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The gut microbiota is implicated in the pathogenesis of hyperuricemia (HUA) and gout. However, it remains unclear whether probiotics residing in the host gut, such as Lactobacillus , can prevent HUA development. Herein, we isolated Lactobacillus plantarum SQ001 from the cecum of HUA geese and conducted in vitro assays on uric acid (UA) and nucleoside co-culture. Metabolomics and genome-wide analyses, revealed that this strain may promote nucleoside uptake and hydrolysis through its nucleoside hydrolase gene. The functional role of iunH gene was confirmed via heterologous expression and gene knockout studies. Oral administration of L. plantarum SQ001 resulted in increased abundance of Lactobacillus species and reduced serum UA levels. Furthermore, it downregulated hepatic xanthine oxidase, a key enzyme involved in UA synthesis, as well as renal reabsorption protein GLUT9, while enhancing the expression of renal excretion protein ABCG2. Our findings suggest that L. plantarum has potential to ameliorate gut microbial dysbiosis with HUA, thereby offering insights into its potential application as a probiotic therapy for individuals with HUA or gout., Competing Interests: YF, XL, JL, QM, XW, YZ, YZ, HL, DX, WM, JC, LW, QD, LB, MK, KM, ZL, HY, QC, YZ, LY, QT, WW No competing interests declared, XJ, JC Affiliated with Biotech Co. Ltd; the author has no financial interests to declare, PZ Affiliated with Chimelong Group Co; the author has no financial interests to declare, (© 2024, Fu et al.)

Laryngeal squamous cell carcinoma (LSCC) is a common cancer with high mortality and tumor mutation burden (TMB), and high TMB is associated with favorable survival. The expression, mutation, and survival data were obtained from The Cancer Genome Atlas database. The mutation and differentially expressed genes were analyzed using limma R package. The function enrichment was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. TMB-related genes were identified by Weighted correlation network analysis. Univariate, multivariate and Lasso cox analyses were used to determine hub genes. The risk model and mRNA expression was validated by Receiver Operating Characteristic curve and qRTPCR. The immune infiltration was analyzed by xCELL. The drug sensitivity was determined through gene set cancer analysis database. We identified 1129 differentially expressed genes related to TMB. Enrichment analysis showed they were associated with immune response. ANKLE1 and PPP1R14A were screened out as hub genes. Receiver Operating Characteristic curve identified that the risk model had an effective prognosis value in progression-free interval of LSCC. Immune infiltration levels of 16 immune cells were significantly changed in high risk score group compared with low risk score group. ANKLE1 and PPP1R14A expressions were significantly upregulated in tumor group, which was consistent with qRTPCR results, and associated with better prognosis. ANKLE1 was negatively related to many drug sensitivities, while PPP1R14A was positively related to some drug sensitivities. We constructed an effective risk model constructed by ANKLE1 and PPP1R14A which was related to TMB in LSCC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To identify the failure patterns and prognostic factors of nonmetastatic nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era., Methods: Data on 847 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2012 and 2016 were retrospectively reviewed. Survival outcome, failure patterns and prognosis factors were analyzed., Results: The 5-year local relapse-free survival, nodal relapse-free survival, distant metastasis-free survival, disease-free survival, and overall survival rates were 94.3%, 95.3%, 84.8%, 76.5% and 85.7%, respectively. The major local recurrence sites were the nasopharynx (91.5%, 43/47) and skull base (68.1%, 32/47); 39 patients had in-field failures, four had marginal failures, and four had out-field failures. Level IIb (62.2%, 23/37) was the most frequent regional recurrence site, followed by IIa (35.1%, 13/37) and retropharyngeal region (32.4%, 12/37); 35 cases had in-field failure alone, one had out-field failure alone, and one had both in- and out-field failure. TNM stage was the most significant factor for prognosis prediction. 402 (47.5%) patients had acute adverse events of grade 3 or 4; leukopenia (31.5%) and mucositis (26.7%) was the most common hematological and non-hematological event, respectively. Late complications were slight or moderate damages; xerostomia (647/847, 76.4%) and hearing impairment (422/847, 49.8%) remained the most troublesome., Conclusion: NPC patients treated with IMRT obtained satisfactory survival outcomes. The key failure pattern was distant metastasis. The main pattern of local-regional failure was in-field failure. Screening high risk patients with distant metastases and optimizing radiotherapy targets should be studied., 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 Ltd. All rights reserved.)

Background: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder. Clinically, the therapeutic strategy of PD could only alleviate the symptoms. Nursing plays a crucial role in providing patient education, symptom management, and psychosocial support. This study aims to analyze the current state and prospects of research in the field of Parkinson's disease (PD) and its associated nursing care through bibliometric methods to explore the trends that May guide its future development., Methods: Literature related to Parkinson's disease and nursing care was systematically searched by the Web of Science database from 1991 to 2023. Quantitative analysis of cooperative networks was conducted using bibliometric tools VOSviewer and CiteSpace., Results: The analysis covered 2,649 publications in the field of PD and nursing care, authored by 12,576 researchers from 3,869 institutions across 94 countries. The number of articles has steadily increased over the past 20 years. In this research field, the United States and the United Kingdom emerged as leading countries, and Radboud Universiteit Nijmegen was positioned as an international hub. Movement Disorders was identified as the journal with the highest output and with the most co-citation. Prof. Bastiaan R. Bloem published the most papers in the area, and Prof. Per Odin had the highest average citation. The major fields of these publications are clinical neurology, geriatrics & gerontology, multidisciplinary sciences, and health care sciences & services. Hot topics in the field predominantly revolve around Parkinson's disease, quality of life, and dementia., Conclusion: Research in Parkinson's disease and nursing care is experiencing a period of rapid growth, with continuous expansion in research scope and depth of investigation. One of the trends identified is the increasing focus on quality of life and the management of dementia in PD patients, reflecting the importance of these areas in research. The study further suggests that future advancements in the field May rely significantly on strengthening international collaborations and addressing global disparities in resource distribution, particularly by promoting research inclusivity and cooperation among low-resource countries., 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 Liao, Fang, Chen, Yin, Li, Zhou, Li, Jiang and Lei.)

To determine the optimal film management technique for garlic planting, this study aimed to investigate the effects of various film cover methods on soil quality and garlic yield in garlic cropping systems. To achieve these goals, trials with different film cover methods were conducted at the Jiangsu Academy of Agricultural Sciences in Nanjing. To investigate the impact of changes in soil quality and garlic yield, we set up four treatments： no film treatment （CK）, black polyethylene film treatment （HPE）, black poly（butylene- adipate-co-terephthalate） （PBAT） with straw composite film treatment （HSJ）, and white PBAT film treatment （BJ） in a garlic cropping system. Our results indicated that specific mulch coverings had a positive effect on both soil quality and garlic yield. The film cover treatments resulted in significant changes in soil physicochemical properties and bacterial and fungal biomasses and indirectly improved soil quality. Compared to that under the no film treatment, the BJ treatment boosted soil quality by 70%, with the most significant impact, followed by that under the HPE and HSJ treatments, with improvements of 52% and 36%. Random forest modeling indicated that soil organic matter and total nitrogen were the most important factors influencing soil quality. The different film covers significantly increased the diameter of garlic bulbs and single quality. The HSJ treatment exhibited the most significant increase in garlic yield, with 46%, 19%, and 6% improvement compared to that in the CK, HPE, and BJ treatments, respectively. Correlation analysis showed that soil quality under film cover was significantly correlated with the starch content of garlic bulbs, garlic diameter, and single quality. This study highlights that selecting the appropriate mulch film aids in the production of garlic and helps to develop farmland that produces both high-quality and high-yield crops.

High entropy alloys (HEAs) are alloys composed of five or more primary elements in equal or nearly equal proportions of atoms. In the present study, the thermophysical properties of the CoCrFeNiCu high entropy alloy (HEA) were investigated by a molecular dynamics (MD) method at nanoscale. The effects of the content of individual elements on lattice thermal conductivity k p were revealed, and the results suggested that adjusting the atomic content can be a way to control the lattice thermal conductivity of HEAs. The effects of temperature on k p were investigated quantitively, and a power-law relationship of k p with T -0.419 was suggested, which agrees with previous findings. The effects of temperature and the content of individual elements on volumetric specific heat capacity C v were also studied: as the temperature increases, the C v of all HEAs slightly decreases and then increases. The effects of atomic content on C v varied with the comprising elements. To further understand heat transfer mechanisms in the HEAs, the phonon density of states (PDOS) at different temperatures and varying atomic composition was calculated: Co and Ni elements facilitate the high-frequency vibration of phonons and the Cu environment weakens the heat transfer via low-frequency vibration of photons. As the temperature increases, the phonon mean free path (MFP) in the equiatomic CoCrFeNiCu HEA decreases, which may be attributed to the accelerated momentum of atoms and intensified collisions of phonons. The present research provides theoretical foundations for alloy design and have implications for high-performance alloy smelting., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier Ltd.)

Chemical looping combustion (CLC) is a promising and novel technology for carbon dioxide (CO 2 ) capture with a relatively low energy consumption and cost. CuO, one of the most attractive oxygen carriers (OCs) for carbon dioxide (CO) oxidation, suffers from sintering and agglomeration during the reduction process. Applying an electric field (EF) may promote the CO oxidation process on the CuO surface, which could mitigate sintering and agglomeration by decreasing operating temperatures with negligible combustion efficiency loss. This study performs density functional theory (DFT) simulations to investigate the effects of EF on the oxidation of CO on the CuO (111) surface. The results indicate that both the orientation and strength of the EF can significantly affect the oxidation characteristics of CO on the CuO (111) surface such as total reaction energy, energy barriers of reactions, CO adsorption, and CO 2 desorption. For the first time, this study reveals the role of EF in enhancing CO oxidation through CLC processes via first-principle calculations. Such findings could provide new strategies to improve the performance of CLC processes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA., (© 2024. The Author(s).)

Background: For children and adolescents, deliberate self-harm (DSH) is becoming a mental health problem of concern. Despite several studies on the prevalence and factors of DSH in the world, there is little information on DSH among children and adolescents in China. This study explores the prevalence, types, associated risk factors and tendency of DSH in pediatric psychiatric inpatients in China., Aim: To understand the situation of DSH among hospitalized children and adolescents and its related factors., Methods: In this study, we retrospectively studied 1414 hospitalized children and adolescents with mental illness at Xiamen Mental Health Center from 2014 to 2019, extracted the demographic and clinical data of all patients, and analyzed clinical risk factors of DSH., Results: A total of 239 (16.90%) patients engaged in at least one type of DSH in our study. Cutting ( n = 115, 48.12%) was the most common type of DSH. Females ( n = 171, 71.55%) were more likely to engage in DSH than males ( n = 68, 28.45%). DSH was positively associated with depressive disorders [OR = 3.845 (2.196-6.732); P < 0.01], female [OR = 2.536 (1.815-3.542); P < 0.01], parental marital status [OR = 5.387 (2.254-12.875); P < 0.01] and negative family history of psychiatric illness [OR = 7.767 (2.952-20.433); P < 0.01], but not with occupation, substance use and history of physical abuse., Conclusion: Our findings suggest that for patients with depression, females, an abnormal marriage of parents, and no history of mental illness, attention should be paid to the occurrence of DSH., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Studies have shown that tripartite motif-containing (TRIM) family proteins function as E3 ubiquitin ligases and play essential roles in cancer biology. In the present study, we validated a contribution of TRIM9 to bladder cancer progression. 296 patients derived from The Cancer Genome Atlas (TCGA) database and 22 clinical specimens were included, in which accumulated TRIM9 correlated with the poor prognosis and higher relapse in bladder patients. In vitro, TRIM9 promoted bladder cancer cells Biu-87 and T24 cell proliferation and migration. Meanwhile, overexpression of TRIM9 reduced the chemosensitivity in Biu-87 and T24 to mitomycin C (MMC) and gemcitabine (GEM). As an underlying mechanism, we found that TRIM9 stimulated carcinoembryonic antigen 6 (CEACAM6) upregulation, which further facilitated Smad2/3-matrix metalloproteinase 2 (MMP2) signaling activation both in vitro and in vivo. Those results indicated that TRIM9 facilitated bladder cancer development and chemoresistance by CEACAM6-Smad2/3 axis. TRIM9 and its associated molecules could be a potential diagnostic indicator and therapeutic target in bladder cancer., (© 2023. The Author(s).)

Endothelial cells, located on the surface of blood vessel walls, are constantly stimulated by mechanical forces from the blood flow. The mechanical forces, i.e., fluid shear stress, induced by the blood flow play a pivotal role in controlling multiple physiological processes at the endothelium and in regulating various pathways that maintain homeostasis and vascular function. In this review, research looking at different blood fluid patterns and fluid shear stress in the circulation system is summarized, together with the interactions between the blood flow and the endothelial cells. This review also highlights the flow profile as a response to the configurational changes of the endothelial glycocalyx, which is less revisited in previous reviews. The role of endothelial glycocalyx in maintaining endothelium health and the strategies for the restoration of damaged endothelial glycocalyx are discussed from the perspective of the fluid shear stress. This review provides a new perspective regarding our understanding of the role that blood flow plays in regulating endothelial functionality., 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 © 2023 Zhou, Jiang and Ventikos.)

Background: Glioma is a prevalent and lethal brain malignancy; despite current treatment options, the prognosis remains poor. Therefore, immunotherapy has emerged as a promising therapeutic strategy. However, research trends and hotspots in glioma immunotherapy have not been systematically analyzed. This study aimed to elucidate global research trends and knowledge structures regarding immunotherapy for glioma using bibliometric analysis., Methods: Publications related to immunotherapy for glioma from 2000-2023 were retrieved from Web of Science Core Collection database (WoSCC). We conducted quantitative analysis and visualization of research trends using various tools, including VOSviewer (1.6.18), CiteSpace (5.7 R3), Microsoft Charticulator, and the Bibliometrix package in R., Results: A total of 4910 publications were included. The number of annual publications exhibited an obvious upward trend since 2019. The USA was the dominant country in terms of publication output and centrality. Frontiers in Immunology published the most articles. Harvard Medical School ranked first in productivity among institutions. Sampson, John H. Ph.D. is the most prolific author in the field with 88 articles and a total of 7055 citations. Clinical Cancer Research has the largest total number and impact factor. Analysis of keywords showed immunotherapy, glioblastoma, immunotherapy, and clinical trials as hot topics. The tumor microenvironment, cell death pathways, chimeric antigen receptor engineering, tumor-associated macrophages, and nivolumab treatment represent indicating shifts in the direction of future glioma immunotherapy development., Conclusion: This bibliometric analysis systematically delineated global landscapes and emerging trends in glioma immunotherapy research. This study highlighted the prominence of Chimeric Antigen Receptor T-cell (CAR-T), Programmed Death-1 (PD-1), and nivolumab in current glioma immunotherapy research. The growing emphasis on specific neoantigens and prognostic tumor markers suggests potential avenues for future exploration. Furthermore, the data underscores the importance of strengthened international collaboration in advancing the field., 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 © 2023 Zhang, Yu, Zhao, Jiang, Gao and Wei.)

Deserts occupy one-third of the Earth's terrestrial surface and represent a potentially significant reservoir of microbial biodiversity, yet the majority of desert microorganisms remain uncharacterized and are seen as "microbial dark matter". Here, we introduce a multi-omics strategy, culturomics-based metagenomics (CBM) that integrates large-scale cultivation, full-length 16S rRNA gene amplicon, and shotgun metagenomic sequencing. The results showed that CBM captured a significant amount of taxonomic and functional diversity missed in direct sequencing by increasing the recovery of amplicon sequence variants (ASVs) and high/medium-quality metagenome-assembled genomes (MAGs). Importantly, CBM allowed the post hoc recovery of microbes of interest (e.g., novel or specific taxa), even those with extremely low abundance in the culture. Furthermore, strain-level analyses based on CBM and direct sequencing revealed that the desert soils harbored a considerable number of novel bacterial candidates (1941, 51.4%), of which 1095 (from CBM) were culturable. However, CBM would not exactly reflect the relative abundance of true microbial composition and functional pathways in the in situ environment, and its use coupled with direct metagenomic sequencing could provide greater insight into desert microbiomes. Overall, this study exemplifies the CBM strategy with high-resolution is an ideal way to deeply explore the untapped novel bacterial resources in desert soils, and substantially expands our knowledge on the microbial dark matter hidden in the vast expanse of deserts., (© 2023. Springer Nature Limited.)

Carbon dioxide (CO 2 ) electroreduction by metal-nitrogen-doped carbon (MNC) catalysts is a promising and efficient method to mitigate global warming by converting CO 2 molecules to value-added chemicals. In this research, we systematically studied the behaviours of single and dual-atom Cu catalysts during the CO 2 electroreduction process using density functional theory (DFT) calculations. Two structures, i.e. , CuNC-4-pyridine and CuCuNC-4a, were found to be beneficial for C 2 chemical generation with relatively high stabilities. Subsequently, we explored the detailed pathways of key products (CO, HCOOH, CH 3 OH, CH 4 , C 2 H 6 O, C 2 H 4 and C 2 H 6 ) during CO 2 electroreduction on CuNC-4-pyridine and CuCuNC-4a. This research reveals the mechanisms of key product formation during CO 2 electroreduction on CuNC-4-pyridine and CuCuNC-4a, which would provide important insights to guide the design of MNC catalysts with low limiting potentials and high product selectivity.

The ^{18}O(α,γ)^{22}Ne reaction is critical for AGB star nucleosynthesis due to its connection to the abundances of several key isotopes, such as ^{21}Ne and ^{22}Ne. However, the ambiguous resonance energy and spin-parity of the dominant 470 keV resonance leads to substantial uncertainty in the ^{18}O(α,γ)^{22}Ne reaction rate for the temperature of interest. We have measured the resonance energies and strengths of the low-energy resonances in ^{18}O(α,γ)^{22}Ne at the Jinping Underground Nuclear Astrophysics experimental facility (JUNA) with improved precision. The key 470 keV resonance energy has been measured to be E&#95;{α}=474.0±1.1  keV, with such high precision achieved for the first time. The spin-parity of this resonance state is determined to be 1^{-}, removing discrepancies in the resonance strengths in earlier studies. The results significantly improve the precision of the ^{18}O(α,γ)^{22}Ne reaction rates by up to about 10 times compared with the previous data at typical AGB temperatures of 0.1-0.3 GK. We demonstrate that such improvement leads to precise ^{21}Ne abundance predictions, with an impact on probing the origin of meteoritic stardust SiC grains from AGB stars.

Objective: To compare the clinical efficacy between Tiaoshen Jieyu acupuncture (acupuncture for regulating mind and relieving depression) combined with sertraline hydrochloride tablet and simple sertraline hydrochloride tablet for post-stroke depression (PSD)., Methods: A total of 76 patients with PSD were randomized into an observation group (38 cases, 6 cases dropped off) and a control group (38 cases, 4 cases dropped off). Both groups were treated with conventional treatment i.e. controlling blood pressure and anti-inflammation. Sertraline hydrochloride tablet was given orally in the control group, 20 mg a time, once a day. On the basis of the treatment in the control group, Tiaoshen Jieyu acupuncture was applied at Baihui (GV 20), Yintang (GV 24 + ), Neiguan (PC 6), Taichong (LR 3), etc. in the observation group, Baihui (GV 20) and Yintang (GV 24 + ) were connected to electroacupuncture, with disperse-dense wave, 2 Hz/100 Hz in frequency, 30 min a time, once a day, 6 times a week. Treatment of 8 weeks was required in both groups. Before and after treatment, the scores of Hamilton depression scale (HAMD), National Institutes of Health stroke scale (NIHSS), Barthel index (BI) and Pittsburgh sleep quality index (PSQI) were observed respectively, the therapeutic efficacy and rate of adverse reactions were evaluated in the two groups., Results: After treatment, the scores of HAMD, NIHSS and PSQI were lower while BI scores were higher than those before treatment in both groups ( P <0.05); the scores of HAMD, NIHSS and PSQI in the observation group were lower while BI score was higher than those in the control group ( P <0.05). The total effective rate was 93.8% (30/32) in the observation group, which was higher than 70.6% (24/34) in the control group ( P <0.05). The rate of adverse reactions was 9.4% (3/32) in the observation group, which was lower than 32.4% (11/34) in the control group ( P <0.05)., Conclusion: Tiaoshen Jieyu acupuncture combined with sertraline hydrochloride tablet can improve the depression degree, neurological function, activity of daily living and sleep quality in patients with post-stroke depression, the clinical efficacy is superior to simple sertraline hydrochloride, and can alleviate the adverse reactions caused by medication.

Objectives: To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma., Methods: A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021., Results: The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N - Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years., Conclusions: Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.

Objective: To investigate long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) interactions and identify the critical gene regulatory network during Schistosoma japonicum infections and praziquantel treatment using whole transcriptome sequencing., Methods: A total of 110 male C57BL/6 mice were randomly divided into the control group, the infection group and the treatment group. Mice in the infection treatment and the control group were infected with S. japonicum cercariae via the abdomen, and liver specimens were sampled from 10 mice 3, 6, 8 weeks post-infection. Praziquantel treatment was given to mice in the treatment group 8 weeks post-infection, and liver specimens were sampled from 10 mice 2, 4, 6, 8, 10 weeks post-treatment. Total RNA was isolated from mouse liver specimens, and the transcriptome library was constructed for highthroughput whole transcriptome sequencing. The significant differentially expressed genes were subjected to functional annotations, Gene Ontology (GO) terms enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Correlation analysis of liver specimens was performed using R Corrplot and Himsc functions, and the lncRNAmiRNA-mRNA interaction network analysis was performed using R MixOmics and Himsc functions., Results: There were 1 176 differentially expressed miRNAs, 5 270 differentially expressed mRNAs, and 2 682 differentially expressed lncRNAs between the infection group and the control group, 1 289 differentially expressed miRNAs, 7 differentially expressed mRNAs, and 69 differentially expressed lncRNAs between the treatment group and the infection group, and 1 210 differentially expressed miRNAs, 4 456 differentially expressed mRNAs, and 2 016 differentially expressed lncRNAs between the treatment group and the control group. Correlation analysis showed a higher correlation of gene expression between the treatment group and the control group. Principal component analysis showed obvious separate clustering between the infection group and the treatment group. The differentially expressed genes with significant relevance were significantly enriched in 24 GO terms, including arachidonic acid metabolic process, xenobiotic catabolic process, unsaturated fatty acid metabolic process, xenobiotic metabolic process, long-chain fatty acid metabolic process, and 8 KEGG metabolic pathways, including cholesterol metabolism, tyrosine metabolism, linoleic acid metabolism, retinol metabolism, and steroid hormone biometabolism., Conclusions: There were 23 mRNAs including Cyp2b9 and 14 lncRNAs including Rmrpr in the core position of the gene regulatory network, which may play a critical role in S. japonicum infections and praziquantel treatment, and 9 miRNAs including miR-8105 may serve as potential molecular markers for diagnosis of S. japonicum infections.

Endothelial glycocalyx (EG) is a carbohydrate-rich layer which lines the lumen side of blood vessel walls. The EG layer is directly exposed to blood flow. The unique physiological location and its strongly coupled interaction with blood flow allow the EG layer to modulate microvascular mass transport and to sense and transmit mechanical signals from the passing blood. Molecular dynamics (MD) simulation is a computational method which focuses on atomic/molecular behavior at the microscale. The last two decades have witnessed a substantial increase in number and a broadening in scope regarding applications of MD in a wide spectrum of areas, including EG-related research. In this mini-review, MD works which solve EG-related problems and provide new insights into the functionality of EG are considered. Challenges of the MD method in EG research are articulated, and the future of MD in solving EG-related problems is also evaluated., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To investigate the effects of body mass index (BMI) levels at different baseline on the risk of new-onset acute pancreatitis (AP). Methods: The subjects were from the Kailuan Study Cohort and divided into 3 groups according to baseline BMI levels: BMI<24 kg/m 2 , normal weight; BMI 24-28 kg/m 2 , overweight; BMI≥28 kg/m 2 , obesity. The incidence of new-onset AP in these three groups was analyzed. The survival curve was plotted by Kaplan-Meier method, the cumulative incidence was calculated and tested by log-rank method. Multivariate Cox proportional hazards regression model was used to calculate HR of baseline BMI levels for AP. Results: A total of 123 841 subjects were included and followed up for (11.94±2.13) years, during which, 395 cases were found with AP. The incidence of AP was 2.67 per 10 000 person years in total population, and the incidences of AP were 2.20, 2.72 and 3.58 per 10 000 person-years in the normal, overweight and obesity groups, respectively. The cumulative incidences of AP was 0.32%, 0.40% and 0.49% in normal, overweight and obesity groups, respectively, which showed a significant inter-group difference by log-rank test ( χ 2 =13.17, P <0.01). The results of multivariable adjusted Cox proportional hazards regression model analysis indicated that obesity group ( HR =1.45, 95% CI : 1.10-1.92) had a higher risk for AP compared with the normal BMI group. The subgroup analyses by age and sex showed that compared with the normal weight group,the HR s for AP in the obesity group was 1.58(95% CI :1.14-2.19) and 1.40(95% CI :1.03-1.90) among subjects younger than 60 years old and male subjects, respectively. After excluded onset AP within two years from baseline,with a control group from normal weight,the results of multivariate Cox proportional hazards regression model analysis indicated that the AP in the obesity group was 1.60 (95% CI : 1.18-2.15). Conclusion: Obesity may increase the risk of developing AP, particularly among young and middle-aged men.

Endothelial glycocalyx plays a crucial role in hemodynamics in health and disease, yet studying it is met by multiple technical hindrances. We attempted to outline our views on some biomechanical properties of endothelial glycocalyx, which are potentially amenable to mathematical modeling. We start with the null-hypothesis ascribing to glycocalyx the properties of a pendulum and reject this hypothesis on the grounds of multiple obstacles for pendulum behavior, such as rich decoration with flexible negatively charged side-chains, variable length and density, fluid fixation to the plasma membrane. We next analyze the current views on membrane attachments to the cortical actin web, its pulsatile contraction-relaxation cycles which rebound to the changes in tension of the plasma membrane. Based on this, we consider the outside-in signaling, the basis for mechanotransduction, and the dampening action of the inside-out signaling. The aperiodic oscillatory motions of glycocalyx and cortical actin web underlie our prediction of two functional pacemakers. We next advance an idea that the glycocalyx, plasma membrane, and cortical actin web represent a structure-functional unit and propose the concept of tensegrity model. Finally, we present our recent data suggesting that erythrocytes are gliding or hovering and rotating over the surface of intact glycocalyx, whereas the rotational and hovering components of their passage along the capillaries are lost when glycocalyx of either is degraded. These insights into the mechanics of endothelial glycocalyx motions may be of value in crosspollination between biomechanics, physiology, and pathophysiology for deeper appreciation of its rich untapped resources in health and pharmacotherapy in disease., Competing Interests: 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., (© 2021 The Author(s).)

Fluorine is one of the most interesting elements in nuclear astrophysics, where the ^{19}F(p,α)^{16}O reaction is of crucial importance for Galactic ^{19}F abundances and CNO cycle loss in first generation Population III stars. As a day-one campaign at the Jinping Underground Nuclear Astrophysics experimental facility, we report direct measurements of the essential ^{19}F(p,αγ)^{16}O reaction channel. The γ-ray yields were measured over E&#95;{c.m.}=72.4-344  keV, covering the Gamow window; our energy of 72.4 keV is unprecedentedly low, reported here for the first time. The experiment was performed under the extremely low cosmic-ray-induced background environment of the China JinPing Underground Laboratory, one of the deepest underground laboratories in the world. The present low-energy S factors deviate significantly from previous theoretical predictions, and the uncertainties are significantly reduced. The thermonuclear ^{19}F(p,αγ)^{16}O reaction rate has been determined directly at the relevant astrophysical energies.

Endothelial glycocalyx (EG) is a forest-like structure, covering the lumen side of blood vessel walls. EG is exposed to the mechanical forces of blood flow, mainly shear, and closely associated with vascular regulation, health, diseases, and therapies. One hallmark function of the EG is mechanotransduction, which means the EG senses the mechanical signals from the blood flow and then transmits the signals into the cells. Using numerical modelling methods or in silico experiments to investigate EG-related topics has gained increasing momentum in recent years, thanks to tremendous progress in supercomputing. Numerical modelling and simulation allows certain very specific or even extreme conditions to be fulfilled, which provides new insights and complements experimental observations. This mini review examines the application of numerical methods in EG-related studies, focusing on how computer simulation contributes to the understanding of EG as a mechanotransducer. The numerical methods covered in this review include macroscopic (i.e., continuum-based), mesoscopic [e.g., lattice Boltzmann method (LBM) and dissipative particle dynamics (DPD)] and microscopic [e.g., molecular dynamics (MD) and Monte Carlo (MC) methods]. Accounting for the emerging trends in artificial intelligence and the advent of exascale computing, the future of numerical simulation for EG-related problems is also contemplated., 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 © 2021 Jiang, Luo and Ventikos.)

Vascular endothelial cells and circulating red blood cell (RBC) surfaces are both covered by a layer of bushy glycocalyx. The interplay between these glycocalyx layers is hardly measurable and insufficiently understood. This study aims to investigate and qualify the possible interactions between the glycocalyces of RBCs and endothelial cells using mathematical modeling and numerical simulation. Dissipative particle dynamics (DPD) simulations are conducted to investigate the response of the endothelial glycocalyx (EG) to varying ambient conditions. A two-compartment model including EG and flow and a three-compartment model comprising EG, RBC glycocalyx, and flow are established. The two-compartment analysis shows that a relatively fast flow is associated with a predominantly bending motion of the EG, whereas oscillatory motions are predominant in a relatively slow flow. Results show that circulating RBCs cause the contactless deformation of EG. Its deformation is dependent on the chain layout, chain length, bending stiffness, RBC-to-EG distance, and RBC velocities. Specifically, shorter EG chains or RBC-to-EG distance leads to greater relative deflections of EG. Deformation of EG is enhanced when the EG chains are rarefied or RBCs move faster. The bending stiffness maintains stretching conformation of EG. Moreover, a compact EG chain layout and shedding EG chains disturb the neighboring flow field, causing disordered flow velocity distributions. In contrast, the movement of EG chains on RBC surfaces exerts a marginal driving force on RBCs. The DPD method is used for the first time, to our knowledge, in the three-compartment system to explore the cross talk between EG and RBC glycocalyx. This study suggests that RBCs drive the EG deformation via the near-field flow, whereas marginal propulsion of RBCs by the EG is observed. These new, to our knowledge, findings provide a new angle to understand the roles of glycocalyx in mechanotransduction and microvascular permeability and their perturbations under idealized pathophysiologic conditions associated with EG degradation., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background: Ultrafast ultrasound imaging has been demonstrated to be an effective method to evaluate carotid stiffness through carotid pulse-wave velocity (PWV) with high reproducibility, but a lack of reference values has precluded its widespread use in clinical practice. The aims of this study were to establish reference values of PWV for ultrafast ultrasound imaging in a prospective, multicenter, population-based cohort study and to investigate the main determinants of carotid PWV., Methods: A total of 1,544 healthy Han Chinese volunteers (581 men [38%]; age range, 18-95 years) were enrolled from 32 collaborating laboratories in China. The participants were categorized by age, blood pressure (BP), and body mass index (BMI). Basic clinical parameters and carotid PWV at the beginning of systole (BS) and at end-systole (ES) were measured using ultrafast ultrasound imaging techniques., Results: PWV at both BS and ES was significantly higher in the left carotid artery than in the right carotid artery. PWV at BS was significantly higher in men than in women; however, no significant difference was noted in PWV at ES between men and women. Multiple linear regression analyses revealed that age, BP, and BMI were independently correlated with PWV at both BS and ES. PWV at BS and ES progressively increased with increases in age, BP, and BMI. Furthermore, age- and sex-specific reference values of carotid PWV for ultrafast ultrasound imaging were established., Conclusions: Reference values of carotid PWV for ultrafast ultrasound imaging, stratified by sex and age, were determined for the first time. Age, BP, and BMI were the dominant determinants of carotid PWV for ultrafast ultrasound imaging, which should be considered in clinical practice for assessing arterial stiffness., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

This study aimed to explore whether APOC1 expression has a function in the biological behavior of clear cell renal cell carcinoma (ccRCC) cells and its possible mechanism. Bioinformatics analysis of data TCGA and OnComine was conducted to explore the expression pattern and prognostic value of APOC1, as well as the relationship between APOC1 expression and clinical indicators. Loss- and gain- of APOC1 function assays were carried out to assess the biological functions of APOC1. Western blotting was applied to detect protein expression. We revealed that APOC1 was upregulated in ccRCC tissues. APOC1 expression was related to gender, grade, pathologic-T, pathologic-stage, and pathologic-M in patients with ccRCC. Meanwhile, Kaplan-Meier analysis evidenced that the high APOC1 expression indicated unfavorable outcomes of ccRCC. Functional experiments in vitro revealed that upregulation of APOC1 in UT33A cells promoted cell proliferation, invasion, and migration, while downregulation of APOC1 in 786-O cells had the opposite effect. Furthermore, epithelial mesenchymal transition (EMT) was activated in cells with upregulated APOC1 but inhibited in cells with down-regulated APOC1. Collectively, our data suggested that APOC1 was overexpressed in ccRCC cells and promoted the malignant biological behaviors and EMT of ccRCC cells., (© 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Objectives: To evaluate carotid stiffening in participants without conventional cardiovascular risk factors (CVRFs) by using ultrafast pulse wave velocity (ufPWV)., Methods: The present study enrolled 517 participants without conventional CVRFs (CVRF-Free total population). Subjects in this population were defined as current non-smokers with untreated blood pressure < 140/90 mmHg, fasting blood glucose (FBG) < 7.0 mmol/L, total cholesterol (TC) < 6.2 mmol/L, low-density lipoprotein cholesterol < 4.1 mmol/L, and high-density lipoprotein cholesterol ≥ 1.0 mmol/L. Participants in the subgroup with optimal CVRFs (CVRF-Optimal subgroup; n = 188) were defined as having blood pressure < 120/80 mmHg, TC < 5.2 mmol/L, and FBG < 5.6 mmol/L. Clinical interviews, physical examinations, serum draw, carotid intima-media thickness (cIMT), and ufPWV were evaluated. Adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression models were used., Results: Carotid stiffening was present in 46.2-54.5% of CVRF-Free subjects. Age, male sex, and body mass index (BMI) were independently associated with carotid stiffening in both the CVRF-Free total population and CVRF-Optimal subgroup (OR for age = 1.10-1.11, OR for male sex = 2.65-7.19, OR for BMI = 1.34-1.62; p < 0.05). Carotid stiffening was associated with TC only in the CVRF-Free total population (OR for TC = 1.84; p = 0.034)., Conclusions: Many CVRF-Free individuals have carotid stiffening. ufPWV for atherosclerotic stiffening aids the assessment of early atherogenesis and may further clarify the true status of healthy adults without CVRFs., Key Points: • CVRF-Optimal individuals have a lower carotid stiffness than CVRF-Free populations. • ufPWV is a quantitative predictor for the early assessment of AS. • Absent major CVRFs cannot be considered low risk for carotid stiffening and atherosclerosis.

BACKGROUND This retrospective study aimed to identify the predictive factors for the progression of grade A, or early biochemical leak, to grade B postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy using preoperative computed tomography (CT) imaging of the pancreas. MATERIAL AND METHODS A total of 156 patients were analyzed retrospectively. Biochemical leakage occurred in 60 patients, who were divided into POPF progression and non-POPF progression groups. Perioperative parameters were collected. Univariate analysis and multivariate logistic regression analysis were done. For the parameters with statistical significance, the area under the curve (AUC) was calculated if possible and the predictive value was assessed. RESULTS Univariate analysis showed that main pancreatic duct diameter, postoperative complications (except POPF), prothrombin time (PT) and serum albumin on postoperative day 3, and pancreatic CT value were risk factors of POPF (P<0.05). Multivariate analysis showed that serum albumin and PT on postoperative day 3 and pancreatic CT value were independent risk factors of POPF (P<0.05). Lower postoperative albumin, lower pancreatic CT value, and longer PT were associated with a higher risk of POPF (P<0.05). The AUC of CT value was 0.808. CT value thresholds of 42.5 Hounsfield units (HU) and 41.5 HU were tied for the highest predictive performance, with Youden indices of 0.486 for both, and sensitivity of 79% and 71%, and specificity of 69% and 78%, respectively. CONCLUSIONS Preoperative laboratory investigations and CT imaging of the pancreas may identify factors associated with early biochemical leakage progressing to grade B POPF following pancreaticoduodenectomy.

Aspergillus sections Usti and Cavernicolarum are accommodated in the subgenus Nidulantes . In the present study, a polyphasic approach using morphology and multi-gene phylogeny was applied to investigate the taxonomy of these two sections. Based on the phylogenetic analysis, Aspergillus section Usti includes 25 species, which can be assigned to four series: Calidousti , Deflecti , Monodiorum and Usti. Aspergillus sigarelli is newly described in this section and this species was isolated from a cigarette from PR China and belongs to series Calidousti . It is clearly distinct from other members in this series based on ITS, BenA , CaM and RPB2 sequences. Aspergillus section Usti members like A. calidoustus and A. granulosus are important opportunistic pathogens, it is speculative that more pathogenetic species will be found by using polyphasic taxonomy approaches. Aspergillus section Cavernicolarum includes five species, the growth rates on agar media and size and ornamentation of conidia are important characters for differentiating species in section Cavernicolarum .

In the present research, the sodium ion transport across the endothelial glycocalyx layer (EGL) under an imposed electric field is investigated, for the first time, using a series of molecular dynamics simulations. The electric field is perpendicularly imposed on the EGL with varying strengths. The sodium ion molarity difference between the inner and outer layers of EGL, Δc, is used to quantify the sodium transport in the presence of the negatively charged glycocalyx sugar chains. Results suggest that a weak electric field increases Δc, regardless of whether the electric field is imposed perpendicularly inward or outward. By contrast, a strong electric field drives sodium ions to travel in the same orientation as the electric field. Scrutiny of the charge distribution of the glycocalyx sugar chains suggests that the electric field modifies the spatial layouts of glycocalyx atoms as it drives the transport of sodium ions. The modification in glycocalyx layouts further changes the inter-molecular interactions between glycocalyx sugar chains and sodium ions, thereby limiting the electric field control of ion transport. The sodium ions, in turn, alter the apparent bending stiffness of glycocalyx. Moreover, the negative charges of the glycocalyx sugar chains play an important role in maintaining structural stability of endothelial glycocalyx. Based on the findings, a hypothesis is proposed regarding the existence of a strength threshold of the electric field in controlling charged particles in the endothelium, which offers an alternative explanation for contrasting results in previous experimental observations.

Talaromyces is a monophyletic genus containing seven sections. The number of species in Talaromyces grows rapidly due to reliable and complete sequence data contributed from all over the world. In this study agricultural soil samples from Fujiang, Guangdong, Jiangxi, Shandong, Tibet and Zhejiang provinces of China were collected and analyzed for fungal diversity. Based on a polyphasic approach including phylogenetic analysis of partial ITS, BenA , CaM and RPB2 gene sequences, macro- and micro-morphological analyses, six of them could not be assigned to any described species, and one cannot be assigned to any known sections. Morphological characters as well as their phylogenetic relationship with other Talaromyces species are presented for these putative new species. Penicillium resedanum is combined in Talaromyces section Subinflati as T. resedanus ., (Bing-Da Sun, Amanda J. Chen, Jos Houbraken, Jens C. Frisvad, Wen-Ping Wu, Hai-Lei Wei, Yu-Guang Zhou, Xian-Zhi Jiang, Robert A. Samson.)

Objective: To investigate the relationship between waist circumference trajectory and new-onset nonalcoholic fatty liver disease (NAFLD) in the non-obese population. Methods: The study cohort was composed of the ones who met the selection criteria in Kailuan study. Waist circumference trajectories of the participants in 2006-2007, 2008-2009 and 2010-2011 were determined by SAS Proc Traj program. Four groups with different waist circumference trajectories were generated, including low-, medium-, medium-high- and high-stability groups. All groups were followed up for their health conditions in 2012-2013, 2014-2015 and 2016-2017, respectively. Incidence rates of NAFLD during physical examination were compared among different waist circumference trajectory groups. Cox regression model was used to analyze the correlation between different waist circumference trajectory groups and new-onset NAFLD. Results: Finally, 12 477 observers were included in the statistical analysis, including 8 181 males and 4 296 females. There were 1 026 (8.2 % ), 5 183 (41.5 % ), 5 481 (44.0 % ) and 787 cases (6.3 % ) in the low, medium, medium-high and high stability-stability groups, respectively. There were 4 123 NAFLD cases occurred during the follow-up period. The cumulative incidence of NAFLD increased along with the increase of waist circumference trajectory (21 % , 43 % , 59 % , 72 % , respectively) ( P <0.01). The risks of NAFLD were 2.411 (95 %CI : 2.021-2.877), 4.050 (95 %CI : 3.402-4.820) and 5.489 (95 %CI : 4.506-6.686) times higher in medium-, medium-high- and high-stability group than that in the low-stability group ( P <0.01). After adjusting for age, sex and other confounding factors, the risks of NAFLD in the medium-, medium-high- and high-stability groups were 2.150 (95 %CI : 1.789-2.582), 3.176 (95 %CI : 2.623-3.846) and 3.732 (95 %CI : 2.987-4.662) times higher than that in the low-stability group. Conclusion: The risk of NAFLD in non-obese people increased along with the increase of waist circumference trajectory, which seemed to have played an independent risk factor for NAFLD.

Objective: We aimed to analyze the risk factors and to establish a predictive tool for the occurrence of bloodstream infections (BSI) in patients with cirrhosis., Methods: A total of 2888 patients with cirrhosis were retrospectively included. Multivariate analysis for risk factors of BSI were tested using logistic regression. Multivariate logistic regression was validated using five-fold cross-validation., Results: Variables that were independently associated with incidence of BSI were white blood cell count (odds ratio [OR] = 1.094, 95% confidence interval [CI] 1.063-1.127)], C-reactive protein (OR = 1.005, 95% CI 1.002-1.008), total bilirubin (OR = 1.003, 95% CI 1.002-1.004), and previous antimicrobial exposure (OR = 4.556, 95% CI 3.369-6.160); albumin (OR = 0.904, 95% CI 0.883-0.926), platelet count (OR = 0.996, 95% CI 0.994-0.998), and serum creatinine (OR = 0.989, 95% CI 0.985-0.994) were associated with lower odds of BSI. The area under receiver operating characteristic (ROC) curve of the risk assessment scale was 0.850, and its sensitivity and specificity were 0.762 and 0.801, respectively. There was no significant difference between the ROC curves of cross-validation and risk assessment., Conclusions: We developed a predictive tool for BSI in patients with cirrhosis, which could help with early identification of such episodes at admission, to improve outcome in these patients.

Aim: Endothelial glycocalyx (EG) plays a pivotal role in a plethora of diseases, like cardiovascular and renal diseases. One hallmark function of the EG as a mechanotransducer which transmits mechanical signals into cytoplasm has been documented for decades. However, the basic question - how the glycocalyx transmits the flow shear stress- is unanswered so far. Our aim is to shed light on the fundamental mode of signal transmission from flow to the endothelial cytoskeleton., Methods: We conduct a series of large-scale molecular dynamics computational experiments to investigate the dynamics of glycocalyx under varying conditions (changing blood flow velocities and shedding of glycocalyx sugar chains)., Results: We have identified that the main pathway of signal transmission in this system manifests as a scissors-like motion of the Syndecan-4 core protein. Results have suggested that the force transmitted into the cytoskeleton with an order of 10 ~ 100 pN, and the main function of sugar chains of a glycocalyx element is to protect the core proteins from severe conformational changes thereby maintaining the functionality of the EG., Conclusion: This research provides a reconciling explanation for a longstanding debate about the force transmission threshold based on our findings. A new explanation has also been provided to relate the role of the EG as a mechanotransducer to its function as a microvascular barrier: the EG regulates the mechanotransduction by altering the median value and variation range of the scissor angle, and the EG governs the microvascular barrier via controlling the scissor angle which will affect the intercellular cleft., (© 2019 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

The lipid membrane of endothelial cells plays a pivotal role in maintaining normal circulatory system functions. To investigate the response of the endothelial cell membrane to changes in vascular conditions, an atomistic model of the lipid membrane interspersed with Syndecan-4 core protein was established based on experimental observations and a series of molecular dynamics simulations were undertaken. The results show that flow results in continuous deformation of the lipid membrane, and the degree of membrane deformation is not in monotonic relationship with the environmental changes (either the changes in blood velocity or the alteration of the core protein configuration). An explanation for such non-monotonic relationship is provided, which agrees with previous experimental results. The elevation of the lipid membrane surface around the core protein of the endothelial glycocalyx was also observed, which can be mainly attributed to the Coulombic interactions between the biomolecules therein. The present study demonstrates that the blood flow can deform the lipid membrane directly via the interactions between water molecules and lipid membrane atoms thereby affecting mechanosensing; it also presents an additional force transmission pathway from the flow to the lipid membrane via the glycocalyx core protein, which complements previous mechanotransduction hypothesis.

Penicillium species in section Lanata-divaricata are common soil-inhabiting fungi, but their presence in acidic soil has rarely been investigated. In an ongoing survey of Penicillium species occurring in China, 465 strains were isolated from soil, and of which 60 belonged to section Lanata-divaricata. The majority of these strains were isolated from acidic soil. The phylogenetic relationship between these 60 isolates and accepted species of section Lanata-divaricata was studied using ITS, BenA, CaM and RPB2 sequences, which revealed the presence of seven accepted species and 13 novel lineages. Combining phylogenetic data with data generated during macro- and microscopic observations resulted in the description of 13 new species. The growth rate of the new species obtained in this study was determined under acidic, neutral and alkaline conditions (pH 4, 7, 10). With the exception of P. hainanense, which was not able to grow at pH 10, all strains were able to grow at the three examined pH levels. Eleven species (i.e. P. austrosinense, P. flaviroseum, P. globosum, P. griseoflavum, P. hainanense, P. jianfenglingense, P. laevigatum, P. rubriannulatum, P. soliforme, P. spinuliferum, P. yunnanense) grew faster at low pH (pH 4) than at pH 7 or 10, and these species are therefore referred to as acid-preferential. Penicillium viridissimum grew fastest on neutral medium and P. guangxiense grew best at pH 10, and is therefore considered to be acid-tolerant. By isolating strains from a unique environment, combined with targeted isolation using a well-designed protocol, we are able to describe new fungal diversity with specific physiological characteristics., (© 2018 The Authors. Cladistics published by John Wiley & Sons Ltd on behalf of Willi Hennig Society.)

Objective: Paclitaxel is one of the most common drugs for cancer treatment. LncRNA DANCR is a regulator of up-regulation in tumors. Our experiment aims to clarify the role of DANCR in paclitaxel sensitivity of prostate cancer., Patients and Methods: We found that the expression of DANCR in prostate cancer tissues and cells was significantly higher than that in normal groups. DANCR knockdown could reduce cell proliferation and induce cell apoptosis in cells. Moreover, DANCR silence enhanced the effect of paclitaxel on cell proliferation and apoptosis in prostate cancer cells., Results: DANCR targeted and negatively regulated the expression of miR-135a. miR-135a overexpression inhibited cell proliferation and promoted cell apoptosis and paclitaxel sensitivity in prostate cancer cells. miR-135a inhibition reversed the promoting effect of DANCR silence on paclitaxel sensitivity in prostate cancer cells., Conclusions: Downregulation of DANCR increased paclitaxel sensitivity in prostate cancer cells by negatively regulating the expression of miR-135a.

Ion transport through the endothelial glycocalyx layer is closely associated with many vascular diseases. Clarification of ion behaviors around the endothelial glycocalyx layer under varying circumstances will benefit pathologies related to cardiovascular and renal diseases. In this research, a series of large-scale molecular dynamics simulations are conducted to study the response of ion transport to the changing blood flow velocity and the shedding of endothelial glycocalyx sugar chains. Results indicate that blood flow promotes the outward Na + transport from the near-membrane region to the lumen via the endothelial glycocalyx layer. Scrutiny of sugar-chain dynamics and their interactions with Na + suggests that corner conformation of endothelial glycocalyx sugar chains confines the movement of the Na + , whereas stretching conformation facilitates the motion of Na + ions. The flow impact on ion transport of Na + is nonlinear. Based on the findings, the Starling principle and its revised version, which are prevailingly used to predict the ion transport of the endothelial glycocalyx layer, are further improved. An estimation based on the further revised Starling principle indicates that physiological flow changes the osmotic part of transendothelial water flux by 8% compared with the stationary situation. NEW & NOTEWORTHY The biophysical roles of negatively charged oligosaccharides of the endothelial glycocalyx have gained increasing attention due to their importance in regulating microvascular fluid exchange. The Starling principle and its revisions are at the heart of the understanding of fluid homeostasis in the periphery. Here, the blood flow changes the conformations of glycocalyx sugar chains, thereby influencing availability of Na + for transport. Based on the findings, the Starling principle and its revision are further improved.

Background: Renal cell carcinoma (RCC) is the most common form of kidney cancer. Recent studies reported that Tescalcin was overexpressed in various tumor types. However, the status of Tescalcin protein expression in RCC and its biological function is uncertain. This study was designed to investigate the expression of Tescalcin in human RCC and its biological function., Methods: shRNA transfection was performed to abrogates the expression of Tescalcin. Quantitative real time PCR and western blotting assays were used to determine mRNA and protein expression levels, respectively. The cell viability was analyzed by MTT and colony formation. Cell flow cytometry was used to assess pHi value and cell apoptosis. Cell invasive and migratory ability was measured with modified Boyden chamber assay. Xenograft model was setup to evaluate tumor growth., Results: Tescalcin was overexpressed in RCC tissues compared with matched normal tissues. It was also overexpressed in RCC cell lines relative that of normal cells. Suppression Tescalcin with specific shRNA resulted in the inhibition of cell proliferation, migration, invasion and apoptosis of RCC cells. Additionally, silencing of Tescalcin also caused the inhibition of the tumor growth in nude mice. Mechanistic study showed that Tescalcin regulated cell proliferation, migration and invasion via NHE1/pHi axis as well as AKT/NF-κB signaling pathway., Conclusions: These findings demonstrate that atopic expression of Tescalcin facilitates the survival, migration and invasion of RCC cells via NHE1/pHi axis as well as AKT/ NF-κB signaling pathway, providing new perspectives for the future study of Tescalcin as a therapeutic target for RCC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Rationale: Follicular occlusion triad (FOT) is an autosomal recessive inherited disease and no more than 3 variants of the triad have been reported. We give a report in which scrotal elephantiasis is a variant of FOT and further perform a literature review., Patient Concerns: A 41-year-old man came to us because of a large scrotal cyst and generalized skin lesions that had occurred over the past 10 years. The generalized skin lesions consisted of hidradenitis suppurativa on the perineum and back, acne conglobata in the armpit, and dissecting cellulitis of the scalp. He took antibiotics for a long time but achieved poor effect. Furthermore, he told his father and elder brother also manifested such skin lesions., Diagnoses: Magnetic resonance showed a mass in the left scrotum with clear boundaries. A routine blood test showed a high leukocyte level of 12 × 10/L and a hemoglobin content of 78 g/L. C-reactive-protein increased. Series of autoimmune antibody tests were negative. The postoperative pathologic findings showed that the mass was an epidermoid cyst, and hematoxylin and eosin staining showed hyperkeratosis of the skin as well as inflammatory and edematous changes. A diagnosis of a variant of FOT was made., Interventions: We removed skin abscesses and lesioned the inner part with hydrogen peroxide. Then we performed an excision of the scrotal lesion., Outcome: The patient recovered well and had no evidence of recurrence at a 16-month follow-up., Lessons: We reported a case in which scrotal elephantiasis was a variant of FOT and surgical intervention played an important role in secondary urologic diseases.

Background: The present study aimed to explore the efficacy of atorvastatin on patients with carotid plaque, applying superb microvascular imaging (SMI), and contrast-enhanced ultrasound (CEUS) for evaluating carotid intraplaque neovascularization., Methods: A total of 82 patients (82 carotid plaques) who were randomized into treatment group and control group underwent conventional ultrasound, CEUS, and SMI examinations. Patients in treatment group received a dose of 20 mg atorvastatin per day for 6 months while those in control group received placebo instead. Lipid parameters were assessed and intraplaque neovascularization were evaluated by CEUS and SMI before and 6 months after atorvastatin treatment., Results: No significant differences were found between the 2 groups at the study entry. Patients with atorvastatin treatment received marked improvement in total cholesterol, triglyceride, and LDL-cholesterol compared with those in control group (P < .001). In treatment group, SMI-detected intraplaque neovascularization reduced from 69.23% to 48.72% while CEUS-detected ones reduced from 76.92% to 69.23%. By contrast, the percentage of intraplaque neovascularization in control group did not change too much either by SMI (65.12%, 67.44%) or CEUS (74.41%, 74.41%). The consistency between CEUS and SMI was above .75 at all assessments (P < .001)., Conclusions: Atorvastatin treatment works for patients with carotid plaque by reducing LDL-cholesterol and improving plaque regression. Second, the consistency between SMI and CEUS in visualizing intraplaque neovascularization is good. That indicates a high possibility to identify carotid plaque instability by a safer and cheaper ultrasonography without contrast agent., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of macrophage migration inhibitory factor (MIF) on the biology of glioma U87MG and U251 cells. Methods: Silencing MIF gene expression in U87MG cells by RNA interference was monitored by Western blot. MIF low expressing U251 cells were treated at different concentrations of recombinant human MIF (rhMIF) and scratching test and flow cytometry were used to detect cell migration and apoptosis. The protein expression of bcl-2, bax, AKT, p-AKT was detected by Western blot. Results: The ability of migration and anti-apoptosis of U87MG cells silenced by siRNA decreased significantly, and the expression levels of p-AKT and anti-apoptotic protein bcl-2 also decreased; in contrast, the expression level of apoptosis protein bax increased. With increase of rhMIF treatment concentration, the expression levels of MIF protein, p-AKT and bcl-2 in U251 cells were gradually enhanced, whereas the level of apoptosis protein bax was inhibited. Conclusion: MIF promotes cell migration and inhibits apoptosis of both U87MG and U251 cells, likely through the regulation of PI3K/AKT signaling pathway.