bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulated Microgravity Potentiates Hematopoietic Differentiation of Human Pluripotent Stem Cells and Supports Formation of 3D Hematopoietic Cluster
Authors: Ma Chiyuan , Xiong Yue , Han Pei , Zhang Xueying , Cao Yujing , Wang Baobei , Zhao Huashan , Duan Enkui , Zhang Jian V. , Lei Xiaohua
Published: January 2022

Microgravity has been shown to induces many changes in proliferation, differentiation and growth behavior of stem cells. Little is known about the effect of microgravity on hematopoietic differentiation of pluripotent stem cells (PSCs). In this study, we used the random position machine (RPM) to investigate whether simulated microgravity (SMG) allows the induction of hematopoietic stem/progenitor cell (HSPC) derived from human embryonic stem cells (hESCs) in vitro. The results showed that SMG facilitates hESCs differentiate to HSPC with more efficient induction of CD34+CD31+ hemogenic endothelium progenitors (HEPs) on day 4 and CD34+CD43+ HSPC on day 7, and these cells shows an increased generation of functional hematopoietic cells in colony-forming unit assay when compared with normal gravity (NG) conditions. Additionally, we found that SMG significantly increased the total number of cells on day 4 and day 7 which formed more 3D cell clusters. Transcriptome analysis of cells identified thousands of differentially expressed genes (DEGs) between NG and SMG. DEGs down-regulated were enriched in the axonogenesis, positive regulation of cell adhesion, cell adhesion molecule and axon guidance, while SMG resulted in the up-regulation of genes were functionally associated with DNA replication, cell cycle, PI3K-Akt signaling pathway and tumorigenesis. Interestingly, some key gene terms were enriched in SMG, like hypoxia and ECM receptor interaction. Moreover, HSPC obtained from SMG culture conditions had a robust ability of proliferation in vitro. The proliferated cells also had the ability to form erythroid, granulocyte and monocyte/macrophage colonies, and can be induced to generate macrophages and megakaryocytes. In summary, our data has shown a potent impact of microgravity on hematopoietic differentiation of hPSCs for the first time and reveals an underlying mechanism for the effect of SMG on hematopoiesis development.
Rubicon in Metabolic Diseases and Ageing
Authors: Minami Satoshi , Nakamura Shuhei , Yoshimori Tamotsu
Published: January 2022

Autophagy is a conserved cellular degradation system that maintains intracellular homeostasis. Cytoplasmic components are engulfed into double-membrane vesicles called autophagosomes, which fuse with lysosomes, and resulting in the degradation of sequestered materials. Recently, a close association between autophagy and the pathogenesis of metabolic diseases and ageing has become apparent: autophagy is dysregulated during metabolic diseases and ageing; dysregulation of autophagy is intimately associated with the pathophysiology. Rubicon (Run domain Beclin-1 interacting and cysteine-rich containing protein) has been identified as a Beclin-1 associated protein. Notably, Rubicon is one of few negative regulators of autophagy whereas many autophagy-related genes are positive regulators of autophagy. Rubicon also has autophagy-independent functions including phagocytosis and endocytosis. In this mini-review, we focus on the various roles of Rubicon in different organs in the settings of metabolic diseases and ageing, and discuss its potential role as a promising therapeutic target.
FAIM-L - SIVA-1: Two Modulators of XIAP in Non-Apoptotic Caspase Function
Authors: Coccia Elena , Solé Montse , Comella Joan X
Published: January 2022

Apoptosis is crucial for the correct development of the nervous system. In adulthood, the same protein machinery involved in programmed cell death can control neuronal adaptiveness through modulation of synaptic pruning and synaptic plasticity processes. Caspases are the main executioners in these molecular pathways, and their strict regulation is essential to perform neuronal remodeling preserving cell survival. FAIM-L and SIVA-1 are regulators of caspase activation. In this review we will focus on FAIM-L and SIVA-1 as two functional antagonists that modulate non-apoptotic caspase activity in neurons. Their participation in long-term depression and neurite pruning will be described in base of the latest studies performed. In addition, the association of FAIM-L non-apoptotic functions with the neurodegeneration process will be reviewed.
An Iron Transporter Is Involved in Iron Homeostasis, Energy Metabolism, Oxidative Stress, and Metacyclogenesis in Trypanosoma cruzi
Authors: Dick Claudia F. , Rocco-Machado Nathália , Dos-Santos André L. A. , Carvalho-Kelly Luiz F. , Alcantara Carolina L. , Cunha-E-Silva Narcisa L. , Meyer-Fernandes José R. , Vieyra Adalberto
Published: January 2022

The parasite Trypanosoma cruzi causes Chagas’ disease; both heme and ionic Fe are required for its optimal growth, differentiation, and invasion. Fe is an essential cofactor in many metabolic pathways. Fe is also harmful due to catalyzing the formation of reactive O2 species; for this reason, all living systems develop mechanisms to control the uptake, metabolism, and storage of Fe. However, there is limited information available on Fe uptake by T. cruzi. Here, we identified a putative 39-kDa Fe transporter in T. cruzi genome, TcIT, homologous to the Fe transporter in Leishmania amazonensis and Arabidopsis thaliana. Epimastigotes grown in Fe-depleted medium have increased TcIT transcription compared with controls grown in regular medium. Intracellular Fe concentration in cells maintained in Fe-depleted medium is lower than in controls, and there is a lower O2 consumption. Epimastigotes overexpressing TcIT, which was encountered in the parasite plasma membrane, have high intracellular Fe content, high O2 consumption—especially in phosphorylating conditions, high intracellular ATP, very high H2O2 production, and stimulated transition to trypomastigotes. The investigation of the mechanisms of Fe transport at the cellular and molecular levels will assist in elucidating Fe metabolism in T. cruzi and the involvement of its transport in the differentiation from epimastigotes to trypomastigotes, virulence, and maintenance/progression of the infection.
Communicating Photograph Content Through Tactile Images to People With Visual Impairments
Authors: Pakėnaitė Karolina , Nedelev Petar , Kamperou Eirini , Proulx Michael J. , Hall Peter M.
Published: January 2022

Millions of people with a visual impairment across the world are denied access to visual images. They are unable to enjoy the simple pleasures of viewing family photographs, those in textbooks or tourist brochures and the pictorial embellishment of news stories etc. We propose a simple, inexpensive but effective approach, to make content accessible via touch. We use state-of-the-art algorithms to automatically process an input photograph into a collage of icons, that depict the most important semantic aspects of a scene. This collage is then printed onto swell paper. Our experiments show that people can recognise content with an accuracy exceeding 70% and create plausible narratives to explain it. This means that people can understand image content via touch. Communicating scene foreground is a step forward, but there are many other steps needed to provide the visually impaired with the fullest possible access to visual content.
Artificial Intelligence in Cardiac MRI: Is Clinical Adoption Forthcoming?
Authors: Fotaki Anastasia , Puyol-Antón Esther , Chiribiri Amedeo , Botnar René , Pushparajah Kuberan , Prieto Claudia
Published: January 2022

Artificial intelligence (AI) refers to the area of knowledge that develops computerised models to perform tasks that typically require human intelligence. These algorithms are programmed to learn and identify patterns from “training data,” that can be subsequently applied to new datasets, without being explicitly programmed to do so. AI is revolutionising the field of medical imaging and in particular of Cardiovascular Magnetic Resonance (CMR) by providing deep learning solutions for image acquisition, reconstruction and analysis, ultimately supporting the clinical decision making. Numerous methods have been developed over recent years to enhance and expedite CMR data acquisition, image reconstruction, post-processing and analysis; along with the development of promising AI-based biomarkers for a wide spectrum of cardiac conditions. The exponential rise in the availability and complexity of CMR data has fostered the development of different AI models. Integration in clinical routine in a meaningful way remains a challenge. Currently, innovations in this field are still mostly presented in proof-of-concept studies with emphasis on the engineering solutions; often recruiting small patient cohorts or relying on standardised databases such as Multi-ethnic Study on atherosclerosis (MESA), UK Biobank and others. The wider incorporation of clinically valid endpoints such as symptoms, survival, need and response to treatment remains to be seen. This review briefly summarises the current principles of AI employed in CMR and explores the relevant prospective observational studies in cardiology patient cohorts. It provides an overview of clinical studies employing undersampled reconstruction techniques to speed up the scan encompassing cine imaging, whole-heart imaging, multi-parametric mapping and magnetic resonance fingerprinting along with the clinical utility of AI applications in image post-processing, and analysis. Specific focus is given to studies that have incorporated CMR-derived prediction models for prognostication in cardiac disease. It also discusses current limitations and proposes potential developments to enable multi-disciplinary collaboration for improved evidence-based medicine. AI is an extremely promising field and the timely integration of clinician's input in the ingenious technical investigator's paradigm holds promise for a bright future in the medical field.
Two-End-Member Mixing in the Fluids Emitted From Mud Volcano Lei-Gong-Huo, Eastern Taiwan: Evidence From Sr Isotopes
Authors: Chao Hung-Chun , You Chen-Feng , Lin In-Tian , Liu Hou-Chun , Chung Ling-Ho , Huang Chun-Chang , Chung Chuan-Hsiung
Published: January 2022

Mud volcano is one of the most important conduits for deep seated materials to migrate upward in sedimentary basins, convergent margins, and subduction zones. Understanding their temporal and spatial characteristics and variations provides us the important information on fluid sources and chemical compositions at depth. Mud volcano Lei-Gong-Huo (MV LGH) is a unique mud volcano, which is located on the mélange formation lying on the andesitic volcanic arc. Fluids emitted from 46 mud pools in MV LGH in eastern Taiwan were sampled and their major trace constitutes as well as H, O, and Sr isotopes (87Sr/86Sr and δ88Sr) were measured. Major constitutes of the fluids are Cl−, Na, and Ca. Compared with seawater, LGH fluids have lower Cl−, δD, δ18O, Na/Cl, K/Cl, and Mg/Cl but higher Ca/Cl ratios, indicating water–rock interaction of igneous rock and the ancient seawater at the source region. This interpretation is further supported by Sr isotopes, which show low value of 87Sr/86Sr ratio down to 0.70708. The result of spatial distribution showing strong negative correlation between Na and Ca concentration as well as Ca and 87Sr/86Sr ratios indicates that two end-member mixing is the major chemical characteristic. The fluids interacting with igneous rock carry high Ca, high δ88Sr, low Na, and low 87Sr/86Sr ratio, while those interacting with sedimentary rock carry low Ca, low δ88Sr, high Na, and high 87Sr/86Sr ratio. The source from the igneous region dominates the eastern and southeastern parts of the mud pools while sedimentary source dominates the western and northwestern parts. Most mud pools show mixing behavior between the two sources. Some of the sedimentary-dominated mud pools reveal existence of residual ancient water as indicated by 87Sr/86Sr. The major factor to fractionate the stable Sr isotopes in LGH waters is the source lithology. In summary, fluids emitted by mud pools in LGH originate from two sources, which are water–rock interactions of igneous rock with the ancient seawater from the east and sedimentary rock from the west at depth, resulting from the complex geologic background of mélange formation.
Research Progress on Cenozoic Volcano Genesis and Fluid Action in Northeast China
Authors: Deng Yufeng , Huang Song , Wu Xueshan , Li Min
Published: January 2022

The tectonic evolution of northeast China is closely related to the subduction of the Pacific plate. The dehydration of the slab subduction process produces metasomatic agents that have important effects on the physical and chemical properties of the mantle wedge, including the decrease of seismic wave velocity and the increase of Poisson’s ratio and electrical conductivity. In order to investigate the tectonic evolution and fluid action of northeast China, this paper compares the previous seismic and electromagnetic imaging results of northeast China and explores the relationship between the genesis of Cenozoic volcanoes and fluid action in northeast China through rheological analysis. The results show that the western Pacific plate subducted into the mantle transition zone beneath northeast China, and sustained dehydration occurred. The upward migration of these released water caused partial melting at the base of the upper mantle. Some of the upwelling streams pierced the weak tectonic boundary under the buoyancy effect, which finally formed the large-scale Cenozoic volcanic events in northeast China.
Associations Between Dietary Inflammatory Index and Sex Hormones Among 6- to 19-Year-Old Children and Adolescents in NHANES 2015–2016
Authors: Ma Yuxia , Li Ruiqiang , Zhan Wenqiang , Huang Xin , Zhou Yutian , Sun Yan , Tian Hao , Zhu Huichen , Yin Bowen
Published: January 2022

Objectives

This study aimed to assess the relationship between dietary inflammatory index (DII) and sex steroids in children (6-11 years old) and adolescents (12-19 years old) in the U.S. National Health and Nutrition Examination Survey, 2015–2016.

Methods

Participants between the ages of 6-19 have 24-hour dietary intake data, serum sex hormones [total testosterone (TT), estradiol (E2)], and sex hormone-binding globulin (SHBG) available data (n = 1382). The free androgen index (FAI) is calculated as TT divided by SHBG and the ratio of TT to E2 (TT/E2). The constructed puberty state is defined as high levels of steroid hormones (TT≥50 ng/dL in men, E2≥20 pg/ml in women) or onset of menarche. Multiple linear regression analysis was stratified by gender-age and gender-pubertal status groups to evaluate the association between DII and sex hormone levels.

Results

After adjusting for covariates, the association between consecutive DII and sex hormone indicators by gender and age group. In male adolescents, DII was always negatively associated with TT (P-trend = 0.09), FAI (P-trend = 0.03) and E2 (P-trend = 0.01), and monotonically positively associated with SHBG (P-trend = 0.02).In female adolescents, with the increase of DII, a significant positive correlation with SHBG was observed (β 0.017, 95%CI: 0.009,0.053) (Table 3). Among female adolescents, a significant negative association between DII and TT and a significant positive association between SHBG were observed in this group. Moreover, DII was positively associated with SHBG of prepubertal males and negatively associated with FAI of prepubertal females.

Conclusions

DII was associated with decreased levels of certain sex steroid hormones (TT, FAI, and E2) and increased levels of SHBG in adolescents or pubertal individuals, with the associations presenting somewhat sex-dependent pattern. However, there is little evidence that there is a significant association in children or prepubertal children. Further research needs to be carried out to verify our results.
Molecular Characterization of a Novel Cathepsin L in Macrobrachium nipponense and Its Function in Ovary Maturation
Authors: Jiang Sufei , Xiong Yiwei , Zhang Wenyi , Zhu Junpeng , Cheng Dan , Gong Yongsheng , Wu Yan , Qiao Hui , Fu Hongtuo
Published: January 2022

Cathepsin L genes, which belonged to cysteine proteases, were a series of multifunctional protease and played important roles in a lot of pathological and physiological processes. In this study, we analyzed the characteristics a cathepsin L (named Mn-CL2) in the female oriental river prawn, Macrobrachium nipponense which was involved in ovary maturation. The Mn-CL2 was1,582 bp in length, including a 978 bp open reading frame that encoded 326 amino acids. The Mn-CL2 was classified into the cathepsin L group by phylogenetic analysis. Real-time PCR (qPCR) analysis indicated that Mn-CL2 was highly expressed in the hepatopancreas and ovaries of female prawns. During the different ovarian stages, Mn-CL2 expression in the hepatopancreas and ovaries peaked before ovarian maturation. In situ hybridization studies revealed that Mn-CL2 was localized in the oocyte of the ovary. Injection of Mn-CL2 dsRNA significantly reduced the expression of vitellogenin. Changes in the gonad somatic index also confirmed the inhibitory effects of Mn-CL2 dsRNA on ovary maturation. These results suggest that Mn-CL2 has a key role in promoting ovary maturation.
Using Machine Learning to Evaluate the Role of Microinflammation in Cardiovascular Events in Patients With Chronic Kidney Disease
Authors: Liu Xiao Qi , Jiang Ting Ting , Wang Meng Ying , Liu Wen Tao , Huang Yang , Huang Yu Lin , Jin Feng Yong , Zhao Qing , Wang Gui Hua , Ruan Xiong Zhong , Liu Bi Cheng , Ma Kun Ling
Published: January 2022

Background

Lipid metabolism disorder, as one major complication in patients with chronic kidney disease (CKD), is tied to an increased risk for cardiovascular disease (CVD). Traditional lipid-lowering statins have been found to have limited benefit for the final CVD outcome of CKD patients. Therefore, the purpose of this study was to investigate the effect of microinflammation on CVD in statin-treated CKD patients.

Methods

We retrospectively analysed statin-treated CKD patients from January 2013 to September 2020. Machine learning algorithms were employed to develop models of low-density lipoprotein (LDL) levels and CVD indices. A fivefold cross-validation method was employed against the problem of overfitting. The accuracy and area under the receiver operating characteristic (ROC) curve (AUC) were acquired for evaluation. The Gini impurity index of the predictors for the random forest (RF) model was ranked to perform an analysis of importance.

Results

The RF algorithm performed best for both the LDL and CVD models, with accuracies of 82.27% and 74.15%, respectively, and is therefore the most suitable method for clinical data processing. The Gini impurity ranking of the LDL model revealed that hypersensitive C-reactive protein (hs-CRP) was highly relevant, whereas statin use and sex had the least important effects on the outcomes of both the LDL and CVD models. hs-CRP was the strongest predictor of CVD events.

Conclusion

Microinflammation is closely associated with potential CVD events in CKD patients, suggesting that therapeutic strategies against microinflammation should be implemented to prevent CVD events in CKD patients treated by statin.
Pentose Phosphate Pathway Regulates Tolerogenic Apoptotic Cell Clearance and Immune Tolerance
Authors: He Dan , Mao Qiangdongzi , Jia Jialin , Wang Zhiyu , Liu Yu , Liu Tingting , Luo Bangwei , Zhang Zhiren
Published: January 2022

The efficient removal of apoptotic cells (ACs), a process termed as efferocytosis, is essential for immune homeostasis. While recent work has established an important interplay between efferocytosis and cellular metabolic changing, underlying mechanisms remain poorly known. Here, we discovered that pentose phosphate pathway (PPP) regulates tolerogenic ACs clearance and immune tolerance. ACs decreased levels of PPP-related genes and metabolites in macrophages. AG1, the agonist of PPP, increased the activity of PPP but greatly reduced macrophage phagocytosis of ACs and enhanced the inflammatory response during efferocytosis. miR-323-5p regulated the expression of PPP-related genes and its levels increased during efferocytosis. miR-323-5p inhibitor greatly promoted levels of PPP-related genes, reduced the macrophage phagocytosis of ACs, and increased inflammatory response during efferocytosis, suggesting that miR-323-5p was essential in regulating PPP activity and ACs clearance in macrophages. Correspondingly, the PPP agonist AG1 exacerbated the lupus-like symptoms in the AC-induced systemic lupus erythematosus (SLE) model. Our study reveals that regulating PPP-dependent metabolic reprogramming is critical for tolerogenic ACs phagocytosis and immune tolerance.
The Potential Mechanism of Cancer Patients Appearing More Vulnerable to SARS-CoV-2 and Poor Outcomes: A Pan-Cancer Bioinformatics Analysis
Authors: Huang Xinwei , Liang Huazheng , Zhang Hong , Tian Li , Cong Peilin , Wu Tingmei , Zhang Qian , Gao Xiaofei , Li Wanrong , Chen Aiwen , Zhang Yuxin , Dong Qianyu , Wan Hanxi , He Mengfan , Dai Danqing , Li Zhen , Xiong Lize
Published: January 2022

To explore the potential mechanism of cancer patients appearing more vulnerable to SARS-CoV-2 infection and poor COVID-19 outcomes, we conducted an integrative bioinformatics analysis for SARS-CoV-2-required genes and host genes and variants related to SARS-CoV-2 susceptibility and COVID-19 severity. BLCA, HNSC, KIRC, KIRP, LGG, PCPG, PRAD, TGCT, and THCA patients carrying rs10774671-A (OAS1) genotype may be more likely to have poor COVID-19 outcomes relative to those who carry rs10774671-G, because individuals carrying rs10774671-A will have lower expression of OAS1, which serves as a protective factor against SARS-CoV-2 processes and poor COVID-19 outcomes. SARS-CoV-2-required genes were correlated with TME, immune infiltration, overall survival, and anti-cancer drug sensitivity. CHOL patients may have a higher risk of SARS-CoV-2 infection than healthy subjects. SARS-CoV-2-induced ACE2 and NPC1 elevation may have a negative influence on the immune responses of LUSC and CD8+T infiltration of LUAD, and negatively affect the sensitivity of anti-lung cancer drugs. LUSC and LUAD patients may have a varying degree of adverse outcomes if they are infected with SARS-CoV-2. miR-760 may target and inhibit ACE2 expression. Cancer patients appearing vulnerable to SARS-CoV-2 infection and having poor COVID-19 outcomes may be partly due to host genetic factors and dysregulation of SARS-CoV-2-required genes. OAS1, ACE2, and miR-760 could serve as the treatment and intervention targets for SARS-CoV-2.
The Spectrum of the Deficiency of Adenosine Deaminase 2: An Observational Analysis of a 60 Patient Cohort
Authors: Barron Karyl S. , Aksentijevich Ivona , Deuitch Natalie T. , Stone Deborah L. , Hoffmann Patrycja , Videgar-Laird Ryan , Soldatos Ariane , Bergerson Jenna , Toro Camilo , Cudrici Cornelia , Nehrebecky Michele , Romeo Tina , Jones Anne , Boehm Manfred , Kanakry Jennifer A. , Dimitrova Dimana , Calvo Katherine R. , Alao Hawwa , Kapuria Devika , Ben-Yakov Gil , Pichard Dominique C. , Hathaway Londa , Brofferio Alessandra , McRae Elisa , Moura Natalia Sampaio , Schnappauf Oskar , Rosenzweig Sofia , Heller Theo , Cowen Edward W. , Kastner Daniel L. , Ombrello Amanda K.
Published: January 2022

The deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessively inherited disease that has undergone extensive phenotypic expansion since being first described in patients with fevers, recurrent strokes, livedo racemosa, and polyarteritis nodosa in 2014. It is now recognized that patients may develop multisystem disease that spans multiple medical subspecialties. Here, we describe the findings from a large single center longitudinal cohort of 60 patients, the broad phenotypic presentation, as well as highlight the cohort’s experience with hematopoietic cell transplantation and COVID-19. Disease manifestations could be separated into three major phenotypes: inflammatory/vascular, immune dysregulatory, and hematologic, however, most patients presented with significant overlap between these three phenotype groups. The cardinal features of the inflammatory/vascular group included cutaneous manifestations and stroke. Evidence of immune dysregulation was commonly observed, including hypogammaglobulinemia, absent to low class-switched memory B cells, and inadequate response to vaccination. Despite these findings, infectious complications were exceedingly rare in this cohort. Hematologic findings including pure red cell aplasia (PRCA), immune-mediated neutropenia, and pancytopenia were observed in half of patients. We significantly extended our experience using anti-TNF agents, with no strokes observed in 2026 patient months on TNF inhibitors. Meanwhile, hematologic and immune features had a more varied response to anti-TNF therapy. Six patients received a total of 10 allogeneic hematopoietic cell transplant (HCT) procedures, with secondary graft failure necessitating repeat HCTs in three patients, as well as unplanned donor cell infusions to avoid graft rejection. All transplanted patients had been on anti-TNF agents prior to HCT and received varying degrees of reduced-intensity or non-myeloablative conditioning. All transplanted patients are still alive and have discontinued anti-TNF therapy. The long-term follow up afforded by this large single-center study underscores the clinical heterogeneity of DADA2 and the potential for phenotypes to evolve in any individual patient.
Back to the Future: Spatiotemporal Determinants of NK Cell Antitumor Function
Authors: Li Joey H. , O’Sullivan Timothy E.
Published: January 2022

NK cells play a crucial role in host protection during tumorigenesis. Throughout tumor development, however, NK cells become progressively dysfunctional through a combination of dynamic tissue-specific and systemic factors. While a number of immunosuppressive mechanisms present within the tumor microenvironment have been characterized, few studies have contextualized the spatiotemporal dynamics of these mechanisms during disease progression and across anatomical sites. Understanding how NK cell immunosuppression evolves in these contexts will be necessary to optimize NK cell therapy for solid and metastatic cancers. Here, we outline the spatiotemporal determinants of antitumor NK cell regulation, including heterogeneous tumor architecture, temporal disease states, diverse cellular communities, as well as the complex changes in NK cell states produced by the sum of these higher-order elements. Understanding of the signals encountered by NK cells across time and space may reveal new therapeutic targets to harness the full potential of NK cell therapy for cancer.
Decreased Serum Maresin 1 Concentration Is Associated With Postmenopausal Osteoporosis: A Cross-Sectional Study
Authors: Wu Jing , Li Xin-Yue , Fang Xia , Teng Fang-Yuan , Xu Yong
Published: January 2022

Background: Maresin 1 plays a role in the regulation of inflammation and metabolic diseases in vivo. An increasing number of studies have reported that postmenopausal osteoporosis (PMOP) is associated with inflammation. However, the potential relationship between the serum Maresin 1 content and PMOP is unclear.

Aims: 1) To evaluate the Maresin 1 content in postmenopausal women with osteopenia, osteoporosis, or without these conditions (normal group) and 2) to analyze the correlations between Maresin 1 concentrations and bone mineral density (BMD) and bone turnover markers.

Methods: In this cross-sectional study, we measured serum Maresin 1 concentrations, serum biochemical parameters, markers of bone metabolism, and BMD of the femoral neck, lumbar spine, and hip in 141 postmenopausal women.

Results: We found that serum Maresin 1 in the osteopenia (140.09 ± 30.54 pg/ml) and PMOP (124.68 ± 31.35 pg/ml) groups were significantly lower than those in the normal group (167.38 ± 24.85 pg/ml) (P < 0.05 and P < 0.001). Serum Maresin 1 levels were positively correlated with femoral neck, lumbar spine, and hip BMD (P < 0.001). Meanwhile, Maresin 1 concentrations were positively associated with 25-hydroxyvitamin D [25(OH)D] levels (P < 0.001), but negatively correlated with β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX) (P = 0.002), procollagen type I amino-terminal propeptide (PINP) (P = 0.004), tartrate-resistant acid phosphatase 5b (TRAP-5b) (P = 0.005), and osteocalcin (OC) levels (P = 0.001). Multivariate logistic regression analysis showed that a decrease in Maresin 1 concentration was still associated with osteopenia (P = 0.035) or PMOP (P = 0.016). Maresin 1 levels had a maximum area under curve of 0.820 for osteopenia and 0.746 for PMOP (P < 0.001). Our results showed that the serum Maresin 1 levels were reduced in osteopenia and PMOP patients compared with that in normal subjects, and were the lowest in the PMOP subjects. The results suggest that Maresin 1 may serve as a new non-invasive diagnostic biomarker for PMOP.
Dual Burden of Malnutrition Among Adolescents With Hunger Aged 12–15 Years in 41 Countries: Findings From the Global School-Based Student Health Survey
Authors: Liu Huaqing , Zhang Min , Fu Peipei , Chen Yan , Zhou Chengchao
Published: January 2022

Background: Hunger is a pandemic among adolescents, resulting in both underweight and obesity, and posing a substantial health challenge.

Objective: To estimate the dual burden of malnutrition among adolescents with hunger.

Design: Data were from the Global school-based Student Health Survey (GSHS). In total, data from 26,986 adolescents with hunger across 5 regions and 41 countries between 2010 and 2015 were analyzed in this study. Weighted prevalence and mean estimates of underweight, overweight, and obesity were calculated by gender, age, and country. Prevalence and 95% confidence intervals (CI) were calculated for regional and country-level income.

Results: The total prevalence of underweight, overweight and obesity among young adolescents with hunger was 6.2% (95% CI: 4.4–8.0%), 25.1% (95% CI: 20.3–29.9%) and 8.9% (95% CI: 6.5–11.3%), respectively. Southeast Asia had the highest prevalence of underweight (17.2%; 95% CI: 7.3–27.0%). America had the highest regional prevalence of obesity (11.1%; 95% CI: 7.2–15.1%) and overweight (28.9%; 95% CI: 21.9–35.9%). Low income countries had relatively high prevalence of underweight (11.5%; 95% CI: 3.2–19.9%). High income countries had the highest prevalence of obesity (17.4%; 95% CI: 14.9–19.9%) and overweight (38.7%; 95% CI: 32.0–45.4%). The co-existence of underweight and overweight among adolescents with hunger was highest in the Eastern Mediterranean region, and in upper-middle and high-income countries.

Conclusions: There is a dual burden of underweight and obesity among adolescents with hunger aged 12–15 years, which differs between geographical regions. The integration of targeted interventions and policies is required to simultaneously address both underweight and increasing rates of obesity among adolescents with hunger in different regions.
Shifting Paradigms for Suppressing Fibrosis in Kidney Transplants: Supplementing Perfusion Solutions With Anti-fibrotic Drugs
Authors: van Leeuwen L. Leonie , Leuvenink Henri G. D. , Olinga Peter , Ruigrok Mitchel J. R.
Published: January 2022

Great efforts have been made toward addressing the demand for donor kidneys. One of the most promising approaches is to use kidneys from donation after circulatory death donors. These kidneys, however, suffer from more severe ischemia and reperfusion injury than those obtained via donation after brain death and are thus more prone to develop interstitial fibrosis and tubular atrophy. Even though machine perfusion is increasingly used to reduce ischemia and reperfusion injury, there are no effective treatments available to ameliorate interstitial fibrosis and tubular atrophy, forcing patients to resume dialysis, undergo re-transplantation, or suffer from premature death. Safe and effective anti-fibrotic therapies are therefore greatly desired. We propose a new therapeutic approach in which machine perfusion solutions are supplemented with anti-fibrotic compounds. This allows the use of higher concentrations than those used in humans whilst eliminating side effects in other organs. To the authors' knowledge, no one has reviewed whether such an approach could reduce interstitial fibrosis and tubular atrophy; we therefore set out to explore its merit. In this review, we first provide background information on ischemia and reperfusion injury as well as interstitial fibrosis and tubular atrophy, after which we describe currently available approaches for preserving donor kidneys. We then present an evaluation of selected compounds. To identify promising compounds, we analyzed publications describing the effects of anti-fibrotic molecules in precision-cut kidneys slices, which are viable explants that can be cultured ex vivo for up to a few days whilst retaining functional and structural features. LY2109761, galunisertib, imatinib, nintedanib, and butaprost were shown to exert anti-fibrotic effects in slices within a relatively short timeframe (<48 h) and are therefore considered to be excellent candidates for follow-up ex vivo machine perfusion studies.
Edelman Revisited: Concepts, Achievements, and Challenges
Authors: Rohrscheib Mark , Sam Ramin , Raj Dominic S. , Argyropoulos Christos P. , Unruh Mark L. , Lew Susie Q. , Ing Todd S. , Levin Nathan W. , Tzamaloukas Antonios H.
Published: January 2022

The key message from the 1958 Edelman study states that combinations of external gains or losses of sodium, potassium and water leading to an increase of the fraction (total body sodium plus total body potassium) over total body water will raise the serum sodium concentration ([Na]S), while external gains or losses leading to a decrease in this fraction will lower [Na]S. A variety of studies have supported this concept and current quantitative methods for correcting dysnatremias, including formulas calculating the volume of saline needed for a change in [Na]S are based on it. Not accounting for external losses of sodium, potassium and water during treatment and faulty values for body water inserted in the formulas predicting the change in [Na]S affect the accuracy of these formulas. Newly described factors potentially affecting the change in [Na]S during treatment of dysnatremias include the following: (a) exchanges during development or correction of dysnatremias between osmotically inactive sodium stored in tissues and osmotically active sodium in solution in body fluids; (b) chemical binding of part of body water to macromolecules which would decrease the amount of body water available for osmotic exchanges; and (c) genetic influences on the determination of sodium concentration in body fluids. The effects of these newer developments on the methods of treatment of dysnatremias are not well-established and will need extensive studying. Currently, monitoring of serum sodium concentration remains a critical step during treatment of dysnatremias.
Genetic Characterization of mcr-1-Positive Multidrug-Resistant Salmonella enterica Serotype Typhimurium Isolated From Intestinal Infection in Children and Pork Offal in China
Authors: Zhang Haoran , Xiang Ying , Huang Yong , Liang Beibei , Xu Xuebin , Xie Jing , Du Xinying , Yang Chaojie , Liu Hongbo , Liu Hongbo , Wang Hui , Yang Mingjuan , Wang Ligui , Hu Xiaofeng , Jin Lianqun , Li Jinsong , Jiang Yongqiang , Qiu Shaofu , Song Hongbin
Published: January 2022

With the rapid emergence of plasmid-mediated colistin resistance gene mcr-1, the increased resistance of Salmonella has attracted extensive attention. This study reports on 11 multidrug-resistant Salmonella enterica serovar Typhimurium strains harboring mcr-1 in China. They all presented resistance to colistin, and additionally, one that was isolated from a child’s stool sample was also resistant to ceftriaxone and azithromycin. We screened 1454 strains of Salmonella for mcr-1 gene through PCR, and these strains are all preserved in our laboratory. Antimicrobial sensitivity analysis was carried out for the screened mcr-1 positive strains. Genetic polymorphism analysis of S. Typhimurium was performed by using the Pulsed-Field Gel Electrophoresis (PFGE). The plasmids harboring mcr-1 were identified by S1-PFGE and southern blotting. Plasmid conjugation assays were used to analyze the transferability of colistin resistance. The plasmids harboring mcr-1 were characterized by sequencing and bioinformatic analysis. Eleven S. Typhimurium strains harboring mcr-1 with colistin resistance (MICs 4μg/ml) were detected, which were isolated from children and pig offal in China. All of them were multidrug-resistant strains. PFGE results revealed that the strains isolated from different samples or locations have identical genotypes. S1-PFGE and southern blotting experiments showed that three plasmids of different sizes (33, 60, and 250 kb) all carried the mcr-1 gene. The plasmid conjugation assays revealed that Salmonella acquired mcr-1 harboring plasmids by horizontal transfer. Sequencing and plasmid type analysis revealed that these plasmids were types IncX4, IncI2, and IncHI2. Among them, IncX4 and IncI2 plasmids had extremely similar backbones and contained one resistant gene mcr-1. IncHI2 plasmid contained multiple resistant genes including blaCTX–M, oqxB, sul, aph, aadA, and blaTEM. We identified 11 mcr-1 harboring S. Typhimurium strains in China and described their characteristics. Our findings indicate that the mcr-1 gene can effectively spread among intestinal bacteria by horizontal transfer of three types of plasmids. Moreover, the IncHI2 plasmid can also mediate the transfer of other drug resistance genes. These results reveal that constant surveillance of mcr-1 harboring S Typhimurium is imperative to prevent the spread of colistin resistance.
Differences of Enzymatic Activity During Composting and Vermicomposting of Sewage Sludge Mixed With Straw Pellets
Authors: Hanc Ales , Dume Bayu , Hrebeckova Tereza
Published: January 2022

The study aims were focused on profiling eight hydrolytic enzymes by fluorescence method using a multifunctional modular reader and studying the proportion of basic microorganism groups during composting and vermicomposting of sewage sludge mixed with straw pellets in several proportions (0, 25, 50, 75, and 100%). The greatest decrease in enzymatic activity occurred in the first half of composting and vermicomposting. After 4 months of these processes, the least enzymatic activity was observed in the sludge with 50% and also 25% straw addition, indicating that straw is an important means for the rapid production of mature compost from sewage sludge. Enzymatic activity was usually less in the presence of earthworms than in the control treatment because some processes took place in the digestive tract of the earthworm. For the same reason, we observed reduced enzyme activity during fresh feedstock vermicomposting than precomposted material. The final vermicompost from fresh feedstocks exhibited less microbial biomass, and few fungi and G− bacteria compared to precomposted feedstock. The enzymatic activity during composting and vermicomposting of sewage sludge and their mixtures stabilized at the following values: β-D-glucosidase—50 μmol MUFG/h/g dw, acid phosphatase—200 μmol MUFP/h/g dw, arylsulphatase—10 μmol MUFS/h/g dw, lipase—1,000 μmol MUFY/h/g dw, chitinase—50 μmol MUFN/h/g dw, cellobiohydrolase—20 μmol MUFC/h/g dw, alanine aminopeptidase—50 μmol AMCA/h/g dw, and leucine aminopeptidase—50 μmol AMCL/h/g dw. At these and lesser values, these final products can be considered mature and stable.
Development of an Aging-Related Gene Signature for Predicting Prognosis, Immunotherapy, and Chemotherapy Benefits in Rectal Cancer
Authors: Wang Yangyang , Liu Yan , Zhu Chunchao , Zhang Xinyu , Li Guodong
Published: January 2022

Objective: Aging is the major risk factor for human cancers, including rectal cancer. Targeting the aging process provides broad-spectrum protection against cancers. Here, we investigate the clinical implications of aging-related genes in rectal cancer.

Methods: Dysregulated aging-related genes were screened in rectal cancer from TCGA project. A LASSO prognostic model was conducted, and the predictive performance was evaluated and externally verified in the GEO data set. Associations of the model with tumor-infiltrating immune cells, immune and stromal score, HLA and immune checkpoints, and response to chemotherapeutic agents were analyzed across rectal cancer. Biological processes underlying the model were investigated through GSVA and GSEA methods. Doxorubicin (DOX)-induced or replicative senescent stromal cells were constructed, and AGTR1 was silenced in HUVECs. After coculture with conditioned medium of HUVECs, rectal cancer cell growth and invasion were investigated.

Results: An aging-related model was established, consisting of KL, BRCA1, CLU, and AGTR1, which can stratify high- and low-risk patients in terms of overall survival, disease-free survival, and progression-free interval. ROC and Cox regression analyses confirmed that the model was a robust and independent predictor. Furthermore, it was in relation to tumor immunity and stromal activation as well as predicted the responses to gemcitabine and sunitinib. AGTR1 knockdown ameliorated stromal cell senescence and suppressed senescent stromal cell-triggered rectal cancer progression.

Conclusion: Our findings suggest that the aging-related gene signature was in relation to tumor immunity and stromal activation in rectal cancer, which might predict survival outcomes and immuno- and chemotherapy benefits.
Progressive Prefrontal Cortex Dysfunction in Parkinson's Disease With Probable REM Sleep Behavior Disorder: A 3-Year Longitudinal Study
Authors: Jia Xiuqin , Fan Wentao , Wang Zhijiang , Liu Yuehong , Li Ying , Li Haibin , Li Hui , Ma Ting , Wang Jing , Yang Qi
Published: January 2022

This study aimed to explore the disrupted prefrontal cortex activity specific to patients with Parkinson's disease (PD) with rapid eye movement sleep behavior disorder (RBD) compared with those without and to further examine the associations between these alterations and neuropsychological measurements. Ninety-six patients with early PD underwent both structural and functional MRI, and also neuropsychological assessments in the Parkinson's Progression Markers Initiative (PPMI) database. Of these, 46 patients who completed 1- and 3-year fMRI follow-up examinations were categorized as PD with probable RBD (PD-pRBD+) and without (PD-pRBD−). The left dorsolateral prefrontal cortex (DLPFC) seed-to-voxel functional connectivity analysis was conducted to evaluate the progressive neural alterations specific to PD-pRBD+ compared with PD-pRBD− over time. Furthermore, relationships between these alterations and neuropsychological performance were examined. Compared with patients with PD-pRBD−, patients with PD-pRBD+ initially exhibited connectivity deficits between the left DLPFC and the medial frontopolar cortex. Moreover, these patients further exhibited disrupted DLPFC connectivity in the lateral frontopolar cortex at the 3-year follow-up evaluation. Correlation analysis revealed that connectivity between the left DLPFC and frontopolar cortex was positively related to executive function in PD-pRBD+ after adjusting for nuisance variables. Progressive prefrontal cortex dysfunction associated with RBD in early PD may provide an effective subtype-specific biomarker of neurodegenerative progression, which may shed light on the neuropathological mechanisms underlying the clinical heterogeneity of this disease.
Cerebral Microbleeds Were Related With Poor Cognitive Performances on the Dual Task Condition in Older Adults
Authors: Li Xuanting , Yang Shuna , Qin Wei , Yang Lei , Li Yue , Hou Yutong , Huang Qixin , Hu Wenli
Published: January 2022

Background: The dual task (DT) was commonly used to assess the risk of falls in older adults and patients with neurological disorders. However, the performance on DT conditions has not been well investigated in patients with cerebral microbleed (CMB). This study is aimed to compare the performance in DT tests between older adults with and without CMB, and to explore the association between CMB and cognitive performances of DT.

Methods: This is a cross-sectional study. A total of 211 old adults participated, involving 68 CMB patients. The task protocol involved two global cognition tests, two single cognitive tests (serial 7 subtraction and semantic fluency), two single motor tasks [8-m walking and timed up and go test (TUG)], and three DT tests [walking and serial subtraction (WSS), walking and semantic fluency (WSF), and TUG and serial subtraction (TUGSS)]. The time taken to complete each task and the number of correct responses were recorded. For each DT condition, the correct response rate (CRR) and the dual-task effect (DTE) for the correct number were calculated.

Results: Compared with subjects without CMB, CMB patients had worse cognitive performances on DT condition in CRR of WSS (p = 0.003), WSF (p = 0.030) and TUGSS (p = 0.006), and DTE of WSS (p = 0.017). Binary logistic regression analysis showed that the presence of CMB was an independent risk factor for the impairment group for CRR of TUGSS (OR, 2.54; 95% CI, 1.11–5.82; p = 0.027) with the adjustment for confounders, rather than CRR of WSS and WSF, or DTE of WSS. Multiple linear regression analysis showed that CRR of TUGSS decreased with the increase of CMB number grades (β, −0.144; 95% CI, −0.027, −0.002; p = 0.028).

Conclusion: The present study indicated that CMBs were closely associated with poor cognitive performances on DT in the elderly. Strongest effect size was seen for CRR of TUGSS, where performance deficits increased in proportion to the degree of CMB burden.
Improving Walking Economy With an Ankle Exoskeleton Prior to Human-in-the-Loop Optimization
Authors: Wang Wei , Chen Jianyu , Ding Jianquan , Zhang Juanjuan , Liu Jingtai
Published: January 2022

Lower limb robotic exoskeletons have shown the capability to enhance human locomotion for healthy individuals or to assist motion rehabilitation and daily activities for patients. Recent advances in human-in-the-loop optimization that allowed for assistance customization have demonstrated great potential for performance improvement of exoskeletons. In the optimization process, subjects need to experience multiple types of assistance patterns, thus, leading to a long evaluation time. Besides, some patterns may be uncomfortable for the wearers, thereby resulting in unpleasant optimization experiences and inaccurate outcomes. In this study, we investigated the effectiveness of a series of ankle exoskeleton assistance patterns on improving walking economy prior to optimization. We conducted experiments to systematically evaluate the wearers' biomechanical and physiological responses to different assistance patterns on a lightweight cable-driven ankle exoskeleton during walking. We designed nine patterns in the optimization parameters range which varied peak torque magnitude and peak torque timing independently. Results showed that metabolic cost of walking was reduced by 17.1 ± 7.6% under one assistance pattern. Meanwhile, soleus (SOL) muscle activity was reduced by 40.9 ± 19.8% with that pattern. Exoskeleton assistance changed maximum ankle dorsiflexion and plantarflexion angle and reduced biological ankle moment. Assistance pattern with 48% peak torque timing and 0.75 N·m·kg−1 peak torque magnitude was effective in improving walking economy and can be selected as an initial pattern in the optimization procedure. Our results provided a preliminary understanding of how humans respond to different assistances and can be used to guide the initial assistance pattern selection in the optimization.