Long-term efficacy, safety and biocompatibility of a novel sirolimus eluting iron bioresorbable scaffold in a porcine model.

Iron is considered as an attractive alternative material for bioresorbable scaffolds (BRS). The sirolimus eluting iron bioresorbable scaffold (IBS), developed by Biotyx Medical (Shenzhen, China), is the only iron-based BRS with an ultrathin-wall design. The study aims to investigate the long-term efficacy, safety, biocompatibility, and lumen changes during the biodegradation process of the IBS in a porcine model. A total of 90 IBSs and 70 cobalt-chromium everolimus eluting stents (EES) were randomly implanted into nonatherosclerotic coronary artery of healthy mini swine. The multimodality assessments including coronary angiography, optical coherence tomography, micro-computed tomography, magnetic resonance imaging, real-time polymerase chain reaction (PCR), and histopathological evaluations, were performed at different time points. There was no statistical difference in area stenosis between IBS group and EES group at 6 months, 1year, 2 years and 5 years. Although the scaffolded vessels narrowed at 9 months, expansive remodeling with increased mean lumen area was found at 3 and 5 years. The IBS struts remained intact at 6 months, and the corrosion was detectable at 9 months. At 5 years, the iron struts were completely degraded and absorbed in situ, without in-scaffold restenosis or thrombosis, lumen collapse, aneurysm formation, and chronic inflammation. No local or systemic toxicity and abnormal histopathologic manifestation were found in all experiments. Results from real-time PCR indicated that no sign of iron overload was reported in scaffolded segments. Therefore, the IBS shows comparable efficacy, safety, and biocompatibility with EES, and late lumen enlargement is considered as a unique feature in the IBS-implanted vessels.

Endoscopic Endonasal Internal Carotid Artery Transposition Technique in Tumor With Parasellar Extension: A Single-Center Experience.

BACKGROUND AND OBJECTIVES: Lateralization or mobilization of the internal carotid artery (ICA) during a midline approach is required to expose lesions behind or lateral to the ICA. However, there have been no published data regarding the surgical outcomes of the endoscopic endonasal internal carotid transposition technique (EEITT). This study aimed to analyze the relevant surgical anatomy around the ICA and propose a grading scheme of EEITT. METHODS: A retrospective review of patients who underwent EEITT at a single institution was performed. Based on structures that limited the ICA and intraoperative findings, an anatomically surgical grading scheme of EEITT was proposed. RESULTS: Forty-two patients (mean age 45.6 years, 57.1% female patients) were included. Of them, 29 cases (69.0%) were Knosp grade 4 pituitary adenoma, 6 cases (14.3%) were chordoma, 6 cases (14.3%) were meningioma, and a single case (2.4%) was meningeal IgG4-related disease. The EEITT was categorized into Grades 1, 2 and 3, which was used in 24 (57.1%), 12 (28.6%), and 6 (14.3%) cases, respectively. The most common symptom was visual disturbance (45.2%). The gross total resection rate in Grade 1 (79.2%) and Grade 2 (83.3%) was much higher than that in Grade 3 (66.6%). The overall rate of visual function improvement, preoperative cranial nerve (CN) palsy improvement, and postoperative hormonal remission was 89.4%, 85.7%, and 88.9%, respectively. The rate for the following morbidities was cerebrospinal fluid leakage, 2.4%; permanent diabetes insipidus, 4.8%; new transient CN palsy, 9.5%; permanent CN palsy, 4.7%; panhypopituitarism, 7.1%; and ICA injury, 2.4%. CONCLUSION: The EEITT is technically feasible and could be graded according to the extent of disconnection of limiting structures. For complex tumor with parasellar extensions, the distinction into Grades 1, 2, and 3 will be of benefit to clinicians in predicting risks, avoiding complications, and generating tailored individualized surgical strategies.

Fluorescence immunosensor based on a specific monoclonal antibody for highly sensitive and rapid detection of gizzerosine in feed.

Gizzerosine is a biogenic amine produced in fish meal drying process and posted higher mortality due to gizzard erosion in poultry than histamine. However, it is difficult to obtain gizzerosine and achieve sensitive practical detection due to its simple structure. Herein, a monoclonal antibody (mAb) specific to gizzerosine was generated based on the new structural design and a fluorescence immunosensor for sensitive and on-site detection of gizzerosine in feed was first established. Molecular modeling of the three-dimensional (3D) structure and surface electrostatic potential of gizzerosine indicated that the carbonyl group of gizzerosine hapten might affect the important sites of antigen-antibody interactions. The proposed structure was used to obtain the sensitive and specific mAb with IC50 of 3.88 ng/mL in indirect competitive ELISA which was approximately 100-fold lower than that of direct competitive ELISA. Considering the practical application scenarios, a fluorescence immunosensor based on microporous dry method integrated with independent quality control line was established to improve detection stability. Under the optimum conditions, the proposed immunosensor showed a good linear relationship from 1.10 to 19.78 ng/mL and provided a low detection limit of 50 ng/g which was approximately 80-fold lower than the maximum recommended amount (0.4 mg/kg) of gizzerosine in feed. The recoveries of 6 kinds of feed ranged from 83.1 % to 114.3 %, which was in good consistence with that of UHPLC-MS/MS. Overall, this work provides a fast, cost-effective and reliable on-site tool for rapid screening of gizzerosine residues in feed samples.

[Human tau N-terminal domain-specific monoclonal antibodies: screening and application in blood detection].

The antibodies to the microtubule-associated protein tau play a role in basic and clinical studies of Alzheimer's disease (AD) and other tauopathies. With the recombinant human tau441 as the immunogen, the hybridoma cell strains secreting the anti-human tau N-terminal domain (NTD-tau) monoclonal antibodies were generated by cell fusion and screened by limiting dilution. The purified monoclonal antibodies were obtained by inducing the mouse ascites and affinity chromatography. The sensitivity and specificity of the monoclonal antibodies were examined by indirect ELISA and Western blotting, respectively. A double antibody sandwich ELISA method for detecting human tau protein was established and optimized. The results showed that the positive cloning rate of hybridoma cells was 83.6%. A stable cell line producing ZD8F7 antibodies was established, and the antibody titer in the supernatant of the cell line was 1:16 000. The antibody titer in the ascitic fluid was higher than 1:256 000; and the titer of purified ZD8F7 monoclonal antibodies was higher than 1:128 000. The epitope analysis showed that the ZD8F7 antibody recognized tau21-37 amino acid in the N-terminal domain. The Western blotting results showed that the ZD8F7 antibody recognized the recombinant human tau protein of 50-70 kDa and the human tau protein of 50 kDa in the brain tissue of transgenic AD model mice (APP/PS1/tau). With ZD8F7 as a capture antibody, a quantitative detection method for human tau protein was established, which showed a linear range of 7.8-500.0 pg/mL and could identify human tau protein in the brain tissue of AD transgenic mice and human plasma but not recognize the mouse tau protein. In conclusion, the human NTD-tau-specific monoclonal antibody and the double antibody sandwich ELISA method established in this study are highly sensitive and can serve as a powerful tool for the detection of tau protein in neurodegenerative diseases.

EXPRESS: Assessing the Causal Relationship Between Obesity and Hypothyroidism Using Mendelian Randomization.

To explore the causal relationship between obesity and hypothyroidism, and identify risk factors and the predictive value of subclinical hypothyroidism (SCH) in obese patients using Mendelian randomization. This study employed five Mendelian randomization methods (MR Egger, Weighted Median, Inverse Variance Weighted, Simple Mode, and Weighted Mode) to analyze clinical data from 308 obese patients at the People's Hospital of Xinjiang Uygur Autonomous Region, from January 2015 to June 2023. Patients were divided based on thyroid function tests into normal (n=173) and SCH groups (n=56). Comparative analyses, along with univariate and multivariate logistic regression, were conducted to identify risk factors for SCH in obese patients. A significant association between obesity and hypothyroidism was established, especially highlighted by the Inverse Variance Weighted method. SCH patients showed higher ages, TSH levels, and thyroid autoantibody positivity rates, with lower T4 and FT4 levels. Age, FT4, thyroid autoantibodies, TPO-Ab, and Tg-Ab were confirmed as risk factors. The predictive value of FT4 levels for SCH in obesity was significant, with an AUC of 0.632. The study supports a potential causal link between obesity and hypothyroidism, identifying specific risk factors for SCH in obese patients. FT4 level stands out as an independent predictive factor, suggesting its utility in early diagnosis and preventive strategies for SCH.

Recurrent joint infection caused by a multidrug-resistant capnophilic Escherichia coli ST131 O25H4 strain.

We report a case of a native knee septic arthritis and subsequent osteomyelitis due to a CO2-dependent (capnophilic) multidrug-resistant E. coli ST131 O25:H4 strain. Capnophilic phenotype made microbiology investigation challenging; susceptibility testing could not be performed and the organism did not grow in the urine culture using standard method. The combination of unique virotype and capnophilia may have contributed to the aggressiveness of this organism and the initial unsuccessful carbapenem course, leading to recurrent infection.

Somatic BrafV600E mutation in the cerebral endothelium induces brain arteriovenous malformations.

Current treatments of brain arteriovenous malformation (BAVM) are associated with considerable risks and at times incomplete efficacy. Therefore, a clinically consistent animal model of BAVM is urgently needed to investigate its underlying biological mechanisms and develop innovative treatment strategies. Notably, existing mouse models have limited utility due to heterogenous and untypical phenotypes of AVM lesions. Here we developed a novel mouse model of sporadic BAVM that is consistent with clinical manifestations in humans. Mice with BrafV600E mutations in brain ECs developed BAVM closely resembled that of human lesions. This strategy successfully induced BAVMs in mice across different age groups and within various brain regions. Pathological features of BAVM were primarily dilated blood vessels with reduced vascular wall stability, accompanied by spontaneous hemorrhage and neuroinflammation. Single-cell sequencing revealed differentially expressed genes that were related to the cytoskeleton, cell motility, and intercellular junctions. Early administration of Dabrafenib was found to be effective in slowing the progression of BAVMs; however, its efficacy in treating established BAVM lesions remained uncertain. Taken together, our proposed approach successfully induced BAVM that closely resembled human BAVM lesions in mice, rendering the model suitable for investigating the pathogenesis of BAVM and assessing potential therapeutic strategies.

E3 ubiquitin ligase UBR5 promotes gemcitabine resistance in pancreatic cancer by inducing O-GlcNAcylation-mediated EMT via destabilization of OGA.

Pancreatic cancer (PC) is among the deadliest malignancies, with an extremely poor diagnosis and prognosis. Gemcitabine (GEM) remains the first-line drug for treating PC; however, only a small percentage of patients benefit from current immunotherapies or targeted therapies. Resistance to GEM is prevalent and affects long-term survival. We found that ubiquitin-protein ligase E3 module N-recognition 5 (UBR5) is a therapeutic target against GEM resistance. UBR5 was markedly upregulated in clinical GEM-resistant PC samples and GEM-resistant PC cells. UBR5 knockdown markedly increased GEM sensitivity in GEM-resistant PC cell lines. UBR5-mediated GEM resistance was accompanied by activation of epithelial-mesenchymal transition (EMT) and could be mitigated by inhibiting EMT. Further analysis revealed that UBR5 promoted GEM resistance in PC cells by enhancing O-GlcNAcylation-mediated EMT. In addition, UBR5 knockdown resulted in increased O-GlcNAase (OGA) levels, an essential negatively regulated enzyme in the O-GlcNAcylation process. We identified a negative association between OGA and UBR5 levels, which further supported the hypothesis that O-GlcNAcylation-mediated GEM resistance induced by UBR5 is OGA-dependent in PC cells. Mechanistic studies revealed that UBR5 acts as an E3 ubiquitin ligase of OGA and regulates O-GlcNAcylation by binding and modulating OGA, facilitating its degradation and ubiquitination. Additionally, high-throughput compound library screening using three-dimensional protein structure analysis and drug screening identified a Food and Drug Administration drug, Y-39983 dihydrochloride, as a potent GEM sensitiser and UBR5 inhibitor. The combination of Y-39983 dihydrochloride and GEM attenuated tumour growth in a mouse xenograft tumour model. Collectively, these data demonstrated that UBR5 plays a pivotal role in the sensitisation of PC to GEM and provides a potential therapeutic strategy to overcome GEM resistance.

Effect of a fall within three months of admission on delirium in critically Ill elderly patients: a population-based cohort study.

BACKGROUND: Delirium is common among elderly patients in the intensive care unit (ICU) and is associated with prolonged hospitalization, increased healthcare costs, and increased risk of death. Understanding the potential risk factors and early prevention of delirium is critical to facilitate timely intervention that may reverse or mitigate the harmful consequences of delirium. AIM: To clarify the effects of pre-admission falls on ICU outcomes, primarily delirium, and secondarily pressure injuries and urinary tract infections. METHODS: The study relied on data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Statistical tests (Wilcoxon rank-sum or chi-squared) compared cohort characteristics. Logistic regression was employed to investigate the association between a history of falls and delirium, as well as secondary outcomes, while Kaplan-Meier survival curves were used to assess short-term survival in delirium and non-delirium patients. RESULTS: Study encompassed 22,547 participants. Delirium incidence was 40%, significantly higher in patients with a history of falls (54.4% vs. 34.5%, p < 0.001). Logistic regression, controlling for confounders, not only confirmed that a history of falls elevates the odds of delirium (OR: 2.11; 95% CI: 1.97-2.26; p < 0.001) but also showed it increases the incidence of urinary tract infections (OR:1.50; 95% CI:1.40-1.62; p < 0.001) and pressure injuries (OR:1.36; 95% CI:1.26-1.47; p < 0.001). Elderly delirium patients exhibited lower 30-, 180-, and 360-day survival rates than non-delirium counterparts (all p < 0.001). CONCLUSIONS: The study reveals that history of falls significantly heighten the risk of delirium and other adverse outcomes in elderly ICU patients, leading to decreased short-term survival rates. This emphasizes the critical need for early interventions and could inform future strategies to manage and prevent these conditions in ICU settings.

Inhibition of SENP5 reduces brain injury in TBI rats by regulating NEDD4L/TCF3 axis.

BACKGROUND: The underlying mechanism of SENP5 influences neuronal regeneration and apoptosis in the context of TBI remains largely unexplored. METHODS: In the present study, PC12 cells treated with scratch for 24 h were regarded as a TBI cell model. The expression of SENP5 in PC12 cells was measured via Quantitative Real-Time PCR (qRT-PCR) and western blot assays. Cell Counting Kit 8 (CCK-8) and Flow cytometry assays were used to evaluate the activity of TBI cells. In addition, we assessed the effect of inhibiting SENP5 in vivo on neurological function deficits and apoptosis in the hippocampal tissues of TBI rats. The relationship between SENP5 and NEDD4L/TCF3 axis was proved via immunoprecipitation (IP) and double luciferase assays. RESULTS: Following TBI cell modeling, an increase in SENP5 expression has been found. Moreover, TBI modeling resulted in reduced cell viability and increased apoptosis, which was rescue by inhibition of SENP5. In vivo experiments demonstrated that SENP5 inhibition could mitigate TBI-induced brain injury in rats. Specifically, this inhibition led to lower neurological impairment scores, improved neuronal morphology and structure, and decreased neuronal apoptosis. In addition, NEDD4L has been proved to be relevant to the enhanced stability of the transcription factor TCF3, which in turn promoted the expression of SENP5. CONCLUSIONS: This study reveals that inhibiting SENP5 can alleviate brain injury following TBI. NEDD4L/TCF3 axis can regulate the expression of SENP5 to affect the development of TBI. However, SENP5 regulates downstream targets of TBI and important mechanisms need to be further explored.

Rational Design of Nitride Phosphor-In-Glass with Robust Stability and Photoluminescence Performance.

Phosphor-in-glass represents a promising avenue for merging the luminous efficiency of high-quality phosphor and the thermal stability of a glass matrix. Undoubtedly, the glass matrix system and its preparation are pivotal factors in achieving high stability and preserving the original performance of embedded phosphor particles. In contrast to the well-established commercial Y3Al5O12:Ce3+ oxide phosphor, red nitride phosphor, which plays a critical role in high-quality lighting, exhibits greater structural instability during the high-temperature synthesis of inorganic glasses. A telluride glass with a refractive index (RI = 2.15@615 nm) akin to that of nitride phosphor (∼2.19) has been devised, demonstrating high efficiency in photon utilization. The lower glass-transition temperature plays a crucial role in safeguarding phosphor particles against erosion resulting from exposure to high-temperature melts. Phosphor-in-glass retains 93% of the quantum efficiency observed for pure phosphor. The assembled white light-emitting diodes module has precise color tuning capabilities, achieving an optimal color rendering index of 93.7, a luminous efficacy of 80.4 lm/W, and a correlated color temperature of 5850 K. These outcomes hold potential for advancing the realm of inorganic package and high-quality white light illumination.

Phenolic constituents with potent α-glucosidase inhibitory and cytotoxic activities from Rumex nepalensis var. remotiflorus.

Quantitative analysis of Rumex nepalensis var. remotiflorus revealed that its roots contain rich anthraquinones, which has emodin, chrysophanol, and physcion contents of up to 0.30, 0.67, and 0.98 mg/g, respectively. Further phytochemical study led to the isolation and purification of seven undescribed phenolic constituents, including one flavan derivative with a 13-membered ring, polygorumin A (1), two dianthrone glucosides, polygonumnolides F and G (2, 3), two diphenylmethanones, rumepalens A and B (4, 5), and a pair of epimeric oxanthrone C-glucosides, rumejaposides K and L (6a, 6b) from the roots of R. nepalensis var. remotiflorus. Furthermore, 1 undescribed natural product, 1-ß-D-glucoside-6'-[(2E)-3-(4-hydroxy-3-methoxyphenyl)-2-propenoate]-3-hydroxy-5-methylphenyl (19), and 21 known phenolic compounds were obtained from the aforementioned plant for the first time. Their structures were elucidated through extensive spectroscopic data analysis. Notably, compounds 1, 4-5, and 7-9 exhibited inhibitory activity on α-glucosidase with IC50 values ranging from 1.61 ± 0.17 to 32.41 ± 0.87 µM. In addition, the isolated dianthrone, chrysophanol bianthrone (14), showed obvious cytotoxicity against four human cancer cell lines (HL-60, SMMC-7721, A-549, and MDA-MB-231) with IC50 values ranging from 3.81 ± 0.17 to 35.15 ± 2.24 µM. In silico target prediction and molecular docking studies demonstrated that the mechanism of the anticancer activity of 14 may be related to the interaction with protein kinase CK2.

The subcommissural organ regulates brain development via secreted peptides.

The subcommissural organ (SCO) is a gland located at the entrance of the aqueduct of Sylvius in the brain. It exists in species as distantly related as amphioxus and humans, but its function is largely unknown. Here, to explore its function, we compared transcriptomes of SCO and non-SCO brain regions and found three genes, Sspo, Car3 and Spdef, that are highly expressed in the SCO. Mouse strains expressing Cre recombinase from endogenous promoter/enhancer elements of these genes were used to genetically ablate SCO cells during embryonic development, resulting in severe hydrocephalus and defects in neuronal migration and development of neuronal axons and dendrites. Unbiased peptidomic analysis revealed enrichment of three SCO-derived peptides, namely, thymosin beta 4, thymosin beta 10 and NP24, and their reintroduction into SCO-ablated brain ventricles substantially rescued developmental defects. Together, these data identify a critical role for the SCO in brain development.

Bone-metastatic lung adenocarcinoma cells bearing CD74-ROS1 fusion interact with macrophages to promote their dissemination.

Approximately 40% of patients with lung adenocarcinoma (LUAD) often develop bone metastases during the course of their disease. However, scarcely any in vivo model of LUAD bone metastasis has been established, leading to a poor understanding of the mechanisms underlying LUAD bone metastasis. Here, we established a multiorgan metastasis model via the left ventricular injection of luciferase-labeled LUAD cells into nude mice and then screened out lung metastasis (LuM) and bone metastasis (BoM) cell subpopulations. BoM cells exhibited greater stemness and epithelial-mesenchymal transition (EMT) plasticity than LuM cells and initially colonized the bone and subsequently disseminated to distant organs after being reinjected into mice. Moreover, a CD74-ROS1 fusion mutation (C6; R34) was detected in BoM cells but not in LuM cells. Mechanistically, BoM cells bearing the CD74-ROS1 fusion highly secrete the C-C motif chemokine ligand 5 (CCL5) protein by activating STAT3 signaling, recruiting macrophages in tumor microenvironment and strongly inducing M2 polarization of macrophages. BoM cell-activated macrophages produce a high level of TGF-ß1, thereby facilitating EMT and invasion of LUAD cells via TGF-ß/SMAD2/3 signaling. Targeting the CD74-ROS1/CCL5 axis with Crizotinib (a ROS1 inhibitor) and Maraviroc (a CCL5 receptor inhibitor) in vivo strongly impeded bone metastasis and secondary metastasis of BoM cells. Our findings reveal the critical role of the CD74-ROS1/STAT3/CCL5 axis in the interaction between LUAD bone metastasis cells and macrophages for controlling LUAD cell dissemination, highlighting the significance of the bone microenvironment in LUAD bone metastasis and multiorgan secondary metastasis, and suggesting that targeting CD74-ROS1 and CCL5 is a promising therapeutic strategy for LUAD bone metastasis.

Improvement of thermostability by increasing rigidity in the finger regions and flexibility in the catalytic pocket area of Pseudoalteromonas porphyrae κ-carrageenase.

Poor thermostability reduces the industrial application value of κ-carrageenase. In this study, the PoPMuSiC algorithm combined with site-directed mutagenesis was applied to improve the thermostability of the alkaline κ-carrageenase from Pseudoalteromonas porphyrae. The mutant E154A with improved thermal stability was successfully obtained using this strategy after screening seven rationally designed mutants. Compared with the wild-type κ-carrageenase (WT), E154A improved the activity by 29.4% and the residual activity by 51.6% after treatment at 50 °C for 30 min. The melting temperature (Tm) values determined by circular dichroism were 66.4 °C and 64.6 °C for E154A and WT, respectively. Molecular dynamics simulation analysis of κ-carrageenase showed that the flexibility decreased within the finger regions (including F1, F2, F3, F5 and F6) and the flexibility improved in the catalytic pocket area of the mutant E154A. The catalytic tunnel dynamic simulation analysis revealed that E154A led to enlarged catalytic tunnel volume and increased rigidity of the enzyme-substrate complex. The increasing rigidity within the finger regions and more flexible catalytic pocket of P. porphyrae κ-carrageenase might be a significant factor for improvement of the thermostability of the mutant κ-carrageenase E154A. The proposed rational design strategy could be applied to improve the enzyme kinetic stability of other industrial enzymes. Moreover, the hydrolysates of κ-carrageenan digested by the mutant E154A demonstrated increased scavenging activities against hydroxyl (OH) radicals and 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) radicals compared with the undigested κ-carrageenan.

Transcriptomic analysis of epicardial adipose tissue reveals the potential crosstalk genes and immune relationship between type 2 diabetes mellitus and atrial fibrillation.

BACKGROUND: The complex relationship between atrial fibrillation (AF) and type 2 diabetes mellitus (T2DM) suggests a potential role for epicardial adipose tissue (EAT) that requires further investigation. This study employs bioinformatics and experimental approaches to clarify EAT's role in linking T2DM and AF, aiming to unravel the biological mechanisms involved. METHOD: Bioinformatics analysis initially identified common differentially expressed genes (DEGs) in EAT from T2DM and AF datasets. Pathway enrichment and network analyses were then performed to determine the biological significance and network connections of these DEGs. Hub genes were identified through six CytoHubba algorithms and subsequently validated biologically, with further in-depth analyses confirming their roles and interactions. Experimentally, db/db mice were utilized to establish a T2DM model. AF induction was executed via programmed transesophageal electrical stimulation and burst pacing, focusing on comparing the incidence and duration of AF. Frozen sections and Hematoxylin and Eosin (H&E) staining illuminated the structures of the heart and EAT. Moreover, quantitative PCR (qPCR) measured the expression of hub genes. RESULTS: The study identified 106 DEGs in EAT from T2DM and AF datasets, underscoring significant pathways in energy metabolism and immune regulation. Three hub genes, CEBPZ, PAK1IP1, and BCCIP, emerged as pivotal in this context. In db/db mice, a marked predisposition towards AF induction and extended duration was observed, with HE staining verifying the presence of EAT. Additionally, qPCR validated significant changes in hub genes expression in db/db mice EAT. In-depth analysis identified 299 miRNAs and 33 TFs as potential regulators, notably GRHL1 and MYC. GeneMANIA analysis highlighted the hub genes' critical roles in stress responses and leukocyte differentiation, while immune profile correlations highlighted their impact on mast cells and neutrophils, emphasizing the genes' significant influence on immune regulation within the context of T2DM and AF. CONCLUSION: This investigation reveals the molecular links between T2DM and AF with a focus on EAT. Targeting these pathways, especially EAT-related ones, may enable personalized treatments and improved outcomes.

MECOM: A Meta-Completion Network for Fine-Grained Recognition with Incomplete Multi-Modalities.

Our work focuses on tackling the problem of fine-grained recognition with incomplete multi-modal data, which is overlooked by previous work in the literature. It is desirable to not only capture fine-grained patterns of objects but also alleviate the challenges of missing modalities for such a practical problem. In this paper, we propose to leverage a meta-learning strategy to learn model abilities of both fast modal adaptation and more importantly missing modality completion across a variety of incomplete multi-modality learning tasks. Based on that, we develop a meta-completion method, termed as MECOM, to perform multimodal fusion and explicit missing modality completion by our proposals of cross-modal attention and decoupling reconstruction. To further improve fine-grained recognition accuracy, an additional partial stream (as a counterpart of the main stream of MECOM, i.e., holistic) and the part-level features (corresponding to fine-grained objects' parts) selection are designed, which are tailored for fine-grained nature to capture discriminative but subtle part-level patterns. Comprehensive experiments from quantitative and qualitative aspects, as well as various ablation studies, on two fine-grained multimodal datasets and one generic multimodal dataset show our superiority over competing methods. Our code is open-source and available at https://github.com/SEU-VIPGroup/MECOM.

Extended Endoscopic Endonasal Approach for Giant Pediatric Craniopharyngiomas: Technical Note and Case Series.

BACKGROUND AND OBJECTIVES: Giant pediatric craniopharyngiomas are rare tumors whose clinical and surgical management is extremely challenging. A variety of open transcranial approaches has been used to resect these lesions. Although there has been an increasing acceptance of the endoscopic endonasal approach (EEA) for the resection of pediatric craniopharyngiomas in recent years, many surgeons continue to recommend against the use of the EEA for giant pediatric craniopharyngiomas. This study aimed to evaluate the feasibility of extended EEA for giant craniopharyngiomas in the pediatric population. METHODS: All consecutive pediatric patients with giant craniopharyngiomas (diameter >4 cm) who underwent endoscopic endonasal surgery at our institution were retrospectively reviewed. Data on demographic information, preoperative assessment, imaging features, surgical results, complications, and recurrences were recorded and analyzed. RESULTS: A total of 16 pediatric patients with an average age of 12 years were identified. The mean maximum diameter and volume of the tumors were 4.35 cm and 24.1 cm3, respectively. Gross total resection was achieved in 13 patients (81.3%) and subtotal resection in 3 patients (18.7%). Postoperatively, partial or complete anterior pituitary insufficiency occurred in 100% of patients, and 62.5% developed new-onset diabetes insipidus. Visual function improved in 9 patients (56.3%) and remained stable in 7 patients (43.7%). Postoperative cerebrospinal fluid leakage occurred in 2 patients and was successfully repaired through the EEA. During a mean follow-up of 44.3 months, 18.8% of patients had a >9% increase in body mass index, and 93.8% of patients successfully returned to school or work. Two patients (12.5%) suffered a recurrence. Disease control was achieved in 16 patients (100%) at final follow-up. CONCLUSION: The extended EEA allows adequate access to this challenging tumor and enables complete resection and visual improvement with a reasonable approach-related complication rate.

Transboundary cooperation in Arctic climate change governance under geopolitical tensions.

Political conflicts or geopolitical tensions can create uncertainty in addressing climate change and environmental management in the Arctic. Dissecting how actors interact with each other and form networks is important for understanding ecological and environmental management challenges during geopolitical tensions, as well as promoting better governance. We construct transboundary networks for Arctic climate change governance (ACCG) from 2013 to 2021 based on the Global Database of Events, Language, and Tone (GDELT). Further, we used network descriptive statistical analysis and Temporal Exponential Random Graph Models (TERGM) to explore the structure of ACCG networks and the key factors influencing cooperation formation. The findings suggest that the overall cooperation density of the ACCG is low, and the dominant position of core actors is continuously strengthening. Non-state actors are less likely to be seen as partners and their participation depends largely on cooperation with states. The results also show that actors with similar stances and problem exposure are more likely to cooperate, but those exposed to high latitudes often choose not to cooperate; first-comers are more likely to perceive as cooperating yet they are inclined to establish internal cooperation. Additionally, two geographically proximate actors are more likely to cooperate. This indicates that under geopolitical tensions, the ACCG faces challenges not only due to the limited capacity of non-state actors to perform transboundary functions but also because the cooperation mechanisms are influenced by regional political logic. Accordingly, we further suggest policy recommendations from developing binding international frameworks to guide transboundary cooperation, enhancing cooperation among non-state actors, and ensuring the representativeness and fairness of non-Arctic actors' participation. This research provides insights into transboundary environmental management under political tensions, while also offering new pathways for analysing large-scale environmental governance structures.