treated in the authors' hospital were retrospectively analyzed using the peritoneal cancer index (PCI). Results: The 46 patients in the study showed CRPC involvement in 203 of the 598 abdominal and pelvic regions studied (33.9%, 203/598). The regional proportions of CRPC involvement, from high to low, were as follows: region 6 (13.8%), region 0 (10.3%), region 1 (9.9%), region 5 (8.9%), region 7 (8.4%), region 3 (8.4%), region 2 (7.4%), region 4 (7.4%), region 11 (6.9%), region 8 (6.4%), region 12 (5.4%), region 9 (3.4%), and region 10 (3.4%). Thirty-three patients had a PCI of <20, and 13 patients had a PCI of ≥20. Those 13 were among the 17 (37% 17/46) who had CRPC involvement in all three regions. According to the location of the primary CRC focus, the 46 patients were divided into three groups: right hemicolon, left hemicolon, and rectum. The frequency of CRPC was greater in the rectum group than in the left hemicolon group, and the SUVmax of CRPC was greater in the right hemicolon group than in the left hemicolon group; these differences were statistically significant (p < 0.05). Conclusions: The distribution of CRPC has certain characteristics in the abdominal and pelvic cavities. The PET-PCI scores can provide a basis for the diagnosis and clinical treatment strategies in patients with CRC.

LncRNA ANRIL negatively regulated chitooligosaccharide-induced radiosensitivity in colon cancer cells by sponging miR-181a-5p.

BACKGROUND: The radiosensitivity of colon cancer cells can be regulated by noncoding RNAs. OBJECTIVES: In this study, the lncRNA antisense non-coding RNA in the INK4 locus (ANRIL) was selected to analyze its regulatory role in chitooligosaccharides (COS)-related radiosensitivity in colon cancer cells. MATERIAL AND METHODS: The ANRIL expression in colon cancer cell lines was examined using real-time quantitative polymerase chain reaction (RT-qPCR), based on which we selected the cell line that presented the highest expression of ANRIL for radiosensitivity research. The cells were exposed to X-rays (0 Gy, 2 Gy, 4 Gy, and 6 Gy) and evaluated for changes in ANRIL and miR-181a-5p expression using RT-qPCR. Cell viability was evaluated using the CCK8 method, while apoptosis was detected with flow cytometry assays. Dual luciferase assays validated the binding between ANRIL and miR-181a-5p. The cell survival rates after differential COS treatments (0 mg/mL, 1.0 mg/mL, 2.0 mg/mL, 3.0 mg/mL, 4.0 mg/mL, and 5.0 mg/mL) were rated using CCK8 assay. The cells with the strongest dosage of COS (5.0 mg/mL) were selected to further investigate the role of ANRIL/miR-181a-5p in modulating the radiosensitivity observed with CCK-8 and flow cytometry assays. RESULTS: The ANRIL was highly expressed in colon cancer cells lines, especially in the SW480 cell line. Irradiation significantly decreased cell viability and ANRIL expression in a dose-dependent manner. The overexpression of ANRIL reduced the cell apoptosis rate after irradiation. MiR-181a-5p directly bound to ANRIL and was upregulated by irradiation in a dose-dependent manner. The suppression of miR-181a-5p decreased cell apoptosis. The COS treatment notably downregulated cell survival and promoted apoptosis in cells exposed to irradiation. The overexpression of ANRIL partially reversed COS-induced apoptosis and the inhibition rate; the upregulation of miR-181a-5p could counteract the impact of ANRIL regulation in cells. CONCLUSIONS: The ANRIL negatively regulated radiosensitivity induced by COS in colon cancer cells by sponging miR-181a-5p.

Glycopolypeptide Nanocarriers Based on Dynamic Covalent Bonds for Glucose Dual-Responsiveness and Self-Regulated Release of Insulin in Diabetic Rats.

An intelligent carrier system is based on fast glucose response mechanism to regulate the insulin release. Here, glucose dual-responsive nanoparticles were quickly and efficiently obtained, by dynamic covalent bonds between phenylboronic acid-containing homopolymer poly(3-acrylamidophenylboronic acid) (PAAPBA) and glycopolypeptide poly(ethylene glycol)-b-poly(aspartic acid-co-aspart-glucosamine) (PEG-b-P(Asp-co-AGA)) through the formation of cycloborates. Meanwhile, insulin and glucose oxidase (GOx) were loaded during the formation of nanoparticles. The cycloborates in the nanoparticles could be destroyed by the replacement of glycosyl moieties by glucose and oxidized by H2O2 generated from the glucose-GOx system, resulting in the rapid insulin release. After subcutaneous delivery of the insulin/GOx-loaded nanoparticles to diabetic mice, a significant hypoglycemic effect was observed over time. Cytotoxicity study, hemolysis assay, and histological analyses suggested that the nanoparticles showed excellent biocompatibility and safety. This work lays the important theoretical and technical foundations for expanding the scope of applications of nanocarriers in diabetes treatment.

Lenalidomide combined with R-GDP in a patient with refractory CD5-positive diffuse large B-cell lymphoma: A promising response and review.

CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) is associated with poor survival compared with CD5-negative DLBCL. The clinical characteristics of CD5+ DLBCL are different from both CD5-negative DLBCL and other CD5+ B cell lymphomas. There is currently no promising chemotherapy for CD5+ DLBCL. Herein, we report a 49-year-old Asian male with refractory CD5+ DLBCL. He complained of aggravated abdominal pain and weight loss. Computed tomography scan revealed abdominal masses, widespread lymphadenopathy, splenomegaly, and intussusception of the ileocecal junction with bowel wall thickening. Core needle aspiration biopsy of an abdominal mass was performed and immunohistochemistry revealed DLBCL of nongerminal center type. In this report, the dose-intensified R-Hyper CVAD (A) regimen as salvage therapy was introduced but failed to result in substantial improvement over the initially standard R-CHOP regimen. Next, the R-GDP regimen was administered as second-line treatment, but only resulted in a partial response. However, the addition of lenalidomide to R-GDP (R2-GDP) resulted in complete remission. The clinical features, pathogenesis, and possible mechanism of action of lenalidomide in CD5+ DLBCL have been described in the literature. The results of the present case report and literature searches indicate that CD5+ DLBCL may share a common pathway with activated B-cell like (ABC) DLBCL as determined by gene expression profiling. Lenalidomide is expected to induce favorable responses in patients with CD5+ DLBCL.

Comparison of the effectiveness and safety of ultrasound- and CT-guided percutaneous radiofrequency ablation of non-operation hepatocellular carcinoma.

To retrospectively compare the effectiveness and safety of ultrasound (US)- and computer tomography (CT)-guided percutaneous radiofrequency ablation (PRFA) in treating patients with non-operation hepatocellular carcinoma (HCC). Forty patients with non-operation HCC who were treated with US-guided PRFA (20 patients with 24 HCC lesions) or CT-guided PRFA (20 patients with 27 HCC lesions) were enrolled in this study. Follow-up was performed with US and CT/MRI. Complete ablation rate, local recurrence rate, and overall survival rate were used to evaluate the efficacy of the two therapeutic choices. The PRFA-related complications including hilar bile duct injury, sepsis, liver failure, renal dysfunction, peritoneal hemorrhage, and skin burn were assessed. The operation time of CT-guided group was significantly longer than that of the US-guided group (P < 0.05). The single ablation times for tumors with similar size showed no significant difference between the two groups (P > 0.05). The differences in complete ablation rate (79.2 vs. 88.9 %, P > 0.05) and local recurrence rate (16.7 vs. 14.8 %, P > 0.05) between US- and CT-guided groups were not statistically significant. In the US-guided group, the 1-, 2-, and 3-year overall survival rates were 85, 74, and 68 %, respectively, while they were 84, 72, and 58 % in the CT-guided group. The differences were not statistically significant (P > 0.05). No severe complications were found in the two groups. Both US- and CT-guided PRFA are safe and effective therapies for patients with HCC when surgical options are precluded.

A quicker degradation rate is yielded by a novel kind of transgenic silk fibroin consisting of shortened silk fibroin heavy chains fused with matrix metalloproteinase cleavage sites.

Degradation performance of silk fibroin is an important property for its medical applications. Herein we constructed a shortened silk fibroin heavy chain protein fused with a matrix metalloproteinase cleavage site (SSFH-MMP) along with a glutathione S-transferase tag ahead. The digestion assay shows it can be cut by matrix metalloproteinase-2 (MMP-2) at its MMP cleavage site. Furthermore, we introduced the SSFH-MMP into silk fibroin by genetic modification of silkworms in order to increase the degradation rate of the silk fibroin. After acquisition of a race of transgenic silkworms with the coding sequence of the MMP cleavage site in their genomic DNA, we tested some properties of their silk fibroin designated TSF-MMP. The results show that the TSF-MMP has MMP cleavage sites and yields a quicker degradation rate during dilution in MMP-2 enzyme buffer or implantation into tumor tissues compared with that of normal silk fibroin. Moreover, the TSF-MMP is in vitro non-toxic to human bone marrow mesenchymal stem cells (hBM-MSCs) indicating that the TSF-MMP may become a biomaterial with a quicker degradation rate for its medical applications.

A novel method of silkworm embryo preparation for immunohistochemistry.

It is difficult to obtain intact embryos, especially intact early embryos, from insect eggs because of their small sizes. Based on the means traditionally used to get silkworm embryos and the previous approaches used for getting Drosophila embryos, we established a novel method of silkworm embryo preparation. The new method is straightforward and easy to operate. Silkworm embryos could be prepared without severe damage in large quantities by this new protocol. In addition, the novel method of silkworm embryo preparation is quite suitable for immunohistochemistry.

Electrochemical impedance spectroscopy and atomic force microscopic studies of electrical and mechanical properties of nano-black lipid membranes and size dependence.

We present electrochemical impedance spectroscopic (EIS) and two-chamber AFM investigations of the electrical and mechanical properties of solvent-containing nano-BLMs suspended on chip-based nanopores of diameter of 200, 400, and 700 nm. The chips containing nanoporous silicon nitride membranes are fabricated based on low-cost colloidal lithography with low aspect ratio of the nanopores. BLMs of DPhPC lipid molecules are constructed across the nanopores by the painting method. Two equivalent circuits are compared in view of their adequacy in description of the EIS performances of the nano-BLMs and more importantly the structures associated with the nano-BLMs systems. The BLM resistance and capacitance as well as their size and time dependence are studied by EIS. The breakthrough forces, elasticity in terms of apparent spring constant, and lateral tension of the solvent-containing nano-BLMs are investigated by AFM force measurements. The exact relationship of the breakthrough force of the nano-BLM as a function of pore size is revealed. Both EIS and AFM studies show increasing lifetime and mechanical stability of the nano-BLMs with decreasing pore size. Finally, the robust 200 nm diameter nanopores are used to accommodate functional BLMs containing DPhPC lipid molecules and gramicidins by using a painting method with drop of mixture solutions of DPhPC and gramicidins. EIS investigation of the functional nano-BLMs is also performed.

Comparative electrochemical scanning tunneling microscopy study of nonionic fluorosurfactant zonyl FSN self-assembled monolayers on Au(111) and Au(100): a potential-induced structural transition.

We investigate the structure of nonionic fluorosurfactant zonyl FSN self-assembled monolayers on Au(111) and Au(100) in 0.05 M H(2)SO(4) as a function of the electrode potential by electrochemical scanning tunneling microscopy (ECSTM). On Au(111), a (3(1/2) × 3(1/2))R30° arrangement of the FSN SAMs is observed, which remains unchanged in the potential range where the redox reaction of FSN molecules does not occur. On Au(100), some parallel corrugations of the FSN SAMs are observed, which originate from the smaller distance and the repulsive interaction between FSN molecules to make the FSN molecules deviate from the bridging sites, and ECSTM reveals a potential-induced structural transition of the FSN SAMs. The experimental observations are rationalized by the effect of the intermolecular interaction. The smaller distance between molecules on Au(100) results in the repulsive force, which increases the probability of structural change induced by external factors (i.e., the electrode potential). The appropriate distance and interactions of FSN molecules account for the stable structure of FSN SAMs on Au(111). Surface crystallography may influence the intermolecular interaction through changing the molecular arrangements of the SAMs. The results benefit the molecular-scale understanding of the behavior of the FSN SAMs under electrochemical potential control.

Growth and shape-ordering of iron nanostructures on Au single crystalline electrodes in an ionic liquid: a paradigm of magnetostatic coupling.

Fe electrodeposition on Au(111) and Au(100) in BMIBF(4) ionic liquid is found to form hitherto unreported shape-ordered nanoscale morphologies of pseudorods and pseudosquare rings, respectively, both composed of grains of 4-7 nm. The manner of growth of the square rings is a ring-on-ring structure with enlarging side length and slightly protruding four corners. The generality of the growth mechanism is verified by the formation of almost exactly the same shape-ordered Fe nanostructures on Pt, i.e., pseudorod structure on Pt(111) and pseudosquare rings Pt(100). These structures are explained within the framework of magnetostatic interactions of spontaneously magnetized grains under crystallographic constraint of the substrate surface, which result in an antiparallel arrangement in magnetization of the grains at pseudorods and magnetic flux closure at the pseudosquare rings. The closed magnetic flux further leads to magnetic field-enhanced growth at the four corners and the outer peripheries of the pseudosquare rings. The observed shape-ordering of the Fe thin film serves as a paradigm of magnetostatic coupling, in which the roles of ionic liquid as surfactant and magnetic media may not be underestimated. The present work adds a new dimension to electrodeposition in ionic liquid, by which new magnetic film structures may be expected.

STM study on nonionic fluorosurfactant zonyl FSN Self-Assembly on Au(100): [array: see text] molecular lattice, corrugations, and adsorbate-enhanced mobility.

Nonionic fluorosurfactant zonyl FSN self-assembly on Au(100) is investigated by using scanning tunneling microscopy under ambient conditions. High-resolution STM images reveal that a [array: see text] arrangement of the FSN SAMs is formed on Au(100). Different from the uniform structure of FSN SAMs on Au(111), the adsorption sites of FSN molecules on Au(100) change gradually and form a kind of corrugated structure. The change in the adsorption sites probably originates from the repulsive force among FSN molecules because the nearest-neighbor distance of FSN molecules is 0.41 nm, which is smaller than 0.50 nm on Au(111). The mobility of surface atoms on the Au substrate is enhanced by the interaction between FSN molecules and the Au substrate; therefore, no Au island is observed on the FSN-SAM-covered Au(100).