bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of LGR5-positive mesenchymal cells in craniofacial development
Authors: Olbertová Kristýna , Hrčkulák Dušan , Kříž Vítězslav , Jesionek Wojciech , Kubovčiak Jan , Ešner Milan , Kořínek Vladimír , Buchtová Marcela
Published: September 2022

Leucine Rich Repeat Containing G Protein-Coupled Receptor 5 (LGR5), a Wnt pathway member, has been previously recognised as a stem cell marker in numerous epithelial tissues. In this study, we used Lgr5-EGFP-CreERT2 mice to analyse the distribution of LGR5-positive cells during craniofacial development. LGR5 expressing cells were primarily located in the mesenchyme adjacent to the craniofacial epithelial structures undergoing folding, such as the nasopharyngeal duct, lingual groove, and vomeronasal organ. To follow the fate of LGR5-positive cells, we performed lineage tracing using an inducible Cre knock-in allele in combination with Rosa26-tdTomato reporter mice. The slight expansion of LGR5-positive cells was found around the vomeronasal organ, in the nasal cavity, and around the epithelium in the lingual groove. However, most LGR5 expressing cells remained in their original location, possibly supporting their signalling function for adjacent epithelium rather than exerting their role as progenitor cells for the craniofacial structures. Moreover, Lgr5 knockout mice displayed distinct defects in LGR5-positive areas, especially in the reduction of the nasopharyngeal duct, the alteration of the palatal shelves shape, abnormal epithelial folding in the lingual groove area, and the disruption of salivary gland development. The latter defect manifested as an atypical number and localisation of the glandular ducts. The gene expression of several Wnt pathway members (Rspo1-3, Axin2) was altered in Lgr5-deficient animals. However, the difference was not found in sorted EGFP-positive cells obtained from Lgr5+/+ and Lgr5−/− animals. Expression profiling of LGR5-positive cells revealed the expression of several markers of mesenchymal cells, antagonists, as well as agonists, of Wnt signalling, and molecules associated with the basal membrane. Therefore, LGR5-positive cells in the craniofacial area represent a very specific population of mesenchymal cells adjacent to the epithelium undergoing folding or groove formation. Our results indicate a possible novel role of LGR5 in the regulation of morphogenetic processes during the formation of complex epithelial structures in the craniofacial areas, a role which is not related to the stem cell properties of LGR5-positive cells as was previously defined for various epithelial tissues.
Flow-induced glycocalyx formation and cell alignment of HUVECs compared to iPSC-derived ECs for tissue engineering applications
Authors: Lindner Marcus , Laporte Anna , Elomaa Laura , Lee-Thedieck Cornelia , Olmer Ruth , Weinhart Marie
Published: September 2022

The relevance of cellular in vitro models highly depends on their ability to mimic the physiological environment of the respective tissue or cell niche. Static culture conditions are often unsuitable, especially for endothelial models, since they completely neglect the physiological surface shear stress and corresponding reactions of endothelial cells (ECs) such as alignment in the direction of flow. Furthermore, formation and maturation of the glycocalyx, the essential polysaccharide layer covering all endothelial surfaces and regulating diverse processes, is highly dependent on applied fluid flow. This fragile but utterly important macromolecular layer is hard to analyze, its importance is often underestimated and accordingly neglected in many endothelial models. Therefore, we exposed human umbilical vein ECs (HUVECs) and human induced pluripotent stem cell-derived ECs (iPSC-ECs) as two relevant EC models in a side-by-side comparison to static and physiological dynamic (6.6 dyn cm−2) culture conditions. Both cell types demonstrated an elongation and alignment along the flow direction, some distinct changes in glycocalyx composition on the surface regarding the main glycosaminoglycan components heparan sulfate, chondroitin sulfate or hyaluronic acid as well as an increased and thereby improved glycocalyx thickness and functionality when cultured under homogeneous fluid flow. Thus, we were able to demonstrate the maturity of the employed iPSC-EC model regarding its ability to sense fluid flow along with the general importance of physiological shear stress for glycocalyx formation. Additionally, we investigated EC monolayer integrity with and without application of surface shear stress, revealing a comparable existence of tight junctions for all conditions and a reorganization of the cytoskeleton upon dynamic culture leading to an increased formation of focal adhesions. We then fabricated cell sheets of EC monolayers after static and dynamic culture via non-enzymatic detachment using thermoresponsive polymer coatings as culture substrates. In a first proof-of-concept we were able to transfer an aligned iPSC-EC sheet to a 3D-printed scaffold thereby making a step in the direction of vascular modelling. We envision these results to be a valuable contribution to improvements of in vitro endothelial models and vascular engineering in the future.
Delineation of proteome changes driven by cell size and growth rate
Authors: Zatulovskiy Evgeny , Lanz Michael C. , Zhang Shuyuan , McCarthy Frank , Elias Joshua E. , Skotheim Jan M.
Published: September 2022

Increasing cell size drives changes to the proteome, which affects cell physiology. As cell size increases, some proteins become more concentrated while others are diluted. As a result, the state of the cell changes continuously with increasing size. In addition to these proteomic changes, large cells have a lower growth rate (protein synthesis rate per unit volume). That both the cell’s proteome and growth rate change with cell size suggests they may be interdependent. To test this, we used quantitative mass spectrometry to measure how the proteome changes in response to the mTOR inhibitor rapamycin, which decreases the cellular growth rate and has only a minimal effect on cell size. We found that large cell size and mTOR inhibition, both of which lower the growth rate of a cell, remodel the proteome in similar ways. This suggests that many of the effects of cell size are mediated by the size-dependent slowdown of the cellular growth rate. For example, the previously reported size-dependent expression of some senescence markers could reflect a cell’s declining growth rate rather than its size per se. In contrast, histones and other chromatin components are diluted in large cells independently of the growth rate, likely so that they remain in proportion with the genome. Finally, size-dependent changes to the cell’s growth rate and proteome composition are still apparent in cells continually exposed to a saturating dose of rapamycin, which indicates that cell size can affect the proteome independently of mTORC1 signaling. Taken together, our results clarify the dependencies between cell size, growth, mTOR activity, and the proteome remodeling that ultimately controls many aspects of cell physiology.
Pathogenesis and treatment of neuropsychiatric systemic lupus erythematosus: A review
Authors: Liu Yuhong , Tu Zhihua , Zhang Xi , Du Keqian , Xie Zhengquan , Lin Zhiming
Published: September 2022

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease with a complex pathogenesis. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious complication of SLE that involves the nervous system and produces neurological or psychiatric symptoms. After decades of research, it is now believed that the diverse clinical manifestations of NPSLE are associated with intricate mechanisms, and that genetic factors, blood-brain barrier dysfunction, vascular lesions, multiple autoimmune antibodies, cytokines, and neuronal cell death may all contribute to the development of NPSLE. The complexity and diversity of NPSLE manifestations and the clinical overlap with other related neurological or psychiatric disorders make its accurate diagnosis difficult and time-consuming. Therefore, in this review, we describe the known pathogenesis and potential causative factors of NPSLE and briefly outline its treatment that may help in the diagnosis and treatment of NPSLE.
Exploring of the property of epoxy resins based on diselenide and disulfide dynamic linkers
Authors: Wei Xiao , Liu Feng , Guo Xinru , Gao Fei , Li Yingjia , Zhu Dongtao , Zhou Zhi , Shen Liang
Published: September 2022

Over the last decade, there has been a lot of interest in incorporating dynamic covalent bonds (DCBs) into epoxy resins. Because diselenide and disulfide bonds have similar properties, they are frequently used as DCBs in self-healing epoxy networks. In this paper, we present diselenide and disulfide dynamic linkers containing epoxy networks by analyzing the effects of mechanical properties, thermal stability, activation energies, and self-healing properties. The glass transition temperature (Tg) values, mechanical properties, crosslinking density (ve), and thermal stability of disulfide linkers networks were higher than those of diselenide linkers networks, according to our research. The activation energies of disulfide linkers were higher than those of diselenide linkers (up to 14 kJ/mol), but their healing efficiency was lower than that of the diselenide network. These findings demonstrate the advantages of diselenide and disulfide dynamic linkers in epoxy networks systems, as well as a method for designing and preparing the appropriate diselenide dynamic linkers or disulfide dynamic linkers incorporated into epoxy networks for the appropriate application and processing technology.
Crosstalk between gut microbiota and renal ischemia/reperfusion injury
Authors: Huang Peng , Cao Jianwei , Chen Jingyi , Luo Yanrong , Gong Xiaofang , Wu Chengyi , Wang Yu
Published: September 2022

Renal ischemia-reperfusion injury (IRI) is the main cause of acute kidney injury and the cause of rapid renal dysfunction and high mortality. In recent years, with the gradual deepening of the understanding of the intestinal flora, exploring renal IRI from the perspective of the intestinal flora has become a research hotspot. It is well known that the intestinal flora plays an important role in maintaining human health, and dysbiosis is the change in the composition and function of the intestinal tract, which in turn causes intestinal barrier dysfunction. Studies have shown that there are significant differences in the composition of intestinal flora before and after renal IRI, and this difference is closely related to the occurrence and development of renal IRI and affects prognosis. In addition, toxins produced by dysregulated gut microbes enter the bloodstream, which in turn exacerbates kidney damage. This article reviews the research progress of intestinal flora and renal IRI, in order to provide new treatment ideas and strategies for renal IRI.
Association between trauma exposure and respiratory disease-A Mendelian randomization study
Authors: Ma Yuchao , Meng Changjiang , Weng Liang
Published: September 2022

Background

Trauma is a well-known risk factor for many disease, but the effect of trauma on respiratory disease is unclarified. In the present study, we aimed to evaluate the association between trauma and respiratory disease.

Method

Using both United Kingdom biobank and Finnish biobank genome-wide association study data (GWAS), we performed a two-sample Mendelian randomization (MR) analysis to evaluate the relationship between trauma and respiratory disease. We used four methods including inverse-variance weighted (IVW), weighted median, Maximum likelihood, and MR-Egger in this MR analysis. The IVW MR was selected as the main method. We also performed multivariable Mendelian randomization (MVMR) to simultaneously assess the independent impact of trauma exposure on respiratory disease.

Results

In the main two-sample MR analysis, trauma exposure was significantly associated with increased risk of respiratory disease (OR 1.15, 95%CI: 1.05-1.25). Besides, there was no heterogeneity and horizontal pleiotropy observed in the sensitivity analysis. After adjusting for pack years of smoking and body mass index (BMI), trauma exposure retained its association with respiratory disease (OR, 1.13, 95%CI, 1.04-1.23 adjusted by pack years of smoking; and OR, 1.11, 95%CI, 1.04-1.18 adjusted by BMI).

Conclusion

Our study discovered the association between trauma exposure and the increased risk of respiratory disease, suggesting the prevention and treatment with trauma to reduce the risk of respiratory disease.
Dual-tracer PET/CT imaging to determine tumor heterogeneity in a patient with metastatic ACTH-secreting neuroendocrine neoplasm: A case report and literature review
Authors: Ryzhkova Daria , Mitrofanova Lubov , Tsoy Uliana , Grineva Elena , Schlyakhto Evgeny
Published: September 2022

Introduction

We present a case of a patient with disseminated ACTH-secreting neuroendocrine neoplasm with biologic heterogeneity between a primary tumor and metastases. The diagnosis was obtained and multidisciplinary management was conducted with a positron emission tomography/computed tomography (PET/CT) scan with Gallium-68 [68Ga]-labeled dodecanetetraacetic acid-tyrosine-3-octreotate ([68Ga]-DOTA-TATE) and Fluor-18 [18F]-fluorodeoxyglucose ([18F]-FDG).

Case report

A PET/CT scan revealed a difference between [68Ga]-DOTA-TATE and [18F]-FDG uptake in primary tumor and several metastases. PET/CT showed high [18F]-FDG uptake and lack of [68Ga]-DOTA-TATE in the primary tumor, whereas both [68Ga]-DOTA-TATE and [18F]-FDG hyperaccumulation were identified in the majority of metastases. Despite positive [68Ga]-DOTA-TATE PET/CT, which is associated with high affinity with the somatostatin receptor 2 subtype, immunohistochemical examination revealed overexpression of the somatostatin receptor 5 subtype only. Perhaps, this explained the ineffectiveness of the treatment with “cold” somatostatin analogs.

Conclusion

This case had an aggressive clinical course, despite cytoreductive surgical treatment and somatostatin analog therapy. PET/CT imaging with two tracers is a molecular tool that demonstrates a biologic heterogeneity between a primary tumor and metastases and yields additional information that may influence the choice of the patient management strategy.
Specific gut bacterial and fungal microbiota pattern in the first half of pregnancy is linked to the development of gestational diabetes mellitus in the cohort including obese women
Authors: Vavreckova Marketa , Galanova Natalie , Kostovcik Martin , Krystynik Ondrej , Ivanovova Eliska , Roubalova Radka , Jiraskova Zakostelska Zuzana , Friedecky David , Friedecka Jaroslava , Haluzik Martin , Karasek David , Kostovcikova Klara
Published: September 2022

Aims

Gestation is linked to changes in gut microbiota composition and function. Since gestational diabetes mellitus (GDM) can develop at any time of the pregnancy, we stratified the women into four groups according to the time and test used for the diagnosis. We focused on the gut microbiota pattern in early pregnancy to detect changes which could be linked to later GDM development.

Methods

We collected stool samples from 104 pregnant women including obese individuals (first trimester body mass index median was 26.73). We divided the women into four groups according to routine screening of fasting plasma glucose (FPG) levels and oral glucose tolerance test (oGTT) in the first and third trimesters, respectively. We processed the stool samples for bacterial 16S rRNA and fungal ITS1 genes sequencing by Illumina MiSeq approach and correlated the gut microbiota composition with plasma short-chain fatty acid levels (SCFA).

Results

We found that gut bacterial microbiota in the first trimester significantly differs among groups with different GDM onset based on unweighted UniFrac distances (p=0.003). Normoglycemic women had gut microbiota associated with higher abundance of family Prevotellaceae, and order Fusobacteriales, and genus Sutterella. Women diagnosed later during pregnancy either by FGP levels or by oGTT had higher abundances of genera Enterococcus, or Erysipelotrichaceae UCG-003, respectively. We observed significant enrichment of fungal genus Mucor in healthy pregnant women whereas Candida was more abundant in the group of pregnant women with impaired oGTT. Using correlation analysis, we found that Holdemanella negatively correlated with Blautia and Candida abundances and that Escherichia/Shigella abundance positively correlated and Subdoligranulum negatively correlated with plasma lipid levels. Coprococcus, Akkermansia, Methanobrevibacter, Phascolarctobacterium and Alistipes positively correlated with acetate, valerate, 2-hydroxybutyrate and 2-methylbutyrate levels, respectively, in women with GDM.

Conclusions

We conclude that there are significant differences in the gut microbiota composition between pregnant women with and without GDM already at the early stage of pregnancy in our cohort that included also overweight and obese individuals. Specific microbial pattern associated with GDM development during early pregnancy and its correlation to plasma lipid or SCFA levels could help to identify women in higher risk of GDM development.
Effectiveness of multiple eHealth-delivered lifestyle strategies for preventing or intervening overweight/obesity among children and adolescents: A systematic review and meta-analysis
Authors: Qiu Li-Ting , Sun Gui-Xiang , Li Ling , Zhang Ji-Dong , Wang Dan , Fan Bo-Yan
Published: September 2022

Objective

To investigate the effect of multiple eHealth-delivered lifestyle interventions on obesity-related anthropometric outcomes in children and adolescents.

Methods

The Medline (via PubMed), Embase, Cochrane Library, Web of Science, CBM, VIP, CNKI, and Wanfang electronic databases were systematically searched from their inception to March 18, 2022, for randomized controlled trials (RCTs). Meta-analyses were performed to investigate the effect of multiple eHealth-delivered lifestyle interventions on obesity-related anthropometric outcomes (body mass index [BMI], BMI Z-score, waist circumference, body weight, and body fat%). Two independent investigators reviewed the studies for accuracy and completeness. All included studies were evaluated using the Cochrane Risk-of-Bias (ROB) Tool.

Results

Forty trials comprising 6,403 patients were selected for the meta-analysis. The eligible trials were published from 2006 to 2022. Compared with the control group, the eHealth-intervention group was more effective in reducing BMI (weighted mean difference [WMD] = −0.32, 95% confidence interval [CI]: −0.50 to −0.13, I2 = 85.9%), BMI Z-score (WMD = −0.08, 95% CI: −0.14 to −0.03, I2 = 89.1%), waist circumference (WMD = −0.87, 95% CI: −1.70 to −0.04, I2 = 43.3%), body weight (WMD = −0.96, 95% CI: −1.55 to −0.37, I2 = 0.0%), and body fat% (WMD = −0.59, 95% CI: −1.08 to −0.10, I2 = 0.0%). The subgroup analysis showed that parental or school involvement (WMD = −0.66, 95% CI: −0.98 to −0.34), eHealth-intervention duration of >12 weeks (WMD = −0.67, 95% CI: −0.96 to −0.38), and mobile-based interventions (WMD = −0.78, 95% CI: −1.13 to −0.43) had a significantly greater intervention effect size on BMI.

Conclusions

This review recommends that multiple eHealth-delivered lifestyle strategies may be useful for preventing or treating overweight and obesity among children and adolescents. However, our results should be cautiously interpreted due to certain limitations in our study.
Adaptive finite-time parameter estimation for grid-connected converter with LCL filter
Authors: Xi Xinze , Shi Zhenghao , Wang Xian , Xing Chao , Li Shengnan
Published: September 2022

This study proposes an online finite-time adaptive parameter estimation method for grid-connected voltage source inverter (VSI) with LCL filter. In this framework, a time-continuous state-space system model is first developed, which is different from the nonparametric frequency-response-based method. Then, the parameter estimation error information is extracted by introducing a series of filter operations. Moreover, a sliding mode term is studied and cooperated with the obtained parameter estimation error to design the parameter estimation error-based finite-time adaptive parameter estimation algorithm. With the help of this novel adaptive law, the physical parameters of electrical components can be driven to their true values accurately and fast. Theoretical analysis is conducted in terms of the Lyapunov theory to demonstrate the convergence of the parameter estimation error. Finally, numerical simulation results are provided to illustrate the superiority of the proposed method over the conventional method.
Exergy-economic analysis and evaluation method of park-level integrated energy system
Authors: Mo Lili , Liu Xin , Chen Haoyong , Zhao Zhendong , Chen Jinbin , Deng Zeyu
Published: September 2022

The park-level integrated energy system (PIES) has been developing rapidly in recent years due to its economic and environmental advantages. PIES is a typical user-side energy supply system with multiple energy forms such as solar energy, electrical energy, cool energy, and heat energy inside the system. The coupling between these energy sources and the differences in the quality of these energy sources make its analysis and evaluation a difficult task for PIES research. In order to solve the problems, an analysis and evaluation method of PIES based on exergy economics is proposed, which lays the foundation for the subsequent optimization of system operation. First, a unified analysis model of PIES is developed based on exergy economics theory. Second, the corresponding analysis and evaluation method for this model is proposed. In this method, the exergy efficiency and exergy loss are used as the evaluation index of system energy consumption characteristics, while the exergy loss cost and exergy economic coefficient are used as the evaluation index of system economic characteristics. Meanwhile, an evaluation procedure for using this method is also designed. Lastly, the effectiveness of the given approach is validated in a PIES case in Guangzhou. The results show that the proposed model can accurately calculate the exergy cost of each energy link. The proposed evaluation method can not only analyze the performance of subsystems within a single system but also compare the advantages and disadvantages between different systems.
State estimation for dynamic systems with higher-order autoregressive moving average non-Gaussian noise
Authors: Zhang Guanghua , Zeng Linghao , Lian Feng , Liu Xinqiang , Fu Na , Dai Shasha
Published: September 2022

The classical Kalman filter is a very important state estimation approach, which has been widely used in many engineering applications. The Kalman filter is optimal for linear dynamic systems with independent Gaussian noises. However, the independence and Gaussian assumptions may not be satisfied in practice. On the one hand, modeling physical systems usually results in discrete-time state-space models with correlated process and measurement noises. On the other hand, the noise is non-Gaussian when the system is disturbed by heavy-tailed noise. In this case, the performance of the Kalman filter will deteriorate, or even diverge. This paper is devoted to addressing the state estimation problem of linear dynamic systems with high-order autoregressive moving average (ARMA) non-Gaussian noise. First, a triplet Markov model is introduced to model the system with high-order ARMA noise, since this model relaxes the independence assumption of the hidden Markov model. Then, a new filter is derived based on correntropy, instead of the commonly used minimum mean square error (MMSE), to deal with non-Gaussian noise. Unlike the MMSE, which uses only second-order statistics of error, correntropy can capture second-order and higher-order statistics. Finally, simulation results verify the effectiveness of the proposed algorithm.
An empirical analysis of cultural inheritance and ICT role on learning practice in a working environment; A PLS-SEM analysis
Authors: Guanghui Feng , Meng Zhou , Delin Huang
Published: September 2022

A review of the relevant research reveals that the concept of “professional growth” is understood to refer to an all-encompassing developmental process that occurs throughout a person’s career as well as their entire life, and it is acknowledged as a phrase that is connected to other ideas. In addition, we can say that human attributes and circumstances are not the only factors that play a role in the process of professional development, but social and institutional experience also play a role in it. After that, this research is shown, which has personal dimensions for beliefs (B), co-workers (CW), culture inheritance (CI), customs (C), information and communications technology (ICT), and learning practice (LP). The research is formed to illustrate that promotion of professional growth in workplaces is connected to the mentioned variables. This study was based on the working experience of different backgrounds people. We tried to check how their attributes could influence their working practices and learning practices. A semi-structured questionnaire was adopted from existing literature and modified as per the study area. B > LP (β = 0.022; p 0.010), CI- > LP (β = 0.368; p 0.000), C- > LP (β = 0.210; p 0.000), and ICT- > LP (β = 0.410; p 0.000) were found to be significant using PLS-SEM direct path analysis.These results offer support to hypotheses H1, H3-H6 accepted and H2 rejected. As control variables, we looked at the respondents’ age, education, and gender. Gender (β = 0.006; p 0.846) showed insignificant relationships with LP, whereas age (β = −0.103; p 0.001) and education (β = −0.072; p 0.034) showed significant relationships with the dependent variable. gender does not have any relationship with learning practices (LP), but age and education can be favorable control variables, and an aged and experienced person can have more impacts on LP and impacts on independent variables.
Model integration methods for hydro-model platform under cloud computing environments
Authors: Liu Ronghua , Wei Jiahua , Wang Zhongjing , Zhang Bingyu , Zhang Chi
Published: September 2022

Computing platforms providing cloud simulation services have raised new challenges on the model integration. Unlike calls to the model programs (components) in traditional simulation software, here the models should be dynamically integrated in the “plug and play” mode regardless of the differences in model type and developer. To this end two integration methods have been proposed, i.e., coarse-grained EXE integration and interactive integration. In an EXE integration method, the simulation program is directly called and thus only a data conversion interface is needed while rewriting of the model source code is not required. In contrast, an interactive integration method wraps the model components using the standard wrapper with communication interfaces, and therefore, it can communicate and exchange data with the platform in a real time. The first method is suitable for the integration of legacy models, while the second one can control the progress of simulation schemes and facilitate the scheduling of computing resources. Examples of the model integration and platform application have been presented in hydraulics/hydrodynamics to demonstrate the effectiveness of the integration method and the cloud computing platform.
RETRACTED: Foreign inflows, commercial law, and dutch disease: Evidence from developing economies
Authors: Guo Qiaoyun , Chen Jie , Xiao He , Mouneer Salma
Published: September 2022

It is commonly believed that developing markets require inflows of foreign capital to achieve their growth targets; however, recent research has shown that these inflows are either ineffective or even harmful to the economy. A surge in foreign inflows, such as foreign aid, remittances, and foreign direct investment, into developing markets, particularly, have been connected to the Dutch disease hypothesis. A sharp rise in such inflows will stimulate real exchange rate in receiving nations due to the uptick in the non-tradable sector and the downturn in the tradable sector. The purpose of this research is to investigate, using quantitative approaches, the variations of real exchange rate adjustments that occur in response to official development assistance, foreign direct investments, and international remittances flowing into developing markets. To investigate the onset of Dutch Disease over the period 2001–2020, this analysis makes use of panel data estimation techniques in the form of fixed and random effect models The findings of a substantial amount of econometric investigation revealed that Dutch Disease is present in developing countries. The scope of the study has been broadened to include an investigation of the expansion of both tradable and non-tradable industries. According to the findings of this study, larger inflows of foreign capital slow growth in the tradable sector (the industrial sector), while simultaneously boosting growth in the non-tradable sector (Service sector).
A necroptosis -related signature for predicting prognosis and immunotherapy in hepatocellular carcinoma
Authors: Fu Xing , Yang Yuling , Zhang Xiaozhi
Published: September 2022

Background: Hepatocellular Carcinoma (HCC) is an aggressive tumor with an inferior prognosis. Necroptosis is a new form of programmed death that plays a dual effect on the tumor. However, the role of necroptosis-related genes(NRGs) in HCC remains unknown.

Methods: All datasets were downloaded from publicly available databases. The consensus clustering analysis was used to classify patients into different subtypes based on NRGs. The Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression were used to develop a prognostic signature. Tumor Immune Dysfunction and Exclusion (TIDE) was used to predict immunotherapy response.

Results: The genetic and transcriptional changes of NRGs were observed in HCC. Patients were classified into three clusters based on differentially expressed NRGs, of which Cluster-3 had the worst prognosis and the highest immune infiltration. The prognostic signature was developed based on 8-NRGs, which have shown excellent prognostic performance. The high-risk group in the signature presented significantly higher immune infiltration, such as aDCs, iDCs, macrophages, and Treg, compared to the low-risk group. TMB and immune checkpoints were also higher in the high-risk group. Moreover, a lower TIDE score was observed in the high-risk group, indicating the patients with high risk-score may be suitable for immunotherapy. Via the dataset of IMvigor210, we found a higher risk score in the immunotherapy response group.

Conclusion: We developed a new necroptosis-related signature for predicting prognosis with the potential to predict immunotherapy for HCC patients.
Inferring human miRNA–disease associations via multiple kernel fusion on GCNII
Authors: Lu Shanghui , Liang Yong , Li Le , Liao Shuilin , Ouyang Dong
Published: September 2022

Increasing evidence shows that the occurrence of human complex diseases is closely related to the mutation and abnormal expression of microRNAs(miRNAs). MiRNAs have complex and fine regulatory mechanisms, which makes it a promising target for drug discovery and disease diagnosis. Therefore, predicting the potential miRNA-disease associations has practical significance. In this paper, we proposed an miRNA–disease association predicting method based on multiple kernel fusion on Graph Convolutional Network via Initial residual and Identity mapping (GCNII), called MKFGCNII. Firstly, we built a heterogeneous network of miRNAs and diseases to extract multi-layer features via GCNII. Secondly, multiple kernel fusion method was applied to weight fusion of embeddings at each layer. Finally, Dual Laplacian Regularized Least Squares was used to predict new miRNA–disease associations by the combined kernel in miRNA and disease spaces. Compared with the other methods, MKFGCNII obtained the highest AUC value of 0.9631. Code is available at https://github.com/cuntjx/bioInfo.
Increased risk of early-onset childhood systemic lupus erythematosus for children born to affected parents: A nationwide child-parent cohort study
Authors: Wu Chun-Hsin , Chen Chih-An , Lin Sheng-Hsiang , Weng Chia-Tse , Kuo Pao-Lin , Shieh Chi-Chang
Published: September 2022

Objective

Children of women with systemic lupus erythematosus (SLE) are at risk for childhood-onset SLE (cSLE). This study evaluated the incidence of early-onset cSLE and associated risk factors, including concomitant maternal and paternal autoimmune diseases, for these children.

Methods

A population-based cohort study was conducted using national databases including the linked information of children and parents. Children of women with SLE and those of women without SLE were identified between 2004 and 2015. The cumulative cSLE incidence was estimated using the Kaplan-Meier method. The marginal Cox model was used to calculate the hazard ratio (HR) for cSLE events.

Results

A total of 4,419 singletons of women with SLE and 1,996,759 singletons of women without SLE were identified. There were 9 (0.20%) and 503 (0.03%) incident cases of early-onset cSLE for offspring of women with and without SLE, respectively (incidence rate ratio, 8.34; 95% confidence interval [CI], 3.79–15.95]. The adjusted HR of incident cSLE in children of women with SLE was 4.65 (95% CI 2.11–10.24). Other risks for cSLE included pregnancy-induced hypertension/preeclampsia/eclampsia, paternal SLE, paternal Sjögren’s syndrome (SS), and maternal SS.

Conclusions

This national child-parent cohort study demonstrated that children of women with SLE are at significantly higher risk for cSLE during early childhood. Moreover, paternal SLE and parental SS increase the risk of cSLE for offspring.
IL4I1 binds to TMPRSS13 and competes with SARS-CoV-2 spike
Authors: Gatineau Jérôme , Nidercorne Charlotte , Dupont Aurélie , Puiffe Marie-Line , Cohen José L. , Molinier-Frenkel Valérie , Niedergang Florence , Castellano Flavia
Published: September 2022

The secreted enzyme interleukin four-induced gene 1 (IL4I1) is involved in the negative control of the adaptive immune response. IL4I1 expression in human cancer is frequent and correlates with poor survival and resistance to immunotherapy. Nevertheless, its mechanism of action remains partially unknown. Here, we identified transmembrane serine protease 13 (TMPRSS13) as an immune cell-expressed surface protein that binds IL4I1. TMPRSS13 is a paralog of TMPRSS2, of which the protease activity participates in the cleavage of SARS-CoV-2 spike protein and facilitates virus induced-membrane fusion. We show that TMPRSS13 is expressed by human lymphocytes, monocytes and monocyte-derived macrophages, can cleave the spike protein and allow SARS-CoV-2 spike pseudotyped virus entry into cells. We identify regions of homology between IL4I1 and spike and demonstrate competition between the two proteins for TMPRSS13 binding. These findings may be relevant for both interfering with SARS-CoV-2 infection and limiting IL4I1-dependent immunosuppressive activity in cancer.
Immunotherapy of targeting MDSCs in tumor microenvironment
Authors: Sui Hongshu , Dongye Shengyi , Liu Xiaocui , Xu Xinghua , Wang Li , Jin Christopher Q. , Yao Minhua , Gong Zhaoqing , Jiang Daniel , Zhang Kexin , Liu Yaling , Liu Hui , Jiang Guomin , Su Yanping
Published: September 2022

Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous cells which are abnormally accumulated during the differentiation of myeloid cells. Immunosuppression is the main functional feature of MDSCs, which inhibit T cell activity in the tumor microenvironment (TME) and promote tumoral immune escape. The main principle for immunotherapy is to modulate, restore, and remodel the plasticity and potential of immune system to have an effective anti-tumor response. In the TME, MDSCs are major obstacles to cancer immunotherapy through reducing the anti-tumor efficacy and making tumor cells more resistant to immunotherapy. Therefore, targeting MDSCs treatment becomes the priority of relevant studies and provides new immunotherapeutic strategy for cancer treatment. In this review, we mainly discuss the functions and mechanisms of MDSCs as well as their functional changes in the TME. Further, we review therapeutic effects of immunotherapy against MDSCs and potential breakthroughs regarding immunotherapy targeting MDSCs and immune checkpoint blockade (ICB) immunotherapy.
Evaluating the growth and cost–benefit analysis of feeding improved indigenous chicken with diets containing black soldier fly larva meal
Authors: Waithaka Mwangi K. , Osuga Isaac M. , Kabuage Lucy W. , Subramanian Sevgan , Muriithi Beatrice , Wachira Ann M. , Tanga Chrysantus M.
Published: September 2022

The high cost of feed has been the major hindrance to a hindrance to the growth, sustainability, profitability, and expansion of poultry production. Black soldier fly larva (BSFL) meal is one of the most promising alternative protein sources widely accepted globally. This study evaluated the growth performance of improved indigenous chicken (IIC)-fed diets containing different inclusion levels of BSFL meals. The BSFL meal inclusion rates included 0% (Diet0), 5% (Diet1), 10% (Diet2), 15% (Diet3), and 20% (Diet4) as replacement to the expensive fish meal in chick and grower diets. Our results showed that diet significantly affected the average daily feed intake, feed conversion ratio, and average daily weight gain of the chicks. The average daily weight gain and feed conversion ratio, except average daily feed intake of the growers, was not significantly affected by diets. The gross profit margin, cost–benefit ratio, and return on investment of feeding birds with BSFL meal varied significantly. The highest cost–benefit ratio of 2.12 was recorded for birds fed on Diet4. Our findings demonstrate that insect-based feeds can successfully and cost-effectively replace fish meal up to 20% without compromising the growth performance of the birds. Therefore, BSFL meal could be incorporated as an essential part of poultry feed production for IIC, potentially reducing the total feed cost while maintaining optimal production and reducing the cost of meat and egg products.
Global coral bleaching event detection from satellite monitoring of extreme heat stress
Authors: Little Christine M. , Liu Gang , De La Cour Jacqueline L. , Eakin C. Mark , Manzello Derek , Heron Scott F.
Published: September 2022

Over the past four decades, coral bleaching events have occurred with increasing frequency and severity, directly linked to increasing ocean temperature due to climate change. For the latter half of that period, satellite monitoring by NOAA Coral Reef Watch in near real-time has provided invaluable insight into bleaching risk. Here, we describe a novel application of those products to develop basin-scale tools for tracking the development of extreme heat events that enable monitoring of global coral bleaching events. Case studies of historical extreme events (1982-2018) across the three tropical ocean basins (Indian, Pacific and Atlantic) were analysed using this basin-scale approach to identify key thresholds of heat stress extent for the definition of global bleaching. Global-scale events are apparent when all three tropical basins experience heat stress in at least 10% of reef-containing locations. An 8-month ‘detection window’ was determined as the optimal period of time through which pixels exposed to heat stress should continue to be counted as part of a basin-scale event to account for seasonal variations across ocean basins. Understanding the broader context of basin-scale conditions can inform management of individual reefs, management networks and other reef stakeholders. Operationalising this product for near real-time delivery will provide an effective communication of the status of coral reefs around the world during an era of unprecedented climate threats.
Interaction analysis of hemolymph extracellular vesicles miRNA and hemocytes mRNA reveals genes and pathways associated with molting in Scylla paramamosain
Authors: Qiao Ying , Ma Xiaowan , Huang Lixing , Zhong Shengping , Xing Yongze , Chen Xuyang
Published: September 2022

Molting is a key biological process in crustaceans, with impacts on their growth, development and reproduction. Extracellular vesicles (EVs) serve as bio-cargo carrying such as nucleic acids, proteins, and lipids which mediate intercellular communication and participate in various cell biological processes. In this study, we obtained hemocyte transcriptome data during the intermolt, premolt, and postmolt stages of the mud crab Scylla paramamosain. We analyzed the differentially expressed genes in the three stages of molt and identified a number of immune-related genes and structural cuticle genes. We then isolated and characterized the EVs from the hemolymph of S. paramamosain and sequenced their miRNA. In total, we characterized 89 EVs microRNAs (miRNAs) targeting 1447 genes that are potentially involved in the molting process of S. paramamosain. The EVs miRNAs mainly regulated the immune-related genes and affected the molting process by mediating ecdysone signaling and insulin signaling pathways during the mud crab molt cycle. This is the first study of EVs miRNAs and their interaction with mRNA to identify important candidate genes associated with, or regulating, the molting process. This study provides a better understanding of, and novel insights into, the molting cycle of crustaceans and offers baseline information for further studies in the mechanisms regulating molt.
Pathogenicity and antibiotic resistance analysis of Vibrio species found in coastal water at mainly beach of Shenzhen, China
Authors: Huang Ziwei , Anokyewaa Melody Abena , Wang Junlin , Jian Jichang , Lu Yishan
Published: September 2022

Offshore industries and resources are the links between humans and the marine ecosystem. Several risk factors are associated with beach activities. The risk of Vibrio infection at bathing beaches is often overlooked as there are virtually no regulations regarding them. In this study, we investigated the current prevalence of pathogenic Vibrio spp. on the main beaches of Shenzhen. The risk indicator levels of pathogenic Vibrio species obtained were analyzed using 17 virulence genes mainly associated with Vibrio species and are responsible for several ailments and infections. A total of 60 Vibrio strains were isolated and identified by morphological observation, evolutionary tree alignment, and biochemical testing. There was a high abundance of Vibrio in the seawater. Also, a positive correlation was observed between the presence of virulence genes and the exhibition of high pathogenicity after artificially infecting fish with some of the virulent Vibrio species. In the infection experiment, it was observed that all the zebrafish infected with MEDF7 (Vibrio alginolyticus) and JSW-YELLOW (Vibrio harveyi) died a day after injection, with varying degrees of abdominal enlargement and skin ulceration. The mortality rates for strains with medium risk and low risk were 65% and 45%, respectively. Lethal dose 50 (LD50) values were 5.67 ×104 CFU/fish, 3.72 ×105 CFU/fish, and 4.31 ×105 CFU/fish for the high-risk, medium-risk, and low-risk strains of zebrafish, respectively. The results of the antibiotic sensitivity test showed that all the six experimental strains, except JSW-YELLOW, were resistant to doxycycline and neopenicillin. In summary, our study first identified and evaluated the pathogenicity of Vibrio in the Shenzhen beach baths, serving as a scientific benchmark for Vibrio risk prevention and control as well as guidance for Vibrio diagnosis through virulence factor detection and risk classification.
Study on the relationship between the particle size distribution characteristics of ground granulated blast furnace slag and its mortar properties
Authors: He Tusheng , Xu Zengwei , Li Zaibo , Zhao Xuguang , Zhao Sanyin , Liu Yang
Published: September 2022

This study adopted the Rosin-Rammler-Bennett (RRB) equation to model the particle size distribution (PSD) of ground granulated blast furnace slag (GGBFS) and prepared four groups of GGBFS powders with a characteristic particle size De = 8–20 μm and uniformity coefficient n = 0.9–1.4 by means of grading and combining blast furnace slag. In cases both with and without polycarboxylate superplasticizers (PCE), the fluidity and strength of the mortar were measured. The study found that without PCE, the aggregation of GGBFS had a significant negative impact on the mortar fluidity and hardened paste strength. With the addition of PCE, the properties of the mortar mainly depended on two factors, the specific surface area of the GGBFS and the differences in De and n between the GGBFS and Portland cement. At a given specific surface area of GGBFS, high hardened paste strength can be obtained through simultaneously lowering the De and increasing the n.
Value assessment of medicinal products by the Italian Medicines Agency (AIFA) and French National Authority for Health (HAS): Similarities and discrepancies
Authors: Xoxi Entela , Di Bidino Rossella , Leone Serena , Aiello Andrea , Prada Mariangela
Published: September 2022

The evaluation of pharmaceutical innovation and therapeutic value is an increasingly complex exercise for which different approaches are adopted at the national level, despite the need for standardisation of processes and harmonisation of public health decisions. The objective of our analysis was to compare the approaches of the AIFA (Agenzia Italiana del Farmaco) and the HAS (Haute Autorité de Santé) in assessing the same medicinal products. In Italy, the 1525/2017 AIFA Deliberation introduces a transparent scheme for the evaluation of innovative status (innovative, conditional, not innovative) based on the therapeutic added value (TAV), therapeutic need, and quality of evidence. In contrast, in France, the HAS makes judgements using the effective clinical benefit (Service Médical Rendu) and improvement of effective clinical benefit (Amélioration du Service Médical Rendu, ASMR). This analysis focused on medicinal products evaluated both by the AIFA and by the HAS from July 2017 to September 2021. Similarities between AIFA and HAS evaluations were investigated in terms of the TAV, recognition of innovativeness, and the ASMR. Both total and partial agreements were considered relevant. Therefore, raw agreement, Cohen's kappa (weighted and unweighted), and Bangdiwala's B-statistic were estimated. A total of 102 medicinal products were included in this study. Out of these, 38 (37.2%) were orphan drugs, while 56 (54.9%) had a clinical indication for the treatment of cancer. The AIFA and HAS reached a higher level of agreement on the innovativeness status compared with the TAV. A moderate total agreement emerged in the recognition of innovativeness (k = 0.463, p-value ≤0.0001), and partial agreement was substantial (equal weight k = 0.547, squared k = 0.638), while a lack of agreement resulted in a comparison of the TAV according to the AIFA and the ASMR recognised by the HAS. Indeed, whereas the AIFA determined the TAV to be important, the HAS considered it to be moderate. In addition, whereas the AIFA identified a bias towards a moderate TAV, the HAS identified a bias towards a minor ASMR. A higher level of agreement was reached, both on the TAV and on innovative status, for less critical medical products (non-cancer-related, or non-orphan, or with a standard European Medicines Agency approval). These results underline the importance of implementing European procedures that are more broadly aligned in terms of value definition criteria.