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OBJECTIVE: To investigate the excess mortality and life-years lost associated with diabetes and prediabetes in China. RESEARCH DESIGN AND METHODS: This national cohort study enrolled 135,405 participants aged 18 years or older from the general population in China. Cox proportional hazards regression models were used to estimate adjusted mortality rate ratio (RR). The life table method was used to estimate life expectancy. RESULTS: Among the 135,405 participants, 10.5% had diabetes and 36.2% had prediabetes in 2013. During a median follow-up of 6 years, 5517 deaths were recorded, including 1428 and 2300 deaths among people with diabetes and prediabetes, respectively. Diabetes and prediabetes were significantly associated with increased risk of all-cause (diabetes: RR, 1.61 [95% CI 1.49, 1.73]; prediabetes: RR, 1.08 [95% CI 1.01, 1.15]), and cardiovascular disease (diabetes: RR, 1.59 [95% CI 1.41, 1.78]; prediabetes: RR, 1.10 [95% CI 1.00, 1.21]) mortality. Additionally, diabetes was significantly associated with increased risks of death resulting from cancer, respiratory disease, liver disease, and diabetic ketoacidosis or coma. Compared with participants with normoglycemia, life expectancy of those with diabetes and prediabetes was shorter, on average, by 4.2 and 0.7 years at age 40 years, respectively. The magnitude of the associations of diabetes and prediabetes with all-cause and cardiovascular disease mortality varied by age and residence. CONCLUSIONS: In this national study, diabetes and prediabetes were significantly associated with reduced life expectancy and increased all-cause and cause-specific mortality risks. The disparities in excess mortality associated with diabetes and prediabetes between different ages and residences have implications for diabetes and prediabetes prevention and treatment programs.

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OBJECTIVE: This study aimed to establish a multimodal deep-learning network model to enhance the diagnosis of benign and malignant pulmonary ground glass nodules [GGNs]. METHODS: Retrospective data on pulmonary GGNs were collected from multiple centers across China, including North, Northeast, Northwest, South, and Southwest China. The data were divided into a training set and a validation set in an 8:2 ratio. In addition, a GGN dataset was also obtained from our hospital database and used as the test set. All patients underwent chest computed tomography [CT], and the final diagnosis of the nodules was based on postoperative pathological reports. The Residual Network [ResNet] was used to extract imaging data, the Word2Vec method for semantic information extraction, and the Self Attention method for combining imaging features and patient data to construct a multimodal classification model. Then, the diagnostic efficiency of the proposed multimodal model was compared with that of existing ResNet and VGG models and radiologists. RESULTS: The multicenter dataset comprised 1020 GGNs, including 265 benign and 755 malignant nodules, and the test dataset comprised 204 GGNs, with 67 benign and 137 malignant nodules. In the validation set, the proposed multimodal model achieved an accuracy of 90.2%, a sensitivity of 96.6%, and a specificity of 75.0%, which surpassed that of the VGG [73.1%, 76.7%, and 66.5%] and ResNet [78.0%, 83.3%, and 65.8%] models in diagnosing benign and malignant nodules. In the test set, the multimodal model accurately diagnosed 125 [91.18%] malignant nodules, outperforming radiologists [80.37% accuracy]. Moreover, the multimodal model correctly identified 54 [accuracy, 80.70%] benign nodules, compared to radiologists' accuracy of 85.47%. The consistency test comparing radiologists' diagnostic results with the multimodal model's results in relation to postoperative pathology showed strong agreement, with the multimodal model demonstrating closer alignment with gold standard pathological findings [Kappa=0.720, P<0.01]. CONCLUSION: The multimodal deep learning network model exhibited promising diagnostic effectiveness in distinguishing benign and malignant GGNs and, therefore, holds potential as a reference tool to assist radiologists in improving the diagnostic accuracy of GGNs, potentially enhancing their work efficiency in clinical settings.

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Mutations in SF3B1 are common in many types of cancer, which promotes cancer progression through aberrant RNA splicing. Recently, mRNA nuclear export has been reported to be defective in cells with SF3B1 K700E mutation. However, the mechanism remains unclear. Our study reveals that the K700E mutation in SF3B1 attenuates its interaction with THOC5, an essential component of mRNA nuclear export complex THO. Furthermore, SF3B1 mutation caused reduced binding of THOC5 with some mRNA and inhibited the nuclear export of these mRNA. Interestingly, THOC5 overexpression restores the nuclear export of these mRNA in cells with SF3B1 K700E mutation. Importantly, other types of cancer-associated SF3B1 mutations also inhibited mRNA nuclear export similarly, suggesting that it is common for cancer-associated SF3B1 mutation to inhibit mRNA nuclear export. Our research highlights the critical role of the THOC5-SF3B1 interaction in the regulation of mRNA nuclear export and provides valuable insights into the impact of SF3B1 mutations on mRNA nuclear export.

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BACKGROUND: China has undergone a significant socioeconomic transformation over the past few decades due to the implementation of family planning policies. These societal changes have resulted in an increased susceptibility among females to developing cardiometabolic diseases (CMD). Unfortunately, studies investigating the correlation between family planning policies in China and the incidence of CMD remain scarce. METHODS: Data from 1,226 females, aged 30 years or older with ≥ 1 live birth, undergoing routine physical examinations between January 2018 and December 2021 were collected, and they were grouped by number of live births 1, 2, and ≥ 3. A binary logistic regression model was employed to examine the association between the number of live births with CMD. Furthermore, the subgroup analysis was performed to elucidate the impact of the implementation of family planning policies with CMD. RESULTS: Women with live births ≥ 3 tended to be older, had higher gravidities, a greater proportion of central obesity, general obesity, hypertension, and dyslipidemia (all P < 0.05). Across the three groups (live birth = 1, =2 and ≥ 3), the odds ratio (OR) with 95% CI for obesity were: 1.00, 3.32 (2.36-4.69), and 5.73 (3.79-8.68); for dyslipidemia were: 1.00, 1.75 (1.29-2.39), and 2.02 (1.38-2.94); and for CMD were: 1.00, 1.91 (1.44-2.54), and 2.15 (1.46-3.15), respectively (all P < 0.05). In addition, based on the different periods of the childbearing policy in China, a subgroup analysis (where age was divided into ≤ 45, 45-65, and ≥ 65 years old) found that each additional live birth increased the prevalence risk of obesity and CMD in the younger generations, while hypertension and dyslipidemia in the elder generation. CONCLUSIONS: Higher live births are positively associated with the prevalence of CMD among women in Southwest China. Moreover, giving birth after the implementation of the one-child policy tends to have a higher risk of developing CMD.

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Whey protein isolate (WPI) has the potential to be a Pickering stabilizer, but its applications in emulsions are restricted due to its structural susceptibility to external environments. Proanthocyanidin (PAC) is a natural antioxidant polyphenol that can improve protein properties and enhance the stability and longevity of emulsions. In the current work, PACs were employed to bind WPIs, forming a complex to stabilize Pickering emulsion. Fluorescence spectroscopy, infrared spectroscopy, confocal microscopy, quartz crystal microbalance with dissipation monitoring (QCM-D), and antioxidant stability of the emulsion were performed to characterize the structural changes of the protein/polyphenol complexes and their effects on the interfacial properties and stability of the emulsion. Results indicated that PACs and WPIs might bind through hydrogen bonding and hydrophobic interactions, effectively increasing the hydrophilicity of the complexes. QCM-D and emulsion stability showed that adsorption at the oil-water interface of the complexes was the largest, and the stability of the Pickering emulsion was optimal when the concentration ratio of PAC to WPI exceeded 1:1. The antioxidant properties of Pickering emulsions were positively correlated with the addition of PACs. These findings demonstrated that PACs could improve the properties of WPIs and enhance the stability and antioxidant properties of WPI Pickering emulsions.

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BACKGROUND: Advancements in laparoscopic technology have popularized laparoscopic total gastrectomy over traditional open surgery, yet postoperative complications like anastomotic leakage and stenosis persist, particularly in esophagojejunostomy. To address this, since 2017, the authors have introduced the "Pant-Shaped" esophagojejunostomy as an improvement over the classic Roux-en-Y method, especially beneficial for patients with small intestinal diameters or those with gastric body cancer or Siewert III. OBJECTIVE: To assess the viability and safety of employing 'Pant-Shaped' anastomosis following laparoscopic-assisted total gastrectomy. METHODS: A method of descriptive case study was used. In our department of the First Affiliated Hospital of Wannan Medical College, records of 210 patients who underwent laparoscopic-assisted total gastrectomy for gastric body cancer or adenocarcinoma at the junction of esophagus and jejunum with "Pant-Shaped" anastomosis between January 2017 and December 2022 were examined. Clinicopathological features and postoperative conditions were also examined and assessed. RESULTS: The mean age of the 164 male and 46 female research participants was 69.2 ± 8.3 years. There was a mean estimated blood loss of 63.4 ± 29.7 ml, an anastomosis time of 25.9 ± 3.0 minutes, an operation time of 208.2 ± 40.4 minutes, and a postoperative hospital stay of 12.2 ± 8.0 days. Nine patients (4.3%) experienced postoperative problems (Clavien-Dindo > grade II), including two episodes of anastomotic leakage that were resolved with irrigation and drainage, anti-infection therapy, and nutritional assistance. After an unforeseen reoperation, two cases of duodenal stump leaking were resolved. Anastamotic hemorrhage was treated with hemostasis and blood transfusion, and the patient made a full recovery. Due to a Peterson's hernia, one patient required emergent open surgery. three months subsequent to LATG. CONCLUSIONS: The "Pant-Shaped" anastomosis method after laparoscopic-assisted total gastrectomy is simple, easy to promote, and has fewer complications. It is a safe and feasible modified method for esophagojejunostomy, especially suitable for patients with poor intestinal dilation and contraction ability and small jejunal diameter.

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Background: Phase angle (PhA) is a variable obtained from bioelectrical impedance analysis (BIA). It is highly sensitive and specific and is commonly used in clinical nutrition assessment. Recently, PhA has shown promise in predicting clinical outcomes, especially as a new indicator of mortality, but its use in pediatric research is limited. This study aims to investigate the association between PhA measured at admission using BIA and PICU length of stay (LOS) and 60-day mortality in critically ill children and adolescents. Methods: A consecutive series of pediatric patients in the PICU underwent BIA measurements within 72 h of admission. All patients met the inclusion and exclusion criteria. Patient demographics, anthropometric measurements, pediatric index of mortality 2 score (PIM-2), and laboratory exams were recorded. Kaplan-Meier (K-M) survival curves were constructed based on the critical PhA value to assess differences in survival status within the 60-day window. Multivariate cox regression model was employed to illustrate the relationship between PhA and 60-day mortality rates. The Youden's index method was used to identify the critical cut-off value for PhA in relation to mortality rates. ROC curves provided the area under the curve (AUC) and a 95% confidence interval (CI). Results: A total of 205 pediatric patients (118 boys) were included, with a mean age of 9.2 years (±6.0). Survival curves indicated a cutoff value of 3.1°, with higher survival in patients with PhA ≥3.1° compared to those with PhA <3.1° (F = 10.51, p < 0.0001). The area under the ROC curve was 0.70, with a sensitivity of 0.65 and specificity of 0.72. Total hospital LOS was longer in the PhA <3.1° group compared to the PhA ≥3.1° group (p = 0.000). The PhA <3.1° group had a longer PICU LOS (adjusted for age and sex, HR 1.871, p = 0.000, log-rank test, p = 0.000). PhA and PIM-2 were two independently significant correlated variables (p < 0.05) for the 60-day mortality rate in this study. Conclusion: Low PhA in patients is associated with longer PICU LOS and an increased risk of PICU patient mortality. PhA not only serves as an indicator for monitoring pediatric nutrition but also as a prognostic indicator for PICU patients.

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Objectives: In-depth understanding of osteonecrosis of femoral head (ONFH) has revealed that degeneration of the hip cartilage plays a crucial role in ONFH progression. However, the underlying molecular mechanisms and susceptibility to environmental factors in hip cartilage that contribute to ONFH progression remain elusive. Methods: We conducted a multiomics study and chemical-gene interaction analysis of hip cartilage in ONFH. The differentially expressed genes (DEGs) involved in ONFH progression were identified in paired hip cartilage samples from 36 patients by combining genome-wide DNA methylation profiling, gene expression profiling, and quantitative proteomics. Gene functional enrichment and pathway analyses were performed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Functional links between proteins were discovered through protein-protein interaction (PPI) networks. The ONFH-associated chemicals were identified by integrating the DEGs with the chemical-gene interaction sets in the Comparative Toxicogenomics Database (CTD). Finally, the DEGs, including MMP13 and CHI3L1, were validated via quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Results: Twenty-two DEGs were identified across all three omics levels in ONFH cartilage, 16 of which were upregulated and six of which were downregulated. The collagen-containing extracellular matrix (ECM), ECM structural constituents, response to amino acids, the relaxin signaling pathway, and protein digestion and absorption were found to be primarily involved in cartilage degeneration in ONFH. Moreover, ten major ONFH-associated chemicals were identified, including, benzo(a)pyrene, valproic acid, and bisphenol A. Conclusion: Overall, our study identified several candidate genes, pathways, and chemicals associated with cartilage degeneration in ONFH, providing novel clues into the etiology and biological processes of ONFH progression.

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As a kind of antibiotic, tetracycline (TC) might remain in animal blood and milk products during use, which poses a risk to humans after consumption. Therefore, a ratiometric fluorescence probe was proposed for the detection of TC, which was based on an Eu3+ functionalized hydrogen-bonded organic framework (HOF). Since there are a large number of N and O atoms in the skeleton of HOF, more Eu3+ could be loaded onto HOF by forming coordinate bonds, while preserving the fluorescence of luminol monomer in HOF. In the presence of TC, the fluorescence of luminol monomer was attenuated at 425 nm due to inner filter effect (IFE), while TC selectively enhanced the fluorescence peak at 617 nm of Eu3+ under the influence of antenna effect (AE). This highly sensitive probe could detect TC in the range of 0.1-60 µM and had a low limit of detection of 8.51 nM. Besides, the HOF@Eu probe was able to detect TC in actual samples (milk and tap water) with good recoveries (95.09%-111.51%) and precision (R < 4.78%), indicating this probe has great application potential for the detection of TC in food.

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Background: Rosacea has a high incidence, significantly impacts quality of life, and lacks sufficient diagnostic techniques. This study aimed to investigate the feasibility of laser speckle contrast imaging (LSCI) for measuring facial blood perfusion in patients with rosacea and to identify differences in blood flow among various facial regions associated with different rosacea subtypes. Methods: From June to December 2023, 45 patients were recruited, with 9 excluded, leaving 36 subjects: 12 with erythematotelangiectatic rosacea (ETR), 12 with papulopustular rosacea (PPR), and 12 healthy controls. The Think View multispectral imaging analyzer assessed inflammation via gray reading values across the full face and five facial areas: forehead, nose, cheeks, and chin. LSCI measured and analyzed blood perfusion in the same areas. Plasma biomarkers interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) were tested in different groups. Results: Both ETR and PPR groups showed increased average blood perfusion and facial inflammation intensity by gray values compared to controls, with statistically significant differences. Average blood perfusion of ETR and PPR groups showed increased values in the forehead, cheeks, and nose, compared to controls, and the values in the cheeks were statistically different between ETR and PPR. The facial inflammation intensity of the ETR group showed increased values in the forehead and cheeks, and the PPR group showed increased gray values in the forehead, cheeks, nose, and chin compared to controls, and the values for the cheeks, nose, and chin were statistically significantly different between ETR and PPR. Plasma biomarkers IL-6, IL-1ß, and TNF-α were significantly elevated in both ETR and PPR groups compared to controls. Conclusion: LSCI is a valuable, non-invasive tool for assessing blood flow dynamics in rosacea, providing a data foundation for clinical research. Different rosacea subtypes exhibit distinct lesion distribution and blood flow patterns, and both ETR and PPR could affect all facial areas, particularly the cheeks in ETR and the forehead, nose, and chin in PPR.

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Constipation, a widespread gastrointestinal disorder, often leads to the exploration of natural remedies. This study examines the efficacy of Golden Flower Tibetan Tea Polysaccharides (GFTTPs) in alleviating constipation in mice. Chemical analyses reveal that GFTTPs possess O-H, carboxyl, carboxylic acid (-COOH), and C-O-C groups, alongside a porous crystal structure with thermal stability. In animal experiments, GFTTPs significantly upregulated aquaporin 3 (AQP3) and aquaporin 8 (AQP8) expressions in the colon, enhancing water absorption and reducing fecal water content. At a 400 mg/kg dosage, GFTTPs notably improved colonic tissue alterations and serum levels of excitatory neurotransmitters caused by loperamide hydrochloride. They also beneficially altered gut microbiota, increasing Coprococcus, Lactobacillus, and Pediococcus populations. These changes correlated with improved stool frequency, consistency, and weight in constipated mice. Importantly, GFTTPs at 200 and 400 mg/kg doses exhibited comparable effects to the normal control group in key parameters, such as gastrointestinal transit rate and fecal moisture. These findings suggest that GFTTPs may serve as a potent natural remedy for constipation, offering significant therapeutic potential within the context of gut health and with promising implications for human applications.

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BACKGROUND: Numerous metabolic illnesses have obesity as a risk factor. The composition of the gut microbiota and endogenous metabolism are important factors in the onset and progression of obesity. Recent research indicates that cordycepin (CRD), derived from fungi, exhibits anti-inflammatory and antioxidant properties, showing potential in combating obesity. However, further investigation is required to delineate its precise impacts on endogenous metabolism and gut microbiota. METHODS: In this work, male C57BL/6J mice were used as models of obesity caused by a high-fat diet (HFD) and given CRD. Mice's colon, liver, and adipose tissues were stained with H&E. Serum metabolome analysis and 16S rRNA sequencing elucidated the effects of CRD on HFD-induced obese mice and identified potential mediators for its anti-obesity effects. RESULTS: CRD intervention alleviated HFD-induced intestinal inflammation, improved blood glucose levels, and reduced fat accumulation. Furthermore, CRD supplementation demonstrated the ability to modulate endogenous metabolic disorders by regulating the levels of key metabolites, including DL-2-aminooctanoic acid, inositol, and 6-deoxyfagomine. CRD influenced the abundance of important microbiota such as Parasutterella, Alloprevotella, Prevotellaceae_NK3B31_group, Alistipes, unclassified_Clostridia_vadinBB60_group, and unclassified_Muribaculaceae, ultimately leading to the modulation of endogenous metabolism and the amelioration of gut microbiota disorders. CONCLUSIONS: According to our research, CRD therapies show promise in regulating fat accumulation and stabilizing blood glucose levels. Furthermore, through the modulation of gut microbiota composition and key metabolites, CRD interventions have the dual capacity to prevent and ameliorate obesity.

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Simultaneous localization and mapping (SLAM) is an essential component for smart robot operations in unknown confined spaces such as indoors, tunnels and underground. This paper proposes a novel tightly-coupled ranging-LiDAR-inertial simultaneous localization and mapping framework, namely RLI-SLAM, which is designed to be high-accuracy, fast and robust in the long-term fast-motion scenario, and features two key innovations. The first one is tightly fusing the ultra-wideband (UWB) ranging and the inertial sensor to prevent the initial bias and long-term drift of the inertial sensor so that the point cloud distortion of the fast-moving LiDAR can be effectively compensated in real-time. This enables high-accuracy and robust state estimation in the long-term fast-motion scenario, even with a single ranging measurement. The second one is deploying an efficient loop closure detection module by using an incremental smoothing factor graph approach, which seamlessly integrates into the RLI-SLAM system, and enables high-precision mapping in a challenging environment. Extensive benchmark comparisons validate the superior accuracy of the proposed new state estimation and mapping framework over other state-of-the-art systems at a low computational complexity, even with a single ranging measurement and/or in a challenging environment.

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BACKGROUND: Circular RNAs (circRNAs) belong to a family of covalently closed single-stranded RNAs that have been implicated in cancer progression. Previous studies have reported that hsa_circ_0087784 was abnormally expressed in breast cancer. However, the role of hsa_circ_0087784 in non-small cell lung cancer (NSCLC) is unknown. METHODS: Here, we used RT-qPCR and FISH to examine hsa_circ_0087784 expression in NSCLC cells and tissue samples. The dual-luciferase reporter assay was used to identify downstream targets of hsa_circ_0087784. Transwell migration, 5-ethynyl-2´-deoxyuridine, and CCK-8 assays were used to examine migration and proliferation. Tumorigenesis and metastasis assays were used to determine the role of hsa_circ_0087784 in NSCLC progression in a mouse tumor xenograft model in vivo. RESULTS: We found that hsa_circ_0087784 was expressed at significantly high levels in NSCLC tissue samples and cell lines. Downregulation of hsa_circ_0087784 suppressed NSCLC cellular proliferation, as well as migration. Our dual-luciferase reporter assay revealed that miR-576-5p and CDCA4 were downstream targets of hsa_circ_0087784. CDCA4 overexpression or miR-576-5p suppression reversed the effects of hsa_circ_0087784 silencing on NSCLC cell migration, and EMT-related protein expression levels. CONCLUSION: Our findings suggested that downregulation of hsa_circ_0087784 inhibited NSCLC metastasis and progression through the regulation of CDCA4 expression and miR-576-5psponging.

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Primordial germ cells (PGCs) are vital for producing sperm and eggs and are crucial for conserving chicken germplasm and creating genetically modified chickens. However, efforts to use PGCs for preserving native chicken germplasm and genetic modification via CRISPR/Cas9 are limited. Here we show that we established 289 PGC lines from eight Chinese chicken populations with an 81.6% success rate. We regenerated Piao chickens by repropagating cryopreserved PGCs and transplanting them into recipient chickens, achieving a 12.7% efficiency rate. These regenerated chickens carried mitochondrial DNA from female donor PGC and the rumplessness mutation from both male and female donors. Additionally, we created the TYRP1 (tyrosinase-related protein 1) knockout (KO) PGC lines via CRISPR/Cas9. Transplanting KO cells into male recipients and mating them with wild-type hens produced four TYRP1 KO chickens with brown plumage due to reduced eumelanin production. Our work demonstrates efficient PGC culture, cryopreservation, regeneration, and gene editing in chickens.

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Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) mediated by CD4+ T helper (Th) cells, and characterized by immune cell infiltration, demyelination and neurodegeneration, with no definitive cure available. Thus, it is pivotal and imperative to acquire more profound comprehension of the underlying mechanisms implicated in MS. Dysregulated immune responses are widely believed to play a primary role in the pathogenesis of MS. Recently, a plethora of studies have demonstrated the involvement of T follicular helper (Tfh) cells and tertiary lymphoid-like structures (TLSs) in the pathogenesis and progression of MS. Cathepsin C (CatC) is a cysteine exopeptidase which is crucial for the activation of immune-cell-associated serine proteinases in many inflammatory diseases in peripheral system, such as rheumatoid arthritis and septicemia. We have previously demonstrated that CatC is involved in neuroinflammation and exacerbates demyelination in both cuprizone-induced and experimental autoimmune encephalomyelitis (EAE) mouse models. However, the underlying immunopathological mechanism remains elusive. In the present study, we established a recombinant myelin oligodendrocyte glycoprotein 35-55 peptide-induced EAE model using conditional CatC overexpression mice to investigate the effects of CatC on the alteration of CD4+ Th subsets, including Th1, Th2, Th17, Tfh and T regulatory cells. Our findings demonstrated that CatC particularly enhanced the population of Tfh cell in the brain, resulting in the earlier onset and more severe chronic syndrome of EAE. Furthermore, CatC promoted the formation of TLSs in the brain, leading to persistent neuroinflammation and exacerbating the severity of EAE in the chronic phase. Conversely, treatment with AZD7986, a specific inhibitor of CatC, effectively attenuated the syndrome of EAE and its effects caused by CatC both in vivo and in vitro. These findings provide a novel insight into the critical role of CatC in innate and adaptive immunity in EAE, and specific inhibitor of CatC, AZD7986, may contribute to potential therapeutic strategies for MS.

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OBJECTIVE: The aim of this study was to evaluate the feasibility and plan quality of spot-scanning proton arc therapy (SPArc) using a synchrotron-accelerator-based proton therapy system compared to intensity-modulated proton therapy (IMPT). APPROACH: Five representative disease sites, including head and neck, lung, liver, brain chordoma, and prostate cancers, were retrospectively selected. Both IMPT and SPArc plans are generated with the HITACHI ProBEAT PBS system's minimum MU constraints and physics beam model. The SPArc plans are generated with 2.5° sampling frequency. The static delivery time was simulated based on the previously published synchrotron delivery sequence model, and the dynamic delivery time was simulated using a proton arc gantry mechanical model integrated with the synchrotron delivery sequence. Both dosimetric plan quality and delivery efficiency are evaluated. MAIN RESULTS: A superior plan quality is reached compared with the IMPT plans generated for the same disease site. However, a relatively prolonged static and dynamic delivery time post new challenge, as static time increased by 49.22% and dynamic time 59.10% on average. SIGNIFICANCE: This study presents the first simulation results of delivering the SPArc plans using a synchrotron-accelerated proton therapy system. The result shows its feasibility and limitations, which could guide future development.

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PURPOSE: The stimulator of interferon genes (STING) is a critical component of the innate immune system and plays a pivotal role in tumor immunotherapy. Developing non-invasive in vivo diagnostic methods for visualizing STING is highly valuable for STING-related immunotherapy. This work aimed to build a noninvasive imaging platform that can dynamically and quantitatively monitor tumor STING expression. METHODS: We investigated the in vivo positron emission tomography (PET) imaging of STING-expressing tumors (B16F10, MC38, and Panc02) with STING-targeted radioprobe ([18F]F-CRI1). The expression of STING in tumors was quantified, and correlation analysis was performed between these results and the outcomes of PET imaging. Furthermore, we optimized the structure of [18F]F-CRIn with polyethylene glycol (PEG) to improve the pharmacokinetic characteristics in vivo. A comprehensive comparison of the imaging and biodistribution results obtained with the optimized probes was conducted in the B16F10 tumors. RESULTS: The PET imaging results showed that the uptake of [18F]F-CRI1 in tumors was positively correlated with the expression of STING in tumors (r = 0.9184, P < 0.001 at 0.5 h). The lipophilicity of the optimized probes was significantly reduced. As a result of employing optimized probes, B16F10 tumor-bearing mice exhibited significantly improved tumor visualization in PET imaging, along with a marked reduction in retention within non-target areas such as the gallbladder and intestines. Biodistribution experiments further validated the efficacy of probe optimization in reducing uptake in non-target areas. CONCLUSION: In summary, this work demonstrated a promising pathway for the development of STING-targeted radioprobes, advancing in vivo PET imaging capabilities.

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Hepatic proteomes are intricately controlled through biosynthesis, extracellular secretion, and intrahepatic degradation. Autophagy governs lysosome-mediated intrahepatic degradation and the hepatic proteome. When autophagy is impaired, it leads to the accumulation of intrahepatic proteins, causing proteinopathy. This study investigates whether autophagy can modulate the hepatic proteome non-degradatively. Utilizing conditional, inducible, and hepatotoxin models of hepatic autophagy impairment, we assessed the overall hepatic proteome expression using Coomassie brilliant blue (CBB) staining and liquid chromatography-tandem mass spectrometry (LC/MS). We pinpointed and confirmed four specific hepatic proteins-Cps1, Ahcy, Ca3, and Gstm1-that were selectively modified in autophagy-deficient livers. Expression of Cps1, Ahcy, and Ca3 were significantly reduced, while Gstm1 expression increased in livers with autophagy impairment. Interestingly, these changes in hepatic protein levels were not due to defective autophagic degradation but were associated with alterations in mRNA transcript levels. Moreover, as a result of autophagic dysfunction, sustained activation of the nuclear erythroid-derived 2-like 2 (Nrf2) transcription factor, transcriptionally regulated the mRNA levels of these proteins. Our findings indicate that autophagy can influence hepatic proteins not solely via traditional degradative routes but also through non-degradative transcriptional processes by modulating Nrf2.

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[This corrects the article DOI: 10.3389/fendo.2024.1266761.].