Unveiling the impact of interprofessional education on shaping students' interprofessional identity and collaboration perception: a mixed-method study.

BACKGROUND: Interprofessional education (IPE) has the potential to shape students' collaboration perception and interprofessional identity but remains understudied. This study aims to understand the effects of the IPE program as a contextual trigger to promote collaboration perception change and interprofessional identity formation among healthcare professional students. METHODS: Using concurrent triangulation mixed-methods, we examined the relationship between collaboration perception and interprofessional identity change among health profession students (N = 263), and explored their perspectives on how their IPE experiences influenced their perception and identity. Participants completed the Interdisciplinary Education Perception Scale and Extended Professional Identity Scale and responded to open-ended questions before and after the IPE intervention. Pearson's correlation, t-tests, regression (quantitative), and thematic analysis (qualitative) were conducted. RESULTS: Teams with initially lower collaboration perception (M = 3.59) and lower interprofessional identity (M = 3.59) showed a significant increase in collaboration perception (M = 3.76, t = 2.63; p = .02) and interprofessional identity (M = 3.97, t = 4.86; p < .001) after participating in IPE. The positive relationship between collaboration perception and interprofessional identity strengthened after participating in IPE, as evident from the correlation (Time 1: r = .69; p < .001; Time 2: r = .79; p < .001). Furthermore, collaboration perception in Time 1 significantly predicted the variance in interprofessional identity at Time 2 (ß = 0.347, p < .001). Qualitative findings indicated that 85.2% of students expressed that IPE played a role in promoting their interprofessional identity and collaboration attitudes. CONCLUSIONS: Incorporating the IPE program into the curriculum can effectively enhance students' collaboration perception and interprofessional identity, ultimately preparing them for collaborative practice in the healthcare system. By engaging students in interprofessional teamwork, communication, and joint decision-making processes, the IPE program provides a valuable context for students to develop a sense of belonging and commitment to interprofessional collaboration.

CDK9 inhibitors for the treatment of solid tumors.

Cyclin-dependent kinase 9 (CDK9) regulates mRNA transcription by promoting RNA Pol II elongation. CDK9 is now emerging as a potential therapeutic target for cancer, since its overexpression has been found to correlate with cancer development and worse clinical outcomes. While much work on CDK9 inhibition has focused on hematologic malignancies, the role of this cancer driver in solid tumors is starting to come into focus. Many solid cancers also overexpress CDK9 and depend on its activity to promote downstream oncogenic signaling pathways. In this review, we summarize the latest knowledge of CDK9 biology in solid tumors and the studies of small molecule CDK9 inhibitors. We discuss the results of the latest clinical trials of CDK9 inhibitors in solid tumors, with a focus on key issues to consider for improving the therapeutic impact of this drug class.

Analyzing the barriers and enablers to internet hospital implementation: a qualitative study of a tertiary hospital using TDF and COM-B framework.

Background: Internet hospitals have become an important way to improve the accessibility of medical services and promote medical equity in China. However, there is still lack of research on the behavior of medical personnel during the process of using Internet medical services, and the elements of behavior that motivate doctors to actively use or resist the use of Internet hospitals are still not fully analyzed. The study applied the Theoretical Domains Framework to examine the factors affecting the engagement of medical personnel in Internet hospitals, with the aim of guiding the design of intervention to enhance Internet hospital participation. Methods: This study utilized qualitative analysis. Semi-structured questionnaires based on the Theoretical Domains Framework (TDF) and Capability-Opportunity-Motivation-Behavior (COM-B) model was developed and administered to 40 doctors and nurses at a Grade A tertiary hospital in Guangdong Province. Data was coded and analyzed using qualitative methods including Nvivo software. Results: The research displayed 19 barriers and 7 enablers for the implementation of Internet hospitals, all 14 TDF domains impacted participation with motivation cited most frequently. Despite challenges, medical personnel exhibited a generally optimistic stance towards utilization of the Internet hospital. Major barriers include the higher requirement of diagnostic ability, objective difficulties brought by online consultation to the decision-making process, limitation of time and other resources, not ideal technological and institutional environment, lack of self-efficacy and negative expectation of results in online consultation. Key enablers include patient needs and the positive impact of online care on the medical process and patient experience. Discussion: This qualitative study identified a range of barriers and enablers to Internet hospital participation according to medical personnel, providing an conceptual framework to guide further research evaluating implementation strategies. Expanded research and targeted interventions design can help optimize participation in this evolving healthcare delivery model.

[Determination of the derivatization reactivity between α/ß-dicarbonyl compounds and standard citrullinated peptides based on matrix-assisted laser desorption ionization-time-of-flight mass spectrometry].

Protein citrullination is an irreversible post-translational modification process regulated by peptidylarginine deiminases (PADs) in the presence of Ca2+. This process is closely related to the occurrence and development of autoimmune diseases, cancers, neurological disorders, cardiovascular and cerebrovascular diseases, and other major diseases. The analysis of protein citrullination by biomass spectrometry confronts great challenges owing to its low abundance, lack of affinity tags, small mass-to-charge ratio change, and susceptibility to isotopic and deamidation interferences. The methods commonly used to study the protein citrullination mainly involve the chemical derivatization of the urea group of the guanine side chain of the peptide to increase the mass-to-charge ratio difference of the citrullinated peptide. Affinity-enriched labels are then introduced to effectively improve the sensitivity and accuracy of protein citrullination by mass spectrometry. 2,3-Butanedione or phenylglyoxal compounds are often used as derivatization reagents to increase the mass-to-charge ratio difference of the citrullinated peptide, and the resulting derivatives have been observed to contain α-dicarbonyl structures. To date, however, no relevant studies on the reactivity of dicarbonyl compounds with citrullinated peptides have been reported. In this study, we determined whether six α-dicarbonyl and two ß-dicarbonyl compounds undergo derivatization reactions with standard citrullinated peptides using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Among the α-dicarbonyl compounds, 2,3-butanedione and glyoxal reacted efficiently with several standard citrullinated peptides, but yielded a series of by-products. Phenylglyoxal, methylglyoxal, 1,2-cyclohexanedione, and 1,10-phenanthroline-5,6-dione also derivated efficiently with standard citrullinated peptides, generating a single derivative. Thus, a new derivatization method that could yield a single derivative was identified. Among the ß-dicarbonyl compounds, 1,3-cyclohexanedione and 2,4-pentanedione successfully reacted with the standard citrullinated peptides, and generated a single derivative. However, their reaction efficiency was very low, indicating that the ß-dicarbonyl compounds are unsuitable for the chemical derivatization of citrullinated peptides. The above results indicate that the α-dicarbonyl structure is necessary for realizing the efficient and specific chemical derivatization of citrullinated peptides. Moreover, the side chains of the α-dicarbonyl structure determine the structure of the derivatives, derivatization efficiency, and generation (or otherwise) of by-products. Therefore, the specific enrichment and precise identification of citrullinated peptides can be achieved by synthesizing α-dicarbonyl structured compounds containing affinity tags. The proposed method enables the identification of citrullinated proteins and their modified sites by MS, thereby providing a better understanding of the distribution of citrullinated proteins in different tissues. The findings will be beneficial for studies on the mechanism of action of citrullinated proteins in a variety of diseases.

The lowdown on breakdown: Open questions in plant proteolysis.

Proteolysis, including post-translational proteolytic processing as well as protein degradation and amino acid recycling, is an essential component of the growth and development of living organisms. In this article, experts in plant proteolysis pose and discuss compelling open questions in their areas of research. Topics covered include the role of proteolysis in the cell cycle, DNA damage response, mitochondrial function, the generation of N-terminal signals (degrons) that mark many proteins for degradation (N-terminal acetylation, the Arg/N-degron pathway, and the chloroplast N-degron pathway), developmental and metabolic signaling (photomorphogenesis, abscisic acid and strigolactone signaling, sugar metabolism, and post-harvest regulation), plant responses to environmental signals (endoplasmic-reticulum associated degradation, chloroplast-associated degradation, drought tolerance, the growth-defense tradeoff)), and the functional diversification of peptidases. We hope these thought-provoking discussions help to stimulate further research.

Prior Bariatric Surgery Predicts Lower Life-Threatening Morbidity in Patients Admitted for Acute Allergic Reaction and Anaphylaxis: a Propensity Score-Matched Analysis of the U.S. Nationwide Inpatient Sample, 2005-2018.

PURPOSE: Acute allergic reactions may occur in susceptible individuals following exposure to various allergens. Obesity is linked to allergic reactions, and weight loss from bariatric surgery may attenuate the severity of certain conditions such as airway hyperresponsiveness in asthma. This retrospective observational study investigates associations between prior bariatric surgery and lower risk for life-threatening conditions in patients hospitalized with acute allergic reactions and anaphylaxis. MATERIALS AND METHODS: Adults ≥ 18 years old diagnosed with morbid obesity and admitted to US hospitals with acute allergic reactions/anaphylaxis were included. All data were extracted from the US Nationwide Inpatient Sample (NIS) database 2005-2018. Patients without information on in-hospital mortality, discharge destination, hospital costs, and length of stay (LOS) were excluded. Patients were divided into two groups based on prior bariatric surgery or not. All diagnoses were verified through ICD-9 and ICD-10 codes. Between-group differences and associations between variables were evaluated using logistic regression analysis. RESULTS: After matching, patients with prior bariatric surgery had significantly lower proportions of any life-threatening morbidity (37.2% vs. 47.4%), respiratory distress or failure (11.2% vs. 17.0%), pneumonia or severe infection (7.4% vs. 10.2%), sepsis/septic shock (15.2% vs. 20.9%), intubation and mechanical ventilation (11.2% vs. 14.6%), prolonged LOS (10.3% vs. 20.6%) and unfavorable discharge (6.9% vs. 12.5%) than those without prior bariatric surgery. CONCLUSION: Prior bariatric surgery predicts a lower risk of life-threatening morbidity and prolonged LOS among adults hospitalized for acute allergic reaction and anaphylaxis. Future prospective studies are warranted to confirm the present findings and reveal underlying mechanisms.

Membranous aplasia cutis congenita: A rare case report highlighting clinical presentation, genetic insights, and the need for comprehensive evaluation.

Introduction: Membranous aplasia cutis congenita (MACC) is the most common clinical subtype of aplasia cutis congenita (ACC). It is typified by a localized skin lesion devoid of hair and features a membranous surface. While most MACC individuals do not present with concurrent abnormalities, it can sometimes co-occur with additional physical anomalies and various malformation syndromes. Moreover, the underlying causes of MACC remain elusive. Case presentation: We describe a case of a 6-month-old female infant diagnosed with MACC. The patient presented with a midline skin lesion on the occipital scalp, characterized by a glistening surface and a hair collar sign. Dermoscopic examination revealed specific features, including translucency, telangiectasia, and hypertrichosis. The infant had a history of patent foramen ovale, and further examination uncovered an asymptomatic ventricular septal defect. Whole exome sequencing revealed 20 gene variants relevant to the clinical phenotype of the patient, suggesting a possible association with MACC. Conclusion: MACC is a rare and underreported condition, primarily diagnosed based on its distinctive clinical features. It is imperative to emphasize the significance of thorough evaluations in MACC patients, encompassing developmental, cardiac, neurological, and genetic assessments to facilitate early detection and the exclusion of potentially life-threatening comorbidities. Importantly, genetic characterization, as demonstrated in this case, contributes to our understanding of MACC's etiology and highlights the need for further research in this field.

Mesenteric lymph nodes: a critical site for the up-regulatory effect of hUC-MSCs on Treg cells by producing TGF-ß1 in colitis treatment.

BACKGROUND: Mesenchymal stem cells (MSCs) demonstrate a wide range of therapeutic capabilities in the treatment of inflammatory bowel disease (IBD). The intraperitoneal injection of MSCs has exhibited superior therapeutic efficacy on IBD than intravenous injection. Nevertheless, the precise in vivo distribution of MSCs and their biological consequences following intraperitoneal injection remain inadequately understood. Additional studies are required to explore the correlation between MSCs distribution and their biological effects. METHODS: First, the distribution of human umbilical cord MSCs (hUC-MSCs) and the numbers of Treg and Th17 cells in mesenteric lymph nodes (MLNs) were analyzed after intraperitoneal injection of hUC-MSCs. Subsequently, the investigation focused on the levels of transforming growth factor beta1 (TGF-ß1), a key cytokine to the biology of both Treg and Th17 cells, in tissues of mice with colitis, particularly in MLNs. The study also delved into the impact of hUC-MSCs therapy on Treg cell counts in MLNs, as well as the consequence of TGFB1 knockdown hUC-MSCs on the differentiation of Treg cells and the treatment of IBD. RESULTS: The therapeutic effectiveness of intraperitoneally administered hUC-MSCs in the treatment of colitis was found to be significant, which was closely related to their quick migration to MLNs and secretion of TGF-ß1. The abundance of hUC-MSCs in MLNs of colitis mice is much higher than that in other organs even the inflamed sites of colon. Intraperitoneal injection of hUC-MSCs led to a significant increase in the number of Treg cells and a decrease in Th17 cells especially in MLNs. Furthermore, the concentration of TGF-ß1, the key cytokine for Treg differentiation, were also found to be significantly elevated in MLNs after hUC-MSCs treatment. Knockdown of TGFB1 in hUC-MSCs resulted in a noticeable reduction of Treg cells in MLNs and the eventually failure of hUC-MSCs therapy in colitis. CONCLUSIONS: MLNs may be a critical site for the regulatory effect of hUC-MSCs on Treg/Th17 cells and the therapeutic effect on colitis. TGF-ß1 derived from hUC-MSCs promotes local Treg differentiation in MLNs. This study will provide new ideas for the development of MSC-based therapeutic strategies in IBD patients.

Assessment of soft and hard tissue changes following micro crestal flap-Alveolar ridge preservation and augmentation at molar extraction sites in patients with stage III/IV periodontitis: A randomized controlled trial.

AIM: This study aimed to assess hard and soft tissue contour changes following micro crestal flap-alveolar ridge preservation (MCF-ARP) and natural healing (NH) in periodontally compromised molar extraction sites and to analyse the feasibility and need for bone augmentation during implant therapy. MATERIALS AND METHODS: Fifty-six patients with 70 sites were randomized into two groups at the site level (35 sites from 31 patients in the test group and 35 sites from 29 patients in the control group). Among whom, four patients contributed one tooth to the control group and one tooth to the test group. Hard tissue indicators were measured using cone beam computed tomography performed before tooth extraction and 6 months after surgery. Soft tissue contour changes were assessed using intraoral scanning performed before and immediately after surgery and also 2 weeks and 1, 3 and 6 months after surgery. RESULTS: Six months after surgery, the MCF-ARP group showed less resorption in buccal bone height (p = .032) and greater augmentation in central bone height (p = .001) and ridge width (p = .009). The mean, vertical and horizontal collapse of buccal soft tissue contour in the MCF-ARP group were 0.95 mm (p = .010), 0.61 mm (p = .019) and 0.56 mm (p = .013) less than that in the NH group, respectively. There were significantly (p = .007) fewer sites in the MCF-ARP group than in the NH group (0% vs. 26.7%) for staged bone augmentation and more sites that could be treated with simple implant procedure in the MCF-ARP group than in the NH group (71.9% vs. 56.6%). CONCLUSIONS: Compared with NH, MCF-ARP reduced bone resorption in periodontally compromised molar extraction sites and maintained the buccal soft tissue contour. MCF-ARP reduces the need for complex bone augmentation procedures in implant therapy. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR) ChiCTR2200056335. Registered on 4 February 2022, Version 1.0.

Large-scale deployment of intelligent transportation to help achieve low-carbon and clean sustainable transportation.

Sustained deep emission reduction in road transportation is encountering bottleneck. The Intelligent Transportation-Speed Guidance System (ITSGS) is anticipated to overcome this challenge and facilitate the achievement of low-carbon and clean transportation. Here, we compiled vehicle emission datasets collected from real-world road experiments and identified the mapping relationships between four pollutants (CO2, CO, NOx, and THC) and their influencing factors through machine learning. We developed random forest models for each pollutant and achieved strong predictive performance, with an R2 exceeding 0.85 on the test dataset for all models. The environmental benefits of ITSGS at the urban scale were quantified by combining emission models with large-scale real trajectory data from Zibo, Shandong Province. Based on temporal and spatial analyses, we found that ITSGS has varying degrees of emission reduction potential during the morning peak, flat peak, and evening peak hours. Values can range from 5.71 %-8.16 % for CO2 emissions, 13.63 %-16.25 % for NOx emissions, 13.69 %-16.45 % for CO emissions, and 4.84-7.07 % for THC emissions, respectively. Additionally, ITSGS can significantly expand the area of low transient emission zones. The best time for achieving maximum environmental benefits from ITSGS is during the workday flat peak. ITSGS limits high-speed and aggressive driving behavior, thereby smoothing the driving trajectory, reducing the frequency of speed switches, and lowering road traffic emissions. The results of the ITSGS environmental benefits evaluation will provide new insights and solutions for sustainable road traffic emission reduction. SYNOPSIS: Large-scale deployment of Intelligent Transportation - Speed Guidance System is a sustainable solution to help achieve low-carbon and clean transportation.

Impaired thyroid hormone sensitivity exacerbates the effect of PM2.5 and its components on dyslipidemia in schizophrenia.

BACKGROUND: Dyslipidemia in schizophrenia causes a serious loss of healthy life expectancy, making it imperative to explore key environmental risk factors. We aimed to assess the effect of PM2.5 and its constituents on dyslipidemia in schizophrenia, identify the critical hazardous components, and investigate the role of impaired thyroid hormones (THs) sensitivity in this association. METHODS: We collected disease data on schizophrenia from the Anhui Mental Health Center from 2019 to 2022. Logistic regression was constructed to explore the effect of average annual exposure to PM2.5 and its components [black carbon (BC), organic matter (OM), sulfate (SO42-), ammonium (NH4+), and nitrate (NO3-)] on dyslipidemia, with subgroup analyses for age and gender. The degree of impaired THs sensitivity in participants was reflected by the Thyroid Feedback Quantile-based Index (TFQI), and its role in the association of PM2.5 components with dyslipidemia was explored. RESULTS: A total of 5125 patients with schizophrenia were included in this study. Exposure to PM2.5 and its components (BC, OM, SO42-, NH4+, and NO3-) were associated with dyslipidemia with the odds ratios and 95 % confidence interval of 1.13 (1.04, 1.23), 1.16 (1.07, 1.26), 1.15 (1.06, 1.25), 1.11 (1.03, 1.20), 1.09 (1.00, 1.18), 1.12 (1.04, 1.20), respectively. Mixed exposure modeling indicated that BC played a major role in the effects of the mixture. More significant associations were observed in males and groups <45 years. In addition, we found that the effect of PM2.5 and its components on dyslipidemia was exacerbated as impaired THs sensitivity in the patients. CONCLUSIONS: Exposure to PM2.5 and its components is associated with an increased risk of dyslipidemia in schizophrenia, which may be exacerbated by impaired THs sensitivity. Our results suggest a new perspective for the management of ambient particulate pollution and the protection of thyroid function in schizophrenia.

Light regulates nuclear detainment of intron-retained transcripts through COP1-spliceosome to modulate photomorphogenesis.

Intron retention (IR) is the most common alternative splicing event in Arabidopsis. An increasing number of studies have demonstrated the major role of IR in gene expression regulation. The impacts of IR on plant growth and development and response to environments remain underexplored. Here, we found that IR functions directly in gene expression regulation on a genome-wide scale through the detainment of intron-retained transcripts (IRTs) in the nucleus. Nuclear-retained IRTs can be kept away from translation through this mechanism. COP1-dependent light modulation of the IRTs of light signaling genes, such as PIF4, RVE1, and ABA3, contribute to seedling morphological development in response to changing light conditions. Furthermore, light-induced IR changes are under the control of the spliceosome, and in part through COP1-dependent ubiquitination and degradation of DCS1, a plant-specific spliceosomal component. Our data suggest that light regulates the activity of the spliceosome and the consequent IRT nucleus detainment to modulate photomorphogenesis through COP1.

Personality portraits, resilience, and professional identity among nursing students: a cross-sectional study.

BACKGROUND: The lack of professional identity can impede the transition from nursing students to qualified nurses and exacerbate the shortage of health care professionals. Personality is important to resilience-building and professional identity development in nursing students. However, the associations among personality, resilience, and professional identity are less explored. The study aims to identify latent subtypes of personality, to evaluate the mediating role of resilience between personality and professional identity in nursing students, and to provide practical guidance for educators' subsequent interventions with nursing students' professional identity. METHODS: 1397 nursing students were recruited from Be Resilient to Nursing Career (BRNC) between October 2020 and April 2022 by cluster sampling from 4 universities in China. NEO Five-Factor Inventory, 10-item Connor-Davidson Resilience Scale, and Professional Identity Questionnaire for Undergraduate Students were administered. Analyses of latent profiles and mediations were performed. RESULTS: Three latent personality types were identified: Over-sensitivity (35.4%), Ordinary (53.8%), and Flexibility (10.8%). Nursing role model was found to be a significant indicator of personality (Ordinary as ref, Over-sensitivity: OR = 0.73, 95% CI: 0.57-0.93, P = 0.010; Flexibility: OR = 1.85, 95% CI: 1.29-2.65, P = 0.001). The association between personality portraits and professional identity were significantly mediated by resilience (P < 0.05). CONCLUSIONS: There exists heterogeneity in nursing students' personality. Resilience plays a significant role in mediating the relationship between personality and professional identity.

Uncovering ghost introgression through genomic analysis of a distinct eastern Asian hickory species.

Ghost introgression, or the transfer of genetic material from extinct or unsampled lineages to sampled species, has attracted much attention. However, conclusive evidence for ghost introgression, especially in plant species, remains scarce. Here, we newly assembled chromosome-level genomes for both Carya sinensis and Carya cathayensis, and additionally re-sequenced the whole genomes of 43 C. sinensis individuals as well as 11 individuals representing 11 diploid hickory species. These genomic datasets were used to investigate the reticulation and bifurcation patterns within the genus Carya (Juglandaceae), with a particular focus on the beaked hickory C. sinensis. By combining the D-statistic and BPP methods, we obtained compelling evidence that supports the occurrence of ghost introgression in C. sinensis from an extinct ancestral hickory lineage. This conclusion was reinforced through the phylogenetic network analysis and a genome scan method VolcanoFinder, the latter of which can detect signatures of adaptive introgression from unknown donors. Our results not only dispel certain misconceptions about the phylogenetic history of C. sinensis but also further refine our understanding of Carya's biogeography via divergence estimates. Moreover, the successful integration of the D-statistic and BPP methods demonstrates their efficacy in facilitating a more precise identification of introgression types.

Sustained release hypoxia-activated prodrug-loaded BSA nanoparticles enhance transarterial chemoembolization against hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is the standard of care for patients with advanced hepatocellular carcinoma (HCC), but facing the problem of low therapeutic effect. Conventional TACE formulations contain Lipiodol (LP) and chemotherapeutic agents characterized by burst release due to the unstable emulsion. Herein, we developed a novel TACE system by inducing bovine serum albumin (BSA) loaded hypoxia-activated prodrug (tirapazamine, TPZ) nanoparticle (BSATPZ) for sustained drug release. In the rabbit VX2 liver cancer model, TACE treatment induced a long-term hypoxic tumor microenvironment as demonstrated by increased expression of HIF-1α in the tumor. BSATPZ nanoparticles combined with LP greatly enhanced the anti-tumor effects of the TACE treatment. Compared to conventional TACE treatment, BSATPZ nanoparticle-based TACE therapy more significantly delayed tumor progression and inhibited the metastases in the lungs. The effects could be partially mediated by the rebuilt immune responses, as BSATPZ nanoparticle can served as an immunogenic cell death (ICD) inducer. Collectively, our results suggest that BSATPZ nanoparticle-based TACE therapy could be a promising strategy to improve clinical outcomes for patients with HCC and provide a preclinical rationale for evaluating TPZ therapy in clinical studies.

Distinctive Pattern of Metal Deposition in Neurologic Wilson Disease: Insights From 7T Susceptibility-Weighted Imaging.

BACKGROUND AND OBJECTIVES: Noninvasive and accurate biomarkers of neurologic Wilson disease (NWD), a rare inherited disorder, could reduce diagnostic error or delay. Excessive subcortical metal deposition seen on susceptibility imaging has suggested a characteristic pattern in NWD. With submillimeter spatial resolution and increased contrast, 7T susceptibility-weighted imaging (SWI) may enable better visualization of metal deposition in NWD. In this study, we sought to identify a distinctive metal deposition pattern in NWD using 7T SWI and investigate its diagnostic value and underlying pathophysiologic mechanism. METHODS: Patients with WD, healthy participants with monoallelic ATP7B variant(s) on a single chromosome, and health controls (HCs) were recruited. NWD and non-NWD (nNWD) were defined according to the presence or absence of neurologic symptoms during investigation. Patients with other diseases with comparable clinical or imaging manifestations, including early-onset Parkinson disease (EOPD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and neurodegeneration with brain iron accumulation (NBIA), were additionally recruited and assessed for exploratory comparative analysis. All participants underwent 7T T1, T2, and high-resolution SWI scanning. Quantitative susceptibility mapping and principal component analysis were performed to illustrate metal distribution. RESULTS: We identified a linear signal intensity change consisting of a hyperintense strip at the lateral border of the globus pallidus in patients with NWD. We termed this feature "hyperintense globus pallidus rim sign." This feature was detected in 38 of 41 patients with NWD and was negative in all 31 nNWD patients, 15 patients with EOPD, 30 patients with MSA, 15 patients with PSP, and 12 patients with NBIA; 22 monoallelic ATP7B variant carriers; and 41 HC. Its sensitivity to differentiate between NWD and HC was 92.7%, and specificity was 100%. Severity of the hyperintense globus pallidus rim sign measured by a semiquantitative scale was positively correlated with neurologic severity (ρ = 0.682, 95% CI 0.467-0.821, p < 0.001). Patients with NWD showed increased susceptibility in the lenticular nucleus with high regional weights in the lateral globus pallidus and medial putamen. DISCUSSION: The hyperintense globus pallidus rim sign showed high sensitivity and excellent specificity for diagnosis and differential diagnosis of NWD. It is related to a special metal deposition pattern in the lenticular nucleus in NWD and can be considered as a novel neuroimaging biomarker of NWD. CLASSIFICATION OF EVIDENCE: The study provides Class II evidence that the hyperintense globus pallidus rim sign on 7T SWI MRI can accurately diagnose neurologic WD.

Bmi-1 promotes the proliferation, migration and invasion, and inhibits cell apoptosis of human retinoblastoma cells via RKIP.

Retinoblastoma is one of the most common ocular malignancies in children. Bmi-1, a member of the Polycomb group family of transcriptional repressors, is expressed in a variety of tumors. The purpose of our study was to explore the role of Bmi-1 in retinoblastoma. RT-qPCR and western blot were used for calculating the mRNA and protein levels of Bmi-1 and RKIP. MTT, Wound healing and Transwell assays were performed to measure the proliferation, migration and invasion in retinoblastoma cells. Cell apoptosis was detected by flow cytometry. The volume and mass of transplanted tumors were detected in nude mice. Bmi-1 was over expressed, and RKIP was low expressed in retinoblastoma cells. Bmi-1 promoted cell proliferation, migration and invasion and suppressed cell apoptosis of Y79 and SO-RB50 cells. Downregulation of Bmi-1 and overexpression of RKIP inhibited cell proliferation, migration and invasion, and increased cell apoptosis. The functions of Bmi-1 knockdown on retinoblastoma cells were blocked by RKIP knockdown, but promoted by RKIP. Down-regulated Bmi-1 inhibited xenograft tumor growth, and RKIP exacerbated this inhibitory effect. Bmi-1 served as a potential therapeutic target for improving the efficacy of clinical treatment in retinoblastoma. All the findings revealed the functions of Bmi-1/RKIP axis in retinoblastoma tumorigenesis.

ppGpp is a dual-role regulator involved in balancing iron absorption and prodiginine biosynthesis in Pseudoalteromonas.

Iron is an essential element for microbial survival and secondary metabolism. However, excess iron availability and overloaded secondary metabolites can hinder microbial growth and survival. Microorganisms must tightly control iron homeostasis and secondary metabolism. Our previous studies have found that the stringent starvation protein A (SspA) positively regulates prodiginine biosynthesis by activating iron uptake in Pseudoalteromonas sp. strain R3. It is believed that the interaction between SspA and the small nucleotide ppGpp is important for iron to exert regulation functions. However, the roles of ppGpp in iron absorption and prodiginine biosynthesis, and the underlying relationship between ppGpp and SspA in strain R3 remain unclear. In this study, we found that ppGpp accumulation in strain R3 could be induced by limiting iron. In addition, ppGpp not only positively regulated iron uptake and prodiginine biosynthesis via increasing the SspA level but also directly repressed iron uptake and prodiginine biosynthesis independent of SspA, highlighting the finding that ppGpp can stabilize both iron levels and prodiginine production. Notably, the abolishment of ppGpp significantly increased prodiginine production, thus providing a theoretical basis for manipulating prodiginine production in the future. This dynamic ppGpp-mediated interaction between iron uptake and prodiginine biosynthesis has significant implications for understanding the roles of nutrient uptake and secondary metabolism for the survival of bacteria in unfavorable environments.

JEV infection leads to dysfunction of lysosome by downregulating the expression of LAMP1 and LAMP2.

Japanese Encephalitis Virus (JEV), the predominant cause of viral encephalitis in many Asian countries, affects approximately 68,000 people annually. Lysosomes are dynamic structures that regulate cellular metabolism by mediating lysosomal biogenesis and autophagy. Here, we showed that lysosome-associated membrane protein 1 (LAMP1) and LAMP2 were downregulated in cells after JEV infection, resulting in a decrease in the quantity of acidified lysosomes and impaired lysosomal catabolism. What's more, JEV nonstructural protein 4B plays key roles in the reduction of LAMP1/2 via the autophagy-lysosome pathway. JEV NS4B also promoted abnormal aggregation of SLA-DR, an important component of the swine MHC-II molecule family involved in antigen presentation and CD4+ cell activation initiation. Mechanistically, NS4B localized to the ER during JEV infection and interacted with GRP78, leading to the activation of ER stress-mediated autophagy. The 131-204 amino acid (aa) region of NS4B is essential for autophagy induction and LAMP1/2 reduction. In summary, our findings reveal a novel pathway by which JEV induces autophagy and disrupts lysosomal function.