bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term remission of type 2 diabetes after very-low-calorie restriction and related predictors
Authors: Wei Jie , Chen Jie , Wei Xiao , Xiang Xiaoduo , Cheng Qing , Xu Jiechao , Xu Shuhang , Chen Guofang , Liu Chao
Published: September 2022

Purpose

Very low-calorie restriction (VLCR) can induce remission of type 2 diabetes mellitus (T2DM), but its long-term remission and related predictors have not been clarified. The aim of present study is to investigate the effect of VLCR in inducing long-term T2DM remission, and the underlying predictors.

Methods

A total of 61 participants with T2DM who received 9 days of VLCR from Dec 2012 to Oct 2020 were followed up in Nov 2021, and divided into responders and non-responders groups. Responders were defined as HbA1c < 6.5% over at least 3 months in the absence of pharmacotherapy. Clinical characteristics were compared between responders and non-responders. Potential predictors were examined by logistic regression analyses based on clinical data before and after VLCR.

Results

Forty-four participants were successfully followed up, including 19 males and 25 females. Long-term remission was observed in 17 participants (38.64%) after VLCR, with a median 7.83 years. Compared with non-responders, responders had a shorter disease duration, a lower fasting blood glucose (FBG) level, a higher fasting insulin level, and better HOMA-β after VLCR. Besides, acute insulin response (AIR), insulin area under curve in intravenous and oral glucose tolerance test (IVGTT-IAUC and OGTT-IAUC) in responders were higher than those in non-responders after VLCR. Multivariable logistic analysis showed that higher post-VLCR IVGTT-IAUC predicted a longer T2DM remission.

Conclusions

After VLCR, more than one third of the participants presented remission over up to 8 years. The improvement of β-cell function, especially the restoration of first-phase insulin-secreting capacity, could prolongate the remission.
Improved liver lipid catabolism and utilization in growth hormone transgenic common carp (Cyprinus carpio L.) through enhanced lipolytic and fatty acid β-oxidation pathways
Authors: Wu Yunya , Li Rui , Wu Xingxing , Guo Wei , Li Yongming , Song Yanlong , Tao Binbin , Chen Ji , Han Dong , Xie Shouqi , Wang Yaping , Zhu Zuoyan , Hu Wei
Published: September 2022

Growth hormone (GH) transgenic common carp (Cyprinus carpio L.) show desirable aquaculture traits. Their specific growth rate (SGR) and feed efficiency (FE) are approximately 12% and 17% higher than the wild-type (WT) common carp, respectively. However, the mechanisms of lipid catabolism (lipolysis and fatty acid β-oxidation) and utilization in GH transgenic common carp are still unclear. In this study, we firstly compared the lipid metabolism of GH transgenic (initial weight 3.72 ± 0.32 g) and WT (initial weight 3.30 ± 0.28 g) common carp fed with a normal fat level diet (6% lipid, 33% protein) for two months, then compared the growth performance of GH transgenic (initial weight 3.65 ± 0.33 g) and WT (initial weight 3.27 ± 0.26 g) common carp fed with different fat levels diets (6% lipid and 12% lipid, 33% protein) for two months. We found that the lipid content in serum, liver and whole body was significantly reduced in GH transgenic common carp, the hepatic activities of the lipolytic enzymes hormone-sensitive lipase and adipose triglyceride lipase were enhanced, and the hepatic expression level of hormone-sensitive lipase was upregulated. In addition, the mitochondrion numbers were increased, and the expression level of carnitine palmitoyltransferase-1a and carnitine palmitoyltransferase-1b was upregulated in the liver of GH transgenic common carp. GH transgenic common carp showed higher weight gain and SGR than that in WT carp when fed with a normal-fat diet as they did when fed with a high-fat diet, and GH transgenic common carp showed higher FE than that in WT carp when fed with a high-fat diet. These results suggested that the lipid catabolism and utilization was improved in the GH transgenic common carp liver through enhanced lipolytic and fatty acid β-oxidation pathways. Our study provides new insights into improving lipid utilization in some aquaculture fish species.
ER stress promotes mitochondrial DNA mediated type-1 interferon response in beta-cells and interleukin-8 driven neutrophil chemotaxis
Authors: Vig Saurabh , Lambooij Joost M. , Dekkers Mette C. , Otto Frank , Carlotti Françoise , Guigas Bruno , Zaldumbide Arnaud
Published: September 2022

Beta-cell destruction in type 1 diabetes (T1D) results from the combined effect of inflammation and recurrent autoimmunity. Accumulating evidence suggests the engagement of cellular stress during the initial stage of the disease, preceding destruction and triggering immune cell infiltration. While the role of the endoplasmic reticulum (ER) in this process has been largely described, the participation of the other cellular organelles, particularly the mitochondria which are central mediator for beta-cell survival and function, remains poorly investigated. Here, we have explored the contribution of ER stress, in activating type-I interferon signaling and innate immune cell recruitment. Using human beta-cell line EndoC-βH1 exposed to thapsigargin, we demonstrate that induction of cellular stress correlates with mitochondria dysfunction and a significant accumulation of cytosolic mitochondrial DNA (mtDNA) that triggers neutrophils migration by an IL8-dependent mechanism. These results provide a novel mechanistic insight on how ER stress can cause insulitis and may ultimately facilitate the identification of potential targets to protect beta-cells against immune infiltration.
A prediction on the impacts of China’s national emissions trading scheme on CO2 emissions from electricity generation
Authors: Solaymani Saeed
Published: September 2022

One of the government policies that can reduce CO2 emissions is the Emissions Trading Scheme (ETS), which was implemented in the Chinese economy on 16 July 2021. It is the largest ETS in the world, covering 12% of global CO2 emissions. Since this policy has not been experienced in China, it is necessary to predict its impact on CO2 emissions in this country. Furthermore, electricity and heat production is the major contributor to total CO2 emissions from fuel combustion. Therefore, this study attempts to predict the impact of the emissions trading scheme on CO2 emissions from the combustion of coal, oil and natural gas in electricity generation using annual data from 1985 to 2019. For this purpose, this study first predicts CO2 emissions from the combustion of coal, oil and natural gas for electricity generation in power plants using ARIMA and structural Vector Autoregression (SVAR) techniques over the 2020–2030 period. It then estimates the short- and long-run impact of the ETS policy on CO2 emissions from the combustion of coal, oil and natural gas in power plants over the projected period (2020–2030) by employing the ARDL methodology. The results suggest that the ETS policy is effective in reducing the CO2 emissions from the combustion of all fuels in electricity generation over the long-run. This is because of the increase in CO2 emissions from the combustion of these fuels in power plants in the long run, which exceed the threshold value. But in the short-run, it has a negative and statistically significant impact only on CO2 emissions from the natural gas power plants. These results suggest that improving the efficiency of all fuels can significantly reduce CO2 emissions in electricity generation from coal, oil and natural gas in the short- and long-run. They also enable China’s energy policymakers to update the ETS policy in its next phases.
A Study on China coal Price forecasting based on CEEMDAN-GWO-CatBoost hybrid forecasting model under Carbon Neutral Target
Authors: Wang Xiang , Mao Yaqi , Duan Yonghui , Guo Yibin
Published: September 2022

The emission peak and carbon neutrality targets pose a great challenge to carbon emission reduction in the coal industry, and the coal industry will face an all-around deep adjustment. The forecast of coal price is crucial for reducing carbon emissions in the coal industry in an orderly manner under the premise of ensuring national energy security. The volatility and instability of coal prices are a result of multiple influencing factors, making it very difficult to make accurate predictions of coal price changes. We propose in this paper an innovative hybrid forecasting method (CEEMDAN-GWO-CatBoost) for forecasting coal price indexes by combining machine learning models, feature selections, data decomposition, and model interpretation. By combining high forecasting accuracy with good interpretability, this method fills a gap in the field of coal price forecasting. Initially, we examine the factors that influence coal prices from five angles: Supply, demand, macroeconomic factors, freight costs, and substitutes; and we employ Spearman correlation analysis to reduce the complexity of the attribute set and devise a coal price forecasting index system. Secondly, the CEEMDAN method is used to decompose the raw coal price index data into seven intrinsic modal functions and one residual term in order to weaken the volatility of the data caused by complex factors. Next, the CatBoost model hyperparameters are optimized using the Grey Wolf Optimizer algorithm, while the coal price data is fed into the combined forecasting model. Lastly, the SHAP interpretation method is introduced for studying the important indicators affecting coal prices. The experimental results show that the combined CEEMDAN-GWO-CatBoost forecasting model proposed in this paper has significantly better forecasting performance than other comparative models, and the SHAP method employed in this study identifies the macroeconomic environment, freight costs, and coal import volume as significant factors affecting coal prices. As part of the contribution of this paper, specific recommendations are made to the government regarding the formulation of a regulatory policy for the coal industry in the context of carbon neutrality based on the findings of this research.
A cancer stem cell associated gene signature for predicting overall survival of hepatocellular carcinoma
Authors: Liang Xin-Yi , Zhang Yue , He Ya-Nan , Liu Xue-Yi , Ding Zhi-Hao , Zhang Xiao-Dong , Dong Ming-You , Du Run-Lei
Published: September 2022

Hepatocellular carcinoma (HCC) is the most prevalent type of primary liver cancer characterized by high mortality and morbidity rate. The lack of effective treatments and the high frequency of recurrence lead to poor prognosis of patients with HCC. Therefore, it is important to develop robust prediction tools for predicting the prognosis of HCC. Recent studies have shown that cancer stem cells (CSC) participate in HCC progression. The aim of this study was to explore the prognostic value of CSC-related genes and establish a prediction model based on data from The Cancer Genome Atlas (TCGA) database. In this study, 475 CSC-related genes were obtained from the Molecular Signature Database and 160 differentially expressed CSC-related genes in HCC patients were identified using the limma R package in the TCGA database. A total of 79 CSC-related genes were found to be associated with overall survival (OS). Using the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regressions, a 3-gene signature (RAB10, TCOF1, and PSMD14) was constructed. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were constructed to test the prediction performance of the signature. Performance of the signature was validated using the International Cancer Genome Consortium (ICGC) dataset. In addition, immune feature and functional enrichment analyses were carried out to explore the underlying mechanisms. Moreover, a co-expression network was constructed using the weighted gene correlation network analysis (WGCNA) method to select genes significantly associated with risk scores in HCC in the TCGA dataset. The SGO2 gene was found to be significantly associated with risk scores of HCC. In vitro experiments revealed that it can promote HCC cell proliferation. Therefore, SGO2 may be a potential therapeutic target for HCC treatment. The constructed nomogram can help clinicians make decisions about HCC treatment.
Identification and molecular analysis of 11 cases of the PTS gene variants associated with tetrahydrobiopterin deficiency
Authors: Li Lulu , Yang Haihe , Zhao Jinqi , Yang Nan , Gong Lifei , Tang Yue , Kong Yuanyuan
Published: September 2022

Background: Tetrahydrobiopterin deficiency (BH4D) is a rare autosomal recessive amino acid metabolic disease that belongs to a kind of hyperphenylalaninemia (HPA), and 6-pyruvyltetrahydrotrexate synthase (PTPS) deficiency is the most common type of BH4D. This study investigates the clinical and genetic characteristics of 11 PTPS deficiency cases in the Beijing area, identifies the genetic pathogenic factors, and evaluates the value of high-throughput sequencing in the precise diagnosis of PTPS deficiency.

Methods: The Beijing Neonatal Disease Screening Center diagnosed patients with HPA. The study used phenylalanine (Phe) in blood, the ratio of Phe to Thr, urotrexate spectrum analysis, erythrocyte dihydrotrexate reductase (DHPR) activity determination, and high-throughput sequencing as methods. Bioinformatics software analyzed the variants’ pathogenicity and used RT-PCR to identify deep intron variants’ pathogenicity.

Result: Among 635 cases with HPA, 38 cases were diagnosed with BH4D, of which the incidence in HPA was 5.98%. Nine kinds of PTS gene variants were detected, including seven missense variants, one splicing variant, and one deletion variant. The splicing variant c.84–291A>G had three splicing results in vivo: normal length, 79bp pseudoexon insertion, and exon 3 skipping. Bioinformatics and Sanger sequencing were performed to verify the identified variants.

Conclusion: High-throughput sequencing is a helpful tool for clinical diagnosis and differential diagnosis of BH4D. This study confirms that c.84–291A>G is the hot spot variant of PTPS deficiency, and it is the first reported variant with a new splicing pattern in vivo. A novel deletion variant c.84_163del (p.Lys29Cysfs∗9) was found to enrich the genetic variant spectrum of the disease.
Comprehensive analysis of the expression of N6-methyladenosine RNA methylation regulators in pulmonary artery hypertension
Authors: Zheng Hao , Hua Jing , Li Hongpeng , He Wenjuan , Chen Xiangyu , Ji Yingqun , Li Qiang
Published: September 2022

Background: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary vascular remodeling. The development of PAH involves N6-methyladenosine (m6A) modification. However, the functional role of m6A regulators in PAH and the underlying regulatory mechanisms remain unknown so far.

Methods: Microarray data (GSE149713) for monocrotaline induced PAH (MCT-PAH) rat models were downloaded and screened for differentially expressed genes (DEGs) and m6A regulators. Next, we screened for differentially expressed m6A regulators in endothelial cells (ECs), smooth muscle cells (SMCs), fibroblasts, interstitial macrophages, NK cells, B cells, T cells, regulatory T cells (Tregs) using scRNA sequencing data. The target DEGs of m6A regulators in ECs, SMCs, fibroblasts, and Tregs were functionally annotated using the Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In addition, the cellular interaction analysis was performed to reveal the receptor—ligand pairs regulated by m6A regulators. Pseudo-time trajectory analyses were performed and a ceRNA network of lncRNAs-miRNAs-mRNAs was constructed in SMCs. Furthermore, the RNA transcriptome sequencing data for the SMCs isolated from idiopathic PAH (IPAH) patients (GSE144274) were validated for differentially expressed m6A regulators. Moreover, the HNRNPA2B1 levels in the lung samples from PAH patients and MCT-PAH were determined using immunohistochemistry.

Results: The m6A regulators were observed to be dysregulated in PAH. HNRNPA2B1expression level was increased in the PASMCs of scRNAs and IPAH patients. The target DEGs of HNRNPA2B1 were enriched in the regulation of muscle cell differentiation and vasculature development in PASMCs. The HNRNPA2B1 expression levels determined were consistent with the proliferation-related and collagen synthesis-related gene COL4A1. Moreover, the predicted transcription factors (TFs) foxd2/3 and NFκB could be involved in the regulation of HNRNPA2B1. HNRNPA2B1 might be regulating SMCs proliferation and phenotypic transition via rno-miR-330–3p/TGFβR3 and rno-miR-125a-3p/slc39a1. In addition, HNRNPA2B1 was observed to be highly expressed in the lung samples from MCT-PAH rat models and patients with PAH.

Conclusion: In summary, the present study identified certain key functional m6A regulators that are involved in pulmonary vascular remodeling. The investigation of m6A patterns might be promising and provide biomarkers for diagnosis and treatment of PAH in the future.
The oxygen carrier M101 alleviates complement activation, which may be beneficial for donor organ preservation
Authors: Puissant-Lubrano Bénédicte , Bouthemy Charlène , Congy-Jolivet Nicolas , Milhes Jean , Minville Vincent , Kamar Nassim , Demini Leïla , Zal Franck , Renaudineau Yves
Published: September 2022

During organ transplantation, ischemia/reperfusion injury and pre-formed anti-HLA antibodies are the main cause of delayed graft function and recovery through the activation of the complement system. By supplying oxygen during transplantation, M101 is suspected to avoid complement activation, however, a direct effect exerted by M101 on this pathway is unknown. This was tested by using functional assays (lymphocytotoxic crossmatch test, C3d Luminex-based assay, 50% complement hemolysis [CH50], and 50% alternative complement pathway [AP50/AH50]), and quantitative assays (C3, C3a, C4, C5, C5a, C6, C7, C8, C9 and sC5b-9). M101 interferes with the anti-HLA lymphocytotoxic crossmatch assay, and this effect is complement-dependent as M101 inhibits the classical complement pathway (CH50) in a dose-dependent and stable manner. Such inhibition was independent from a proteolytic effect (fractions C3 to C9) but related to a dose-dependent inhibition of the C3 convertase as demonstrated by exploring downstream the release of the anaphylatoxins (C3a and C5a), C3d, and sC5b-9. The C3 convertase inhibition in the presence of M101 was further demonstrated in the AP50/AH50 assay. In conclusion, the use of M101 avoids the activation of the complement pathway, which constitutes an additional advantage for this extracellular hemoglobin to preserve grafts from ischemia/reperfusion injury and preformed anti-HLA antibodies.
Immunoregulation and clinical significance of neutrophils/NETs-ANGPT2 in tumor microenvironment of gastric cancer
Authors: Yang Shifeng , Zou Xiaoming , Li Jiacheng , Yang Hao , Zhang Ange , Zhu Yanli , Zhu Lei , Zhang Lisha
Published: September 2022

Although significant progress has been made in the study of gastric cancer (GC), clinicians lack reliable protein markers for accurate diagnosis and tumor stratification. Neutrophil extracellular traps (NETs) are networks of extracellular fibers composed of DNA from neutrophils. We have previously reported that abundant NETs are deposited in GC, damaging human umbilical vein endothelial cells (HUVECs) and triggering the release of tissue factors, leading to a hypercoagulable state in GC. However, the specific effects of NETs on HUVECs are unclear. We aimed to explore the functional changes caused by NETs on HUVECs, providing evidence that NETs may fuel GC progression. Through quantitative proteomics, we identified 6182 differentially expressed proteins in NET-stimulated HUVECs by TMT. The reliability of the TMT technique was confirmed by parallel reaction monitoring (PRM) analysis of 17 differentially expressed proteins. Through bioinformatics analysis, we found that NETs upregulate ANGPT2 in HUVECs. We comprehensively analyzed the prognosis, biological function, immune response, and therapeutic value of ANGPT2 in GC. We found that overexpression of ANGPT2 in GC is associated with poor prognosis and potentially regulates multiple biological functions. At the same time, ANGPT2 also predicted immunotherapeutic and chemotherapeutic responses in GC. In conclusion, NETs promoted ANGPT2 overexpression in the GC microenvironment. In the future, the neutrophil/NETs-ANGPT2 axis may provide a new target for the treatment of GC.
Single-cell transcriptome analysis reveals T-cell exhaustion in denosumab-treated giant cell tumor of bone
Authors: Yang Meiling , Wang Fen , Lu Guohao , Cheng Mingzhe , Zhao Wei , Zou Changye
Published: September 2022

Denosumab (DMAB), a human monoclonal antibody against the receptor activator of the nuclear factor-kappa B ligand, is used for the treatment for unresectable giant cell tumor of bone (GCTB). However, little is known about the molecular and functional characteristics of GCTB-infiltrating lymphocytes after DMAB treatment. Here, we performed single-cell RNA sequencing and immunostaining assays to delineate the immune landscape of GCTB in the presence and absence of DMAB. We found that exhausted CD8+ T cells were preferentially enriched in DMAB-treated GCTB. A distinct M2-skewed type of tumor-associated macrophages (TAMs) comprises the majority of GCTB TAMs. We identified cytokines, including interleukin-10, and inhibitory receptors of M2 TAMs as important mediators of CD8+ T cell exhaustion. We further revealed that DMAB treatment notably increased the expression levels of periostin (POSTN) in GCTB cells. Furthermore, POSTN expression was transcriptionally regulated by c-FOS signaling and correlated with GCTB recurrence in patients after DMAB treatment. Collectively, our findings reveal that CD8+ T-cells undergo unappreciated exhaustion during DMAB therapy and that GCTB cell-derived POSTN educates TAMs and establishes a microenvironmental niche that facilitates GCTB recurrence.
HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm
Authors: Adorni Maria Pia , Palumbo Marcella , Marchi Cinzia , Zimetti Francesca , Ossoli Alice , Turri Marta , Bernini Franco , Hollan Ivana , Moláček Jiří , Treska Vladislav , Ronda Nicoletta
Published: September 2022

Background

The etiopathogenesis of abdominal aortic aneurysm (AAA) is still unclarified, but vascular inflammation and matrix metalloproteases activation have a recognized role in AAA development and progression. Circulating lipoproteins are involved in tissue inflammation and repair, particularly through the regulation of intracellular cholesterol, whose excess is associated to cell damage and proinflammatory activation. We analyzed lipoprotein metabolism and function in AAA and in control vasculopathic patients, to highlight possible non-atherosclerosis-related, specific abnormalities.

Methods

We measured fluorometrically serum esterified/total cholesterol ratio, as an index of lecithin-cholesterol acyltransferase (LCAT) activity, and cholesteryl ester transfer protein (CETP) activity in patients referred to vascular surgery either for AAA (n=30) or stenotic aortic/peripheral atherosclerosis (n=21) having similar burden of cardiovascular risk factors and disease. We measured high-density lipoprotein (HDL)-cholesterol efflux capacity (CEC), through the ATP-binding cassette G1 (ABCG1) and A1 (ABCA1) pathways and serum cell cholesterol loading capacity (CLC), by radioisotopic and fluorimetric methods, respectively.

Results

We found higher LCAT (+23%; p < 0.0001) and CETP (+49%; p < 0.0001) activity in AAA sera. HDL ABCG1-CEC was lower (−16%; p < 0.001) and ABCA1-CEC was higher (+31.7%; p < 0.0001) in AAA. Stratification suggests that smoking may partly contribute to these modifications. CEC and CETP activity correlated with CLC only in AAA.

Conclusions

We demonstrated that compared to patients with stenotic atherosclerosis, patients with AAA had altered HDL metabolism and functions involved in their anti-inflammatory and tissue repair activity, particularly through the ABCG1-related intracellular signaling. Clarifying the relevance of this mechanism for AAA evolution might help in developing new diagnostic parameters and therapeutic targets for the early management of this condition.
Tissue-resident memory T cells in chronic liver diseases: Phenotype, development and function
Authors: Li Yikang , You Zhengrui , Tang Ruqi , Ma Xiong
Published: September 2022

Tissue-resident memory (TRM) T cells are a unique subset of memory T cells that are critical for the first line of defense against pathogens or antigens in peripheral non-lymphoid tissues such as liver, gut, and skin. Generally, TRM cells are well adapted to the local environment in a tissue-specific manner and typically do not circulate but persist in tissues, distinguishing them from other memory T cell lineages. There is strong evidence that liver TRM cells provide a robust adaptive immune response to potential threats. Indeed, the potent effector function of hepatic TRM cells makes it essential for chronic liver diseases, including viral and parasite infection, autoimmune liver diseases (AILD), nonalcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC) and liver transplantation. Manipulation of hepatic TRM cells might provide novel promising strategies for precision immunotherapy of chronic liver diseases. Here, we provide insights into the phenotype of hepatic TRM cells through surface markers, transcriptional profiles and effector functions, discuss the development of hepatic TRM cells in terms of cellular origin and factors affecting their development, analyze the role of hepatic TRM cells in chronic liver diseases, as well as share our perspectives on the current status of hepatic TRM cell research.
IL36G is associated with cutaneous antiviral competence in psoriasis
Authors: Lu You-Wang , Chen Yong-Jun , Shi Nian , Yang Lu-Hui , Wang Hong-Mei , Dong Rong-Jing , Kuang Yi-Qun , Li Yu-Ye
Published: September 2022

Background

Psoriasis is a common inflammatory skin disease that has a great impact on patients’ physical and mental health. However, the causes and underlying molecular mechanisms of psoriasis are still largely unknown.

Methods

The expression profiles of genes from psoriatic lesion samples and skin samples from healthy controls were integrated via the sva software package, and differentially expressed genes (DEGs) between psoriasis and healthy skin were screened by the limma package. Furthermore, GO and KEGG pathway enrichments for the DEGs were performed using the Clusterprofiler package. Protein–protein interaction (PPI) networks for the DEGs were then constructed to identify hub genes. scGESA analysis was performed on a single-cell RNA sequencing dataset via irGSEA. In order to find the cytokines correlated with the hub genes expression, single cell weighted gene co-expression network analyses (scWGCNA) were utilized to build a gene co-expression network. Furthermore, the featured genes of psoriasis found in suprabasal keratinocytes were intersected with hub genes. We then analyzed the expression of the intersection genes and cytokines in the integrated dataset. After that, we used other datasets to reveal the changes in the intersection genes’ expression levels during biological therapy. The relationship between intersection genes and PASI scores was also explored.

Results

We identified 148 DEGs between psoriatic and healthy samples. GO and KEGG pathway enrichment analysis suggested that DEGs are mainly involved in the defense response to other organisms. The PPI network showed that 11 antiviral proteins (AVPs) were hub genes. scGSEA analysis in the single-cell transcriptome dataset showed that those hub genes are highly expressed in keratinocytes, especially in suprabasal keratinocytes. ISG15, MX1, IFI44L, and IFI27 were the characteristic genes of psoriasis in suprabasal keratinocytes. scWGCNA showed that three cytokines—IL36G, MIF, and IL17RA—were co-expressed in the turquoise module. Only interleukin-36 gamma (IL36G) was positively correlated with AVPs in the integrated dataset. IL36G and AVPs were found co-expressed in a substantial number of suprabasal keratinocytes. Furthermore, we found that the expression levels of IL36G and the 4 AVPs showed positive correlation with PASI score in patients with psoriasis, and that these levels decreased significantly during treatment with biological therapies, but not with methotrexate.

Conclusion

IL36G and antiviral proteins may be closely related with the pathogenesis of psoriasis, and they may represent new candidate molecular markers for the occurrence and severity of psoriasis.
Cigarette smoke exposure reduces hemorrhagic shock induced circulatory dysfunction in mice with attenuated glucocorticoid receptor function
Authors: Wepler Martin , Preuss Jonathan M. , Tilp Cornelia , Keck Martina , Blender Jochen , Wachter Ulrich , Merz Tamara , Vogt Josef , Kress Sandra , Gröger Michael , Hoffmann Andrea , Fink Marina , Calzia Enrico , Burret Ute , Radermacher Peter , Tuckermann Jan P. , Vettorazzi Sabine
Published: September 2022

Introduction

We previously showed that attenuated glucocorticoid receptor (GR) function in mice (GRdim/dim) aggravates systemic hypotension and impairs organ function during endotoxic shock. Hemorrhagic shock (HS) causes impaired organ perfusion, which leads to tissue hypoxia and inflammation with risk of organ failure. Lung co-morbidities like chronic obstructive pulmonary disease (COPD) can aggravate tissue hypoxia via alveolar hypoxia. The most common cause for COPD is cigarette smoke (CS) exposure. Therefore, we hypothesized that affecting GR function in mice (GRdim/dim) and pre-traumatic CS exposure would further impair hemodynamic stability and organ function after HS.

Methods

After 3 weeks of CS exposure, anesthetized and mechanically ventilated GRdim/dim and GR+/+ mice underwent pressure-controlled HS for 1h via blood withdrawal (mean arterial pressure (MAP) 35mmHg), followed by 4h of resuscitation with re-transfusion of shed blood, colloid fluid infusion and, if necessary, continuous intravenous norepinephrine. Acid–base status and organ function were assessed together with metabolic pathways. Blood and organs were collected at the end of the experiment for analysis of cytokines, corticosterone level, and mitochondrial respiratory capacity. Data is presented as median and interquartile range.

Results

Nor CS exposure neither attenuated GR function affected survival. Non-CS GRdim/dim mice had a higher need of norepinephrine to keep target hemodynamics compared to GR+/+ mice. In contrast, after CS exposure norepinephrine need did not differ significantly between GRdim/dim and GR+/+ mice. Non-CS GRdim/dim mice presented with a lower pH and increased blood lactate levels compared to GR+/+ mice, but not CS exposed mice. Also, higher plasma concentrations of some pro-inflammatory cytokines were observed in non-CS GRdim/dim compared to GR+/+ mice, but not in the CS group. With regards to metabolic measurements, CS exposure led to an increased lipolysis in GRdim/dim compared to GR+/+ mice, but not in non-CS exposed animals.

Conclusion

Whether less metabolic acidosis or increased lipolysis is the reason or the consequence for the trend towards lower catecholamine need in CS exposed GRdim/dim mice warrants further investigation.
Dok3 restrains neutrophil production of calprotectin during TLR4 sensing of SARS-CoV-2 spike protein
Authors: Loh Jia Tong , Teo Joey Kay Hui , Lam Kong-Peng
Published: September 2022

Increased neutrophils and elevated level of circulating calprotectin are hallmarks of severe COVID-19 and they contribute to the dysregulated immune responses and cytokine storm in susceptible patients. However, the precise mechanism controlling calprotectin production during SARS-CoV-2 infection remains elusive. In this study, we showed that Dok3 adaptor restrains calprotectin production by neutrophils in response to SARS-CoV-2 spike (S) protein engagement of TLR4. Dok3 recruits SHP-2 to mediate the de-phosphorylation of MyD88 at Y257, thereby attenuating downstream JAK2-STAT3 signaling and calprotectin production. Blocking of TLR4, JAK2 and STAT3 signaling could prevent excessive production of calprotectin by Dok3-/- neutrophils, revealing new targets for potential COVID-19 therapy. As S protein from SARS-CoV-2 Delta and Omicron variants can activate TLR4-driven calprotectin production in Dok3-/- neutrophils, our study suggests that targeting calprotectin production may be an effective strategy to combat severe COVID-19 manifestations associated with these emerging variants.
Mechanisms on chemotherapy resistance of colorectal cancer stem cells and research progress of reverse transformation: A mini-review
Authors: Chen Lei , Yang Funing , Chen Si , Tai Jiandong
Published: September 2022

Tumor recurrence and chemotherapy resistance are mainly responsible for poor prognosis in colorectal cancer (CRC) patients. Cancer stem cell (CSC) has been identified in many solid tumors, including CRC. Additionally, CSC cannot be completely killed during chemotherapy and develops resistance to chemotherapeutic drugs, which is the main reason for tumor recurrence. This study reviews the main mechanisms of CSC chemotherapy resistance in CRC, including activation of DNA damage checkpoints, epithelial-mesenchymal transition (EMT), inhibition of the overexpression of antiapoptotic regulatory factors, overexpression of ATP-binding cassette (ABC) transporters, maintenance of reactive oxygen species (ROS) levels, and the dormant state of CSC. Advances in research to reverse chemotherapy resistance are also discussed. Our study can provide the promising potential for eliminating CSC and preventing tumor progression for CRC treatment.
Relationships among microbiota, gastric cancer, and immunotherapy
Authors: Li Yuzhen , Huang Xiaona , Tong Desheng , Jiang Chenyu , Zhu Xiaodan , Wei Zhipeng , Gong Tingjie , Jin Chunhui
Published: September 2022

Currently, conventional neoadjuvant therapy or postoperative adjuvant therapy, such as chemotherapy and radiation therapy, can only bring limited survival benefits to gastric cancer (GC). Median survival after palliative chemotherapy is also low, at about 8–10 months. Immunotargeting is a new option for the treatment of GC, but has not been widely replicated. The highly immunosuppressed tumor microenvironment (TME) discounts the efficacy of immunotherapy for GC. Therefore, new strategies are needed to enhance the immune response of the TME. This paper reviewed the relationship between microorganisms and GC, potential links between microorganisms and immunotherapy and research of microorganisms combined immunotherapy.
Long-term postural control in elite athletes following mild traumatic brain injury
Authors: Al-Husseini Ali , Gard Anna , Fransson Per-Anders , Tegner Yelverton , Magnusson Måns , Marklund Niklas , Tjernström Fredrik
Published: September 2022

Background

Traumas to the head and neck are common in sports and often affects otherwise healthy young individuals. Sports-related concussions (SRC), defined as a mild traumatic brain injury (mTBI), may inflict persistent neck and shoulder pain, and headache, but also more complex symptoms, such as imbalance, dizziness, and visual disturbances. These more complex symptoms are difficult to identify with standard health care diagnostic procedures.

Objective

To investigate postural control in a group of former elite athletes with persistent post-concussive symptoms (PPCS) at least 6 months after the incident.

Method

Postural control was examined using posturography during quiet stance and randomized balance perturbations with eyes open and eyes closed. Randomized balance perturbations were used to examine motor learning through sensorimotor adaptation. Force platform recordings were converted to reflect the energy used to maintain balance and spectrally categorized into total energy used, energy used for smooth corrective changes of posture (i.e., <0.1 Hz), and energy used for fast corrective movements to maintain balance (i.e., >0.1 Hz).

Results

The mTBI group included 20 (13 males, mean age 26.6 years) elite athletes with PPCS and the control group included 12 athletes (9 males, mean age 26.4 years) with no history of SRC. The mTBI group used significantly more energy during balance perturbations than controls: +143% total energy, p = 0.004; +122% low frequency energy, p = 0.007; and +162% high frequency energy, p = 0.004. The mTBI subjects also adapted less to the balance perturbations than controls in total (18% mTBI vs. 37% controls, p = 0.042), low frequency (24% mTBI vs. 42% controls, p = 0.046), and high frequency (6% mTBI vs. 28% controls, p = 0.040). The mTBI subjects used significantly more energy during quiet stance than controls: +128% total energy, p = 0.034; +136% low-frequency energy, p = 0.048; and +109% high-frequency energy, p = 0.015.

Conclusion

Athletes with previous mTBI and PPCS used more energy to stand compared to controls during balance perturbations and quiet stance and had diminished sensorimotor adaptation. Sports-related concussions are able to affect postural control and motor learning.
Clinical relevance of glucose metrics during the early brain injury period after aneurysmal subarachnoid hemorrhage: An opportunity for continuous glucose monitoring
Authors: Santana Daniel , Mosteiro Alejandra , Pedrosa Leire , Llull Laura , Torné Ramón , Amaro Sergi
Published: September 2022

Hyperglycaemia, hypoglycaemia and higher glucose variability during the Early Brain Injury (EBI) period of aneurysmal subarachnoid hemorrhage (aSAH) have been associated with poor clinical outcome. However, it is unclear whether these associations are due to direct glucose-driven injury or if hyperglycaemia simply acts as a marker of initial severity. Actually, strict glucose control with intensive insulin therapy has not been demonstrated as an effective strategy for improving clinical outcomes after aSAH. Currently published studies describing an association between hyperglycaemia and prognosis in aSAH patients have been based on isolated glucose measurements and did not incorporate comprehensive dynamic evaluations, such as those derived from subcutaneous continuous glucose monitoring devices (CMG). Arguably, a more accurate knowledge on glycaemic patterns during the acute phase of aSAH could increase our understanding of the relevance of glycaemia as a prognostic factor in this disease as well as to underpin its contribution to secondary focal and diffuse brain injury. Herein, we have summarized the available evidence on the diagnostic and prognostic relevance of glucose metrics during the acute phase of cerebrovascular diseases, focusing in the EBI period after aSAH. Overall, obtaining a more precise scope of acute longitudinal glucose profiles could eventually be useful for improving glucose management protocols in the setting of acute aSAH and to advance toward a more personalized management of aSAH patients during the EBI phase.
Exploring the effects of head movements and accompanying gaze fixation switch on steady-state visual evoked potential
Authors: Duan Junyi , Li Songwei , Ling Li , Zhang Ning , Meng Jianjun
Published: September 2022

In a realistic steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) application like driving a car or controlling a quadrotor, observing the surrounding environment while simultaneously gazing at the stimulus is necessary. This kind of application inevitably could cause head movements and variation of the accompanying gaze fixation point, which might affect the SSVEP and BCI’s performance. However, few papers studied the effects of head movements and gaze fixation switch on SSVEP response, and the corresponding BCI performance. This study aimed to explore these effects by designing a new ball tracking paradigm in a virtual reality (VR) environment with two different moving tasks, i.e., the following and free moving tasks, and three moving patterns, pitch, yaw, and static. Sixteen subjects were recruited to conduct a BCI VR experiment. The offline data analysis showed that head moving patterns [F(2, 30) = 9.369, p = 0.001, effect size = 0.384] resulted in significantly different BCI decoding performance but the moving tasks had no effect on the results [F(1, 15) = 3.484, p = 0.082, effect size = 0.188]. Besides, the canonical correlation analysis (CCA) and filter bank canonical correlation analysis (FBCCA) accuracy were better than the PSDA and MEC methods in all of the conditions. These results implied that head movement could significantly affect the SSVEP performance but it was possible to switch gaze fixation to interact with the surroundings in a realistic BCI application.
The sense of agency in emerging technologies for human–computer integration: A review
Authors: Cornelio Patricia , Haggard Patrick , Hornbaek Kasper , Georgiou Orestis , Bergström Joanna , Subramanian Sriram , Obrist Marianna
Published: September 2022

Human–computer integration is an emerging area in which the boundary between humans and technology is blurred as users and computers work collaboratively and share agency to execute tasks. The sense of agency (SoA) is an experience that arises by a combination of a voluntary motor action and sensory evidence whether the corresponding body movements have somehow influenced the course of external events. The SoA is not only a key part of our experiences in daily life but also in our interaction with technology as it gives us the feeling of “I did that” as opposed to “the system did that,” thus supporting a feeling of being in control. This feeling becomes critical with human–computer integration, wherein emerging technology directly influences people’s body, their actions, and the resulting outcomes. In this review, we analyse and classify current integration technologies based on what we currently know about agency in the literature, and propose a distinction between body augmentation, action augmentation, and outcome augmentation. For each category, we describe agency considerations and markers of differentiation that illustrate a relationship between assistance level (low, high), agency delegation (human, technology), and integration type (fusion, symbiosis). We conclude with a reflection on the opportunities and challenges of integrating humans with computers, and finalise with an expanded definition of human–computer integration including agency aspects which we consider to be particularly relevant. The aim this review is to provide researchers and practitioners with guidelines to situate their work within the integration research agenda and consider the implications of any technologies on SoA, and thus overall user experience when designing future technology.
A quasi-experimental study provides evidence that registered dietitian nutritionist care is aligned with the Academy of Nutrition and Dietetics evidence-based nutrition practice guidelines for type 1 and 2 diabetes
Authors: Lamers-Johnson Erin , Kelley Kathryn , Knippen Kerri Lynn , Feddersen Kimberly , Sánchez Damien M. , Parrott J. Scott , Colin Casey , Papoutsakis Constantina , Jimenez Elizabeth Yakes
Published: September 2022

Background

One previous study examined implementation of evidence-based nutrition practice guidelines (EBNPG).

Objectives

To describe alignment of registered dietitian nutritionists' (RDNs) documented nutrition care with the Academy of Nutrition and Dietetics' EBNPG for Type 1 and Type 2 diabetes and examine impact of a midpoint training on care alignment with the guideline.

Methods

In this 2-year, quasi-experimental study, 19 RDNs providing outpatient medical nutrition therapy to adults with diabetes (n= 562) documented 787 initial and follow-up encounters. At study midpoint, RDNs received a guideline content training. A validated, automated tool was used to match standardized nutrition care process terminology (NCPT) in the documentation to NCPT expected to represent guideline implementation. A congruence score ranging from 0 (recommendation not identified) to 4 (recommendation fully implemented) was generated based on matching. Multilevel linear regression was used to examine pre-to-post training changes in congruence scores.

Results

Most patients (~75%) had only one documented RDN encounter. At least one guideline recommendation was fully implemented in 67% of encounters. The recommendations “individualize macronutrient composition” and “education on glucose monitoring” (partially or fully implemented in 85 and 79% of encounters, respectively) were most frequently implemented. The mean encounter congruence scores were not different from pre-to-post guideline training (n= 19 RDNs, 519 encounters pre-training;n= 14 RDNs, 204 encounters post-training; β = −0.06, SE = 0.04; 95% CI: −0.14, 0.03).

Conclusions

Most RDN encounters had documented evidence that at least one recommendation from the EBNPG was implemented. The most frequently implemented recommendations were related to improving glycemic control. A midpoint guideline training had no impact on alignment of care with the guideline.
Quick classification of strong-aroma types of base Baijiu using potentiometric and voltammetric electronic tongue combined with chemometric techniques
Authors: Ao Ling , Guo Kai , Dai Xinran , Dong Wei , Sun Xiaotao , Sun Baoguo , Sun Jinyuan , Liu Guoying , Li Anjun , Li Hehe , Zheng Fuping
Published: September 2022

Nowadays, the classification of strong-aroma types of base Baijiu (base SAB) is mainly achieved by human sensory evaluation. However, prolonged tasting brings difficulties for sommeliers in guaranteeing the consistency of results, and may even cause health problems. Herein, an electronic tongue (E-Tongue) combined with a gas chromatography-mass spectrometry (GC-MS) method was successfully developed to grade high-alcoholic base SAB. The E-tongue was capable of identifying base SAB samples into four grades by a discriminant function analysis (DFA) model based on human sensory evaluation results. More importantly, it could effectively and rapidly predict the quality grade of unknown base SAB with an average accuracy up to 95%. The differences of chemical components between base SAB samples were studied by the GC-MS analysis and 52 aroma compounds were identified. The qualitative and quantitative results showed that with the increase of base SAB grade, the varieties and contents of aroma compounds increased. Overall, the comprehensive analysis of E-tongue data and GC-MS results could be in good agreement with human sensory evaluation results, which also proved that the newly developed method has a potential to be a useful alternative to the overall quality grading of base Baijiu.