bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychosocial Aspects of Adaptation of International Students in Pakistan
Authors: Zahra Ali Syeda , Mubashar Tahira , Khan Soulat , Akhtar Tanvir
Published: April 2021

This study examined the psychosocial aspects (acculturation stress, ethnic discrimination, nostalgia, and sentimentality) of socio cultural and psychological adaptation of international students in Pakistan. Sample of 143 international students was taken from different government and private universities of Pakistan. Measures of Acculturative Stress Scale for International Students (Sandhu & Asarbadi, 1994), Brief Perceived Ethnic Discrimination Questionnaire-Community Version (Brondolo et al., 2005), Index of Nostalgia Proneness (Holak, Havlena, & Matveev, 2006), Emotionality Subscale of the HEXACO Personality Inventory (Lee & Ashton, 2009), Brief Psychological Adaptation Scale (Demes & Geeraert, 2014), and Brief Socio-Cultural Adaptation Scale (Demes & Geeraert, 2014) were used. Results showed that ethnic discrimination, acculturation stress, nostalgia, and sentimentality were negatively correlated with psychological and socio-cultural adaptation. Sentimentality moderated the relationship of ethnic discrimination with socio-cultural and psychological adaptation. Moreover, sentimentality also moderated the relationship between nostalgia and psychological adaptation.
Study on the Design and Optimization of a Portable Monitoring and Auxiliary Treatment Device for Upper Extremity Lymphedema–Focus on the Rehabilitation Function of the Device
Authors: Yanmin Xue , Xuyang Zhang , Wen Yan , Suihuai Yu , Sinan Li
Published: April 2021

Female patients suffer from the risk of upper limb lymphedema after breast cancer removal surgery. At present, the detection and the adjuvant treatment of this disease are not convenient enough, leading to delay of the disease and increase in the burden of patients. This paper presents a portable monitoring and treatment device for upper extremity lymphedema, enabling patients to monitor the symptoms of upper limb lymphedema and auxiliary rehabilitation. This design utilizes the arm circumference measurement and contrast method to realize symptom monitoring. The device realizes auxiliary rehabilitation using the regional pressure method to imitate traditional manual lymphatic drainage technology. According to the MRI images of volunteers’ upper limbs, the upper arm and forearm’s finite element models are reconstructed in ANSYS. The static simulation experiment is completed. The working mode and parameter design of each rehabilitation module of the device are obtained. The experimental results show that the integrated design principle of monitoring and treatment proposed in this paper has good feasibility, has auxiliary rehabilitation effect, and meets the principle of human comfort. The device can help patients find lymphedema in time and implement auxiliary treatment, which can effectively avoid the further deterioration of lymphedema.
Human Pluripotent Stem Cell-Derived Cardiac Cells: Application in Disease Modeling, Cell Therapy, and Drug Discovery
Authors: Huang Juan , Feng Qi , Wang Li , Zhou Bingying
Published: April 2021

Cardiac diseases are the leading cause of deaths worldwide; however, to date, there has been limited progress in the development of therapeutic options for these conditions. Animal models have been the most extensively studied methods to recapitulate a wide variety of cardiac diseases, but these models exhibit species-specific differences in physiology, metabolism and genetics, which lead to inaccurate and unpredictable drug safety and efficacy results, resulting in drug attrition. The development of human pluripotent stem cell (hPSC) technology in theory guarantees an unlimited source of human cardiac cells. These hPSC-derived cells are not only well suited for traditional two-dimensional (2-D) monoculture, but also applicable to more complex systems, such as three-dimensional (3-D) organoids, tissue engineering and heart on-a-chip. In this review, we discuss the application of hPSCs in heart disease modeling, cell therapy, and next-generation drug discovery. While the hPSC-related technologies still require optimization, their advances hold promise for revolutionizing cell-based therapies and drug discovery.
Physicochemical Characterization of Ethoxylation Products of Fatty Acid Esters
Authors: Lukosek Marek , Emmons-Burzyńska Magdalena , Alejski Krzysztof , Szwach Iwona
Published: April 2021

The processes of direct ethoxylation of methyl and ethyl esters of unsaturated fatty acids have been described. Two different types of catalysts were employed in those tests: calcium-based catalyst and aluminum-magnesium-based catalyst. Compositions of the synthesized oxyethylates were analyzed with the use of the GC/FID, GC/MS, GPC, and HPLC, HPLC/MS, MALDI methods. Comparative evaluation of the obtained products for both types of catalysts was run in terms of reaction by-products. Biodegradation tests of the oxyethylated products were carried out according to OECD guidelines and physical and chemical properties of oxyethylates were specified which affects the directions of their applications.
circ_0003204 Regulates Cell Growth, Oxidative Stress, and Inflammation in ox-LDL-Induced Vascular Endothelial Cells via Regulating miR-942-5p/HDAC9 Axis
Authors: Wan Huan , You Ting , Luo Wei
Published: April 2021

Background: Atherosclerosis (AS) is a typical inflammatory vascular disease. Many reports corroborated that circular RNAs (circRNAs) is involved in AS progression. However, the potential function and possible mechanism of circ_0003204 in AS progression remain indistinct.

Methods: Expression level analysis was performed using qRT-PCR and western blot. Cell viability and apoptosis were determined using Cell Counting Kit-8 (CCK-8), flow cytometry, and western blot assays. The status of oxidative stress and inflammation was determined via commercial detection kits and ELISA assay, respectively. The binding relationship was verified via dual-luciferase reporter and RNA immunoprecipitation assays.

Results: ox-LDL increased circ_0003204 and HDAC9 levels and decreased miR-942-5p level. Silencing of circ_0003204 enhanced cell viability and inhibited cell apoptosis, oxidative stress and inflammation in ox-LDL-disposed HUVECs. In addition, circ_0003204 targeted miR-942-5p to regulate ox-LDL-resulted HUVECs injury. Also, miR-942-5p affected ox-LDL-triggered HUVECs injury by targeting HDAC9. Furthermore, circ_0003204 elevated HDAC9 expression via decoying miR-942-5p.

Conclusion: circ_0003204 aggravated ox-LDL-induced HUVECs damage via modulating miR-942-5p/HDAC9 pathway.
Microzoning Tsunami Hazard by Combining Flow Depths and Arrival Times
Authors: Zamora Natalia , Catalán Patricio A. , Gubler Alejandra , Carvajal Matías
Published: April 2021

Tsunami hazard is typically assessed from inundation flow depths estimated from one or many earthquake scenarios. However, information about the exact time when such inundation occurs is seldom considered, yet it is crucial for pedestrian evacuation planning. Here, we propose an approach to estimating tsunami hazard by combining tsunami flow depths and arrival times to produce a nine-level, qualitative hazard scale that is translated into a simple tsunami hazard map. To do this, one of the most populated regions of the coast of Chile is considered as the sample site, using a large set of 2,800 tsunamigenic sources from earthquakes with magnitudes in the rangeMw8.6−9.2, modeled from generation to inundation at high resolution. Main outcomes show great dependency of the hazard categorization on the tsunami time arrival, and less to the flow depths. Also, these results demonstrate that incorporating different sources of variability such as different earthquake magnitudes and locations as well as stochastic slip distributions is essential. Moreover, this proof-of-concept exercise clearly shows that the qualitative hybrid categorization of the tsunami hazard allows for its more effective understanding, which can be beneficial for designing mitigation strategies such as evacuation planning, and its management.
Structural Style and Kinematic History of the Colombian Eastern Cordillera
Authors: Costantino Diego , Paton Douglas , Mora Andrés
Published: April 2021

Fold-and-thrust belts and their associated structures are among the most common geological features of convergent margins. They provide significant information about crustal shortening and mountain-building processes. In subaerial belts, where the erosional rates are high and the growth strata are mostly eroded, methodologies such as that presented here can provide insights into to their formation. Two 2D cross-sections located in the Eastern Cordillera of Colombia are presented in this research. These sections extend from the Bogota Savanna to The Llanos, parallel to the regional deformation direction. Section construction was carried out using commercial surface data, and seismic information provided by Ecopetrol. Published thermochronometric data, gravel-clast petrography analysis, and paleoflora analysis were used to construct a viable tectono-evolutionary history of the study area. This evolutionary model is presented here in two palinpastic restorations from the Early Paleogene to Recent (∼65 Ma to Present-day). Section 1 and Section 10 accumulated 17.3 km and 19.5 km of shortening, respectively. The section reconstruction displays two major tectonic events – post-rift subsidence during the Early-Mid Paleogene, and positive inversion from the Oligocene to Recent (∼33 Ma to Present-day). This investigation focuses on the compressional period, where the structural analysis evidences an acceleration in the shortening rate, as well as a progressive migration of the deformation from northwest to southeast. This research discusses the extent and limitation of this methodology, as well as the principal structural aspects of the reconstruction.
Modeling the Ecological Responses of Tree Species to the Flood Pulse of the Amazon Negro River Floodplains
Authors: Householder John Ethan , Schöngart Jochen , Piedade Maria T. F. , Junk Wolfgang J. , ter Steege Hans , Montero Juan Carlos , de Assis Rafael L. , de Aguiar Daniel Praia Portela , Pombo Maihyra Marina , Quaresma Adriano Costa , Demarchi Layon O. , Parolin Pia , Lopes Aline , Feitoza Gildo Vieira , Durgante Flávia Machado , Albuquerque Bianca Weiss , Chu Antonia , Enßlin Daniel , Fabian Tobias , Fettweiß Kirke , Hirsch Moritz , Hombach Myriam , Hubbuch Alisa , Hutter Benedikt , Jäger Timo , Kober-Moritz Ronja , Lindner Meike K. R. , Maier Felix , Nowak Julia , Petridis Zoe , Schierling Larissa , Snjaric Erika , Egger Gregory , Schneider Erika , Damm Christian , Wittmann Florian
Published: April 2021

The large flood pulse of the Amazon basin is a principal driver of environmental heterogeneity with important implications for ecosystem function and the assembly of natural communities. Understanding species ecological response to the flood pulse is thus a key question with implications for theories of species coexistence, resource management, and conservation. Yet these remain largely undescribed for most species, and in particular for trees. The large flood pulse and high tree diversity of the Negro River floodplain makes it an ideal system to begin filling this knowledge gap. We merged historical hydrologic data with 41 forest inventories under variable flooding conditions distributed across the Negro River basin, comprising a total area of 34 ha, to (i) assess the importance of flood duration as a driver of compositional variation, (ii) model the response curve shapes of 111 of the most frequent tree species in function of flood duration, and (iii) derive their niche properties (optima and tolerance). We found that flood duration is a strong driver of compositional turnover, although the majority site-to-site variation in forest composition still remains unexplained. About 73% of species responded to the flood duration gradient, exhibiting a diversity of shapes, but most frequently skewed. About 29% of species were clearly favored by flood durations >120 days year–1, and 44% of species favored by shorter floods. The median niche breadth was 85 flood days year–1, corresponding to approximately 30% of the flood duration gradient. A significant subset of species (27%) did not respond to flooding, but rather exhibited wide tolerance to the flood gradient. The response models provided here offer valuable information regarding tree species differential capacity to grow, survive, and regenerate along an ecologically important gradient and are spatially valid for the Amazon Negro basin. These attributes make them an appealing tool with wide applicability for field and experimental studies in the region, as well as for vegetation monitoring and simulation models of floodplain forest change in the face of hydrologic alteration.
Interpretable Feature Generation in ECG Using a Variational Autoencoder
Authors: Kuznetsov V. V. , Moskalenko V. A. , Gribanov D. V. , Zolotykh Nikolai Yu.
Published: April 2021

We propose a method for generating an electrocardiogram (ECG) signal for one cardiac cycle using a variational autoencoder. Our goal was to encode the original ECG signal using as few features as possible. Using this method we extracted a vector of new 25 features, which in many cases can be interpreted. The generated ECG has quite natural appearance. The low value of the Maximum Mean Discrepancy metric, 3.83 × 10−3, indicates good quality of ECG generation too. The extracted new features will help to improve the quality of automatic diagnostics of cardiovascular diseases. Generating new synthetic ECGs will allow us to solve the issue of the lack of labeled ECG for using them in supervised learning.
Hepcidin Upregulation in Lung Cancer: A Potential Therapeutic Target Associated With Immune Infiltration
Authors: Fan Yumei , Liu Bing , Chen Fei , Song Zhiyuan , Han Bihui , Meng Yanxiu , Hou Jiajie , Cao Pengxiu , Chang Yanzhong , Tan Ke
Published: April 2021

Lung cancer has the highest death rate among cancers globally. Hepcidin is a fascinating regulator of iron metabolism; however, the prognostic value of hepcidin and its correlation with immune cell infiltration in lung cancer remain unclear. Here, we comprehensively clarified the prognostic value and potential function of hepcidin in lung cancer. Hepcidin expression was significantly increased in lung cancer. High hepcidin expression was associated with sex, age, metastasis, and pathological stage and significantly predicted an unfavorable prognosis in lung cancer patients. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) results suggested that hepcidin is involved in the immune response. Furthermore, hepcidin expression was positively correlated with the infiltration levels of immune cells and the expression of diverse immune cell marker sets. Importantly, hepcidin may affect prognosis partially by regulating immune infiltration in lung cancer patients. Hepcidin may serve as a candidate prognostic biomarker for determining prognosis associated with immune infiltration in lung cancer.
Genetics Insight for COVID-19 Susceptibility and Severity: A Review
Authors: Fricke-Galindo Ingrid , Falfán-Valencia Ramcés
Published: April 2021

Coronavirus disease (COVID-19) presents a broad spectrum of clinical manifestations ranging from an asymptomatic to a severe clinical course. The host genetic background influence on the susceptibility and outcome of multiples infectious diseases has been previously reported. Herein, we aimed to describe relevant identified genetic variants and those potentially related to the inter-individual variability of COVID-19 susceptibility and/or severity considering the physiopathological pathway of the disease TheHLA-A*25:01, -B*15:27,-B*46:01,-C*01:02, and-C*07:29alleles have been associated with COVID-19 susceptibility; whileHLA-A*02:02,-B*15:03, and-C*12:03have been identified as low-risk alleles. Variants in cytokine genes such asIL1B,IL1R1,IL1RN,IL6,IL17A,FCGR2A, andTNFcould be related to disease susceptibility and cytokine storm, and/or COVID-19 complications (e.g., venous thrombosis). Several variants inACE2andTMPRSS2affecting the expression of the receptors related to COVID-19 have been associated with the disease susceptibility and risk factors. Finally, two GWAS have identified theloci3p21.31 (LZTFL1,SLC6A20,CCR9,FYCO1,CXCR6, andXCR1) and 9q34.2 (ABO) with COVID-19 severity. Heterogeneous results in the association of genetic variants with COVID-19 susceptibility and severity were observed. The mechanism of identified risk-genes and studies in different populations are still warranted.
Function and Role of Regulatory T Cells in Rheumatoid Arthritis
Authors: Jiang Qi , Yang Guocan , Liu Qi , Wang Shengjun , Cui Dawei
Published: April 2021

Rheumatoid arthritis (RA) is a systemic and heterogeneous autoimmune disease with symmetrical polyarthritis as its critical clinical manifestation. The basic cause of autoimmune diseases is the loss of tolerance to self or harmless antigens. The loss or functional deficiency of key immune cells, regulatory T (Treg) cells, has been confirmed in human autoimmune diseases. The pathogenesis of RA is complex, and the dysfunction of Tregs is one of the proposed mechanisms underlying the breakdown of self-tolerance leading to the progression of RA. Treg cells are a vital component of peripheral immune tolerance, and the transcription factor Foxp3 plays a major immunosuppressive role. Clinical treatment for RA mainly utilizes drugs to alleviate the progression of disease and relieve disease activity, and the ideal treatment strategy should be to re-induce self-tolerance before obvious tissue injury. Treg cells are one of the ideal options. This review will introduce the classification, mechanism of action, and characteristics of Treg cells in RA, which provides insights into clinical RA treatment.
Emerging Role of Exosomes in Tuberculosis: From Immunity Regulations to Vaccine and Immunotherapy
Authors: Sun Yin-Fu , Pi Jiang , Xu Jun-Fa
Published: April 2021

Exosomes are cell-derived nanovesicles carrying protein, lipid, and nucleic acid for secreting cells, and act as significant signal transport vectors for cell-cell communication and immune modulation. Immune-cell-derived exosomes have been found to contain molecules involved in immunological pathways, such as MHCII, cytokines, and pathogenic antigens. Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains one of the most fatal infectious diseases. The pathogen for tuberculosis escapes the immune defense and continues to replicate despite rigorous and complicate host cell mechanisms. The infected-cell-derived exosomes under this circumstance are found to trigger different immune responses, such as inflammation, antigen presentation, and activate subsequent pathways, highlighting the critical role of exosomes in anti-MTB immune response. Additionally, as a novel kind of delivery system, exosomes show potential in developing new vaccination and treatment of tuberculosis. We here summarize recent research progress regarding exosomes in the immune environment during MTB infection, and further discuss the potential of exosomes as delivery system for novel anti-MTB vaccines and therapies.
In vitro Evaluation of Programmed Cell Death in the Immune System of Pacific Oyster Crassostrea gigas by the Effect of Marine Toxins
Authors: Estrada Norma , Núñez-Vázquez Erick J. , Palacios Alejandra , Ascencio Felipe , Guzmán-Villanueva Laura , Contreras Rubén G.
Published: April 2021

Programmed cell death (PCD) is an essential process for the immune system's development and homeostasis, enabling the remotion of infected or unnecessary cells. There are several PCD's types, depending on the molecular mechanisms, such as non-inflammatory or pro-inflammatory. Hemocytes are the main component of cellular immunity in bivalve mollusks. Numerous infectious microorganisms produce toxins that impair hemocytes functions, but there is little knowledge on the role of PCD in these cells. This study aims to evaluate in vitro whether marine toxins induce a particular type of PCD in hemocytes of the bivalve mollusk Crassostrea gigas during 4 h at 25°C. Hemocytes were incubated with two types of marine toxins: non-proteinaceous toxins from microalgae (saxitoxin, STX; gonyautoxins 2 and 3, GTX2/3; okadaic acid/dynophysistoxin-1, OA/DTX-1; brevetoxins 2 and 3, PbTx-2,-3; brevetoxin 2, PbTx-2), and proteinaceous extracts from bacteria (Vibrio parahaemolyticus, Vp; V. campbellii, Vc). Also, we used the apoptosis inducers, staurosporine (STP), and camptothecin (CPT). STP, CPT, STX, and GTX 2/3, provoked high hemocyte mortality characterized by apoptosis hallmarks such as phosphatidylserine translocation into the outer leaflet of the cell membrane, exacerbated chromatin condensation, DNA oligonucleosomal fragments, and variation in gene expression levels of apoptotic caspases 2, 3, 7, and 8. The mixture of PbTx-2,-3 also showed many apoptosis features; however, they did not show apoptotic DNA oligonucleosomal fragments. Likewise, PbTx-2, OA/DTX-1, and proteinaceous extracts from bacteria Vp, and Vc, induced a minor degree of cell death with high gene expression of the pro-inflammatory initiator caspase-1, which could indicate a process of pyroptosis-like PCD. Hemocytes could carry out both PCD types simultaneously. Therefore, marine toxins trigger PCD's signaling pathways in C. gigas hemocytes, depending on the toxin's nature, which appears to be highly conserved both structurally and functionally.
New Insights Into Biomphalysin Gene Family Diversification in the Vector Snail Biomphalaria glabrata
Authors: Pinaud Silvain , Tetreau Guillaume , Poteaux Pierre , Galinier Richard , Chaparro Cristian , Lassalle Damien , Portet Anaïs , Simphor Elodie , Gourbal Benjamin , Duval David
Published: April 2021

Aerolysins initially characterized as virulence factors in bacteria are increasingly found in massive genome and transcriptome sequencing data from metazoans. Horizontal gene transfer has been demonstrated as the main way of aerolysin-related toxins acquisition in metazoans. However, only few studies have focused on their potential biological functions in such organisms. Herein, we present an extensive characterization of a multigene family encoding aerolysins - named biomphalysin - inBiomphalaria glabratasnail, the intermediate host of the trematodeSchistosoma mansoni. Our results highlight that duplication and domestication of an acquired bacterial toxin gene in the snail genome result in the acquisition of a novel and diversified toxin family. Twenty-three biomphalysin genes were identified. All are expressed and exhibited a tissue-specific expression pattern. Anin silicostructural analysis was performed to highlight the central role played by two distinct domains i) a large lobe involved in the lytic function of these snail toxins which constrained their evolution and ii) a small lobe which is structurally variable between biomphalysin toxins and that matched to various functional domains involved in moiety recognition of targets cells. A functional approach suggests that the repertoire of biomphalysins that bind to pathogens, depends on the type of pathogen encountered. These results underline a neo-and sub-functionalization of the biomphalysin toxins, which have the potential to increase the range of effectors in the snail’s immune arsenal.
Humanized Mice for the Evaluation of Novel HIV-1 Therapies
Authors: Abeynaike Shawn , Paust Silke
Published: April 2021

With the discovery of antiretroviral therapy, HIV-1 infection has transitioned into a manageable but chronic illness, which requires lifelong treatment. Nevertheless, complete eradication of the virus has still eluded us. This is partly due to the virus’s ability to remain in a dormant state in tissue reservoirs, ‘hidden’ from the host’s immune system. Also, the high mutation rate of HIV-1 results in escape mutations in response to many therapeutics. Regardless, the development of novel cures for HIV-1 continues to move forward with a range of approaches from immunotherapy to gene editing. However, to evaluatein vivopathogenesis and the efficacy and safety of therapeutic approaches, a suitable animal model is necessary. To this end, the humanized mouse was developed by McCune in 1988 and has continued to be improved on over the past 30 years. Here, we review the variety of humanized mouse models that have been utilized through the years and describe their specific contribution in translating HIV-1 cure strategies to the clinic.
Case Report: Combination Therapy With PD-1 Blockade for Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation Resulted in Fatal GVHD
Authors: Yao Sun , Jianlin Chen , Zhuoqing Qiao , Yuhang Li , Jiangwei Hu , Guoliang Hu , Hongmei Ning , Bin Zhang , Liangding Hu
Published: April 2021

Background:Azacitidine is commonly used in the treatment of relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the effectiveness of this monotherapy is still very low. A possible mechanism of resistance to hypomethylating agents (HMAs) is the upregulation of the expression of inhibitory checkpoint receptors and their ligands, making the combination of HMAs and immune checkpoint blockade therapy a rational approach. Although the safety of anti-programmed cell death protein (PD)-1 antibodies for patients with post-allo-HSCT remains a complicated issue, the preliminary clinical result of combining azacitidine with anti-PD-1 antibodies is encouraging; however, the safety and efficacy of this approach need further investigation.

Case Presentation:We reported a case of treated secondary (ts)-AML in a patient who received tislelizumab (an anti-PD-1 antibody) in combination with azacitidine. The patient relapsed after allo-HSCT and was previously exposed to HMAs-based therapy. The patient received tislelizumab for compassionate use. After the combination treatment, the patient achieved complete remission with incomplete hematologic recovery, negative minimal residual disease (MRD) by flow cytometry (FCM), and negative Wilms' tumor protein 1 (WT1). However, the patient successively developed serious immune-related adverse events (irAEs) and graft vs. host disease (GVHD) and eventually died from complications of GVHD.

Conclusion:To our knowledge, this is the first case to report the combined use of tislelizumab and azacitidine to treat relapsed AML posttransplantation. This report highlights the safety concerns of using an anti-PD-1 antibody in combination with azacitidine after allo-HSCT, especially the risk of GVHD, and provides a basis for future studies.
Epigallocatechin Gallate Can Protect Mice From Acute Stress Induced by LPS While Stabilizing Gut Microbes and Serum Metabolites Levels
Authors: Ma Yong , Liu Gang , Tang Muyang , Fang Jun , Jiang Hongmei
Published: April 2021

Epigallocatechin gallate (EGCG) has potent biological activity as well as strong antioxidant and anti-inflammatory effects. This study aims to explore the protective effect of EGCG on LPS-induced acute injury. We randomly divided 18 mice into three groups: CON, LPS, and EGCG-LPS. We gave the EGCG-LPS group gavage treatment with EGCG on day 8–15 and an intraperitoneal injection of LPS on day 16 to induce acute injury. The results showed that, compared with the LPS group, the bodyweight of the mice in the EGCG-LPS group increased significantly and effectively inhibited the morphological damage of the jejunum and liver. We measured liver tissue and found that the EGCG gavage treatment significantly inhibited the pro-inflammatory factors (TNF-α, IL-1β, IL-6, MCP-1, MIP-2, IFN-γ) and oxidation indicators (MPO, NO, ALT, and AST) levels increase. The microbiological results showed that the EGCG gavage treatment reshaped the disturbance done to the intestinal microbial community in the mice by LPS, reversed the changes in the abundance ratio of Firmicutes/Bacteroidetes, and significantly reduced the abundance of Enterobacteriales. Finally, the serum metabolomics results showed that, when compared with the LPS group, the gavage treatment of EGCG significantly increased the concentration of sphingomyelin (d17:1/17:0), sphingomyelin (d16:1/20:0), and significantly reduced the content of trans-Hexadec-2-enoyl carnitine, and so on. Therefore, we believe that EGCG can protect mice from acute stress induced by LPS while stabilizing gut microbes in general, improving the metabolism of sphingolipids, and inhibiting the content of harmful metabolites.
Complement Initiation Varies by Sex in Intestinal Ischemia Reperfusion Injury
Authors: Wu Miaomiao , Rowe Jennifer M. , Fleming Sherry D.
Published: April 2021

Intestinal ischemia reperfusion (IR)-induced tissue injury represents an acute inflammatory response with significant morbidity and mortality. The mechanism of IR-induced injury is not fully elucidated, but recent studies suggest a critical role for complement activation and for differences between sexes. To test the hypothesis that complement initiation differs by sex in intestinal IR, we performed intestinal IR on male and female WT C57B6L/, C1q-/-, MBL-/-, or properdin (P)-/-mice. Intestinal injury, C3b and C5a production andex vivosecretions were analyzed. Initial studies demonstrated a difference in complement mRNA and protein in male and female WT mice. In response to IR, male C1q-, MBL- and P-deficient mice sustained less injury than male WT mice. In contrast, only female MBL-/-mice sustained significantly less injury than female wildtype mice. Importantly, wildtype, C1q-/-and P-/-female mice sustained significant less injury than the corresponding male mice. In addition, both C1q and MBL expression and deposition increased in WT male mice, while only elevated MBL expression and deposition occurred in WT female mice. These data suggested that males use both C1q and MBL pathways, while females tend to depend on lectin pathway during intestinal IR. Females produced significantly less serum C5a in MBL-/-and P-/-mice. Our findings suggested that complement activation plays a critical role in intestinal IR in a sex-dependent manner.
Proteomic Analysis of the Hemolymph After Metschnikowia bicuspidata Infection in the Chinese Mitten Crab Eriocheir sinensis
Authors: Jiang Hongbo , Bao Jie , Xing Yuenan , Feng Chengcheng , Li Xiaodong , Chen Qijun
Published: April 2021

The “milky disease” of the Chinese mitten crab, Eriocheir sinensis, is a highly lethal fungal disease caused by Metschnikowia bicuspidata infection. To elucidate the immune responses of the hemolymph of E. sinensis to M. bicuspidata infection, a comparative analysis of the hemolymph of E. sinensis infected with M. bicuspidata and that treated with phosphate buffered saline was performed using label-free quantitative proteomics. A total of 429 proteins were identified. Using a 1.5-fold change in expression as a physiologically significant benchmark, 62 differentially expressed proteins were identified, of which 38 were significantly upregulated and 24 were significantly downregulated. The upregulated proteins mainly included cytoskeleton-related proteins (myosin regulatory light chain 2, myosin light chain alkali, tubulin α-2 chain, and tubulin β-1 chain), serine protease and serine protease inhibitor (clip domain-containing serine protease, leukocyte elastase inhibitor, serine protein inhibitor 42Dd), catalase, transferrin, and heat shock protein 70. Upregulation of these proteins indicated that phenoloxidase system, phagocytosis and the ROS systems were induced by M. bicuspidata. The downregulated proteins were mainly organ and tissue regeneration proteins (PDGF/VEGF-related factor protein, integrin-linked protein kinase homing pat-4 gene) and hemagglutination-associated proteins (hemolymph clottable protein, hemocyte protein-glutamine gamma-glutamyltransferase). Downregulation of these proteins indicated that M. bicuspidata inhibited hemocyte regeneration and hemolymph agglutination. Fifteen differentially expressed proteins related to immunity were verified using a parallel reaction monitoring method. The expression trend of these proteins was similar to that of the proteome. To the best of our knowledge, this is the first report on the proteome of E. sinensis in response to M. bicuspidata infection. These results not only provide new and important information on the immune response of crustaceans to yeast infection but also provide a basis for further understanding the molecular mechanism of complex host pathogen interactions between crustaceans and fungi.
Interaction Networks Converging on Immunosuppressive Roles of Granzyme B: Special Niches Within the Tumor Microenvironment
Authors: Wang Weinan , Zou Rui , Qiu Ye , Liu Jishuang , Xin Yu , He Tianzhu , Qiu Zhidong
Published: April 2021

Granzyme B is a renowned effector molecule primarily utilized by CTLs and NK cells against ill-defined and/or transformed cells during immunosurveillance. The overall expression of granzyme B within tumor microenvironment has been well-established as a prognostic marker indicative of priming immunity for a long time. Until recent years, increasing immunosuppressive effects of granzyme B are unveiled in the setting of different immunological context. The accumulative evidence confounded the roles of granzyme B in immune responses, thereby arousing great interests in characterizing detailed feature of granzyme B-positive niche. In this paper, the granzyme B-related regulatory effects of major suppressor cells as well as the tumor microenvironment that defines such functionalities were longitudinally summarized and discussed. Multiplex networks were built upon the interactions among different transcriptional factors, cytokines, and chemokines that regarded to the initiation and regulation of granzyme B-mediated immunosuppression. The conclusions and prospect may facilitate better interpretations of the clinical significance of granzyme B, guiding the rational development of therapeutic regimen and diagnostic probes for anti-tumor purposes.
Recent Progress of 2D Nanomaterials for Application on Microwave Absorption: A Comprehensive Study
Authors: Kallumottakkal Muhammed , Hussein Mousa I. , Iqbal Muhammad Z.
Published: April 2021

Rapid advancements and wide spread of microwave- and RF-communication systems over the years have led to an abundant increase in electromagnetic energy radiation in our living environment. Such an increase in microwave sources is due to the development and advancement in communication techniques (mobile phones, laptops, and antennas for aeronautics or automobile) and electronic warfare in the military field (radar and satellite). Recently research efforts are focused on finding solutions to guarantee protection from electromagnetic (EM) radiations. The EM absorbing materials are used to overcome these issues to ensure public protection as well as safe military operations. Various types of EM absorbing materials comprising composite materials have been progressively developed and researched. This kind of material is developed by impeding absorbing charges (magnetic or dielectric) into a host matrix material. Recently, carbon allotropes such as graphene, MXenes, carbon nanotubes (CNTs), and carbon fibers have attracted increasing attention owing to their EMI shielding characteristics and lightweight. This work presents a comprehensive study on the recent research progress on the application of nanomaterials for electromagnetic shielding and absorption. The review will cover the microwave absorption mechanism and absorption performance using graphene, MXenes, carbon nanotubes (CNTs), carbides, and ferromagnetic metals. Overall, the review will present a timely update on the research progress of microwave absorption performance of various nanomaterials.
Direct Ink Writing of Materials for Electronics-Related Applications: A Mini Review
Authors: Hou Zhenzhong , Lu Hai , Li Ying , Yang Laixia , Gao Yang
Published: April 2021

Recently, the fabrication of electronics-related components via direct ink writing (DIW) has attracted much attention. Compared to the conventionally fabricated electronic components, DIW-printed ones have more complicated structures, higher accuracy, improved efficiency, and even enhanced performances that arise from well-designed architectures. The DIW technology allows directly print materials on a variety of flat substrates, even a conformal one, well suiting them to applications such as wearable devices and on-chip integrations. Here, recent developments in DIW printing of emerging components for electronics-related applications are briefly reviewed, including electrodes, electronic circuits, and functional components. The printing techniques, processes, ink materials, advantages, and properties of DIW-printed architectures are discussed. Finally, the challenges and outlooks on the manufacture of 3D structured electronic devices by DIW are outlined, pointing out future designs and developments of DIW technology for electronics-related applications. The combination of DIW and electronic devices will help to improve the quality of human life and promote the development of science and society.
Polyene-Producing Streptomyces spp. From the Fungus-Growing Termite Macrotermes barneyi Exhibit High Inhibitory Activity Against the Antagonistic Fungus Xylaria
Authors: Li Jingjing , Sang Moli , Jiang Yutong , Wei Jianhua , Shen Yulong , Huang Qihong , Li Yaoyao , Ni Jinfeng
Published: April 2021

Fungus-growing termites are engaged in a tripartite mutualism with intestinal microbes and a monocultivar (Termitomyces sp.) in the fungus garden. The termites are often plagued by entomopathogen (Metarhizium anisopliae) and fungus garden is always threatened by competitors (Xylaria spp.). Here, we aim to understand the defensive role of intestinal microbes, the actinomycetes which were isolated from the gut of Macrotermes barneyi. We obtained 44 antifungal isolates, which showed moderate to strong inhibition to Xylaria sp. HPLC analysis indicated that different types of polyenes (tetraene, pentene, and heptaene) existed in the metabolites of 10 strong antifungal Streptomyces strains. Two pentene macrolides (pentamycin and 1′14-dihydroxyisochainin) were firstly purified from Streptomyces strain HF10, both exhibiting higher activity against Xylaria sp. and M. anisopliae than cultivar Termitomyces. Subsequently, tetraene and heptaene related gene disruption assay showed that the mutant strains lost the ability to produce corresponding polyenes, and they also had significantly decreased activities against Xylaria sp. and M. anisopliae compared to that of wild type strains. These results indicate that polyene-producing Streptomyces from the guts of M. barneyi have strong inhibition to competitor fungus and polyenes contribute to inhibitory effects on Xylaria sp.
CCR7 Has Potential to Be a Prognosis Marker for Cervical Squamous Cell Carcinoma and an Index for Tumor Microenvironment Change
Authors: Tian Wei-Jie , Feng Peng-Hui , Wang Jun , Yan Ting , Qin Qing-Feng , Li Dong-Lin , Liang Wen-Tong
Published: April 2021

The tumor microenvironment (TME) has an essential role in the development of cervical squamous cell carcinoma (CSCC); however, the dynamic role of the stromal and immune cells is still unclear in TME. We downloaded data from The Cancer Genome Atlas (TCGA) database and applied ESTIMATE and CIBERSORT algorithms to measure the quantity of stromal and immune cells and the composition of tumor-infiltrating immune cell (TIC) in 253 CSCC cases. The protein-protein interaction (PPI) network and Cox regression analysis presented the differentially expressed genes (DEGs). Then, C-C chemokine receptor type 7 (CCR7) was screened out as a prognostic marker by the univariate Cox and intersection analysis of PPI. Further analysis showed a positive correlation between the expression of CCR7 and the survival of CSCC patients. The result of the Gene Set Enrichment Analysis (GSEA) of genes in the high CCR7 expression group displayed a predominant enrichment in immune-related pathways. An enrichment in metabolic activities was observed in the low CCR7 expression group. CIBERSORT analysis showed a positive correlation between Plasma cells, CD8+ T cells, and regulatory T cells and the CCR7 expression, suggesting that CCR7 might play a crucial role in maintaining the immunological dominance status for TME. Therefore, the expression level of CCR7 might help predict the survival of CSCC cases and be an index that the status of TME transitioned from immunological dominance to metabolic activation, which presented a new insight into the treatment of CSCC.
The Molecular Pathophysiology of Psoriatic Arthritis—The Complex Interplay Between Genetic Predisposition, Epigenetics Factors, and the Microbiome
Authors: Carvalho Ana L. , Hedrich Christian M.
Published: April 2021

Psoriasis is a symmetric autoimmune/inflammatory disease that primarily affects the skin. In a significant proportion of cases, it is accompanied by arthritis that can affect any joint, the spine, and/or include enthesitis. Psoriasis and psoriatic arthritis are multifactor disorders characterized by aberrant immune responses in genetically susceptible individuals in the presence of additional (environmental) factors, including changes in microbiota and/or epigenetic marks. Epigenetic changes can be heritable or acquired (e.g., through changes in diet/microbiota or as a response to therapeutics) and, together with genetic factors, contribute to disease expression. In psoriasis, epigenetic alterations are mainly related to cell proliferation, cytokine signaling and microbial tolerance. Understanding the complex interplay between heritable and acquired pathomechanistic factors contributing to the development and maintenance of psoriasis is crucial for the identification and validation of diagnostic and predictive biomarkers, and the introduction of individualized effective and tolerable new treatments. This review summarizes the current understanding of immune activation, genetic, and environmental factors that contribute to the pathogenesis of psoriatic arthritis. Particular focus is on the interactions between these factors to propose a multifactorial disease model.
Increased Brain Age Gap Estimate (BrainAGE) in Young Adults After Premature Birth
Authors: Hedderich Dennis M. , Menegaux Aurore , Schmitz-Koep Benita , Nuttall Rachel , Zimmermann Juliana , Schneider Sebastian C. , Bäuml Josef G. , Daamen Marcel , Boecker Henning , Wilke Marko , Zimmer Claus , Wolke Dieter , Bartmann Peter , Sorg Christian , Gaser Christian
Published: April 2021

Recent evidence suggests increased metabolic and physiologic aging rates in premature-born adults. While the lasting consequences of premature birth on human brain development are known, its impact on brain aging remains unclear. We addressed the question of whether premature birth impacts brain age gap estimates (BrainAGE) using an accurate and robust machine-learning framework based on structural MRI in a large cohort of young premature-born adults (n = 101) and full-term (FT) controls (n = 111). Study participants are part of a geographically defined population study of premature-born individuals, which have been followed longitudinally from birth until young adulthood. We investigated the association between BrainAGE scores and perinatal variables as well as with outcomes of physical (total intracranial volume, TIV) and cognitive development (full-scale IQ, FS-IQ). We found increased BrainAGE in premature-born adults [median (interquartile range) = 1.4 (−1.3–4.7 years)] compared to full-term controls (p = 0.002, Cohen’s d = 0.443), which was associated with low Gestational age (GA), low birth weight (BW), and increased neonatal treatment intensity but not with TIV or FS-IQ. In conclusion, results demonstrate elevated BrainAGE in premature-born adults, suggesting an increased risk for accelerated brain aging in human prematurity.
Changes in Walking Speed After High-Intensity Treadmill Training Are Independent of Changes in Spatiotemporal Symmetry After Stroke
Authors: Cleland Brice , Madhavan Sangeetha
Published: April 2021

Objectives: Decreased walking speeds and spatiotemporal asymmetry both occur after stroke, but it is unclear whether and how they are related. It is also unclear whether rehabilitation-induced improvements in walking speed are associated with improvements in symmetry or greater asymmetry. High-intensity speed-based treadmill training (HISTT) is a recent rehabilitative strategy whose effects on symmetry are unclear. The purpose of this study was to: (1) assess whether walking speed is cross-sectionally associated with spatiotemporal symmetry in chronic stroke, (2) determine whether HISTT leads to changes in the spatiotemporal symmetry of walking, and (3) evaluate whether HISTT-induced changes in walking speed are associated with changes in spatiotemporal symmetry.

Methods: Eighty-one participants with chronic stroke performed 4 weeks of HISTT. At pre, post, and 3-month follow-up assessments, comfortable and maximal walking speed were measured with the 10-meter walk test, and spatiotemporal characteristics of walking were measured with the GAITRite mat. Step length and swing time were expressed as symmetry ratios (paretic/non-paretic). Changes in walking speed and symmetry were calculated and the association was determined.

Results: At pre-assessment, step length and swing time asymmetries were present (p < 0.001). Greater temporal symmetry was associated with faster walking speeds (p ≤ 0.001). After HISTT, walking speeds increased from pre-assessment to post-assessment and follow-up (p ≤ 0.002). There were no changes in spatiotemporal symmetry (p ≥ 0.10). Change in walking speed was not associated with change in spatial or temporal symmetry from pre- to post-assessment or from post-assessment to follow-up (R2 ≤ 0.01, p ≥ 0.37).

Conclusions: HISTT improves walking speed but does not systematically improve or worsen spatiotemporal symmetry. Clinicians may need to pair walking interventions like HISTT with another intervention designed to improve walking symmetry simultaneously. The cross-sectional relation between temporal symmetry and walking speed may be mediated by other factors, and not be causative.