Case report: Exploring the utility of whole-body bone scintigraphy for pediatric Langerhans cell histiocytosis: insights from clinical practice.

Purpose: This mini-review delves into the realm of Langerhans cell histiocytosis (LCH) in children, focusing on its skeletal involvement. By synthesizing pertinent literature, we sought to provide a comprehensive understanding of LCH's clinical and radiographic spectrum. Our study then demonstrates the diagnostic prowess of whole-body 99mTc-methyl diphosphonate (MDP) scintigraphy in LCH cases, underscoring its value in tandem with existing knowledge. Methods: Our approach involved an extensive literature review that contextualized LCH within the current medical landscape. Subsequently, we presented a case series featuring five pediatric instances of skeletal LCH, one accompanied by soft tissue infiltration. The principal aim was to illuminate the diagnostic and staging potential of whole-body 99mTc-MDP scintigraphy, augmenting existing insights. Results: Through meticulous literature synthesis, we highlighted pediatric LCH's protean clinical manifestations and radiological variability. Aligning with this spectrum, our case series underscored the role of 99mTc-MDP scintigraphy in diagnosing and staging LCH. Among the five pediatric cases, one demonstrated concurrent soft tissue involvement. This aligns with the multifaceted nature of LCH presentations. Conclusion: Pediatric LCH can present with a wide range of clinical and radiologic features. By amalgamating our cases with extant literature, we stress the necessity of a multimodal strategy. 99mTc-MDP scintigraphy emerged as an indispensable tool for accurate staging and soft tissue detection. Our findings collectively advocate for a holistic approach to managing LCH, ensuring informed therapeutic decisions for optimal patient outcomes.

Na2CO3-responsive mechanism insight from quantitative proteomics and SlRUB gene function in Salix linearistipularis seedlings.

Mongolian willow (Salix linearistipularis) is a naturally occurring woody dioecious plant in the saline soils of north-eastern China, which has a high tolerance to alkaline salts. Although transcriptomics studies have identified a large number of salinity-responsive genes, the mechanism of salt tolerance in Mongolian willow is not clear. Here, we found that in response to Na2CO3 stress, Mongolian willow regulates osmotic homeostasis by accumulating proline and soluble sugars and scavenges reactive oxygen species (ROS) by antioxidant enzymes and non-enzymatic antioxidants. Our quantitative proteomics study identified 154 salt-sensitive proteins mainly involved in maintaining the stability of the photosynthetic system and ROS homeostasis to cope with Na2CO3 stress. Among them, Na2CO3-induced rubredoxin (RUB) was predicted to be associated with 122 proteins for the modulation of these processes. The chloroplast-localized S. linearistipularis rubredoxin (SlRUB) was highly expressed in leaves and was significantly induced under Na2CO3 stress. Phenotypic analysis of overexpression, mutation and complementation materials of RUB in Arabidopsis suggests that SlRUB is critical for the regulation of photosynthesis, ROS scavenging and other metabolisms in the seedlings of Mongolian willow to cope with Na2CO3 stress. This provides more clues to better understand the alkali-responsive mechanism and RUB functions in the woody Mongolian willow.

Artificial Light for Improving Tomato Recovery Following Grafting: Transcriptome and Physiological Analyses.

Grafting is widely used to enhance the phenotypic traits of tomatoes, alleviate biotic and abiotic stresses, and control soil-borne diseases of the scion in greenhouse production. There are many factors that affect the healing and acclimatization stages of seedlings after grafting. However, the role of light has rarely been studied. In this study, we compared the effects of artificial light and traditional shading (under shaded plastic-covered tunnels) on the recovery of grafted tomato seedlings. The results show that the grafted tomato seedlings recovered using artificial light had a higher healthy index, leaf chlorophyll content, shoot dry weight, and net photosynthetic rate (Pn) and water use efficiency (WUE) compared with grafted seedling recovered using the traditional shading method. Transcriptome analysis showed that the differentially expressed genes (DEGs) of grafted seedlings restored using artificial light were mainly enriched in the pathways corresponding to plant hormone signal transduction. In addition, we measured the endogenous hormone content of grafted tomato seedlings. The results show that the contents of salicylic acid (SA) and kinetin (Kin) were significantly increased, and the contents of indoleacetic acid (IAA) and jasmonic acid (JA) were decreased in artificial-light-restored grafted tomato seedlings compared with those under shading treatments. Therefore, we suggest that artificial light affects the morphogenesis and photosynthetic efficiency of grafted tomato seedlings, and it can improve the performance of tomato seedlings during grafting recovery by regulating endogenous hormone levels.

Integrated Secondary Metabolomic and Antioxidant Ability Analysis Reveals the Accumulation Patterns of Metabolites in Momordica charantia L. of Different Cultivars.

Bitter gourd (Momordica charantia L.) contains rich bioactive ingredients and secondary metabolites; hence, it has been used as medicine and food product. This study systematically quantified the nutrient contents, the total content of phenolic acids (TPC), flavonoids (TFC), and triterpenoids (TTC) in seven different cultivars of bitter gourd. This study also estimated the organic acid content and antioxidative capacity of different cultivars of bitter gourd. Although the TPC, TFC, TTC, organic acid content, and antioxidative activity differed significantly among different cultivars of bitter gourd, significant correlations were also observed in the obtained data. In the metabolomics analysis, 370 secondary metabolites were identified in seven cultivars of bitter gourd; flavonoids and phenolic acids were significantly more. Differentially accumulated metabolites identified in this study were mainly associated with secondary metabolic pathways, including pathways of flavonoid, flavonol, isoflavonoid, flavone, folate, and phenylpropanoid biosyntheses. A number of metabolites (n = 27) were significantly correlated (positive or negative) with antioxidative capacity (r ≥ 0.7 and p < 0.05). The outcomes suggest that bitter gourd contains a plethora of bioactive compounds; hence, bitter gourd may potentially be applied in developing novel molecules of medicinal importance.

Effects of Light Intensity on Growth and Quality of Lettuce and Spinach Cultivars in a Plant Factory.

The decreased quality of leafy vegetables and tipburn caused by inappropriate light intensity are serious problems faced in plant factories, greatly reducing the economic benefits. The purpose of this study was to comprehensively understand the impact of light intensity on the growth and quality of different crops and to develop precise lighting schemes for specific cultivars. Two lettuce (Lactuca sativa L.) cultivars-Crunchy and Deangelia-and one spinach (Spinacia oleracea L.) cultivar-Shawen-were grown in a plant factory using a light-emitting diode (LED) under intensities of 300, 240, 180, and 120 µmol m-2 s-1, respectively. Cultivation in a solar greenhouse using only natural light (NL) served as the control. The plant height, number of leaves, and leaf width exhibited the highest values under a light intensity of 300 µmol m-2 s-1 for Crunchy. The plant width and leaf length of Deangelia exhibited the smallest values under a light intensity of 300 µmol m-2 s-1. The fresh weight of shoot and root, soluble sugar, soluble protein, and ascorbic acid contents in the three cultivars increased with the increasing light intensity. However, tipburn was observed in Crunchy under 300 µmol m-2 s-1 light intensity, and in Deangelia under both 300 and 240 µmol m-2 s-1 light intensities. Shawen spinach exhibited leaf curling under all four light intensities. The light intensities of 240 and 180 µmol m-2 s-1 were observed to be the most optimum for Crunchy and Deangelia (semi-heading lettuce variety), respectively, which would exhibit relative balance growth and morphogenesis. The lack of healthy leaves in Shawen spinach under all light intensities indicated the need to comprehensively optimize cultivation for Shawen in plant factories to achieve successful cultivation. The results indicated that light intensity is an important factor and should be optimized for specific crop species and cultivars to achieve healthy growth in plant factories.

Numerical investigation of the cavitation bubble near the solid wall with a gas-entrapping hole based on a fully compressible three-phase model.

The solid surface with several cavities containing gas strongly influences the bubble's dynamical behaviors. To reveal the underlying physical mechanism of the cavitation bubble near a rigid boundary with a gas-entrapping hole, a fully compressible three-phase model, accounting for the three-phase volume transport equation, was implemented in OpenFOAM. The predicted bubble shape was validated with the corresponding experimental photos, and good agreement was achieved. The bubble's primary physical features (e.g., the expanding shock wave, upward and downward liquid jet, and high-pressure region) are well reproduced, which helps understand the underlying mechanisms. The numerical results show that the solid wall with a gas-entrapping hole could affect the morphology of both the bubble and liquid jet, as well as shortens the bubble's first oscillation period in comparison to an intact rigid wall. The relationship among the prolongation factor, the standoff distance, and the relative size ratio is analyzed. It is found the prolongation factor increases as the relative size ratio decrease. As the standoff distance decreases, the gas entrapping hole plays a significant role in the oscillation period of the bubble. The current model can be further extended to reveal the microscopic mechanism of aeration avoiding cavitation damage and investigate the interaction between air bubbles and cavitation bubbles, which is of great interest to practical applications.

Cysteine-rich receptor-like protein kinases: emerging regulators of plant stress responses.

Cysteine-rich receptor-like kinases (CRKs) belong to a large DUF26-containing receptor-like kinase (RLK) family. They play key roles in immunity, abiotic stress response, and growth and development. How CRKs regulate diverse processes is a long-standing question. Recent studies have advanced our understanding of the molecular mechanisms underlying CRK functions in Ca2+ influx, reactive oxygen species (ROS) production, mitogen-activated protein kinase (MAPK) cascade activation, callose deposition, stomatal immunity, and programmed cell death (PCD). We review the CRK structure-function relationship with a focus on the roles of CRKs in immunity, the abiotic stress response, and the growth-stress tolerance tradeoff. We provide a critical analysis and synthesis of how CRKs control sophisticated regulatory networks that determine diverse plant phenotypic outputs.

A multicenter retrospective analysis of the clinical outcome following endovascular treatment of extremity arteriovenous malformation.

BACKGROUND: The arteriovenous malformation (AVM) represents a complicated pathology with high recurrence risk. This study aimed at reporting the clinical outcome of embolotherapy in treating extremity AVMs and exploring the potential risk factors for the recurrence of the lesion. METHODS: A multicenter retrospective review of the electronic medical records database was performed to enroll extremity AVM cases. Based on the follow-up findings, patients were allocated into the recurrence group and non-recurrence group. Univariable comparisons were performed to find relevant factors for AVM recurrence, then each potential factor was assessed by Kaplan-Meier analysis to determine whether it could influence the time-dependent recurrence possibility. RESULTS: Between January 2010 and December 2020, we screened 339 cases and enrolled 35 patients (24 male, average age: 45.23±17.57 years). During an average follow-up period of 5.91±3.22 months, recurrence of AVM was found in 18 cases. Univariable analysis documented type IIIb AVM and previous surgical attempts potentially indicated a high recurrence possibility, whereas type II, application of coil and ethanol during the intervention, as well as optimal embolization might be helpful to control the pathology. Of these relevant factors, further Kaplan-Meier analysis found that previous surgical attempts (P=0.002), application of ethanol (P=0.015), AVM type II (P=0.048), and IIIb (P=0.030) might have a significant impact on recurrence probability. CONCLUSIONS: Previous surgical attempts might increase the recurrence risk after embolotherapy of the AVM, whereas using ethanol as the embolic agent seems to contribute to a lower recurrence probability. Type II AVM may respond better to embolization than type IIIb.

A novel urokinase plasminogen activator receptor-targeted peptide-based probe for in-vivo molecular imaging of glioblastoma.

AIM: The urokinase plasminogen activator receptor (uPAR) is a promising biomarker for cancer diagnosis and therapy. We herein fabricated a new type of uPAR-targeted imaging probe Al18F-NOTA-VC and preliminarily evaluated its potential application in PET imaging of the glioma model in vivo. METHODS: Peptide VC was synthesized and identified by MALDI-TOF-MS. The IC50 between VC/precursor NOTA-VC and uPAR was then determined before the synthesis and purification of Al18F-NOTA-VC, followed by further studies of in-vitro properties of Al18F-NOTA-VC. Meanwhile, the AE105-based probe followed a similar procedure in-vitro test. Finally, the PET imaging properties, including uPAR-targeting ability and the metabolism of Al18F-NOTA-VC, were investigated. RESULTS: The VC and NOTA-VC were obtained successfully and demonstrated a good affinity with uPAR. Followed by Al18F labeling successfully, excellent properties, including the serum stability, water solubility, and specificity of Al18F-NOTA-VC, were obtained in-vitro test compared with AE105 based probe. An excellent tumor uptake and renal excretion data of Al18F-NOTA-VC were acquired from in-vivo U87MG tumor model PET imaging, consistent with the subsequent biodistribution study. CONCLUSION: In addition to the excellent specificity and high tumor/normal tissue contrast for uPAR-targeted PET imaging of U87MG tumor, Al18F-NOTA-VC possessed promising clearance ability by renal system route. These excellent properties facilitated Al18F-NOTA-VC to be a promising imaging agent for uPAR high-expressing tumors and, thus, provided a paradigm for developing peptide-based probes for uPAR-associated disease diagnosis.

A simplified model for the gas-vapor bubble dynamics.

This paper presents a full numerical model accounting for the heat transfer and phase-change by combining the modified Keller-Miksis equation with the second order term of compressibility of liquid, partial differential equations (PDEs), and Hertz-Knudsen-Langmuir equation. Then, a simplified model for studying the dynamics of the cavitation bubble or bubble excited by the acoustic waves is proposed. The major contribution is to simplify the full model with PDEs to a set of coupled ordinary differential equations (ODEs). Specifically, two energy PDEs are converted to three ODEs by coupling the boundary conditions. The comparison among the full model and other simplified models is used to validate the accuracy and superiority of the simplified model, from which the application range of the proposed simplified model can be determined.

Development and Evaluation of a Peptide Heterodimeric Tracer Targeting CXCR4 and Integrin αvß3 for Pancreatic Cancer Imaging.

Nowadays, pancreatic cancer is still a formidable disease to diagnose. The CXC chemokine receptor 4 (CXCR4) and integrin αvß3 play important roles in tumor development, progression, invasion, and metastasis, which are overexpressed in many types of human cancers. In this study, we developed a heterodimeric tracer 68Ga-yG5-RGD targeting both CXCR4 and integrin αvß3, and evaluated its feasibility and utility in PET imaging of pancreatic cancer. The 68Ga-yG5-RGD could accumulate in CXCR4/integrin αvß3 positive BxPC3 tumors in a high concentration and was much higher than that of 68Ga-yG5 (p < 0.001) and 68Ga-RGD (p < 0.001). No increased uptake of 68Ga-yG5-RGD was found in MX-1 tumors (CXCR4/integrin αvß3, negative). In addition, the uptake of 68Ga-yG5-RGD in BxPC3 was significantly blocked by excess amounts of AMD3100 (an FDA-approved CXCR4 antagonist) and/or unlabeled RGD (p < 0.001), confirming its dual-receptor targeting properties. The ex vivo biodistribution and immunohistochemical results were consistent with the in vivo imaging results. The dual-receptor targeting strategy achieved improved tumor-targeting efficiency and prolonged tumor retention in BxPC3 tumors, suggesting 68Ga-yG5-RGD is a promising tracer for the noninvasive detection of tumors that express either CXCR4 or integrin αvß3 or both, and therefore may have good prospects for clinical translation.

Evaluation of a CD13 and Integrin αvß3 Dual-Receptor Targeted Tracer 68Ga-NGR-RGD for Ovarian Tumor Imaging: Comparison With 18F-FDG.

Ovarian cancer has the highest mortality rate of gynecologic malignancy. 18F-FDG positron emission tomography (PET) adds an important superiority over traditional anatomic imaging modalities in oncological imaging but has drawbacks including false negative results at the early stage of ovarian cancer, and false positives when inflammatory comorbidities are present. Aminopeptidase N (APN, also known as CD13) and integrin αvß3 are two important targets overexpressed on tumor neo-vessels and frequently on ovarian cancerous cells. In this study, we used subcutaneous and metastatic models of ovarian cancer and muscular inflammation models to identify 68Ga-NGR-RGD, a heterodimeric tracer consisting of NGR and RGD peptides targeting CD13 and integrin αvß3, respectively, and compared it with 18F-FDG. We found that 68Ga-NGR-RGD showed greater contrast in SKOV3 and ES-2 tumors than 18F-FDG. Low accumulation of 68Ga-NGR-RGD but avid uptake of 18F-FDG were observed in inflammatory muscle. In abdominal metastasis models, PET imaging with 68Ga-NGR-RGD allowed for rapid and clear delineation of both peritoneal and liver metastases (3-6 mm), whereas, 18F-FDG could not distinguish the metastasis lesions due to the relatively low metabolic activity in tumors and the interference of intestinal physiological 18F-FDG uptake. Due to the high tumor-targeting efficacy, low inflammatory uptake, and higher tumor-to-background ratios compared to that of 18F-FDG, 68Ga-NGR-RGD presents a promising imaging agent for diagnosis, staging, and follow-up of ovarian tumors.

Genome-wide identification and expression analysis reveals spinach brassinosteroid-signaling kinase (BSK) gene family functions in temperature stress response.

BACKGROUND: Brassinosteroid (BR)- signaling kinase (BSK) is a critical family of receptor-like cytoplasmic kinase for BR signal transduction, which plays important roles in plant development, immunity, and abiotic stress responses. Spinach (Spinacia oleracea) is cold- tolerant but heat- sensitive green leafy vegetable. A study on BSK family members and BSKs- mediated metabolic processes in spinach has not been performed. RESULTS: We identified and cloned seven SoBSKs in spinach. Phylogenetic and collinearity analyses suggested that SoBSKs had close relationship with dicotyledonous sugar beet (Beta vulgaris) rather than monocotyledons. The analyses of gene structure and conserved protein domain/ motif indicated that most SoBSKs were relative conserved, while SoBSK6 could be a truncated member. The prediction of post-translation modification (PTM) sites in SoBSKs implied their possible roles in signal transduction, redox regulation, and protein turnover of SoBSKs, especially the N-terminal myristoylation site was critical for BSK localization to cell periphery. Cis-acting elements for their responses to light, drought, temperature (heat and cold), and hormone distributed widely in the promoters of SoBSKs, implying the pivotal roles of SoBSKs in response to diverse abiotic stresses and phytohormone stimuli. Most SoBSKs were highly expressed in leaves, except for SoBSK7 in roots. Many SoBSKs were differentially regulated in spinach heat- sensitive variety Sp73 and heat- tolerant variety Sp75 under the treatments of heat, cold, as well as exogenous brassinolide (BL) and abscisic acid (ABA). The bsk134678 mutant Arabidopsis seedlings exhibited more heat tolerance than wild- type and SoBSK1- overexpressed seedlings. CONCLUSIONS: A comprehensive genome- wide analysis of the BSK gene family in spinach presented a global identification and functional prediction of SoBSKs. Seven SoBSKs had relatively- conserved gene structure and protein function domains. Except for SoBSK6, all the other SoBSKs had similar motifs and conserved PTM sites. Most SoBSKs participated in the responses to heat, cold, BR, and ABA. These findings paved the way for further functional analysis on BSK- mediated regulatory mechanisms in spinach development and stress response.

Pto Interaction Proteins: Critical Regulators in Plant Development and Stress Response.

Pto interaction (Pti) proteins are a group of proteins that can be phosphorylated by serine/threonine protein kinase Pto, which have diverse functions in plant development and stress response. In this study, we analyzed the phylogenetic relationship, gene structure, and conserved motifs of Pti1s and predicted the potential cis-elements in the promoters of Pti1 genes using bioinformatics methods. Importantly, we systematically summarized the diverse functions of Pti1s in tomato, rice, Arabidopsis, potato, apple, and cucumber. The potential cis-elements in promoters of Pti1s decide their functional diversity in response to various biotic and abiotic stresses. The protein kinase Pti1 was phosphorylated by Pto and then modulated the downstream signaling pathways for PTI and ETI in the disease insistence process. In addition, some transcription factors have been defined as Ptis (e.g., Pti4, Pti5, and Pti6) originally, which actually were ethylene-response factors (ERFs). Pti4, Pti5, and Pti6 were modulated by salicylic acid (SA), jasmonate (JA), and ethylene signaling pathways and regulated diverse defense-related gene expression to cope with Pst infection and insect wounding.

Protein disulfide isomerase modulation of TRPV1 controls heat hyperalgesia in chronic pain.

Protein disulfide isomerase (PDI) plays a key role in maintaining cellular homeostasis by mediating protein folding via catalyzing disulfide bond formation, breakage, and rearrangement in the endoplasmic reticulum. Increasing evidence suggests that PDI can be a potential treatment target for several diseases. However, the function of PDI in the peripheral sensory nervous system is unclear. Here we report the expression and secretion of PDI from primary sensory neurons is upregulated in inflammatory and neuropathic pain models. Deletion of PDI in nociceptive DRG neurons results in a reduction in inflammatory and neuropathic heat hyperalgesia. We demonstrate that secreted PDI activates TRPV1 channels through oxidative modification of extracellular cysteines of the channel, indicating that PDI acts as an unconventional positive modulator of TRPV1. These findings suggest that PDI in primary sensory neurons plays an important role in development of heat hyperalgesia and can be a potential therapeutic target for chronic pain.

Endovascular treatment of complicated aortic aneurysms using a modified flow-diverting strategy: Mid- to long-term outcome from a multicenter cohort study.

OBJECTIVES: Frequently reported adverse events following flow-diverting stents' treatment of aortic aneurysms indicate further refinements of this technique are required. This study aims at evaluating the clinical efficacy of an improved flow-diverting strategy. METHODS: A modified flow-diverting procedure was utilized in selected patients, in which stent-grafts were used to cover the non-branched segment of the aneurysmal lesion while flow-diverting multilayered bare metal stents were applied to cover the reno-visceral segment. The safety and efficacy of this joint procedure were assessed by regular follow-up. RESULTS: We screened 497 patients and included 67 cases (mean age: 67.07 ± 12.14 years; 53 males) between February 2012 and March 2018. The median number of stent-grafts and bare metal stents used in the procedure were 1 (range: 1 to 3) and 3 (range: 2 to 4), respectively. During a mean follow-up period of 34.54 ± 20.28 months, aneurysm maximum diameter decreased from 64.79 ± 10.31 to 59.32 ± 10.20 mm (p = 0.002), while sac thrombosis ratio increased from 26.01±10.99% to 98.46±4.84% (p<0.001). Aneurysm-related death or conversion to open repair was documented in three patients. The majority side-branches (198/201) remained patent during follow-up. Overall clinical success rate reached 91.04% (61/67). CONCLUSIONS: The joint procedure is characterized by significant aneurysm thrombosis along with high aneurysm stabilization/shrinkage and side-branches' patency rate. It might represent a potential improvement of the flow-diverting strategy in treating complex aortic lesions, yet large-scale, prospective, and randomized trials are anticipated to draw a robust conclusion. ADVANCES IN KNOWLEDGE: The joint procedure could potentially exclude complex aortic aneurysms from circulation while maintaining the collateral branches.

Evaluating two respiratory correction methods for abdominal PET/MRI imaging.

BACKGROUND: To evaluate two respiratory correction methods for abdominal PET/MRI images and further to analyse the effects on standard uptake values (SUVs) of respiratory motion correction, 17 patients with 25 abdominal lesions on 18F-FDG PET/CT were scanned with PET/MRI. PET images were reconstructed using end-expiratory respiratory gating and multi-bin respiratory gating. Meanwhile, full data and the first 3 min and 20 s of data acquired both without respiratory gating were reconstructed for evaluation. Five parameters, including the SUVmax and SUVmean in the lesions, the SUVmean and standard deviation (SD) in the background, and the signal-to-noise ratio (SNR), were calculated and used for statistical comparisons. The differences in multi-bin respiratory gating and reconstruction of full data, relative to the reconstruction of the first 3 min and 20 s of data acquired, were calculated. RESULTS: Compared with PET/CT, the longer scanning time of abdominal PET/MRI makes respiratory motion correction necessary. The multi-bin respiratory gating correction could reduce the PET image blur and increase the SUVmax (11.98%) and SUVmean (13.12%) of the lesions significantly (p = 0.00), which was much more effective than end-expiratory respiratory gating for abdominal PET/MRI. The added value of SUVmax caused by respiratory motion correction has no significant difference compared with that caused by count loss with the correction (p = 0.39), which was rarely reported by previous studies. CONCLUSION: Based on the current parameters, the method of multi-bin respiratory gating was more effective for respiratory motion correction in abdominal PET/MRI in comparisons with the method of end-respiratory gating. However, the increased noise in gated images, due to the fact that PET data get discarded, is partly responsible for the increase in SUVmax.