bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes of Peripheral Th17 Cells Subset in Overweight and Obese Children After Body Weight Reduction
Authors: Artemniak-Wojtowicz Dorota , Kucharska Anna M. , Stelmaszczyk-Emmel Anna , Majcher Anna , Pyrżak Beata
Published: July 2022

Background

Obesity has been a growing problem in young patients leading to serious metabolic complications. There are many studies supporting the idea, that obesity should be considered as a chronic inflammation closely associated with immune system alterations. Th17 subpopulation is strongly involved in this process. The aim of our study was to evaluate circulating Th17 cells in overweight and obese children and explore the relationships between Th17 subset and metabolic parameters.

Methods

We evaluated peripheral Th17 cells in fresh peripheral blood samples from 27 overweight and obese and 15 normal-weight children. Th17 cells were identified by flow cytometry using monoclonal antibody and intracellular IL-17A staining. Th17 cells were defined as CD3+CD4+CD196+IL-17Aic+. The analysis involved anthropometric and metabolic parameters measured at baseline and three months after the change of lifestyle and diet. We evaluated the relationship between metabolic parameters and Th17 cells.

Results

In overweight and obese children we found significantly higher Th17 cells percentage compared to normal weight controls (median 0.097% (0.044 - 0.289) vs 0.041% (0.023 - 0.099), p = 0.048). The percentage of Th17 cells decreased statistically significantly in children who reduced weight after the intervention (0.210% (0.143 - 0.315) vs 0.039% (0.028 - 0.106), p = 0.004). In this group we also noticed statistically significant reduction of TC and LDL-C concentration (p = 0.01, p = 0.04, respectively).

Conclusions

Obesity in children is associated with increased percentage of peripheral Th17 cells. Weight reduction leads to significant decrease of circulating Th17 cells and improvement of lipid parameters. This significant reduction of proinflammatory Th17 cells is a promising finding suggesting that obesity-induced inflammation in children could be relatively easily reversible.
Cushing’s Disease Management: Glimpse Into 2051
Authors: Dalan Rinkoo , Bornstein Stefan R. , Boehm Bernhard O.
Published: July 2022

Major advancements are expected in medicine and healthcare in the 21st century- “Digital Age”, mainly due to the application of data technologies and artificial intelligence into healthcare. In this perspective article we share a short story depicting the future Cushings’ Disease patient and the postulated diagnostic and management approaches. In the discussion, we explain the advances in recent times which makes this future state plausible. We postulate that endocrinology care will be completely reinvented in the Digital Age.
Survival in Pandemic Times: Managing Energy Efficiency, Food Diversity, and Sustainable Practices of Nutrient Intake Amid COVID-19 Crisis
Authors: Geng Jianli , Haq Shamsheer Ul , Abbas Jaffar , Ye Hongwei , Shahbaz Pomi , Abbas Azhar , Cai Yuyang
Published: July 2022

The COVID-19 pandemic led to an economic crisis and health emergency, threatening energy efficiency consumption, sustainable food diversity, and households’ nutrition security. The literature documented that environmental threats can divert attention from renewable energy and food security challenges that affect humans’ environmental behaviors. The COVID-19 crisis has consistently influenced environmental behaviors, as it primarily decreased income and disrupted food systems worldwide. This study investigated the COVID-19 consequences on household income, sustainable food diversity, sustainable energy consumption, and nutritional security challenges. The study used a self-structured online survey due to non-pharmaceutical restrictions and collected data from 728 households. The investigators applied t-test and logit regression to analyze the data for drawing results. Descriptive statistics show that COVID-19 has adversely affected the income of more than two-thirds (67%) of households. The pandemic has influenced households’ food consumption, energy, and dietary patterns to safeguard their income. The t-test analysis indicated that households’ food diversity and energy consumption significantly declined during the pandemic, and households consumed low-diversified food to meet their dietary needs more than twofold compared to pre-pandemic levels. The results showed that all nutrient consumption remained considerably lower in the COVID-19. Cereals are the primary source of daily dietary needs, accounting for over two-thirds of total energy and half of the nutrient consumption amid COVID-19. The share of vegetables and fruits in household energy consumption dropped by 40 and 30%. Results exhibited that increasing monthly income was inversely associated with worsening food diversity and intake with energy efficiency. Compared with farmers and salaried employment, wage earners were 0.15 and 0.28 times more likely to experience a decline in consuming food diversity. Medium and large households were 1.95 times and 2.64 times more likely than small, to experience decreased food diversity consumption. Launching a nutrition-sensitive program will help minimize the COVID-19 impacts on energy consumption, food diversity, and nutritional security for low-income individuals. This survey relied on the recall ability of the households for the consumed quantities of food commodities, which may lack accuracy. Longitudinal studies employing probability sampling with larger samples can verify this study’s insightful results.
Predictors of Mammalian Diversity in the New York Metropolitan Area
Authors: Bradfield Angelinna A. , Nagy Christopher M. , Weckel Mark , Lahti David C. , Habig Bobby
Published: July 2022

Urbanization can have profound consequences for mammalian biodiversity and is thought to contribute to patterns of species richness and community composition. Large cities can be particularly challenging environments for mammals because these habitats are often impacted by anthropogenic perturbations, including high human population density, fragmented habitats, and extensive human development. In this study, we investigated mammalian species richness, Shannon–Wiener diversity, and evenness in the most densely populated region in the United States: the New York metropolitan area. Specifically, we deployed camera traps from 2015 to 2019 to investigate six drivers of mammalian diversity across 31 greenspaces: (1) human population density, (2) patch size, (3) habitat type, (4) surrounding land cover, (5) geographical barriers to dispersal, and (6) habitat heterogeneity. We found that mammal community composition is largely influenced by a multitude of anthropogenic factors. Specifically, mammal species richness was higher in greenspaces with larger patch sizes and lower in greenspaces surrounded by more development. Moreover, Shannon–Wiener diversity and evenness were higher in urban natural landscapes than human-altered landscapes. In a subset of data that only included carnivores, we found that carnivore Shannon–Wiener diversity was higher in urban natural habitats and in sites with lower human population densities. Finally, we found that geographical barriers to dispersal contributed to both patterns of mammalian diversity and patterns of carnivore diversity: mammal taxa richness, Shannon–Wiener diversity, and evenness were all significantly higher on the continent (Bronx/Westchester) than on Long Island. These results suggest that preserving urban greenspaces is important for maintaining both mammalian and carnivore biodiversity and that management of mammals in cities should concentrate on maintaining large, connected, natural greenspaces.
Identification of a Gene Signature of Cancer-Associated Fibroblasts to Predict Prognosis in Ovarian Cancer
Authors: Zeng Li , Wang Xuehai , Wang Fengxu , Zhao Xinyuan , Ding Yiqian
Published: July 2022

Ovarian cancer (OvCa) is one of the most widespread malignant tumors, which has the highest morbidity and unsatisfactory clinical outcomes among all gynecological malignancies in the world. Previous studies found that cancer-associated fibroblasts (CAFs) play significant roles in tumor growth, progression, and chemoresistance. In the current research, weighted gene co-expression network analysis (WGCNA), univariable COX regression, and the least absolute shrinkage and selection operator (LASSO) analysis were applied to recognize CAF-specific genes. After multiple bioinformatic analyses, four genes (AXL, GPR176, ITGBL1, and TIMP3) were identified as OvCa-specific CAF markers and used to construct the prognostic signature (CAFRS). Furthermore, the specificity of the four genes' expression was further validated at the single-cell level, which was high-selectively expressed in CAFs. In addition, our results showed that CAFRS is an independent significant risk factor affecting the clinical outcomes of OvCa patients. Meanwhile, patients with higher CAFRS were more likely to establish chemoresistance to platinum. Besides, the CAFRS were notably correlated with well-known signal pathways that were related to tumor progression. In summary, our study identifies four CAF-specific genes and constructs a novel prognostic signature, which may provide more insights into precise prognostic assessment in OvCa.
In-Silico Study of Brassinosteroid Signaling Genes in Rice Provides Insight Into Mechanisms Which Regulate Their Expression
Authors: Ahmar Sunny , Gruszka Damian
Published: July 2022

Brassinosteroids (BRs) regulate a diverse spectrum of processes during plant growth and development and modulate plant physiology in response to environmental fluctuations and stress factors. Thus, the BR signaling regulators have the potential to be targeted for gene editing to optimize the architecture of plants and make them more resilient to environmental stress. Our understanding of the BR signaling mechanism in monocot crop species is limited compared to our knowledge of this process accumulated in the model dicot species - Arabidopsis thaliana. A deeper understanding of the BR signaling and response during plant growth and adaptation to continually changing environmental conditions will provide insight into mechanisms that govern the coordinated expression of the BR signaling genes in rice (Oryza sativa) which is a model for cereal crops. Therefore, in this study a comprehensive and detailed in silico analysis of promoter sequences of rice BR signaling genes was performed. Moreover, expression profiles of these genes during various developmental stages and reactions to several stress conditions were analyzed. Additionally, a model of interactions between the encoded proteins was also established. The obtained results revealed that promoters of the 39 BR signaling genes are involved in various regulatory mechanisms and interdependent processes that influence growth, development, and stress response in rice. Different transcription factor-binding sites and cis-regulatory elements in the gene promoters were identified which are involved in regulation of the genes’ expression during plant development and reactions to stress conditions. The in-silico analysis of BR signaling genes in O. sativa provides information about mechanisms which regulate the coordinated expression of these genes during rice development and in response to other phytohormones and environmental factors. Since rice is both an important crop and the model species for other cereals, this information may be important for understanding the regulatory mechanisms that modulate the BR signaling in monocot species. It can also provide new ways for the plant genetic engineering technology by providing novel potential targets, either cis-elements or transcriptional factors, to create elite genotypes with desirable traits.
Acute Thermoregulatory and Cardiovascular Response to Submaximal Exercise in People With Multiple Sclerosis
Authors: Gervasoni Elisa , Bertoni Rita , Anastasi Denise , Solaro Claudio , Di Giovanni Rachele , Grange Erica , Gunga Hanns-Christian , Rovaris Marco , Cattaneo Davide , Maggioni Martina Anna , Merati Giampiero
Published: July 2022

Background

Heat sensitivity occurs in a high percentage of people with multiple sclerosis (PwMS), in response to environmental or exercise-induced increase in body temperature. However, the kinetic and magnitude of adaptation of the internal load and of the core body temperature (CBT) to a submaximal continuous exercise has been poorly addressed in PwMS; this may be relevant for the brief exercise bouts usually occurring in normal daily life. The aim of this work was to evaluate whether multiple sclerosis influences the acute adaptation of the internal load, the CBT and the perceptual load in response to a constant submaximal work step.

Methods

CBT has been continuously monitored (0.5 Hz) by a validated wearable heat-flux sensor and electrocardiography was recorded (250 Hz) by a wearable device during a standard 6-minute walk test (6MWT) in 14 PwMS (EDSS, 4.7 ± 1.2; disease duration: 13.0 ± 10.2 years; m ± SD) and 14 age, sex and BMI-matched healthy subjects (HS). The rate of perceived exertion (RPE) of the lower limbs was assessed during the 6MWT by the Borg scale (6-20).

Results

As expected, PwMS walked a significantly shorter distance (361 ± 98 m) than the HS group (613 ± 62 m, p<0.001 vs PwMS). However, the kinetics of adaptation of CBT and the magnitude of CBT change from baseline did not differ between groups. Similarly, heart rate (HR) kinetics and HR change from baseline were comparable between groups during the 6MWT. Finally, lower limbs RPE gradually increased during the exercise test, but without significant differences between groups.

Conclusion

The internal load, the metabolic heat production, and the perceptive load due to a standard submaximal walking exercise seems to be preserved in PwMS, suggesting a comparable acute heat production and dissipation during exercise. Therefore, it is unlikely that the different distance achieved during the 6MWT may be caused by altered thermoregulatory responses to exercise. Rather, this appears to be a consequence of the known increased energy cost of locomotion in PwMS.
Immunotherapy: Reshape the Tumor Immune Microenvironment
Authors: LV Bingzhe , Wang Yunpeng , Ma Dongjiang , Cheng Wei , Liu Jie , Yong Tao , Chen Hao , Wang Chen
Published: July 2022

Tumor immune microenvironment (TIME) include tumor cells, immune cells, cytokines, etc. The interactions between these components, which are divided into anti-tumor and pro-tumor, determine the trend of anti-tumor immunity. Although the immune system can eliminate tumor through the cancer-immune cycle, tumors appear to eventually evade from immune surveillance by shaping an immunosuppressive microenvironment. Immunotherapy reshapes the TIME and restores the tumor killing ability of anti-tumor immune cells. Herein, we review the function of immune cells within the TIME and discuss the contribution of current mainstream immunotherapeutic approaches to remolding the TIME. Changes in the immune microenvironment in different forms under the intervention of immunotherapy can shed light on better combination treatment strategies.
Single-Cell Transcriptomics of Immune Cells Reveal Diversity and Exhaustion Signatures in Non-Small-Cell Lung Cancer
Authors: Zhao Ying , Zhang Qilin , Tu Kailin , Chen Yanmei , Peng Yuxuan , Ni Yinyun , Zhu Guonian , Cheng Cheng , Li Yangqian , Xiao Xue , Yu Chunyan , Lu Keying , Chen Yaxin , Li Chengpin , Tang Jun , Wang Gang , Luo Wenxin , Zhang Wengeng , Che Guowei , Li Weimin , Wang Zhoufeng , Xie Dan
Published: July 2022

Understanding immune cell phenotypes in the tumor microenvironment (TME) is essential for explaining and predicting progression of non-small cell lung cancer (NSCLC) and its response to immunotherapy. Here we describe the single-cell transcriptomics of CD45+ immune cells from tumors, normal tissues and blood of NSCLC patients. We identified three clusters of immune cells exerting immunosuppressive effects: CD8+ T cells with exhausted phenotype, tumor-associated macrophages (TAMs) with a pro-inflammatory M2 phenotype, and regulatory B cells (B regs) with tumor-promoting characteristics. We identified genes that may be mediating T cell phenotypes, including the transcription factors ONECUT2 and ETV4 in exhausted CD8+ T cells, TIGIT and CTL4 high expression in regulatory T cells. Our results highlight the heterogeneity of CD45+ immune cells in the TME and provide testable hypotheses about the cell types and genes that define the TME.
Soluble Immune Checkpoint-Related Proteins in Blood Are Associated With Invasion and Progression in Non-Small Cell Lung Cancer
Authors: Wang Qinchuan , He Yue , Li Wanlu , Xu Xiaohang , Hu Qingfeng , Bian Zilong , Xu Andi , Tu Huakang , Wu Ming , Wu Xifeng
Published: July 2022

Background

Immune checkpoint inhibition therapy has been achieved significant success in the treatment of non-small cell lung cancer (NSCLC). However, the role of soluble immune checkpoint- related proteins in NSCLC remains obscure.

Methods

We evaluated the circulating levels of 14 immune checkpoint-related proteins panel (BTLA, LAG-3, GITR, IDO, PD-L2, PD-L1, PD-1, HVEM, Tim-3, CD28, CD27, CD80, CD137 and CTLA-4) and their associations with the risk of invasive disease and the risk of NSCLC in 43 pre-invasive (AIS), 81 invasive NSCLC (IAC) patients and matched 35 healthy donors using a multiplex Luminex assay. Gene expression in tumors from TCGA were analyzed to elucidate potential mechanisms. The multivariate logistic regression model was applied in the study. ROC(receiver operator characteristic) curve and calibration curve were used in the performance evaluation.

Results

We found that sCD27, sCD80, CD137 and sPDL2 levels were significantly increased in IAC cases compared to AIS cases (P= 1.05E-06, 4.44E-05, 2.30E-05 and 1.16E-06, respectively), whereas sPDL1 and sPDL2 levels were significantly increased in NSCLC cases compared to healthy controls (P=3.25E-05 and 1.49E-05, respectively). Unconditional univariate logistic regression analysis indicated that increased sCD27, sCD80, sCD137, and sPDL2 were significantly correlated with the risk of invasive diseases. The model with clinical variables, sCD27 and sPDL2 demonstrated the best performance (AUC=0.845) in predicting the risk of IAC. CD27 and PDCD1LG2 (PDL2) showed significant association with cancer invasion signature in TCGA dataset.

Conclusion

Our study provides evidence that soluble immune checkpoint-related proteins may associate with the risk of IAC, and we further established an optimized multivariate predictive model, which highlights their potential application in the treatment of NSCLC patients. Future studies may apply these biomarkers to test their predictive value of survival and treatment outcome during immunotherapy in NSCLC patients.
Systematic Review of Safety and Efficacy of IL-1-Targeted Biologics in Treating Immune-Mediated Disorders
Authors: Arnold Dennis D. , Yalamanoglu Ayla , Boyman Onur
Published: July 2022

Background

The cytokine interleukin (IL)-1 plays a pivotal role in immune-mediated disorders, particularly in autoinflammatory diseases. Targeting this cytokine proved to be efficacious in treating numerous IL-1-mediated pathologies. Currently, three IL-1 blockers are approved, namely anakinra, canakinumab and rilonacept, and two additional ones are expected to receive approval, namely gevokizumab and bermekimab. However, there is no systematic review on the safety and efficacy of these biologics in treating immune-mediated diseases.

Objective

To evaluate safety and efficacy of anakinra, canakinumab, rilonacept, gevokizumab, and bermekimab for the treatment of immune-mediated disorders compared to placebo, standard-of-care treatment or other biologics.

Methods

The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 1 January 1984 and 31 December 2020 focusing on immune-mediated disorders. Our PubMed literature search identified 7363 articles. After screening titles and abstracts for the inclusion and exclusion criteria and assessing full texts, 75 articles were included in a narrative synthesis.

Results

Anakinra was both efficacious and safe in treating cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), gout, macrophage activation syndrome, recurrent pericarditis, rheumatoid arthritis (RA), and systemic juvenile idiopathic arthritis (sJIA). Conversely, anakinra failed to show efficacy in graft-versus-host disease, Sjögren’s syndrome, and type 1 diabetes mellitus (T1DM). Canakinumab showed efficacy in treating CAPS, FMF, gout, hyper-IgD syndrome, RA, Schnitzler’s syndrome, sJIA, and TNF receptor-associated periodic syndrome. However, use of canakinumab in the treatment of adult-onset Still’s disease and T1DM revealed negative results. Rilonacept was efficacious and safe for the treatment of CAPS, FMF, recurrent pericarditis, and sJIA. Contrarily, Rilonacept did not reach superiority compared to placebo in the treatment of T1DM. Gevokizumab showed mixed results in treating Behçet’s disease-associated uveitis and no benefit when assessed in T1DM. Bermekimab achieved promising results in the treatment of hidradenitis suppurativa.

Conclusions

This systematic review of IL-1-targeting biologics summarizes the current state of research, safety, and clinical efficacy of anakinra, bermekimab, canakinumab, gevokizumab, and rilonacept in treating immune-mediated disorders.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021228547.
Dengue Infection - Recent Advances in Disease Pathogenesis in the Era of COVID-19
Authors: Yong Yean Kong , Wong Won Fen , Vignesh Ramachandran , Chattopadhyay Indranil , Velu Vijayakumar , Tan Hong Yien , Zhang Ying , Larsson Marie , Shankar Esaki M.
Published: July 2022

The dynamics of host-virus interactions, and impairment of the host’s immune surveillance by dengue virus (DENV) serotypes largely remain ambiguous. Several experimental and preclinical studies have demonstrated how the virus brings about severe disease by activating immune cells and other key elements of the inflammatory cascade. Plasmablasts are activated during primary and secondary infections, and play a determinative role in severe dengue. The cross-reactivity of DENV immune responses with other flaviviruses can have implications both for cross-protection and severity of disease. The consequences of a cross-reactivity between DENV and anti-SARS-CoV-2 responses are highly relevant in endemic areas. Here, we review the latest progress in the understanding of dengue immunopathogenesis and provide suggestions to the development of target strategies against dengue.
[68Ga]Ga-DOTA-Siglec-9 Detects Pharmacodynamic Changes of FAP-Targeted IL2 Variant Immunotherapy in B16-FAP Melanoma Mice
Authors: Viitanen Riikka , Virtanen Helena , Liljenbäck Heidi , Moisio Olli , Li Xiang-Guo , Nicolini Valeria , Richard Marine , Klein Christian , Nayak Tapan , Jalkanen Sirpa , Roivainen Anne
Published: July 2022

Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible adhesion molecule, which supports contact between leukocytes and inflamed endothelium. There is evidence that VAP-1 is involved in the recruitment of leukocytes to melanoma tumors. Interleukin-2 (IL-2)-based immunotherapy is an efficient therapy that promotes immune system activity against cancers but is associated with toxicity. In the present study, we evaluated the feasibility of PET/CT imaging using the radiotracer [68Ga]Ga-DOTA-Siglec-9, which is targeted to VAP-1, to monitor pharmacodynamic effects of a novel FAP-IL2v immunocytokine (a genetically engineered variant of IL-2 fused with fibroblast activation protein) in the B16-FAP melanoma model. At 9 days after the inoculation of B16-FAP melanoma cells, mice were studied with [68Ga]Ga-DOTA-Siglec-9 PET/CT as a baseline measurement. Immediately after baseline imaging, mice were treated with FAP-IL2v or vehicle, and treatment was repeated 3 days later. Subsequent PET/CT imaging was performed 3, 5, and 7 days after baseline imaging. In addition toin vivoPET imaging,ex vivoautoradiography, histology, and immunofluorescence staining were performed on excised tumors. B16-FAP tumors were clearly detected with [68Ga]Ga-DOTA-Siglec-9 PET/CT during the follow-up period, without differences in tumor volume between FAP-IL2v-treated and vehicle-treated groups. Tumor-to-muscle uptake of [68Ga]Ga-DOTA-Siglec-9 was significantly higher in the FAP-IL2v-treated group than in the vehicle-treated group 7 days after baseline imaging, and this was confirmed by tumor autoradiography analysis. FAP-IL2v treatment did not affect VAP-1 expression on the tumor vasculature. However, FAP-IL2v treatment increased the number of CD8+T cells and natural killer cells in tumors. The present study showed that [68Ga]Ga-DOTA-Siglec-9 can detect B16-FAP tumors and allows monitoring of FAP-IL2v treatment.
Roles of Mast Cells in Cutaneous Diseases
Authors: Numata Takafumi , Harada Kazutoshi , Nakae Susumu
Published: July 2022

Mast cells are present in all vascularized tissues of the body. They are especially abundant in tissues that are in frequent contact with the surrounding environment and act as potential sources of inflammatory and/or regulatory mediators during development of various infections and diseases. Mature mast cells’ cytoplasm contains numerous granules that store a variety of chemical mediators, cytokines, proteoglycans, and proteases. Mast cells are activatedviavarious cell surface receptors, including FcϵRI, toll-like receptors (TLR), Mas-related G-protein-coupled receptor X2 (MRGPRX2), and cytokine receptors. IgE-mediated mast cell activation results in release of histamine and other contents of their granules into the extracellular environment, contributing to host defense against pathogens. TLRs, play a crucial role in host defense against various types of pathogens by recognizing pathogen-associated molecular patterns. On the other hand, excessive/inappropriate mast cell activation can cause various disorders. Here, we review the published literature regarding the known and potential inflammatory and regulatory roles of mast cells in cutaneous inflammation, including atopic dermatitis, psoriasis, and contact dermatitis GVHD, as well as in host defense against pathogens.
Beneficial Bacteria in the Intestines of Housefly Larvae Promote Larval Development and Humoral Phenoloxidase Activity, While Harmful Bacteria do the Opposite
Authors: Zhang Qian , Wang Shumin , Zhang Xinyu , Zhang Kexin , Li Ying , Yin Yansong , Zhang Ruiling , Zhang Zhong
Published: July 2022

The gut microenvironment of houseflies provides unique conditions for microbial colonization. Some gut microorganisms provide benefits for the development of the host by regulating the interaction between the host and intestinal pathogens. Gut microbial alterations can stimulate the host’s immune mechanism to resist pathogen invasion and affect the development of insects. In this study, we isolated 10 bacterial strains from housefly larval intestines. The isolated bacteria were added to the larval diet to analyze the effects of microecological regulation of gut bacteria on larval development. Dynamic changes in gut flora composition after oral administration of specific bacteria were analyzed although 16S rRNA gene high-throughput sequencing technology. To explore the interaction between gut bacteria and the host, the immune response of larvae against the invasion of foreign microorganisms was observed through a phenoloxidase activity experiment. Our results showed that the oral administration of various isolated bacteria had different effects on larval development. Oral administration of beneficial bacteria, including Enterobacter hormaechei, Klebsiella pneumoniae, Acinetobacter bereziniae, Enterobacter cloacae, Lysinibacillus fusiformis and Bacillus safensis, promoted larval development by increasing gut community diversity and the humoral immunity of larvae, while harmful bacteria, including Pseudomonas aeruginosa, Providencia stuartii and Providencia vermicola, influenced larval development by inhibiting the growth of beneficial bacteria and reducing the humoral immunity of larvae. The beneficial bacteria isolated in our research could be applied as good probiotic additives for the intensive feeding of larvae, while isolation of the harmful bacteria provides a basis for the development of pest inhibitors. Furthermore, our research revealed the immune response of housefly phenoloxidase to exogenous microorganism stimulation, providing richer and more comprehensive knowledge of the larval innate immune response.
Models and Tools for Investigating Eosinophilic Esophagitis at the Bench
Authors: Uchida Amiko M. , Ro Gabrielle , Garber John J. , Peterson Kathryn A. , Round June L.
Published: July 2022

Eosinophilic esophagitis (EoE) is an increasingly common food allergy disease of the esophagus that received its medical designation code in 2008. Despite this recency, great strides have been made in the understanding of EoE pathophysiology and type 2 immunity through basic and translational scientific investigations conducted at the bench. These advances have been critical to our understanding of disease mechanisms and generating new hypotheses, however, there currently is only one very recently approved FDA-approved therapy for EoE, leaving a great deal to be uncovered for patients with this disease. Here we review some of the innovative methods, models and tools that have contributed to the advances in EoE discovery and suggest future directions of investigation to expand upon this foundation.
Flexible Ferroelectric Materials-Based Triboelectric Nanogenerators for Mechanical Energy Harvesting
Authors: Dan Huiyu , Li Hongyu , Yang Ya
Published: July 2022

Triboelectric nanogenerators are widely used in a variety of applications including wearable electronics, self-driven sensors, electrochemistry, and other fields. A lot of work has been done by researchers to increase the performance of triboelectric nanogenerators. Changing device structure, physical surface engineering and chemical composition modification are common effective methods. Some recent studies have found that the polarization of ferroelectric materials can regulate the output of triboelectric nanogenerators. Compared with other materials, ferroelectric materials have the advantages of polarization characteristics and large dielectric constant, which can improve the output performance by regulating the electric potential on the surface of the material, and can also collect the pyroelectric -piezoelectric-triboelectric coupling energy. However, most ferroelectric materials are rigid and therefore difficult to apply to flexible wearable electronics. In this paper, we briefly describe the mechanism of ferroelectric polarization triboelectric output and the working mechanism of coupled generators, then introduce some flexible ferroelectric materials and finally introduce some of their recent applications.
A Review of Artificial Intelligence and Robotics in Transformed Health Ecosystems
Authors: Denecke Kerstin , Baudoin Claude R.
Published: July 2022

Health care is shifting toward become proactive according to the concept of P5 medicine–a predictive, personalized, preventive, participatory and precision discipline. This patient-centered care heavily leverages the latest technologies of artificial intelligence (AI) and robotics that support diagnosis, decision making and treatment. In this paper, we present the role of AI and robotic systems in this evolution, including example use cases. We categorize systems along multiple dimensions such as the type of system, the degree of autonomy, the care setting where the systems are applied, and the application area. These technologies have already achieved notable results in the prediction of sepsis or cardiovascular risk, the monitoring of vital parameters in intensive care units, or in the form of home care robots. Still, while much research is conducted around AI and robotics in health care, adoption in real world care settings is still limited. To remove adoption barriers, we need to address issues such as safety, security, privacy and ethical principles; detect and eliminate bias that could result in harmful or unfair clinical decisions; and build trust in and societal acceptance of AI.
Gut Fungal Microbiome Responses to Natural Cryptosporidium Infection in Horses
Authors: Wang Yaping , Li Xuwen , Chen Xiushuang , Kulyar Muhammad Fakhar-e-Alam , Duan Kun , Li Huade , Bhutta Zeeshan Ahmad , Wu Yi , Li Kun
Published: July 2022

It is critical to characterize changes in the structure and composition of the host fungal community in natural Cryptosporidium infection, because it gives the possible overview of gut microbiome in host homeostasis and disease progression. A total of 168 rectal fecal samples were collected and examined using nPCR. The positive samples were double-checked using 18S rDNA high-throughput sequencing. After confirmation, ITS high-throughput sequencing was utilized to investigate the fungal community’s response to natural Cryptosporidium infection. Results showed that a total of three positive samples (1.79%) were identified with an increased abundance of fungi associated with health hazards, such as class Dothideomycetes, families, i.e., Cladosporiaceae, Glomerellaceae, and genera, i.e., Wickerhamomyces, Talaromyces, Cladosporium, Dactylonectria, and Colletotrichum. On the contrary, taxa associated with favorable physiological effects on the host were shown to have the reverse impact, such as families, i.e., Psathyrellaceae, Pseudeurotiaceae and genera (Beauveria, Nigrospora, and Diversispora). For the first time, we evaluated the condition of natural Cryptosporidium infection in horses in Wuhan, China, and discovered distinct variations in the fungal microbiome in response to natural infection. It might prompt a therapy or prevention strategy to apply specific fungal microorganisms that are probably responsible for decreased susceptibility or increased resistance to infection.
Downregulation of TCF1 in HIV Infection Impairs T-cell Proliferative Capacity by Disrupting Mitochondrial Function
Authors: Cai Hong-Jiao , Shi Jue , Yin Lin-Bo , Zheng Jie-Fu , Fu Ya-Jing , Jiang Yong-Jun , Shang Hong , Zhang Zi-Ning
Published: July 2022

Background

Despite the benefits of antiretroviral therapy (ART) for people with HIV, T-cell dysfunction cannot be fully restored. Metabolic dysregulation is associated with dysfunction of HIV-1-specific T-cells. Exploration of the factors regulating metabolic fitness can help reverse T-cell dysfunction and provide new insights into the underlying mechanism.

Methods

In this study, HIV-infected individuals and HIV-negative control individuals (NCs) were enrolled. T-cell factor (TCF)1 expression in cells was determined by quantitative reverse-transcriptase polymerase chain reaction and flow cytometry. Relevant microarray data from the GEO database were analyzed to explore the underlying mechanism. The effects of TCF1 on T-cell function and metabolic function were assessed in vitro.

Results

TCF7 mRNA expression in peripheral blood mononuclear cells was downregulated in rapid progressors compared with long-term non-progressors individuals and NCs. TCF1 expression on CD4+ and CD8+ T-cells was downregulated in treatment-naïve HIV-infected individuals compared with NCs. Interleukin (IL)2 production and proliferative capacity were impaired in TCF1 knockdown T-cells. Moreover, glycolytic capacity and mitochondrial respiratory function were decreased in TCF1 knockdown T-cells, and depolarized mitochondria were increased in TCF1 knockdown T-cells.

Conclusion

Downregulation of TCF1 in HIV infection impairs T-cell proliferative capacity by disrupting mitochondrial function. These findings highlight the metabolic regulation as a pivotal mechanism of TCF1 in the regulation of T-cell dysfunction.
Response of Bacterial Community to the Occurrence of Clubroot Disease in Chinese Cabbage
Authors: Ni Haiping , Zong Rui , Sun Jianjun , Wu Yuxia , Yu Lei , Liu Yuanyuan , Liu Jin , Ju Ruicheng , Sun Xianli , Zheng Yulian , Tan Lekun , Liu Lumin , Dong Yachao , Li Tao , Zhang Youming , Tu Qiang
Published: July 2022

Clubroot disease is a common soilborne disease caused by Plasmodiophora brassicas Wor. and widely occurs in Chinese cabbage. Soil microorganisms play vital roles in the occurrence and development of plant diseases. The changes in the soil bacterial community could indicate the severity of plant disease and provide the basis for its control. This study focused on the bacterial community of the clubroot disease-infected soil–root system with different severity aiming to reveal the composition and structure of soil bacteria and identified potential biomarker bacteria of the clubroot disease. In the clubroot disease-infected soil, the bacterial community is mainly composed of Actinobacteria, Gammaproteobacteria, Alphaproteobacteria, Bacilli, Thermolrophilia, Bacteroidia, Gemmatimonadetes, Subgroup_6, Deltaproteobacteria, KD4-96, and some other classes, while the major bacterial classes in the infected roots were Oxyphotobacteria, Gammaproteobacteria, Alphaproteobacteria, Actinobacteria, Bacilli, Bacteroidia, Saccharimonadia, Thermoleophilia, Clostridia, Chloroflexia, and some other classes. The severe clubroot disease soil–root system was found to possess a poorer bacterial richness, evenness, and better coverage. Additionally, a significant difference was observed in the structure of the bacterial community between the high-severity (HR) and healthy (LR) soil–root system. Bacillus asahii and Noccaea caerulescens were identified as the differential bacteria between the LR and HR soil and roots, respectively. pH was demonstrated as a vital factor that was significantly associated with the abundance of B. asahii and N. caerulescens. This study provides novel insight into the relationship between soil bacteria and the pathogen of clubroot disease in Chinese cabbage. The identification of resistant species provides candidates for the monitoring and biocontrol of the clubroot disease.
A Cocktail of Three Virulent Phages Controls Multidrug-Resistant Salmonella Enteritidis Infection in Poultry
Authors: Li Yue , Lv Peilin , Shi Deshi , Zhao Hongze , Yuan Xu , Jin Xiue , Wang Xiliang
Published: July 2022

Salmonella enterica is not only the most common pathogen of poultry and poultry-derived products but is also a significant foodborne pathogen. In recent years, many S. enterica isolates have exhibited multi-drug resistance, which places huge pressure on global economy and health. Since phages are an attractive alternative to biocontrol pathogens, we isolated a total of 15 Salmonella phages from sewage effluent, sediment, and chicken manure. The GRNsp1, GRNsp3, GRNsp6, GRNsp21, GRNsp27, GRNsp30, GRNsp50, and GRNsp51 phages exhibited a wide host range against S. enterica serovars Enteritidis and Typhimurium in vitro. In particular, GRNsp51 exerted highly efficient lytic effects against a large proportion of S. Enteritidis and S. Typhimurium strains isolated from different regions of China. Meanwhile, GRNsp8 expanded the host range of GRNsp6 and GRNsp51. Based on their host ranges and lytic capacities, GRNsp6, GRNssp8, and GRNsp51 were selected for further investigation. Morphology, one-step growth curves, and stability assays revealed that GRNsp6, GRNsp8, and GRNsp51 all belong to the Caudovirales order and display relatively short latency periods with broad pH and thermal stability. Genomic analysis indicated that the genomes of these three phages contained no genes related to virulence, antibiotic resistance, or lysogeny. In addition, we tested the effectiveness of a cocktail composed of these three phages against S. Enteritidis in a chicken model. Treatment with the oral phage cocktail 24 h before or alongside Salmonella challenge significantly reduced colonization of the intestinal tract and decreased the mRNA expression of IL-6, IFN-γ, and IL-1β in the duodenum. Together, these findings indicate that a cocktail of the GRNsp6, GRNsp8, and GRNsp51 phages could serve as an effective antimicrobial therapeutic agent against multidrug-resistant Salmonella in animal production to mitigate infections by multiple zoonotic Salmonella species.
Practice Effect of Repeated Cognitive Tests Among Older Adults: Associations With Brain Amyloid Pathology and Other Influencing Factors
Authors: Zheng Bang , Udeh-Momoh Chinedu , Watermeyer Tamlyn , de Jager Loots Celeste A. , Ford Jamie K. , Robb Catherine E. , Giannakopoulou Parthenia , Ahmadi-Abhari Sara , Baker Susan , Novak Gerald P. , Price Geraint , Middleton Lefkos T.
Published: July 2022

Background

Practice effects (PE), after repeated cognitive measurements, may mask cognitive decline and represent a challenge in clinical and research settings. However, an attenuated practice effect may indicate the presence of brain pathologies. This study aimed to evaluate practice effects on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale, and their associations with brain amyloid status and other factors in a cohort of cognitively unimpaired older adults enrolled in the CHARIOT-PRO SubStudy.

Materials and Methods

502 cognitively unimpaired participants aged 60-85 years were assessed with RBANS in both screening and baseline clinic visits using alternate versions (median time gap of 3.5 months). We tested PE based on differences between test and retest scores in total scale and domain-specific indices. Multiple linear regressions were used to examine factors influencing PE, after adjusting for age, sex, education level, APOE-ε4 carriage and initial RBANS score. The latter and PE were also evaluated as predictors for amyloid positivity status based on defined thresholds, using logistic regression.

Results

Participants’ total scale, immediate memory and delayed memory indices were significantly higher in the second test than in the initial test (Cohen’s dz = 0.48, 0.70 and 0.35, P < 0.001). On the immediate memory index, the PE was significantly lower in the amyloid positive group than the amyloid negative group (P = 0.022). Older participants (≥70 years), women, non-APOE-ε4 carriers, and those with worse initial RBANS test performance had larger PE. No associations were found between brain MRI parameters and PE. In addition, attenuated practice effects in immediate or delayed memory index were independent predictors for amyloid positivity (P < 0.05).

Conclusion

Significant practice effects on RBANS total scale and memory indices were identified in cognitively unimpaired older adults. The association with amyloid status suggests that practice effects are not simply a source of measurement error but may be informative with regard to underlying neuropathology.
Event-Based Circular Detection for AUV Docking Based on Spiking Neural Network
Authors: Zhang Feihu , Zhong Yaohui , Chen Liyuan , Wang Zhiliang
Published: July 2022

In this paper, a circular objects detection method for Autonomous Underwater Vehicle (AUV) docking is proposed, based on the Dynamic Vision Sensor (DVS) and the Spiking Neural Network (SNN) framework. In contrast to the related work, the proposed method not only avoids motion blur caused by frame-based recognition during docking procedure but also reduces data redundancy with limited on-chip resources. First, four coplanar and rectangular constrained circular light sources are constructed as the docking landmark. By combining asynchronous Hough circle transform with the SNN model, the coordinates of landmarks in the image are detected. Second, a Perspective-4-Point (P4P) algorithm is utilized to calculate the relative pose between AUV and the landmark. In addition, a spatiotemporal filter is also used to eliminate noises generated by the background. Finally, experimental results are demonstrated from both software simulation and experimental pool, respectively, to verify the proposed method. It is concluded that the proposed method achieves better performance in accuracy and efficiency in underwater docking scenarios.
The Roles of ATP13A2 Gene Mutations Leading to Abnormal Aggregation of α-Synuclein in Parkinson’s Disease
Authors: Zhang Fan , Wu Zhiwei , Long Fei , Tan Jieqiong , Gong Ni , Li Xiaorong , Lin Changwei
Published: July 2022

Parkinson’s disease (PD) is the second most common neurodegenerative disease. PARK9 (also known as ATP13A2) is recognized as one of the key genes that cause PD, and a mutation in this gene was first discovered in a rare case of PD in an adolescent. Lewy bodies (LBs) formed by abnormal aggregation of α-synuclein, which is encoded by the SNCA gene, are one of the pathological diagnostic criteria for PD. LBs are also recognized as one of the most important features of PD pathogenesis. In this article, we first summarize the types of mutations in the ATP13A2 gene and their effects on ATP13A2 mRNA and protein structure; then, we discuss lysosomal autophagy inhibition and the molecular mechanism of abnormal α-synuclein accumulation caused by decreased levels and dysfunction of the ATP13A2 protein in lysosomes. Finally, this article provides a new direction for future research on the pathogenesis and therapeutic targets for ATP13A2 gene-related PD from the perspective of ATP13A2 gene mutations and abnormal aggregation of α-synuclein.
Sex-Related Microglial Perturbation Is Related to Mitochondrial Changes in a Model of Alzheimer’s Disease
Authors: O’Neill Eoin , Mela Virginia , Gaban Aline Sayd , Bechet Sibylle , McGrath Aoife , Walsh Aife , McIntosh Allison , Lynch Marina A.
Published: July 2022

Many studies implicate microglia in the pathogenesis of Alzheimer’s disease (AD) but precisely how these cells make their impact has not been determined to date. One contributory factor is likely to be the enhanced production of inflammatory mediators and it is now known that microglia with this secretory phenotype exhibit other adaptations including in their morphology, function, and metabolism. AD, like many neurological disorders, demonstrates a sex bias and recent evidence indicates that the sexual dimorphism in microglial function, which has been recognized for many years in early development, persists into adulthood and aging. Here, we demonstrate sex-related differences in microglia from post mortem tissue of male and female AD patients and a marked increase in the number of dystrophic and rod-shaped microglia in tissue from female AD patients compared with males. Furthermore, there was an increase in iron-laden microglia in tissue from female AD patients and this has been reported to reflect mitochondrial changes. To address this further, we assessed changes in microglia from male and female APP/PS1 mice and demonstrate that iron accumulation in microglia is increased to a greater extent in tissue prepared from females compared with males. This was associated with altered expression of genes coding for proteins that modulate mitochondrial function. The findings suggest that sex-related differences in the severity and perhaps incidence of AD may, at least in part, arise from sexual dimorphism in microglia.