bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of subclass distribution of insulin antibody with glucose control in insulin-treated type 2 diabetes mellitus: a retrospective observational study
Authors: Chen Shuang , Chen Heng , Jiang Yin , Zheng Xuqin , Zhang Mei , Yang Tao , Gu Yong
Published: April 2023

Objective

To examine the distribution and effects of the subclass of insulin antibodies on glucose control and side events in patients with type 2 diabetes treated with premixed insulin analog.

Methods

A total of 516 patients treated with premixed insulin analog were sequentially enrolled from the First Affiliated Hospital of Nanjing Medical University from June 2016 to August 2020. Subclass-specific insulin antibodies (IAs) (IgG1-4, IgA, IgD, IgE, and IgM) were detected in IA-positive patients by electrochemiluminescence. We analyzed glucose control, serum insulin, and insulin-related events between IA-positive and IA-negative groups, as well as among patients with different IA subclasses.

Results

Overall, 98 of 516 subjects (19.0%) were positive for total IAs after premixed insulin analog therapy; of these participants, 92 had subclass IAs, and IgG-IA was the predominant subclass, followed by IgE-IA. IAs were associated with serum total insulin increase and local injection-site reactions but not glycemic control and hypoglycemia. In the subgroup analysis in patients with IA-positive, the IgE-IA and IA subclass numbers were more associated with increased serum total insulin levels. Additionally, IgE-IA might be correlated more strongly with local responses and weakly with hypoglycemia, while IgM-IA might be correlated more strongly with hypoglycemia.

Conclusion

We concluded that IAs or IA subclasses might be associated with unfavorable events in patients receiving premixed insulin analog therapy, which can be used as an adjunctive monitoring indicator in clinical insulin trials.
Glucocorticoid regulation of cancer development and progression
Authors: Khadka Stuti , Druffner Sara R. , Duncan Benjamin C. , Busada Jonathan T.
Published: April 2023

Glucocorticoids are steroid hormones that regulate a host of cellular and physiological functions. However, they are arguably best known for their potent anti-inflammatory properties. Chronic inflammation is well-known to promote the development and progression of numerous types of cancer, and emerging evidence suggests that glucocorticoid regulation of inflammation affects cancer development. However, the timing, intensity, and duration of glucocorticoid signaling have important but often contradictory effects on cancer development. Moreover, glucocorticoids are widely used in parallel with radiation and chemotherapy to control pain, dyspnea, and swelling, but their use may compromise anti-tumor immunity. This review will explore the effects of glucocorticoids on cancer development and progression with particular focus on pro and anti-tumor immunity.
Detailed analysis of the association between urate deposition and bone erosion in gout: a dual-energy computed tomography study
Authors: Zheng Wan-Yi , Zhan Wen-Feng , Wang Jing-Yi , Deng Wei-Ming , Hung Yu-Kai , Wang Wei , Jiang Gui-Hua
Published: April 2023

Objective

This study aimed to analyze the effect of urate deposition (UD) on bone erosion and examine the association between the volume of monosodium urate (MSU) crystals and an improved bone erosion score method, as measured in the metatarsophalangeal (MTP) joints of patients with gout.

Materials and methods

Fifty-six patients diagnosed with gout using the 2015 European League Against Rheumatism and American College of Rheumatology criteria were enrolled. MSU crystals volume at each MTP joint was measured using dual-energy computed tomography (DECT) images. The degree of bone erosion was evaluated with the modified Sharp/van der Heijde (SvdH) erosion scoring system based on CT images. Differences in clinical features between patients with (UD group) and without (non-UD group) UD were assessed, and the correlation between erosion scores and urate crystal volume was analyzed.

Results

The UD and non-UD groups comprised 30 and 26 patients, respectively. Among the 560 MTP joints assessed, 80 showed MSU crystal deposition, and 108 showed bone erosion. Bone erosion occurred in both groups but was significantly less severe in the non-UD group (p <0.001). Both groups had equivalent levels of serum uric acid (p=0.200). Symptom duration was significantly longer in the UD group (p=0.009). The UD group also had a higher rate of kidney stones (p=0.023). The volume of MSU crystals was strongly and positively associated with the degree of bone erosion (r=0.714, p <0.001).

Conclusion

This study found that patients with UD show significant increased bone erosion than those without UD. The volume of MSU crystals is associated with the improved SvdH erosion score based on CT images, regardless of serum uric acid level, demonstrating the potential of combining DECT and serum uric acid measurements in helping optimize the management of patients with gout.
Ovarian cancer-associated immune exhaustion involves SPP1+ T cell and NKT cell, symbolizing more malignant progression
Authors: Wang Kunyu , Hou Hongyi , Zhang Yanan , Ao Miao , Luo Haixia , Li Bin
Published: April 2023

Background

Ovarian cancer (OC) is highly heterogeneous and has a poor prognosis. A better understanding of OC biology could provide more effective therapeutic paradigms for different OC subtypes.

Methods

To reveal the heterogeneity of T cell-associated subclusters in OC, we performed an in-depth analysis of single-cell transcriptional profiles and clinical information of patients with OC. Then, the above analysis results were verified by qPCR and flow cytometry examine.

Results

After screening by threshold, a total of 85,699 cells in 16 ovarian cancer tissue samples were clustered into 25 major cell groups. By performing further clustering of T cell-associated clusters, we annotated a total of 14 T cell subclusters. Then, four distinct single-cell landscapes of exhausted T (Tex) cells were screened, and SPP1 + Tex significantly correlated with NKT cell strength. A large amount of RNA sequencing expression data combining the CIBERSORTx tool were labeled with cell types from our single-cell data. Calculating the relative abundance of cell types revealed that a greater proportion of SPP1 + Tex cells was associated with poor prognosis in a cohort of 371 patients with OC. In addition, we showed that the poor prognosis of patients in the high SPP1 + Tex expression group might be related to the suppression of immune checkpoints. Finally, we verified in vitro that SPP1 expression was significantly higher in ovarian cancer cells than in normal ovarian cells. By flow cytometry, knockdown of SPP1 in ovarian cancer cells could promote tumorigenic apoptosis.

Conclusion

This is the first study to provide a more comprehensive understanding of the heterogeneity and clinical significance of Tex cells in OC, which will contribute to the development of more precise and effective therapies.
Klotho’s impact on diabetic nephropathy and its emerging connection to diabetic retinopathy
Authors: Tang Anqi , Zhang Yu , Wu Ling , Lin Yong , Lv Lizeyu , Zhao Liangbin , Xu Bojun , Huang Youqun , Li Mingquan
Published: April 2023

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide and is a significant burden on healthcare systems. α-klotho (klotho) is a protein known for its anti-aging properties and has been shown to delay the onset of age-related diseases. Soluble klotho is produced by cleavage of the full-length transmembrane protein by a disintegrin and metalloproteases, and it exerts various physiological effects by circulating throughout the body. In type 2 diabetes and its complications DN, a significant decrease in klotho expression has been observed. This reduction in klotho levels may indicate the progression of DN and suggest that klotho may be involved in multiple pathological mechanisms that contribute to the onset and development of DN. This article examines the potential of soluble klotho as a therapeutic agent for DN, with a focus on its ability to impact multiple pathways. These pathways include anti-inflammatory and oxidative stress, anti-fibrotic, endothelial protection, prevention of vascular calcification, regulation of metabolism, maintenance of calcium and phosphate homeostasis, and regulation of cell fate through modulation of autophagy, apoptosis, and pyroptosis pathways. Diabetic retinopathy shares similar pathological mechanisms with DN, and targeting klotho may offer new insights into the prevention and treatment of both conditions. Finally, this review assesses the potential of various drugs used in clinical practice to modulate klotho levels through different mechanisms and their potential to improve DN by impacting klotho levels.
A review of the effects of different parameters on salt-based solar thermal energy storage systems
Authors: Kumar Anil , Maithani Rajesh , Sharma Sachin , Alam Tabish , Gupta Naveen Kumar , Deifalla Ahmed Farouk
Published: April 2023

Phase change materials (PCMs) used for thermal energy storage (TES) have shown to be particularly promising, especially in light of the growing need for a wide variety of energy-related applications. This article discusses the usage of packed beds made from phase change materials in solar energy storage devices for variable temperature environments. The primary heating/cooling technologies and associated thermal energy storage difficulties have also been examined from the perspective of engineering applications. The packed bed’s history from a thermodynamic perspective, the temperature dispersion inside the packed bed, and several design factors that influence its performance are all covered in the brief description of the packed bed. Energy and exergy efficacy are the foundations of its analysis. The article delves into numerous thermal energy storage methods, with phase change materials being the primary topic and a beneficial means of storing thermal energy. In addition, phase change materials also keep latent thermal energy during phase transitions at almost constant temperatures.
Optimal operation strategy for distribution network with high penetration of dispersed wind power
Authors: Duan Jiandong , Chen Lupeng , Lu Wenchao , Zhu Darui , Sun Qian
Published: April 2023

As a significant approach to local utilization of clean renewable energy, the dispersed wind power (DWP) is becoming more and more widespread in engineering applications. With the fluctuating wind power widely and dispersedly integrated into distribution networks, it is urgent and pressing to effectively enhance the penetration rate of wind power based on the safe operation of distribution networks. This paper takes full advantage of the power regulation ability of wind turbines to actively participate in the operation of distribution networks, and then an optimal operation model of distribution networks is established with the optimization objectives of high penetration of DWP and maximum correntropy of node voltage. Aiming at the characteristics of the proposed model, the multi-objective brain storm optimization algorithm is adopted to solve the model to achieve the Pareto solution set, and the fuzzy membership function is used to determine the optimal operation scheme from the solution set. The simulation results on the expanded IEEE 33 bus system indicate the rationality of the proposed optimal operation strategy for distribution networks with high penetration of DWP. Meanwhile, the feasibility of the optimal operation scheme is verified through the case of a practical demonstration project.
Metal composition and contamination assessment of urban roadway dusts on the Abu Dhabi-Liwa Highway, UAE
Authors: Al-Taani Ahmed A. , Nazzal Yousef , Howari Fares M. , Iqbal Jibran , Naseem Muhammad , Sharma Manish , Xavier Cijo , Papandreou Dimitrios , Maloukh Lina , Ambika Lakshmi , Ben Salem Imen , Al Bsoul Abeer , Farok Haitham M.
Published: April 2023

The metal composition of road-deposited dust along the Abu Dhabi-Liwa Highway was investigated to provide insight into the contamination profile and levels of road dust. The average concentrations of metals decreased in the order Al (28668 ± 4631 mg/kg)> Fe (21461 ± 2594 mg/kg) > Mn (711.8 ± 76.3 mg/kg) > Zn (210.6 ± 51.6 mg/kg) > Cu (94.9 ± 15.8 mg/kg) > Pb (83.6 ± 5.3 mg/kg) > Cd (75.1 ± 1.6 mg/kg) > Co (62.6 ± 6.4 mg/kg) > As (4.7 ± 2.9 mg/kg) > Ni (0.10 ± 0.19 mg/kg) > Cr (0.08 ± 0.06 mg/kg). The spatial variations of metals suggest different sources and contributing factors for these metals, with most dust metals having mixed traffic and non-traffic origins. The contamination factor (CF) and enrichment factor (EF) showed identically the same order, Cd> Pb> As> Zn> Co> Cu> Mn> Ni> Cr, whereas the geoaccumulation index (Igeo) follows a slightly different ranking, Cd> Pb> Zn> Co> As> Cu> Mn> Ni> Cr. Based on EF and CF levels, roadway dusts are enriched in all metals, except for Ni and Cr. Similarly, the average Igeo values show differing rates of pollution for all metals except for Mn, Ni, and Cr. All pollution indicators suggest extreme pollution with Cd. The pollution loading index values showed sites 1–10 are generally polluted, while sampling sites from 11 to 19 are unpolluted with decreasing pollution loadings. Dusts collected from both sides of highway were higher in metal content than those obtained from the central reservation area. This may be due to the prevailing southeast wind direction, resuspension of road dust, and farmlands, among others. Soils bordering the highway showed high metal contents with potential consequences on the agricultural products.
The effect of aboveground long-term low-dose ionizing radiation on soil microbial diversity and structure
Authors: Cheng Feng , Huang Xiaofei , Qin Qingao , Chen Zijian , Li Fei , Song Wenchen
Published: April 2023

Studies investigating the diversity and structure of soil microbial systems in response to ionizing radiation are scarce. In particular, effects of long-term low-dose radiation is rarely studied because of its unique conditions. In this study, an area in Chengdu, China, which has been irradiated by the radionuclide thorium-232 for more than 10 years was investigated. Four groups of samples with absorbed dose rates ranging from 192.906 ± 5.05 to 910.964 ± 41.09 nGy/h were collected to analyze the compositional and functional changes of the soil microbial systems in the region. The diversity and structure of the soil microbial systems were determined using high-throughput sequencing. Our results showed that long-term low-dose ionizing radiation had no significant effect on soil bacterial diversity, but had a great impact on fungal diversity. Long-term ionizing radiation strongly affected soil microbial community structure. Long-term low-dose ionizing radiation was shown to have a promoting effect on iron-oxidizing bacteria and ectomycorrhizal fungi and have an inhibiting effect on predatory or parasitic fungi, further affecting the soil C/N ratio. This study is of great reference significance for future research on the impact of long-term low-dose ionizing radiation on soil ecosystems.
Niche models as a tool to inform restoration and conservation strategies: the case of Jubaea chilensis (palm, Arecaceae) and its seed disperser Octodon degus (rodent, Octodontidae)
Authors: Núñez-Hidalgo Ignacio , Fleury Marina , Bustamante Ramiro O.
Published: April 2023

Introduction

Biotic interactions are a crucial component of the plant regeneration process, which has been traditionally studied at more local scales, providing the tools for planning and decision-making. Studies showing the signature of species interactions at coarser spatial scales contrasting with animal-plant interactions at fine scales have been scarce. This study aimed at integrating an approach, over both biogeographic and local scales, by testing two endemic species of Mediterranean central Chile: the relict and southernmost threatened Chilean palm Jubaea chilensis (Chilean palm; Molina; Baillón) and the caviomorph scatter-hoarding rodent Octodon degus (Degu; Molina), on which this palm currently relies for seed dispersal.

Methods

Integrating Geographic Information Systems and Ecological Niche Modeling, the intensity of seed-rodent interactions from a territorial perspective was evaluated in the range of the palm, at a biogeographic scale, identifying areas with greater or lesser potential for seed-rodent interactions; and in local populations, incorporating a variety of environmental factors that might affect palm regeneration.

Results

The present results show that the rodent (Octodon degus) may play a role in Chilean palm (Jubaea chilensis) seed dispersal and seed establishment, since; Chilean palm regeneration is higher in areas where both species co-occur. At a local scale, a prominent overlap between palm seedlings and degu burrows was also found, which, allied with other abiotic variables such as altitude and topographic humidity, are crucial for successful palm regeneration.

Discussion

Understanding the full extent of animal-plant interactions and how they are affected by habitat perturbation in a wide range will provide essential information for the design of effective conservation and management strategies, such as rewilding based on plant species.
Improving the accuracy of forest aboveground biomass using Landsat 8 OLI images by quantile regression neural network for Pinus densata forests in southwestern China
Authors: Zhang Xiaoli , Li Lu , Liu Yanfeng , Wu Yong , Tang Jing , Xu Weiheng , Wang Leiguang , Ou Guanglong
Published: April 2023

It is a challenge to reduce the uncertainties of the underestimation and overestimation of forest aboveground biomass (AGB) which is common in optical remote sensing imagery. In this study, four models, namely, the linear stepwise regression (LSR), artificial neural network (ANN), quantile regression (QR), and quantile regression neural network (QRNN) were used to estimate Pinus densata forest AGB data by collecting 146 sample plots combined with Landsat 8-Operational Land Imager (OLI) images in Shangri-La City, Yunnan Province, southwestern China. The results showed that compared with the LSR, the R2 and mean square error (RMSE) of the ANN, QR, and QRNN had improved significantly. In particular, the QRNN was able to significantly improve the situation of overestimation and underestimation when we estimated forest biomass, which had the highest R2 (0.971) and lowest RMSE (9.791 Mg/ha) for the whole biomass segment. Meanwhile, through model validation, we found that the QRNN had the highest R2 (0.761) and lowest RMSE (6.486 Mg/ha) on the biomass segment of <40 Mg/ha. Furthermore, it had the highest R2 (0.904) and lowest RMSE (9.059 Mg/ha) on the biomass segment of >160 Mg/ha, which offered great potential for improving the estimation accuracy of the Pinus densata forest AGB. In conclusion, the QRNN, combining the advantages of QR and ANN, provides great potential for reducing the precision influence caused by the overestimation and underestimation in forest AGB estimation using optical remote sensing data.
Comparative mitogenomic and evolutionary analysis of Lycaenidae (Insecta: Lepidoptera): Potential association with high-altitude adaptation
Authors: Chen Wen-Ting , Li Min , Hu Shi-Yun , Wang Su-Hao , Yuan Ming-Long
Published: April 2023

Harsh environments (e.g., hypoxia and cold temperatures) of the Qinghai–Tibetan Plateau have a substantial influence on adaptive evolution in various species. Some species in Lycaenidae, a large and widely distributed family of butterflies, are adapted to the Qinghai–Tibetan Plateau. Here, we sequenced four mitogenomes of two lycaenid species in the Qinghai–Tibetan Plateau and performed a detailed comparative mitogenomic analysis including nine other lycaenid mitogenomes (nine species) to explore the molecular basis of high-altitude adaptation. Based on mitogenomic data, Bayesian inference, and maximum likelihood methods, we recovered a lycaenid phylogeny of [Curetinae + (Aphnaeinae + (Lycaeninae + (Theclinae + Polyommatinae)))]. The gene content, gene arrangement, base composition, codon usage, and transfer RNA genes (sequence and structure) were highly conserved within Lycaenidae. TrnS1 not only lacked the dihydrouridine arm but also showed anticodon and copy number diversity. The ratios of non-synonymous substitutions to synonymous substitutions of 13 protein-coding genes (PCGs) were less than 1.0, indicating that all PCGs evolved under purifying selection. However, signals of positive selection were detected in cox1 in the two Qinghai–Tibetan Plateau lycaenid species, indicating that this gene may be associated with high-altitude adaptation. Three large non-coding regions, i.e., rrnS-trnM (control region), trnQ-nad2, and trnS2-nad1, were found in the mitogenomes of all lycaenid species. Conserved motifs in three non-coding regions (trnE-trnF, trnS1-trnE, and trnP-nad6) and long sequences in two non-coding regions (nad6-cob and cob-trnS2) were detected in the Qinghai-Tibetan Plateau lycaenid species, suggesting that these non-coding regions were involved in high-altitude adaptation. In addition to the characterization of Lycaenidae mitogenomes, this study highlights the importance of both PCGs and non-coding regions in high-altitude adaptation.
Identification of the genetic basis of sow pelvic organ prolapse
Authors: Bhatia Vishesh , Stevens Tomas , Derks Martijn F. L. , Dunkelberger Jenelle , Knol Egbert F. , Ross Jason W. , Dekkers Jack C. M.
Published: April 2023

Introduction: Pelvic organ prolapse (POP) is one contributor to recent increases in sow mortality that have been observed in some populations and environments, leading to financial losses and welfare concerns.

Methods: With inconsistent previous reports, the objective here was to investigate the role of genetics on susceptibility to POP, using data on 30,429 purebred sows, of which 14,186 were genotyped (25K), collected from 2012 to 2022 in two US multiplier farms with a high POP incidence of 7.1% among culled and dead sows and ranging from 2% to 4% of all sows present by parity. Given the low incidence of POP for parities 1 and >6, only data from parities 2 to 6 were retained for analyses. Genetic analyses were conducted both across parities, using cull data (culled for POP versus another reason), and by parity, using farrowing data. (culled for POP versus culled for another reason or not culled).

Results and Discussion: Estimates of heritability from univariate logit models on the underlying scale were 0.35 ± 0.02 for the across-parity analysis and ranged from 0.41 ± 0.03 in parity 2 to 0.15 ± 0.07 in parity 6 for the by-parity analyses. Estimates of genetic correlations of POP between parities based on bivariate linear models indicated a similar genetic basis of POP across parities but less similar with increasing distance between parities. Genome wide association analyses revealed six 1 Mb windows that explained more than 1% of the genetic variance in the across-parity data. Most regions were confirmed in several by-parity analyses. Functional analyses of the identified genomic regions showed a potential role of several genes on chromosomes 1, 3, 7, 10, 12, and 14 in susceptibility to POP, including the Estrogen Receptor gene. Gene set enrichment analyses showed that genomic regions that explained more variation for POP were enriched for several terms from custom transcriptome and gene ontology libraries.

Conclusion: The influence of genetics on susceptibility to POP in this population and environment was confirmed and several candidate genes and biological processes were identified that can be targeted to better understand and mitigate the incidence of POP.
Promotion of BST2 expression by the transcription factor IRF6 affects the progression of endometriosis
Authors: Li Jixin , He Yanan , Qu Yanjun , Ren Chengcheng , Wang Xiaotong , Cheng Yan , Sun Liyuan , Zhang Xin , Zhang Guangmei
Published: April 2023

Background

Endometriosis (EM) is a benign, multifactorial, immune-mediated inflammatory disease that is characterized by persistent activation of the NF‐κB signaling pathway and some features of malignancies, such as proliferation and lymphangiogenesis. To date, the pathogenesis of EM is still unclear. In this study, we investigated whether BST2 plays a role in the development of EM.

Methods

Bioinformatic analysis was performed with data from public databases to identify potential candidate targets for drug treatment. Experiments were conducted at the cell, tissue, and mouse EM model levels to characterize the aberrant expression patterns, molecular mechanisms, biological behaviors of endometriosis as well as treatment outcomes.

Results

BST2 was significantly upregulated in ectopic endometrial tissues and cells compared with control samples. Functional studies indicated that BST2 promoted proliferation, migration, and lymphangiogenesis and inhibited apoptosis in vitro and in vivo. The transcription factor (TF) IRF6 induced high BST2 expression by directly binding the BST2 promoter. The underlying mechanism by which BST2 functions in EM was closely related to the canonical NF‐κB signaling pathway. New lymphatic vessels may serve as a channel for the infiltration of immune cells into the endometriotic microenvironment; these immune cells further produce the proinflammatory cytokine IL-1β, which in turn further activates the NF‐κB pathway to promote lymphangiogenesis in endometriosis.

Conclusion

Taken together, our findings provide novel insight into the mechanism by which BST2 participates in a feedback loop with the NF‐κB signaling pathway and reveal a novel biomarker and potential therapeutic target for endometriosis.
Case Report: Molecular autopsy underlie COVID-19-associated sudden, unexplained child mortality
Authors: Unuma Kana , Tomomasa Dan , Noma Kosuke , Yamamoto Kouhei , Matsuyama Taka-aki , Makino Yohsuke , Hijikata Atsushi , Wen Shuheng , Ogata Tsutomu , Okamoto Nobuhiko , Okada Satoshi , Ohashi Kenichi , Uemura Koichi , Kanegane Hirokazu
Published: April 2023

Herein, we report a child with COVID-19 and seemingly no underlying disease, who died suddenly. The autopsy revealed severe anemia and thrombocytopenia, splenomegaly, hypercytokinemia, and a rare ectopic congenital coronary origin. Immunohistochemical analysis demonstrated that the patient had acute lymphoblastic leukemia of the B-cell precursor phenotype (BCP-ALL). The complex cardiac and hematological abnormalities suggested the presence of an underlying disease; therefore, we performed whole-exome sequencing (WES). WES revealed a leucine-zipper-like transcription regulator 1 (LZTR1) variant, indicating Noonan syndrome (NS). Therefore, we concluded that the patient had underlying NS along with coronary artery malformation and that COVID-19 infection may have triggered the sudden cardiac death due to increased cardiac load caused by high fever and dehydration. In addition, multiple organ failure due to hypercytokinemia probably contributed to the patient’s death. This case would be of interest to pathologists and pediatricians because of the limited number of NS patients with LZTR1 variants; the complex combination of an LZTR1 variant, BCP-ALL, and COVID-19; and a rare pattern of the anomalous origin of the coronary artery. Thus, we highlight the significance of molecular autopsy and the application of WES with conventional diagnostic methods.
Hemagglutinin expressed by yeast reshapes immune microenvironment and gut microbiota to trigger diverse anti-infection response in infected birds
Authors: Xie Ruyu , Zhang Huixia , Zhang Han , Li Changyan , Cui Daqing , Li Shujun , Li Zexing , Liu Hualei , Huang Jinhai
Published: April 2023

Introduction

The H5N8 influenza virus is a highly pathogenic pathogen for poultry and human. Vaccination is the most effective method to control the spread of the virus right now. The traditional inactivated vaccine, though well developed and used widely, is laborious during application and more interests are stimulated in developing alternative approaches.

Methods

In this study, we developed three hemagglutinin (HA) gene-based yeast vaccine. In order to explore the protective efficacy of the vaccines, the gene expression level in the bursa of Fabricius and the structure of intestinal microflora in immunized animals were analyzed by RNA seq and 16SrRNA sequencing, and the regulatory mechanism of yeast vaccine was evaluated.

Results

All of these vaccines elicited the humoral immunity, inhibited viral load in the chicken tissues, and provided partial protective efficacy due to the high dose of the H5N8 virus. Molecular mechanism studies suggested that, compared to the traditional inactivated vaccine, our engineered yeast vaccine reshaped the immune cell microenvironment in bursa of Fabricius to promote the defense and immune responses. Analysis of gut microbiota further suggested that oral administration of engineered ST1814G/H5HA yeast vaccine increased the diversity of gut microbiota and the increasement of Reuteri and Muciniphila might benefit the recovery from influenza virus infection. These results provide strong evidence for further clinical use of these engineered yeast vaccine in poultry.
Performance comparison of TCR-pMHC prediction tools reveals a strong data dependency
Authors: Deng Lihua , Ly Cedric , Abdollahi Sina , Zhao Yu , Prinz Immo , Bonn Stefan
Published: April 2023

The interaction of T-cell receptors with peptide-major histocompatibility complex molecules (TCR-pMHC) plays a crucial role in adaptive immune responses. Currently there are various models aiming at predicting TCR-pMHC binding, while a standard dataset and procedure to compare the performance of these approaches is still missing. In this work we provide a general method for data collection, preprocessing, splitting and generation of negative examples, as well as comprehensive datasets to compare TCR-pMHC prediction models. We collected, harmonized, and merged all the major publicly available TCR-pMHC binding data and compared the performance of five state-of-the-art deep learning models (TITAN, NetTCR-2.0, ERGO, DLpTCR and ImRex) using this data. Our performance evaluation focuses on two scenarios: 1) different splitting methods for generating training and testing data to assess model generalization and 2) different data versions that vary in size and peptide imbalance to assess model robustness. Our results indicate that the five contemporary models do not generalize to peptides that have not been in the training set. We can also show that model performance is strongly dependent on the data balance and size, which indicates a relatively low model robustness. These results suggest that TCR-pMHC binding prediction remains highly challenging and requires further high quality data and novel algorithmic approaches.
Comparative transcriptomic analysis of gill reveals genes belonging to mTORC1 signaling pathway associated with the resistance trait of shrimp to VPAHPND
Authors: Liu Yuan , Yu Yang , Li Shihao , Sun Mingzhe , Li Fuhua
Published: April 2023

Selective breeding for acute hepatopancreatic necrosis disease (AHPND) resistant shrimp is an effective way to deal with heavy losses to shrimp aquaculture caused by AHPND. However, knowledge about the molecular mechanism of susceptibility or resistance to AHPND is very limited. We herein performed a comparative transcriptomic analysis of gill tissue between AHPND susceptible and resistant families of the white Pacific shrimp Litopenaeus vannamei during Vibrio parahaemolyticus (VPAHPND) infection. A total of 5,013 genes that were differentially expressed between the two families at 0 and 6 h post-infection, and 1,124 DEGs were shared for both two time points. Both GO and KEGG analyses in each or two time point’s comparisons showed DEGs involved in endocytosis, protein synthesis and cell inflammation were significantly enriched. Several immune DEGs including PRRs, antioxidants and AMPs were also identified. The susceptible shrimp showed enhanced endocytosis, higher aminoacyl-tRNA ligase activity and occurrence of inflammatory response, while the resistant shrimp had much more strong ability in ribosome biogenesis, antioxidant activity and pathogen recognition and clearance. These genes and processes were mostly associated with mTORC1 signaling pathway, which could reflect differences in cell growth, metabolism and immune response between the two families. Our findings indicate a close link between mTORC1 signaling-related genes and Vibrio-resistance phenotype of shrimp, and provide new clues for further research on resistance strategy of shrimp to AHPND.
Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution
Authors: Garcia-Donas Jesus , Martínez-Urbistondo Diego , Velázquez Kennedy Kyra , Villares Paula , Barquin Arántzazu , Dominguez Andrea , Rodriguez-Moreno Juan Francisco , Caro Elena , Suarez del Villar Rafael , Nistal-Villan Estanislao , Yagüe Monica , Ortiz Maria , Barba Maria , Ruiz-Llorente Sergio , Quiralte Miguel , Zanin Massimiliano , Rodríguez Cristina , Navarro Paloma , Berraondo Pedro , Madurga Rodrigo
Published: April 2023

Background

Managing the inflammatory response to SARS-Cov-2 could prevent respiratory insufficiency. Cytokine profiles could identify cases at risk of severe disease.

Methods

We designed a randomized phase II clinical trial to determine whether the combination of ruxolitinib (5 mg twice a day for 7 days followed by 10 mg BID for 7 days) plus simvastatin (40 mg once a day for 14 days), could reduce the incidence of respiratory insufficiency in COVID-19. 48 cytokines were correlated with clinical outcome.

Participants

Patients admitted due to COVID-19 infection with mild disease.

Results

Up to 92 were included. Mean age was 64 ± 17, and 28 (30%) were female. 11 (22%) patients in the control arm and 6 (12%) in the experimental arm reached an OSCI grade of 5 or higher (p = 0.29). Unsupervised analysis of cytokines detected two clusters (CL-1 and CL-2). CL-1 presented a higher risk of clinical deterioration vs CL-2 (13 [33%] vs 2 [6%] cases, p = 0.009) and death (5 [11%] vs 0 cases, p = 0.059). Supervised Machine Learning (ML) analysis led to a model that predicted patient deterioration 48h before occurrence with a 85% accuracy.

Conclusions

Ruxolitinib plus simvastatin did not impact the outcome of COVID-19. Cytokine profiling identified patients at risk of severe COVID-19 and predicted clinical deterioration.

Trial registration

https://clinicaltrials.gov/, identifier NCT04348695.
Effects of rumen cannulation combined with different pre-weaning feeding intensities on the intestinal, splenic and thymic immune system in heifer calves several month after surgery
Authors: Liermann Wendy , Tümmler Lisa-Maria , Kuhla Björn , Viergutz Torsten , Hammon Harald Michael
Published: April 2023

Fistulation is a helpful procedure in animal nutritional research and also common practise in human medicine. However, there are indications that alterations in the upper gastrointestinal tract contribute to intestinal immune modulations. The present study aimed to investigate effects of a rumen cannulation in week 3 of life on the intestinal and tissue specific immune system of 34-week old heifers. Nutrition influences the development of the neonatal intestinal immune system to a high extent. Therefore, rumen cannulation was investigated in combination with different pre-weaning milk feeding intensities (20% (20MR) vs. 10% milk replacer feeding (10MR). Heifers of 20MR without rumen cannula (NRC) showed higher cluster of differentiation (CD)8+ T cell subsets in mesenteric lymph nodes (MSL) compared to heifers with rumen cannula (RC) and 10MRNRC heifers. CD4+ T cell subsets in jejunal intraepithelial lymphocytes (IELs) were higher in 10MRNRC heifers compared to 10MRRC heifers. CD4+ T cell subsets in ileal IELs were lower and CD21+ B cell subsets were higher in NRC heifers compared to RC heifers. CD8+ T cell subsets in spleen tended to be lower in 20MRNRC heifers compared to all other groups. Splenic CD21+ B cell subsets were higher in 20MRNRC heifers compared to RC heifers. Splenic toll like receptor (TLR) 6 expression was increased and IL4 expression tended to be increased in RC heifers than NRC heifers. Splenic TLR2, 3 and 10 gene expression was higher in 20MR compared to 10MR heifers. Jejunal prostaglandin endoperoxide synthase 2 expression was higher in RC heifers than NRC heifers, and MUC2 expression tended to increase in 20MR heifers compared to 10MR heifers. In conclusion, rumen cannulation modulated T and B cell subsets in the down streaming gastrointestinal tract and spleen. Pre-weaning feeding intensity seemed to affect intestinal mucin secretion and T and B cell subsets in MSL, spleen and thymus until several month later. Interestingly, in MSL, spleen and thymus the 10MR feeding regime evoked similar modulations of T and B cell subsets like rumen cannulation.
Human adenovirus infection induces pulmonary inflammatory damage by triggering noncanonical inflammasomes activation and macrophage pyroptosis
Authors: Li Lexi , Fan Huifeng , Zhou Jinyu , Xu Xuehua , Yang Diyuan , Wu Minhao , Cao Can , Lu Gen
Published: April 2023

Introduction

Human adenovirus (HAdV) is a common respiratory virus, which can lead to severe pneumonia in children and immunocompromised persons, and canonical inflammasomes are reported to be involved in anti-HAdV defense. However, whether HAdV induced noncanonical inflammasome activation has not been explored. This study aims to explore the broad roles of noncanonical inflammasomes during HAdV infection to investigate the regulatory mechanism of HAdV-induced pulmonary inflammatory damage.

Methods

We mined available data on GEO database and collected clinical samples from adenovirus pneumonia pediatric patients to investigate the expression of noncanonical inflammasome and its clinical relevance. An in vitro cell model was employed to investigate the roles of noncanonical inflammasomes in macrophages in response to HAdV infection.

Results

Bioinformatics analysis showed that inflammasome-related genes, including caspase-4 and caspase-5, were enriched in adenovirus pneumonia. Moreover, caspase-4 and caspase-5 expression levels were significantly increased in the cells isolated from peripheral blood and broncho-alveolar lavage fluid (BALF) of pediatric patients with adenovirus pneumonia, and positively correlated with clinical parameters of inflammatory damage. In vitro experiments revealed that HAdV infection promoted caspase-4/5 expression, activation and pyroptosis in differentiated THP-1 (dTHP-1) human macrophages via NF-κB, rather than STING signaling pathway. Interestingly, silencing of caspase-4 and caspase-5 in dTHP-1 cells suppressed HAdV-induced noncanonical inflammasome activation and macrophage pyroptosis, and dramatically decreased the HAdV titer in cell supernatants, by influencing virus release rather than other stages of virus life cycle.

Discussion

In conclusion, our study demonstrated that HAdV infection induced macrophage pyroptosis by triggering noncanonical inflammasome activation via a NF-kB-dependent manner, which may explore new perspectives on the pathogenesis of HAdV-induced inflammatory damage. And high expression levels of caspase-4 and caspase-5 may be a biomarker for predicting the severity of adenovirus pneumonia.
NETosis as an oncologic therapeutic target: a mini review
Authors: Jaboury Sarah , Wang Kenny , O’Sullivan Kim Maree , Ooi Joshua Daniel , Ho Gwo Yaw
Published: April 2023

Neutrophil Extracellular Traps (NETs) are a key form of pro-inflammatory cell death of neutrophils characterized by the extrusion of extracellular webs of DNA containing bactericidal killing enzymes. NETosis is heavily implicated as a key driver of host damage in autoimmune diseases where injurious release of proinflammatory enzymes damage surrounding tissue and releases 70 known autoantigens. Recent evidence shows that both neutrophils and NETosis have a role to play in carcinogenesis, both indirectly through triggering DNA damage through inflammation, and directly contributing to a pro-tumorigenic tumor microenvironment. In this mini-review, we summarize the current knowledge of the various mechanisms of interaction and influence between neutrophils, with particular attention to NETosis, and cancer cells. We will also highlight the potential avenues thus far explored where we can intercept these processes, with the aim of identifying promising prospective targets in cancer treatment to be explored in further studies.
Interplay between systemic inflammation, anemia, and mycobacterial dissemination and its impact on mortality in TB-associated HIV: a prospective cohort study
Authors: Araújo-Pereira Mariana , Schutz Charlotte , Barreto-Duarte Beatriz , Barr David , Villalva-Serra Klauss , Vinhaes Caian L. , Ward Amy , Meintjes Graeme , Andrade Bruno B.
Published: April 2023

Introduction

Anemia frequently affects people living with HIV (PLHIV). Nevertheless, the impact of anemia on treatment outcomes of patients with HIV-associated tuberculosis (TB) and the underlying molecular profiles are not fully characterized. The aim of this study was to investigate the interplay between anemia, the systemic inflammatory profile, dissemination of TB and death in HIV-TB patients in an ad hoc analysis of results from a prospective cohort study.

Methods

496 hospitalized PLHIV ≥18 years old, with CD4 count <350 cells/μL and high clinical suspicion of new TB infection were enrolled in Cape Town between 2014-2016. Patients were classified according to anemia severity in non-anemic, mild, moderate, or severe anemia. Clinical, microbiologic, and immunologic data were collected at baseline. Hierarchical cluster analysis, degree of inflammatory perturbation, survival curves and C-statistics analyses were performed.

Results

Through the analysis of several clinical and laboratory parameters, we observed that those with severe anemia exhibited greater systemic inflammation, characterized by high concentrations of IL-8, IL-1RA and IL-6. Furthermore, severe anemia was associated with a higher Mtb dissemination score and a higher risk of death, particularly within 7 days of admission. Most of the patients who died had severe anemia and had a more pronounced systemic inflammatory profile.

Discussion

Therefore, the results presented here reveal that severe anemia is associated with greater TB dissemination and increased risk of death in PLHIV. Early identification of such patients through measurement of Hb levels may drive closer monitoring to reduce mortality. Future investigations are warranted to test whether early interventions impact survival of this vulnerable population.
NLRP3 inflammasome as a sensor of micro- and nanoplastics immunotoxicity
Authors: Alijagic Andi , Hedbrant Alexander , Persson Alexander , Larsson Maria , Engwall Magnus , Särndahl Eva
Published: April 2023

Micro- and nanoplastics (MNPs) are emerging pollutants with scarcely investigated effects on human innate immunity. If they follow a similar course of action as other, more thoroughly investigated particulates, MNPs may penetrate epithelial barriers, potentially triggering a cascade of signaling events leading to cell damage and inflammation. Inflammasomes are intracellular multiprotein complexes and stimulus-induced sensors critical for mounting inflammatory responses upon recognition of pathogen- or damage-associated molecular patterns. Among these, the NLRP3 inflammasome is the most studied in terms of activation via particulates. However, studies delineating the ability of MNPs to affect NLRP3 inflammasome activation are still rare. In this review, we address the issue of MNPs source and fate, highlight the main concepts of inflammasome activation via particulates, and explore recent advances in using inflammasome activation for assessment of MNP immunotoxicity. We also discuss the impact of co-exposure and MNP complex chemistry in potential inflammasome activation. Development of robust biological sensors is crucial in order to maximize global efforts to effectively address and mitigate risks that MNPs pose for human health.
Assessing the host range of Anastatus orientalis, an egg parasitoid of spotted lanternfly (Lycorma delicatula) using Eastern U.S. non-target species
Authors: Broadley Hannah J. , Sipolski Steven J. , Pitt Danielle B. , Hoelmer Kim A. , Wang Xiao-yi , Cao Liang-ming , Tewksbury Lisa A. , Hagerty Tyler J. , Bartlett Charles R. , Russell Alana D. , Wu Yunke , Davis Shannon C. , Kaser Joe M. , Elkinton Joseph S. , Gould Juli R.
Published: April 2023

The spotted lanternfly, Lycorma delicatula (Hemiptera: Fulgoridae), an invasive planthopper discovered in Pennsylvania, U.S. in 2014, has spread to many surrounding states despite quarantines and control efforts, and further spread is anticipated. A classical (importation) biological control program would contribute to the long-term management of L. delicatula in the eastern U.S. In its native range of China, Anastatus orientalis (Hymenoptera: Eupelmidae), an egg parasitoid, causes significant mortality. Anastatus orientalis consists of multiple haplotypes that differ in important biological parameters. To delineate the physiological host range of A. orientalis Haplotype C, we completed no-choice and choice testing. No-choice testing of non-target eggs from 36 insect species spanning six orders and 18 families showed that physiologically this haplotype of A. orientalis can develop in a variety of host species eggs from the families Coreidae, Fulgoridae, Pentatomidae, and Saturniidae. Ten of the 16 species that were attacked in the no-choice tests were also attacked in the choice tests. The production of progeny on non-target egg masses was significantly lower than on the controls (L. delicatula egg masses run simultaneously) in the no-choice and choice tests. For the non-target species that were attacked and resulted in female wasp progeny, these females were able to produce their own progeny at the same rate as control females that were reared from the L. delicatula eggs. Larger host eggs corresponded to an increased female-biased sex ratio of the progeny, suggesting that gravid females select them for fertilized eggs. Results from these studies suggest that A. orientalis Haplotype C prefers to parasitize L. delicatula egg masses but is capable of developing in some non-target species.