bluuebunny/crossref_metadata_2025 huggingface dataset:
Lignin phenols as a basis for biopreparations
Authors: Kovalev Ivan V. , Kovaleva Natalia O.
Published: September 2021

The content and composition of lignin phenols in plants and soils of latitudinal zones and vertical natural zones of the North Caucasus and Northwest Tien Shan have been studied. The special role of lignin phenols of underground plant organs in the process of humification was revealed. It was shown that the oxidation degree of the biopolymer increases during the transformation of organic matter from living plant tissues to humic acids in soils. The fraction of lignin fragments that remain unchanged during the biotransformation of the polymer in the row plant tissues – fall – litter – soils – humic acids – buried humic acids is calculated. It has also been demonstrated that the biochemical composition of plants has a decisive effect on the structure of humic acids in soils. With the help of quantitative analysis of lignin phenols and 13C NMR spectroscopy, it is proved that lignin of higher plants is involved in the formation of humic acids, both aliphatic and aromatic parts of molecules. The areas of application of lignin phenols in the practice of agriculture and medicine are proposed.
Post-COVID-19 Pulmonary Fibrosis: Report of Two Cases
Authors: Karmakar Saurabh , Sharma Priya , Harishkumar Ameet , Rai Deependra Kumar
Published: September 2021

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 has led to a pandemic situation worldwide. However, remarkable progress has been made in evolving policies, strengthening healthcare efforts, and pharmacotherapy. As more patients are recovering from COVID-19, clearer concepts about possible short- and long-term complications are emerging. Respiratory failure is the most common morbidity in hospitalised patients, and post-COVID-19 pulmonary fibrosis is the most common respiratory complication after recovery. The authors report two cases of COVID-19 pneumonia with respiratory failure who were cured but developed pulmonary fibrosis with restrictive lung disease in the follow-up period.
A mulher no mercado de trabalho uberizado em tempos de pandemia: breve análise sobre os caminhos da desigualdade de gênero laborativo no Brasil
Authors: Mata Catrine Cadja Indio do Brasil da , Araújo Miquéias Moreira de , Melo João Kleber Ferreira de , Souza Leonilson Alves Araújo de , Silva Antônio Igor Gama da , Cruz Jackson Ramos da , Soares Luana Rodrigues , Guimarães Neuraci Silva , Azevedo Valdênia da Glória Máximo , Santos Luiz Justiniano dos
Published: September 2021

Este estudo visou analisar os problemas decorrentes da uberização do trabalho a partir da cultura digital, focalizado em compreender como as mulheres se situam neste contexto. A partir desta compreensão, visou-se encontrar um paralelo entre a inserção das mulheres no crescente trabalho informal e a crise do trabalho provocada pela pandemia da COVID-19. O artigo se desenvolve a partir de uma construção da análise histórica, utilizando metodologicamente a pesquisa documental e revisão bibliográfica sob a ótica do papel da mulher nos espaços formais/informais de trabalho, ante ao crescimento e tomadas de espaços de trabalho que pertenciam apenas à figura masculina. É nesse contexto que se discute a uberização do trabalho e suas implicações na vida laboral feminina, frente a ausência de direitos e garantias trabalhistas que podem culminar em um maior acirramento da desigualdade de gênero no país.
The Synergistic Effect of Nicotine and Staphylococcus aureus on Peri-Implant Infections
Authors: Hu Yao , Zhou Wen , Zhu Chengguang , Zhou Yujie , Guo Qiang , Huang Xiaoyu , Yang Bina , Ren Biao , Cheng Lei
Published: September 2021

Smoking is considered a key risk factor for implant survival; however, how it interacts with the pathogens in peri-implant infections is not clear. Here, we identified that nicotine, the key component of cigarette smoking, can interact with Staphylococcus aureus and synergistically induce peri-implant infections in a rat osteolysis model. The nicotine–S. aureus combination group increased the gross bone pathology, osteolysis, periosteal reactions, and bone resorption compared to the nicotine or S. aureus single treated group (p < 0.05). Nicotine did not promote the proliferation of S. aureus both in vitro and in vivo, but it can significantly upregulate the expression of staphylococcal protein A (SpA), a key virulence factor of S. aureus. The nicotine–S. aureus combination also synergistically activated the expression of RANKL (receptor activator of nuclear factor-kappa B ligand, p < 0.05) to promote the development of peri-implant infections. The synergistic effects between nicotine and S. aureus infection can be a new target to reduce the peri-implant infections.
Ex Vivo and In Vivo Properties of an Injectable Hydrogel Derived From Acellular Ear Cartilage Extracellular Matrix
Authors: Gong Danni , Yu Fei , Zhou Meng , Dong Wei , Yan Dan , Zhang Siyi , Yan Yan , Wang Huijing , Tan Yao , Chen Ying , Feng Bei , Fu Wei , Fu Yao , Lu Yang
Published: September 2021

Extracellular matrix (ECM) hydrogels provide advantages such as injectability, the ability to fill an irregularly shaped space, and the adequate bioactivity of native matrix. In this study, we developed decellularized cartilage ECM (dcECM) hydrogels from porcine ears innovatively via the main method of enzymatic digestion and verified good biocompatible properties of dcECM hydrogels to deliver chondrocytes and form subcutaneous cartilage in vivo. The scanning electron microscopy and turbidimetric gelation kinetics were used to characterize the material properties and gelation kinetics of the dcECM hydrogels. Then we evaluated the biocompatibility of hydrogels via the culture of chondrocytes in vitro. To further explore the dcECM hydrogels in vivo, grafts made from the mixture of dcECM hydrogels and chondrocytes were injected subcutaneously in nude mice for the gross and histological analysis. The structural and gelation kinetics of the dcECM hydrogels altered according to the variation in the ECM concentrations. The 10 mg/ml dcECM hydrogels could support the adhesion and proliferation of chondrocytes in vitro. In vivo, at 4 weeks after transplantation, cartilage-like tissues were detected in all groups with positive staining of toluidine blue, Safranin O, and collagen II, indicating the good gelation of dcECM hydrogels. While with the increasing concentration, the tissue engineering cartilages formed by 10 mg/ml dcECM hydrogel grafts were superior in weights, volumes, collagen, and glycosaminoglycan (GAG) content compared to the dcECM hydrogels of 1 mg/ml and 5 mg/ml. At 8 weeks after grafting, dcECM hydrogel grafts at 10 mg/ml showed very similar qualities to the control, collagen I grafts. After 12 weeks of in vivo culture, the histological analysis indicated that 10 mg/ml dcECM hydrogel grafts were similar to the normal cartilage from pig ears, which was the source tissue. In conclusion, dcECM hydrogel showed the promising potential as a tissue engineering biomaterial to improve the regeneration and heal injuries of ear cartilage.
Insight in the Recent Application of Polyphenols From Biomass
Authors: Yan Bowen , Chen Zhefan Stephen , Hu Yingying , Yong Qiang
Published: September 2021

Biomass polyphenols are bio-active macromolecules with distinct chemical structures in a variety of biomass. In recent years, the study of biomass polyphenols and their application in food and medicine fields has become a research hotspot, which predominantly focuses on the preparation, purification, structural identifications, and measurements of biological activities. Many studies describe methodologies for extraction and application of polyphenols, but comprehensive work to review its physiological activities like drugs and health products are lacking. This paper comprehensively unlocks the bioactivities of antioxidant, antibacterial, antitumor, anticancer, neuroprotection, control of blood sugar, regulation of blood fat, and promotion of gastrointestinal health functions of polyphenols from different biomass sources. This review will serve as an illuminating resource for the global scientific community, especially for those who are actively working to promote the advances of the polyphenols research field.
Recreating the Bone Marrow Microenvironment to Model Leukemic Stem Cell Quiescence
Authors: O’Reilly Eimear , Zeinabad Hojjat Alizadeh , Nolan Caoimhe , Sefy Jamileh , Williams Thomas , Tarunina Marina , Hernandez Diana , Choo Yen , Szegezdi Eva
Published: September 2021

The main challenge in the treatment of acute myeloid leukemia (AML) is relapse, as it has no good treatment options and 90% of relapsed patients die as a result. It is now well accepted that relapse is due to a persisting subset of AML cells known as leukemia-initiating cells or leukemic stem cells (LSCs). Hematopoietic stem cells (HSCs) reside in the bone marrow microenvironment (BMM), a specialized niche that coordinates HSC self-renewal, proliferation, and differentiation. HSCs are divided into two types: long-term HSCs (LT-HSCs) and short-term HSCs, where LT-HSCs are typically quiescent and act as a reserve of HSCs. Like LT-HSCs, a quiescent population of LSCs also exist. Like LT-HSCs, quiescent LSCs have low metabolic activity and receive pro-survival signals from the BMM, making them resistant to drugs, and upon discontinuation of therapy, they can become activated and re-establish the disease. Several studies have shown that the activation of quiescent LSCs may sensitize them to cytotoxic drugs. However, it is very difficult to experimentally model the quiescence-inducing BMM. Here we report that culturing AML cells with bone marrow stromal cells, transforming growth factor beta-1 and hypoxia in a three-dimensional system can replicate the quiescence-driving BMM. A quiescent-like state of the AML cells was confirmed by reduced cell proliferation, increased percentage of cells in the G0 cell cycle phase and a decrease in absolute cell numbers, expression of markers of quiescence, and reduced metabolic activity. Furthermore, the culture could be established as co-axial microbeads, enabling high-throughput screening, which has been used to identify combination drug treatments that could break BMM-mediated LSC quiescence, enabling the eradication of quiescent LSCs.
Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate
Authors: Tang Wanbo , He Jian , Huang Tao , Bai Zhijie , Wang Chaojie , Wang Haizhen , Yang Ruichuang , Ni Yanli , Hou Jun , Wang Junliang , Zhou Jie , Yao Yingpeng , Gong Yandong , Hou Siyuan , Liu Bing , Lan Yu
Published: September 2021

In the aorta-gonad-mesonephros (AGM) region of mouse embryos, pre-hematopoietic stem cells (pre-HSCs) are generated from rare and specialized hemogenic endothelial cells (HECs) via endothelial-to-hematopoietic transition, followed by maturation into bona fide hematopoietic stem cells (HSCs). As HECs also generate a lot of hematopoietic progenitors not fated to HSCs, powerful tools that are pre-HSC/HSC-specific become urgently critical. Here, using the gene knockin strategy, we firstly developed an Hlf-tdTomato reporter mouse model and detected Hlf-tdTomato expression exclusively in the hematopoietic cells including part of the immunophenotypic CD45– and CD45+ pre-HSCs in the embryonic day (E) 10.5 AGM region. By in vitro co-culture together with long-term transplantation assay stringent for HSC precursor identification, we further revealed that unlike the CD45– counterpart in which both Hlf-tdTomato-positive and negative sub-populations harbored HSC competence, the CD45+ E10.5 pre-HSCs existed exclusively in Hlf-tdTomato-positive cells. The result indicates that the cells should gain the expression of Hlf prior to or together with CD45 to give rise to functional HSCs. Furthermore, we constructed a novel Hlf-CreER mouse model and performed time-restricted genetic lineage tracing by a single dose induction at E9.5. We observed the labeling in E11.5 AGM precursors and their contribution to the immunophenotypic HSCs in fetal liver (FL). Importantly, these Hlf-labeled early cells contributed to and retained the size of the HSC pool in the bone marrow (BM), which continuously differentiated to maintain a balanced and long-term multi-lineage hematopoiesis in the adult. Therefore, we provided another valuable mouse model to specifically trace the fate of emerging HSCs during development.
Nrf2 Is a Potential Modulator for Orchestrating Iron Homeostasis and Redox Balance in Cancer Cells
Authors: Zhang Lingyan , Zhang Jian , Jin Yuanqing , Yao Gang , Zhao Hai , Qiao Penghai , Wu Shuguang
Published: September 2021

Iron is an essential trace mineral element in almost all living cells and organisms. However, cellular iron metabolism pathways are disturbed in most cancer cell types. Cancer cells have a high demand of iron. To maintain rapid growth and proliferation, cancer cells absorb large amounts of iron by altering expression of iron metabolism related proteins. However, iron can catalyze the production of reactive oxygen species (ROS) through Fenton reaction. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is an important player in the resistance to oxidative damage by inducing the transcription of antioxidant genes. Aberrant activation of Nrf2 is observed in most cancer cell types. It has been revealed that the over-activation of Nrf2 promotes cell proliferation, suppresses cell apoptosis, enhances the self-renewal capability of cancer stem cells, and even increases the chemoresistance and radioresistance of cancer cells. Recently, several genes involving cellular iron homeostasis are identified under the control of Nrf2. Since cancer cells require amounts of iron and Nrf2 plays pivotal roles in oxidative defense and iron metabolism, it is highly probable that Nrf2 is a potential modulator orchestrating iron homeostasis and redox balance in cancer cells. In this hypothesis, we summarize the recent findings of the role of iron and Nrf2 in cancer cells and demonstrate how Nrf2 balances the oxidative stress induced by iron through regulating antioxidant enzymes and iron metabolism. This hypothesis provides new insights into the role of Nrf2 in cancer progression. Since ferroptosis is dependent on lipid peroxide and iron accumulation, Nrf2 inhibition may dramatically increase sensitivity to ferroptosis. The combination of Nrf2 inhibitors with ferroptosis inducers may exert greater efficacy on cancer therapy.
Glycocalyx Impairment in Vascular Disease: Focus on Inflammation
Authors: Qu Jing , Cheng Yue , Wu Wenchao , Yuan Lixing , Liu Xiaojing
Published: September 2021

The glycocalyx is a complex polysaccharide-protein layer lining the lumen of vascular endothelial cells. Changes in the structure and function of the glycocalyx promote an inflammatory response in blood vessels and play an important role in the pathogenesis of many vascular diseases (e.g., diabetes, atherosclerosis, and sepsis). Vascular endothelial dysfunction is a hallmark of inflammation-related diseases. Endothelial dysfunction can lead to tissue swelling, chronic inflammation, and thrombosis. Therefore, elimination of endothelial inflammation could be a potential target for the treatment of vascular diseases. This review summarizes the key role of the glycocalyx in the inflammatory process and the possible mechanism by which it alleviates this process by interrupting the cycle of endothelial dysfunction and inflammation. Especially, we highlight the roles of different components of the glycocalyx in modulating the inflammatory process, including components that regulate leukocyte rolling, L-selectin binding, inflammasome activation and the signaling interactions between the glycocalyx components and the vascular cells. We discuss how the glycocalyx interferes with the development of inflammation and the importance of preventing glycocalyx impairment. Finally, drawing on current understanding of the role of the glycocalyx in inflammation, we consider a potential strategy for the treatment of vascular diseases.
Empirical Evaluation of Understandability and Usability of Health Handbooks Commonly Used in Japan
Authors: Nomura Marika , Goto Aya , Osawa Eri , Miura Hiroko
Published: September 2021

Objective: Various types of handbooks that summarize and record health information (health handbooks) have been used in Japan for many years. The purpose of this study was to explore ways to evaluate the understandability and usability of commonly used printed health handbooks in Japan.

Methods: An internet search was performed to identify health handbooks used in Japan. The handbooks were then collected, searched, and evaluated for the quality and functionality of the health-information. The overall understandability was assessed using the Suitability Assessment of Material (SAM) and the Centers for Disease Control and Prevention Clear Communication Index (CCI), and overall usability was assessed using a purpose-user matrix.

Results: A total of 14 health handbooks were extracted and analyzed. The median scores for SAM and CCI were 39 (min 25, max 45) and 81.5% (60%, 100%), respectively, and no significant association was observed between the two evaluation scores. Based on the matrix, the most common type of handbook was those designed for preventive purposes that the user or their family completed (n = 9).

Conclusion: Our sampled health handbooks were used mostly for preventive purposes and their understandability varied. SAM and CCI assess different aspects of written materials and it is recommended they be used together when evaluating the understandability of health handbooks. To facilitate more effective use of health handbooks in public health activities, we suggest the content of handbooks be assessed by a purpose-user matrix.
Triglyceride Glucose Index Associated With Arterial Stiffness in Chinese Community-Dwelling Elderly
Authors: Su Yongkang , Wang Shuxia , Sun Jin , Zhang Yan , Ma Shouyuan , Li Man , Zhang Anhang , Cheng Bokai , Cai Shuang , Bao Qiligeer , Zhu Ping
Published: September 2021

Background: The population of older adults is growing rapidly with the increasing pace of aging worldwide. The triglyceride glucose (TyG) index has been a convenient and reliable surrogate marker of insulin resistance (IR). This study aimed to determine the association between the TyG index and arterial stiffness assessed by brachial-ankle pulse wave velocity (baPWV) in Chinese older adults.

Methods: A total of 2,035 participants aged 60 years or above were enrolled. Demographic, anthropometric, and cardiovascular risk factors were collected. TyG index was calculated using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Arterial stiffness was measured using baPWV.

Results: The participants, with the mean [standard deviation (SD)] age of 71.32 (6.75) years, the female proportion of 39.65%, the mean (SD) baPWV of 1,998 (437) cm/s, and the mean (SD) TyG index of 8.86 (0.54), were divided into four groups according to TyG index quartiles. Age-adjusted baPWV presented an increasing trend according to TyG index quartiles. In the fully adjusted linear regression model, the baPWV increased 49 cm/s, with the 95% confidence interval (CI) from 24 to 75 cm/s, per-SD increase in the TyG index. In the fully-adjusted logistic regression model, the odds ratio (95% CI) of high baPWV (>75th percentile) was 1.32 (1.09, 1.60) for each SD increase in the TyG index. The generalized additive model analysis also confirmed the significant association of the TyG index with baPWV and high baPWV.

Conclusion: The TyG index is significantly associated with arterial stiffness assessed by baPWV in Chinese older adults.
Using GRACE Data to Estimate Climate Change Impacts on the Earth’s Moment of Inertia
Authors: Ren Diandong , Hu Aixue
Published: September 2021

The widely used 15-year Gravity Recovery and Climate Experiment (GRACE) measured mass redistribution shows an increasing trend in the nontidal Earth’s moment of inertia (MOI). Various contributing components are independently evaluated using five high-quality atmospheric reanalysis datasets and a novelty numerical modeling system. We found a steady, statistically robust (passed a two-tailed t-test atp= 0.04 for dof = 15) rate of MOI increase reaching ∼11.0 × 1027kg m2/yr, equivalent to a 11.45 sμ/yr increase in the length of day, during 2002–2017. Further analysis suggests that the Antarctic ice sheet contributes the most, followed by the Greenland ice sheet, the precipitation-driven land hydrological cycle, mountain glaciers, and the fluctuation of atmosphere, in this order. Short-term MOI spikes from the GRACE measurements are mostly associated with major low/mid-latitude earthquakes, fitting closely with the MOI variations from the hydrological cycle. Atmospheric fluctuation contributes the least but has a steady trend of 0.5 sμ/yr, with horizontal mass distribution contributing twice as much as the vertical expansion and associated lift of the atmosphere’s center of mass. The latter is a previously overlooked term affecting MOI fluctuation. The contribution to the observed MOI trend from a warming climate likely will persist in the future, largely due to the continuous mass loss from the Earth’s ice sheets.
Accounting for the SES-Math Achievement Gap at School Entry: Unique Mediation Paths via Executive Functioning and Behavioral Self-Regulation
Authors: Ng Ee Lynn , Bull Rebecca , Khng Kiat Hui
Published: September 2021

Childhood socioeconomic status (SES) is strongly predictive of math achievement in early childhood and beyond. In this study, we aimed to further our understanding of the mechanisms underpinning the SES-achievement gap by examining whether two aspects of self-regulation—executive functions (EF) and behavioral self-regulation (BSR)—mediate between SES and math achievement. Using data from a longitudinal study in Singapore (n = 1,257, 49% males), we examined the predictive link from SES to math achievement at entry to formal education (age 7), and the role of EF (child-assessed) and BSR (child-assessed and teacher-rated) as mediators of the SES-math achievement relationship. After accounting for children’s non-verbal reasoning and prior math achievement, EF and BSR (both child-assessed) emerged as significant partial mediators between SES and math. A key contribution of our study is in demonstrating that both components of self-regulation play a small role in explaining SES disparities in math achievement. Our findings further suggest that a balanced focus on enhancing EF and BSR skills of children from low-SES families may help to attenuate the SES-math achievement gap. More generally, our research contributes new insights to the ongoing debate about the theoretical distinctions between EF and BSR.
Gene Expression Profiling of Tricarboxylic Acid Cycle and One Carbon Metabolism Related Genes for Prognostic Risk Signature of Colon Carcinoma
Authors: Zhang Zheying , Zhu Huifang , Li Qian , Gao Wuji , Zang Dan , Su Wei , Yang Rui , Zhong Jiateng
Published: September 2021

Colorectal cancer (CRC) is one of the most prevalent malignant tumors worldwide. Colon adenocarcinoma (COAD) is the most common pathological type of CRC and several biomarkers related to survival have been confirmed. Yet, the predictive effect of a single gene biomarker is not enough. The tricarboxylic acid (TCA) cycle and carbon metabolism play an important role in tumors. Thus, we aimed to identify new gene signatures from the TCA cycle and carbon metabolism to better predict the survival of COAD. This study performed mRNA expression profiling in large COAD cohorts (n = 417) from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression and multivariate Cox regression analysis were performed, and receiver operating characteristic (ROC) curve was used to screen the variable combinations model which is most relevant to patient prognosis survival mostly. Univariable or multivariate analysis results showed that SUCLG2, SUCLG1, ACLY, SUCLG2P2, ATIC and ACO2 have associations with survival in COAD. Combined with clinical variables, we confirmed model 1 (AUC = 0.82505), most relevant to patient prognosis survival. Model 1 contains three genes: SUCLG2P2, SUCLG2 and ATIC, in which SUCLG2P2 and SUCLG2 were low-expressed in COAD, however, ATIC was highly expressed, and the expressions above are related to stages of CRC. Pearson analysis showed that SUCLG2P2, SUCLG2 and ATIC were correlated in normal COAD tissues, while only SUCLG2P2 and SUCLG2 were correlated in tumor tissues. Finally, we verified the expressions of these three genes in COAD samples. Our study revealed a possible connection between the TCA cycle and carbon metabolism and prognosis and showed a TCA cycle and carbon metabolism related gene signature which could better predict survival in COAD patients.
Prognostic Role of ceRNA Network in Immune Infiltration of Hepatocellular Carcinoma
Authors: Xu Qianhui , Chen Shaohuai , Hu Yuanbo , Huang Wen
Published: September 2021

Background: Increasing evidence supports that competing endogenous RNAs (ceRNAs) and tumor immune infiltration act as pivotal players in tumor progression of hepatocellular carcinoma (HCC). Nonetheless, comprehensive analysis focusing on ceRNAs and immune infiltration in HCC is lacking.

Methods: RNA and miRNA sequencing information, corresponding clinical annotation, and mutation data of HCC downloaded from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) project were employed to identify significant differentially expressed mRNAs (DEMs), miRNAs (DEMis), and lncRNAs (DELs) to establish a ceRNA regulatory network. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO) enrichment pathways were analyzed to functionally annotate these DEMs. A multigene-based risk signature was developed utilizing least absolute shrinkage and selection operator method (LASSO) algorithm. Moreover, survival analysis and receiver operating characteristic (ROC) analysis were applied for prognostic value validation. Seven algorithms (TIMER, XCELL, MCPcounter, QUANTISEQ, CIBERSORT, EPIC, and CIBERSORT-ABS) were utilized to characterize tumor immune microenvironment (TIME). Finally, the mutation data were analyzed by employing “maftools” package.

Results: In total, 136 DELs, 128 DEMis, and 2,028 DEMs were recognized in HCC. A specific lncRNA–miRNA–mRNA network consisting of 3 lncRNAs, 12 miRNAs, and 21 mRNAs was established. A ceRNA-based prognostic signature was established to classify samples into two risk subgroups, which presented excellent prognostic performance. In additional, prognostic risk-clinical nomogram was delineated to assess risk of individual sample quantitatively. Besides, risk score was significantly associated with contexture of TIME and immunotherapeutic targets. Finally, potential interaction between risk score with tumor mutation burden (TMB) was revealed.

Conclusion: In this work, comprehensive analyses of ceRNAs coexpression network will facilitate prognostic prediction, delineate complexity of TIME, and contribute insight into precision therapy for HCC.
Effects of Combinatorial Ubiquitinated Protein-Based Nanovaccine and STING Agonist in Mice With Drug-Resistant and Metastatic Breast Cancer
Authors: Huang Fang , Pan Ning , Wei Yiting , Zhao Jinjin , Aldarouish Mohanad , Wang Xuru , Sun Xiaotong , Wen Zhifa , Chen Yongqiang , Wang Lixin
Published: September 2021

We previously reported that enriched ubiquitinated proteins (UPs) from tumor cells have the potential to be used as immunotherapy vaccine against cancer. Here we enriched UPs from epirubicin (EPB)-induced multi-drug-resistant cancer stem-like breast cancer cell line (4T1/EPB) and tested the efficacy of α-Al2O3-UPs-4T1/EPB (short for UPs-4T1/EPB) as therapeutic vaccine alone and in combination with the stimulator of interferon genes (STING) agonist in mice with drug-resistant and metastatic breast cancer. Vaccination with UPs-4T1/EPB exerted profound anti-tumor effects through augmented specific CD8+ T cell responses and amplified T cell receptor diversity of tumor-infiltrating lymphocytes (TILs). Importantly, the combination with STING agonist further facilitated the migration of mature CD8α+ dendritic cells to the lymph nodes and the infiltration of TILs within tumors, resulting in primary tumor regression and pulmonary metastasis eradication in mice. Moreover, the cured mice were completely resistant against a subsequent rechallenge with the same tumor. Our study indicates that this novel combinatorial immunotherapy with UPs-4T1/EPB vaccine and STING agonist is effective in mice with drug-resistant and metastatic breast cancer.
Variable Effects on Benthic Community From Diking to Eradicate Invasive Plants in the Yangtze Estuary Salt Marsh
Authors: Wang Sikai , Sheng Qiang , Zhao Feng , Zhang Tingting , Zhuang Ping
Published: September 2021

The removal of invasive plants is a global concern, and ecological restoration methods have been a major research topic in recent years. In the estuarine salt marsh of the Yangtze River, dikes are typically used in ecological restoration projects to eradicate the invasive plantSpartina alterniflora. We explored ways of optimizing dike construction and of providing an effective basis for the wetland ecological control and protection of biodiversity and analyzed the effects on the macrobenthos of fully and partially dikes. The measurement of the quantitative change in macrobenthos diversity and species composition was carried out in the project area and in a control before (2013) and after (2016) dike construction. Results showed that the number of species and average density decreased significantly in the fully diked enclosed area but increased in the partially diked semi-enclosed area. Outside the project area, all site samples showed increased species richness and average density after dike construction. This study indicated that macrobenthos was negatively affected by the dike project in the inside diked area. However, when the tidewater canals were preserved to maintain the connection between the inside and outside areas, there was a positive effect on macrobenthos in the project area. We suggest that canals are preserved while diking in the salt marsh and that gates are opened regularly to maintain the water and nutrient connectedness inside and outside the dike. The diking project mostly affected mollusks and polychaetes, which are the indispensable food sources for birds and fish. The study provides valid evidence for the management of estuarine salt marsh and the protection of macrobenthos.
Antimicrobial Activities of Alginate and Chitosan Oligosaccharides Against Staphylococcus aureus and Group B Streptococcus
Authors: Asadpoor Mostafa , Ithakisiou Georgia-Nefeli , van Putten Jos P. M. , Pieters Roland J. , Folkerts Gert , Braber Saskia
Published: September 2021

The bacterial pathogensStreptococcus agalactiae(GBS) andStaphylococcus aureus(S. aureus) cause serious infections in humans and animals. The emergence of antibiotic-resistant isolates and bacterial biofilm formation entails the urge of novel treatment strategies. Recently, there is a profound scientific interest in the capabilities of non-digestible oligosaccharides as antimicrobial and anti-biofilm agents as well as adjuvants in antibiotic combination therapies. In this study, we investigated the potential of alginate oligosaccharides (AOS) and chitosan oligosaccharides (COS) as alternative for, or in combination with antibiotic treatment. AOS (2–16%) significantly decreased GBS V growth by determining the minimum inhibitory concentration. Both AOS (8 and 16%) and COS (2–16%) were able to prevent biofilm formation byS. aureuswood 46. A checkerboard biofilm formation assay demonstrated a synergistic effect of COS and clindamycin on theS. aureusbiofilm formation, while AOS (2 and 4%) were found to sensitize GBS V to trimethoprim. In conclusion, AOS and COS affect the growth of GBS V andS. aureuswood 46 and can function as anti-biofilm agents. The promising effects of AOS and COS in combination with different antibiotics may offer new opportunities to combat antimicrobial resistance.
Selenium Nanoparticles as an Innovative Selenium Fertilizer Exert Less Disturbance to Soil Microorganisms
Authors: Liu Jun , Qi Wen-Yu , Chen Hui , Song Chao , Li Qiang , Wang Shu-Guang
Published: September 2021

Selenium (Se) is an essential trace element in the human body. Se-enriched agricultural products, obtained by applying Se fertilizer, are important sources of Se supplement. However, Se fertilizer may cause a series of environmental problems. This study investigated the transformation of exogenous selenium nanoparticles (SeNPs) and selenite (SeO32–) in soil and explored their effects on soil microbial community and typical microorganisms. SeNPs exhibited a slow-release effect in soil, which promoted the growth of soil microorganisms and enriched soil probiotics. SeO32– was converted to a stable and low toxic state in soil, increasing persistent free radicals and decreasing microbial abundance and diversity. The influences of SeNPs and SeO32– on two typical soil microorganisms (Bacillus sp. and Escherichia coli) were also evaluated, and SeNPs were more difficult to enter into microorganisms directly, with lower toxicity and higher safety. These results indicated that SeNPs were a more environment-friendly Se additive for agriculture applications. This work provides useful information for better understanding the environmental fate and behavior of Se fertilizer in the soil.
Organization of the Catecholaminergic System in the Short-Lived Fish Nothobranchius furzeri
Authors: Borgonovo Janina , Ahumada-Galleguillos Patricio , Oñate-Ponce Alejandro , Allende-Castro Camilo , Henny Pablo , Concha Miguel L.
Published: September 2021

The catecholaminergic system has received much attention based on its regulatory role in a wide range of brain functions and its relevance in aging and neurodegenerative diseases. In the present study, we analyzed the neuroanatomical distribution of catecholaminergic neurons based on tyrosine hydroxylase (TH) immunoreactivity in the brain of adult Nothobranchius furzeri. In the telencephalon, numerous TH+ neurons were observed in the olfactory bulbs and the ventral telencephalic area, arranged as strips extending through the rostrocaudal axis. We found the largest TH+ groups in the diencephalon at the preoptic region level, the ventral thalamus, the pretectal region, the posterior tuberculum, and the caudal hypothalamus. In the dorsal mesencephalic tegmentum, we identified a particular catecholaminergic group. The rostral rhombencephalon housed TH+ cells in the locus coeruleus and the medulla oblongata, distributing in a region dorsal to the inferior reticular formation, the vagal lobe, and the area postrema. Finally, scattered TH+ neurons were present in the ventral spinal cord and the retina. From a comparative perspective, the overall organization of catecholaminergic neurons is consistent with the general pattern reported for other teleosts. However, N. furzeri shows some particular features, including the presence of catecholaminergic cells in the midbrain. This work provides a detailed neuroanatomical map of the catecholaminergic system of N. furzeri, a powerful aging model, also contributing to the phylogenetic understanding of one of the most ancient neurochemical systems.
Role of Exosomes in Brain Diseases
Authors: Zhang Nan , He Fengling , Li Ting , Chen Jinzhi , Jiang Liping , Ouyang Xin-Ping , Zuo Lielian
Published: September 2021

Exosomes are a subset of extracellular vesicles that act as messengers to facilitate communication between cells. Non-coding RNAs, proteins, lipids, and microRNAs are delivered by the exosomes to target molecules (such as proteins, mRNAs, or DNA) of host cells, thereby playing a key role in the maintenance of normal brain function. However, exosomes are also involved in the occurrence, prognosis, and clinical treatment of brain diseases, such as Alzheimer's disease, Parkinson's disease, stroke, and traumatic brain injury. In this review, we have summarized novel findings that elucidate the role of exosomes in the occurrence, prognosis, and treatment of brain diseases.
Can Tirofiban Improve the Outcome of Patients With Acute Ischemic Stroke: A Propensity Score Matching Analysis
Authors: Cai Lingxin , Yu Xiaobo , Yu Jun , Xu Jing , Xu Liang , Ling Chenhan , Lou Min , Yu Cheng , Qian Cong
Published: September 2021

Objective: To evaluate the efficacy and safety of tirofiban for patients with acute ischemic stroke (AIS), especially posterior circulation stroke (PCS).

Methods: We enrolled consecutive patients with AIS who suffered large artery occlusion (LAO) and underwent mechanical thrombectomy (MT) between January 2016 and May 2020. Patients were divided into two groups according to whether tirofiban was used during MT. The primary efficacy outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0–2 at 3 months. The safety outcomes were the rate of mortality at 3 months and the presence of intracranial hemorrhage (ICH) and symptomatic intracranial hemorrhage (sICH). Cohorts were balanced using 1:1 propensity score matching (PSM). Subgroup analysis was further performed to compare the efficacy and safety of tirofiban between the anterior circulation stroke (ACS) and PCS groups.

Results: A total of 292 patients were eligible for this study and divided into the tirofiban group (n = 51) and the no-tirofiban group (n = 241). In the propensity-score-matched cohort, the tirofiban group had a higher rate of favorable outcomes than the no-tirofiban group (49.0 vs. 25.5%, p = 0.014), and the mortality at 3 months showed a greater downward trend in the tirofiban group than the no-tirofiban group (15.6 vs. 33.3% p = 0.064). The risk of sICH and ICH was the same between the tirofiban and control groups (17.6 vs. 27.4% p = 0.236, 31.3 vs. 45.1% p = 0.154, respectively). Tirofiban use was predictive of favorable outcomes [adjusted odds ratio (aOR) = 2.87, 95% confidence interval (CI) 1.52–6.44, p = 0.043] after multiple logistic regression analysis. Subgroup analysis revealed that tirofiban use was significantly associated with favorable outcomes in ACS (aOR = 3.66, 95% CI 1.24–5.22, p = 0.019) but not in PCS (aOR = 1.12, 95% CI 0.47–7.52, p = 0.570).

Conclusion: We demonstrated that tirofiban may be associated with improving favorable outcome for the AIS patients who underwent MT, without increasing ICH or sICH. Furthermore, our results indicated that for PCS patients tirofiban may not be associated with favorable outcome, and more comprehensive randomized controlled trials are needed to confirm this finding.
Skeletal Muscle Mitochondrial Physiology in Children With Cerebral Palsy: Considerations for Healthy Aging
Authors: Dayanidhi Sudarshan
Published: September 2021

Skeletal muscle contractile proteins require a constant supply of energy to produce force needed for movement. Energy (ATP) is primarily produced by mitochondrial organelles, located within and around muscle fibers, by oxidative phosphorylation that couples electron flux through the electron transport chain to create a proton gradient across the inner mitochondrial membrane that is in turn used by the ATP synthase. Mitochondrial networks increase in size by biogenesis to increase mitochondrial abundance and activity in response to endurance exercise, while their function and content reduce with constant inactivity, such as during muscle atrophy. During healthy aging, there is an overall decline in mitochondrial activity and abundance, increase in mitochondrial DNA mutations, potential increase in oxidative stress, and reduction in overall muscular capacity. Many of these alterations can be attenuated by consistent endurance exercise. Children with cerebral palsy (CP) have significantly increased energetics of movement, reduced endurance capacity, and increased perceived effort. Recent work in leg muscles in ambulatory children with CP show a marked reduction in mitochondrial function. Arm muscles show that mitochondrial protein content and mitochondria DNA copy number are lower, suggesting a reduction in mitochondrial abundance, along with a reduction in markers for mitochondrial biogenesis. Gene expression networks are reduced for glycolytic and mitochondrial pathways and share similarities with gene networks with aging and chronic inactivity. Given the importance of mitochondria for energy production and changes with aging, future work needs to assess changes in mitochondria across the lifespan in people with CP and the effect of exercise on promoting metabolic health.
Serum Irisin as a Potential Biomarker for Cognitive Decline in Vascular Dementia
Authors: Zhang Feng , Hou Guangshun , Hou Guangjian , Wang Congan , Shi Bin , Zheng Yuekun
Published: September 2021

Background: Irisin, a new exercise-related myokine, has been shown to be associated with a variety of diseases including serious neurological disorders. However, whether irisin is involved in the pathogenesis of vascular dementia (VD) has not yet been reported. Our aim is to determine the serum irisin level in patients with VD and investigate its relationship with cognitive function.

Methods: The subjects of the study were VD patients and controls with normal cognitive function who were hospitalized in the Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University from July 2018 to June 2020. Upon admission, a cognitive function assessment was performed. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of irisin in serum.

Results: During the study period, 187 subjects (82 controls and 105 VD patients) were included in the analysis. The serum irisin level of VD patients was significantly lower than that of the control group (p < 0.001). Spearman analysis showed that irisin was positively correlated with HLD-C and MoCA, and negatively correlated with all clinical characteristics except for HCY. Logistic regression analysis showed that after adjusting for all clinical characteristics, the serum irisin of VD patients still had a significant correlation with MoCA (β = 0.304, p = 0.029). According to receiver operating characteristic (ROC) curve analysis, the diagnostic accuracy for serum irisin levels on VD was 76% with the sensitivity and 71% with specificity respectively.

Conclusions: These data indicate that a decrease in serum irisin levels is a powerful biological marker for cognitive decline in patients with VD, even after adjustment for risk factors. Further multi-center studies need to confirm this connection, which may pave the way for new treatment options.
Behavioral and Neural Dynamics of Interpersonal Synchrony Between Performing Musicians: A Wireless EEG Hyperscanning Study
Authors: Zamm Anna , Palmer Caroline , Bauer Anna-Katharina R. , Bleichner Martin G. , Demos Alexander P. , Debener Stefan
Published: September 2021

Interpersonal synchrony refers to the temporal coordination of actions between individuals and is a common feature of social behaviors, from team sport to ensemble music performance. Interpersonal synchrony of many rhythmic (periodic) behaviors displays dynamics of coupled biological oscillators. The current study addresses oscillatory dynamics on the levels of brain and behavior between music duet partners performing at spontaneous (uncued) rates. Wireless EEG was measured from N = 20 pairs of pianists as they performed a melody first in Solo performance (at their spontaneous rate of performance), and then in Duet performances at each partner’s spontaneous rate. Influences of partners’ spontaneous rates on interpersonal synchrony were assessed by correlating differences in partners’ spontaneous rates of Solo performance with Duet tone onset asynchronies. Coupling between partners’ neural oscillations was assessed by correlating amplitude envelope fluctuations of cortical oscillations at the Duet performance frequency between observed partners and between surrogate (re-paired) partners, who performed the same melody but at different times. Duet synchronization was influenced by partners’ spontaneous rates in Solo performance. The size and direction of the difference in partners’ spontaneous rates were mirrored in the size and direction of the Duet asynchronies. Moreover, observed Duet partners showed greater inter-brain correlations of oscillatory amplitude fluctuations than did surrogate partners, suggesting that performing in synchrony with a musical partner is reflected in coupled cortical dynamics at the performance frequency. The current study provides evidence that dynamics of oscillator coupling are reflected in both behavioral and neural measures of temporal coordination during musical joint action.
Fixel-Based Analysis Effectively Identifies White Matter Tract Degeneration in Huntington’s Disease
Authors: Oh Sher Li , Chen Chiung-Mei , Wu Yih-Ru , Valdes Hernandez Maria , Tsai Chih-Chien , Cheng Jur-Shan , Chen Yao-Liang , Wu Yi-Ming , Lin Yu-Chun , Wang Jiun-Jie
Published: September 2021

Microstructure damage in white matter might be linked to regional and global atrophy in Huntington’s Disease (HD). We hypothesize that degeneration of subcortical regions, including the basal ganglia, is associated with damage of white matter tracts linking these affected regions. We aim to use fixel-based analysis to identify microstructural changes in the white matter tracts. To further assess the associated gray matter damage, diffusion tensor-derived indices were measured from regions of interest located in the basal ganglia. Diffusion weighted images were acquired from 12 patients with HD and 12 healthy unrelated controls using a 3 Tesla scanner. Reductions in fixel-derived metrics occurs in major white matter tracts, noticeably in corpus callosum, internal capsule, and the corticospinal tract, which were closely co-localized with the regions of increased diffusivity in basal ganglia. These changes in diffusion can be attributed to potential axonal degeneration. Fixel-based analysis is effective in studying white matter tractography and fiber changes in HD.