bluuebunny/crossref_metadata_2025 huggingface dataset:
Island microgrid power control system based on adaptive virtual impedance
Authors: Su Hongsheng , Zhang Zhiqiang , Wang Shaohua
Published: January 2023

When the microgrid is in the islanding operation mode, affected by the line impedance difference between the distributed power sources (DGs), the traditional droop control strategy will lead to the fact that the reactive power of the system cannot be reasonably distributed according to the droop gain, which makes the power grid prone to failure. To solve this problem, an improved sag control strategy based on adaptive virtual impedance is proposed in this paper. The central controller calculates the given power according to the capacity of each inverter and the total load capacity of the line, and then sends it to each inverter, and the inverter determines the value range of the virtual impedance according to the given reactive power. A voltage compensation link is added to the control strategy to compensate for the voltage drop difference caused by the line impedance difference, thereby ensuring the stability of the output power and realizing the power control of the microgrid. The MATLAB/Simulink simulation platform was built to establish the microgrid simulation model in island mode. The simulation results show that when the inverters with the same capacity are connected in parallel, the output active power is the most stable, and the reactive power maintains an equalized state; When inverters of different capacities are connected in parallel, the output active power takes the shortest time to stabilize, and the reactive power basically matches the rated capacity ratio. Therefore, it is fully demonstrated that this method has a good control effect on the power control and operation of the islanded microgrid.
The impact of top management support, perceived justice, supplier management, and sustainable supply chain management on moderating the role of supply chain agility
Authors: Men Feng , Yaqub Rana Muhammad Shahid , Yan Rui , Irfan Muhammad , Haider Ali
Published: January 2023

Sustainable supply chain management (SSCM) is a new area of interest to scientists and industrial practitioners through which to maintain productivity, reduce costs, and enhance agility. SSCM is especially important to protect the environment and reduce pollution by heavy industries. It considers the environment the main stakeholder in minimizing the carbon footprint during production, lowering emissions of dangerous gases, and reducing industrial pollution. Considering the aforementioned purposes, the aim of this study was to explore the relationships between top management support, perceived justice, supplier management, and SSCM and assess the moderating role of supply chain agility. This quantitative study was conducted in the vast textile sector in Pakistan. We collected data through a questionnaire and found that top management support, perceived justice, and supplier management are positively and significantly associated with SSCM. However, there was no significant moderating effect of supply chain agility on the independent variables and SSCM. These findings have practical implications for production managers and top management in enhancement of their roles in promoting environmental wellbeing. By developing rules at the organizational and governmental levels that consider the role of top management, perceived justice, and improved supplier management, the sustainability of the supply chain can be improved. This analysis provides academics who study the supply chain a practical prescription and adds to the body of knowledge about the validity of top SSCM pillars.
Impact of digital transformation on renewable energy companies’ performance: Evidence from China
Authors: Ren Yangjun , Li Botang , Liang Dong
Published: January 2023

The rapid growth of the renewable energy industry provides essential opportunities for China to achieve the goal of carbon peaking and carbon neutrality. A rising number of renewable energy companies are positively embracing digital transformation in the digital age. However, the relationship between digital transformation and the performance of renewable energy companies remains unclear. To fill this gap, leveraging the latest advances in textual analysis, we quantify the extent of a renewable energy enterprise’s digital transformation. Meanwhile, based on fixed effect model and mediating effect model, we investigate the influence of digital transformation on firm performance using a panel data of Chinese A-share listed renewable energy companies. The results indicate that digital transformation enhances a renewable energy enterprise’s performance. Further, the promotion effect of digital transformation is greater among state-owned enterprises and large firms and is only helpful for firms in the eastern area. Moreover, we document that when a renewable energy enterprise adopts digital transformation, it has higher operating efficiency, lower cost, and better innovation success resulting in better performance. This research elucidates the role of digital transformation in forwarding the development of renewable energy companies and bears significant policy implications.
Prediction of groundwater pollution diffusion path based on multi-source data fusion
Authors: Zhang Yanhong , Huo Xiaofeng , Luo Yue
Published: January 2023

In order to improve the prediction accuracy of groundwater pollution diffusion path, this paper combines multivariate data fusion technology to predict and analyze the groundwater pollution diffusion path. Under the special two-strategy swarm game model of water pollution particle swarm, this paper introduces replication dynamics with bounded continuous time-delay. Moreover, considering the dynamic behavior in both cases of constant kernel function and exponential kernel function, the hawk-dove game model is a special case of the model we are discussing. In addition, this paper proposes a method combining leaching surface and flux concentration, and applies numerical simulation method to simulate and analyze transient leakage monitoring of similar point and line source pollution in planar two-dimensional heterogeneous aquifers. The experimental study verifies that the multivariate data fusion proposed in this paper can play an important role in the prediction of groundwater pollution diffusion path.
Informing policy and practice on insect pollinator declines: Tensions between conservation and animal welfare
Authors: Barrett Meghan , Fischer Bob , Buchmann Stephen
Published: January 2023

Climate change, agricultural intensification, and other anthropogenic ecosystem challenges have caused declines in the diversity and abundance of insect pollinators. In response to these declines, entomologists have called for greater attention to insect pollinator conservation. Conservation primarily aims to protect groups of non-human animals—populations or species—with only secondary concern for the welfare of individual animals. While conservation and animal welfare goals are sometimes aligned, they often are not. And because animal welfare comes second, it tends to be sacrificed when in tension with conversation priorities. Consider, for example, lethal sampling to monitor many pollinator populations. Growing evidence suggests that the welfare of individual insect pollinators may be morally significant, particularly in the Hymenoptera and Diptera. Considering insect welfare in conservation practices and policies presents many challenges as, in the face of rapid, anthropogenic change, it may be impossible to avoid harming individual animals while promoting diverse populations. We suggest some practical, implementable strategies that can allow for more robust integration of animal welfare goals into insect pollinator conservation. By following these strategies, entomologists may be able to find policies and practices that promote the health of ecosystems and the individual animals within them.
Habitat suitability for Dickcissels (Spiza americana) during spring and fall migration: A species distribution modeling approach
Authors: Glass Alex , Eichholz Michael W. , Brown Jason L.
Published: January 2023

Introduction

Migratory songbirds have experienced consistent population declines over the past half-century. An important, though often overlooked, contributor to these declines is the loss and degradation of stopover areas during migration, which are critical for allowing migrants to rest and refuel, and arrive in good condition at breeding and nonbreeding grounds.

Methods

Here, we used publicly available eBird occurrence data to build species distribution models examining habitat suitability of the Dickcissel, a grassland-associated neotropical migrant, during spring and fall migration. Our models included variables representing land cover type, climate, and net primary productivity.

Results

Land cover variables were consistently better predictors of Dickcissel occurrence than climate or net primary productivity, suggesting that land cover type has a stronger impact on stopover habitat suitability than environmental factors. During spring migration, Dickcissel occurrence probability decreased with shrubland cover and precipitation seasonality. During fall migration, occurrence probability increased with proximity to water and human development, and decreased with increasing net primary productivity. We detected positive associations during both spring and fall with annual mean temperature and temperature seasonality, and a negative association with forest cover. Surprisingly, our models detected no strong associations with grassland or agriculture, despite the importance of these habitat types for Dickcissels during the breeding and nonbreeding seasons.

Discussion

Ultimately, our results suggest that Dickcissels exhibit greater flexibility when selecting stopover sites compared to breeding or nonbreeding areas, although their avoidance of forest and shrubland may indicate that they will be negatively impacted by further woody encroachment into open habitats across their migratory routes.
Transcriptomic data analysis coupled with copy number aberrations reveals a blood-based 17-gene signature for diagnosis and prognosis of patients with colorectal cancer
Authors: Kaya Ibrahim H. , Al-Harazi Olfat , Colak Dilek
Published: January 2023

Background: Colorectal cancer (CRC) is the third most common cancer and third leading cause of cancer-associated deaths worldwide. Diagnosing CRC patients reliably at an early and curable stage is of utmost importance to reduce the risk of mortality.

Methods: We identified global differentially expressed genes with copy number alterations in patients with CRC. We then identified genes that are also expressed in blood, which resulted in a blood-based gene signature. We validated the gene signature’s diagnostic and prognostic potential using independent datasets of gene expression profiling from over 800 CRC patients with detailed clinical data. Functional enrichment, gene interaction networks and pathway analyses were also performed.

Results: The analysis revealed a 17-gene signature that is expressed in blood and demonstrated that it has diagnostic potential. The 17-gene SVM classifier displayed 99 percent accuracy in predicting the patients with CRC. Moreover, we developed a prognostic model and defined a risk-score using 17-gene and validated that high risk score is strongly associated with poor disease outcome. The 17-gene signature predicted disease outcome independent of other clinical factors in the multivariate analysis (HR = 2.7, 95% CI = 1.3–5.3, p = 0.005). In addition, our gene network and pathway analyses revealed alterations in oxidative stress, STAT3, ERK/MAPK, interleukin and cytokine signaling pathways as well as potentially important hub genes, including BCL2, MS4A1, SLC7A11, AURKA, IL6R, TP53, NUPR1, DICER1, DUSP5, SMAD3, and CCND1.

Conclusion: Our results revealed alterations in various genes and cancer-related pathways that may be essential for CRC transformation. Moreover, our study highlights diagnostic and prognostic value of our gene signature as well as its potential use as a blood biomarker as a non-invasive diagnostic method. Integrated analysis transcriptomic data coupled with copy number aberrations may provide a reliable method to identify key biological programs associated with CRC and lead to improved diagnosis and therapeutic options.
Whole-genome resequencing reveals genetic diversity and selection characteristics of dairy goat
Authors: Xiong Jinke , Bao Jingjing , Hu Wenping , Shang Mingyu , Zhang Li
Published: January 2023

The dairy goat is one of the earliest dairy livestock species, which plays an important role in the economic development, especially for developing countries. With the development of agricultural civilization, dairy goats have been widely distributed across the world. However, few studies have been conducted on the specific characteristics of dairy goat. In this study, we collected the whole-genome data of 89 goat individuals by sequencing 48 goats and employing 41 publicly available goats, including five dairy goat breeds (Saanen, Nubian, Alpine, Toggenburg, and Guanzhong dairy goat; n = 24, 15, 11, 6, 6), and three goat breeds (Guishan goat, Longlin goat, Yunshang Black goat; n = 6, 15, 6). Through compared the genomes of dairy goat and non-dairy goat to analyze genetic diversity and selection characteristics of dairy goat. The results show that the eight goats could be divided into three subgroups of European, African, and Chinese indigenous goat populations, and we also found that Australian Nubian, Toggenburg, and Australian Alpine had the highest linkage disequilibrium, the lowest level of nucleotide diversity, and a higher inbreeding coefficient, indicating that they were strongly artificially selected. In addition, we identified several candidate genes related to the specificity of dairy goat, particularly genes associated with milk production traits (GHR, DGAT2, ELF5, GLYCAM1, ACSBG2, ACSS2), reproduction traits (TSHR, TSHB, PTGS2, ESR2), immunity traits (JAK1, POU2F2, LRRC66). Our results provide not only insights into the evolutionary history and breed characteristics of dairy goat, but also valuable information for the implementation and improvement of dairy goat cross breeding program.
Effect of CX3CL1/CX3CR1 gene polymorphisms on the clinical efficacy of carboplatin therapy in Han patients with ovarian cancer
Authors: Wang Xin-Chen , Zhou Hong , Jiang Wen-Jing , Jiang Peng , Sun Yan-Cai , Ni Wei-Jian
Published: January 2023

Gene polymorphisms have a close relationship with the clinical effects of carboplatin for ovarian cancer. Here, we investigated the relationship between CX3CL1 and CX3CR1 genotypes and the clinical efficacy of carboplatin in ovarian cancer, thereby clarifying the unidentified genetic factors that influence the efficacy of carboplatin in ovarian cancer. Based on the above purposes, we used Sequenom Mass ARRAY technology to detect CX3CL1 and CX3CR1 gene polymorphisms in 127 patients with carboplatin-treated ovarian cancer. We performed various statistical analyses to evaluate the effects of CX3CL1 and CX3CR1 genetic variants, demographic data, and clinical characteristics on the effect of carboplatin therapy. The results show that the CX3CL1 genotypes rs223815 (G>C) and rs682082 (G>A) will significantly affect the clinical efficacy of carboplatin for ovarian cancer (p < 0.05), while the other six genotypes and all CX3CR1 genotypes have no significant effect (p > 0.05). In addition, only one population factor, age, had a significant effect on the clinical efficacy of carboplatin-treated ovarian cancer (p < 0.05). Based on the above research results, we concluded that the clinical efficacy of carboplatin in ovarian cancer patients was significantly correlated with age and CX3CL1 polymorphism factors; however, more in-depth effects and mechanisms need to be explored by large-scale, multicenter studies.
Differences in MB-COMT DNA methylation in monozygotic twins on phenotypic indicators of impulsivity
Authors: Smederevac Snežana , Delgado-Cruzata Lissette , Mitrović Dušanka , Dinić Bojana M. , Bravo Toni-Ann T. , Delgado Maria , Bugarski Ignjatović Vojislava , Sadiković Selka , Milovanović Ilija , Vučinić Nataša , Branovački Bojan , Prinz Mechthild , Budimlija Zoran , Kušić‐Tišma Jelena , Nikolašević Željka
Published: January 2023

Epigenetic modifications of the membrane bound catechol-O-methyltransferase (MB-COMT) gene may affect the enzymatic degradation of dopamine, and consequently, human behavior. This study investigated the association between membrane bound catechol-O-methyltransferase DNA methylation (DNAm) differences in 92 monozygotic (MZ) twins with phenotypic manifestations of cognitive, behavioral, and personality indicators associated with reward-related behaviors and lack of control. We used pyrosequencing to determine DNAm of the regulatory region of membrane bound catechol-O-methyltransferase in saliva DNA. Results of intrapair differences in the percentage of membrane bound catechol-O-methyltransferase DNAm at each of five CpG sites show that there are associations between phenotypic indicators of lack of control and membrane bound catechol-O-methyltransferase DNAm differences on CpG1, CpG2 and CpG4, suggesting the common epigenetic patterns for personality traits, cognitive functions, and risk behaviors.
SLC25A1-associated prognostic signature predicts poor survival in acute myeloid leukemia patients
Authors: Liu Fangshu , Deng Suqi , Li Yue , Du Juan , Zeng Hui
Published: January 2023

Background: Acute myeloid leukemia (AML) is a heterogeneous malignant disease. SLC25A1, the gene encoding mitochondrial carrier subfamily of solute carrier proteins, was reported to be overexpressed in certain solid tumors. However, its expression and value as prognostic marker has not been assessed in AML.

Methods: We retrieved RNA profile and corresponding clinical data of AML patients from the Beat AML, TCGA, and TARGET databases (TARGET_AML). Patients in the TCGA cohort were well-grouped into two group based on SLC25A1 and differentially expressed genes were determined between the SLC25A1 high and low group. The expression of SLC25A1 was validated with clinical samples. The survival and apoptosis of two AML cell lines were analyzed with SLC25A1 inhibitor (CTPI-2) treatment. Cox and the least absolute shrinkage and selection operator (LASSO) regression analyses were applied to Beat AML database to identify SLC25A1-associated genes for the construction of a prognostic risk-scoring model. Survival analysis was performed by Kaplan-Meier and receiver operator characteristic curves.

Results: Our analysis revealed that high expressed level of SLC25A1 in AML patients correlates with unfavorable prognosis. Moreover, SLC25A1 expression was positively associated with metabolism activity. We further demonstrated that the inhibition of SLC25A1 could inhibit the proliferation and increase the apoptosis of AML cells. In addition, a panel of SLC25A1-associated genes, was identified to construct a prognostic risk-scoring model. This SLC25A1-associated prognostic signature (SPS) is an independent risk factor with high area under curve (AUC) values of receiver operating characteristic (ROC) curves. A high SPS in leukemia patients is associated with poor survival. A Prognostic nomogram including the SPS and other clinical parameters, was constructed and its predictive efficiency was confirmed.

Conclusion: We have successfully established a SPS prognostic model that predict outcome and risk stratification in AML. This risk model can be used as an independent biomarker to assess prognosis of AML.
A CRISPR way for accelerating cereal crop improvement: Progress and challenges
Authors: Basu Umer , Riaz Ahmed Syed , Bhat Basharat Ahmad , Anwar Zunaira , Ali Ahmad , Ijaz Aqsa , Gulzar Addafar , Bibi Amir , Tyagi Anshika , Nebapure Suresh M. , Goud Chengeshpur Anjali , Ahanger Shafat Ahmad , Ali Sajad , Mushtaq Muntazir
Published: January 2023

Humans rely heavily on cereal grains as a key source of nutrients, hence regular improvement of cereal crops is essential for ensuring food security. The current food crisis at the global level is due to the rising population and harsh climatic conditions which prompts scientists to develop smart resilient cereal crops to attain food security. Cereal crop improvement in the past generally depended on imprecise methods like random mutagenesis and conventional genetic recombination which results in high off targeting risks. In this context, we have witnessed the application of targeted mutagenesis using versatile CRISPR-Cas systems for cereal crop improvement in sustainable agriculture. Accelerated crop improvement using molecular breeding methods based on CRISPR-Cas genome editing (GE) is an unprecedented tool for plant biotechnology and agriculture. The last decade has shown the fidelity, accuracy, low levels of off-target effects, and the high efficacy of CRISPR technology to induce targeted mutagenesis for the improvement of cereal crops such as wheat, rice, maize, barley, and millets. Since the genomic databases of these cereal crops are available, several modifications using GE technologies have been performed to attain desirable results. This review provides a brief overview of GE technologies and includes an elaborate account of the mechanisms and applications of CRISPR-Cas editing systems to induce targeted mutagenesis in cereal crops for improving the desired traits. Further, we describe recent developments in CRISPR-Cas–based targeted mutagenesis through base editing and prime editing to develop resilient cereal crop plants, possibly providing new dimensions in the field of cereal crop genome editing.
Duck TRIM29 negatively regulates type I IFN production by targeting MAVS
Authors: Li Weiqiang , Song Yating , Du Yuqing , Huang Zhanhong , Zhang Meng , Chen Zuxian , He Zhuoliang , Ding Yangbao , Zhang Junsheng , Zhao Luxiang , Sun Hailiang , Jiao Peirong
Published: January 2023

The innate immune response is a host defense mechanism that induces type I interferon and proinflammatory cytokines. Tripartite motif (TRIM) family proteins have recently emerged as pivotal regulators of type I interferon production in mammals. Here, we first identified duck TRIM29, which encodes 571 amino acids and shows high sequence homology with other bird TRIM29 proteins. DuTRIM29 inhibited IFN-β and IRF7 promoter activation in a dose-dependent manner and downregulated the mRNA expression of IFN-β, IRF7, Mx and IL-6 mediated by duRIG-I. Moreover, duTRIM29 interacted and colocalized with duMAVS in the cytoplasm. DuTRIM29 interacted with duMAVS via its C-terminal domains. In addition, duTRIM29 inhibited IFN-β and IRF7 promoter activation and significantly downregulated IFN-β and immune-related gene expression mediated by duMAVS in ducks. Furthermore, duTRIM29 induced K29-linked polyubiquitination and degradation of duMAVS to suppress the expression of IFN-β. Overall, our results demonstrate that duTRIM29 negatively regulates type I IFN production by targeting duMAVS in ducks. This study will contribute to a better understanding of the molecular mechanism regulating the innate immune response by TRIM proteins in ducks.
Increased Myosin light chain 9 expression during Kawasaki disease vasculitis
Authors: Kobayashi Hironobu , Kimura Motoko Y. , Hasegawa Ichita , Suganuma Eisuke , Ikehara Yuzuru , Azuma Kazuhiko , Ito Toshihiro , Ebata Ryota , Kurashima Yosuke , Kawasaki Yohei , Shiko Yuki , Saito Naoki , Iwase Hirotaro , Lee Youngho , Noval Rivas Magali , Arditi Moshe , Zuka Masahiko , Hamada Hiromichi , Nakayama Toshinori
Published: January 2023

Introduction

Kawasaki disease (KD) is an acute systemic vasculitis that predominantly afflicts children. KD development is known to be associated with an aberrant immune response and abnormal platelet activation, however its etiology is still largely unknown. Myosin light chain 9 (Myl9) is known to regulate cellular contractility of both non-muscle and smooth muscle cells, and can be released from platelets, whereas any relations of Myl9 expression to KD vasculitis have not been examined.

Methods

Plasma Myl9 concentrations in KD patients and children with febrile illness were measured and associated with KD clinical course and prognosis. Myl9 release from platelets in KD patients was also evaluated in vitro. Myl9 expression was determined in coronary arteries from Lactobacillus casei cell wall extract (LCWE)-injected mice that develop experimental KD vasculitis, as well as in cardiac tissues obtained at autopsy from KD patients.

Results and discussion

Plasma Myl9 levels were significantly higher in KD patients during the acute phase compared with healthy controls or patients with other febrile illnesses, declined following IVIG therapy in IVIG-responders but not in non-responders. In vitro, platelets from KD patients released Myl9 independently of thrombin stimulation. In the LCWE-injected mice, Myl9 was detected in cardiac tissue at an early stage before inflammatory cell infiltration was observed. In tissues obtained at autopsy from KD patients, the highest Myl9 expression was observed in thrombi during the acute phase and in the intima and adventitia of coronary arteries during the chronic phase. Thus, our studies show that Myl9 expression is significantly increased during KD vasculitis and that Myl9 levels may be a useful biomarker to estimate inflammation and IVIG responsiveness to KD.
Oral pretreatment with β-lactoglobulin derived peptide and CpG co-encapsulated in PLGA nanoparticles prior to sensitizations attenuates cow’s milk allergy development in mice
Authors: Liu Mengshan , Thijssen Suzan , Hennink Wim E. , Garssen Johan , van Nostrum Cornelus F. , Willemsen Linette E. M.
Published: January 2023

Cow’s milk allergy is a common food allergy among infants. Improved hygiene conditions and loss of microbial diversity are associated with increased risk of allergy development. The intestinal immune system is essential for oral tolerance induction. In this respect, bacterial CpG DNA is known to drive Th1 and regulatory T-cell (Treg) development via Toll-Like-Receptor 9 (TLR-9) signaling, skewing away from the allergic Th2 phenotype. We aimed to induce allergen specific tolerance via oral delivery of poly (lactic-co-glycolic acid) nanoparticles (NP) co-encapsulated with a selected β-lactoglobulin derived peptide (BLG-Pep) and TLR-9 ligand CpG oligodeoxynucleotide (CpG). In vivo, 3-4-week-old female C3H/HeOuJ mice housed in individually ventilated cages received 6-consecutive-daily gavages of either PBS, whey, BLG-Pep/NP, CpG/NP, a mixture of BLG-Pep/NP plus CpG/NP or co-encapsulated BLG-Pep+CpG/NP, before 5-weekly oral sensitizations with whey plus cholera toxin (CT) or only CT (sham) and were challenged with whey 5 days after the last sensitization. The co-encapsulated BLG-Pep+CpG/NP pretreatment, but not BLG-Pep/NP, CpG/NP or the mixture of BLG-Pep/NP plus CpG/NP, prevented the whey-induced allergic skin reactivity and prevented rise in serum BLG-specific IgE compared to whey-sensitized mice. Importantly, co-encapsulated BLG-Pep+CpG/NP pretreatment reduced dendritic cell (DC) activation and lowered the frequencies of PD-L1+ DC in the mesenteric lymph nodes compared to whey-sensitized mice. By contrast, co-encapsulated BLG-Pep+CpG/NP pretreatment increased the frequency of splenic PD-L1+ DC compared to the BLG-Pep/NP plus CpG/NP recipients, in association with lower Th2 development and increased Treg/Th2 and Th1/Th2 ratios in the spleen. Oral administration of PLGA NP co-encapsulated with BLG-Pep and CpG prevented rise in serum BLG-specific IgE and symptom development while lowering splenic Th2 cell frequency in these mice which were kept under strict hygienic conditions.
National experience with adenosine deaminase deficiency related SCID in Polish children
Authors: Dąbrowska-Leonik Nel , Piątosa Barbara , Słomińska Ewa , Bohynikova Nadezda , Bernat-Sitarz Katarzyna , Bernatowska Ewa , Wolska-Kuśnierz Beata , Kałwak Krzysztof , Kołtan Sylwia , Dąbrowska Anna , Goździk Jolanta , Ussowicz Marek , Pac Małgorzata
Published: January 2023

Introduction

Deficiency of adenosine deaminase (ADA) manifests as severe combined immunodeficiency (SCID), caused by accumulation of toxic purine degradation by-products. Untreated patients develop immune and non-immune symptoms with fatal clinical course. According to ESID and EBMT recommendations enzyme replacement therapy (ERT) should be implemented as soon as possible to stabilize the patient’s general condition, normalize transaminases, treat pulmonary proteinosis, bone dysplasia, and protect from neurological damage. Hematopoietic stem cell transplantation (HSCT) from a matched related donor (MRD) is a treatment of choice. In absence of such donor, gene therapy (GT) should be considered. HSCT from a matched unrelated donor (MUD) and haploidentical hematopoietic stem cell transplantation (hHSCT) are associated with worse prognosis.

Material and methods

We retrospectively evaluated the clinical course and results of biochemical, immunological and genetic tests of 7 patients diagnosed in Poland with ADA deficiency since 2010 to 2022.

Results

All patients demonstrated lymphopenia affecting of T, B and NK cells. Diagnosis was made on the basis of ADA activity in red blood cells and/or genetic testing. Patients manifested with various non-immunological symptoms including: lung proteinosis, skeletal dysplasia, liver dysfunction, atypical hemolytic-uremic syndrome, and psychomotor development disorders. Five patients underwent successful HSCT: 3 patients from matched unrelated donor, 2 from matched sibling donor, and 1 haploidentical from a parental donor. In 4 patients HSCT was preceded by enzyme therapy (lasting from 2 to 5 months). One patient with multiple organ failure died shortly after admission, before the diagnosis was confirmed. None of the patients had undergone gene therapy.

Conclusions

It is important to diagnose ADA SCID as early as possible, before irreversible multi-organ failure occurs. In Poland HSCT are performed according to international immunological societies recommendations, while ERT and GT are less accessible. Implementation of Newborn Screening (NBS) for SCID in Poland could enable recognition of SCID, including ADA-SCID.
Impact of the flame retardant 2,2’4,4’-tetrabromodiphenyl ether (PBDE-47) in THP-1 macrophage-like cell function via small extracellular vesicles
Authors: Longo Valeria , Aloi Noemi , Lo Presti Elena , Fiannaca Antonino , Longo Alessandra , Adamo Giorgia , Urso Alfonso , Meraviglia Serena , Bongiovanni Antonella , Cibella Fabio , Colombo Paolo
Published: January 2023

2,2’4,4’-tetrabromodiphenyl ether (PBDE-47) is one of the most widespread environmental brominated flame-retardant congeners which has also been detected in animal and human tissues. Several studies have reported the effects of PBDEs on different health issues, including neurobehavioral and developmental disorders, reproductive health, and alterations of thyroid function. Much less is known about its immunotoxicity. The aim of our study was to investigate the effects that treatment of THP-1 macrophage-like cells with PBDE-47 could have on the content of small extracellular vesicles’ (sEVs) microRNA (miRNA) cargo and their downstream effects on bystander macrophages. To achieve this, we purified sEVs from PBDE-47 treated M(LPS) THP-1 macrophage-like cells (sEVsPBDE+LPS) by means of ultra-centrifugation and characterized their miRNA cargo by microarray analysis detecting the modulation of 18 miRNAs. Furthermore, resting THP-1 derived M(0) macrophage-like cells were cultured with sEVsPBDE+LPS, showing that the treatment reshaped the miRNA profiles of 12 intracellular miRNAs. This dataset was studied in silico, identifying the biological pathways affected by these target genes. This analysis identified 12 pathways all involved in the maturation and polarization of macrophages. Therefore, to evaluate whether sEVsPBDE+LPS can have some immunomodulatory activity, naïve M(0) THP-1 macrophage-like cells cultured with purified sEVsPBDE+LPS were studied for IL-6, TNF-α and TGF-β mRNAs expression and immune stained with the HLA-DR, CD80, CCR7, CD38 and CD209 antigens and analyzed by flow cytometry. This analysis showed that the PBDE-47 treatment does not induce the expression of specific M1 and M2 cytokine markers of differentiation and may have impaired the ability to make immunological synapses and present antigens, down-regulating the expression of HLA-DR and CD209 antigens. Overall, our study supports the model that perturbation of miRNA cargo by PBDE-47 treatment contributes to the rewiring of cellular regulatory pathways capable of inducing perturbation of differentiation markers on naïve resting M(0) THP-1 macrophage-like cells.
Identification of the osteoarthritis signature gene PDK1 by machine learning and its regulatory mechanisms on chondrocyte autophagy and apoptosis
Authors: Meng Jinzhi , Du Huawei , Lv Haiyuan , Lu Jinfeng , Li Jia , Yao Jun
Published: January 2023

Background

Osteoarthritis (OA) is a degenerative joint disease frequently diagnosed in the elderly and middle-aged population. However, its specific pathogenesis has not been clarified. This study aimed to identify biomarkers for OA diagnosis and elucidate their potential mechanisms for restoring OA-dysregulated autophagy and inhibiting chondrocyte apoptosis in vitro.

Material and methods

Two publicly available transcriptomic mRNA OA-related datasets (GSE10575 and GSE51588) were explored for biomarker identification by least absolute shrinkage and selection operator (LASSO) regression, weighted gene co-expression network analysis (WGCNA), and support vector machine recursive feature elimination (SVM-RFE). We applied the GSE32317 and GSE55457 cohorts to validate the markers’ efficacy for diagnosis. The connections of markers to chondrocyte autophagy and apoptosis in OA were also comprehensively explored in vitro using molecular biology approaches, including qRT-PCR and Western blot.

Results

We identified 286 differentially expressed genes (DEGs). These DEGs were enriched in the ECM-receptor interaction and PI3K/AKT signaling pathway. After external cohort validation and protein-protein interaction (PPI) network construction, PDK1 was finally identified as a diagnostic marker for OA. The pharmacological properties of BX795-downregulated PDK1 expression inhibited LPS-induced chondrocyte inflammation and apoptosis and rescued OA-dysregulated autophagy. Additionally, the phosphorylation of the mediators associated with the MAPK and PI3K/AKT pathways was significantly downregulated, indicating the regulatory function of PDK1 in apoptosis and autophagy via MAPK and PI3K/AKT-associated signaling pathways in chondrocytes. A significantly positive association between the PDK1 expression and Neutrophils, Eosinophils, Plasma cells, and activated CD4 memory T cells, as well as an evident negative correlation between T cells follicular helper and CD4 naive T cells, were detected in the immune cell infiltration analysis.

Conclusions

PDK1 can be used as a diagnostic marker for OA. Inhibition of its expression can rescue OA-dysregulated autophagy and inhibit apoptosis by reducing the phosphorylation of PI3K/AKT and MAPK signaling pathways.
BNT162b2 COVID-19 vaccination elicited protective robust immune responses in pediatric patients with inborn errors of metabolism
Authors: Zubarioglu Tanyel , Dinc Harika Oyku , Hopurcuoglu Duhan , Gulmez Ruveyda , Uygur Esma , Yilmaz Gizem , Ahmadzada Saffa , Uzunyayla-Inci Gozde , Oge-Enver Ece , Kiykim Ertugrul , Kocazeybek Bekir , Aktuglu-Zeybek Cigdem
Published: January 2023

Introduction

SARS-CoV-2 infection can lead to a life-threatening acute metabolic decompensation in children with inborn errors of metabolism (IEM), so vaccination is mandatory. However, IEMs can also impair innate or adaptive immunity, and the impact of these immune system alterations on immunogenicity and vaccine efficacy is still unknown. Here, we investigated humoral immune responses to the BNT162b2 mRNA COVID-19 vaccine and clinical outcomes in pediatric IEM patients.

Methods

Fifteen patients between 12-18 years of age with a confirmed diagnosis of IEM, and received BNT162b2 were enrolled to the study. Patients with an anti-SARS-CoV-2 IgG concentration >50 AU/mL before vaccination were defined as “COVID-19 recovered” whereas patients with undetectable anti-SARS-CoV-2 IgG concentration were defined as “COVID-19 naïve”. Anti-SARS-CoV-2 Immunoglobulin G (IgG) and SARS-CoV-2 neutralizing antibody (nAb) titers were measured to assess humoral immune response.

Results

Anti-SARS-CoV-2 IgG titers and nAb IH% increased significantly after the first dose. The increase in antibody titers after first and second vaccination remained significant in COVID-19 naïve patients. Complete anti-SARS-CoV-2 IgG seropositivity and nAb IH% positivity was observed in all patients after the second dose. Vaccination appears to be clinically effective in IEM patients, as none of the patients had COVID-19 infection within six months of the last vaccination.

Discussion

Humoral immune response after two doses of BNT162b2 in pediatric IEM patients was adequate and the immune response was not different from that of healthy individuals.
α1-adrenoceptor stimulation ameliorates lipopolysaccharide-induced lung injury by inhibiting alveolar macrophage inflammatory responses through NF-κB and ERK1/2 pathway in ARDS
Authors: Cong Zhukai , Yang Cui , Zeng Zhaojin , Wu Changyi , Zhao Feng , Shen Ziyuan , Xiao Han , Zhu Xi
Published: January 2023

Introduction

Catecholamines such as norepinephrine or epinephrine have been reported to participate in the development of acute respiratory distress syndrome (ARDS) by activating adrenergic receptors (ARs). But the role of α1-AR in this process has yet to be elucidated.

Methods

In this study, ARDS mouse model was induced by intratracheal instillation of lipopolysaccharide. After treatment with α1-AR agonist phenylephrine or antagonist prazosin, lung pathological injury, alveolar barrier disruption and inflammation, and haemodynamic changes were evaluated. Cytokine levels and cell viability of alveolar macrophages were measured in vitro. Nuclear factor κB (NF-κB), mitogen-activated protein kinase, and Akt signalling pathways were analysed by western blot.

Results

It showed that α1-AR activation alleviated lung injuries, including reduced histopathological damage, cytokine expression, and inflammatory cell infiltration, and improved alveolar capillary barrier integrity of ARDS mice without influencing cardiovascular haemodynamics. In vitro experiments suggested that α1-AR stimulation inhibited secretion of TNF-α, IL-6, CXCL2/MIP-2, and promoted IL-10 secretion, but did not affect cell viability. Moreover, α1-AR stimulation inhibited NF-κB and enhanced ERK1/2 activation without significantly influencing p38, JNK, or Akt activation.

Discussion

Our studies reveal that α1-AR stimulation could ameliorate lipopolysaccharide-induced lung injury by inhibiting NF-κB and promoting ERK1/2 to suppress excessive inflammatory responses of alveolar macrophages.
Investigating regulatory patterns of NLRP3 Inflammasome features and association with immune microenvironment in Crohn’s disease
Authors: Wu Huihuan , Zeng Ruijie , Qiu Xinqi , Chen Kequan , Zhuo Zewei , Guo Kehang , Xiang Yawen , Yang Qi , Jiang Rui , Leung Felix W. , Lian Qizhou , Sha Weihong , Chen Hao
Published: January 2023

Introduction

Crohn’s disease is characterized of dysregulated inflammatory and immune reactions. The role of the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome in Crohn’s disease remains largely unknown.

Methods

The microarray-based transcriptomic data and corresponding clinical information of GSE100833 and GSE16879 were obtained from the Gene Expression Omnibus (GEO) database. Identification of in the NLRP3 inflammasome-related genes and construction of LASSO regression model. Immune landscape analysis was evaluated with ssGSEA. Classification of Crohn’s-disease samples based on NLRP3 inflammasome-related genes with ConsensusClusterPlus. Functional enrichment analysis, gene set variation analysis (GSVA) and drug-gene interaction network.

Results

The expressions of NLRP3 inflammasome-related genes were increased in diseased tissues, and higher expressions of NLRP3 inflammasome-related genes were correlated with generally enhanced immune cell infiltration, immune-related pathways and human leukocyte antigen (HLA)-gene expressions. The gene-based signature showed well performance in the diagnosis of Crohn’s disease. Moreover, consensus clustering identified two Crohn’s disease clusters based on NLRP3 inflammasome-related genes, and cluster 2 was with higher expressions of the genes. Cluster 2 demonstrated upregulated activities of immune environment in Crohn’s disease. Furthermore, four key hub genes were identified and potential drugs were explored for the treatment of Crohn’s disease.

Conclusions

Our findings indicate that NLRP3 inflammasome and its related genes could regulate immune cells and responses, as well as involve in the pathogenesis of Crohn’s disease from transcriptomic aspects. These findings provide in silico insights into the diagnosis and treatment of Crohn’s disease and might assist in the clinical decision-making process.
CcGSDMEa functions the pore-formation in cytomembrane and the regulation on the secretion of IL-lβ in common carp (Cyprinus carpio haematopterus)
Authors: Zhao Yanjing , Zhang Jie , Qiao Dan , Gao Feng , Gu Yanlong , Jiang Xinyu , Zhu Lei , Kong Xianghui
Published: January 2023

GSDME is the only direct executor of caspase-dependent pyroptosis in both canonical and non-canonical inflammasomes known to date in fish, and plays an important role in anti-bacterial infection and inflammatory response. In order to determine the regulation of GSDMEa on antibacterial infection in innate immune response, the CcGSDMEa gene in common carp (Cyprinus carpio haematopterus) was first identified and characterized, and then its function related to immune defense was investigated. Our results showed that the expressions of CcGSDMEa at the mRNA and protein levels were both significantly increased after Aeromonas hydrophila intraperitoneal infection at the early stage than that in the control group. We found that CcGSDMEa could be cleaved by inflammatory caspase (CcCaspase-1b) and apoptotic caspases (CcCaspase-3a/b and CcCaspase-7a/b). Interestingly, only the CcGSDMEa-NT (1-252 aa) displayed bactericidal activity to Escherichia coli and could punch holes in the membrane of HEK293T cells, whereas CcGSDMEa-FL (1-532 aa) and CcGSDMEa-CT (257-532 aa) showed no above activity and pore-forming ability. Overexpression of CcGSDMEa increased the secretion of CcIL-1β and the release of LDH, and could reduce the A. hydrophila burdens in fish. On the contrary, knockdown of CcGSDMEa reduced the secretion of CcIL-1β and the release of LDH, and could increase the A. hydrophila burdens in fish. Taken together, the elevated expression of CcGSDMEa was a positive immune response to A. hydrophila challenge in fish. CcGSDMEa could perform the pore-formation in cell membrane and the regulation on the secretion of IL-lβ, and further regulate the bacterial clearance in vivo. These results suggested that CcGSDMEa played an important role in immune defense against A. hydrophila and could provide a new insight into understanding the immune mechanism to resist pathogen invasion in teleost.
Towards a unified eco-evolutionary framework for fisheries management: Coupling advances in next-generation sequencing with species distribution modelling
Authors: Baltazar-Soares Miguel , Lima André R. A. , Silva Gonçalo , Gaget Elie
Published: January 2023

The establishment of high-throughput sequencing technologies and subsequent large-scale genomic datasets has flourished across fields of fundamental biological sciences. The introduction of genomic resources in fisheries management has been proposed from multiple angles, ranging from an accurate re-definition of geographical limitations of stocks and connectivity, identification of fine-scale stock structure linked to locally adapted sub-populations, or even the integration with individual-based biophysical models to explore life history strategies. While those clearly enhance our perception of patterns at the light of a spatial scale, temporal depth and consequently forecasting ability might be compromised as an analytical trade-off. Here, we present a framework to reinforce our understanding of stock dynamics by adding also a temporal point of view. We propose to integrate genomic information on temporal projections of species distributions computed by Species Distribution Models (SDMs). SDMs have the potential to project the current and future distribution ranges of a given species from relevant environmental predictors. These projections serve as tools to inform about range expansions and contractions of fish stocks and suggest either suitable locations or local extirpations that may arise in the future. However, SDMs assume that the whole population respond homogenously to the range of environmental conditions. Here, we conceptualize a framework that leverages a conventional Bayesian joint-SDM approach with the incorporation of genomic data. We propose that introducing genomic information at the basis of a joint-SDM will explore the range of suitable habitats where stocks could thrive in the future as a function of their current evolutionary potential.
Spatial variability of dissolved nickel is enhanced by mesoscale dynamics in the Gulf of Mexico
Authors: Félix-Bermúdez Armando , Delgadillo-Hinojosa Francisco , Lares María Lucila , Torres-Delgado Eunise Vanessa , Huerta-Díaz Miguel Angel , Tovar-Sanchez Antonio , Camacho-Ibar Víctor Froylan
Published: January 2023

The Gulf of Mexico (GoM) is one of the most dynamic marginal seas in the world owing to the intrusion of the Loop Current and the shedding of anticyclonic eddies (LCE) that travel westward across the Gulf. However, the impacts of these mesoscale dynamics on the supply and removal of bioessential trace metals in surface waters remain unclear. We study the impact of mesoscale eddies on the distribution of dissolved nickel (Ni), a biologically active element scarcely studied in the region. The vertical distribution of Ni was determined in the deep-water region of the GoM during summer of 2017, when two anticyclonic LCE (Quantum and Poseidon) were present. Nutrient-like profiles of Ni in the GoM resemble those from the Atlantic Ocean, but they showed high spatial variability within the first 1000 m, which was associated with the impact of mesoscale eddies. Similarly to subtropical gyres, macronutrients were almost depleted in surface waters, while Ni never fell below 1.51 nmol kg-1, suggesting low Ni lability or alternatively, slow biological uptake compared to that of macronutrients. In particular, lowest levels of Ni and macronutrients (PO4 and NO3) were recorded in surface waters of the anticyclonic eddies and the Loop Current area. Anticyclonic LCEs deepened these Ni-poor waters pushing the Ni-rich core of Tropical Atlantic Central Water up to 600 m, whereas its shallowest position (up to 200 m) was recorded under cyclonic conditions in Campeche Bay. This eddy-induced vertical displacement of water masses also affected the integrated Ni and macronutrient concentrations in the upper 350 m but without modifying their stoichiometries. We suggest that a significant decrease in surface inventories of Ni and macronutrient in areas impacted by LCEs is a consequence of the trapping of the water within eddies, the biological uptake of Ni and macronutrients combined with their limited replenishment from below, which likely affects autotrophic groups. In conclusion, the mesoscale dynamic permanently present in the GoM play an important role in modifying the vertical distribution of Ni and macronutrients as well as their availability in the upper water column of this marginal sea.