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Summary: 4-Octyl itaconate (4-OI), a derivative of itaconate, inhibits inflammation by alkylating its target proteins. Here, we present a click-chemistry-based protocol for detecting 4-OI-alkylated proteins in mouse primary bone-marrow-derived macrophages (BMDMs) by using an itaconate-alkyne (ITalk) probe. We describe steps for culturing and treating BMDMs and details on using click chemistry in the cell lysate. We also detail procedures for detecting alkylated proteins by western blot.For complete details on the use and execution of this protocol, please refer to Su et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Objectives This study aims to develop an innovative, deep model for thymoma risk stratification using preoperative CT images. Current algorithms predominantly focus on radiomic features or 2D deep features and require manual tumor segmentation by radiologists, limiting their practical applicability. Methods The deep model was trained and tested on a dataset comprising CT images from 147 patients (82 female; mean age, 54 years ± 10) who underwent surgical resection and received subsequent pathological confirmation. The eligible participants were divided into a training cohort (117 patients) and a testing cohort (30 patients) based on the CT scan time. The model consists of two stages: 3D tumor segmentation and risk stratification. The radiomic model and deep model (2D) were constructed for comparative analysis. Model performance was evaluated through dice coefficient, area under the curve (AUC), and accuracy. Results In both the training and testing cohorts, the deep model demonstrated better performance in differentiating thymoma risk, boasting AUCs of 0.998 and 0.893 respectively. This was compared to the radiomic model (AUCs of 0.773 and 0.769) and deep model (2D) (AUCs of 0.981 and 0.760). Notably, the deep model was capable of simultaneously identifying lesions, segmenting the region of interest (ROI), and differentiating the risk of thymoma on arterial phase CT images. Its diagnostic prowess outperformed that of the baseline model. Conclusions The deep model has the potential to serve as an innovative decision-making tool, assisting on clinical prognosis evaluation and the discernment of suitable treatments for different thymoma pathological subtypes. Key Points • This study incorporated both tumor segmentation and risk stratification. • The deep model, using clinical and 3D deep features, effectively predicted thymoma risk. • The deep model improved AUCs by 16.1pt and 17.5pt compared to radiomic model and deep model (2D) respectively.

BackgroundAffiliate stigma experienced by family caregivers of individuals with dementia may seriously affect home care and prognosis of these patients. This study aimed to explore the levels of perceived affiliate stigma and its influencing factors among family caregivers of patients with dementia in mainland China, which remains a relatively unexplored topic.MethodsIn this cross-sectional study, purposive sampling was used to recruit dementia family caregivers from an online communication group between April and May 2022. A total of 727 eligible caregivers were included and asked to complete the demographic questionnaire, the affiliate stigma scale, and the caregiver burden inventory. Descriptive statistics, independent sample t-test, one-way analysis of variance, Pearson correlation analysis, and multiple linear regression were used to explore the factors that influence perceived affiliate stigma among dementia family caregivers.ResultsThe mean score for affiliate stigma of dementia family caregivers was 48.09 ± 16.38 (range: 22–86). Whether there were regular breaks during patient care, time-dependent burden, developmental burden, physical burden, and social burden were significant factors influencing the affiliate stigma of dementia family caregivers.ConclusionDementia family caregivers showed a moderate to high level of affiliate stigma. Those who had regular breaks during patient care, higher time-dependent burden, developmental burden, and physical burden and lower social burden exhibited higher levels of affiliate stigma.

Abstract Psoriasis is a common, chronic, and inflammatory skin disease with a high burden on individuals, health systems, and society worldwide. With the immunological pathologies and pathogenesis of psoriasis becoming gradually revealed, the therapeutic approaches for this disease have gained revolutionary progress. Nevertheless, the mechanisms of less common forms of psoriasis remain elusive. Furthermore, severe adverse effects and the recurrence of disease upon treatment cessation should be noted and addressed during the treatment, which, however, has been rarely explored with the integration of preliminary findings. Therefore, it is crucial to have a comprehensive understanding of the mechanisms behind psoriasis pathogenesis, which might offer new insights for research and lead to more substantive progress in therapeutic approaches and expand clinical options for psoriasis treatment. In this review, we looked to briefly introduce the epidemiology, clinical subtypes, pathophysiology, and comorbidities of psoriasis and systematically discuss the signaling pathways involving extracellular cytokines and intracellular transmission, as well as the cross-talk between them. In the discussion, we also paid more attention to the potential metabolic and epigenetic mechanisms of psoriasis and the molecular mechanistic cascades related to its comorbidities. This review also outlined current treatment for psoriasis, especially targeted therapies and novel therapeutic strategies, as well as the potential mechanism of disease recurrence.

This study explores the intersection of mindfulness practice and environmental activism within the Earth Holder Berlin (EHB) group, a part of the Order of Interbeing (O of I) inspired by Thich Nhat Hanh. EHB, established in 2020, integrates the principles of engaged Buddhism and endeavors to advance social and ecological justice through mindful actions. Using a qualitative methodology, this research employs semi-structured interviews and participant observation to investigate the experiences of EHB members. The findings demonstrate the transformative potential of Buddhism in ecological discourse, illustrating how EHB members embody epistemic entanglement, intertwining their Buddhist backgrounds with climate knowledge. This integration not only enhances personal transformation but also serves as a catalyst for social and ecological justice, enriching our understanding of engaged Buddhism in contemporary environmental movements.

ABSTRACTBackground Dental caries is a multifactorial disease, and the bacteria such as Streptococcus mutans (S. mutans) is one of the risk factors. The poor effect of existing anti-bacterial is mainly related to drug resistance, the short time of drug action, and biofilm formation.Methods To address this concern, we report here on the cinnamaldehyde (CA) loaded chitosan (CS) nanocapsules (CA@CS NC) sustained release CA for antibacterial treatment. The size, ζ-potential, and morphology were characterized. The antibacterial activities in vitro were studied by growth curve assay, pH drop assay, biofilm assay, and qRT-PCR In addition, cytotoxicity assay, organ index, body weight, and histopathology results were analyzed to evaluate the safety and biocompatibility in a rat model.Results CA@CS NC can adsorb the bacterial membrane due to electronic interaction, releasing CA slowly for a long time. At the same time, it has reliable antibacterial activity against S. mutans and downregulated the expression levels of QS, virulence, biofilm, and adhesion genes. In addition, it greatly reduced the cytotoxicity of CA and significantly inhibited dental caries in rats without obvious toxicity.Conclusion Our results showed that CA@CS NC had antibacterial and antibiofilm effects on S. mutans and inhibit dental caries. Besides, it showed stronger efficacy and less toxicity, and was able to adsorb bacteria releasing CA slowly, providing a new nanomaterial solution for the treatment of dental caries.

Background: Captisol®-enabled-fosphenytoin sodium (CE-fosphenytoin sodium) injection is a modified formulation of fosphenytoin sodium.Objective: We aim to compare the intravenous and intramuscular bioavailability and safety between CE-fosphenytoin sodium, fosphenytoin sodium (Cerebyx®), and phenytoin sodium (intravenous injection only).Methods: In pivotal study 1, 54 subjects were divided into three sequence groups that receive intravenous injection of 250 mg of phenytoin sodium equivalent (PE), CE-fosphenytoin sodium (T), or fosphenytoin sodium (R1) and 250 mg of phenytoin sodium (R2) in period 1. After a 14-day washout period, 36 subjects were randomized to two treatment sequence groups (T-R1 or R1-T, n = 18 per group) in period 2, in which the subjects who received R2 in period 1 were removed, those who received T in period 1 used R1 (T-R1), while those who previously received R1 used T (R1-T). In pivotal study 2, a single intramuscular dose of T (400 mg PE) or R1 (400 mg PE) was administered according to the individual sequential treatment assignment in each period. There was a washout (14 days) period before receiving the next period study drug.Results: T and R1 have similar pharmacokinetic characteristics regarding total and free phenytoin, showing bioequivalence of both drugs in the intravenous and intramuscular administration. The geometric mean ratio was close to 1 (0.98–1.06). The AUC of total and free phenytoin in subjects who intravenously received T and R1 was very similar to those who received R2, although their Cmax was lower than that of the subjects who received R2. Overall, treatment with T and R1 was safe and well-tolerated, without serious adverse events (SAEs) or grade III adverse events (AEs). With intravenous (i.v.) or intramuscular (i.m.) treatment, the incidence of drug-related AEs using T was similar to that using R1. Treatment with T and R1 had clearly superior tolerability than that with R2.Conclusion: CE-fosphenytoin sodium is a promising substitute for fosphenytoin sodium.Clinical Trial Registration:http://www.chinadrugtrials.org.cn/, CTR20202154 (11 November 2020).

Owing to the structural errors in the optical phased array, an initial random phase reduces the quality of the deflection beam. The most commonly applied approach to phase calibration is based on adaptive optics. However, adaptive optimisation approaches have slow convergence and low diffraction efficiency. We proposed a pointwise optimisation approach to achieve fast and accurate beam deflection. This approach conducts phase calibration, combining global traversal and local searches individually for each array element. We built a phase-calibration optical system containing a one-dimensional optical waveguide phase array for further verification and designed the relevant mechanics. The simulation and experimental results demonstrate that the pointwise optimisation approach accelerates the calibration process and improves the diffraction efficiency.

Abstract Background Promoting self-directed learning (SDL) among nursing undergraduates is crucial to meet the new requirements of the healthcare system and to adapt to online learning contexts during the COVID-19 pandemic. Therefore, identifying the classification features of SDL ability and developing targeted interventions are both critical. Professional identity (PI) may contribute to the cultivation of SDL ability, but their relationship remains relatively unknown. This study aimed to explore the subgroups of SDL ability and their differences in PI among nursing undergraduates during the COVID-19 pandemic. Methods A total of 2438 nursing undergraduates at four universities in China were enrolled in this cross-sectional study from November 2021 to February 2022. The Self-Directed Learning Scale of Nursing Undergraduates (SLSNU) and the Professional Identity Scale for Nursing Students (PISNS) were administered. A latent profile analysis was performed to explore SDL ability latent profiles. Multinomial logistic regression analysis was conducted to examine the predictors of profile membership, and a one-way analysis of variance was applied to compare the PI scores in each latent profile. Results Three latent profiles were identified and labeled ‘low SDL ability’ (n = 749, 30.7%), ‘low initiative of help-seeking’ (n = 1325, 54.4%) and ‘high SDL ability’ (n = 364, 14.9%). Multinomial logistic regression analysis suggested that nursing undergraduates who voluntarily chose a nursing major, had served as a student cadre, and had participated in clinical practicum were less likely to be included in the “low SDL ability” group. The average PI score was statistically different across the three profiles (F = 884.40, p

Ernst Faber’s 34 years of literary missionary works reveal his commitment to refining his approach to indigenizing Christianity in China. Employing three linguistic and cultural adaptation strategies—translation and commentary of the Bible, examination and analysis of missionary practical outcomes in Western society, and the revision and reinterpretation of Chinese classics incorporating Christian insights—Faber adapted his methods gradually into China’s specific conditions, indicating a prolonged path of indigenization. Despite expressing appreciation for Chinese culture, a critical examination reveals the preservation of his cultural biases and an unwavering commitment to Christianity as a means of purifying and enriching the spirit of the Chinese people. Rooted in the political context of his time and confidence in European historical world missions, Faber’s indigenization strategy in his Chinese literary works represents an interplay of cultural adaptation and resistance.

Abstract U-Shaped Steel Sheet Piles (USSSP) have buckling and bending problems during construction. In this research, the structural measure of stiffened plates applied along the longitudinal direction of USSSP is analyzed and proposed. A theoretical calculation method of stiffening effect is proposed based on the dynamic correlation coefficient method and the formula for the critical buckling load of locally stiffened USSSP is derived. A parametric analysis of the number, width, and arrangement scheme of the stiffened plates on the USSSP with different lengths is examined. The empirical formula derived for the total stiffening area and the critical load of the axial compression members of the USSSP is compared with practical results from an engineering case study. The results show a quadratic function under the condition of arranging the different number of stiffened plates at equal intervals, which is accurate in deriving the critical load values USSSP after local stiffening, and provide a theoretical basis for the optimization design of local reinforcement of USSSP axial compression members in engineering projects.

Background Developmental hypothyroidism impairs learning and memory in offspring, which depend on extensive neuronal circuits in the entorhinal cortex, together with the hippocampus and neocortex. The entorhinal-dentate gyrus pathway is the main entrance of memory circuits. We investigated whether developmental hypothyroidism impaired the morphological development of the entorhinal-dentate gyrus pathway. Methods We examined the structure and function of the entorhinal-dentate gyrus pathway in response to developmental hypothyroidism induced using 2-mercapto-1-methylimidazole. Results 1,1´-Dioctadecyl-3,3,3´,3´-tetramethylindocarbocyanine perchlorate tract tracing indicated that entorhinal axons showed delayed growth in reaching the outer molecular layer of the dentate gyrus at postnatal days 2 and 4 in hypothyroid conditions. The proportion of fibers in the outer molecular layer was significantly smaller in the hypothyroid group than in the euthyroid group at postnatal day 4. At postnatal day 10, the pathway showed a layer-specific distribution in the outer molecular layer, similar to the euthyroid group. However, the projected area of entorhinal axons was smaller in the hypothyroid group than in the euthyroid group. An electrophysiological examination showed that hypothyroidism impaired the long-term potentiation of the perforant and the cornu ammonis 3–cornu ammonis 1 pathways. Many repulsive axon guidance molecules were involved in the formation of the entorhinaldentate gyrus pathway. The hypothyroid group had higher levels of erythropoietin-producing hepatocyte ligand A3 and semaphorin 3A than the euthyroid group. Conclusion We demonstrated that developmental hypothyroidism might influence the development of the entorhinal-dentate gyrus pathway, contributing to impaired long-term potentiation. These findings improve our understanding of neural mechanisms for memory function.

Nucleus, as the machinery for genome transcription, play prominent roles to support the fundamental cellular functions, the destruction of any of these specific parts would significantly modulate the cell function. Therefore, troumendous drug delivery systems with enhanced nucleus targeting ability have been studied for nucleus-related disease regulation. The purpose of this review is to sort out the fundamental nuclear targeting strategy, especially the active mechanism of various nuclear targeting ligands and their extensive applications based on cancer targeting therapy. Various nuclear targeting ligands are first introduced to understand their nuclear entry mechanism. Next, to overcome biological barriers and avoid the serum protein absorption, diverse robust delivery strategies based on different nuclear targeting ligands are discussed. Moreover, other sophisticated carrier systems with enhanced nuclear entry, while without nuclear targeting ligands are also assembled. At the end the challenges and future opportunities in the field of nuclear targeting nanotherapeutics are tentatively proposed, to speed up their clinical translation.

Glioma is the most common tumour of the central nervous system, with a poor prognosis and an increasing trend of incidence in recent years; it is also beginning to affect younger age groups more. Added to this, cuproptosis is a new form of cell death. Indeed, when a certain amount of copper accumulates in a cell, it affects specific mitochondrial metabolic enzymes in that cell and leads to cell death–a phenomenon known as cuproptosis. In this study, we applied bioinformatics analysis, and, according to the results of the study analysis and Gene Ontology (GO), as well as the Kyoto Encyclopedia of Genes and Genomes KyotoEncyclopediaofGenesandGenomes, the glutaminase (GLS) genes affect the prognosis and tumour mutation of glioma patients through cuproptosis. Interestingly, however, GLS is not involved in the immune escape of glioma. Glutaminase genes are a class of glucose metabolism-related genes that are involved in the tricarboxylic acid cycle of cells. At the same time, the expression of the glutaminase gene was positively correlated with the degree of immune cell infiltration and the expression of various immune cell markers, and thus affected the prognosis of glioma patients. Therefore, we believe that the cuproptosis-related glutaminase gene can be an important factor in determining the prognosis of glioma patients.

Abstract Background Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by increased bone fragility and a series of extraskeletal manifestations. Approximately 90 % of OI cases are caused by type I collagen variants encoded by the collagen type I alpha 1 (COL1A1) or type I alpha 2 (COL1A2) gene. Lumbar Scheuermann’s disease is an atypical type of Scheuermann’s disease accompanied by Schmorl’s nodes and irregular endplates but without pronounced kyphosis. Although the etiology of Scheuermann’s disease is unclear, genetic and environmental factors are likely. Case presentation Here, we report a 32-year-old male patient who experienced multiple brittle fractures. Gene sequencing revealed a heterozygous mutation, c.4048G > A (p.G1350S), in the COL1A2 gene, and the patient was diagnosed with OI. Magnetic resonance imaging of his thoracolumbar spine revealed multiple Schmorl’s nodes. Conclusions This is the first reported case of OI coexisting with the spinal presentation of Scheuermann’s disease. It is speculated that the COL1A2 gene mutation might be an underlying novel genetic cause of Scheuermann’s disease. In conclusion, this case demonstrates the relationship between Scheuermann’s disease and OI for the first time and enriches the genotype-phenotype spectrum of OI.

ObjectiveThis study aimed to investigate the relationship between prognostic and tumor parameters of cervical cancer patients, such as tumor size (TS), tumor volume (TV), and tumor volume reduction rate (TVRR) after external beam radiotherapy.MethodsA total of 217 patients with advanced cervical cancer, classified as Federation of Gynecology and Obstetrics (FIGO) IIa–IVa, were enrolled in the study. Pre- and mid-RT pelvic magnetic resonance imaging (MRI) were performed twice, during RT and just before brachytherapy.ResultsThe median follow-up time was 51 months (range, 7–111 months). The 5-year overall survival (OS), progression-free survival (PFS), and local failure-free survival (LFFS) rates were 81.3, 85.1, and 92.9%, respectively. Multivariate analysis revealed that tumor parameters including FIGO stage >II (Hazard Ratio, 2.377 and 95% confidence interval [CI], 1.091–5.182; P = 0.029), pre-RT TV >61.6 cm3 (HR, 0.417 and 95% CI, 0.188–0.926; P = 0.032), and mid-RT TV >11.38 cm3 (HR, 3.192 and 95% CI, 1.094–9.316; P = 0.034) were observably associated with OS. Univariate analysis showed that the tumor volume reduction rate (TVRR) was dramatically associated with overall survival (HR, 0.204 and 95% CI 0.033–1.282; P

Multidrug resistance (MDR) of tumors is one of the clinical direct reasons for chemotherapy failure. MDR directly leads to tumor recurrence and metastasis, with extremely grievous mortality. Engineering a novel nano-delivery system for the treatment of MDR tumors has become an important part of nanotechnology. Herein, this review will take those different mechanisms of MDR as the classification standards and systematically summarize the advances in nanotechnology targeting different mechanisms of MDR in recent years. However, it still needs to be seriously considered that there are still some thorny problems in the application of the nano-delivery system against MDR tumors, including the excessive utilization of carrier materials, low drug-loading capacity, relatively narrow targeting mechanism, and so on. It is hoped that through the continuous development of nanotechnology, nano-delivery systems with more universal uses and a simpler preparation process can be obtained, for achieving the goal of defeating cancer MDR and accelerating clinical transformation.

BackgroundKeratinocytes of psoriasis have anti-apoptotic properties including delayed apoptosis process, accelerated proliferation metabolism and postponed differentiation process. However, the specific mechanism leading to the abnormal biological behavior of keratinocytes remains unclear.ObjectivesWe investigated the role of increased RPL22 expression in regulating the abnormal biological behavior of keratinocytes and the mechanism of regulation of RPL22 expression in skin lesions of psoriatic patients.MethodsWe examined clinical samples and utilized cytokine-induced cell and IMQ-treated mouse models. We determined the expression and functions of RPL22 in vitro and in vivo.ResultsWe showed that RPL22 expression was significantly increased in the skin lesions of psoriasis patients and IMQ-treated psoriatic-like mice. Such increased expression is attributed to hyperacetylation of histone H3K27 in the promoter region of RPL22. Interestingly, overexpression of RPL22 enhanced keratinocyte proliferation by increasing cyclinD1 expression and accelerated CD4+T cells recruitment via upregulating CXCL10 expression. Finally, we demonstrated that RPL22 overexpression promoted psoriasiform phenotypes in IMQ-induced mouse skins.ConclusionsThese findings suggested that RPL22 regulates keratinocytes abnormal biological behavior and contributes to the development of psoriatic phenotypes. Thus, RPL22 might be a novel potential molecular target for treatment of psoriasis.

With the development of information technology, films, music, and other publications are inclined to be distributed in digitalized form. However, the low cost of data replication and dissemination leads to digital rights problems and brings huge economic losses. Up to now, existing digital rights management (DRM) schemes have been powerless to deter attempts of infringing digital rights and recover losses of copyright holders. This paper presents a YODA-based digital watermark management system (Y-DWMS), adopting non-repudiation of smart contract and blockchain, to implement a DRM mechanism to infinitely amplify the cost of infringement and recover losses copyright holders suffered once the infringement is reported. We adopt game analysis to prove that in Y-DWMS, the decision of non-infringement always dominates rational users, so as to fundamentally eradicate the infringement of digital rights, which current mainstream DRM schemes cannot reach.

A smart watch is a kind of emerging wearable device in the Internet of Things. The security and privacy problems are the main obstacles that hinder the wide deployment of smart watches. Existing security mechanisms do not achieve a balance between the privacy-preserving and data access control. In this paper, we propose a fine-grained privacy-preserving access control architecture for smart watches (FPAS). In FPAS, we leverage the identity-based authentication scheme to protect the devices from malicious connection and policy-based access control for data privacy preservation. The core policy of FPAS is two-fold: (1) utilizing a homomorphic and re-encrypted scheme to ensure that the ciphertext information can be correctly calculated; (2) dividing the data requester by different attributes to avoid unauthorized access. We present a concrete scheme based on the above prototype and analyze the security of the FPAS. The performance and evaluation demonstrate that the FPAS scheme is efficient, practical, and extensible.

ObjectiveAutoimmune thyroid disease (AITD) is an organ-specific disorder due to the interplay between environmental and genetic factors. Toll-like receptors (TLRs) are pattern recognition receptors expressed abundantly on monocytes. There is a paucity of data on TLR expression in AITD. The aim of this study was to examine TLR expression, activation, ligands, and downstream signaling adaptors in peripheral blood mononuclear cells (PBMCs) extracted from untreated AITD patients and healthy controls.MethodWe isolated PBMC of 30 healthy controls, 36 patients with untreated Hashimoto’s thyroiditis, and 30 patients with newly onset Graves’ disease. TLR mRNA, protein expression, TLR ligands, and TLR adaptor molecules were measured using real-time PCR, Western blot, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). PBMC was simulated with TLR agonists. The effects of TLR agonists on the viability of human PBMC were evaluated using the MTT assay. The supernatants of cell cultures were measured for the pro-inflammatory cytokines, interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and IL-10 by ELISA.ResultsTLR2, TLR3, TLR9, and TLR10 mRNA were significantly increased in AITD patients compared with controls. TLR2, TLR3, TLR9, high mobility group box 1 (HMGB1), and RAGE expression on monocytes was higher in patients than control at baseline and TLR agonists’ stimulation. The release of TNF-α and IL-6 was significantly increased in PBMCs from AITD patients with TLR agonists, while IL-10 was significantly decreased. Downstream targets of TLR, myeloid differentiation factor 88 (MyD88), and myeloid toll/IL-1 receptor-domain containing adaptor-inducing interferon-β were significantly elevated in AITD patients. Levels of TLR2 ligands, HMGB1, and heat shock protein 60 were significantly elevated in AITD patients compared with those in controls and positively correlated with TgAb and TPOAb, while sRAGE concentration was significantly decreased in AITD patients.ConclusionThis work is the first to show that TLR2, TLR3, and TLR9 expression and activation are elevated in the PBMCs of patients with AITD and TLRs may participate in the pathogenesis of AITD.