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Xiang Li,1 Mengtian Pan,1 Xinjuan Tian,1 Lele Zixin Yang,2 Jingjing Zhang,1 Dongmei Yan,3 Baohui Xu,4 Li Zhao,1 Weirong Fang1 1Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China; 2The Pennsylvania State University, Eberly College of Science, State College, PA, USA; 3Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, People’s Republic of China; 4Department of Surgery, Stanford University School of Medicine, Stanford, CA, USACorrespondence: Li Zhao; Weirong Fang, Email zhaoli@cpu.edu.cn; weirongfang@cpu.edu.cnBackground: Tripartite motif containing 59 (TRIM59) is a ubiquitin ligase and is involved in the pathogenesis of various diseases, including cancers, sepsis, and other immune-related diseases. However, it has not been defined whether TRIM59 plays a role in ischemic stroke in mice.Methods: This study determined the influence of Trim59 deficiency on experimental stroke outcomes and the cerebral proteomic profile using myeloid cell Trim59 conditional knockout (Trim59-cKO) mice and a label-free quantitative proteomic profiling technique. The possible mechanisms by which TRIM59 affected stroke onset were elucidated by in vivo and in vitro experiments.Results: Immunofluorescence staining results showed that TRIM59 expression was up-regulated after cerebral ischemia and co-localized with macrophages. Myeloid cell Trim59 deficiency exacerbated ischemic injury on day 3 after experimental stroke. In proteomic analysis, 23 differentially expressed proteins were identified in ischemic brain of Trim59-cKO mice as compared to Trim59flox/flox mice. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed proteins were enriched in complement and coagulation cascades. Protein–protein interaction analysis suggested the central role of clusterin in the interaction network. ELISA and Western blot assays confirmed the reduced levels of clusterin protein in the ischemic brains of Trim59-cKO mice. Further experimental results showed that clusterin was expressed in neurons. Conditional co-culture experiments of primary neurons and bone marrow-derived macrophages demonstrated that LPS stimulated macrophages to secrete complement C3. In addition, TRIM59 may affect the changes in clusterin expression in an indirect manner by influencing the secretion of complement C3 in macrophages. In vivo experiments also proved a significant increase in C3 levels in the brains of Trim59-cKO mice after ischemia.Conclusion: Myeloid cell Trim59 deficiency aggravated ischemic stroke outcomes in conjunction with a distinct cerebral proteomic profile, and the underlying mechanism may be related to the regulation of macrophage C3 expression by TRIM59.Keywords: Trim59, ischemic stroke, proteomic profile, complement and coagulation cascades, C3

Wei-Ting Hsu,* I-Wei Shang, Min Pan* Department of Physical Education and Kinesiology, National Dong Hwa University, Hualien, Taiwan*These authors contributed equally to this workCorrespondence: Min Pan, Email pan13min@gmail.comPurpose: This study aims to validate the Chinese version of the Novelty Need Satisfaction Scale (NNSS) within physical education (PE) contexts, incorporating three distinct studies to examine its reliability, validity, and measurement invariance across gender and different samples.Methods: Study 1 involved translating the original NNSS into Chinese and evaluating it through confirmatory factor analysis, item analysis, and assessments of internal consistency reliability among 390 students (53.8% male, 46.2% female), averaging 14.5 years in age. Study 2 assessed the discriminant validity of the Chinese NNSS by exploring correlations between novelty need satisfaction and three conventional basic psychological needs (BPNs) - autonomy, competence, and relatedness, in a larger cohort of 845 students (51.7% male, 48.3% female), with an average age of 14.8 years. This study also investigated the relationships between novelty need satisfaction, autonomous motivation, and enjoyment in PE. Study 3 examined the measurement invariance of the Chinese NNSS across gender and different samples, using a sample of 1235 students (52.6% male, 47.4% female), with an average age of 14.6 years.Results: The one-factor, five-item structure of the Chinese NNSS was confirmed in Study 1. Study 2 demonstrated the distinct yet covariant nature of novelty need satisfaction among BPNs and its predictive capability for enjoyment in PE through autonomous motivation. Study 3 confirmed the measurement invariance of the Chinese NNSS across gender and samples, validating its reliability and applicability.Conclusion: The validation of the Chinese NNSS within PE settings not only adds the need for novelty to the motivational sequence proposed by self-determination theory (SDT) but also emphasizes its significant role in enhancing autonomous motivation and enjoyment. This study suggests the scale’s utility for future research in exploring the dynamics among BPNs and provides deeper insights into the motivational processes in PE.Keywords: self-determination theory, basic psychological needs, cross-cultural validation, need for novelty

Shiyu Zhang,1,2 Caili Chen,1,2 Yi Zhou,1,2 Meirong Pan,1,2 Haimei Li,1,2 Mengjie Zhao,1,2 Min Dong,1,2 Feifei Si,1,2 Lu Liu,1,2 Yufeng Wang,1,2 Qiujin Qian1,2 1Peking University Sixth Hospital/ Institute of Mental Health, Beijing, 100191, People’s Republic of China; 2NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, People’s Republic of ChinaCorrespondence: Qiujin Qian, Peking University Sixth Hospital/ Institute of Mental Health, No. 51 Hua Yuan Bei Road, Haidian District, Beijing, 100191, People’s Republic of China, Email qianqiujin@bjmu.edu.cnPurpose: With the further development of attention-deficit/hyperactivity disorder (ADHD) research, more and more assessment tools related to ADHD have been used. However, there is still no measurement instrument to evaluate the compensatory behavior of ADHD in China. This study aimed to examine the reliability and validity of the Compensatory ADHD Behaviors Scale (CABS) adapted in Chinese and explore ecological characteristics in adults with ADHD using the CABS.Patients and Methods: Data were collected from a sample of 306 adults (Mage = 26.43 years, SD = 5.32; 46.08% male). The original version CABS was translated into Chinese using the forward and backward translation procedures. Participants completed the CABS and questionnaires assessing ADHD symptoms and executive function. We utilized content validity, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and criterion validity to test the validity. Internal consistency and test-retest reliability were employed to test the reliability. Analysis of variance (ANOVA) was employed to compare ADHD subgroups based on gender, ADHD subtype, comorbidities, and medication status, while controlling for demographic variables as covariates.Results: CABS exhibited good construct validity (two factors: present-oriented and future-oriented), content validity (content validity index: 0.98), internal consistency reliability (Cronbach’s alpha coefficient: 0.85 to 0.87) and test-retest reliability (intraclass correlation coefficient: 0.59 to 0.88). The results of CFA showed acceptable fitness for each subscale. CABS demonstrated significant associations with inattention symptoms and plan/organizational abilities. Medicated ADHD individuals scored higher on future-oriented effectiveness subscale of CABS than non-medicated (F = 6.106, p = 0.014).Conclusion: The results indicate that the Chinese CABS exhibited good validity and reliability. It can be considered a valid tool for assessing compensatory behaviors in Chinese adults with ADHD. Further research is needed to explore the connection between medication and compensatory behavior.Keywords: attention-deficit/hyperactivity disorder, adult, compensatory behaviors, reliability, validity, ecological characteristics

Xiaodan Yu,1 Meizhu Pan,2 Lili Jiang,1,&ast; Kuiran Liu1,&ast; 1Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kuiran Liu; Lili Jiang, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang, Liaoning Province, 110004, People’s Republic of China, Email liukr0412@163.com; jiangll311@163.comPurpose: This study focuses on evaluating the prognostic value of the NDC80 kinetochore complex in ovarian cancer (OC) using the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database and reveals the relationship between the NDC80 complex and immune infiltrates in OC.Methods: We collected data on NDC80 complex expression levels in both OC tissues and non-OC ovarian tissues from the University of California Santa Cruz Xena and GEO databases. The clinicopathological characteristics correlated with overall survival were analyzed using Cox regression and the Kaplan–Meier method. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, gene set enrichment analysis and CIBERSORT were performed using data from TCGA database. Immunohistochemical staining was used to verify the higher expression level of NUF2 protein in OC in vitro. Meanwhile, we utilized the Tumor Immune Estimation Resource to analyze the correlation between the NDC80 complex and immunocyte infiltration.Results: The NDC80 complex expression level was prominently higher in OC tissues than in non-OC ovarian tissues and correlated with advanced histologic grade characteristics. Gene expression profiling interactive analysis and the Kaplan–Meier survival curve uncovered a close relationship between high expression of the NDC80 complex and poor overall survival in OC patients. The univariate Cox regression hazard model produced age, pathologic stage, tumor status, primary therapy outcome, SPC24 expression level, and Karnofsky performance score as prognostic factors for OC patients. NDC80 complex expression levels were highly associated with immune cell infiltration, showing NK CD56 bright cells and NK cells with a negative correlation and T helper 2 cells with a positive correlation (P< 0.05).Conclusion: These findings provide evidence that an increased expression level of the NDC80 complex is closely associated with the progression of OC and could also serve as a novel target of immunotherapy in OC.Keywords: bioinformatics analysis, gene expression omnibus, NDC80 kinetochore complex, epithelial ovarian cancer, immunoinfiltration

Ye Zhou, Yangliang Yang, Liang Yi, Mengzhi Pan, Weiqing Tang, Hongwei Duan Department of Anesthesiology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of ChinaCorrespondence: Hongwei Duan, Email duanhongwei120@126.comBackground: Sepsis is recognized as a multiorgan and systemic damage caused by dysregulated host response to infection. Its acute systemic inflammatory response highly resembles that of lipopolysaccharide (LPS)-induced endotoxemia. Propofol and dexmedetomidine are two commonly used sedatives for mechanical ventilation in critically ill patients and have been reported to alleviate cognitive impairment in many diseases. In this study, we aimed to explore and compare the effects of propofol and dexmedetomidine on the encephalopathy induced by endotoxemia and to investigate whether ferroptosis is involved, finally providing experimental evidence for multi-drug combination in septic sedation.Methods: A total of 218 C57BL/6J male mice (20– 25 g, 6– 8 weeks) were used. Morris water maze (MWM) tests were performed to evaluate whether propofol and dexmedetomidine attenuated LPS-induced cognitive deficits. Brain injury was evaluated using Nissl and Fluoro-Jade C (FJC) staining. Neuroinflammation was assessed by dihydroethidium (DHE) and DCFH-DA staining and by measuring the levels of three cytokines. The number of Iba1+ and GFAP+ cells was used to detect the activation of microglia and astrocytes. To explore the involvement of ferroptosis, the levels of ptgs2 and chac1; the content of iron, malondialdehyde (MDA), and glutathione (GSH); and the expression of ferroptosis-related proteins were investigated.Conclusion: The single use of propofol and dexmedetomidine mitigated LPS-induced cognitive impairment, while the combination showed poor performance. In alleviating endotoxemic neural loss and degeneration, the united sedative group exhibited the most potent capability. Both propofol and dexmedetomidine inhibited neuroinflammation, while propofol’s effect was slightly weaker. All sedative groups reduced the neural apoptosis, inhibited the activation of microglia and astrocytes, and relieved neurologic ferroptosis. The combined group was most prominent in combating genetic and biochemical alterations of ferroptosis. Fpn1 may be at the core of endotoxemia-related ferroptosis activation.Keywords: propofol, dexmedetomidine, endotoxemia, encephalopathy, ferroptosis

The emergence of Internet has greatly revolutionized the way that geospatial information is collected, managed, processed and integrated. There are several important research issues to be addressed for distributed geospatial applications. First, the performance of geospatial applications is needed to be considered in the Internet environment. In this regard, the Grid as an effective distributed computing paradigm is a good choice. The Grid uses a series of middleware to interconnect and merge various distributed resources into a super-computer with capability of high performance computation. Secondly, it is necessary to ensure the secure use of independent geospatial applications in the Internet environment. The Grid just provides the utility of secure access to distributed geospatial resources. Additionally, it makes good sense to overcome the heterogeneity between individual geospatial information systems in Internet. The Open Geospatial Consortium (OGC) proposes a number of generalized geospatial standards e.g. OGC Web Services (OWS) to achieve interoperable access to geospatial applications. The OWS solution is feasible and widely adopted by both the academic community and the industry community. Therefore, we propose an integrated framework by incorporating OWS standards into Grids. Upon the framework distributed geospatial queries can be performed in an interoperable, high-performance and secure Grid environment.

Recently, more and more geospatial data are generated and distributed with the promising data acquirement techniques like satellite imaging and digital cartography. So, it is an important issue to effectively make use of these huge geospatial data resources. This means that effective data processing technologies need to be developed to support distributed query and analysis operations onto the distributed resources. The emergence of grid computing technology offers a good solution to accomplish this goal. To combine the grid computing technique with geospatial database we design and implement a GGDS (Grid Geospatial Database System) prototype named GEOBARN. Key modules and detailed implementation methods of GEOBARN are discussed in this paper. By using the GEOBARN system, both reliable data management and effective distributed geospatial query can be achieved.

Jiayi Yang,&ast; Lihong Chen,&ast; Ruofei Shi, Xiaoqing Zhao, Meng Pan, Jie Zheng Department of Dermatology, School of Medicine, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meng Pan, Email pm10633@rjh.com.cnBackground: Cytophagic histiocytic panniculitis (CHP) is a rare form of nodular panniculitis characterized by clinical manifestations such as skin erythema, nodules, fever, pancytopenia, liver failure, plasmacytosis, and hepatosplenomegaly. We report a case of CHP that was initially misdiagnosed as subcutaneous panniculitis-like T-cell lymphoma (SPTCL) but achieved complete remission with a favorable prognosis.Methods: A 38-year-old female presented to the dermatology department with a 15-day history of subcutaneous nodules, generalized edema, and continuous fever.Results: The patient was diagnosed as CHP combined with hemophagocytic syndrome by typical clinical manifestations, low value of SUVmax in positron emission tomography/computed tomography (PET/CT), benign differentiated T cells, negative TCR gene rearrangement, pancytopenia, abnormal coagulation, hypertriglyceridemia, decreased NK cell count, impaired liver function, and the presence of hemophagocytic cells observed in bone biopsy smears.Conclusion: In our case, the patient presented with hemophagocytic syndrome with hemodynamic instability, indicating an intensive treatment is needed. The diagnosis of SPTCL necessitates a meticulous process of differential diagnosis, along with the cautious administration of an aggressive chemotherapy regimen. Extended follow-up is imperative to ascertain the long-term outcomes.Keywords: cytophagic histiocytic panniculitis, SPTCL, HLH

We propose and investigate a novel coherent laser array design based on laterally coupled photonic crystal surface-emitting lasers (PCSELs). As a new type of semiconductor laser technology, PCSELs have field confinement in a planar cavity and laser beam emission in the surface normal direction. By engineering lateral couplings between PCSELs with heterostructure photonic crystal designs, we can achieve coherent operations from an array of PCSELs. In this paper, we demonstrate coherent operation from a passively coupled PCSEL array design. We fabricated PCSEL array devices on a GaAs-based quantum well heterostructure at a target wavelength of 1040 nm. Experimental results show that the 2-by-2 PCSEL arrays have spectral linewidth of 0.14–0.22 nm. Beam combining performance was characterized by self-interference experiments. Similar coherency between the PCSEL array and single PCSEL device was observed. Our compact PCSEL array designs by passive lateral coupling have potential applications in fields of on-chip photonic computing, quantum, and information processing. [ABSTRACT FROM AUTHOR]

Xuejun Tan,1 Yukun Xu,1 Sirui Zhou,1 Mingyue Pan,1 Yue Cao,1 Xiuping Cai,2 Qing Zhao,1,2,&ast; Kewei Zhao1,2,&ast; 1The Third Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Guangzhou Key Laboratory of Chinese Medicine Research on Prevention and Treatment of Osteoporosis, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kewei Zhao; Qing Zhao, Department of Laboratory Medicine, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, 261 Longxi Avenue, Liwan District, Guangzhou, Guangdong, People’s Republic of China, Tel +86-13711355225 ; +86-18825144487, Email zkw2011@gzucm.edu.cn; zhaoqing900116@126.comAbstract: All humans are universally affected by inflammatory diseases, and there is an urgent need to identify new anti-inflammatory drugs with good therapeutic benefits and minimal side effects to the organism. Recently, it has been found that plant-derived vesicle-like nanoparticles (PDVLNs) have good biocompatibility, with their active ingredients exhibiting good therapeutic effects on inflammation. They can also be used as drug carriers for targeted delivery of anti-inflammatory drugs. Therefore, PDVLNs represent a popular research area for novel anti-inflammatory drugs. This paper details the origin, biological functions, isolation and purification, and identification of PDVLNs, as well as the therapeutic effects of their intrinsic bioactive components on inflammatory diseases. It also introduces their targets as drug carriers to facilitate the development and application of PDVLNs anti-inflammatory drugs.Keywords: plant, vesicle-like nanoparticles, inflammation, inflammatory diseases

Xiao-Jie Zhang,1 Jian-Guo Zhou,1 Miao Pan,1 Wei Yuan,2 Bo Gao1 1Department of Pharmacy, General Hospital of Yangquan Coal Industry Group, Yangquan, People’s Republic of China; 2Department of Oncology and Interventional Radiology, Yangquan Hospital of Shanxi Medical University, Yangquan, People’s Republic of ChinaCorrespondence: Wei Yuan, Department of Oncology and Interventional Radiology, Yangquan Hospital of Shanxi Medical University, No. 218 of North Street, Mining District, Yangquan, 045000, People’s Republic of China, Tel/Fax +86 131 6212 9135, Email lvyingyw@126.com Bo Gao, Department of Pharmacy, General Hospital of Yangquan Coal Industry Group, Yangquan, People’s Republic of China, Tel/Fax +86 139 3539 8859, Email gaobo12@um.gt.cnObjective: Through analyzing the characteristics and influencing factors of adverse drug reactions/adverse events (ADR/ADE) in a hospital to promote rational drug use in the clinic.Methods: A total of 1221 ADR/ADE reports collected from a hospital in 2022 were retrieved through the National Adverse Drug Reaction Monitoring Center. The effective reports were screened according to the Guiding Principles for Collection and Reporting of Individual Adverse Drug Reactions, and classified the standardized drugs. The systems/organs and main clinical symptoms affected by ADR/ADE were classified according to the WHO Glossary of Adverse Drug Reaction Terms. The severity, age and gender, occupational distribution, drug category, route of administration, drug dosage form, system/organ involved, and main clinical symptoms of ADR/ADE reports were analyzed.Results: Among 1221 ADR/ADE reports, 890 cases (75.27%) reported by doctors; 144 cases (11.79%) were serious; Precisely 49.22% of ADR/ADE occurred in patients aged 51 to 70 years old; The highest incidence of adverse reactions was 636 cases (52.09%) by intravenous infusion, 406 cases (33.25%) by oral administration. The top categories of reported cases were anti-infective drugs (29.40%) and anti-tumor drugs (27.52%); Systems/organs involved in ADR/ADE were mainly the skin and its accessories (24.96%) and blood system (21.35%). 166 cases were cured, 893 cases were symptomatic, 160 cases were unknown, and 2 cases had sequelae.Conclusion: The occurrence of ADR/ADE is related to many influencing factors such as age, drug categories, and route of administration. Therefore, it is recommended that hospitals strengthen the monitoring of ADR/ADE, especially the elderly, anti-infective drugs and intravenous administration.Keywords: adverse drug reactions, adverse events, report analysis, the rational use of drugs

Wenzhe Zhao,1 Haiqin Zhu,1 Xiaoqing Zhao,1 Xinyi Wu,1 Fei Sun,1 Meng Pan,1,&ast; Shengru Zhou2,&ast; 1Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), Suzhou, 215123, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengru Zhou, Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University, (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), No. 9, Chongwen Road, Suzhou, 215123, People’s Republic of China, Tel +86-17717453465, Fax +86-2164669691, Email zhoushengru1989@foxmail.comPurpose: Direct immunofluorescence (DIF) on frozen sections (DIF-F) plays a key role in the identification and differential diagnosis of bullous dermatoses, which are a group of critical autoimmune diseases that include pemphigus, bullous pemphigoid (BP), and epidermolysis bullosa acquisita (EBA). However, this technique requires specialized laboratory equipment conditions, sample acquisition and sample preservation. In this study, the application value of DIF on paraffin-embedded tissue sections (DIF-P) detecting IgG using heat-induced antigen retrieval (HIAR) in the diagnosis of bullous dermatosis was explored.Patients and Methods: Samples from 12 patients with pemphigus vulgaris (PV), 10 patients with pemphigus foliaceus (PF), 17 patients with BP, and 4 patients with EBA were retrospectively studied for DIF-P IgG detection. Formalin-fixed, paraffin-embedded tissue (FFPE) was used, and the antigen retrieval method used in the experiment was HIAR. All patients were diagnosed with the autoimmune bullous disease (AIBD) based on clinical presentation, histopathology, DIF-F, and enzyme-linked immunosorbent assay (ELISA).Results: Intercellular staining for IgG in the epidermis was successful in paraffin-embedded tissue sections in 11 of 12 PV samples and in all 10 PF samples. IgG at the basement membrane zone (BMZ) was not detected by immunofluorescent staining in 17 BP samples and 4 EBA samples.Conclusion: The detection of IgG by DIF-P using HIAR can be used for the diagnosis of pemphigus as an alternative method to DIF-F.Keywords: pemphigus, bullous dermatoses, direct immunofluorescence, IgG, paraffin-embedded section, heat-induced antigen retrieval

Yan Lin,1,&ast; Jiaoning Fang,1,&ast; Ruilan Ni,1,&ast; Li Zhang,1 Jie Zhao,1 Xiumin Jiang,2 Yuping Lin,2 Mian Pan1 1Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Nurse, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mian Pan, Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-13178031273 ; +86-591-86329321, Email panmian1973@126.com Xiumin Jiang, Department of Nurse, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Email jzc0427@163.comObjective: Cervical cerclage is an effective method to prevent preterm birth. However, the clinical indicators that can predict cervical cerclage remain limited. This study aimed to explore whether dynamically inflammatory markers are valuable biomarkers for the prognosis of cervical cerclage.Methods: This study included 328 participants. Inflammatory markers were calculated using maternal peripheral blood before and after the cervical cerclage procedure. The Chi-square test, linear regression, and logistic regression were performed to evaluate the dynamic change of inflammatory markers with the prognosis of cervical cerclage. And the optimal cut-off values of inflammatory markers were calculated.Results: Totally 328 pregnant women were analyzed in the study. 223 (67.99%) participants obtained successful cervical cerclage. This study revealed that the maternal age, the baseline BMI (cm2/kg), the times of gravida, the rate of recurrent abortion, the PPROM, cervical length shorter (< 1.5cm), cervical dilation (≥ 2cm), the bulging membrane, the Pre-SII, the Pre-SIRI, the Post-SII, the Post-SIRI, and the ΔSII were significantly associated with outcomes after cervical cerclage (all P< 0.05). Pre-SII, Pre-SIRI, Post-SII, Post-SIRI, and ΔSII levels were mainly related to maternal-neonatal outcomes. Furthermore, the results demonstrated that the ΔSII level had the highest OR (OR=14.560; 95% CI (4.461– 47.518)). In addition, we revealed that Post-SII and ΔSII levels had the highest AUC (0.845/0.840) and relatively higher sensitivity/specificity (68.57/92.83% and 71.43/90.58%) and PPV/ NPV (81.82/86.25% and 78.13/87.07%) compared with other indicators.Conclusion: This study suggested that the dynamic change of SII level and SIRI level are important biochemical markers to predict the prognosis of cervical cerclage and maternal-neonatal prognosis, especially the Post-SII and ΔSII levels. They can help to determine candidates for cervical cerclage before surgical procedure and enhance postoperative surveillance.Keywords: cervical cerclage, maternal-neonatal, outcome, inflammatory markers, peripheral blood

No abstract available.

Jiaoning Fang,1,&ast; Yingying Lin,2,&ast; Zhiwei Chen,3,&ast; Yan Lin,1 Mian Pan1 1Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Healthcare, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Gynecologic, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mian Pan; Yan Lin, Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Medical University, Fuzhou, People’s Republic of China, Tel +86-13178031273 ; +86-591-86329321 ; +86-13665051036, Email panmian1973@126.com; 571313649@qq.comObjective: Cervical cerclage is effective in prolonging the number of weeks gestation in patients with cervical insufficiency(CI). However, valuable predictors with successful cervical cerclage remain limited. It aimed to evaluate the value of the systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) to predict the outcomes of cervical cerclage.Methods: This study analyzed 374 participants. Inflammatory markers were calculated using maternal peripheral blood. The association of inflammatory markers and the outcome of cervical cerclage were analyzed. And the optimal cut-off values of inflammatory markers were calculated. Also, the Chi-square test and logistic and linear regression analyses were performed to evaluate inflammatory markers with the maternal outcome and neonatal outcomes.Results: 374 pregnancies were included in this study. Finally, 268 (71.7%) participants suffered successful cervical cerclage. This study demonstrated that the baseline BMI (cm2/kg), the bulging membrane, cervical dilation (≥ 2cm), the amniotic sac herniation, the neutrophils counts, the systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) were significant difference between the successful and unsuccessful groups (all P< 0.05). Additionally, maternal blood inflammatory markers, such as WBC, lymphocyte, neutrophils, monocyte, platelet counts, SII, and SIRI, were significantly associated with maternal-neonatal outcomes. Furthermore, the results demonstrated that the SII level had the highest OR (OR=4.626; 95% CI (2.500– 8.560)), as well as the following: SIRI level (OR = 3.795; 95% CI (1.989– 7.242)), cervical dilation (≥ 2cm) (OR =3.477; 95% CI (1.458– 10.844)), and amniotic sac herniation (OR = 1.796; 95% (0.473– 4.975)).Conclusion: This study demonstrated that the baseline SII level and SIRI level are important biochemical markers for predicting the outcome of cervical cerclage and maternal-neonatal outcomes with non-invasive procedures. They can help to provide personalized treatment before surgery and enhance postoperative surveillance.Keywords: cervical cerclage, maternal-neonatal, outcome, inflammatory markers, peripheral blood

Hongxing Hu,1 Hang Zhang,2 Ziheng Bu,3 Zhongtang Liu,3 Fang Lv,4,5 Mingmang Pan,5 Xuan Huang,3 Liming Cheng1 1Department of Orthopedics Tongji Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2School of Mechanical Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Orthopedics Changhai Hospital Affiliated to the Second Military Medical University, Shanghai, People’s Republic of China; 4Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Science and School of Life Science, East China Normal University, Shanghai, People’s Republic of China; 5Department of orthopedics, Shanghai Fengxian District Central Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Xuan Huang, Department of Orthopedics Changhai Hospital Affiliated to the Second Military Medical University, 168 Changhai Road, Shanghai, People’s Republic of China, Tel +86 18930172772, Email 11791709@qq.com Liming Cheng, Department of Orthopedics Tongji Hospital Affiliated to Tongji University, Tongji University School of Medicine, 389 Xincun Road, Shanghai, People’s Republic of China, Tel +86-21-56051080, Email limingcheng@tongji.edu.cnBackground: The treatment of critical-size bone defect is a great difficulty in orthopedics. Osteogenesis and angiogenesis are critical issue during the process of bone repair and remodeling. Mesenchymal stem cells (MSCs)-derived exosomes have the same therapeutic effect to MSCs-based therapies. The effect of human umbilical cord MSCs-derived sEVs (hUC-MSCs-sEVs) on vascularized bone regeneration and the potential mechanism remains to be investigated. Herein, we aimed to explore the therapeutic effect and the mechanism of hUC-MSCs-sEVs on critical-size bone defect.Methods: To investigate the potential osteogenesis and angiogenesis effects of sEVs in vitro, we extracted sEVs from hUC-MSCs, and then sEVs were co-incubated with BMSCs and HUVECs. We next investigated the effect and potential mechanism of sEVs on the effects of osteogenesis and angiogenesis. We fabricated 3D-printed bioglass scaffold with Gelma/nanoclay hydrogel coatings to load sEVs (BG-gel-sEVs) to ensure in vivo sustained efficacy of sEVs. Finally, the skull defect model was used to evaluate the capacity of vascularized bone regeneration of the composited scaffolds.Results: hUC-MSCs-sEVs facilitated calcium deposition and the endothelial network formation, inducing osteogenic differentiation and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway. Additionally, the BG-gel-sEVs composited scaffold achieved vascularized bone regeneration in vivo.Conclusion: This finding illuminated that hUC-MSCs-sEVs promoted osteogenesis and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway, achieving vascularized bone regeneration.Keywords: small extracellular vesicles, bone regeneration, angiogenesis, miR-23a-3p, bioglass scaffolds

The vertical distribution of dust in debris disks is sensitive to the number and size of large planetesimals dynamically stirring the disk, and is therefore well-suited for constraining the prevalence of otherwise unobservable Uranus and Neptune analogs. Information regarding stirring bodies has previously been inferred from infrared and optical observations of debris disk vertical structure, but theoretical works predict that the small particles traced by short-wavelength observations will be puffed up by radiation pressure, yielding only upper limits. The large grains that dominate the disk emission at millimeter wavelengths are much less sensitive to the effects of stellar radiation or stellar winds, and therefore trace the underlying mass distribution more directly. Here we present ALMA 1.3 mm dust continuum observations of the debris disk around the nearby M star AU Mic. The 3 au spatial resolution of the observations, combined with the favorable edge-on geometry of the system, allows us to measure the vertical thickness of the disk. We report a scale height-to-radius aspect ratio of = -h 0.031+0.004 0.005 between radii of ∼23 au and ∼41 au. Comparing this aspect ratio to a theoretical model of size-dependent velocity distributions in the collisional cascade, we find that the perturbing bodies embedded in the local disk must be larger than about 400 km, and the largest perturbing body must be smaller than roughly 1.8M. These measurements rule out the presence of a gas giant or Neptune analog near the ∼40 au outer edge of the debris ring, but are suggestive of large planetesimals or an Earth-sized planet stirring the dust distribution.

Suke Xing,1,2 Hui Zhang,2 Ye Qiu,3 Mianluan Pan,1 Wen Zeng,2 Jianquan Zhang1 1Department of Respiratory and Critical Medicine, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518000, People’s Republic of China; 2Department of Respiratory Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Comprehensive Internal Medicine, the Affiliated Tumour Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Jianquan Zhang, Department of Respiratory and Critical Medicine, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518000, Guangdong, People’s Republic of China, Tel +8613978123845, Fax +86755-23482484, Email jqzhang2002@126.comPurpose: To summarize the clinical characteristics, treatment and outcomes of transplant recipients infected with Talaromyces marneffei (TM).Materials and Methods: A retrospective analysis was performed on 2 patients with Talaromycosis marneffei (TSM) and transplants at the First Affiliated Hospital of Guangxi Medical University, and a systematic literature review was conducted simultaneously.Results: This article reported two patients after kidney transplantation who developed fever, cough within 3– 4 months. Their haemoglobin was decreased. Their chest computed tomography (CT) showed nodules. TM was detected in their blood or bronchoalveolar lavage fluid samples by next-generation sequencing (NGS). After antifungal treatment with voriconazole (VOR), one patient worsened, the other patient died. A total of 21 patients with TSM after transplants were reported in the literature review. Fourteen underwent kidney transplantation, 4 underwent liver transplantation, 2 underwent lung transplantation, and 1 underwent bone marrow transplantation. The median time from initiating the postoperative immunosuppressive therapy to the onset of symptoms or disease changes was 18 (0.5– 140) months. Among them, 9 patients developed fever, 7 patients developed cough or expectoration and 4 patients developed dyspnoea. Haemoglobin was decreased in 10 patients. Pulmonary nodules were found in 7 patients. Among the 21 patients, 7 were diagnosed by positive culture, 6 by biopsy, 5 by culture and biopsy. Of the 21 patients, 13 patients improved by antifungal therapy, 8 patients worsened or died. Seven patients who received amphotericin B followed by itraconazole (ITR) therapy all improved. Regarding the use of immunosuppressants in 12 patients, 9 patients had to discontinue or reduce their medications (6 patients improved, 3 patients worsened or died).Conclusion: Patients with TSM after transplant often have disseminated infections, involving the respiratory, hematopoietic and so on. Fever, cough, decreased haemoglobin and pulmonary nodules often occur approximately 18 months after surgery. The combined applications of culture, biopsy, NGS are helpful for an early diagnosis. Antifungal therapy with amphotericin B followed by itraconazole is recommended, and the dosage of the immunosuppressant should be adjusted timely.Keywords: Talaromyces marneffei, Talaromycosis marneffei, transplant recipients, immunosuppressants, antifungal drug

Lei Dong,1,&ast; Nana Li,1,&ast; Xixi Wei,2 Yongling Wang,2 Liansheng Chang,3 Hongwei Wu,4 Liujiang Song,5 Kang Guo,6 Yuqiao Chang,1 Yaling Yin,2 Min Pan,7 Yuanyuan Shen,8 Feng Wang1 1Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 2Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 3Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 4Department of Chemistry, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 5Department of Ophthalmology, Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27517, USA; 6Department of Oncology, The Third affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 7Department of Ultrasound, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, 518034, People’s Republic of China; 8National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Wang, Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453002, People’s Republic of China, Email wfeng100@126.com Min Pan, Department of Ultrasound, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, No. 6001 Beihuan Avenue, Shenzhen, 518034, People’s Republic of China, Email min.pan@siat.ac.cnBackground: The blood–brain barrier (BBB) inhibits the delivery of macromolecular chemotherapeutic drugs to brain tumors, leading to low utilization rates and toxic side effects to surrounding tissues and organs. Ultrasonic targeted microbubble destruction (UTMD) technology can open the BBB, leading to a new type of drug delivery system with particular utility in glioma.Purpose: We have developed a new type of drug-loaded microbubble complex based on poly(lactic-co-glycolic acid) (PLGA) that targets gambogic acid (GA) to the area of brain tumors through UTMD.Methods: GA/PLGA nanoparticles were prepared by the double emulsification method, and cationic microbubbles (CMBs) were prepared by a thin film hydration method. The GA/PLGA-CMB microbubble complex was assembled through electrostatic attractions and was characterized chemically. The anti-glioblastoma effect of GA/PLGA-CMB combined with focused ultrasound (FUS) was evaluated by biochemical and imaging assays in cultured cells and model mice.Results: GA/PLGA-CMB combined with FUS demonstrated a significant inhibitory effect on glioblastoma cell lines U87 and U251 as compared with controls (P< 0.05). Tumor access and imaging analyses demonstrated that administration of GA/PLGA-CMBs combined with FUS can open the BBB and target the treatment of glioblastoma in a mouse model, as compared with control groups (P< 0.05).Conclusion: The combination of PLGA-CMB with FUS provides an effective and biocompatible drug delivery system, and its application to the delivery of GA in a mouse glioblastoma model was successful.Keywords: microbubbles, cavitation effect, glioblastoma, focused ultrasound

Sirui Fu,1,2,&ast; Meiqing Pan,2,3,&ast; Jie Zhang,4,&ast; Hui Zhang,2,3,5,&ast; Zhenchao Tang,2,3,5 Yong Li,1 Wei Mu,2,3,5 Jianwen Huang,1 Di Dong,3 Chongyang Duan,6 Xiaoqun Li,7 Shuo Wang,2,3 Xudong Chen,8 Xiaofeng He,9 Jianfeng Yan,10 Ligong Lu,1 Jie Tian2,3,5,11 1Zhuhai Interventional Medical Centre, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, People’s Republic of China; 2Beijing Advanced Innovation Centre for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, People’s Republic of China; 3CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People’s Republic of China; 4Department of Radiology, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, People’s Republic of China; 5Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, People’s Republic of China; 6Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, People’s Republic of China; 7Department of Interventional Treatment, Zhongshan City People’s Hospital, Zhongshan, People’s Republic of China; 8Department of Radiology, Shenzhen People’s Hospital, Shenzhen, People’s Republic of China; 9Interventional Diagnosis and Treatment Department, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 10Department of Radiology, Yangjiang People’s Hospital, Yangjiang, People’s Republic of China; 11University of Chinese Academy of Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie TianBeijing Advanced Innovation Centre for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, 100191, People’s Republic of ChinaEmail tian@ieee.orgLigong LuZhuhai Interventional Medical Centre, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Kangning Road, Zhuhai, 519000, Guangdong Province, People’s Republic of ChinaEmail llg0902@sina.comPurpose: For timely treatment of extrahepatic metastasis and macrovascular invasion (aggressive progressive disease [PD]) in hepatocellular carcinoma, models aimed at stratifying the risks of subsequent aggressive PD should be constructed.Patients and Methods: After dividing 332 patients from five hospitals into training (n = 236) and validation (n = 96) datasets, non-invasive models, including clinical/semantic factors (ModelCS), deep learning radiomics (ModelD), and both (ModelCSD), were constructed to stratify patients according to the risk of aggressive PD. We examined the discrimination and calibration; similarly, we plotted a decision curve and devised a nomogram. Furthermore, we performed analyses of subgroups who received different treatments or those in different disease stages and compared time to aggressive PD and overall survival in the high- and low-risk subgroups.Results: Among the constructed models, ModelCSD, combining clinical/semantic factors and deep learning radiomics, outperformed ModelCS and ModelD (areas under the curve [AUCs] for the training dataset: 0.741, 0.815, and 0.856; validation dataset: 0.780, 0.836, and 0.862), with statistical difference per the net reclassification improvement, the integrated discrimination improvement, and/or the DeLong test in both datasets. Besides, ModelCSD had the best calibration and decision curves. The performance of ModelCSD was not affected by treatment types (AUC: resection = 0.839; transarterial chemoembolization = 0.895; p = 0.183) or disease stages (AUC: BCLC [Barcelona Clinic Liver Cancer] stage 0 and A = 0.827; BCLC stage AB &B = 0.861; p = 0.537). Moreover, the high-risk group had a significantly shorter median time to aggressive PD than the low-risk group (training dataset hazard ratio [HR] = 0.108, p < 0.001; validation dataset HR = 0.058, p < 0.001) and poorer overall survival (training dataset HR = 0.357, p < 0.001; validation dataset HR = 0.204, p < 0.001).Conclusion: Our deep learning-based model successfully stratified the risks of aggressive PD. In the high-risk population, current guideline indicates that first-line treatments are insufficient to prevent extrahepatic metastasis and macrovascular invasion and ensure survival benefits, so more therapies may be explored for these patients.Keywords: aggressive disease progression, deep learning radiomics, clinical factors, high-risk, risk prediction

Wen Zeng,1,2 Ye Qiu,1,2 Mengxin Tang,1,2 Hui Zhang,2 Mianluan Pan,1 Shudan Tang,2 Jianquan Zhang1 1Department of Respiratory and Critical Medicine, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, 518000, People’s Republic of China; 2Department of Respiratory and Critical Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Jianquan ZhangDepartment of Respiratory and Critical Medicine, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, 518000, People’s Republic of ChinaTel +8613978123845Fax +86755-23482484Email jqzhang2002@126.comAbstract: A high titer of neutralizing anti-interferon-γ autoantibodies can cause immunodeficiency associated with severe or disseminated infections caused by Talaromyces marneffei in human immunodeficiency virus-negative patients. Herein, we reported a rare case of disseminated Talaromyces marneffei and Burkholderia cepacia infection. The patient’s lungs, lymph nodes, and bronchi were involved, and he had neck abscesses and osteomyelitis. We measured the neutralizing anti-interferon-γ autoantibodies in the peripheral blood and found that the patient had a persistently high positive titer. Despite aggressive treatment, the patient developed disseminated intravascular coagulation and died. Thus, high-titer nAIGAs may be associated with multiple opportunistic, persistent and disseminated infections.Keywords: Burkholderia cepacia, Talaromyces marneffei, adult immunodeficiency, neutralizing anti-interferon-γ autoantibodies

Recent Atacama Large Millimeter/submillimeter Array observations present mounting evidence for the presence of exocometary gas released within Kuiper Belt analogs around nearby main-sequence stars. This represents a unique opportunity to study their ice reservoir at the younger ages when volatile delivery to planets is most likely to occur. We here present the detection of CO J = 2-1 emission colocated with dust emission from the cometary belt in the 440 Myr old Fomalhaut system. Through spectrospatial filtering, we achieve a 5.4σ detection and determine that the ring's sky-projected rotation axis matches that of the star. The CO mass derived ((0.65-42) × 10-7 M⊕) is the lowest of any circumstellar disk detected to date and must be of exocometary origin. Using a steady-state model, we estimate the CO+CO2 mass fraction of exocomets around Fomalhaut to be between 4.6% and 76%, consistent with solar system comets and the two other belts known to host exocometary gas. This is the first indication of a similarity in cometary compositions across planetary systems that may be linked to their formation scenario and is consistent with direct interstellar medium inheritance. In addition, we find tentative evidence that (49 ± 27)% of the detected flux originates from a region near the eccentric belt's pericenter. If confirmed, the latter may be explained through a recent impact event or CO pericenter glow due to exocometary release within a steady-state collisional cascade. In the latter scenario, we show how the azimuthal dependence of the CO release rate leads to asymmetries in gas observations of eccentric exocometary belts.

We present ALMA mosaic observations at 1.3 mm (223 GHz) of the Fomalhaut system with a sensitivity of 14 μJy/beam. These observations provide the first millimeter map of the continuum dust emission from the complete outer debris disk with uniform sensitivity, enabling the first conclusive detection of apocenter glow. We adopt an MCMC modeling approach that accounts for the eccentric orbital parameters of a collection of particles within the disk. The outer belt is radially confined with an inner edge of 136.3 ± 0.9 au and width of 13.5 ± 1.8 au. We determine a best-fit eccentricity of 0.12 ± 0.01. Assuming a size distribution power-law index of q = 3.46 ± 0.09, we constrain the dust absorptivity power-law index β to be 0.9 < β < 1.5. The geometry of the disk is robustly constrained with inclination 65.°6 ± 0.°3, position angle 337.°9 ± 0.°3, and argument of periastron 22.°5 ± 4.°3. Our observations do not confirm any of the azimuthal features found in previous imaging studies of the disk with Hubble Space Telescope, SCUBA, and ALMA. However, we cannot rule out structures ≤10 au in size or that only affect smaller grains. The central star is clearly detected with a flux density of 0.75 ± 0.02 mJy, significantly lower than predicted by current photospheric models. We discuss the implications of these observations for the directly imaged Fomalhaut b and the inner dust belt detected at infrared wavelengths.

Cancer cells depend on glutamine to sustain their increased proliferation and manage oxidative stress, yet glutamine is often depleted at tumor sites owing to excessive cellular consumption and poor vascularization. We have previously reported that p53 protein, although a well-known tumor suppressor, can contribute to cancer cell survival and adaptation to low-glutamine conditions. However, the TP53 gene is frequently mutated in tumors, and the role of mutant p53 (mutp53) in response to metabolic stress remains unclear. Here, we demonstrate that tumor-associated mutp53 promotes cancer cell survival upon glutamine deprivation both in vitro and in vivo. Interestingly, cancer cells expressing mutp53 proteins are more resistant to glutamine deprivation than cells with wild-type p53. Depletion of endogenous mutp53 protein in human lymphoma cells leads to cell sensitivity to glutamine withdrawal, whereas expression of mutp53 in p53 null cells results in resistance to glutamine deprivation. Furthermore, we found that mutp53 proteins hyper-transactivate p53-target gene CDKN1A upon glutamine deprivation, thus triggering cell cycle arrest and promoting cell survival. Together, our results reveal an unidentified mechanism by which mutp53 confers oncogenic functions by promoting cancer cell adaptation to metabolic stress.

Accurate global mapping of soil moisture is the goal of the Soil Moisture Active Passive (SMAP) mission, which is expected to improve the estimation of water, energy, and carbon exchanges between the land and the atmosphere. Like other satellite products, the SMAP soil moisture retrievals need to be validated, with the validation relying heavily on in situ measurements. However, a one-to-one comparison is ill advised due to the spatial mismatch of the large SMAP footprint (∼40 km) and the point scale in situ measurements. This study uses a recently developed hyper-resolution land surface model—HydroBlocks—as a tool to upscale in situ soil moisture measurements for the SMAPVEX15 (SMAP Validation Experiment 2015) field campaign during 2–18 August 2015. Calibrated against in situ observation, HydroBlocks shows a satisfactory Kling-Gupta efficiency (KGE) of 0.817 and RMSE of 0.019 m3/m3 for the calibration period. These results indicate that HydroBlocks can be used to upscale in situ measurements for this site. Different from previous studies, here in situ measurements are upscaled using a land surface model without bias correction. The upscaled soil moisture is then used to evaluate SMAP (passive) soil moisture products. The comparison of the upscaled network to SMAP shows that the retrievals are generally able to capture the areal-averaged soil moisture temporal variations. However, SMAP appears to be oversensitive to summer precipitation. We expect these findings can be used to improve the SMAP soil moisture product and thus facilitate its usage in studying the water, energy, and carbon cycles.

Yangliang Yang, Jing Yi, Mengzhi Pan, Baoji Hu, Hongwei Duan Department of Anesthesiology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of ChinaCorrespondence: Hongwei DuanDepartment of Anesthesiology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, No. 2800 Gongwei Road, Shanghai, 201399, People’s Republic of ChinaEmail duanhongwei120@126.comBackground: To investigate the neuroprotective effect of edaravone on excessive-dose propofol-induced neurotoxicity in the hippocampus of newborn rats and HT22 cells.Methods: Cell proliferation was investigated by assessing ki67 expression in the neural stem of the hippocampus of newborn rats and by cell counting kit-8 (CCK8) assay in HT22 cells. Cell apoptosis was assessed in vivo by caspase 3 detection in Western blots and measurement of apoptosis in neurons and glial cells by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Apoptosis was analyzed by flow cytometry in HT22 cells. The Morris water maze was used to evaluate the long-term learning and memory ability of rats. Inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The expression of mBDNF/TrkB/PI3K pathway-related proteins was detected by Western blot and quantitative reverse transcription-polymerase chain reaction (q-RT PCR).Results: In neonatal rat hippocampus and HT22 cells, edaravone increased cell proliferation and decreased cell apoptosis after excessive propofol-induced neurotoxicity. In addition, the levels of proinflammatory factors interleukin (IL)-6 and tumor necrosis factor (TNF)-α were reduced by edaravone pretreatment. The use of the tropomyosin receptor kinase B (TrkB) antagonist ANA-12 and TrkB agonist 7,8DHF with propofol groups showed that edaravone mitigated excessive propofol-induced neurotoxicity through the mature brain-derived neurotrophic factor (mBDNF)/TrkB/phosphoinositide 3-kinase (PI3K) pathway. However, the current dose of propofol did not significantly affect long-term learning and memory in rats.Conclusion: Edaravone pretreatment ameliorated propofol-induced proliferation inhibition, neuroapoptosis, and neural inflammation by activating the mBDNF/TrkB/PI3K pathway.Keywords: edaravone, propofol, hippocampus, the brain-derived neurotrophic factor, BDNF, the tyrosine kinase receptor B, TrkB, 7,8-dihydroxyflavone, 7,8-DHF, ANA-12

Lei Li, Zhihai Wang, Tao Lu, Yanshi Li, Min Pan, Dan Yu, Guohua Hu Department of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Guohua HuDepartment of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaTel +86-23-89012945Fax +86-23-89012981Email hghcq@sina.comPurpose: The purpose of this study is to investigate the expression and functional role of Annexin (ANXA1) in lymph node (LN) metastasis of hypopharyngeal carcinoma (HSCC).Methods: Differentially expressed genes in tissue from HSCC with or without LN metastasis were obtained from a previous RNA sequencing experiment. The presence of LN metastasis is determined by pathological diagnosis after neck dissection. ANXA1 expression was detected by qRT-PCR and Western blotting. Immunohistochemistry was used to detect the expression of ANXA1 in 74 cases of HSCC and normal control tissues. We also evaluated the clinical significance of ANXA1 in HSCC. Differentially expressed genes related to ANXA1 were analyzed using bioinformatic tools, and potential mechanisms of action of ANXA1 were assessed using in vitro experiments. In these in vitro experiments, cell proliferation was detected by CCK8 staining, and colony formation, migration and invasion were assessed using Transwell assays, and apoptosis as well as cell cycle status were quantified by flow cytometry.Results: ANXA1 was significantly downregulated in HSCC with LN metastasis. The survival rate of patients with low ANXA1 expression was significantly worse than that of patients with high ANXA1 expression (p< 0.05). Silencing ANXA1 in cell culture experiments promoted the proliferation, migration and invasion of FaDu cells, inhibited apoptosis, and increased the proportion of cells in S phase. We furthermore found that the mRNA expression of ANXA1 was positively correlated with Yap1 expression (p< 0.0001). Our in vitro experiments showed that ANXA1 regulates the expression of Yap1, and over-expression of Yap1 could reverse the effect of ANXA1 silencing on cancer cell progression.Conclusion: Our findings suggest that ANXA1 is a putative LN metastasis suppressor gene in tumor, which may suppress the LN metastasis of HSCC by regulating the expression of Yap1.Keywords: HSCC, ANXA1, Yap1, LN metastasis

Jingshan Wei,1 Ye Qiu,1 Wen Zeng,1 Mianluan Pan,1 Jianquan Zhang1,2 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, Pepole’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518033, Pepole’s Republic of ChinaCorrespondence: Jianquan ZhangDepartment of Respiratory and Critical Care Medicine, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518033, Pepole’s Republic of ChinaTel +86 139 7812 3845Fax +86 0771 535 0031Email jqzhang2002@126.comPurpose: Talaromyces marneffei is a highly invasive fungus, causing fatal mycosis in patients with or without HIV in Southeast and Eastern Asia. However, its presence in patients with systemic lupus erythematosus is rarely reported.Methods: We reported two SLE patients infected by T. marneffei and reviewed other patients reported in the English literature. All cases were pooled for analysis.Results: Eleven patients with SLE infected with T. marneffei infection were identified, including the two presented here. Three were male and eight were female; all were HIV negative. All the patients, except two where data were missing, had received immunosuppressants before T. marneffei infection. The main clinical features included fever, cough, lymph node enlargement, gastrointestinal symptoms, and rash. Five patients were misdiagnosed as having SLE exacerbation. T. marneffei was detected via culture or histopathologic analysis, with the fungus most commonly found in the blood. Seven of the 11 patients were successfully treated by timely antifungal therapy with concomitant SLE control, while four patients who did not receive antifungal therapy died.Conclusion: T. marneffei infection should be excluded when SLE patients, especially if on long-term immunosuppressants, present with fever, cough, lymph node enlargement, gastrointestinal symptoms, and rash. Controlling the lupus and timely antifungal treatment can improve the outcomes of SLE patients with T. marneffei infection.Keywords: Talaromyces marneffei, systemic lupus erythematosus, immunosuppressant

At the end of its first year of operation, we compare soil moisture retrievals from the Soil Moisture Active Passive (SMAP) mission to simulations from a land surface model with meteorological forcing downscaled from observations/reanalysis and in situ observations from sparse monitoring networks within continental United States (CONUS). The radar failure limits the duration of comparisons for the active and combined products (~3 months). Nevertheless, the passive product compares very well against in situ observations over CONUS. On average, SMAP compares to the in situ data even better than the land surface model and provides significant added value on top of the model and thus good potential for data assimilation. At large scale, SMAP is in good agreement with the model in most of CONUS with less-than-expected degradation over mountainous areas. Lower correlation between SMAP and the model is seen in the forested east CONUS and significantly lower over the Canadian boreal forests.