bluuebunny/crossref_metadata_2025 huggingface dataset:
A new study of multi-phase mass and heat transfer in natural gas hydrate reservoir with an embedded discrete fracture model
Authors: Cui Yudong , Teng Bailu , Luo Wanjing , Lu Cheng , Zhou Yingfang
Published: February 2023

Studies of the hydrate cores have shown that natural fractures can be frequently observed in hydrate reservoirs, resulting in a fracture-filled hydrate. Therefore, it is highly necessary for industries to predict the gas well productivity of fracture-filled hydrate reservoirs. In this work, an embedded discrete fracture model is applied to characterize the natural fractures of fracture-filled gas-hydrate reservoirs. The non-linear mass and energy conservation equations which are discretized with the finite-difference method are solved by the fully implicit approach, and the proposed model is justified by a commercial simulator. On the basis of the proposed model, we investigate the influences of natural fractures, fracture conductivity, and hydrate dissociation rate on the gas well productivity and the distributions of pressure, temperature, and hydrate saturation. The simulation results show that hydraulic and natural fractures exert significant impacts on the gas well productivity of the fracture-filled hydrate reservoirs, and the cumulative gas production is increased by 45.6% due to the existence of the connected natural fractures. The connected natural fractures can impose a more important influence on the gas well productivity than the unconnected natural fractures. The cumulative gas production is increased by 6.48% as Nnf is increased from 2 to 50, whereas the increase is 43.38% as Nf_con is increased from 0 to 4. In addition, A higher hydraulic fracture conductivity can be more favorable than a higher natural fracture conductivity for improving the gas well productivity, and a higher hydrate dissociation rate can lead to a lower temperature along fractures due to a more noticeable reduction of solid hydrate. This study provides a theoretical basis for developing fracture-filled hydrate reservoirs efficiently in the future.
The impact of social comparison processes on self-evaluation of performance, self-concept, and task interest
Authors: Bosch Jannis , Wilbert Jürgen
Published: February 2023

Development of self-concept and task interest has been shown to be affected by social comparison processes in a variety of cross-sectional studies. A potential explanation for these effects is an effect of social comparative performance feedback on an individual’s self-evaluation of performance, which in turn influences development of self-concept and task interest. There are, however, only few studies addressing this topic with experimental designs. This study was aimed at closing this research gap by experimentally manipulating social comparative performance. Feedback given was based on 2 × 2 experimental conditions: social position (high vs. low) and average performance of the reference group (high vs. low). Results show a strong effect of social position on self-evaluation of performance and smaller effects on self-concept and task interest.
Enhanced insulin activity achieved in VDRa/b ablation zebrafish
Authors: Liu Ruolan , Lu Yao , Peng Xuyan , Jia Jingyi , Ruan Yonglin , Shi Shengchi , Shu Tingting , Li Tianhui , Jin Xia , Zhai Gang , He Jiangyan , Lou Qiyong , Yin Zhan
Published: February 2023

Introduction

1α,25-dihydroxyvitamin D3 (1α,25[OH]2VD3) is a hormone known for its key roles in calcium absorption and nutrient metabolism. In teleost fishes, 1α,25(OH)2VD3 insufficiency causes impaired glucose metabolism and lipid oxidation. However, the cascade and mechanisms of 1α,25(OH)2VD3 and the vitamin d receptor (VDR) signaling are unclear.

Results

In this study, two genes (vdra and vdrb) encoding paralogs of VDRs were genetically knocked out in zebrafish. Growth retardation and accumulated visceral adipose tissue have been observed in vdra-/-;vdrb-/- deficient line. In the liver elevated accumulation of triglycerides and suppressed lipid oxidation were detected. Morover significantly elevated 1α,25(OH)2VD3 levels were detected in vdra-/-;vdrb-/- zebrafish due to cyp24a1 transcription repression. Furthermore VDRs ablation Enhanced insulin signaling including elevated insulin/insra trancriptional levels, glycolysis, lipogenesis and promoted AKT/mTOR activity.

Discussion

In conclusion, our present studies provides a zebrafish model with an elevated 1α,25(OH)2VD3 levels in vivo. The 1α,25(OH)2VD3/VDRs signaling promote lipid oxidation activity. However 1α,25(OH)2VD3 activity of regulation of glucose homeostasis through Insulin/Insr was independent of nuclear VDRs in teleosts.
Ectopic lipid metabolism in anterior pituitary dysfunction
Authors: Baumgartner Clemens , Krššák Martin , Vila Greisa , Krebs Michael , Wolf Peter
Published: February 2023

Over the past decades, adapted lifestyle and dietary habits in industrialized countries have led to a progress of obesity and associated metabolic disorders. Concomitant insulin resistance and derangements in lipid metabolism foster the deposition of excess lipids in organs and tissues with limited capacity of physiologic lipid storage. In organs pivotal for systemic metabolic homeostasis, this ectopic lipid content disturbs metabolic action, thereby promotes the progression of metabolic disease, and inherits a risk for cardiometabolic complications. Pituitary hormone syndromes are commonly associated with metabolic diseases. However, the impact on subcutaneous, visceral, and ectopic fat stores between disorders and their underlying hormonal axes is rather different, and the underlying pathophysiological pathways remain largely unknown. Pituitary disorders might influence ectopic lipid deposition indirectly by modulating lipid metabolism and insulin sensitivity, but also directly by organ specific hormonal effects on energy metabolism. In this review, we aim to I) provide information about the impact of pituitary disorders on ectopic fat stores, II) and to present up-to-date knowledge on potential pathophysiological mechanisms of hormone action in ectopic lipid metabolism.
Diabetes management in patients undergoing total pancreatectomy: A single center cohort study
Authors: Zhao Tianyi , Fu Yong , Zhang Taiping , Guo Junchao , Liao Quan , Song Shuoning , Duo Yanbei , Gao Yuting , Yuan Tao , Zhao Weigang
Published: February 2023

Background

Total pancreatectomy (TP) has been increasingly performed in recent years. However, studies on diabetes management after TP during different postoperative periods are still limited.

Objectives

This study aimed to evaluate the glycemic control and insulin therapy of patients undergoing TP during the perioperative and long-term follow-up period.

Methods

Ninety-three patients undergoing TP for diffuse pancreatic tumors from a single center in China were included. Based on preoperative glycemic status, patients were divided into three groups: nondiabetic group (NDG, n = 41), short-duration diabetic group (SDG, preoperative diabetes duration ≤12 months, n = 22), and long-duration diabetic group (LDG, preoperative diabetes duration >12 months, n = 30). Perioperative and long-term follow-up data, including the survival rate, glycemic control, and insulin regimens, were evaluated. Comparative analysis with complete insulin-deficient type 1 diabetes mellitus (T1DM) was conducted.

Results

During hospitalization after TP, glucose values within the target (4.4-10.0 mmol/L) accounted for 43.3% of the total data, and 45.2% of the patients experienced hypoglycemic events. Patients received continuous intravenous insulin infusion during parenteral nutrition at a daily insulin dose of 1.20 ± 0.47 units/kg/day. In the long-term follow-up period, glycosylated hemoglobin A1c levels of 7.43 ± 0.76% in patients following TP, as well as time in range and coefficient of variation assessed by continuous glucose monitoring, were similar to those in patients with T1DM. However, patients after TP had lower daily insulin dose (0.49 ± 0.19 vs 0.65 ± 0.19 units/kg/day, P < 0.001) and basal insulin percentage (39.4 ± 16.5 vs 43.9 ± 9.9%, P = 0.035) than patients with T1DM, so did those using insulin pump therapy. Whether in the perioperative or long-term follow-up period, daily insulin dose was significantly higher in LDG patients than in NDG and SDG patients.

Conclusions

Insulin dose in patients undergoing TP varied according to different postoperative periods. During long-term follow-up, glycemic control and variability following TP were comparable to complete insulin-deficient T1DM but with fewer insulin needs. Preoperative glycemic status should be evaluated as it could guide insulin therapy after TP.
Cardiovascular-renal protective effect and molecular mechanism of finerenone in type 2 diabetic mellitus
Authors: Lv Ruolin , Xu Lili , Che Lin , Liu Song , Wang Yangang , Dong Bingzi
Published: February 2023

Chronic kidney diseases (CKD) and cardiovascular diseases (CVD) are the main complications in type 2 diabetic mellitus (T2DM), increasing the risk of cardiovascular and all-cause mortality. Current therapeutic strategies that delay the progression of CKD and the development of CVD include angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), sodium-glucose co-transporter 2 inhibitors (SGLT-2i) and GLP-1 receptor agonists (GLP-1RA). In the progression of CKD and CVD, mineralocorticoid receptor (MR) overactivation leads to inflammation and fibrosis in the heart, kidney and vascular system, making mineralocorticoid receptor antagonists (MRAs) as a promising therapeutic option in T2DM with CKD and CVD. Finerenone is the third generation highly selective non-steroidal MRAs. It significantly reduces the risk of cardiovascular and renal complications. Finerenone also improves the cardiovascular-renal outcomes in T2DM patients with CKD and/or chronic heart failure (CHF). It is safer and more effective than the first- and second-generation MRAs due to its higher selectivity and specificity, resulting in a lower incidence of adverse effects including hyperkalemia, renal insufficiency and androgen-like effects. Finerenone shows potent effect on improving the outcomes of CHF, refractory hypertension, and diabetic nephropathy. Recently studies have shown that finerenone may have potential therapeutic effect on diabetic retinopathy, primary aldosteronism, atrial fibrillation, pulmonary hypertension and so on. In this review, we discuss the characteristics of finerenone, the new third-generation MRA, and compared with the first- and second-generation steroidal MRAs and other nonsteroidal MRAs. We also focus on its safety and efficacy of clinical application on CKD with T2DM patients. We hope to provide new insights for the clinical application and therapeutic prospect.
A network analysis of carbon emission flows among marine industries in China
Authors: Wang Lili , Zhou Xinli , Wei Liping , Xiao Wenwen
Published: February 2023

In recent years, environmental problems have become an important bottleneck restricting the sustainable development of Marine economy in China. CO2 is one of the main greenhouse gases which contributes to marine environmental problems. As CO2 emissions can transfer among industries, identifying the industries that release CO2 most and clarifying the carbon emission flows among marine industries are helpful for decision-makers to curb CO2 emissions of marine industries. This paper applies the network method to measure carbon emission flows. First, carbon transfer coefficient is calculated. Second, carbon transfer network of marine industry is constructed based on carbon transfer coefficient. Then the structure of marine industry carbon transfer network is analyzed. Finally, the method proposed in this paper is applied to the case of China and some suggestions for carbon reduction is put forward.
Exploring the spatiotemporal changes and influencing factors of urban resilience based on Scale-Density-Morphology—A case study of the Chengdu-Deyang-Mianyang Economic Belt, China
Authors: He Wei , Zheng ShiWei , Zhao XiaoQuan
Published: February 2023

It is of great significance to carry out research on the evolution of urban resilience and the detection of influencing factors to promote urban safety management and guide urban planning. This paper constructs urban resilience evaluation indicators based on Scale-Density-Morphology, adopts the “polyhedron method” to evaluate the urban resilience of the Chengdu-Deyang-Mianyang Economic Belt from 2010 to 2020, analyzes the temporal and spatial changes in urban resilience, and explores the impact of natural, social, economic and other factors on urban resilience, to provide a basis for regional sustainable development. The results show that 1) The overall level of urban resilience is not high, showing a clear downward trend and imbalance. Urban resilience decreased from 0.296 in 2010 to 0.213 in 2020. The proportion of districts and counties with high urban resilience is relatively small and continues to decline. The differences in urban resilience in the region are significant and gradually increasing, and there is an obvious imbalance in urban resilience. 2) Urban resilience presents the spatial distribution characteristics of continuous expansion of low-resilience and lower-resilience urban, and shrinkage of the distribution of high-resilience and higher-resilience urban. The types of evolution are mainly manifested as rapid decline and fluctuation decline. 3) The influencing factors affecting the spatial differentiation of urban resilience are different. Ecological factors represented by per capita ecological land area have gradually become the primary factor. The influence of factor interactions is greater than that of individual factors, including both non-linear enhancement and two-factor enhancement.
A household-scale life cycle assessment model for understanding the food-energy-water nexus
Authors: Daignault Jessica , Wallace Charles , Watkins David , Handler Robert , Yang Yi , Heaney Danielle , Ahamed Sonya
Published: February 2023

The household is an important locus of decision-making regarding food, energy, and water (FEW) consumption. Changes in household FEW consumption behaviors can lead to significant reductions in environmental impacts, but it can be difficult for consumers to compare the relative impacts of their consumption quantitatively, or to recognize the indirect impacts of their household consumption patterns. We describe two novel tools designed to address this problem: A hybrid life cycle assessment (LCA) framework to translate household consumption of food, energy, and water into key environmental impacts including greenhouse gas emissions, energy use, and water use; and a novel software application called HomeTracker that implements the framework by collecting household FEW data and providing environmental impact feedback to households. We explore the question: How can a life cycle assessment-based software application facilitate collection and translation of household consumption data to meaningful environmental impact metrics? A case study in Lake County, Illinois is presented to illustrate use of the HomeTracker application. Output data describing environmental impacts attributable to household FEW consumption in the study area are shown in order to illustrate key features and trends observed in the case study population. The framework and its associated output data can be used to support experimental research at the household scale, allowing for examination of what users purchase and consume over an extended period of time as well as increased understanding of household behavior trends and environmental impacts, and as future work.
Analysis of temporal and spatial changes and influencing factors of sewage treatment rates of small towns in Chongqing
Authors: Zhou Chao , Yu Zhihan , Wang Qin
Published: February 2023

Small towns are the bridge between urban and rural areas, and their sewage treatment is the focus and problem of urban construction. With Chongqing as the research object, this study explores the influencing factors and the characteristics of temporal and spatial changes in sewage treatment rates of 756 small towns in Chongqing from 2014 to 2020 from four aspects: the overall situation, space, population, and industry. The results show that 1) the sewage treatment rates of small towns showed a certain trend of improvement since 2014 and that the polarization between small towns continued to decrease. 2) The sewage treatment rates of small towns presented a significant spatial correlation in their entirety, but the correlation weakened year by year. In 2014, the sewage treatment rates of small towns were mainly high-high clusters, while those in 2017 were mainly low-low clusters and those in 2020 were low-low clusters in a scattered manner. 3) The sewage treatment rates of small towns with a population of 40,000–60,000 and over 60,000 in 2014 were relatively high, but the gap narrowed year by year. Small towns with more than 60,000 people had the highest sewage treatment rate in 2020, but the gap between the lowest values was reduced to 11.94%. 4) In 2014, small towns with tourism as the leading industry had a significant advantage, but three types of small towns, including industrial and mining towns, were improving fast. 5) Land urbanization, the radiation effect of county towns, the investment in urban construction, population size, and leading industries all had notable driving effects on the increase in sewage treatment rates of small towns, but the impact of urban construction investment was relatively weak because it contained a large scale of real estate investment.
The impact of new ambient air quality standards on green total factor energy efficiency: Evidence from an environmental information disclosure policy in China
Authors: Liu Xing-Yuan , Wen Hong-Xing , Ding Duo-Dong
Published: February 2023

The implementation of the new ambient air quality standards (NAAQS) in 2012 is a milestone in China’s environmental information disclosure process. The fully automated collection and publication of pollution information provides a convenient way to measure the environmental protection process around the country. This paper investigates the association between NAAQS and green total factor energy efficiency (GTFEE) enhancement in Chinese resource-based cities, using the generalized multiperiod DID method and 2004–2019 panel data from 282 prefecture-level cities. We find that the implementation of this NAAQS significantly promotes GTFEE’s improvement in China’s resource-based cities. Furthermore, we discover that both the type of industrial base and the initial public monitoring motivation influence the improvement effect of the NAAQS on GTFEE. In further studies, NAAQS enhances GTFEE through industrial structure optimization, and the magnitude of the local NAAQS effect is influenced by the level of green innovation. Finally, we make recommendations including implementing targeted environmental regulations and enhancing environmental information regulation.
Exploring plastic transport dynamics in the Odaw river, Ghana
Authors: Pinto Rose Boahemaa , Barendse Tom , van Emmerik Tim , van der Ploeg Martine , Annor Frank Ohene , Duah Kwame , Udo Job , Uijlenhoet Remko
Published: February 2023

Plastic pollution in rivers threatens ecosystems, increases flood risk due to its accumulations at hydraulic structures and its final emissions into the ocean threaten aquatic life, especially and probably most in coastal urbanized areas. Previous work suggests that plastic pollution in these urban rivers is influenced by hydrometeorological and anthropogenic factors. However, the transport dynamics of the plastics in such rivers are non-linear and complex and remain largely unresolved. Here, we show that tidal dynamics can be the main driver of plastic transport closest to the river mouth. Outside the tidal zone, rainfall and river discharge were identified to be more important drivers. We monitored plastic transport in the Odaw river, Ghana during the dry season. The Odaw drains the densely populated city of Accra and discharges into the Gulf of Guinea. Data were collected between March and May 2021 (dry season), using visual counting at four bridges along the river, of which two were located within the tidal zone. We explored the correlations between river plastic transport, and rainfall, tidal dynamics, and river discharge. Finally, we estimated the total plastic mass transport by using item-to-mass conversion data from previously published literature. We observed a peak in plastic transport at the upstream bridge within the tidal zone after an increase in rainfall (7.3 times larger). We found a gradient of the hydrometeorological factors driving plastic transport. Closer to the river mouth, tidal dynamics were more strongly correlated with plastic transport than upstream. The daily mass transport was estimated to be between 1.4–3.8 × 102 kg/d, which is lower than previous model estimates. These results add to the evidence of inconsistent correlations between plastic transport and hydrometeorological variables. Long-term monitoring data is required to further investigate this. The results also support the hypothesis that tidal dynamics are a crucial factor in controlling the emissions of plastics from rivers into the ocean. The findings provide a baseline for the Odaw river during the dry season and allow for comparison with the wet season. The approach adopted here also serves as a blueprint for similar urban river systems, regionally and globally.
Both temporal and spatial aspects of predator management influence survival of a temperate ungulate through early life
Authors: McMillan Brock R. , Hall Jacob T. , Freeman Eric D. , Hersey Kent R. , Larsen Randy T.
Published: February 2023

Recent meta-analyses indicate that predator removal experiments result in marginal increases in prey abundance at best. However, most predator removal studies take place for less than the target prey’s generation time and lack a targeted spatial approach. Our objective was to determine how temporal and spatial aspects of predator control influenced neonate survival of a temperate ungulate. We conducted multiyear coyote (Canis latrans) removals using a crossover experimental design. We found that consecutive years of predator removal increased survival of neonate mule deer (Odocoileus hemionus) more than a single year of removal. We also found that removing coyotes from areas near fawn birth sites increased fawn survival, whereas removing coyotes from areas farther from birth sites did not influence fawn survival. Our results underscore the need for coyote removal programs to (1) employ removal efforts over consecutive years to maximize effectiveness, (2) conduct spatially explicit removal efforts targeting fawning habitat, and (3) occur when the likelihood of additive mortality is high and prey populations have the resources available to grow.
Extensive set of African ancestry-informative markers (AIMs) to study ancestry and population health
Authors: Boudeau Samantha , Ramakodi Meganathan P. , Zhou Yan , Liu Jeffrey C. , Ragin Camille , Kulathinal Rob J.
Published: February 2023

Introduction: Human populations are often highly structured due to differences in genetic ancestry among groups, posing difficulties in associating genes with diseases. Ancestry-informative markers (AIMs) aid in the detection of population stratification and provide an alternative approach to map population-specific alleles to disease. Here, we identify and characterize a novel set of African AIMs that separate populations of African ancestry from other global populations including those of European ancestry.

Methods: Using data from the 1000 Genomes Project, highly informative SNP markers from five African subpopulations were selected based on estimates of informativeness (In) and compared against the European population to generate a final set of 46,737 African ancestry-informative markers (AIMs). The AIMs identified were validated using an independent set and functionally annotated using tools like SIFT, PolyPhen. They were also investigated for representation of commonly used SNP arrays.

Results: This set of African AIMs effectively separates populations of African ancestry from other global populations and further identifies substructure between populations of African ancestry. When a subset of these AIMs was studied in an independent dataset, they differentiated people who self-identify as African American or Black from those who identify their ancestry as primarily European. Most of the AIMs were found to be in their intergenic and intronic regions with only 0.6% in the coding regions of the genome. Most of the commonly used SNP array investigated contained less than 10% of the AIMs.

Discussion: While several functional annotations of both coding and non-coding African AIMs are supported by the literature and linked these high-frequency African alleles to diseases in African populations, more effort is needed to map genes to diseases in these genetically diverse subpopulations. The relative dearth of these African AIMs on current genotyping platforms (the array with the highest fraction, llumina’s Omni 5, harbors less than a quarter of AIMs), further demonstrates a greater need to better represent historically understudied populations.
Flames of transformation: Igniting better mental and physical health for racialized and gendered North Americans
Authors: Shroff Farah Mahrukh Coomi
Published: February 2023

COVID-19 is catalyzing both crises and opportunities for communities of color.1 The crisis of high mental and physical morbidities and mortalities exposes persistent inequities while providing opportunities to celebrate the power of rejuvenated anti-racism movements, fueled partly in response to the extremism of ultra-conservative governments, the circumstances to reflect deeply on racism because of forced stay-at-home-orders, and digital technologies primarily driven by youth. In marking this historical moment of longstanding anti-racism and decolonial struggles, I assert the importance of foregrounding women’s needs. In analyzing racism, rooted in colonialism and white supremacy, and its impacts on mental and physical health status, I focus on improving racialized women’s lives within the larger context, concentrating on the determinants of health. I contend that fanning the flames to scathe the racist and sexist foundations of North American society will break new ground for sharing wealth, bolstering solidarity and sisterhood, and ultimately improving Black, Indigenous, and Women of Color (BIWOC) health. Canadian BIWOC earn approximately 59 cents to the dollar earned by non-racialized men, creating vulnerabilities to economic downturns, such as the one Canada is currently in. BIWOC care aides, at the bottom of the healthcare hierarchy, are emblematic of other Black, Indigenous, and People of Color (BIPOC), who face risks of frontline work, low wages, poor job security, unpaid sick days and so forth. To that end, policy recommendations include employment equity initiatives that hire groups of racialized women who consciously express solidarity with each other. Cultural shifts within institutions will be key to providing safe environments. Improving food security, internet access and BIWOC-related data collection linked to community-based programming while prioritizing research on BIWOC will go a long way toward improving BIWOC health. Addressing racism and sexism within the healthcare system, aiming for equitable diagnostic and treatment foci, will require transformative efforts including determined leadership and buy-in from all levels of staff, long-term training and evaluation programs, audited by BIPOC communities.
Lipid metabolism-related gene signature predicts prognosis and depicts tumor microenvironment immune landscape in gliomas
Authors: Li Junhong , Zhang Shuxin , Chen Siliang , Yuan Yunbo , Zuo Mingrong , Li Tengfei , Wang Zhihao , Liu Yanhui
Published: February 2023

Background

Glioma is the most common primary brain tumor in adults and accounts for more than 70% of brain malignancies. Lipids are crucial components of biological membranes and other structures in cells. Accumulating evidence has supported the role of lipid metabolism in reshaping the tumor immune microenvironment (TME). However, the relationship between the immune TME of glioma and lipid metabolism remain poorly described.

Materials and methods

The RNA-seq data and clinicopathological information of primary glioma patients were downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). An independent RNA-seq dataset from the West China Hospital (WCH) also included in the study. Univariate Cox regression and LASSO Cox regression model was first to determine the prognostic gene signature from lipid metabolism-related genes (LMRGs). Then a risk score named LMRGs-related risk score (LRS) was established and patients were stratified into high and low risk groups according to LRS. The prognostic value of the LRS was further demonstrated by construction of a glioma risk nomogram. ESTIMATE and CIBERSORTx were used to depicted the TME immune landscape. Tumor Immune Dysfunction and Exclusion (TIDE) was utilized to predict the therapeutic response of immune checkpoint blockades (ICB) among glioma patients.

Results

A total of 144 LMRGs were differentially expressed between gliomas and brain tissue. Finally, 11 prognostic LMRGs were included in the construction of LRS. The LRS was demonstrated to be an independent prognostic predictor for glioma patients, and a nomogram consisting of the LRS, IDH mutational status, WHO grade, and radiotherapy showed a C-index of 0.852. LRS values were significantly associated with stromal score, immune score, and ESTIMATE score. CIBERSORTx indicated remarkable differences in the abundance of TME immune cells between patients with high and low LRS risk levels. Based on the results of TIDE algorithm, we speculated that the high-risk group had a greater chance of benefiting from immunotherapy.

Conclusion

The risk model based upon LMRGs could effectively predict prognosis in patients with glioma. Risk score also divided glioma patients into different groups with distinct TME immune characteristics. Immunotherapy is potentially beneficial to glioma patients with certain lipid metabolism profiles.
An mRNA mix redirects dendritic cells towards an antiviral program, inducing anticancer cytotoxic stem cell and central memory CD8+ T cells
Authors: de Mey Wout , Locy Hanne , De Ridder Kirsten , De Schrijver Phaedra , Autaers Dorien , Lakdimi Asma , Esprit Arthur , Franceschini Lorenzo , Thielemans Kris , Verdonck Magali , Breckpot Karine
Published: February 2023

Dendritic cell (DC)-maturation stimuli determine the potency of these antigen-presenting cells and, therefore, the quality of the T-cell response. Here we describe that the maturation of DCs via TriMix mRNA, encoding CD40 ligand, a constitutively active variant of toll-like receptor 4 and the co-stimulatory molecule CD70, enables an antibacterial transcriptional program. Besides, we further show that the DCs are redirected into an antiviral transcriptional program when CD70 mRNA in TriMix is replaced with mRNA encoding interferon-gamma and a decoy interleukin-10 receptor alpha, forming a four-component mixture referred to as TetraMix mRNA. The resulting TetraMixDCs show a high potential to induce tumor antigen-specific T cells within bulk CD8+ T cells. Tumor-specific antigens (TSAs) are emerging and attractive targets for cancer immunotherapy. As T-cell receptors recognizing TSAs are predominantly present on naive CD8+ T cells (TN), we further addressed the activation of tumor antigen-specific T cells when CD8+ TN cells are stimulated by TriMixDCs or TetraMixDCs. In both conditions, the stimulation resulted in a shift from CD8+ TN cells into tumor antigen-specific stem cell-like memory, effector memory and central memory T cells with cytotoxic capacity. These findings suggest that TetraMix mRNA, and the antiviral maturation program it induces in DCs, triggers an antitumor immune reaction in cancer patients.
Modulation by luminal factors on the functions and migration of intestinal innate immunity
Authors: Higashiyama Masaaki , Miura Soichiro , Hokari Ryota
Published: February 2023

Luminal antigens, nutrients, metabolites from commensal bacteria, bile acids, or neuropeptides influence the function and trafficking of immune cells in the intestine. Among the immune cells in the gut, innate lymphoid cells, including macrophages, neutrophils, dendritic cells, mast cells, and innate lymphoid cells, play an important role for the maintenance of intestinal homeostasis through a rapid immune response to luminal pathogens. These innate cells are influenced by several luminal factors, possibly leading to dysregulated gut immunity and intestinal disorders such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and intestinal allergy. Luminal factors are sensed by distinct neuro-immune cell units, which also have a strong impact on immunoregulation of the gut. Immune cell trafficking from the blood stream through the lymphatic organ to lymphatics, an essential function for immune responses, is also modulated by luminal factors. This mini-review examines knowledge of luminal and neural factors that regulate and modulate response and migration of leukocytes including innate immune cells, some of which are clinically associated with pathological intestinal inflammation.
Single-cell clonal tracking of persistent T-cells in allogeneic hematopoietic stem cell transplantation
Authors: Obermayer Benedikt , Keilholz Luisa , Conrad Thomas , Frentsch Marco , Blau Igor-Wolfgang , Vuong Lam , Lesch Stella , Movasshagi Kamran , Tietze-Stolley Carola , Loyal Lucie , Henze Larissa , Penack Olaf , Stervbo Ulrik , Babel Nina , Haas Simon , Beule Dieter , Bullinger Lars , Wittenbecher Friedrich , Na Il-Kang
Published: February 2023

The critical balance between intended and adverse effects in allogeneic hematopoietic stem cell transplantation (alloHSCT) depends on the fate of individual donor T-cells. To this end, we tracked αβT-cell clonotypes during stem cell mobilization treatment with granulocyte-colony stimulating factor (G-CSF) in healthy donors and for six months during immune reconstitution after transfer to transplant recipients. More than 250 αβT-cell clonotypes were tracked from donor to recipient. These clonotypes consisted almost exclusively of CD8+ effector memory T cells (CD8TEM), which exhibited a different transcriptional signature with enhanced effector and cytotoxic functions compared to other CD8TEM. Importantly, these distinct and persisting clonotypes could already be delineated in the donor. We confirmed these phenotypes on the protein level and their potential for selection from the graft. Thus, we identified a transcriptional signature associated with persistence and expansion of donor T-cell clonotypes after alloHSCT that may be exploited for personalized graft manipulation strategies in future studies.
The clinical value of neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) for predicting the occurrence and severity of pneumonia in patients with intracerebral hemorrhage
Authors: Wang Rui-Hong , Wen Wan-Xin , Jiang Ze-Ping , Du Zhen-Ping , Ma Zhao-Hui , Lu Ai-Li , Li Hui-Ping , Yuan Fang , Wu Shi-Biao , Guo Jian-Wen , Cai Ye-Feng , Huang Yan , Wang Li-Xin , Lu Hong-Ji
Published: February 2023

Background

Inflammatory mechanisms play important roles in intracerebral hemorrhage (ICH) and have been linked to the development of stroke-associated pneumonia (SAP). The neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) are inflammatory indexes that influence systemic inflammatory responses after stroke. In this study, we aimed to compare the predictive value of the NLR, SII, SIRI and PLR for SAP in patients with ICH to determine their application potential in the early identification of the severity of pneumonia.

Methods

Patients with ICH in four hospitals were prospectively enrolled. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. Data on the NLR, SII, SIRI and PLR were collected at admission, and the correlation between these factors and the clinical pulmonary infection score (CPIS) was assessed through Spearman’s analysis.

Results

A total of 320 patients were enrolled in this study, among whom 126 (39.4%) developed SAP. The results of the receiver operating characteristic (ROC) analysis revealed that the NLR had the best predictive value for SAP (AUC: 0.748, 95% CI: 0.695-0.801), and this outcome remained significant after adjusting for other confounders in multivariable analysis (RR=1.090, 95% CI: 1.029-1.155). Among the four indexes, Spearman’s analysis showed that the NLR was the most highly correlated with the CPIS (r=0.537, 95% CI: 0.395-0.654). The NLR could effectively predict ICU admission (AUC: 0.732, 95% CI: 0.671-0.786), and this finding remained significant in the multivariable analysis (RR=1.049, 95% CI: 1.009-1.089, P=0.036). Nomograms were created to predict the probability of SAP occurrence and ICU admission. Furthermore, the NLR could predict a good outcome at discharge (AUC: 0.761, 95% CI: 0.707-0.8147).

Conclusions

Among the four indexes, the NLR was the best predictor for SAP occurrence and a poor outcome at discharge in ICH patients. It can therefore be used for the early identification of severe SAP and to predict ICU admission.
Positive faecal immunochemical test predicts the onset of inflammatory bowel disease: A nationwide, propensity score-matched study
Authors: Lee Eunyoung , Lee Gil Ho , Park Bumhee , Ahn Sung Soo , Noh Choong-Kyun
Published: February 2023

Background & aims

The faecal immunochemical test (FIT), a non-invasive test for screening colorectal cancer (CRC), is being increasingly understood to reflect heightened inflammation. We aimed to investigate the association between abnormal FIT results and onset of inflammatory bowel disease (IBD), a disease characterized with chronic gut mucosal inflammation.

Methods

Participants in the Korean National Cancer Screening Program for CRC between 2009–2013 were analysed and divided into positive and negative FIT result groups. The incidence rates of IBD after screening were calculated after excluding cases of haemorrhoids, CRC, and IBD at baseline. Cox proportional hazard analyses were used to identify independent risk factors for IBD occurrence during follow-up, and 1:2 propensity score matching was performed as a sensitivity analysis.

Results

In total, 229,594 and 815,361 participants were assigned to the positive and negative FIT result groups, respectively. The age- and sex-adjusted incidence rates of IBD in participants with positive and negative test results were 1.72 and 0.50 per 10,000 person-years, respectively. Adjusted Cox analysis revealed that FIT positivity was associated with a significantly higher risk of IBD (hazard ratio 2.93, 95% confidence interval: 2.46, 3.47, P <.001), which was consistent for both disease subtypes of ulcerative colitis and Crohn’s disease. The results of Kaplan–Meier analysis in the matched population yielded identical findings.

Conclusions

Abnormal FIT results could be a preceding sign of incident IBD in the general population. Those with positive FIT results and suspected IBD symptoms could benefit from regular screening for early disease detection.
Therapeutic targeting of HCMV-encoded chemokine receptor US28: Progress and challenges
Authors: Berg Christian , Rosenkilde Mette M.
Published: February 2023

The pervasive human cytomegalovirus (HCMV) causes significant morbidity in immunocompromised individuals. Treatment using the current standard-of-care (SOC) is limited by severe toxic adverse effects and anti-viral resistance development. Furthermore, they only affect HCMV in its lytic phase, meaning viral disease is not preventable as latent infection cannot be treated and the viral reservoirs persist. The viral chemokine receptor (vCKR) US28 encoded by HCMV has received much attention in recent years. This broad-spectrum receptor has proven to be a desirable target for development of novel therapeutics through exploitation of its ability to internalize and its role in maintaining latency. Importantly, it is expressed on the surface of infected cells during both lytic and latent infection. US28-targeting small molecules, single-domain antibodies, and fusion toxin proteins have been developed for different treatment strategies, e.g. forcing reactivation of latent virus or using internalization of US28 as a toxin shuttle to kill infected cells. These strategies show promise for providing ways to eliminate latent viral reservoirs and prevent HCMV disease in vulnerable patients. Here, we discuss the progress and challenges of targeting US28 to treat HCMV infection and its associated diseases.
The loss of glycocalyx integrity impairs complement factor H binding and contributes to cyclosporine-induced endothelial cell injury
Authors: Teoh Chia Wei , Riedl Khursigara Magdalena , Ortiz-Sandoval Carolina G. , Park Jee Woo , Li Jun , Bohorquez-Hernandez Arlette , Bruno Valentina , Bowen Emily E. , Freeman Spencer A. , Robinson Lisa A. , Licht Christoph
Published: February 2023

Background

Calcineurin inhibitors (CNIs) are associated with nephrotoxicity, endothelial cell dysfunction, and thrombotic microangiopathy (TMA). Evolving evidence suggests an important role for complement dysregulation in the pathogenesis of CNI-induced TMA. However, the exact mechanism(s) of CNI-induced TMA remain(s) unknown.

Methods

Using blood outgrowth endothelial cells (BOECs) from healthy donors, we evaluated the effects of cyclosporine on endothelial cell integrity. Specifically, we determined complement activation (C3c and C9) and regulation (CD46, CD55, CD59, and complement factor H [CFH] deposition) as these occurred on the endothelial cell surface membrane and glycocalyx.

Results

We found that exposing the endothelium to cyclosporine resulted in a dose- and time-dependent enhancement of complement deposition and cytotoxicity. We, therefore, employed flow cytometry, Western blotting/CFH cofactor assays, and immunofluorescence imaging to determine the expression of complement regulators and the functional activity and localization of CFH. Notably, while cyclosporine led to the upregulation of complement regulators CD46, CD55, and CD59 on the endothelial cell surface, it also diminished the endothelial cell glycocalyx through the shedding of heparan sulfate side chains. The weakened endothelial cell glycocalyx resulted in decreased CFH surface binding and surface cofactor activity.

Conclusion

Our findings confirm a role for complement in cyclosporine-induced endothelial injury and suggest that decreased glycocalyx density, induced by cyclosporine, is a mechanism that leads to complement alternative pathway dysregulation via decreased CFH surface binding and cofactor activity. This mechanism may apply to other secondary TMAs—in which a role for complement has so far not been recognized—and provide a potential therapeutic target and an important marker for patients on calcineurin inhibitors.
Effects of polysaccharides from Lyophyllum decastes (Fr.) Singer on gut microbiota via in vitro-simulated digestion and fermentation
Authors: Zhang Fangfang , Xiao Ying , Pan Liang , Yu Ling , Liu Yanfang , Li Deshun , Liu Xiaojie
Published: February 2023

Introduction

Lyophyllum decastes (Fr.) Singer polysaccharides (LDSPs) have been verified to possess strong biological properties. However, the effects of LDSPs on intestinal microbes and their metabolites have rarely been addressed.

Methods

The in vitro-simulated saliva-gastrointestinal digestion and human fecal fermentation were used to evaluate the effects of LDSPs on non-digestibility and intestinal microflora regulation in the present study.

Results

The results showed a slight increase in the content of the reducing end of the polysaccharide chain and no obvious change in the molecular weight during in vitro digestion. After 24 h in vitro fermentation, LDSPs were degraded and utilized by human gut microbiota, and LDSPs could be transformed into short-chain fatty acids leading to significant (p < 0.05) decrease in the pH of the fermentation solution. The digestion did not remarkably affect the overall structure of LDSPs and 16S rRNA analysis revealed distinct shifts in the gut microbial composition and community diversity of the LDSPs-treated cultures, compared with the control group. Notably, the LDSPs group directed a targeted promotion of the abundance of butyrogenic bacteria, including Blautia, Roseburia, and Bacteroides, and an increase in the n-butyrate level.

Discussion

These findings suggest that LDSPs might be a potential prebiotic to provide a health benefit.
Two new species of Antrodia (Polyporales, Basidiomycota) in western China
Authors: Zhou Hong-Min , Liu Shun , Deng Xiao-Juan , Liu Hong-Gao , Xing Rui , Dai Yu-Cheng , Wu Ying-Da
Published: February 2023

Two new species of Antrodia, A. aridula and A. variispora, are described from western China. Phylogeny based on a six-gene dataset (ITS + nLSU + nSSU + mtSSU + TEF1 + RPB2) demonstrates that samples of the two species form two independent lineages within the clade of Antrodia s.s. and are different in morphology from the existing species of Antrodia. Antrodia aridula is characterized by its annual and resupinate basidiocarps with angular to irregular pores of 2–3 mm each and oblong ellipsoid to cylindrical basidiospores measuring 9–12 × 4.2–5.3 μm, growing on gymnosperm wood in a dry environment. Antrodia variispora is characterized by its annual and resupinate basidiocarps with sinuous or dentate pores with a size of 1–1.5 mm each and oblong ellipsoid, fusiform, pyriform, or cylindrical basidiospores measuring 11.5–16 × 4.5–5.5 μm, growing on the wood of Picea. The differences between the new species and morphologically similar species are discussed in this article.
Francisella tularensis subsp. holarctica wild-type is able to colonize natural aquatic ex vivo biofilms
Authors: Schaudinn Christoph , Rydzewski Kerstin , Meister Beate , Grunow Roland , Heuner Klaus
Published: February 2023

Biofilms are a matrix-associated lifestyle of microbial communities, often enabling survivability and persistence of such bacteria. The objective of this study was to investigate the survival of the wild-type strain A-271 of Francisella tularensis subsp. holarctica (Fth) in a natural aquatic ex vivo biofilm. To that purpose, we allowed Fth A-271 to produce its own biofilm on solid surfaces but also to colonize naturally formed biofilms from aquatic habitats, which were infected with Francisella in the laboratory. The survival rates of the bacteria in biofilms were compared to those of planktonic bacteria as a function of the employed culture condition. It could be shown by light- and electron microscopy that Fth is able to form a complex, matrix-associated biofilm. The biofilm form of Francisella showed longer cultivability on agar plates in natural water when compared to planktonic (free-living) bacteria. Be it as a part of the existing ex vivo biofilm or free-floating above as planktonic bacteria, more than 80% of Francisella were not only able to survive under these conditions for 28 days, but even managed to establish microcolonies and areas with their own exclusive biofilm architecture within the ex vivo biofilm. Here, we can demonstrate for the first time that a Francisella tularensis wild-type strain (Type B) is able to successfully colonize an aquatic multi-species ex vivo biofilm. It is worthwhile to speculate that Fth might become more persistent in the environment when it forms its own biofilm or integrates in an existing one. Multi-species biofilms have been shown to be more resistant against stress compared to single-species biofilms. This may have an important impact on the long-term survival of Francisella in aquatic habitats and infection cycles in nature.