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Abstract Background Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on autoimmune diseases, particularly type 1 diabetes (T1D) and the related cellular and molecular mechanisms, are yet to be addressed. Method Herein in this report, we treated NOD mice with fluvoxamine for 2 weeks starting from 10-week of age to dissect the impact of fluvoxamine on the prevention of type 1 diabetes. We compared the differences of immune cells between 12-week-old control and fluvoxamine-treated mice by flow cytometry analysis. To study the mechanism involved, we extensively examined the characteristics of CD4+ T cells with fluvoxamine stimulation using RNA-seq analysis, real-time PCR, Western blot, and seahorse assay. Furthermore, we investigated the relevance of our data to human autoimmune diabetes. Result Fluvoxamine not only delayed T1D onset, but also decreased T1D incidence. Moreover, fluvoxamine-treated NOD mice showed significantly attenuated insulitis coupled with well-preserved β cell function, and decreased Th1 and Th17 cells in the peripheral blood, pancreatic lymph nodes (PLNs), and spleen. Mechanistic studies revealed that fluvoxamine downregulated glycolytic process by inhibiting phosphatidylinositol 3-kinase (PI3K)-AKT signaling, by which it restrained effector T (Teff) cell differentiation and production of proinflammatory cytokines. Conclusion Collectively, our study supports that fluvoxamine could be a viable therapeutic drug against autoimmunity in T1D setting.

ObjectiveThe aim of this study was to investigate the predictive value of systemic immune inflammation index (SII), systemic inflammatory response index (SIRI), and pan-immune inflammation value (PIV) in predicting intravenous immunoglobulin (IVIG) resistance in children diagnosed with Kawasaki disease (KD).MethodsThe clinical data of pediatric patients diagnosed with Kawasaki disease and admitted to our hospital between January 2006 and December 2022 were retrospectively analyzed.ResultsIn total, 771 children diagnosed with KD were included in this study, 86 (11.2%) of whom were diagnosed with IVIG resistance. The correlation between SII, SIRI, PIV and IVIG resistance was evaluated using univariate testing, binary logistic regression analysis, and receiver operating characteristic (ROC) curve analysis. Our study found that the SII, SIRI, and PIV were independent risk factors (p=0.001, p

Summary: High salt (HS) consumption is a risk factor for multiple autoimmune disorders via disturbing immune homeostasis. Nevertheless, the exact mechanisms by which HS exacerbates rheumatoid arthritis (RA) pathogenesis remain poorly defined. Herein, we found that heightened phosphorylation of PDPK1 and SGK1 upon HS exposure attenuated FoxO1 expression to enhance the glycolytic capacity of CD4 T cells, resulting in strengthened Th17 but compromised Treg program. GSK2334470 (GSK), a dual PDPK1/SGK1 inhibitor, effectively mitigated the HS-induced enhancement in glycolytic capacity and the overproduction of IL-17A. Therefore, administration of GSK markedly alleviated HS-exacerbated RA progression in collagen-induced arthritis (CIA) model. Collectively, our data indicate that HS consumption subverts Th17/Treg homeostasis through the PDPK1-SGK1-FoxO1 signaling, while GSK could be a viable drug against RA progression in clinical settings.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in neonates, particularly preterm infants. Many factors can lead to NEC, but microbial dysbiosis is one of the most important risk factors that can induce this disease. Given the major role of the gut virome in shaping bacterial homeostasis, virome research is a fledgling but rapidly evolving area in the field of microbiome that is increasingly connected to human diseases, including NEC. This review provides an overview of the development of the gut virome in newborns, discusses its emerging role in NEC, and explores promising therapeutic applications, including phage therapy and fecal virome transplantation.

Many efforts have been taken in recent years to push atomic gravimeters toward practical applications. We demonstrate an atomic gravimeter named NIM-AGRb2 that is transportable and suitable for high-precision gravity measurements. Constraint-structured active vibration isolation (CS-AVI) is used to reduce the ground vibration noise. The constraint structure in CS-AVI ensures that the isolation platform only has vertical translation, with all other degrees of freedom (DoFs) being constrained. Therefore, the stability of active vibration isolation is enhanced. With the implementation of CS-AVI, the sensitivity of NIM-AGRb2 reached as low as 20.5 μGal/Hz1/2. The short-term sensitivity could be further reduced to 10.8 μGal/Hz1/2 in a seismologic observation station. Moreover, we evaluated the system noise of the gravimeter, and the results were consistent with our observations.

Currently, 1060 aluminum alloy is widely applied in the electronics industry, construction, the aerospace field, traffic engineering, decorations, and the consumer goods market for its good chemical, physical, and mechanical properties. In general, excellent processing property is necessary and important for the manufacturing of complicated panels. In this paper, a special 2D ultrasonic vibration incremental forming method is designed to improve its plasticity and mechanical properties. Three kind of processing methods, including traditional single-point incremental forming, longitudinal ultrasonic vibration incremental forming, and 2D ultrasonic vibration incremental forming, are used for the flexible manufacturing of cones and cylindrical cups of 1060 aluminum alloy sheet. Then, micro-hardness tests, residual stress tests, and scanning electron microscopy tests are carried out to probe the changes in micro-structure and mechanical properties and to analyze the effects of different types of ultrasonic vibration on the plasticity and fracture characteristic of 1060 aluminum alloy. It is proven that 2D ultrasonic vibration facilitates the improvement of plasticity and surface qualities of 1060 aluminum alloy better than the other two processing methods. Therefore, the novel 2D ultrasonic vibration incremental forming process possesses substantial application value for the flexible and rapid manufacturing of complicated thin-walled component of aluminum alloy.

A quiet quadruple revolution has been in the making in systems science with convergence of (1) artificial intelligence, machine learning, and other digital technologies; (2) multiomics big data integration; (3) growing interest in the "variability science" of precision/personalized medicine that aims to account for patient-to-patient and between-population differences in disease susceptibilities and responses to health interventions such as drugs, nutrition, vaccines, and radiation; and (4) planetary health scholarship that both scales up and integrates biological, clinical, and ecological contexts of health and disease. Against this overarching background, this article presents and highlights some of the salient challenges and prospects of multiomics research, emphasizing the attendant pivotal role of systems medicine and systems biology. In addition, we emphasize the rapidly growing importance of planetary health research for systems medicine, particularly amid climate emergency, ecological degradation, and loss of planetary biodiversity. Looking ahead, we anticipate that the integration and utilization of multiomics big data and artificial intelligence will drive further progress in systems medicine and systems biology, heralding a promising future for both human and planetary health. [ABSTRACT FROM AUTHOR]

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The genus Impatiens comprises more than 1000 species and displays enormous morphological diversity. As a taxon that is notoriously difficult to classify morphologically, the taxonomic significance of pollen morphology has been discussed in previous studies. However, there was only limited study on the evolution of palynological and macroscopic character in this genus before. In this paper, we observed pollen of 143 species of Impatiens, including all representatives of infrageneric groups and discussed their taxonomic value. Meanwhile, based on the reconstructed phylogenetic framework, we selected five pollen traits, and nine macroscopic traits including both vegetative and reproductive organs for evolutionary analysis. The character reconstruction showed that the morphology and number of aperture, granules in lumina, seed number of per capsule, number of sepals, lateral united petals connate, spur length, and phyllotaxy could be identified as unambiguous, while other characters were ambiguous in the last common ancestor of Impatiens. The results of comprehensively macroscopic characters and palynological evidence suggest that these traits experienced a complicated evolution, exhibit high levels of instability and variability and occur character multiple reversals in the evolutionary processes of Impatiens due to different selection pressures. In addition, we found that there is an evident mosaic evolution in this genus. Pollen and macroscopic character are conserved with a slower evolutionary rate in the I. subgen. Clavicarpa, however, these characters showed higher diversity with a rapid rate of evolution in the I. subgen. Impatiens. Furthermore, the relationship between floral morphology and pollinators was discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases (CVDs), but there is a lack of research on whether they were causally linked. We conducted a Mendelian Randomization (MR) study to explore causal relationships between loneliness and isolation and multiple CVDs. METHODS Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study (GWAS) of 455,364 individuals of European ancestry in the IEU GWAS database. Summary data for 15 CVDs were also obtained from the IEU GWAS database. We used three MR methods including inverse variance weighting, MR-Egger, and weighted median estimation to assess the causal effect of exposure on outcomes. Cochran's Q test and MR-Egger intercept test were used to evaluate the heterogeneity and pleiotropy. RESULTS MR analysis showed that loneliness and isolation were significantly associated with essential hypertension (OR = 1.07, 95% CI: 1.03-1.12), atherosclerotic heart disease (OR = 1.04; 95% CI: 1.02-1.06), myocardial infarction (OR = 1.02; 95% CI: 1-1.04) and angina (OR = 1.04; 95% CI =1.02-1.06). No heterogeneity and pleiotropy effects were found in this study. CONCLUSIONS Causal relationship of loneliness and isolation with CVDs were found in this study. [ABSTRACT FROM AUTHOR]

With the rapid development of wireless communication technology and electronic devices, the issue of electromagnetic interference (EMI) is becoming increasingly severe. Developing a new and flexible electromagnetic interference shielding material has become a challenging task. Here, a sandwich-structured EMI shielding composite film was prepared using electrospinning and vacuum filtration methods. In this process, a porous MXene was synthesized through a reaction with cobalt acetate and served as the intermediate layer in the composite film to shield electromagnetic waves. The electrospun polyimide (PI) fibers were used as the top and bottom layers of the composite film, which can protect the porous MXene from oxidation. This lightweight and flexible composite film integrates electromagnetic interference shielding and thermal insulation capabilities, showing excellent comprehensive performance. The composite film achieves an EMI shielding effectiveness of 48.8 dB in X-band (8.2–12.4 GHz), and absolute shielding effectiveness of the composite film reached a satisfying 4142.43 (dB·cm2)/g. Owing to the design of a multi-layer porous structure, the density of the composite film is 0.65 g/cm3. Furthermore, the thermal conductivity of the film is 0.042 W/(m·K) due to the clamping of electrospun PI fibers, showing excellent thermal insulation performance. Additionally, the composite film exhibits excellent high and low-temperature resistance. In summary, this work provides a feasible strategy for preparing a lightweight polymer-based EMI shielding film. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension, and surgery is currently the main treatment for hypertensive cerebral hemorrhage, but the bleeding caused by surgery will cause damage to the patient's nerve cells, resulting in cognitive and motor dysfunction, resulting in a decline in the patient's quality of life., Aim: To investigate associations between cerebral arterial blood flow and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage., Methods: Eighty-nine patients with depression after acute hypertensive cerebral hemorrhage who were admitted to our hospital between January 2019 and July 2021 were selected as the observation group, while 100 patients without depression who had acute hypertensive cerebral hemorrhage were selected as the control group. The attention span of the patients was assessed using the Paddle Pin Test while executive function was assessed using the Wisconsin Card Sorting Test (WCST) and cognitive function was assessed using the Montreal Cognitive Assessment Scale (MoCA). The Hamilton Depression Rating Scale (HAMD-24) was used to evaluate the severity of depression of involved patients. Cerebral arterial blood flow was measured in both groups., Results: The MoCA score, net scores I, II, III, IV, and the total net score of the scratch test in the observation group were significantly lower than those in the control group ( P < 0.05). Concurrently, the total number of responses, number of incorrect responses, number of persistent errors, and number of completed responses of the first classification in the WCST test were significantly higher in the observation group than those in the control group ( P < 0.05). Blood flow in the basilar artery, left middle cerebral artery, right middle cerebral artery, left anterior cerebral artery, and right anterior cerebral artery was significantly lower in the observation group than in the control group ( P < 0.05). The basilar artery, left middle cerebral artery, right middle cerebral artery, left anterior cerebral artery, and right anterior cerebral artery were positively correlated with the net and total net scores of each part of the Paddle Pin test and the MoCA score ( P < 0.05), and negatively correlated with each part of the WCST test ( P < 0.05). In the observation group, the post-treatment improvement was more prominent in the Paddle Pin test, WCST test, HAMD-24 score, and MoCA score compared with those in the pre-treatment period ( P < 0.05). Blood flow in the basilar artery, left middle cerebral artery, right middle cerebral artery, left anterior cerebral artery, and right anterior cerebral artery significantly improved in the observation group after treatment ( P < 0.05)., Conclusion: Impaired attention, and executive and cognitive functions are correlated with cerebral artery blood flow in patients with depression after acute hypertensive cerebral hemorrhage and warrant further study., Competing Interests: Conflict-of-interest statement: There is no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Icariin has been shown the promising therapeutic potential to treat inflammatory airway diseases, yet its poor lung distribution and retention restrict the clinical applications. To this end, this work aimed to prepare an icariin-phospholipid complex (IPC) formulation for sustained nebulization delivery that enabled excellent inhalability, improved lung exposure and prolonged duration of action. Icariin was found to react with soybean phospholipid to form supramolecular IPC, which was able to self-assemble into nanoparticle suspension. The suspension was stable during steam sterilization and nebulization processes, and its aerosols generated by a commercial nebulizer exhibited excellent aerodynamic properties and delivery efficiency. In vitro studies showed that the formation of complex sustained drug release, enhanced lung affinity and slowed lung clearance. The drug distribution in lung epithelial lining fluid (ELF) also demonstrated in vivo sustained release after intratracheal administration to mice. In addition, compared to free icariin, IPC improved the drug exposure to lung tissues and immune cells in the ELF by 4.61-fold and 39.5-fold, respectively. This resulted in improved and prolonged local anti-inflammatory effects up to 24 h in mice with lipopolysaccharide (LPS)-induced acute lung injury. Moreover, IPC improved survival rate of mice with acute respiratory distress syndrome (ARDS). Overall, the present phospholipid complex represented a promising formulation of icariin for the treatment of acute lung injury/ARDS by nebulization delivery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)