Histopathological changes in salivary glands after radioactive iodine treatment for thyroid diseases.

OBJECTIVES: We aimed to evaluate the histopathological alterations in human salivary glands after radioactive iodine (RAI) treatment for thyroid diseases. STUDY DESIGN: We retrospectively selected patients with a history of RAI treatment for thyroid diseases from a database of patients who underwent surgery for oral and maxillofacial diseases and had specimens of salivary glands at Peking University School of Stomatology between December 2012 and July 2023. The patients' clinical records and histopathological slides of the salivary glands were carefully reviewed. RESULTS: Sixteen patients were included. Three symptomatic patients showed duct cell cytoplasmic vacuolization and increased numbers of disordered duct cell layers (3/3), severe duct stenosis and dilation (2/3), and exfoliated epithelial cells in the duct lumen (1/3). The glandular parenchyma showed severe acinar atrophy (2/2), fat content enhancement (2/2), and severe periductal fibrosis (3/3). Thirteen asymptomatic patients showed duct cell cytoplasmic vacuolization (5/13), acinar atrophy and increased fat content in the parenchyma (5/13), and periductal fibrosis (5/13). CONCLUSION: Main histopathologic changes in the salivary glands after RAI treatment for thyroid diseases are cytoplasmic vacuolization of duct cells, acinar atrophy, fat content enhancement, and periductal fibrosis. These changes were evident in symptomatic cases, and were also seen in some asymptomatic patients.

Diagnosis and Treatment of Radioactive Iodine-Induced Sialadenitis: A 10-Year Endoscopic Experience.

OBJECTIVES: The aim of this study was to explore the endoscopic characteristics of radioactive iodine-induced sialadenitis (RAIS), and to evaluate the treatment outcomes of endoscopic intervention for RAIS. STUDY DESIGN: Retrospective case series. METHODS: Eighty-two consecutive patients (11 males and 71 females) diagnosed as RAIS from Nov. 2012 to Sep. 2023 were retrospectively included. All patients underwent endoscopic exploration and intervention of the affected glands. The endoscopic features were collected, and treatment outcomes were followed-up and evaluated through post to pre-operative comparisons of gland status. RESULTS: Overall, endoscopic procedures were undertaken for 162 parotid glands (PGs) and 62 submandibular glands (SMGs). Endoscopy showed severe lumen stricture (49.3%) and ductal atresia (23.5%) in PGs, as well as severe stenosis of the anterior duct and ectasia of the proximal duct (59.7%) in SMGs. During a median six months' follow-up, the treatment outcomes of PGs were evaluated as "improvement" in 23.4%，"lesion maintenance" in 45.1% and "lesion aggravation" in 31.5% of the glands. As for SMGs, the treatment outcomes were scored as "improvement"in 29.0%，"lesion maintenance"in 54.8%, and"lesion aggravation"in 16.1% of the glands. No significant differences of treatment outcomes were found relative to RAI treatment sessions and cumulative dosage. CONCLUSION: RAIS is characteristic of severe lumen stricture and ductal atresia in PGs, and stenosis of the distal duct and ectasia of the proximal duct in SMGs. Endoscopy can alleviate clinical symptoms of RAIS and help to preserve the gland function. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Exosome-delivered miR-410-3p reverses epithelial-mesenchymal transition, migration and invasion of trophoblasts in spontaneous abortion.

Current studies have indicated that insufficient trophoblast epithelial-mesenchymal transition (EMT), migration and invasion are crucial for spontaneous abortion (SA) occurrence and development. Exosomal miRNAs play significant roles in embryonic development and cellular communication. Hereon, we explored the roles of serum exosomes derived from SA patients on trophoblast EMT, migration and invasion. Exosomes were isolated from normal control (NC) patients with abortion for unplanned pregnancy and SA patients, then characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting. Exosomal miRNA profiles were identified by miRNA sequencing. The effects of serum exosomes on trophoblast migration and invasion were detected by scratch wound healing and transwell assays, and other potential mechanisms were revealed by quantitative real-time PCR (RT-PCR), western blotting and dual-luciferase reporter assay. Finally, animal experiments were used to explore the effects of exosomal miR-410-3p on embryo absorption in mice. The serum exosomes from SA patients inhibited trophoblast EMT and reduced their migration and invasion ability in vitro. The miRNA sequencing showed that miR-410-3p was upregulated in SA serum exosomes. The functional experiments showed that SA serum exosomes restrained trophoblast EMT, migration and invasion by releasing miR-410-3p. Mechanistically, SA serum exosomal miR-410-3p inhibited trophoblast cell EMT, migration and invasion by targeting TNF receptor-associated factor 6 (TRAF6) at the post-transcriptional level. Besides, SA serum exosomal miR-410-3p inhibited the p38 MAPK signalling pathway by targeting TRAF6 in trophoblasts. Moreover, milk exosomes loaded with miR-410-3p mimic reached the maternal-fetal interface and aggravated embryo absorption in female mice. Clinically, miR-410-3p and TRAF6 expression were abnormal and negatively correlated in the placental villi of SA patients. Our findings indicated that exosome-derived miR-410-3p plays an important role between SA serum and trophoblasts in intercellular communication, suggesting a novel mechanism by which serum exosomal miRNA regulates trophoblasts in SA patients.

Imaging-based diagnosis and classification of radioactive iodine-induced sialadenitis.

OBJECTIVES: To establish an inflammation grading system for radioactive iodine-induced sialadenitis (RAIS) based on spiral computed tomography (CT), ultrasonography and sialography. METHODS: In all, 120 RAIS patients (18 males and 102 females) were retrospectively included. Spiral CT, ultrasonography and sialography appearances were analysed and categorized as follows: grade I, approximately normal or mild sialadenitis; grade II, moderate sialadenitis; and grade III, severe sialadenitis. Adenitis severity was analysed relative to sex, age, RAI treatment sessions and cumulative doses. RESULTS: Spiral CT showed heterogeneous (78.9%) and atrophic changes (36.8%) in the parotid glands (PGs) and duct ectasia (24.8%) in the submandibular glands (SMGs). Ultrasonography showed heterogeneous echogenicity (54.3%) and diminished gland size (30.2%) in PGs and duct ectasia in SMGs (34.7%). Sialography showed duct obliteration in 25.3% PGs and 3.2% SMGs. Statistical analysis showed good consistency among the three imaging grading results. The incidence and severity of PG lesions were significantly higher than that of SMGs (p < 0.001). As for PGs, adenitis severity was associated with both treatment sessions and cumulative doses; but in SMGs, disease severity was only related to treatment sessions. CONCLUSIONS: A grading system for severity of RAIS was established based on spiral CT, ultrasonography and sialography appearances.

Single-crystal ZrCo nanoparticle for advanced hydrogen and H-isotope storage.

Hydrogen-isotope storage materials are essential for the controlled nuclear fusion. However, the currently used smelting-ZrCo alloy suffers from rapid degradation of performance due to severe disproportionation. Here, we reveal a defect-derived disproportionation mechanism and report a nano-single-crystal strategy to solve ZrCo's problems. Single-crystal nano-ZrCo is synthesized by a wet-chemistry method and exhibits excellent comprehensive hydrogen-isotope storage performances, including ultrafast uptake/release kinetics, high anti-disproportionation ability, and stable cycling, far superior to conventional smelting-ZrCo. Especially, a further incorporation of Ti into nano-ZrCo can almost suppress the disproportionation reaction. Moreover, a mathematical relationship between dehydrogenation temperature and ZrCo particle size is established. Additionally, a microwave method capable of nondestructively detecting the hydrogen storage state of ZrCo is developed. The proposed disproportionation mechanism and anti-disproportionation strategy will be instructive for other materials with similar problems.

Confirmation of eosinophilic sialodochitis by terminal duct biopsy.

OBJECTIVE: To analyse the histopathological features of eosinophilic sialodochitis by using terminal duct biopsy. METHODS: Sixty-five patients with suspected eosinophilic sialodochitis and four with chronic obstructive sialadenitis were prospectively enrolled. Clinical features, laboratory tests and sialograms were comparatively analysed. Terminal duct biopsy of the parotid or submandibular glands was performed concomitantly with endoscopy-assisted duct dilatation to determine the histopathological features of eosinophilic sialodochitis. RESULTS: Based on eosinophil quantification, the samples of suspected patients were scored as 'definite', 'highly suspected' and 'negative' in 26 (40%), 15 (23.1%) and 24 (36.9%) cases, respectively. Gland types and peripheral blood eosinophil counts were significantly different among these three groups. The proportions of itching glands, mucus plug exudations and elevated immunoglobulin E levels were higher in the 'definite' group than in the other two groups; however, the intergroup differences were insignificant. The primary pathological features of eosinophilic sialodochitis were abundant eosinophils and lymphocytes infiltrated around the duct, degranulation of eosinophils, extensive fibrosis and scattered mastocytes. Periductal eosinophils were not found in cases of chronic obstructive sialadenitis. CONCLUSION: Our findings suggest that terminal duct biopsy is safe and valuable for the pathological confirmation of eosinophilic sialodochitis, and can be used simultaneously with endoscopy-assisted duct dilatation.

Structure and anti-inflammatory activity of neo-clerodane diterpenoids from Scutellaria barbata.

Herein, 13 previously undescribed neo-clerodane diterpenoids (1-13) and 27 known analogs (14-40) were isolated from the aerial parts of Scutellaria barbata. Absolute configurations of undescribed compounds were assigned based on single-crystal X-ray diffraction analysis and comparison of experimental and circular dichroism. All isolates were evaluated for the inhibition of nitric oxide generation induced by lipopolysaccharide in RAW 264.7 macrophages. Compound 36 was found to be the most active with an IC50 value of 10.6 µM. Structure-activity relations of these neo-clerodane diterpenoids revealed that the α, ß-unsaturated-γ-lactone moiety with an exocyclic conjugated double bond was necessary for maintaining and increasing its activity. Further mechanistic studies show that compound 36 suppressed nitric oxide synthase enzymes (iNOS) expression without affecting iNOS activity. Additionally, compound 36 suppresses NF-κB signaling by inhibiting IκBα phosphorylation.

Reconfigurable, Solvent-Processable, NIR-Triggerable Shape Memory Cyanate Esters for Smart Molds.

Shape memory polymer (SMP)-based smart molds, which could provide high-resolution mold shape and morph in response to external stimuli for readily demolding the complex structure, attract extensive attention. However, the suitable SMP for smart molds is usually confined with low stretchability that likely causes damage during demolding. Herein, we present a cyanate ester smart composite (CESC) with a reconfigurable, solvent-processable, and near-infrared (NIR)-triggerable shape memory effect (SME), which enables the 2D sheet with a variety of morphed complex shapes through deformation in a mild situation. Notably, the reconfigurable SME and the recyclability of the shape memory cyanate ester (SMCE) were addressed for the first time, attributed to the dynamic covalent bonds of transesterification and the novel cyanurate exchange. In addition, we found that the mechanism of solvent-processable SME is attributed to the varied cross-linking density and the mobility of the polymer chain. Integrating the multiple responsive SME and reconfigurable SME, the CESC demonstrated versatile applications as a smart mold. The results demonstrate a wide scope of application of the integrated SME and provide a new design strategy for thermoset cyanate materials.

LncRNA NEAT1 inhibits apoptosis and autophagy of ovarian granulosa cells through miR-654/STC2-mediated MAPK signaling pathway.

Long non-coding RNA (lncRNA) anomalies cause early ovarian failure. LncRNA nuclear enriched abundant transcript 1 (NEAT1) was down-regulated in premature ovarian failure (POF) mice and connected to the illness, however, the mechanism remained unclear. The levels of gene and protein were measured by using quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence. Follicle stimulating hormone (FSH), estradiol (E2), and luteinizing hormone (LH) levels were determined using enzyme-linked immunosorbent assay (ELISA). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry were used to determine cell viability and apoptosis. The interaction of NEAT1, miR-654, and stanniocalcin-2 (STC2) was verified by dual-luciferase reporter assay or RNA binding protein immunoprecipitation (RIP) assays. The results showed NEAT1 and STC2 down-regulated, while miR-654 up-regulated in POF mice. Overexpression of NEAT1 reduced apoptosis and autophagy in cyclophosphamide (CTX)-treated ovarian granulosa cells (OGCs), and Bax, cleaved-caspase3, LC3B, LC3II/LC3I ratio were decreased and Bcl-2 and p62 were raised. NEAT1 suppressed miR-654 expression by directly targeting miR-654. The inhibition of NEAT1 overexpression on apoptosis and autophagy in OGCs was reversed by miR-654 mimics. STC2 was a target gene of miR-654, and miR-654 inhibitor reduced the apoptosis and autophagy by regulating the STC2/MAPK axis. To sum up, NEAT1 reduced miR-654 expression and modulated the STC2/MAPK pathway to decrease apoptosis and autophagy in POF, indicating a potential therapeutic target.

Ligand Relay Catalysis Enables Asymmetric Migratory Reductive Acylation of Olefins or Alkyl Halides.

Design of ligands in transition-metal catalyzed reactions is challenging, especially in asymmetric transformations. With each step in the catalytic cycle promoted by its privileged ligand and different steps well-connected by dynamic ligand exchange, synergistic combination of multiple ligands could potentially enhance the catalytic efficiency and selectivity. Now, this concept has been applied to the NiH-catalyzed asymmetric remote hydroacylation of olefins and migratory acylation of alkyl halides with excellent regio- and enantioselectivity, utilizing two simple ligands, one for chain-walking and the other for asymmetric acylation. Starting from abundant alkenes/alkyl halides and carboxylic acids, a wide range of enantioenriched chiral α-aryl ketones can be efficiently accessed under mild conditions.

Synthesis and anticancer activity of novel histone deacetylase inhibitors that inhibit autophagy and induce apoptosis.

The combination of histone deacetylase (HDAC) and autophagy inhibitor has been considered as a novel cancer therapeutic strategy. To find novel HDAC inhibitors that can inhibit autophagy, several new series of oxazole- and thiazole-based HDAC inhibitors were designed and synthesized by replacing the phenyl cap in SAHA with 5-phenyloxazoles and 5-phenylthiazoles. The representative oxazole derivative, compound 21, showed better enzymatic inhibitory activity than SAHA (vorinostat). Compound 21 induced G2/M cell cycle arrest and its antiproliferative activity is 10-fold better than SAHA in multiple tumor cell lines. Western blot analysis showed that compound 21 can markedly increase the acetylation levels of tubulin, histone H3, and histone H4. Contrary to SAHA, compound 21 was found to inhibit autophagy. Additionally, compound 21 induced cell apoptosis via the Bax/Bcl-2 and caspase-3 pathways. Ultimately, compound 21 exhibited higher oral antitumor potency than SAHA in a A549 xenograft model. Our results indicated that compound 21 may be further developed as a promising anticancer agent.

MXene-Reinforced Liquid Metal/Polymer Fibers via Interface Engineering for Wearable Multifunctional Textiles.

Stretchable conductive fibers are an important component of wearable electronic textiles, but often suffer from a decrease in conductivity upon stretching. The use of liquid metal (LM) droplets as conductive fillers in elastic fibers is a promising solution. However, there is an urgent need to develop effective strategies to achieve high adhesion of LM droplets to substrates and establish efficient electron transport paths between droplets. Here, we use large-sized MXene two-dimensional conductive materials to modify magnetic LM droplets and prepare MXene/magnetic LM/poly(styrene-butadiene-styrene) composite fibers (MLMS fibers). The MXene sheets decorated on the surface of magnetic LM droplets not only enhance the droplet adhesion to substrate but also bridge adjacent droplets to establish efficient conductive paths. MLMS fibers show several-fold improvements in tensile strength and elongation and a 30-fold increase in conductivity compared with pure LM-filled fibers. These conductive fibers can be easily woven into multifunctional textiles, which exhibit strong electromagnetic interference shielding and stable Joule heating performances even under large tensile deformation. In addition, other advantages of MLMS textiles, such as high gas/liquid permeability, strong chemical resistance (acid and alkaline conditions), high/low-temperature tolerance (-40-150 °C) and water washability, make them particularly suitable for wearable applications.

Noise-Tolerant Optomechanical Entanglement via Synthetic Magnetism.

Entanglement of light and multiple vibrations is a key resource for multichannel quantum information processing and memory. However, entanglement generation is generally suppressed, or even fully destroyed, by the dark-mode (DM) effect induced by the coupling of multiple degenerate or near-degenerate vibrational modes to a common optical mode. Here we propose how to generate optomechanical entanglement via DM breaking induced by synthetic magnetism. We find that at nonzero temperature, light and vibrations are separable in the DM-unbreaking regime but entangled in the DM-breaking regime. Remarkably, the threshold thermal phonon number for preserving entanglement in our simulations has been observed to be up to 3 orders of magnitude stronger than that in the DM-unbreaking regime. The application of the DM-breaking mechanism to optomechanical networks can make noise-tolerant entanglement networks feasible. These results are quite general and can initiate advances in quantum resources with immunity against both dark modes and thermal noise.

Tuning intramolecular charge transfer and spin-orbit coupling of AIE-active type-I photosensitizers for photodynamic therapy.

Development of photosensitizers (PSs) featuring type-I reactive oxygen species (ROS) with aggregation-induced emission (AIE) properties is a judicious approach to overcome the deficit of conventional photodynamic therapy (PDT). However, it remains a challenge to design AIE-active type-I ROS PSs using a simple theranostic scaffold paired with a delicate balance between intramolecular charge transfer (ICT) and large spin-orbit coupling (SOC) features to facilitate intersystem crossing (ISC) and hence to intensify triplet excitons for type-I ROS generation as well as to improve optical properties for the desired biomedical applications. In this work, a rationally designed series of PSs based on C-6-substituted tetraphenylethylene-fused benzothiazole-coumarin scaffolds, named TPE-nCUMs, were synthesized via a fused-ring-electron-acceptor (FREA) strategy, endowed with AIE properties in aqueous solution and thus self-monitoring type-I ROS generation under white-light irradiation to study the effects of diverse ICT and SOC potentials on their photochemical and optical properties. Both experimental and theoretical results revealed that the concomitantly increasing strengths of both ICT and SOC features promote type-I ROS generation by TPE-nCUMs. The key role of the SOC-promoting carbonyl group towards the ROS generation ability of TPE-nCUMs was then examined. Among TPE-nCUMs, gem-2OMe-TPE-2CUM displayed highly efficient type-I ROS generation. Importantly, gem-OMe-TPE-1CUM acts as a fluorescent indicator in HeLa cells (in vitro), revealing its excellent diffusion capability in both lysosomal and mitochondrial organelles with low dark toxicity, high cytotoxicity under white-light and remarkable PDT efficiency. Our study has thus elucidated a rationally designed strategy at the molecular level to fine-tune ICT and SOC features for the advance of AIE-active type-I ROS PSs, opening a new avenue for cancer treatment and image-guided therapy.

LncRNA GATA3-AS1 promoted invasion and migration in human endometrial carcinoma by regulating the miR-361/ARRB2 axis.

Endometrial carcinoma (EC) is a kind of fatal female malignancy. lncRNA GATA3-AS1 has been identified as an oncogene in various cancers. However, the functions and mechanisms of GATA3-AS1 in EC remain to be explored. Human EC tissues and four EC cell lines were used. Western blotting and quantitative real-time PCR (qRT-PCR) were used to evaluate the expression of GATA3-AS1, miR-361, and ARRB2. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction among GATA3-AS1, miR-361, and ARRB2. Flow cytometry, colony formation assay, scratch assay, and transwell assay were used to examine the cell apoptosis, proliferation, migration, and invasion of EC cells, respectively. In vivo tumor growth was monitored in nude mice. GATA3-AS1 and ARRB2 were upregulated while miR-361 was downregulated in human EC tissues and EC cells. GATA3-AS1 knockdown constrained cell proliferation, invasion, migration, and EMT while promoting the apoptosis of EC cells by upregulating miR-361. GATA3-AS1 negatively regulated miR-361 expression. ARRB2 was the direct target of miR-361 and could activate the Src/Akt pathway. In vivo, GATA3-AS1 knockdown suppressed tumor progression by upregulating the miR-361 expression. lncRNA GATA3-AS1 promoted EC invasion and migration by the miR-361/ARRB2 axis, which indicated that GATA3-AS1 might be a promising therapeutic option for advanced EC progression. KEY MESSAGES: GATA3-AS1 knockdown suppressed EC proliferation, invasion, and migration. GATA3-AS1 directly inhibited miR-361 as a ceRNA. MiR-361 knockdown reversed the tumor suppressive effect caused by GATA3-AS1 knockdown. MiR-361 bound to ARRB2 directly and suppressed its expression. The GATA3-AS1/miR-361/ARRB2 axis regulated EC cell proliferation, invasion, and migration.

Alteration of gut microbiota in high-fat diet-induced obese mice using carnosic acid from rosemary.

Rosmarinus officinalis (rosemary) is widely used as a food ingredient. Rosemary extract (containing 40% carnosic acid) exhibited potent antiobesity activity. However, the relationship between carnosic acid (CA) and changes in the gut microbiota of high-fat diet (HFD)-induced obese mice has not been fully investigated. C57BL/6 mice were fed a normal diet, an HFD, or an HFD containing 0.1% or 0.2% CA for 10 weeks. CA exhibited promising antiobesity effects and caused marked alterations in the gut microbiota of HFD-induced obese mice. CA caused the prevalence of probiotics and functional bacteria, including Akkermansia muciniphila, Muribaculaceae unclassified, and Clostridium innocuum group, and inhibited diabetes-sensitive bacteria, including Proteobacteria and Firmicutes. The ratio of Firmicutes to Bacteroidetes was regulated by CA in a dose-dependent manner, decreasing it from 13.22% to 2.42%. Additionally, CA reduced bile acid-metabolizing bacteria, such as Bilophila, Clostridium, Lactobacillus, and Leuconostoc. The results of the linear discriminant analysis and effect size analysis indicated that CA attenuated the microbial changes caused by HFD. The high CA (HCA) group (HFD containing 0.2% CA) exhibited a greater abundance of Verrucomicrobiae (including Akkermansia muciniphila, genus Akkermansia, family Akkermansiaceae, and order Verrucomicrobiales), Eubacterium, and Erysipelatoclostridium, and the low CA (LCA) group (HFD containing 0.1% CA) exhibited a greater abundance of Eisenbergiella, Intestinimonas, and Ruminococcaceae. Our results demonstrate that the antiobesity effects of CA might be strongly related to its prebiotic effects.

[Research progress on common pesticide residues in Chinese medicinal materials].

Chinese medicinal materials are the precious resources of China and favored by patients at home and abroad because of their natural sources and curative effects. Pesticides are often used to prevent and control diseases and insect pests and regulate the growth of Chinese medicinal plants, so as to improve the yield and quality of Chinese medicinal materials. Most of the pesticides can play a role in pest control through systemic action, stomach toxicity, contact, fumigation and other ways, especially the systemic pesticides can kill hidden pests by entering the Chinese medicinal plants. Despite the good pest control effect, it is difficult to remove the systemic pesticides by simple cleaning, which poses a great risk to the safety of Chinese medicinal materials. At the same time, excessive or non-standard use of pesticides leads to serious pesticide residues in Chinese medicinal materials, which affects not only the quality and efficacy of the materials and harm human health but also the international development of Chinese medicinal materials industry. Pesticide residues have become a bottleneck affecting the industry development and hindering the export of Chinese medicinal materials. Therefore, it is of great significance to study how to quickly, sensitively, and accurately detect and remove pesticide residues in Chinese medicinal materials. We reviewed the common pesticide residues in Chinese medicinal materials in recent years in terms of characteristics, harm, and detection and removal techniques, and discussed the future development of the detection and removal deve-lopment. With this review, we aimed to provide a reference for the quality control of Chinese medicinal materials and promote the healthy development of Chinese medicine industry.