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Jun Wang,1 Yue-Tao Zhao,2,3 Meng-Jiao Sun,1 Feng Chen,3 Hong-Li Guo3 1Department of Hematology and Oncology, Children’s Hospital of Nanjing Medical University, Nanjing, 210008, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China; 3Pharmaceutical Sciences Research Center, Department of Pharmacy, Children’s Hospital of Nanjing Medical University, Nanjing, 210008, People’s Republic of ChinaCorrespondence: Hong-Li Guo, Children’s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, 210008, People’s Republic of China, Email guomomohl@163.comAbstract: High-dose methotrexate (HDMTX) is a pivotal component of the chemotherapeutic regimens of osteosarcoma. However, the use of HDMTX is limited by an increased risk of dose-dependent toxicity. It is thought that the plasma levels and therapy-related toxicity of MTX could be associated with single nucleotide polymorphisms (SNPs) within MTX metabolism pathway genes. Here, we report a case of a paediatric osteosarcoma girl with delayed MTX excretion who was successfully managed using supportive measures and continuous veno-venous haemodiafiltration. We further identified the cause that could account for delayed elimination by genotyping analysis. The results showed that variations have been found in SLCO1B1, SLC19A1, ABCB1 and MTHFR, all those were reported to have a strong association with delayed elimination of MTX in clinical studies. After comprehensive consideration of genotype and clinical phenotype, the second course of HDMTX was administered to this patient at a half reduced dose. We also performed a literature review to summarize the pharmacogenetic factors that influence HDMTX pharmacokinetics or MTX-related adverse effects in osteosarcoma patients. It is suggested that the potential risk of delayed MTX elimination is worthy of clinical attention, and the implementation of genotyping should be considered to ensure therapeutic safety.Graphical Abstract: Keywords: high-dose methotrexate, osteosarcoma, delayed excretion, single nucleotide polymorphisms

Peng Zou,1,* Han-Lin Gong,2,* Jian-Min Wei,3,* Dong-Mei Wei,4 Li-Xiong Qian,1 Peng Liu,1 Ding-Jun Hao,1 Jun-Song Yang,1 Yuan-Ting Zhao1 1Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, People’s Republic of China; 3Department of Spine Surgery, Baoji City Hospital of Traditional Chinese Medicine, Shaanxi, People’s Republic of China; 4Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuan-Ting Zhao Tel +86 15229376812Email zytqy@163.comJun-Song Yang Tel +86 18792883498Email yangjunsong1988@126.comObjective: To present the case of a patient on long-term anticoagulants who developed acute spinal epidural hematoma (SEH) after percutaneous kyphoplasty (PKP) without signs of major cement extravasation to the spinal canal.Methods: A 64-year-old woman with long-term oral antiplatelet drugs underwent the L1 PKP. Immediately after the operation, the back pain improved significantly without neurological deficit. However, 12 hours later, she developed progressive weakness of the bilateral lower limbs. No intraspinal cement leakage was obvious on the postoperative lumbar radiograph and computed tomography.Results: An emergency MRI examination revealed a high signal aggregation in front of the spinal cord from T12 to L1, indicating spinal cord compression. The SEH was verified and removed during the laminectomy from T12–L1. Following the decompression surgery, the neurological deficit of the lower limbs improved. On follow-up after 6 months, the muscle strength of the bilateral lower limbs had returned to normal.Conclusion: For the patient with long-term oral antiplatelet drugs or coagulation malfunction, the transpedicle approach or that via the costovertebral joint with a smaller abduction angle is recommended to reduce the risk of injury to the inner wall of the pedicle. For progressive aggravation of neurological dysfunction after surgery, SEH formation should be suspected despite the absence of intraspinal bone cement leakage. Secondary emergency decompression should be considered to avoid permanent damage to spinal cord nerve function caused by continuous compression.Keywords: spinal epidural hematoma, percutaneous vertebroplasty, percutaneous kyphoplasty, spinal cord compression, coagulation malfunction

Xuan Zheng,1,* Bo Chen,1,* Jian-Xiong Wu,2 Angela Y Jia,3 Wei-Qi Rong,2 Li-Ming Wang,2 Fan Wu,2 Yu-Ting Zhao,1 Ye-Xiong Li,4 Wei-Hu Wang5 1Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Abdominal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA; 4Department of Radiation Oncology, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China *These authors contributed equally to this work Purpose: To evaluate the role of adjuvant radiotherapy after narrow-margin (

Yu-Ting Zhao,1,* Zhi-Kai Liu,2,* Qiu-Wen Wu,3 Jian-Rong Dai,1 Tao Zhang,1 Angela Y Jia,4 Jing Jin,1 Shu-Lian Wang,1 Ye-Xiong Li,1 Wei-Hu Wang5 1Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 2Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 3Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA; 4Department of Medicine, Weill Cornell Medicine, New York, NY, USA; 5Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, China *These authors contributed equally to this work Aims: To assess motion magnitude in different parts of the liver through surgical clips in postoperative patients with hepatocellular carcinoma and to examine the correlation between the clip and diaphragm motion.Methods: Four-dimensional computed tomography images from 30 liver cancer patients under thermoplastic mask immobilization were selected for this study. Three to seven surgical clips were placed in the resection cavity of each patient. The liver volume on computed tomography image was divided into the right upper (RU), right middle (RM), right lower (RL), hilar, and left lobes. Agreement between the clip and diaphragm motion was assessed by calculating intraclass correlation coefficient, and Bland–Altman analysis (Diff). Furthermore, population-based and patient-specific margins for internal motion were evaluated.Results: The clips located in the RU lobe showed the largest motion, (7.5±1.6) mm, which was significantly more than in the RM lobe (5.7±2.8 mm, p=0.019), RL lobe (4.8±3.3 mm, p=0.017), and hilar lobe (4.7±2.7 mm, p

Developing aggregation-induced emission (AIE)-based hydrogels that exhibit fluorescence enhancement as to thermal properties is an interesting and challenging task. In this work, we employed the fluorophore 2'-hydroxychalcone (HC), fluorescence properties of which are easily influenced by the excited-state intramolecular proton transfer and twisted intramolecular charge transfer (TICT) effects, to develop a novel type of temperature-sensitive polymers, hydroxychalcone-based polymers (HCPs). By controlling the temperature-dependent water microenvironments in HCPs, the intramolecular hydrogen bonds between water and HCPs can be regulated, thereby influencing the TICT process and leading to thermo-induced fluorescence enhancement, which shows a contrary tendency compared to typical AIEgens that always exhibit fluorescence attenuation as the thermal energy accelerates the molecular motion. Following the decoration with triphenylphosphine, the resulting polymer P-HCP assembled into nanohydrogels and served as a fluorescent probe for intracellular mitochondrial temperature sensing.

Our previous study has shown that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs-exo) alleviated burn-induced acute lung injury (ALI). In this study, we explored a novel mechanism by which hUCMSCs-exo contributed to the inhibition of burn-induced ALI. The ALI rat model with severe burn was established for the in vivo experiments, and rats PMVECs were stimulated with the serum from burn-induced ALI rats for the in vitro experiments. The pathological changes of lung tissues were evaluated by HE staining; the cell viability was measured using CCK-8; the iron level and Fe 2+ concentration were assessed using Iron Assay Kit and Fe 2+ fluorescence detection probe; the mRNA expression of SLC7A11 and GPX4 were measured by qRT-PCR; the protein levels of SLC7A11, GPX4, Nrf2 and HO-1 were detected by western blot. Both the in vivo and in vitro experiments revealed that ferroptosis was significantly induced in burn-induced ALI, which as verified by increased iron level and Fe 2+ concentration, and decreased SLC7A11 and GPX4 mRNA and protein levels. Furthermore, both hUCMSCs-exo and Fer-1 (the inhibitor of ferroptosis) alleviated lung inflammation and up-regulated protein levels of Nrf2 and HO-1 in the lung tissues of burn-induced ALI rats. These results suggested that hUCMSCs-exo exhibited a protective role against burn-induced ALI by inhibiting ferroptosis, partly owing to the activation of Nrf2/HO-1 pathway, thus providing a novel therapeutic strategy for burn-induced ALI., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and fatal disease. Exosomes are extracellular vesicles that plays a vital rule in the progression and metastasis of PDAC. However, the specific mechanism of exosome biogenesis and release in the tumorigenesis and development of pancreatic cancer remains elusive. The aim of this study is to develop novel biomarkers and construct a reliable prognostic signature to accurately stratify patients and optimize clinical decision-making., Methods: Gene expression and clinical data were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate Cox regression analysis, random forest analysis, least absolute shrinkage and selection operator (LASSO) regression analysis, and multivariate Cox regression analysis were used to construct the risk signature. The effectiveness of the model was validated by survival point plot, Kaplan-Meier survival analysis, and receiver operating characteristic (ROC) curve in training, testing and entire cohorts. Meanwhile, single sample gene set enrichment analysis (ssGSEA), ESTIMATE and CIBERSORT algorithm were utilized to assess the association of the risk signature with the immune status in the PDAC tumor microenvironment. We also performed functional enrichment, tumor mutation analysis, and DNA methylation analyses based on the risk signature. The function of the core gene was further verified by polymerase chain reaction (PCR), western blot, bicinchoninic acid (BCA), immunohistochemistry (IHC) and in vitro experiments including cell proliferation, migration, and apoptosis experiments., Results: We constructed an exosome biogenesis- and release-related risk model which could serve as an effective and independent prognosis predictor for PDAC patients. The immune infiltration analysis revealed that our signature was related to the PDAC immune microenvironment, mainly associated with a lower proportion of natural killer (NK) cells and CD8 + T cells. Tissue microarray IHC confirmed the association of RAB27B with poor prognosis in PDAC. Knockdown of RAB27B expression promoted PDAC cells' apoptosis, while decreased cellular proliferation and migration. Also, knockdown of RAB27B expression led to reduced exosome secretion, while RAB27B overexpression promoted exosome secretion., Conclusions: The predictive signature can predict overall survival, help elucidate the mechanism of exosome biogenesis and release, and provide immunotherapy guidance for PDAC patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-54/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Objectives : Sirolimus (SRL), a mammalian target of rapamycin inhibitor, has been widely used to treat patients with vascular anomalies (VAs). The objectives of this study were to summarize the routine blood SRL monitoring data for VAs children, to investigate the factors contributing to the variable blood SRL concentrations and to evaluate the efficacy and safety of SRL therapy. Methods : VAs patients with routine blood SRL monitoring from July 2017 to April 2022 at the Department of Burns and Plastic Surgery, Children's Hospital of Nanjing Medical University were retrospectively collected. Clinical data were obtained from the hospital information system. Results : In total, 67 children (35 females) were enrolled. The therapeutic drug monitoring data showed that the range of measured blood trough concentrations ( C trough ) was 3.6-46.8 ng/mL. At the initial measurements, only 33% of patients were in the target concentration range (10-15 ng/mL). But this proportion became 54% at the last measurements. The whole blood- C trough -to-daily dose ( C trough /Dose) ratio was significantly associated with age and body weight (BW). The patients' laboratory results did not change significantly after SRL treatment. Although the incidence of adverse events was relatively high (44.8%), most of them were mild and tolerable. 70.3% patients had total responses to SRL, whereas 29.7% children exhibited stable disease or progressive disease. No significant differences were found in C trough between the total response group and non-response group. Conclusions : This retrospective study revealed a high variability in SRL blood concentrations in Chinese children with VAs. Of note, pediatric patients with older age and a higher BW had a lower C trough /Dose ratio. It is a concern whether the range of 10-15 ng/mL is feasible for Chinese children based only on our study. Further studies recruiting more patients are required to redefine the target reference range for children with VAs.

Background: The main challenges faced when using sirolimus in children with vascular anomalies (VAs) still include significant pharmacokinetic (PK) variability, uncertainty in the target concentration range, as well as inconsistencies in initial dosing and dosing frequency. The aim of this study is to establish a new population pharmacokinetic (PPK) model for children with VAs to guide the individualized use of sirolimus., Methods: A PPK study was performed using data from children with VAs who received sirolimus between July 2017 and April 2022. A nonlinear mixed-effect modeling with a one-compartment model structure was applied. Monte Carlo simulation was employed to propose specific dosing recommendations to achieve the target trough concentrations ( C trough ) of 5-15 ng/mL., Results: In total, 134 blood concentrations from 49 pediatric patients were used to characterize the sirolimus pharmacokinetics. Covariate analysis identified body weight (BW) as a significant factor affecting clearance ( CL ) in the final PPK model. The typical clearance rate and distribution volume, standardized to a BW of 16 kg, were 4.06 L/h (4% relative standard error, RSE) and 155 L (26% RSE), respectively. Optimal dosing regimens were simulated for different BWs. For a twice-daily regimen, the recommended doses were 0.05, 0.06, 0.07, and 0.08 mg/kg/day for BW of <10, 10-20, 20-40, and ≥40 kg, respectively; for a once-daily regimen, the recommended doses were 0.06, 0.07, 0.08, and 0.09 mg/kg/day for BW of <10, 10-30, 30-50, and ≥50 kg, respectively. Notably, sirolimus C trough could be maintained between 5-15 ng/mL across various dosing frequencies based on the recommended dosing regimen., Conclusion: We established a PPK model of sirolimus for children with VAs and proposed an initial dosing strategy. Integrating initial dose and medication frequency recommendations into sirolimus' guidelines will broaden its clinical options and simplify the clinical management for childhood VAs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fan, Guo, Zhao, Li, Wang, Huang, Hu, Zou and Chen.)

Objective: This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome (HFRS) in Qingdao City, China., Methods: Information was collected on HFRS cases in Qingdao City from 2010 to 2022. Descriptive epidemiologic, seasonal decomposition, spatial autocorrelation, and spatio-temporal cluster analyses were performed., Results: A total of 2,220 patients with HFRS were reported over the study period, with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52%. The male:female ratio was 2.8:1. 75.3% of patients were aged between 16 and 60 years old, 75.3% of patients were farmers, and 11.6% had both "three red" and "three pain" symptoms. The HFRS epidemic showed two-peak seasonality: the primary fall-winter peak and the minor spring peak. The HFRS epidemic presented highly spatially heterogeneous, street/township-level hot spots that were mostly distributed in Huangdao, Pingdu, and Jiaozhou. The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak., Conclusion: The distribution of HFRS in Qingdao exhibited periodic, seasonal, and regional characteristics, with high spatial clustering heterogeneity. The typical symptoms of "three red" and "three pain" in patients with HFRS were not obvious., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Methods: Single-cell transcriptomics and high-throughput transcriptomics were used to screen factors significantly correlated with intervertebral disc degeneration (IDD). Expression changes of CFIm25 were determined via RT-qPCR and Western blot. NP cells were isolated from mouse intervertebral discs and induced to degrade with TNF-α and IL-1β. CFIm25 was knocked out using CRISPR-Cas9, and CFIm25 knockout and overexpressing nucleus pulposus (NP) cell lines were generated through lentiviral transfection. Proteoglycan expression, protein expression, inflammatory factor expression, cell viability, proliferation, migration, gene expression, and protein expression were analyzed using various assays (alcian blue staining, immunofluorescence, ELISA, CCK-8, EDU labeling, transwell migration, scratch assay, RT-qPCR, Western blot). The GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA was designed, and its effects on NP regeneration were assessed through in vitro and mouse model experiments. The progression of IDD in mice was evaluated using X-ray, H&E staining, and Safranin O-Fast Green staining. Immunohistochemistry was performed to determine protein expression in NP tissue. Proteomic analysis combined with in vitro and in vivo experiments was conducted to elucidate the mechanisms of hydrogel action., Results: CFIm25 was upregulated in IDD NP tissue and significantly correlated with disease progression. Inhibition of CFIm25 improved NP cell degeneration, enhanced cell proliferation, and migration. The hydrogel effectively knocked down CFIm25 expression, improved NP cell degeneration, promoted cell proliferation and migration, and mitigated IDD progression in a mouse model. The hydrogel inhibited inflammatory factor expression (IL-6, iNOS, IL-1β, TNF-α) by targeting the p38/NF-κB signaling pathway, increased collagen COLII and proteoglycan Aggrecan expression, and suppressed NP degeneration-related factors (COX-2, MMP-3)., Conclusion: The study highlighted the crucial role of CFIm25 in IDD and introduced a promising therapeutic strategy using a porous spherical GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA. This innovative approach offers new possibilities for treating degenerated intervertebral discs., (© 2024. The Author(s).)

Background: Postoperative urination dysfunction is a common complication after surgery in patients with cervical cancer. Portable bladder ultrasound are commonly utilized in clinical practice for measuring residual urine volume. This study aimed to the effect of bladder function training combined with portable ultrasound monitoring on bladder function recovery in patients with cervical cancer after training., Methods: A total of 40 postoperative patients with cervical cancer were randomly divided into a control group (A) and an experimental group (B) of 20 cases each. Group A was given routine postoperative care, while group B was given bladder function training. Urgent urine bladder volume were taken twice daily after removal of the urinary catheter and monitored for five consecutive days. The difference of urgent urine bladder volume and bladder filling rate were compared by t -test and chi-square test respectively. The 36-item Short Form Health Survey (SF-36) was used to evaluate the quality of life of patients before and after intervention, and compared by Mann-Whitney U test., Results: There was no significant difference in preoperative urgent urine volume between the two groups. After catheter removal, the bladder volume of patients in the B increased, while the bladder volume of patients in the A increased less and fluctuated greatly. The bladder filling rate in the A was significantly lower than that in the B (5/15 vs 17/18, p  < 0.05). After intervention, the quality of life of the experimental group was better than that of the control group, including scores of general health, mental health, vitality, and physical role ( p  < 0.05)., Conclusion: Postoperative cervical cancer patients trained to hold urine by portable ultrasound monitoring are able to recover bladder function., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Intervertebral disc degeneration (IVDD) is a prevalent chronic condition causing spinal pain and functional impairment. This study investigates the role of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in regulating IVDD. Using RNA-seq, we analyzed differential expressions of lncRNA and miRNA in nucleus pulposus tissues from various mouse groups. We identified key regulatory molecules, MALAT1 and miRNA-138-5p, which contribute to IVDD. Further experiments demonstrated that MALAT1 can up-regulate SLC7A11 expression by competitively binding to miR-138-5p, forming a MALAT1/miR-138-5p/SLC7A11 coexpression regulatory network. This study elucidates the molecular mechanism by which hUCMSC-derived EVs regulate IVDD and could help develop novel therapeutic strategies for treating this condition. Our findings demonstrate that hUCMSCs-EVs inhibit ferroptosis in nucleus pulposus cells, thereby improving IVDD. These results highlight the therapeutic potential of hUCMSCs-EVs in ameliorating the development of IVDD, offering significant scientific and clinical implications for new treatments.

The crosstalk between clathrin-mediated endocytosis (CME) and the autophagy pathway has been reported in mammals; however, the interconnection of CME with autophagy has not been established in plants. Here, we report that the Arabidopsis CLATHRIN LIGHT CHAIN (CLC) subunit 2 and 3 double mutant, clc2-1 clc3-1, phenocopies Arabidopsis AUTOPHAGY-RELATED GENE (ATG) mutants in both autoimmunity and nutrient sensitivity. Accordingly, the autophagy pathway is significantly compromised in the clc2-1 clc3-1 mutant. Interestingly, multiple assays demonstrate that CLC2 directly interacts with ATG8h/ATG8i in a domain-specific manner. As expected, both GFP-ATG8h/GFP-ATG8i and CLC2-GFP are subjected to autophagic degradation, and degradation of GFP-ATG8h is significantly reduced in the clc2-1 clc3-1 mutant. Notably, simultaneous knockout of ATG8h and ATG8i by CRISPR-Cas9 results in enhanced resistance against Golovinomyces cichoracearum, supporting the functional relevance of the CLC2-ATG8h/8i interactions. In conclusion, our results reveal a link between the function of CLCs and the autophagy pathway in Arabidopsis., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Integrin α5β1 is crucial for cell attachment and migration in development and tissue regeneration, and α5β1 binding proteins could have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5β1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5β1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin and RGD peptide in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed fibronectin and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine., Competing Interests: Conflict of interest X.W., J.G-M, B.H., and D.B. are co-inventors on an International patent (Serial 63/570,567) filed by the University of Washington covering molecules and their uses described in this manuscript. A.R., X.W., and D.B. are co-founders of Lila Biologics and own stock or stock options in the company. All other authors declare no competing interests.

Immune-mediated thrombotic thrombocytopenia purpura (iTTP) is a rare microvascular disease characterized by severe disseminated microvascular thrombose-bleeding syndrome. Caplacizumab has been approved for the treatment of iTTP in combination with Plasma Exchange (PE) and immunosuppressive therapy, but its role in iTTP therapy remains uncertain. Therefore, we conducted a meta-analysis to investigate the safety and efficacy of caplacizumab for the treatment of patients with iTTP. We searched electronic databases (PubMed, Embase, Cochrane Library, and Scopus) and reference lists of relevant articles to find articles published from 2015 to 2022. The time to normalization of the platelet count of the group caplacizumab is shorter than the group placebo (SMD = -0.72; 95% CI -0.88 to -0.56; P  < 0.05). Caplacizumab reduced the incidence of mortality (OR = 0.41; 95% CI 0.18-0.92; P  < 0.05), exacerbations (OR = 0.10; 95% CI 0.05-0.18; P  < 0.05), and recurrence (OR = 0.17; 95% CI 0.06-0.50; P  < 0.05). However, the bleeding events in the caplacizumab group were higher than those in the placebo group, especially severe bleeding events. There was no difference in ADAMTS13 activity and thromboembolic events between the two groups. Our analysis indicated that caplacizumab is effective and well tolerated for the treatment of iTTP., Systematic Review Registration: PROSPERO CRD42022362370., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To investigate the biocompatibility of coral-like barium titanate nano-piezoelectric coatings and the influence of ultrasound-excited piezoelectric effect on the early osteogenic differentiation. Methods: The barium titanate nano-piezoelectric coating (the coating group) was prepared on the surface of titanium metal by anodic oxidation, hydrothermal reaction and high-temperature annealing, and polished titanium specimens were used as control group. The surface morphology, composition, and crystal phase and hydrophilicity of the two groups of titanium specimens were characterized using scanning electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy and contact angle meter. The piezoelectric properties of the materials were characterized by piezoresponse force microscopy. Rat bone marrow mesenchymal stem cells (BMSC) were cultured and identified and seeded the surface of titanium specimens in two groups. The cells seeded on blank culture plates were used as blank group. After low intensity pulsed ultrasound intervention, cell proliferation and live/dead staining were detected to evaluate cytocompatibility of the coatings. Alkaline phosphatase (ALP) activity of each group was detected by ALP staining kit, and the expression of osteogenesis-related genes [integrin, bone morphogenetic protein 2 (BMP-2), Runt-related transcription factor 2 (RUNX2)] was detected by real-time fluorescent quantitative PCR (RT-qPCR) to evaluate the effect of the coating on promoting the early osteogenic differentiation of BMSC. Results: The surface of titanium specimens in the coating group showed a uniform coral-like morphology, and the diameter of the coral tentacles was 70-100 nm. The main component was tetragonal barium titanate. The surface hydrophilicity of the coating group (water contact angle 10.12°± 0.93°) was significantly better than that of the control group (water contact angle 78.32°±0.71°) ( F= 10 165.91, P< 0.001). The coating has a stable piezoelectric property with a piezoelectric constant of about 5 pC/N. Cell experiments showed that, with or without ultrasound, the cell proliferation activity of the coating group was significantly lower than that of the blank group and the control group on the third day ( P< 0.05). On the fifth day, with or without ultrasound, there was no significant difference in cell proliferation activity between the three groups ( P> 0.05). After 7 days of culture, the ALP activity of the coating group was significantly higher than that of the blank group and the control group ( P< 0.05). The results of RT-qPCR showed that the mRNA expression of integrin and BMP-2 in the coating group with ultrasound was significantly higher than that in the other groups with ultrasound, and was higher than that of the coating group without ultrasound ( P< 0.05). The expression of integrin mRNA in the control group with ultrasound was significantly higher than that in the control group without ultrasound ( P< 0.05). The expression of RUNX2 mRNA in the coating group with ultrasound was significantly higher than that in the coating group without ultrasound ( P< 0.05). Conclusions: The coral-like barium titanate nano-piezoelectric coating exhibits favorable biocompatibility and stable piezoelectric property, and facilitates the early osteogenic differentiation of BMSC under the excitation of low-intensity pulsed ultrasound.

The eukaryotic AGC protein kinase subfamily (protein kinase A/ protein kinase G/ protein kinase C-family) is involved in regulating numerous biological processes across kingdoms, including growth and development, and apoptosis. PDK1(3-phosphoinositide-dependent protein kinase 1) is a conserved serine/threonine kinase in eukaryotes, which is both a member of AGC kinase and a major regulator of many other downstream AGC protein kinase family members. Although extensively investigated in model plant Arabidopsis, detailed reports for tobacco PDK1s have been limited. To better understand the functions of PDK1s in tobacco, CRISPR/CAS9 transgenic lines were generated in tetraploid N. tabacum, cv. Samsun (NN) with 5-7 of the 8 copies of 4 homologous PDK1 genes in tobacco genome (NtPDK1a/1b/1c/1d homologs) simultaneously knocked out. Numerous developmental defects were observed in these NtPDK1a/1b/1c/1d CRISPR/CAS9 lines, including cotyledon fusion leaf shrinkage, uneven distribution of leaf veins, convex veins, root growth retardation, and reduced fertility, all of which reminiscence of impaired polar auxin transport. The severity of these defects was correlated with the number of knocked out alleles of NtPDK1a/1b/1c/1d. Consistent with the observation in Arabidopsis, it was found that the polar auxin transport, and not auxin biosynthesis, was significantly compromised in these knockout lines compared with the wild type tobacco plants. The fact that no homozygous plant with all 8 NtPDK1a/1b/1c/1d alleles being knocked out suggested that knocking out 8 alleles of NtPDK1a/1b/1c/1d could be lethal. In conclusion, our results indicated that NtPDK1s are versatile AGC kinases that participate in regulation of tobacco growth and development via modulating polar auxin transport. Our results also indicated that CRISPR/CAS9 technology is a powerful tool in resolving gene redundancy in polyploidy plants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

It is a new approach to identify legal or illegal use of morphine through information on municipal wastewater. However, the sources of morphine in wastewater are complex, and distinguishing the contribution of different sources has become a key issue. A total of 262 influent samples from 61 representative wastewater treatment plants in a typical city were collected from October 2022 to March 2023. The concentrations of morphine, codeine, thebaine, papaverine, noscapine, and monoacetylmorphine were analyzed in wastewater and poppy straws. Combined with the proportion of alkaloids in poppy straws, the source analysis of alkaloids in wastewater was analyzed using the ratio method and positive matrix factorization model (PMF). Only five alkaloids were detected in wastewater, and monoacetylmorphine, a metabolite of heroin, was not detected. The concentrations of morphine and codeine were significantly higher than those of noscapine, papaverine, and thebaine. By constructing the ratios of codeine/(morphine + codeine) and noscapine/(noscapine + codeine), the source of poppy straw could be qualitatively distinguished. The PMF results showed that three sources of morphine for medical use, poppy straw, and codeine contributed 44.9%, 43.7%, and 9.4%, respectively. The different sources varied in these months due to the COVID-19 and influenza A outbreaks, in which the use of drugs containing poppy straws and codeine was the main source, whereas the use of morphine analgesics remained relatively stable. Inventory analysis further demonstrated the reliability of the source contributions from the PMF model, and morphine was not abused in this city.

Electrocardiographic (ECG) abnormalities are seen in 70%-80% of patients with acute pulmonary embolism (PE). Rarely, acute PE presents with ST-segment elevation (STE) in leads II; III and aVF and V 1 - 3 mimicking ST-segment elevation myocardial infarction (STEMI). Herein, we describe a case of acute PE presenting with STE in II; III and aVF and V 1 - 3., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Salicylic acid (SA) is a key phyto-hormone that is essential for plant immunity. SARD1 (SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1), a member of the CBP60 (CALMODULIN-BINDING PROTEIN60) gene family, is one of the major transcription factors regulating the expression of the genes in SA biosynthesis. SARD1 has been extensively studied in model plant Arabidopsis. However, the function of SARD1 homologues in SA biosynthesis and immune responses have rarely been investigated in other plant species. In this study, the CRISPR/CAS9 (Clustered Regularly Interspersed Short Palindromic Repeats/CAS9) technology was used in creating transgenic tobacco mutant lines with 6-8 alleles of four NtSARD1 homologous genes (NtSARD1a/1b/1c/1d) knocked out. No significant difference in morphological phenotype was observed between the transgenic knockout lines and the wild type tobacco plants, indicating that knocking out NtSARD1s does not affect the growth and development in tobacco. However, knocking out or partially knocking out of NtSARD1a/b/c/d resulted in a significantly reduced expression of NtICS1, the key gene in SA biosynthesis pathway, and thus the subsequently decreased SA/SAG accumulations in response to Pst DC3000 (Pseudomonas syrangae pv.tomato DC3000) infection, indicating a key role of NtSARD1 genes in SA biosynthesis in tobacco. As a consequence of reduced SA/SAG accumulation, the Pst DC3000-induced expression of NtPR genes as well as the resistance to Pst DC3000 were both significantly reduced in these knockout lines compared with the wild type tobacco plants. Interestingly, the reductions in the SA/SAG level, NtPR gene induction and Pst DC3000 resistance were positively correlated with the number of alleles being knocked out. Furthermore, LUC reporter gene driven by the promoter of NtICS1 containing two G(A/T)AATT(T/G) motifs could be activated by NtSARD1a, suggesting that NtSARD1a could bind to the core G(A/T)AATT(T/G) motifs and thus activate the expression of LUC reporter. Taken together, our results demonstrated that the NtSARD1 proteins play essential roles in SA biosynthesis and immune responses in tobacco. Our results also demonstrated that the CRISPR/CAS9 technology can overcome gene redundancy and is a powerful tool to study gene functions in polyploid plant species., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: As a serious complication of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP), infected pancreatic necrosis (IPN) can lead to a prolonged course of interventional therapy. Most predictive models designed to identify such patients are complex or lack validation. The aim of this study was to develop a predictive model for the early detection of IPN in MSAP and SAP., Methods: A total of 594 patients with MSAP or SAP were included in the study. To reduce dimensionality, least absolute shrinkage and selection operator regression analysis was used to screen potential predictive variables, a nomogram was then constructed using logistic regression analysis. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical efficacy of the model. External data were also obtained to further validate the constructed model., Results: There were 476, 118, and 82 patients in the training, internal validation, and external validation cohorts, respectively. Platelet count, hematocrit, albumin/globulin, severity of acute pancreatitis, and modified computed tomography severity index score were independent factors for predicting IPN in MSAP and SAP. The area under the ROC curves were 0.923, 0.940, and 0.817, respectively, in the three groups. There was a good consistency between the actual probabilities and the predicted probabilities. DCA revealed excellent clinical utility., Conclusion: The constructed nomogram is a simple and feasible model that has good clinical predictive value and efficacy in clinical decision-making for IPN in MSAP and SAP., (© 2024 The Authors. Journal of Digestive Diseases published by Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China., Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders., Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms., Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms., Competing Interests: Professor Lei Cheng, Hua‐Bin Li, Jian‐Feng Liu, Zhen‐Lin Wang, Chang‐Qing Zhao and Dong‐Dong Zhu are the members of World Journal of Otorhinolaryngology ‐ Head and Neck Surgery editorial board and are not involved in the peer review process of this article. The other authors declare no conflict of interest., (© 2024 The Authors. World Journal of Otorhinolaryngology ‐ Head and Neck Surgery published by John Wiley & Sons Ltd on behalf of Chinese Medical Association.)

We establish a theoretical model to analyze the photoassociative spectroscopy of 85Rb 133Cs molecules in the (3)3Σ+ state. The vibrational energy, spin-spin coupling constant, and hyperfine interaction constant of the (3)3Σ+ state are determined based on nine observed vibrational levels. Consequently, the Rydberg-Klein-Rees potential energy curve of the (3)3Σ+ state is obtained and compared with the ab initial potential energy curve. Our model can be adopted to analyze the photoassociative spectroscopy of other heteronuclear alkali-metal diatomic molecules in the (3)3Σ+ state., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Hyaluronan and proteoglycan link protein 1 (Hapln1) supports active cardiomyogenesis in zebrafish hearts, but its regulation in mammal cardiomyocytes is unclear. This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) and an adult mouse model of myocardial infarction. HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models, respectively. Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration. The results showed that recombinant human Hapln1 (rhHapln1) promotes the proliferation of hiPSC-CMs in a dose-dependent manner. As a physical binding protein of Hapln1, versican interacted with Nodal growth differentiation factor (NODAL) and growth differentiation factor 11 (GDF11). GDF11, but not NODAL, was expressed by hiPSC-CMs. GDF11 expression was unaffected by rhHapln1 treatment. However, this molecule was required for rhHapln1-mediated activation of the transforming growth factor (TGF)-β/Drosophila mothers against decapentaplegic protein (SMAD)2/3 signaling in hiPSC-CMs, which stimulates cell dedifferentiation and proliferation. Recombinant mouse Hapln1 (rmHapln1) could induce cardiac regeneration in the adult mouse model of myocardial infarction. In addition, rmHapln1 induced hiPSC-CM proliferation. In conclusion, Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway. Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a potential reagent for repairing damaged hearts., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors.)

Background: Peste des petits ruminants (PPR) is a contagious and fatal disease of sheep and goats. PPR virus (PPRV) infection induces endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR). The activation of UPR signaling pathways and their impact on apoptosis and virus replication remains controversial., Objectives: To investigate the role of PPRV-induced ER stress and the IRE1-XBP1 and IRE1-JNK pathways and their impact on apoptosis and virus replication., Methods: The cell viability and virus replication were assessed by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, immunofluorescence assay, and Western blot. The expression of ER stress biomarker GRP78, IRE1, and its downstream molecules, PPRV-N protein, and apoptosis-related proteins was detected by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. 4-Phenylbutyric acid (4-PBA) and STF-083010 were respectively used to inhibit ER stress and IRE1 signaling pathway., Results: The expression of GRP78, IRE1α, p-IRE1α, XBP1s, JNK, p-JNK, caspase-3, caspase-9, Bax and PPRV-N were significantly up-regulated in PPRV-infected cells, the expression of Bcl-2 was significantly down-regulated. Due to 4-PBA treatment, the expression of GRP78, p-IRE1α, XBP1s, p-JNK, caspase-3, caspase-9, Bax, and PPRV-N were significantly down-regulated, the expression of Bcl-2 was significantly up-regulated. Moreover, in PPRV-infected cells, the expression of p-IRE1α, p-JNK, Bax, and PPRV-N was significantly decreased, and the expression of Bcl-2 was increased in the presence of STF-083010., Conclusions: PPRV infection induces ER stress and IRE1 activation, resulting in apoptosis and enhancement of virus replication through IRE1-XBP1s and IRE1-JNK pathways., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)

Dietary-derived substances possess significant potential as anthropogenic markers owing to the large consumption and different intake habit. To investigate and evaluate such markers, wastewater samples from 35 wastewater treatment plants across 29 Chinese cities were collected to analyze artificial sweeteners (acesulfame and cyclamate) and natural spicy compounds (capsaicin and dihydrocapsaicin). Acesulfame (mean: 14.6 μg/L), cyclamate (mean: 24.3 μg/L), and capsaicin (mean: 101 ng/L) can be further investigated as anthropogenic markers due to their high detection frequency at high concentrations. Spatial use patterns revealed that acesulfame (5.31 g/d/1000 inhabitants (inh)) and cyclamate (8.16 g/d/1000 inh) use in northern China notably surpassed that in southern China (1.79 g/d/1000 inh and 3.23 g/d/1000 inh, p < 0.05). Conversely, chili pepper use was significantly higher (p < 0.05) in southern China (6702 g/d/1000 inh) than in northern China (2751 g/d/1000 inh), signifying a preference for sweetness in the northern regions and a predilection for spiciness in the southern regions. The total annual use of acesulfame (1842 t), cyclamate (3110 t), and chili (18.4 million tonnes) in China was estimated by this study, which was close to the national statistical production. In addition, sweetener use was negatively associated with the elderly population ratio, suggesting that the elderly population might not consume sweet foods. This study reveals the dietary sources of anthropogenic markers, highlighting the need for further research on the environmental implications of such markers., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Concerns about the adverse effects of excessive oxygen have grown over the years. This study investigated the relationship between high oxygen saturation and short-term prognosis of patients with spontaneous intracerebral hemorrhage (sICH) after liberal use of oxygen., Methods: This retrospective cohort study collected data from the Medical Information Mart for Intensive Care III (MIMIC-III) database (ICU cohort) and a tertiary stroke center (general ward cohort). The data on pulse oximetry-derived oxygen saturation (SpO 2 ) during the first 24 h in ICU and general wards were respectively extracted., Results: Overall, 1117 and 372 patients were included in the ICU and general ward cohort, respectively. Among the patients from the ICU cohort, a spoon-shaped association was observed between minimum SpO 2 and the risk of in-hospital mortality (non-linear P<0.0001). In comparison with minimum SpO 2 of 93-97%, the minimum SpO 2 >97% was associated with a significantly higher risk of in-hospital mortality after adjustment for confounders. Sensitivity analysis conducted using propensity score matching did not change this significance. The same spoon-shaped association between minimum SpO 2 and the risk of in-hospital mortality was also detected for the general ward cohort. In comparison with the group with 95-97% SpO 2 , the group with SpO 2 >97% showed a stronger association with, but non-significant risk for, in-hospital mortality after adjustment for confounders. The time-weighted average SpO 2 >97% was associated significantly with in-hospital mortality in both cohorts., Conclusion: Higher SpO 2 (especially a minimum SpO 2 >97%) was unrewarding after liberal use of oxygen among patients with sICH and might even be potentially detrimental., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Hypericum perforatum L. (HPL) is a potential traditional Chinese medicine. It could promotes menopausal 'kidney-yin deficiency syndrome' that characterized by renal function decline. However, its potential pharmacological effect and mechanism remains unknown., Objective: The aim of this study was to investigate whether HPL can improve menopausal renal function decline and to explore its mechanism of action., Methods: The mainly ingredients of HPL were identified using UPLC-Q-TOF-MS/MS approach, and the potential therapeutic targets of HPL for renal function decline were chose via network pharmacology technique. The key therapeutic metabolites were selected through non-targeted metabolomic and chemometric methods. Then, the network were constructed and the key targets and metabolites were screened. At last, the validation experiments and mechanism exploring were adopted by using Immunofluorescence, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and western blotting assays., Results: mainly ingredients of HPL were identified and determined 17 compounds and 29 targets were chose as mainly active compounds and potential therapeutic targets. Based on OVX induced renal decline rat model, after chemometric analysis, 59 endo-metabolites were selected as key therapeutic metabolites, and AGE-RAGE signal pathway in diabetes complications was enriched as the key pathway. By constructing a "disease-component-target" network, Hyperoside, Quercetrin, and quinic were selected as the key therapeutic compounds, and the AKT1 and NOS3 were selected as the key therapeutic targets. The results of ELISA, RT-PCR and western blot experiments indicated that HPL could rescue the abnormal expressions both of AKT1 and NOS3, as well as their related metabolites distortion., Conclusion: Our findings indicated that HPL regulated expression of AKT1 and NOS3 through modulating AGE-RAGE signaling pathway in OVX stimulated rats` renal dysfunction, implicating the potential values of HPL in menopause syndromes therapy., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work; there is noprofessional or other personal interest of any nature or kind in any product, serviceand/or company that could be construed as influencing the position presented in,or the review of the manuscript entitled Hypericum perforatum L. protects against renal function decline in OVX rats by regulating expressions of NOS3 and AKT1 in AGE-RAGE pathway., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Scope: Hypertrophic chondrocytes have a decisive regulatory role in the process of fracture healing, and the fate of hypertrophic chondrocytes is not only apoptosis. However, the mechanism of sea cucumber (Stichopus japonicus) intestinal peptide (SCIP) on fracture promotion is still unclear. This study aims to investigate the effect of sea cucumber intestinal peptide on the differentiation fate of hypertrophic chondrocytes in a mouse tibial fracture model., Methods and Results: Mice are subjected to open fractures of the right tibia to establish a tibial fracture model. The results exhibit that the SCIP intervention significantly promotes the mineralization of cartilage callus, decreases the expression of the hypertrophic chondrocyte marker Col X, and increases the expression of the osteoblast marker Col I. Mechanically, SCIP promotes tibial fracture healing by promoting histone acetylation and inhibiting histone methylation, thereby upregulating pluripotent transcription factors induced the differentiation of hypertrophic chondrocytes to the osteoblast lineage in a manner distinct from classical endochondral ossification., Conclusion: This study is the first to report that SCIP can promote tibial fracture healing in mice by inducing the differentiation of hypertrophic chondrocytes to the osteoblast lineage. SCIP may be considered raw material for developing nutraceuticals to promote fracture healing., (© 2023 Wiley-VCH GmbH.)

We report on the experimental observation of the focusing effect of a 50MeV accelerator electron beam in a gas-discharge plasma target. The plasma is generated by igniting an electric discharge in two collinear quartz tubes, with the currents up to 1.5kA flowing in opposite directions in either of the two tubes. In such plasma current configuration, the electron beam is defocused in the first discharge tube and focused with a stronger force in the second one. With symmetric plasma currents, asymmetric effects are, however, induced on the beam transport process and the beam radius is reduced by a factor of 2.6 compared to the case of plasma discharge off. Experimental results are supported by two-dimensional particle-in-cell simulations.

We put forward a novel method for producing ultrarelativistic high-density high-polarization positrons through a single-shot interaction of a strong laser with a tilted solid foil. In our method, the driving laser ionizes the target, and the emitted electrons are accelerated and subsequently generate abundant γ photons via the nonlinear Compton scattering, dominated by the laser. These γ photons then generate polarized positrons via the nonlinear Breit-Wheeler process, dominated by a strong self-generated quasistatic magnetic field B^{S}. We find that placing the foil at an appropriate angle can result in a directional orientation of B^{S}, thereby polarizing positrons. Manipulating the laser polarization direction can control the angle between the γ photon polarization and B^{S}, significantly enhancing the positron polarization degree. Our spin-resolved quantum electrodynamics particle-in-cell simulations demonstrate that employing a laser with a peak intensity of about 10^{23}  W/cm^{2} can obtain dense (≳10^{18}  cm^{-3}) polarized positrons with an average polarization degree of about 70% and a yield of above 0.1 nC per shot. Moreover, our method is feasible using currently available or upcoming laser facilities and robust with respect to the laser and target parameters. Such high-density high-polarization positrons hold great significance in laboratory astrophysics, high-energy physics, and new physics beyond the standard model.