bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploration of the immune microenvironment of breast cancer in large population cohorts
Authors: Deng Youyuan , Wang Jianguo , Hu Zhiya , Cai Yurong , Xu Yiping , Xu Ke
Published: August 2022

Tumor immune microenvironment is associated with tumor progression. However, previous studies have not fully explored the breast cancer (BC) immune microenvironment. All the data analyzed in this study were obtained from the open-access database, including The Cancer Genome Atlas, Gene Expression Omnibus (TCGA), and cBioPortal databases. R software v4.0 and SPSS 13.0 were used to perform all the statistical analysis. Firstly, the clinical and expression profile information of TCGA, GSE20685, GSE20711, GSE48390, GSE58812, and METABRIC cohorts was collected. Then, 53 immune terms were quantified using the single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm. A prognosis model based on HER2_Immune_PCA, IL12_score, IL13_score, IL4_score, and IR7_score was established, which showed great prognosis prediction efficiency in both training group and validation group. A nomogram was then established for a better clinical application. Clinical correlation showed that elderly BC patients might have a higher riskscore. Pathway enrichment analysis showed that the pathway of oxidative phosphorylation, E2F targets, hedgehog signaling, adipogenesis, DNA repair, glycolysis, heme metabolism, and mTORC1 signaling was activated in the high-risk group. Moreover, Tumor Immune Dysfunction and Exclusion and Genomics of Drug Sensitivity in Cancer analysis showed that low-risk patients might be more sensitive to PD-1 therapy, cisplatin, gemcitabine, paclitaxel, and sunitinib. Finally, four genes, XCL1, XCL2, TNFRSF17, and IRF4, were identified for risk group classification. In summary, our signature is a useful tool for the prognosis and prediction of the drug sensitivity of BC.
Cell non-autonomous effect of hepatic growth differentiation factor 15 on the thyroid gland
Authors: Jeong Seonhyang , Lee Seul Gi , Kim Kook Hwan , Zhu Xuguang , Lee Woo Kyung , Lee Hwa Young , Park Sunmi , Lee Myung-Shik , Cheng Sheue-Yann , Lee Jandee , Jo Young Suk
Published: August 2022

The thyroid gland plays an essential role in the regulation of body energy expenditure to maintain metabolic homeostasis. However, to date, there are no studies investigating the morphological and functional changes of the thyroid gland due to mitochondrial stress in metabolic organs such as the liver. We used data from the Genotype-Tissue Expression portal to investigate RNA expression patterns of the thyroid gland according to the expression of growth differentiation factor 15 (GDF15) such as the muscles and liver. To verify the effect of hepatic GDF15 on the thyroid gland, we compared the morphological findings of the thyroid gland from liver-specific GDF15 transgenic mice to that of wild type mice. High GDF15 expression in the muscles and liver was associated with the upregulation of genes related to hypoxia, inflammation (TGF-α via NFκB), apoptosis, and p53 pathway in thyroid glands. In addition, high hepatic GDF15 was related to epithelial mesenchymal transition and mTORC1 signaling. Electron microscopy for liver-specific GDF15 transgenic mice revealed short mitochondrial cristae length and small mitochondrial area, indicating reduced mitochondrial function. However, serum thyroid stimulating hormone (TSH) level was not significantly different. In our human cohort, those with a high serum GDF15 level showed high fasting glucose, alanine transaminase, and alkaline phosphatase but no difference in TSH, similar to the data from our mice model. Additionally, high serum GDF15 increased the risk of lymph node metastasis to lateral neck. The hepatic GDF15 affected thyroid morphogenesis via a TSH-independent mechanism, affecting aggressive features of thyroid cancers.
Eco-Friendly Synthesis and Characterization of Double-Crossed Link 3D Graphene Oxide Functionalized With Chitosan for Adsorption of Sulfamethazine From Aqueous Solution: Experimental and DFT Calculations
Authors: Hamed Rinad , Jodeh Shehdeh , Hanbali Ghadir , Safi Zaki , Berisha Avni , Xhaxhiu Kledi , Dagdag Omar
Published: August 2022

Graphene oxide–chitosan composites are attracting considerable interest as an eco-friendly adsorbent material for most aquatic environmental pollutants. Today, the focus is on the emerging applications of 2D and 3D graphene functionalized with chitosan to enhance its mechanical properties and adsorption efficiency. Herein, the super adsorbent 3D graphene functionalized with chitosan (3D GF-CS) is synthesized to remove sulfamethazine, (SMZ) as a model aquatic antibiotic pharmaceutical. The synthesized materials were characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photon spectroscopy (XPS), Brunauer–Emmett–Teller (BET), and Raman spectroscopy. After that, adsorption experiments were conducted for SMZ adsorption to find out the optimized adsorption parameters, such as pH, temperature, contact time, initial antibiotic concentration, and adsorbent dosage. The results show the optimal adsorption parameters were as pH of 7, temperature of 25°C, initial antibiotic concentration Ci of 50 ppm. Also, the kinetics, isotherms models, and thermodynamics parameters of SMZ adsorption were studied. The experimental results revealed to be best suited by both the pseudo-second-order kinetic and the Freundlich isotherm model compared with other isotherm models. The thermodynamics parameters demonstrated that the adsorption is exothermic, exhibiting higher adsorption efficiency at lower temperature. In addition, Gibb’s free energy suggested the adsorption to be spontaneous as well as entropy indication of the loss of disorder. Furthermore, the regeneration of 3D GF-CS was utilized in ten consecutive cycles, and the SMZ adsorption capacity did not decline significantly. Additionally, this research studied the adsorption energies and how sulfamethazine adsorbs onto 3D GF-CS was determined by applying the density-functional–based tight binding (DFTB) and Monte Carlo simulations at different adsorption positions. The chemical reactivity (local and global) of the free drug was investigated using the density functional theory (DFT), namely, the B3LYP and PBEPBE functionals with the 6–31+G (d, p) basis set in the gas phase and aqueous solution.
Random forests algorithm boosts genetic risk prediction of systemic lupus erythematosus
Authors: Ma Wen , Lau Yu-Lung , Yang Wanling , Wang Yong-Fei
Published: August 2022

Patients with systemic lupus erythematosus (SLE) present varied clinical manifestations, posing a diagnostic challenge for physicians. Genetic factors substantially contribute to SLE development. A polygenic risk scoring (PRS) model has been used to estimate the genetic risk of SLE in individuals. However, this approach assumes independent and additive contribution of genetic variants to disease development. We aimed to improve the accuracy of SLE prediction using machine-learning algorithms. We applied random forest (RF), support vector machine (SVM), and artificial neural network (ANN) to classify SLE cases and controls using the data from our previous genome-wide association studies (GWAS) conducted in either Chinese or European populations, including a total of 19,208 participants. The overall performances of these predictors were assessed by the value of area under the receiver-operator curve (AUC). The analyses in the Chinese GWAS showed that the RF model significantly outperformed other predictors, achieving a mean AUC value of 0.84, a 13% improvement upon the PRS model (AUC = 0.74). At the optimal cut-off, the RF predictor reached a sensitivity of 84% with a specificity of 68% in SLE classification. To validate these results, similar analyses were repeated in the European GWAS, and the RF model consistently outperformed other algorithms. Our study suggests that the RF model could be an additional and powerful predictor for SLE early diagnosis.
Influence of pre-endoscopic duration of esophageal food impaction on endoscopy time and postprocedure adverse events
Authors: DiLeo Daniel Anthony , Zenger Cameron , Quarta Giulio
Published: August 2022

Objectives

Esophageal food bolus impaction is a medical emergency and 10-20% of impacted food boluses will require endoscopic removal. Emergent and prolonged procedures are associated with increased adverse events. We are interested in the relationship between the pre-endoscopic duration of esophageal food impaction and the duration of esophagogastroduodenoscopy (EGD) performed to remove the impacted food bolus.

Methods

Between 2010 and 2021, we examined EGD procedures performed for esophageal food impaction. Subjects were classified according to pre-endoscopic duration of food impaction.

Results

We found a positive correlation between pre-endoscopic duration of food impaction and procedure length (r=0.18). Esophageal impactions with mixed foods resulted in the longest procedure duration (p<0.05). Increasing age, male gender, and duration of impaction greater than 42 hours were significantly associated with increased procedure duration (p<0.05). Esophageal perforations, prolonged intubations, admissions following EGD, and readmissions were associated with EGD duration greater than 25.5 minutes. No adverse events occurred in patients who underwent EGD within 6 hours of symptom onset.

Conclusions

In the case of an esophageal food impaction, the time between symptom onset and endoscopy is positively correlated with procedure length and risk of adverse outcomes. We suggest that food impaction should remain an indication for emergent endoscopy. Prospective studies evaluating the safety and outcomes of prolonged time to endoscopy will further clarify the management of esophageal food impactions.
Comprehensive transcriptome profiling of urothelial cells following TNFα stimulation in an in vitro interstitial cystitis/bladder pain syndrome model
Authors: Kuret Tadeja , Peskar Dominika , Kreft Mateja Erdani , Erman Andreja , Veranič Peter
Published: August 2022

Urothelial cells of the urinary bladder play a critical role in the development and progression of interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic and debilitating inflammatory disease. Given the lack of data on the exact phenotype and function of urothelial cells in an inflammatory setting (as in IC/BPS), we performed the first in-depth characterization of these cells using RNA sequencing, qPCR, ELISA, Western blot, and immunofluorescence. After TNFα stimulation, urothelial cells in the in vitro model of IC/BPS showed marked upregulation of several proinflammatory mediators, such as SAA, C3, IFNGR1, IL1α, IL1β, IL8, IL23A, IL32, CXCL1, CXCL5, CXCL10, CXCL11, TNFAIPR, TNFRSF1B, and BIRC3, involved in processes and pathways of innate immunity, including granulocyte migration and chemotaxis, inflammatory response, and complement activation, as well as TLR-, NOD-like receptor- and NFkB-signaling pathways, suggesting their active role in shaping the local immune response of the bladder. Our study demonstrates that the TNFα-stimulated urothelial cells recapitulate key observations found in the bladders of patients with IC/BPS, underpinning their utility as a suitable in vitro model for understanding IC/BPS mechanisms and confirming the role of TNFα signaling as an important component of the associated pathology. The present study also identifies novel upregulated gene targets of TNFα in urothelial cells, including genes encoding the acute phase protein SAA, complement component C3, and the cytokine receptor IFNGR1, which could be exploited as therapeutic targets of IC/BPS. Altogether, our study provides a reference database of the phenotype of urothelial cells in an inflammatory environment that will not only increase our knowledge of their role in IC/BPS, but also advance our understanding of how urothelial cells shape tissue immunity in the bladder.
Hypoxia and hypoxia-inducible factor signals regulate the development, metabolism, and function of B cells
Authors: Zhang Jinwei , Wu Xiaoqian , Ma Jideng , Long Keren , Sun Jing , Li Mingzhou , Ge Liangpeng
Published: August 2022

Hypoxia is a common hallmark of healthy tissues in physiological states or chronically inflamed tissues in pathological states. Mammalian cells sense and adapt to hypoxia mainly through hypoxia-inducible factor (HIF) signaling. Many studies have shown that hypoxia and HIF signaling play an important regulatory role in development and function of innate immune cells and T cells, but their role in B cell biology is still controversial. B cells experience a complex life cycle (including hematopoietic stem cells, pro-B cells, pre-B cells, immature B cells, mature naïve B cells, activated B cells, plasma cells, and memory B cells), and the partial pressure of oxygen (PO2) in the corresponding developmental niche of stage-specific B cells is highly dynamic, which suggests that hypoxia and HIF signaling may play an indispensable role in B cell biology. Based on the fact that hypoxia niches exist in the B cell life cycle, this review focuses on recent discoveries about how hypoxia and HIF signaling regulate the development, metabolism, and function of B cells, to facilitate a deep understanding of the role of hypoxia in B cell-mediated adaptive immunity and to provide novel strategies for vaccine adjuvant research and the treatment of immunity-related or infectious diseases.
Topoisomerase 2β and DNA topology during B cell development
Authors: Papapietro Olivier , Nejentsev Sergey
Published: August 2022

Topoisomerase 2β (TOP2B) introduces transient double strand breaks in the DNA helix to remove supercoiling structures and unwind entangled DNA strains. Advances in genomic technologies have enabled the discovery of novel functions for TOP2B in processes such as releasing of the paused RNA polymerase II and maintaining the genome organization through DNA loop domains. Thus, TOP2B can regulate transcription directly by acting on transcription elongation and indirectly by controlling interactions between enhancer and promoter regions through genome folding. The identification of TOP2B mutations in humans unexpectedly revealed a unique role of TOP2B in B-cell progenitors. Here we discuss the functions of TOP2B and the mechanisms leading to the B-cell development defect in patients with TOP2B deficiency.
The Atlantic Ocean landscape: A basin-wide cluster analysis of the Atlantic near seafloor environment
Authors: Schumacher Mia , Huvenne Veerle A. I. , Devey Colin W. , Arbizu Pedro Martínez , Biastoch Arne , Meinecke Stefan
Published: August 2022

Landscape maps based on multivariate cluster analyses provide an objective and comprehensive view on the (marine) environment. They can hence support decision making regarding sustainable ocean resource handling and protection schemes. Across a large number of scales, input parameters and classification methods, numerous studies categorize the ocean into seascapes, hydro-morphological provinces or clusters. Many of them are regional, however, while only a few are on a basin scale. This study presents an automated cluster analysis of the entire Atlantic seafloor environment, based on eight global datasets and their derivatives: Bathymetry, slope, terrain ruggedness index, topographic position index, sediment thickness, POC flux, salinity, dissolved oxygen, temperature, current velocity, and phytoplankton abundance in surface waters along with seasonal variabilities. As a result, we obtained nine seabed areas (SBAs) that portray the Atlantic seafloor. Some SBAs have a clear geological and geomorphological nature, while others are defined by a mixture of terrain and water body characteristics. The majority of the SBAs, especially those covering the deep ocean areas, are coherent and show little seasonal and hydrographic variation, whereas other, nearshore SBAs, are smaller sized and dominated by high seasonal changes. To demonstrate the potential use of the marine landscape map for marine spatial planning purposes, we mapped out local SBA diversity using the patch richness index developed in landscape ecology. It identifies areas of high landscape diversity, and is a practical way of defining potential areas of interest, e.g. for designation as protected areas, or for further research. Clustering probabilities are highest (100%) in the center of SBA patches and decrease towards the edges (< 98%). On the SBA point cloud which was reduced for probabilities <98%, we ran a diversity analysis to identify and highlight regions that have a high number of different SBAs per area, indicating the use of such analyses to automatically find potentially delicate areas. We found that some of the highlights are already within existing EBSAs, but the majority is yet unexplored.
Prediction of Mortality Risk After Ischemic Acute Kidney Injury With a Novel Prognostic Model: A Multivariable Prediction Model Development and Validation Study
Authors: Wang Mei , Yan Ping , Zhang Ning-Ya , Deng Ying-Hao , Luo Xiao-Qin , Wang Xiu-Fen , Duan Shao-Bin
Published: August 2022

Background and Objectives:

Acute kidney injury (AKI) that results from ischemia is a common clinical syndrome and correlates with high morbidity and mortality among hospitalized patients. However, a clinical tool to predict mortality risk of ischemic AKI is not available. In this study, we aimed to develop and validate models to predict the 30-day and 1-year mortality risk of hospitalized patients with ischemic AKI.

Methods

A total of 1,836 admissions with ischemic AKI were recruited from 277,898 inpatients admitted to three affiliated tertiary general hospitals of Central South University in China between January 2015 and December 2015. Patients in the final analysis were followed up for 1 year. Study patients were randomly divided in a 7:3 ratio to form the training cohort and validation cohort. Multivariable regression analyses were used for developing mortality prediction models.

Results

Hepatorenal syndrome, shock, central nervous system failure, Charlson comorbidity index (≥2 points), mechanical ventilation, renal function at discharge were independent risk factors for 30-day mortality after ischemic AKI, while malignancy, sepsis, heart failure, liver failure, Charlson comorbidity index (≥2 points), mechanical ventilation, and renal function at discharge were predictors for 1-year mortality. The area under the receiver operating characteristic curves (AUROCs) of 30-day prediction model were 0.878 (95% confidence interval (CI): 0.849-0.908) in the training cohort and 0.867 (95% CI: 0.820–0.913) in the validation cohort. The AUROCs of the 1-year mortality prediction in the training and validation cohort were 0.803 (95% CI: 0.772–0.834) and 0.788 (95% CI: 0.741–0.835), respectively.

Conclusion

Our easily applied prediction models can effectively identify individuals at high mortality risk within 30 days or 1 year in hospitalized patients with ischemic AKI. It can guide the optimal clinical management to minimize mortality after an episode of ischemic AKI.
Profile of specific and associated autoantibodies in patients with idiopathic inflammatory myopathies in a Colombian population
Authors: Hormaza-Jaramillo Andrés , Bedoya-Joaqui Vanessa , Puerta-Sarmiento Germán , Bautista Mario , Rios-Serna Lady J. , Delgado-Mora Tatiana , Nieto-Aristizábal Ivana , Ruiz-Ordoñez Ingrid
Published: August 2022

Objectives

Idiopathic inflammatory myopathies (IIMs) are chronic, autoimmune diseases with several forms of presentation. Diagnosis is mostly clinical in our region. Our aim was to evaluate the autoantibody profile of patients with IIMs.

Methods

This study is a cross-sectional study with a prospective recollection of data, conducted between 2019–2021, in a single center in Cali, Colombia. Patients with a clinical diagnosis or suspicion of IIM were included. The presence of myositis-specific/associated antibodies was evaluated by immunoblotting in serum samples. Phenotypic characterization was performed.

Results

A total of 36 patients were included. The mean age was 50.6 (16.7) years, and 20 (55.6%) were female. Eighteen (50%) patients were seropositive, of which 11 (30.5%) presented one positive antibody, with anti-TIF1ɣbeing the most frequent (n = 4, 11.1%), followed by anti-Ro52 (n = 2, 5.6%). Seven patients (19.4%) showed >1 positive antibody. Dermatomyositis was the most frequent type of IIM in seropositive patients (n = 8, 44.4%), followed by anti-synthetase syndrome (n = 4, 22.2%). Weakness was symmetric and presented in the upper and lower extremities in 11 (61.1%) patients each. Both respiratory insufficiency and weight loss were seen in 7 (38.9%) patients, Gottron papules in six (33.3%) patients, and heliotrope rash, esophageal dysmotility, and myalgia in 5 (27.8%) patients. Pulmonary interstitial disease was seen in 4 (22.2%, with antibodies for anti-Ro52, anti-MDA5 + anti-Jo1 + anti-TIF1ɣ, anti-MDA5 + anti-SAE1 + anti-NXP2, and anti-cN1A + anti-Ro52) patients, and malignancy was seen in 2 (11.1%) patients (1 with anti-Mi2β and 1 with anti-TIF1ɣ + anti-Mi2α). In all, 7 (19.4%) patients required intensive care (2 seropositive, 1 with anti-PL7, 1 with anti-MDA5 + anti-Jo1 + anti-TIF1ɣ), and 1 (2.8%) (seronegative) patient died.

Conclusion

This study is the first study in the Southwest of Colombia that evaluates myositis-specific/associated antibodies in IIM. Half of the patients were seropositive. Anti-TIF1ɣwas the most frequent MSA and anti-Ro52 was the most frequent MAA. Several patients presented antibody combinations. Further studies are needed to fully associate phenotypes with antibodies.
Calibration and validation of the Pneumonia Shock Score in critically ill patients with SARS-CoV-2 infection, a multicenter prospective cohort study
Authors: Carmo Thomas A. , Ferreira Isabella B. B. , Menezes Rodrigo C. , Pina Márcio L. T. , Oliveira Roberto S. , Telles Gabriel P. , Machado Antônio F. A. , Aguiar Tércio C. , Caldas Juliana R. , Arriaga María B. , Akrami Kevan M. , Filgueiras Filho Nivaldo M. , Andrade Bruno B.
Published: August 2022

Background

Prognostic tools developed to stratify critically ill patients in Intensive Care Units (ICUs), are critical to predict those with higher risk of mortality in the first hours of admission. This study aims to evaluate the performance of the pShock score in critically ill patients admitted to the ICU with SARS-CoV-2 infection.

Methods

Prospective observational analytical cohort study conducted between January 2020 and March 2021 in four general ICUs in Salvador, Brazil. Descriptive statistics were used to characterize the cohort and a logistic regression, followed by cross-validation, were performed to calibrate the score. A ROC curve analysis was used to assess accuracy of the models analyzed.

Results

Six hundred five adult ICU patients were included in the study. The median age was 63 (IQR: 49–74) years with a mortality rate of 33.2% (201 patients). The calibrated pShock-CoV score performed well in prediction of ICU mortality (AUC of 0.80 [95% Confidence Interval (CI): 0.77–0.83; p-value < 0.0001]).

Conclusions

The pShock-CoV score demonstrated robust discriminatory capacity and may assist in targeting scarce ICU resources during the COVID-19 pandemic to those critically ill patients most likely to benefit.
DDX56 inhibits PRV replication through regulation of IFN-β signaling pathway by targeting cGAS
Authors: Xie Jingying , Li Xiangrong , Yang Shunyu , Yan Zhenfang , Chen Lei , Yang Yanmei , Li Dianyu , Zhang Xiangbo , Feng Ruofei
Published: August 2022

Pseudorabies virus (PRV) is an agent of Aujeszky's disease, and causes great economic losses to pig farming. Re-outburst of pseudorabies implies that new control measures are urgently needed. We show here that DDX56 possesses the ability to inhibit PRV replication in vitro, which may be an important factor for PRV infection. Overexpression of DDX56 inhibited PRV genomic DNA transcription and lower titers of PRV infection in PK15 cells, whereas down-regulation of the DDX56 expression had a promotion role on virus replication. Further study demonstrated that DDX56 exerted its proliferation-inhibitory effects of PRV through up-regulating cGAS-STING-induced IFN-β expression. Moreover, we found that DDX56 could promote cGAS expression and direct interaction also existed between DDX56 and cGAS. Based on this, DDX56-regulated IFN-β pathway may be targeted at cGAS. To verify this, down-regulated cGAS expression in DDX56 over-expression cells was performed. Results indicated that knockdown of cGAS expression could abrogate the inhibition role of DDX56 on PRV proliferation and weaken the effect of DDX56 on IFN-β expression. In addition, DDX56 played a promotion role in IRF3 phosphorylation and nucleus translocation. Altogether, our results highlight DDX56's antiviral role in PRV infection, and our findings contribute to a better understanding of host factors controlling PRV replication.
Effects of scale worm parasitism on interactions between the symbiotic gill microbiome and gene regulation in deep sea mussel hosts
Authors: Yao Gaoyou , Zhang Hua , Xiong Panpan , Jia Huixia , He Maoxian
Published: August 2022

Diverse adaptations to the challenging deep sea environment are expected to be found across all deep sea organisms. Scale worms Branchipolynoe pettiboneae are believed to adapt to the deep sea environment by parasitizing deep sea mussels; this biotic interaction is one of most known in the deep sea chemosynthetic ecosystem. However, the mechanisms underlying the effects of scale worm parasitism on hosts are unclear. Previous studies have revealed that the microbiota plays an important role in host adaptability. Here, we compared gill-microbiota, gene expression and host-microorganism interactions in a group of deep sea mussels (Gigantidas haimaensis) parasitized by scale worm (PA group) and a no parasitic control group (NPA group). The symbiotic microorganism diversity of the PA group significantly decreased than NPA group, while the relative abundance of chemoautotrophic symbiotic bacteria that provide the host with organic carbon compounds significantly increased in PA. Interestingly, RNA-seq revealed that G. haimaensis hosts responded to B. pettiboneaei parasitism through significant upregulation of protein and lipid anabolism related genes, and that this parasitism may enhance host mussel nutrient anabolism but inhibit the host’s ability to absorb nutrients, thus potentially helping the parasite obtain nutrients from the host. In an integrated analysis of the interactions between changes in the microbiota and host gene dysregulation, we found an agreement between the microbiota and transcriptomic responses to B. pettiboneaei parasitism. Together, our findings provide new insights into the effects of parasite scale worms on changes in symbiotic bacteria and gene expression in deep sea mussel hosts. We explored the potential role of host-microorganism interactions between scale worms and deep sea mussels, and revealed the mechanisms through which scale worm parasitism affects hosts in deep sea chemosynthetic ecosystem.
Analysis and control of fungal deterioration on the surface of pottery figurines unearthed from the tombs of the Western Han Dynasty
Authors: Wang Yu , Wang Cen , Yang Xinyu , Ma Kaixuan , Guo Peifeng , Sun Qirui , Jia Shili , Pan Jiao
Published: August 2022

In April 2020, 232 tombs of the Western Han Dynasty were found in Sundayuan, Heze City. In total, 141 pottery figurines of significant historical, cultural, and artistic value were unearthed from the tombs. Some of the figurines are currently being stored in warehouses, and the surface of some of the figurines show fungal deterioration. To thoroughly analyze the fungal deterioration on the surface of the pottery figurines and find appropriate control methods, we used high-through sequencing, scanning electron microscopy observation, pure cultures of culturable fungi, and optical microscopy observation and molecular identification of culturable fungi. We conducted fungistatic and simulation experiments in the laboratory to find appropriate control methods. We found that the fungi on the surface of the figurines were mainly of the phylum Ascomycota, and a few fungi were of the phyla Basidiomycota and Mucoromycota. We isolated seven culturable fungal strains and observed their colony morphology. The seven fungal strains were Lecanicillium aphanocladii, Penicillium aurantiogriseum, Clonostachys rosea, Mortierella sp., Mortierella alpina, Aspergillus flavus, and Cladosporium halotolerans. Through the fungistatic and simulation experiments conducted in the laboratory, we found that 50 mg/ml cinnamaldehyde and 0.5% K100 (2-methyl-4-isothiazolin-3-one) have a good fungistatic effect. They can not only inhibit the growth of fungi on medium, but also inhibit the growth of fungi on the surface of pottery figurines. This study has good reference significance for the analysis and control of fungal deterioration of unearthed pottery figurines.
Identification of phenolics from miracle berry (Synsepalum dulcificum) leaf extract and its antiangiogenesis and anticancer activities
Authors: Ma Fei-Yue , Zhang Xiu-Mei , Li Ya , Zhang Ming , Tu Xing-Hao , Du Li-Qing
Published: August 2022

Miracle berry is well-known for its ability to convert sour foods to sweet. In this study, the secondary metabolites of miracle berry leaves (MBL) were identified by UPLC-DAD-MS, and its antiangiogenesis and anticancer activities were evaluated by using a zebrafish model and the MCF-7 xenograft mouse model, respectively. The result showed that 18 phenolic compounds were identified in MBL extract, and dominated by the derivatives of quercetin and myricetin. The MBL extract showed low toxicity and high antiangiogenesis activity, it significantly inhibited the subintestinal vein vessels development in zebrafish at very low concentration. Furthermore, the MBL extract could promote the apoptosis of tumor cells and significantly inhibit the growth of MCF-7 xenograft tumor. In addition, the analysis of metabolites revealed that the MBL extract inhibited tumor growth by activating the metabolic pathways of unsaturated fatty acids and purines. Overall, this study suggests that MBL extract can be used as a natural anticancer adjuvant in the fields of functional foods.
Combined systemic inflammatory immunity index and prognostic nutritional index scores as a screening marker for sarcopenia in patients with locally advanced gastric cancer
Authors: Ding Ping'an , Lv Jingxia , Sun Chenyu , Chen Shuya , Yang Peigang , Tian Yuan , Zhou Qin , Guo Honghai , Liu Yang , Zhao Qun
Published: August 2022

Background

Sarcopenia is associated with poor clinical outcomes in patients with locally advanced gastric cancer (LAGC). Currently, the diagnostic criteria for sarcopenia are complex and laborious. Increased evidence suggests the inflammatory state of the body is closely associated with the development of sarcopenia. The systemic immune-inflammatory index (SII) and the prognostic nutritional index (PNI) are representative blood indicators of the status of the systemic inflammatory response, but the clinical significance of the combined testing of these two indicators remains unclear. We aimed to develop a simple and practical risk score (SII-PNI score) to screen patients with LAGC for sarcopenia on admission for early diagnosis.

Methods

We registered a prospective clinical study from January 2011 to May 2016 involving 134 patients with LAGC undergoing radical surgical resection. All patients followed the definition of sarcopenia in the Asian Working Group on Sarcopenia (AWGS) guidelines and were divided into sarcopenia and non-sarcopenia groups. SII-PNI score 0–2 was scored as 2 for high SII (≥432.9) and low PNI ( ≤ 49.5); score 1, either high SII or low PNI; score 0, no high SII or low PNI.

Results

All patients underwent radical surgery, including 31 patients (23.13%) with sarcopenia according to AWGS criteria. The SII-PNI score was significantly lower in the non-sarcopenic patients than in the sarcopenic patients (p < 0.001). Logistic multivariate analysis showed that the SII-PNI score predicted an independent prognostic factor for sarcopenia (p < 0.001). Patients with high SII-PNI scores had significantly worse prognosis than those with low SII-PNI scores (p < 0.001). The SII-PNI score was an independent prognostic factor for predicting overall survival and disease-free survival (p = 0.016, 0.023).

Conclusion

Peripheral blood parameters SII-PNI scores accurately identify sarcopenia in patients with LAGC and could be used as potential systemic markers.
Case report: A rare case of pulmonary mucormycosis caused by Lichtheimia ramosa in pediatric acute lymphoblastic leukemia and review of Lichtheimia infections in leukemia
Authors: He Guo-qian , Xiao Ling , Pan Zhen , Wu Jian-rong , Liang Dong-ni , Guo Xia , Jiang Ming-yan , Gao Ju
Published: August 2022

Mucormycosis caused by Lichtheimia ramosa is an emerging and uncommon opportunistic infection in patients with hematological malignancies, with high mortality rates. Herein, we first report a case of pulmonary mucormycosis with Lichtheimia ramosa in a 3-year-old girl recently diagnosed with B-cell acute lymphoblastic leukemia. The diagnosis was made using computerized tomography of the lung, metagenomic next-generation sequencing (mNGS) of blood and sputum specimens, and microscopic examination to detect the development of Lichtheimia ramosa on the surgical specimen. She was effectively treated after receiving prompt treatment with amphotericin B and posaconazole, followed by aggressive surgical debridement. In our case, the fungal isolates were identified as Lichtheimia ramosa using mNGS, which assisted clinicians in quickly and accurately diagnosing and initiating early intensive treatment. This case also indicated the importance of strong clinical suspicion, as well as aggressive antifungal therapy combined with surgical debridement of affected tissues.
The Role and Therapeutic Potential of Macropinocytosis in Cancer
Authors: Qiu Zejing , Liu Wencheng , Zhu Qianru , Ke Kun , Zhu Qicong , Jin Weiwei , Yu Shuxian , Yang Zuyi , Li Lin , Sun Xiaochen , Ren Shuyi , Liu Yanfen , Zhu Zhiyu , Zeng Jiangping , Huang Xiaoyu , Huang Yan , Wei Lu , Ma Mengmeng , Lu Jun , Chen Xiaoyang , Mou Yiping , Xie Tian , Sui Xinbing
Published: August 2022

Macropinocytosis, a unique endocytosis pathway characterized by nonspecific internalization, has a vital role in the uptake of extracellular substances and antigen presentation. It is known to have dual effects on cancer cells, depending on cancer type and certain microenvironmental conditions. It helps cancer cells survive in nutrient-deficient environments, enhances resistance to anticancer drugs, and promotes invasion and metastasis. Conversely, overexpression of the RAS gene alongside drug treatment can lead to methuosis, a novel mode of cell death. The survival and proliferation of cancer cells is closely related to macropinocytosis in the tumor microenvironment (TME), but identifying how these cells interface with the TME is crucial for creating drugs that can limit cancer progression and metastasis. Substantial progress has been made in recent years on designing anticancer therapies that utilize the effects of macropinocytosis. Both the induction and inhibition of macropinocytosis are useful strategies for combating cancer cells. This article systematically reviews the general mechanisms of macropinocytosis, its specific functions in tumor cells, its occurrence in nontumor cells in the TME, and its application in tumor therapies. The aim is to elucidate the role and therapeutic potential of macropinocytosis in cancer treatment.
Authorization of COVID-19 clinical trials: lessons from 2 years of experience of a national competent authority
Authors: Vignot Stéphane , Dhanani Alban , Sainte-Marie Isabelle , de Ligniville Lajavardi Laure , Even Gwennaelle , Echemann Muriel , Hulin Nina , Ménoret Claire , Maison Patrick , Ratignier-Carbonneil Christelle
Published: August 2022

The COVID-19 pandemic was immediately marked by strong clinical research activity. The French national competent authority presents the data on request for authorization during the first 2 years of COVID-19 pandemic to inform discussions on future clinical research issues. Applications for authorization of interventional COVID-19 trials submitted between March 2020 and February 2022 were analysed. Trials on medicinal products were classified according to market authorization status, mechanism of action of the investigational product, target population and clinical context. In 2 years, 208 clinical trials were submitted. 75% were authorized, 3% refused, 22% withdrawn by the sponsor. Among medicinal products trials, 6% were adaptative, 28% included outpatients and 2% were focused on post COVID-19 symptoms. Vaccines were evaluated in 9% of trials, antivirals in 38% and immunomodulators in 35%; 63% of antiviral and 60% of immunomodulation trials included a drug with a marketing authorization in another indication. The dynamics of authorization prove the involvement of stakeholders but also illustrates the risk of dispersion of research efforts and the risk of decorrelation between trials and the epidemic evolution. The high rate of withdrawal of applications could be explained by changes in the sanitary context and by the dropping of some therapeutic approaches. Most of clinical trials evaluate drugs authorized in another indication and assessment procedures by authorities have to mitigate between the knowledge of safety profile of those drugs and the uncertainty in a new clinical context with rapidly evolving knowledge. COVID-19 experience should now support future evolution in clinical research practices.
An overview of the optically detected magnetic-state-selected cesium beam clock
Authors: Chen Sifei , Liu Chang , Fan Lifeng , Liu Chen , Li Yuanhao , Xu Shaohang , Li Chaojie , Wang Yanhui
Published: August 2022

Among all kinds of compact cesium beam clocks, the optically detected magnetic-state-selected cesium beam clock (OMCC) combines the advantages of the magnetic state selecting scheme and fluorescence detecting method. This paper presents an overview of the OMCC. Technical issues, noise sources, frequency shifts and improvements of OMCC are reviewed. Finally, the frequency stability of five OMCC is given, which is better than the stability of the high-performance version of Microsemi 5071A.
Detecting the pH-dependent liquid-liquid phase separation of single levitated aerosol microdroplets via laser tweezers-Raman spectroscopy
Authors: Tong Yu-Kai , Meng Xiangxinyue , Zhou Bo , Sun Rui , Wu Zhijun , Hu Min , Ye Anpei
Published: August 2022

Ambient atmospheric aerosol particles comprised of various inorganic and organic substances ubiquitously undergo phase transition, such as efflorescence, amorphization, and especially liquid-liquid phase separation (LLPS). Resultant changes of physicochemical properties in aerosols then deeply affect the climate system. However, finely detecting these processes occurring in single aerosol particles, especially under the acidic condition of real atmospheric environment, remains a challenge. In this work, we investigated the pH-dependent phase separation in single levitated microdroplets using a self-developed laser tweezers Raman spectroscopy (LTRS) system. The dynamic process of LLPS in laser-trapped droplets over the course of humidity cycles was detected with the time-resolved cavity-enhanced Raman spectra. These measurements provide the first comprehensive account of the pH-dependent LLPS in single levitated aerosol microdroplets and bring possible implications on phase separation in actual atmospheric particles.
Finasteride Alleviates High Fat Associated Protein-Overload Nephropathy by Inhibiting Trimethylamine N-Oxide Synthesis and Regulating Gut Microbiota
Authors: Wang Zuoyuan , You Li , Ren Yuan , Zhu Xiaoye , Mao Xiaoyi , Liang Xiaowan , Wang Tingting , Guo Yumeng , Liu Te , Xue Jun
Published: August 2022

Unhealthy diet especially high-fat diet (HFD) is the major cause of hyperlipidemia leading to deterioration of chronic kidney diseases (CKD) in patients. Trimethylamine N-oxide (TMAO) is a gut-derived uremic toxin. Our previous clinical study demonstrated that the elevation of TMAO was positively correlated with CKD progression. Finasteride, a competitive and specific inhibitor of type II 5a-reductase, has been reported recently to be able to downregulate plasma TMAO level thus preventing the onset of atherosclerosis by our research group. In this study, we established a protein-overload nephropathy CKD mouse model by bovine serum albumin (BSA) injection to investigate whether hyperlipidemia could accelerate CKD progression and the underlying mechanisms. Finasteride was administrated to explore its potential therapeutic effects. The results of biochemical analyses and pathological examination showed that HFD-induced hyperlipidemia led to aggravated protein-overload nephropathy in mice along with an elevated level of circulating TMAO, which can be alleviated by finasteride treatment possibly through inhibition of Fmo3 in liver. The 16 S rRNA sequencing results indicated that HFD feeding altered the composition and distribution of gut microbiota in CKD mice contributing to the enhanced level of TMAO precursor TMA, while finasteride could exert beneficial effects via promoting the abundance of Alistipes_senegalensis and Akkermansia_muciniphila. Immunofluorescence staining (IF) and qRT-PCR results demonstrated the disruption of intestinal barrier by decreased expression of tight junction proteins including Claudin-1 and Zo-1 in HFD-fed CKD mice, which can be rescued by finasteride treatment. Cytokine arrays and redox status analyses revealed an upregulated inflammatory level and oxidative stress after HFD feeding in CKO mice, and finasteride-treatment could alleviate these lesions. To summarize, our study suggested that finasteride could alleviate HFD-associated deterioration of protein-overload nephropathy in mice by inhibition of TMAO synthesis and regulation of gut microbiota.
nNOS-derived NO modulates force production and iNO-derived NO the excitability in C2C12-derived 3D tissue engineering skeletal muscle via different NO signaling pathways
Authors: Mosqueira Matias , Scheid Lisa-Mareike , Kiemel Dominik , Richardt Talisa , Rheinberger Mona , Ollech Dirk , Lutge Almut , Heißenberg Tim , Pfitzer Lena , Engelskircher Lisa , Yildiz Umut , Porth Isabel
Published: August 2022

Nitric oxide (NO) is a bioactive gas produced by one of the three NO synthases: neuronal NOS (nNOS), inducible (iNOS), and endothelial NOS (eNOS). NO has a relevant modulatory role in muscle contraction; this takes place through two major signaling pathways: (i) activation of soluble guanylate cyclase and, thus, protein kinase G or (ii) nitrosylation of sulfur groups of cysteine. Although it has been suggested that nNOS-derived NO is the responsible isoform in muscle contraction, the roles of eNOS and iNOS and their signaling pathways have not yet been clarified. To elucidate the action of each pathway, we optimized the generation of myooids, an engineered skeletal muscle tissue based on the C2C12 cell line. In comparison with diaphragm strips from wild-type mice, 180 myooids were analyzed, which expressed all relevant excitation–contraction coupling proteins and both nNOS and iNOS isoforms. Along with the biochemical results, myooids treated with NO donor (SNAP) and unspecific NOS blocker (L-NAME) revealed a comparable NO modulatory effect on force production as was observed in the diaphragm strips. Under the effects of pharmacological tools, we analyzed the myooids in response to electrical stimulation of two possible signaling pathways and NO sources. The nNOS-derived NO exerted its negative effect on force production via the sGG-PKG pathway, while iNOS-derived NO increased the excitability in response to sub-threshold electrical stimulation. These results strengthen the hypotheses of previous reports on the mechanism of action of NO during force production, showed a novel function of iNOS-derived NO, and establish the myooid as a novel and robust alternative model for pathophysiological skeletal muscle research.
Determining the efficacy of ginger Zingiber officinale as a potential nutraceutical agent for boosting growth performance and health status of Labeo rohita reared in a semi-intensive culture system
Authors: Rawat Priya , Kaur Vaneet Inder , Tyagi Anuj , Norouzitallab Parisa , Baruah Kartik
Published: August 2022

A 120-day feeding trial was conducted in a pilot field setting to study the nutraceutical properties of ginger powder (GP), focusing on the growth performance and health status of Indian major carp L. rohita reared under a semi-intensive culture system. L. rohita fingerlings (average weight: 20.5 g) were divided into five groups and fed a diet with no GP supplementation (control), or a diet supplemented with GP at 5 g (GP5), 10 g (GP10), 15 g (GP15), and 20 g (GP20) per kg of feed. The study was carried out in outdoor tanks (20 m2) following a complete randomized design with three replicates for each experimental group. Dietary supplementation of GP at 15 g·kg−1 (GP15) of feed caused a significant increase in the growth performances of the fish. Results also showed that feeding of GP15 diet led to a significant improvement in the health status of fish as indicated by a marked change in the tested haematological indices (i.e., higher RBC, WBC, Hb, and Ht values), oxidative status (increased SOD and decreased LPO levels), biochemical parameters (increased HDL, decreased cholesterol, and triglycerides levels), and activities of the liver enzymes (decreased AST and ALT). Overall results suggested that dietary supplementation of GP could positively influence the growth and health status of L. rohita fingerlings, and hence could be an important natural nutraceutical for sustainable farming of carp.