Time transfer over 113†km free space laser communication channel.

The space time frequency transfer plays a crucial role in applications such as space optical clock networks, navigation, satellite ranging, and space quantum communication. Here, we propose a high-precision space time frequency transfer and time synchronization scheme based on a simple intensity modulation/direct detection (IM/DD) laser communication system, which occupies a communication bandwidth of approximately 0.2%. Furthermore, utilizing an optical-frequency comb time frequency transfer system as an out-of-loop reference, experimental verification was conducted on a 113 km horizontal atmospheric link, with a long-term stability approximately 8.3 × 10-16 over a duration of 7800 seconds. Over an 11-hour period, the peak-to-peak wander is approximately 100 ps. Our work establishes the foundation of the time frequency transfer, based on the space laser communication channel, for future ground-to-space and inter-satellite links.

A case report demonstrating the utilization of computer-aided design technology and intramedullary nails for the management of femoral deformity and fracture.

BACKGROUND: To effectively address severe deformities at the fracture site in patients, meticulous preoperative preparation is essential. This involves ensuring the restoration of the normal structural force line of the affected area and prevention of any residual deformities. By utilizing E3D technology prior to surgery, creating models based on individual patient image data and performing osteotomy, the required surgical parameters can be measured, thereby reducing surgical risks and enhancing precision. CASE PRESENTATION: This article documents a case involving a fractured femoral shaft resulting in femoral deformation. In this case, computer-aided design technology was employed for preoperative planning and data measurement to guide the corrective osteotomy and fracture fixation procedures. CONCLUSION: The E3D software utilizes advanced techniques such as customized osteotomy, virtual reduction and internal fixation insertion technology. This enables the software to accurately pre-select the correction of femoral deformities and determine the appropriate specifications and types of internal implants. As a result, the software can create precise, rational, and personalized repair plans tailored to each patient's needs.

T266M variants of ANGPTL4 improve lipid metabolism by modifying their binding affinity to acetyl-CoA carboxylase in obstructive sleep apnea.

BACKGROUND: Angiopoietin-like protein 4 (ANGPTL4) is recognized as a crucial regulator in lipid metabolism. Acetyl-CoA carboxylases (ACACAs) play a role in the ß-oxidation of fatty acids. Yet, the functions of ANGPTL4 and ACACA in dyslipidemia of obstructive sleep apnea (OSA) remain unclear. METHODS: This study included 125 male OSA subjects from the Shanghai Sleep Health Study (SSHS) who were matched for age, body mass index (BMI), and lipid profile. Serum ANGPTL4 levels were measured via ELISA. The ANGPTL4 T266M variants of 4455 subjects along with their anthropometric, fasting biochemical, and standard polysomnographic parameters were collected. Linear regression was used to analyze the associations between quantitative traits and ANGPTL4 T266M. Molecular docking and molecular dynamic simulation were employed to compare the effects of the wild-type ANGPTL4 and its T266M mutation on ACACA. RESULTS: Serum ANGPTL4 levels significantly decreased with increasing OSA severity (non-OSA: 59.6 ± 17.4 ng/mL, mild OSA: 50.0 ± 17.5 ng/mL, moderate OSA: 46.3 ± 15.5 ng/mL, severe OSA: 19.9 ± 14.3 ng/mL, respectively, p = 6.02 × 10-16). No associations were found between T266M and clinical characteristics. Molecular docking indicated that mutant ANGTPL4 T266M had stronger binding affinity for the ACACA protein, compared with wild-type ANGPTL4. In terms of protein secondary structure, mutant ANGTPL4 T266M demonstrated greater stability than wild-type ANGPTL4. CONCLUSIONS: Serum ANGTPL4 levels were significantly decreased in OSA patients, particularly among individuals with severe OSA. Although functional ANGTPL4 T266M variants were not associated with lipid levels in OSA, ANGTPL4 T266M could enhance binding affinity for the ACACA protein, potentially regulating lipid metabolism.

The development of a novel zeolite-based assay for efficient and deep plasma proteomic profiling.

Plasma proteins are considered the most informative source of biomarkers for disease diagnosis and monitoring. Mass spectrometry (MS)-based proteomics has been applied to identify biomarkers in plasma, but the complexity of the plasma proteome and the extremely large dynamic range of protein abundances in plasma make the clinical application of plasma proteomics highly challenging. We designed and synthesized zeolite-based nanoparticles to deplete high-abundance plasma proteins. The resulting novel plasma proteomic assay can measure approximately 3000 plasma proteins in a 45 min chromatographic gradient. Compared to those in neat and depleted plasma, the plasma proteins identified by our assay exhibited distinct biological profiles, as validated in several public datasets. A pilot investigation of the proteomic profile of a hepatocellular carcinoma (HCC) cohort identified 15 promising protein features, highlighting the diagnostic value of the plasma proteome in distinguishing individuals with and without HCC. Furthermore, this assay can be easily integrated with all current downstream protein profiling methods and potentially extended to other biofluids. In conclusion, we established a robust and efficient plasma proteomic assay with unprecedented identification depth, paving the way for the translation of plasma proteomics into clinical applications.

Radiomic signatures associated with tumor immune heterogeneity predict survival in locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma (lrNPC) is limited due to their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in lrNPC. METHODS: This multicenter, retrospective study included 921 patients with lrNPC. A machine learning signature and nomogram based on pretreatment MRI features were developed for predicting overall survival (OS) in a training cohort and validated in two independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index (C-index) and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA sequencing (RNA-seq) analysis. RESULTS: The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving C-indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables significantly improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with significantly distinct OS rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-seq analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. CONCLUSIONS: An MRI-based radiomic signature predicted OS more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for lrNPC patients.

Toxic effect and mRNA mechanism of moon dust simulant induced pulmonary inflammation in rats.

Moon dust presents a significant hazard to manned moon exploration missions, yet our understanding of its toxicity remains limited. The objective of this study is to investigate the pattern and mechanism of lung inflammation induced by subacute exposure to moon dust simulants (MDS) in rats. SD rats were exposed to MDS and silica dioxide through oral and nasal inhalation for 6hours per day continuously for 15 days. Pathological analysis indicated that the toxicity of MDS was lower than that of silica dioxide. MDS led to a notable recruitment and infiltration of macrophages in the rat lungs. Material characterization and biochemical analysis revealed that SiO2, Fe2O3, and TiO2 could be crucial sources of MDS toxicity. The study revealed that MDS-induced oxidative stress response can lead to pulmonary inflammation, which potentially may progress to lung fibrosis. Transcriptome sequencing revealed that MDS suppresses the PI3K-AKT signaling pathway, triggers the Tnfr2 non-classical NF-kB pathway and IL-17 signaling pathway, ultimately causing lung inflammation and activating predominantly antioxidant immune responses. Moreover, the study identified the involvement of upregulated genes IL1b, csf2, and Sod2 in regulating immune responses in rat lungs, making them potential key targets for preventing pulmonary toxicity related to moon dust exposure. These findings are expected to aid in safeguarding astronauts against the hazardous effects of moon dust and offer fresh insights into the implications and mechanisms of moon dust toxicity.

Membranes with Molecular Gatekeepers for Efficient CO2 Capture and H2 Purification.

The urgent need for CO2 capture and hydrogen energy has attracted great attention owing to greenhouse gas emissions and global warming problems. Efficient CO2 capture and H2 purification with membrane technology will reduce greenhouse gas emissions and help reach a carbon-neutral society. Here, 4-sulfocalix[4]arene (SC), which has an intrinsic cavity, was embedded into the Matrimid membrane as a molecular gatekeeper for CO2 capture and H2 purification. The interactions between SC and the Matrimid polymer chains immobilize SC molecules into the interchain gaps of the Matrimid membrane, and the strong hydrogen and ionic bondings were able to form homogeneous mixed-matrix membranes. The incorporation of the SC molecular gatekeeper with exceptional molecular-sieving properties improved the gas separation performance of the mixed-matrix membranes. Compared with that of the Matrimid membrane, the CO2 permeability of the Matrimid-SC-3% membrane increased from 16.75 to 119.78 Barrer, the CO2/N2 selectivity increased from 29.39 to 106.95, and the CO2/CH4 selectivity increased from 29.91 to 140.92. Furthermore, when the permeability of H2 was increased to 172.20 Barrer, the H2/N2 and H2/CH4 selectivities reached approximately 153.75 and 202.59, respectively, which are far superior to those of most existing Matrimid-based materials. The mixed-matrix membranes also exhibited excellent long-term operation stability, with separation performance for several important gas pairs still overtaking the Robeson upper limit after aging for 400 days.

Copper and Copper Complexes in Tumor Therapy.

Copper (Cu), a crucial trace element in physiological processes, has garnered significant interest for its involvement in cancer progression and potential therapeutic applications. The regulation of cellular copper levels is essential for maintaining copper homeostasis, as imbalances can lead to toxicity and cell death. The development of drugs that target copper homeostasis has emerged as a promising strategy for anticancer treatment, with a particular focus on copper chelators, copper ionophores, and novel copper complexes. Recent research has also investigated the potential of copper complexes in cancer therapy.

VLDL and LDL Subfractions Enhance the Risk Stratification of Individuals Who Underwent Epstein-Barr Virus-Based Screening for Nasopharyngeal Carcinoma: A Multicenter Cohort Study.

Serological tests for Epstein-Barr virus (EBV) antibodies have been widely conducted for the screening of nasopharyngeal carcinoma (NPC) in endemic areas. Further risk stratification of NPC can be achieved through plasma lipoprotein and metabolic profiles. A total of 297 NPC patients and 149 EBV-positive participants are enrolled from the NCT03919552 and NCT05682703 cohorts for plasma nuclear magnetic resonance (NMR) metabolomic analysis. Small, dense very low density lipoprotein particles (VLDL-5) and large, buoyant low density lipoprotein particles (LDL-1) are found to be closely associated with nasopharyngeal carcinogenesis. Herein, an NMR-based risk score (NRS), which combines lipoprotein subfractions and metabolic biomarkers relevant to NPC, is developed and well validated within a multicenter cohort. Combining the median cutoff value of the NRS (N50) with that of the serological test for EBV antibodies, the risk stratification model achieves a satisfactory performance in which the area under the curve (AUC) is 0.841 (95% confidence interval: 0.811-0.871), and the positive predictive value (PPV) reaches 70.08% in the combined cohort. These findings not only suggest that VLDL-5 and LDL-1 particles can serve as novel risk factors for NPC but also indicate that the NRS has significant potential in personalized risk prediction for NPC.

The Physiological Basis of Alfalfa Plant Height Establishment.

Plant height plays an important role in crop yield, product quality, and cultivation management. However, the physiological mechanisms that regulate the establishment of plant height in alfalfa plants remain unclear. Herein, we measured plant height traits, leaf characteristics, photosynthetic physiology, cell wall composition, and endogenous hormone contents of tall- and short-stalked alfalfa materials at different reproductive periods. We analyzed the physiology responsible for differences in plant height. The results demonstrated that the number of internodes in tall- and short-stalked alfalfa materials tended to converge with the advancement of the fertility period. Meanwhile, the average internode length (IL) of tall-stalked materials was significantly higher than that of short-stalked materials at different fertility periods, with internode length identified as the main trait determining the differences in alfalfa plant height. Leaf characteristics, which are closely related to photosynthetic capacity, are crucial energy sources supporting the expression of plant height traits, and we found that an increase in the number of leaves contributed to a proportional increase in plant height. Additionally, a significant positive correlation was observed between plant height and leaf dry weight per plant during the branching and early flowering stages of alfalfa. The leaves of alfalfa affect plant height through photosynthesis, with the budding stage identified as the key period for efficient light energy utilization. Plant height at the budding stage showed a significant positive correlation with soluble sugar (SS) content and a significant negative correlation with intercellular CO2 concentration. Moreover, we found that alfalfa plant height was significantly correlated with the contents of indole-3-acetic acid in stem tips (SIAA), gibberellin A3 in leaves (LGA3), zeatin in stem tips (SZT), and abscisic acid in leaves (LABA). Further investigation revealed that SS, SIAA, and LGA3 contents were important physiological indicators affecting alfalfa plant height. This study provides a theoretical basis for understanding the formation of alfalfa plant height traits and for genetic improvement studies.

Exploring the influence of microstructure and phospholipid type of liposomes on their interaction with lung.

Liposome is a promising carrier for pulmonary drug delivery and the nano-sized liposomes have been widely investigated in the treatment of lung diseases. However, there still lack the knowledge of micron-sized liposomes for lung delivery, which have more advantages in terms of drug loading and sustained drug release capacity. The micron-sized liposomes can be classified into multilamellar liposome (MLL) and multivesicular liposome (MVL) according to their microstructure, thus, this study focused on exploring how the micron-sized liposomes with different microstructure and phospholipid composition influence their interaction with the lung. The MLL and MVL were prepared from different types of phospholipids (including soya phosphatidylcholine (SPC), egg yolk phosphatidylcholine (EPC), and dipalmitoyl phosphatidylcholine (DPPC)) with geometric diameter around 5 µm, and their in vitro pulmonary cell uptake, in vivo lung retention and organ distribution were investigated. The results showed that the microstructure of liposomes didn't affect pulmonary cellular uptake, in vivo lung retention and organ distribution. MLL and MVL prepared with the same phospholipid had similar cellular uptake in both NR8383 cells and A549 cells, and both of them possessed prolonged lung retention and limited distribution in other organs during 72 h. Notably, the phospholipid type presented remarkable influence on liposomes' interaction with the lung. SPC-based liposomes exhibited higher cellular uptake than the DPPC-based ones in both NR8383 cells and A549 cells, also possessed a better lung retention behavior. In conclusion, this study might provide theoretical knowledge for designing micron-sized liposomes intended for lung delivery.

Enhanced brain distribution of Ginsenoside F1 via intranasal administration in combination with absorption enhancers.

Ginsenoside F1 (GF1) is a potential drug candidate for the treatment of Alzheimer's disease. Nevertheless, its low oral bioavailability and poor solubility limit clinical application. By utilizing either a direct or indirect approach, intranasal administration is a non-invasive drug delivery method that can deliver drugs to the brain rapidly. But large molecule drug delivered to the brain through intranasal administration may be insufficient to reach required concentration for therapeutic effect. In this study, using GF1 as a model drug, the feasibility of intranasal administration in combination with absorption enhancers to increase brain distribution of GF1 was explored. First of all, the appropriate absorption enhancers were screened by in situ nasal perfusion study. GF1-HP-ß-CD inclusion complex was prepared and characterized. Thereafter, in vivo absorption of GF1 after intranasal or intravenous administration of its inclusion complex with/without absorption enhancers was investigated, and safety of the formulations was evaluated. The results showed that 2% Solutol HS 15 was a superior absorption enhancer. HP-ß-CD inclusion complex improved GF1 solubility by 150 fold. Following intranasal delivery, the absolute bioavailability of inclusion complex was 46%, with drug brain targeting index (DTI) 247% and nose-to-brain direct transport percentage (DTP) 58%. Upon further addition of 2% Solutol HS 15, the absolute bioavailability was increased to 75%, with DTI 315% and DTP 66%. Both nasal cilia movement and biochemical substances (total protein and lactate dehydrogenase) leaching studies demonstrated 2% Solutol HS 15 was safe to the nasal mucosa. In conclusion, intranasal administration combining with safe absorption enhancers is an effective strategy to enhance drug distribution in the brain, showing promise for treating disorders related to the central nervous system.

Association between multiple sleep dimensions in obstructive sleep apnea and the early sign of atherosclerosis.

STUDY OBJECTIVES: We investigated the associations between multiple sleep dimensions in obstructive sleep apnea (OSA) and carotid intima-media thickness (CIMT), an early sign of atherosclerosis, in subjects from the Shanghai Sleep Health Study (SSHS). METHODS: We performed secondary analysis of SSHS in a group of subjects performed the ultrasound evaluation from 2018 to 2022. Multiple sleep dimensions were measured using standard polysomnography. CIMT was measured from ultrasound images as an early sign of atherosclerosis. Multivariable-adjusted linear regression and logistic regression analyses were performed to detect associations between sleep traits in OSA and CIMT. RESULTS: CIMT was found to increase with increasing severity of OSA (P < 0.001). When adjusted for conventional risk factors, microarousal index (MAI) and hypoxic burden (HB) were positively correlated with CIMT while slow wave sleep (SWS) and mean apnea-hypopnea event duration (MAHD) showed negative correlation with CIMT (all P < 0.01). In binary logistic regression analysis, participants with high MAI, less SWS, higher HB and shorter MAHD showed a higher prevalence of thick CIMT with no evidence of interaction by age, sex, or body mass index (P-interaction > 0.05). CONCLUSIONS: Subjects with more severe sleep fragmentation, more severe hypoxemia and increased arousability were more likely to have increased CIMT after adjusting for potential confounders. It is important to evaluate novel indices of sleep fragmentation, hypoxemia and arousability in OSA for early detection and prevention of cardiovascular disease, including stroke. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry; URL: http://www.chictr.org.cn/showproj.aspx?proj=43057; No. ChiCTR1900025714.

Heterogeneity of work alienation and its relationship with job embeddedness among Chinese nurses: a cross-sectional study using latent profile analysis.

OBJECTIVE: To identify the distinct profiles of work alienation among Chinese nurses, examine the demographic factors associated with profile memberships, and then explore the relationship between latent categories of work alienation and job embeddedness. METHODS: A cross-sectional survey of 523 nurses was conducted from July to August 2023. Latent profile analysis (LPA) was performed to identify distinct profiles of nurses based on three aspects: powerlessness, helplessness, and meaningfulness. A multinomial logistic regression analysis was conducted to explore the predictors of profile membership. Hierarchical regression analysis was carried out to examine the association between profile memberships and job embeddedness. RESULTS: Three subgroups of work alienation of nurses were identified: 23.1%, 57.8%, and 19.1% in the low work alienation group (profile 1), the moderate work alienation group (profile 3), and the high work alienation group (profile 2), respectively. Nurses with college degrees were more likely to be grouped into moderate work alienation. Nurses who did not work night shifts were more likely to have low or moderate levels of work alienation. Nurses earning 2,000-3,000 and 3,001-5,000 yuan per month were likely to be in the low work alienation group. The different categories of work alienation significantly predicted job embeddedness among nurses (ΔR2 = 0.103, p < 0.001). CONCLUSIONS: Work alienation has an important impact on clinical nurses' job embeddedness. Nursing managers should pay attention to the differences in individual work alienation status and adopt reasonable management strategies to improve the level of job embeddedness, ensure the quality of care, and reduce nursing turnover.

A Survey of 6DoF Object Pose Estimation Methods for Different Application Scenarios.

Recently, 6DoF object pose estimation has become increasingly important for a broad range of applications in the fields of virtual reality, augmented reality, autonomous driving, and robotic operations. This task involves extracting the target area from the input data and subsequently determining the position and orientation of the objects. In recent years, many new advances have been made in pose estimation. However, existing reviews have the problem of only summarizing category-level or instance-level methods, and not comprehensively summarizing deep learning methods. This paper will provide a comprehensive review of the latest progress in 6D pose estimation to help researchers better understanding this area. In this study, the current methods about 6DoF object pose estimation are mainly categorized into two groups: instance-level and category-level groups, based on whether it is necessary to acquire the CAD model of the object. Recent advancements about learning-based 6DoF pose estimation methods are comprehensively reviewed. The study systematically explores the innovations and applicable scenarios of various methods. It provides an overview of widely used datasets, task metrics, and diverse application scenarios. Furthermore, state-of-the-art methods are compared across publicly accessible datasets, taking into account differences in input data types. Finally, we summarize the challenges of current tasks, methods for different applications, and future development directions.

Enhanced YOLOv5s-Based Algorithm for Industrial Part Detection.

In complex industrial environments, accurate recognition and localization of industrial targets are crucial. This study aims to improve the precision and accuracy of object detection in industrial scenarios by effectively fusing feature information at different scales and levels, and introducing edge detection head algorithms and attention mechanisms. We propose an improved YOLOv5-based algorithm for industrial object detection. Our improved algorithm incorporates the Crossing Bidirectional Feature Pyramid (CBiFPN), effectively addressing the information loss issue in multi-scale and multi-level feature fusion. Therefore, our method can enhance detection performance for objects of varying sizes. Concurrently, we have integrated the attention mechanism (C3_CA) into YOLOv5s to augment feature expression capabilities. Furthermore, we introduce the Edge Detection Head (EDH) method, which is adept at tackling detection challenges in scenes with occluded objects and cluttered backgrounds by merging edge information and amplifying it within the features. Experiments conducted on the modified ITODD dataset demonstrate that the original YOLOv5s algorithm achieves 82.11% and 60.98% on mAP@0.5 and mAP@0.5:0.95, respectively, with its precision and recall being 86.8% and 74.75%, respectively. The performance of the modified YOLOv5s algorithm on mAP@0.5 and mAP@0.5:0.95 has been improved by 1.23% and 1.44%, respectively, and the precision and recall have been enhanced by 3.68% and 1.06%, respectively. The results show that our method significantly boosts the accuracy and robustness of industrial target recognition and localization.

Role of Preoperative Albumin Quotient in Surgical Planning for Posttraumatic Syringomyelia: A Comparative Cohort Study.

OBJECTIVE: Surgical procedures for patients with posttraumatic syringomyelia (PTS) remain controversial. Until now, there have been no effective quantitative evaluation methods to assist in selecting appropriate surgical plans before surgery. METHODS: We consecutively enrolled PTS patients (arachnoid lysis group, n = 42; shunting group, n = 14) from 2003 to 2023. Additionally, 19 intrathecal anesthesia patients were included in the control group. All patients with PTS underwent physical and neurological examinations and spinal magnetic resonance imaging preoperatively, 3-12 months postoperatively and during the last follow-up. Preoperative lumbar puncture was performed and blood-spinal cord barrier disruption was detected by quotient of albumin (Qalb, cerebrospinal fluid/serum). RESULTS: The ages (p = 0.324) and sex (p = 0.065) of the PTS and control groups did not differ significantly. There were also no significant differences in age (p = 0.216), routine blood data and prognosis (p = 0.399) between the arachnoid lysis and shunting groups. But the QAlb level of PTS patients was significantly higher than that of the control group (p < 0.001), and the shunting group had a significantly higher QAlb (p < 0.001) than the arachnoid lysis group. A high preoperative QAlb (odds ratio, 1.091; 95% confidence interval, 1.004-1.187; p = 0.041) was identified as the predictive factor for the shunting procedure, with the receiver operating characteristic curve showing 100% specificity and 80.95% sensitivity for patients with a QAlb > 12.67. CONCLUSION: Preoperative QAlb is a significant predictive factor for the types of surgery. For PTS patients with a QAlb > 12.67, shunting represents the final recourse, necessitating the exploration and development of novel treatments for these patients.

Clinical heterogeneity and five phenotypes identified in pediatric Behçet's syndrome: a cohort study from Shanghai Behçet's syndrome database.

OBJECTIVES: Behçet's syndrome (BS) is a rare disease of unknown etiology, with limited reports especially in pediatric BS. The clinical characteristics and phenotypes of pediatric BS as a highly heterogeneous variable vessel vasculitis were investigated in this study. METHODS: A cross-sectional study was conducted to compare clinical variables and descriptive characteristics of BS by age of onset and gender. Cluster analysis was then performed to identify the phenotypes of pediatric BS. RESULTS: A total of 2082 BS patients were included in this study, 1834 adults and 248 children. Compared with adult-onset BS, pediatric BS had a higher incidence of folliculitis [relative risks (RR) and 95% confidence interval (CI) 1.3 (1.0-1.5)], uveitis of the left eye [RR and 95% CI 2.3 (1.0-5.0)], intestinal ulcer complications [RR and 95% CI 2.1 (1.1-4.2)], pericarditis [RR and 95% CI 2.5 (1.0-6.2)], and psychiatric disorders [RR and 95% CI 2.8(1.0-7.9)], while the incidence of thrombocytopenia was lower [RR 0.2 (0.1-1.0)]. Among pediatric BS, females had more genital ulcers, while males were more likely to have skin lesions, panuveitis, vascular involvement, venous lesions, cardiac involvement, and aortic aneurysms. Cluster analysis classified pediatric BS into five clusters (C1-C5): C1 (n = 61, 24.6%) showed gastrointestinal (GI) involvement; C2 (n = 44, 17.7%) was the central nervous system (CNS) type where 23 cases overlapped joint involvement; in C3 (n = 35, 14.1%), all patients presented with arthritis or arthralgia; all patients in C4 (n = 29, 11.7%) manifested ocular involvement, with a few patients overlapping with GI involvement or joint damage; C5 (n = 79, 31.9%) was the mucocutaneous type, presenting both oral ulcers, genital ulcers, and skin lesions. CONCLUSIONS: The clinical features of pediatric and adult BS differ significantly. Male and female pediatric BS also have a distinct demography. Five phenotypes including GI, CNS, joint, ocular, and mucocutaneous types were identified for pediatric BS.

The Protein Scaffolding Functions of Polyphosphate.

Inorganic polyphosphate (polyP), one of the first high-energy compound on earth, defies its extreme compositional and structural simplicity with an astoundingly wide array of biological activities across all domains of life. However, the underlying mechanism of such functional pleiotropy remains largely elusive. In this review, we will summarize recent studies demonstrating that this simple polyanion stabilizes protein folding intermediates and scaffolds select native proteins. These functions allow polyP to act as molecular chaperone that protects cells against protein aggregation, as pro-amyloidogenic factor that accelerates both physiological and disease-associated amyloid formation, and as a modulator of liquid-liquid phase separation processes. These activities help to explain polyP's known roles in bacterial stress responses and pathogenicity, provide the mechanistic foundation for its potential role in human neurodegenerative diseases, and open a new direction regarding its influence on gene expression through condensate formation. We will highlight critical unanswered questions and point out potential directions that will help to further understand the pleiotropic functions of this ancient and ubiquitous biopolymer.