bluuebunny/crossref_metadata_2025 huggingface dataset:
An Experimental and Comparative Performance Evaluation of a Hybrid Photovoltaic-Thermoelectric System
Authors: Khan Muhammad Ahsan Iqbal , Khan Muhammad Irfan , Kazim Ali Hussain , Shabir Aqsa , Riaz Fahid , Mustafa Nauman , Javed Hassan , Raza Ali , Hussain Mohsin , Salman Chaudhary Awais
Published: September 2021

The majority of incident solar irradiance causes thermalization in photovoltaic (PV) cells, attenuating their efficiency. In order to use solar energy on a large scale and reduce carbon emissions, their efficiency must be enhanced. Effective thermal management can be utilized to generate additional electrical power while simultaneously improving photovoltaic efficiency. In this work, an experimental model of a hybrid photovoltaic-thermoelectric generation (PV-TEG) system is developed. Ten bismuth telluride-based thermoelectric modules are attached to the rear side of a 10 W polycrystalline silicon-based photovoltaic module in order to recover and transform waste thermal energy to usable electrical energy, ultimately cooling the PV cells. The experiment was then carried out for 10 days in Lahore, Pakistan, on both a simple PV module and a hybrid PV-TEG system. The findings revealed that a hybrid system has boosted PV module output power and conversion efficiency. The operating temperature of the PV module in the hybrid system is reduced by 5.5%, from 55°C to 52°C. Due to a drop in temperature and the addition of some recovered energy by thermoelectric modules, the total output power and conversion efficiency of the system increased. The hybrid system’s cumulative output power increased by 19% from 8.78 to 10.84 W, compared to the simple PV system. Also, the efficiency of the hybrid PV-TEG system increased from 11.6 to 14%, which is an increase of 17% overall. The results of this research could provide consideration for designing commercial hybrid PV-TEG systems.
Reducing Uncertainty in 21st Century Sea-Level Predictions and Beyond
Authors: Siegert Martin , Pearson Pam
Published: September 2021

Sea-level rise is one of the most critical issues the world faces under global warming. Around 680 million people (10% of the world’s population) live in low-lying coastal regions that are susceptible to flooding through storm surges and from sea-water infiltration of fresh groundwater reserves, degradation of farmland and accelerated coastal erosion, among other impacts. Rising sea level will exacerbate these problems and lead to societal impacts ranging from crop and water-supply failures to breakdowns of city infrastructures. In time, it is likely such changes will necessitate the migration of people with substantial economic cost and social upheaval. Here, we discuss the physical processes influencing 21st Century sea-level rise, the importance of not using 2100 alone as a benchmark, the changes that are already locked in, especially after 2100, and those that can be avoided. We also consider the need for both adaptation and mitigation measures and early warning systems in this challenging global problem. Finally, we discuss how the scientific prediction of sea level rise can improved through international coordination, cooperation and cost sharing.
Floral Resources Enhance Fecundity, but Not Flight Activity, in a Specialized Aphid Predator, Hippodamia convergens (Coleoptera: Coccinellidae)
Authors: Stowe Hannah E. , Michaud J. P. , Kim Tania N.
Published: September 2021

Adult aphid predators disperse across the landscape seasonally in search of prey aggregations that are patchily distributed and temporally variable. However, flight is energetically costly and consumes resources that could be invested in reproduction. Hippodamia convergens is an important aphid predator in North American cereal crops and other agricultural systems. Consumption of floral resources can enhance adult survival during periods of low prey availability and may improve reproductive success. We tested how an omnivorous adult diet containing floral resources (diluted honey and pulverized bee pollen) interacts with body size to influence reproduction and flight behavior compared to a prey-only diet. Two sizes of beetles were produced by controlling larval access to food—3 h daily access produced small beetles; ad libitum access produced large beetles with faster development. Reproductive performance was tracked for 18 days, and female flight activity was assayed via 3 h bouts of tethered flight. Diet composition and body size interacted to influence preoviposition period, with large females in prey-only treatments delaying oviposition the longest. The omnivorous adult diet improved 18-day fecundity relative to a prey-only diet, but egg fertility was unaffected. Adult size affected oviposition pattern, with small beetles laying smaller, but more numerous, clutches. Females flew up to 7 km in 6 h, but neither body size nor adult diet influenced flight distance, suggesting that all diet treatments generated energy reserves sufficient to power flights of short duration. However, pre-reproductive females flew > 60% further than they did post-reproduction, likely due to the energetic costs of oviposition. Thus, access to pollen and nectar increased reproductive success and altered oviposition patterns in H. convergens, indicating the importance of floral resources in the agricultural landscape to conservation of this predator and its biological control services.
Application of Exosomes-Derived Mesenchymal Stem Cells in Treatment of Fungal Diseases: From Basic to Clinical Sciences
Authors: Ghasemian Seyedeh Ommolbanin
Published: September 2021

Fungal diseases such as candidiasis are some of the deadliest diseases among immunocompromised patients. These fungi naturally exist on human skin and throughout the digestive system. When the microbiota balance becomes upset, these fungi become pathogenic and potentially lethal. At the pathogenesis of fungal diseases, host immune system response is diverse. At the early stages of fungal pathogenesis such as Candida albicans, it was shown that these fungi use the immune cells of the host body and cause malfunction the early induction of proinflammatory cytokines of the host body leading to a reduction in their numbers. However, at some stages of fungal diseases, the immune response is severe. Despite many treatments already being available, it seems that one of the best treatments could be an immune-stimulatory agent. Some of the subsets of MSCs and exosome-derived cells, as a cell-to-cell communicator agent, have many roles in the human body, including anti-inflammatory and immune-modulatory effects. However, the TLR4-primed and IL-17+ subsets of MSCs have been shown to have immune-stimulatory effects. These subsets of the MSCs produce pro-inflammatory cytokines and reduce immunosuppressive cytokines and chemokines. Thus, they could trigger inflammation and stop fungal pathogenesis. As some biological activities and molecules inherit elements of their exosomes from their maternal cells, the exosome-derived TLR4-primed and IL-17+ subsets of MSCs could be a good candidate for fighting against fungal diseases. The applications of exosomes in human diseases are well-known and expanding. It is time to investigate the exosomes application in fungal diseases. In this review, the probable role of exosomes in treating fungal diseases is explored.
Heritability Estimate for Antibody Response to Vaccination and Survival to a Newcastle Disease Infection of Native chicken in a Low-Input Production System
Authors: Hako Touko Blaise Arnaud , Kong Mbiydzenyuy Anold Tatah , Tumasang Tebug Thomas , Awah-Ndukum Julius
Published: September 2021

The Newcastle disease virus (NDV) is the deadliest chicken pathogen in low-input village poultry, and selecting for NDV resistance has been recommended as a sustainable strategy in backyard poultry production systems. However, selecting for disease resistance needs precision data from either a big population sample size or on many generations with good pedigree records for effective prediction of heritability (h2) and breeding values of the foundation stock. Such conditions are almost impossible to meet in low-input backyard production systems. This study aimed at proposing a realistic method for estimating the heritability of the immune response to vaccination and survival of NDV infection in village poultry production to inform a breeding strategy for ND resistance in Cameroon. A 1 and 3% selection intensity of cocks and hens for higher antibody (ab) response (ABR) to vaccination followed by progeny selection of chickens who survived an experimental NDV infection was conducted from an initial population of 1,702 chickens. The selection induced an increase of 1012.47units/ml (p<0.01) of the NDV antibody of the progeny as well as an effective survival rate (ESR) increase of 11.75%. Three methods were used to estimate the heritability (h2) of NDV antibody response to vaccination. h2 was low irrespective of the method with estimates of 0.2227, 0.2442, and 0.2839 for the breeder’s equation method, the graphical method, and the full-sib/half-sib nested design, respectively. The mortality rate of infected chickens was high (86%). The antibody response to selection was not influenced by sex and genetic type even though the opposite was observed (p<0.05) for the ESR to NDV infection with naked neck chickens recording an ESR of 14% against 2.25% for the normal feather type. A very low heritability (0.0891) was observed for the survival against NDV infection. We confirm the evidence of disease resistance and the effect of selection for antibody response to vaccination on the improvement of the survival against NDV disease. Although the full sib/half sib nested design is more appropriate in case of availability of pedigree information, the direct methods are still useful in case of unavailability of full pedigree information. It is recommended that gene expression analysis should be prioritized for disease-resistance assessment and selection of native breeds of poultry.
ILPMDA: Predicting miRNA–Disease Association Based on Improved Label Propagation
Authors: Wang Yu-Tian , Li Lei , Ji Cun-Mei , Zheng Chun-Hou , Ni Jian-Cheng
Published: September 2021

MicroRNAs (miRNAs) are small non-coding RNAs that have been demonstrated to be related to numerous complex human diseases. Considerable studies have suggested that miRNAs affect many complicated bioprocesses. Hence, the investigation of disease-related miRNAs by utilizing computational methods is warranted. In this study, we presented an improved label propagation for miRNA–disease association prediction (ILPMDA) method to observe disease-related miRNAs. First, we utilized similarity kernel fusion to integrate different types of biological information for generating miRNA and disease similarity networks. Second, we applied the weighted k-nearest known neighbor algorithm to update verified miRNA–disease association data. Third, we utilized improved label propagation in disease and miRNA similarity networks to make association prediction. Furthermore, we obtained final prediction scores by adopting an average ensemble method to integrate the two kinds of prediction results. To evaluate the prediction performance of ILPMDA, two types of cross-validation methods and case studies on three significant human diseases were implemented to determine the accuracy and effectiveness of ILPMDA. All results demonstrated that ILPMDA had the ability to discover potential miRNA–disease associations.
Chondrogenically Primed Human Mesenchymal Stem Cells Persist and Undergo Early Stages of Endochondral Ossification in an Immunocompetent Xenogeneic Model
Authors: Fahy Niamh , Palomares Cabeza Virginia , Lolli Andrea , Witte-Bouma Janneke , Merino Ana , Ridwan Yanto , Wolvius Eppo B. , Hoogduijn Martin J. , Farrell Eric , Brama Pieter A. J.
Published: September 2021

Tissue engineering approaches using progenitor cells such as mesenchymal stromal cells (MSCs) represent a promising strategy to regenerate bone. Previous work has demonstrated the potential of chondrogenically primed human MSCs to recapitulate the process of endochondral ossification and form mature bone in vivo, using immunodeficient xenogeneic models. To further the translation of such MSC-based approaches, additional investigation is required to understand the impact of interactions between human MSC constructs and host immune cells upon the success of MSC-mediated bone formation. Although human MSCs are considered hypoimmunogenic, the potential of chondrogenically primed human MSCs to induce immunogenic responses in vivo, as well as the efficacy of MSC-mediated ectopic bone formation in the presence of fully competent immune system, requires further elucidation. Therefore, the aim of this study was to investigate the capacity of chondrogenically primed human MSC constructs to persist and undergo the process of endochondral ossification in an immune competent xenogeneic model. Chondrogenically differentiated human MSC pellets were subcutaneously implanted to wild-type BALB/c mice and retrieved at 2 and 12 weeks post-implantation. The percentages of CD4+ and CD8+ T cells, B cells, and classical/non-classical monocyte subsets were not altered in the peripheral blood of mice that received chondrogenic MSC constructs compared to sham-operated controls at 2 weeks post-surgery. However, MSC-implanted mice had significantly higher levels of serum total IgG compared to sham-operated mice at this timepoint. Flow cytometric analysis of retrieved MSC constructs identified the presence of T cells and macrophages at 2 and 12 weeks post-implantation, with low levels of immune cell infiltration to implanted MSC constructs detected by CD45 and CD3 immunohistochemical staining. Despite the presence of immune cells in the tissue, MSC constructs persisted in vivo and were not degraded/resorbed. Furthermore, constructs became mineralised, with longitudinal micro-computed tomography imaging revealing an increase in mineralised tissue volume from 4 weeks post-implantation until the experimental endpoint at 12 weeks. These findings indicate that chondrogenically differentiated human MSC pellets can persist and undergo early stages of endochondral ossification following subcutaneous implantation in an immunocompetent xenogeneic model. This scaffold-free model may be further extrapolated to provide mechanistic insight to osteoimmunological processes regulating bone regeneration and homeostasis.
Outcome of 313 Czech Patients With IgA Nephropathy After Renal Transplantation
Authors: Maixnerova Dita , Hruba Petra , Neprasova Michaela , Bednarova Kamila , Slatinska Janka , Suchanek Miloslav , Kollar Marek , Novak Jan , Tesar Vladimir , Viklicky Ondrej
Published: September 2021

The recurrence of IgA nephropathy (IgAN) after kidney transplantation occurs in 20–35% of patients. The main aim of this study is to evaluate risk factors affecting the course of IgAN after renal biopsy of native kidney and kidney transplant. We evaluated clinical parameters and histological findings at the time of biopsy of native kidney and after kidney transplantation in 313 patients with IgAN with a follow-up of up to 36 years. Using hierarchical clustering method, patients with graft failure (n=50) were divided into two groups based on the mean time from kidney transplant to graft failure (11.2 versus 6.1 years). The time-to-graft failure corresponded well to the time from the renal biopsy of native kidney to end-stage renal disease (5.9 versus 0.4 years). Body mass index, proteinuria, microscopic hematuria, histological evaluation of fibrosis, and crescents at the time of renal biopsy of native kidney were the main variables for the differentiation of the two groups. Higher age of kidney-transplant donor, histological recurrence of IgAN, antibody-mediated rejection, and the onset of microscopic hematuria and proteinuria within 1 year after kidney transplant were also associated with worse graft survival in multivariate Cox regression analysis.
Hyperinflammatory Immune Response and COVID-19: A Double Edged Sword
Authors: Tan Li Yin , Komarasamy Thamil Vaani , RMT Balasubramaniam Vinod
Published: September 2021

The coronavirus disease-19 (COVID-19) elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused devastating health, economic and social impact worldwide. Its clinical spectrum ranges from asymptomatic to respiratory failure and multi-organ failure or death. The pathogenesis of SARS-CoV-2 infection is attributed to a complex interplay between virus and host immune response. It involves activation of multiple inflammatory pathways leading to hyperinflammation and cytokine storm, resulting in tissue damage, acute respiratory distress syndrome (ARDS) and multi-organ failure. Accumulating evidence has raised concern over the long-term health effects of COVID-19. Importantly, the neuroinvasive potential of SARS-CoV-2 may have devastating consequences in the brain. This review provides a conceptual framework on how the virus tricks the host immune system to induce infection and cause severe disease. We also explore the key differences between mild and severe COVID-19 and its short- and long-term effects, particularly on the human brain.
The Modulatory Activity of Tryptophan Displaying Nanodevices on Macrophage Activation for Preventing Acute Lung Injury
Authors: Sun Liya , Wang Rui , Wu Chenchen , Gong Jiameng , Ma Huiqiang , Fung Shan-Yu , Yang Hong
Published: September 2021

Macrophages play an important role in the initiation, progression and resolution of inflammation in many human diseases. Effective regulation of their activation and immune responses could be a promising therapeutic strategy to manage various inflammatory conditions. Nanodevices that naturally target macrophages are ideal agents to regulate immune responses of macrophages. Here we described a special tryptophan (Trp)-containing hexapeptide-coated gold nanoparticle hybrid, PW, which had unique immunomodulatory activities on macrophages. The Trp residues enabled PW higher affinity to cell membranes, and contributed to inducing mild pro-inflammatory responses of NF-κB/AP-1 activation. However, in the presence of TLR stimuli, PW exhibited potent anti-inflammatory activities through inhibiting multiple TLR signaling pathways. Mechanistically, PW was internalized primarily through micropinocytosis pathway into macrophages and attenuated the endosomal acidification process, and hence preferentially affected the endosomal TLR signaling. Interestingly, PW could induce the expression of the TLR negative regulator IRAK-M, which may also contribute to the observed TLR inhibitory activities. In two acute lung injury (ALI) mouse models, PW could effectively ameliorate lung inflammation and protect lung from injuries. This work demonstrated that nanodevices with thoughtful design could serve as novel immunomodulatory agents to manage the dysregulated inflammatory responses for treating many chronic and acute inflammatory conditions, such as ALI.
Additive Manufacturing and Injection Moulding of High-Performance IF-WS2/PEEK Nanocomposites: A Comparative Study
Authors: Golbang Atefeh , Mokhtari Mozaffar , Harkin-Jones Eileen , Archer Edward , Mcilhagger Alistair
Published: September 2021

In this study, PEEK nanocomposites with 0, 0.5, 1, and 2wt% IF-WS2 were manufactured by injection moulding and Fused Deposition Modelling (FDM). To compare the impact of the two processing methods and the incorporated nanoparticles on the morphology, crystallization and final mechanical properties of the nanocomposites, SEM, DSC and tensile testing were performed. In general, a good distribution of nanoparticles was observed in PEEK, although larger agglomerates were visible at 2 wt% IF-WS2. The crystallization degree of PEEK increased with increasing loading of IF-WS2 nanoparticles up to 1wt% and then declined at 2 wt%, due to lower level of particle dispersion in this sample. The 3D printed samples showed slightly higher crystallinity at each IF-WS2 loading in relation to the injection moulded samples and extruded filaments, because of multiple reheating effect from subsequent layer deposition during FDM, causing recrystallization. In general, incorporation of IF-WS2 nanoparticles increased the mechanical properties of pure PEEK in both 3D printed and injection moulded samples. However, this increment was more noticeable in the 3D-printed nanocomposite samples, resulting in smaller gap between the mechanical properties of the 3D-printed samples and the injection moulded counterparts, in respect to pure PEEK, particularly at 1 wt% IF-WS2. This effect is ascribed to the increased inter-layer bonding of PEEK in the presence of IF-WS2 nanoparticles in FDM. In general, the lower mechanical properties of the 3D printed samples compared with the injection moulded ones are ascribed to poor interlayer bonding between the deposited layers and the presence of voids. However, addition of just 1 wt% of IF-WS2 nanoparticles into PEEK increased the tensile strength and Young’s modulus of the FDM PEEK materials to similar levels to those achieved for unfilled injection moulded PEEK. Therefore, incorporation of IF-WS2 nanoparticles into PEEK is a useful strategy to improve the mechanical performance of FDM PEEK.
Clinical, Pathological, Laboratory Characteristics, and Treatment Regimens of Kimura Disease and Their Relationships With Tumor Size and Recurrence
Authors: Fan Lina , Mo Shiyan , Wang Yanyan , Zhu Jian
Published: September 2021

Objective: As of date, Kimura disease (KD) has an unclear etiology, no accepted diagnostic standard, and no definite treatment regimen. In this study, clinical and pathological laboratory characteristics and treatment regimens of patients with KD with different tumor sizes and status of tumor recurrence were analyzed. This was performed to identify the factors, which determine tumor size and recurrence, and to identify effective treatment methods for patients with KD.

Methods: A total of 33 hospitalized patients with a definite diagnosis of KD were enrolled in this study.

Results: There were 15 patients (45.5%) with a maximum tumor diameter of <3 cm. There were no statistically significant differences in age, gender, clinical symptoms, lesion sites, laboratory indicators, and treatment regimens among patients with a maximum tumor diameter <3 cm or ≥3 cm (P > 0.05). Among the 25 patients who completed the follow-up, there were 18 patients (72%) who had a recurrence of KD. There were no statistically significant differences in age, gender, clinical symptoms, the maximum tumor diameter, lesion sites, laboratory indicators, and initial treatment regimens between patients with or without the recurrence of KD (P > 0.05). There was a statistically significant difference in systolic blood pressure (SBP) between patients with or without the recurrence of KD (P < 0.05). All patients who received only surgical treatment had disease recurrence, 33.3% of patients who received prednisone therapy had no disease recurrence, and 37.5% of patients who received combination therapy showed recurrence.

Conclusion: The current study summarized clinical manifestations, pathological features, laboratory indicators, and treatment regimens of patients with KD. There were no significant differences in these aspects among patients with different tumor sizes, and there was no significant difference in these aspects except in the SBP between patients with or without the recurrence of KD, indicating that SBP is a significant clinical factor affecting disease recurrence in patients. Combination therapy with prednisone was found to be superior to surgical treatment.
Enterocytozoon Bieneusi Infects Children With Inflammatory Bowel Disease Undergoing Immunosuppressive Treatment
Authors: Zajączkowska Żaneta , Akutko Katarzyna , Kváč Martin , Sak Bohumil , Szydłowicz Magdalena , Hendrich Andrzej B. , Iwańczak Barbara , Kicia Marta
Published: September 2021

Objectives: Patients with inflammatory bowel disease (IBD) are susceptible to intestinal opportunistic infections due to both defective mucosal immunity and altered immune response resulting from immunosuppressive treatment. Microsporidia infecting the gastrointestinal tract and causing diarrhoea can potentially affect the course of IBD.

Methods: Stool samples (90 IBD children and 121 healthy age-matched controls) were screened for Encephalitozoon spp. and Enterocytozoon bieneusi by microscopy and polymerase chain reaction followed by sequencing.

Results:E. bieneusi genotype D was found in seven out of 90 (7.8%) IBD children. No children from the control group were infected, making the pathogen prevalence in the IBD group significant (P = 0.002). Furthermore, infection was confirmed only in patients receiving immunosuppressive treatment (P = 0.013).

Conclusions: Children with IBD are at risk of intestinal E. bieneusi infection, especially when receiving immunosuppressive treatment. Therefore, microsporidia should be considered as a significant infectious agent in this group of patients.
Prospecting Endophytic Bacteria Endowed With Plant Growth Promoting Potential Isolated From Camellia sinensis
Authors: Hazarika Shabiha Nudrat , Saikia Kangkon , Borah Atlanta , Thakur Debajit
Published: September 2021

Endophytes are well-acknowledged inoculants to promote plant growth, and extensive research has been done in different plants. However, there is a lacuna about the endophytes associated with tea clones and their benefit to promote plant growth. The present study focuses on isolating and characterizing the beneficial endophytic bacteria (EnB) prevalent in commercially important tea clones cultivated in North Eastern India as plant growth promoters. Diversity of culturable EnB microbiome, in vitro traits for plant growth promotion (PGP), and applicability of potent isolates as bioinoculant for in vivo PGP abilities have been assessed in the present study. A total of 106 EnB identified as members of phyla Proteobacteria, Firmicutes, and Actinobacteria were related to 22 different genera and six major clusters. Regarding PGP traits, the percentage of isolates positive for the production of indole acetic acid, phosphate solubilization, nitrogen fixation siderophore, ammonia, and 1-aminocyclopropane-1-carboxylic acid deaminase production were 86.8, 28.3, 78.3, 30.2, 95.3, and 87.7, respectively. In total, 34.0, 52.8, and 17.0% of EnB showed notable production of hydrolytic enzymes like cellulase, protease, and amylase, respectively. Additionally, based on the bonitur score, the top two isolates K96 identified as Stenotrophomonas sp. and M45 identified as Pseudomonas sp. were evaluated for biofilm formation, motility, and in vivo plant growth promoting activity. Results suggested strong biofilm formation and motility in K96 and M45 which may attribute to the colonization of the strains in the plants. Further in vivo plant growth promotion experiment suggested sturdy efficacy of the K96 and M45 as plant growth promoters in nursery condition in commercial tea clones Tocklai vegetative (TV) TV22 and TV26. Thus, this study emphasizes the opportunity of commercialization of the selected isolates for sustainable development of tea and other crops.
Biocontrol Mechanism of Bacillus subtilis C3 Against Bulb Rot Disease in Fritillaria taipaiensis P.Y.Li
Authors: Ku Yongli , Yang Nan , Pu Peng , Mei Xueli , Cao Le , Yang Xiangna , Cao Cuiling
Published: September 2021

Bulb rot disease has become one of the main diseases that seriously affects the yield and quality of Fritillaria taipaiensis P.Y.Li (F. taipaiensis). In this study, F. taipaiensis was used as the research object to explore the effect and mechanism of Bacillus subtilis C3 in preventing and curing bulb rot. Through isolation and verification of the pathogenic fungi, we determined for the first time that the pathogenic fungus that causes bulb rot in F. taipaiensis is Fusarium oxysporum. The results of the study showed that B. subtilis C3 inhibits the growth of pathogenic fungi, and the inhibition rate is as high as 60%. In the inhibition mechanism, strain C3 inhibits the conidiogenesis of pathogenic fungi and destroys the cell structure of its hyphae, causing protoplast exudation, chromatin concentration, DNA fragmentation, and ultimately cell death. Among the secondary metabolites of C3, antimicrobial proteins and main active components (paeonol, ethyl palmitate, and oxalic acid) inhibited the growth of F. oxysporum. The molecular weight of the antibacterial protein with the highest inhibition rate was approximately 50 kD. The results of a field experiment on the Taibai Mountain F. taipaiensis planting base showed that after the application of strain C3, the incidence of bulb rot in Fritillaria was reduced by 18.44%, and the ratio of bacteria to fungi in the soil increased to 8.21, which verified the control effect of C3 on Fritillaria bulb rot disease. This study provides a theoretical basis for the use of B. subtilis C3 to prevent and control bulb rot in Fritillaria.
Immunosuppressed Miniswine as a Model for Testing Cell Therapy Success: Experience With Implants of Human Salivary Stem/Progenitor Cell Constructs
Authors: Wu Danielle , Lombaert Isabelle M. A. , DeLeon Maximilien , Pradhan-Bhatt Swati , Witt Robert L , Harrington Daniel Anton , Trombetta Mark G , Passineau Michael J , Farach-Carson Mary C.
Published: September 2021

An urgent need exists to develop large animal models for preclinical testing of new cell therapies designed to replace lost or damaged tissues. Patients receiving irradiation for treatment of head and neck cancers frequently develop xerostomia/dry mouth, a condition that could one day be treated by cell therapy to repopulate functional saliva-producing cells. Using immunosuppression protocols developed for patients receiving whole face transplants, we successfully used immunosuppressed miniswine as a suitable host animal to evaluate the long-term stability, biocompatibility, and fate of matrix-modified hyaluronate (HA) hydrogel/bioscaffold materials containing encapsulated salivary human stem/progenitor cells (hS/PCs). An initial biocompatibility test was conducted in parotids of untreated miniswine. Subsequent experiments using hS/PC-laden hydrogels were performed in animals, beginning an immunosuppression regimen on the day of surgery. Implant sites included the kidney capsule for viability testing and the parotid gland for biointegration time periods up to eight weeks. No transplant rejection was seen in any animal assessed by analysis of the tissues near the site of the implants. First-generation implants containing only cells in hydrogel proved difficult to handle in the surgical suite and were modified to adhere to a porcine small intestinal submucosa (SIS) membrane for improved handling and could be delivered through the da Vinci surgical system. Several different surgical techniques were assessed using the second-generation 3D-salivary tissue (3D-ST) for ease and stability both on the kidney capsule and in the capsule-less parotid gland. For the kidney, sliding the implant under the capsule membrane and quick stitching proved superior to other methods. For the parotid gland, creation of a tissue “pocket” for placement and immediate multilayer tissue closure were well tolerated with minimal tissue damage. Surgical clips were placed as fiduciary markers for tissue harvest. Some implant experiments were conducted with miniswine 90 days post-irradiation when salivation decreased significantly. Sufficient parotid tissue remained to allow implant placement, and animals tolerated immunosuppression. In all experiments, viability of implanted hS/PCs was high with clear signs of both vascular and nervous system integration in the parotid implants. We thus conclude that the immunosuppressed miniswine is a high-value emerging model for testing human implants prior to first-in-human trials.
The Effect of Mild Traumatic Brain Injury on Cerebral Microbleeds in Aging
Authors: Toth Luca , Czigler Andras , Horvath Peter , Szarka Nikolett , Kornyei Balint , Toth Arnold , Schwarcz Attila , Ungvari Zoltan , Buki Andras , Toth Peter
Published: September 2021

A traumatic brain injury (TBI) induces the formation of cerebral microbleeds (CMBs), which are associated with cognitive impairments, psychiatric disorders, and gait dysfunctions in patients. Elderly people frequently suffer TBIs, especially mild brain trauma (mTBI). Interestingly, aging is also an independent risk factor for the development of CMBs. However, how TBI and aging may interact to promote the development of CMBs is not well established. In order to test the hypothesis that an mTBI exacerbates the development of CMBs in the elderly, we compared the number and cerebral distribution of CMBs and assessed them by analysing susceptibility weighted (SW) MRI in young (25 ± 10 years old, n = 18) and elder (72 ± 7 years old, n = 17) patients after an mTBI and in age-matched healthy subjects (young: 25 ± 6 years old, n = 20; aged: 68 ± 5 years old, n = 23). We found significantly more CMBs in elder patients after an mTBI compared with young patients; however, we did not observe a significant difference in the number of cerebral microhemorrhages between aged and aged patients with mTBI. The majority of CMBs were found supratentorially (lobar and basal ganglion). The lobar distribution of supratentorial CMBs showed that aging enhances the formation of parietal and occipital CMBs after mTBIs. This suggests that aging and mTBIs do not synergize in the induction of the development of CMBs, and that the different distribution of mTBI-induced CMBs in aged patients may lead to specific age-related clinical characteristics of mTBIs.
Are Noradrenergic Transmission Reducing Drugs Antidepressants?
Authors: Fitzgerald Paul J.
Published: September 2021

Major depressive disorder (MDD) remains a significant public health problem worldwide, and revised treatment strategies are therefore urgently needed, including the creation of novel antidepressant compounds or using existing molecular entities in new ways. Etiologic theories of MDD from decades ago have suggested that synaptic deficiencies of monoaminergic neurotransmitters play a causative role in this neuropsychiatric disorder, and that boosting monoamines with drugs such as SSRIs, SNRIs, TCAs, and MAOIs has antidepressant effects and in some individuals can even induce hypomania or mania. While other factors, such as various intracellular molecular pathways and hippocampal neurogenesis, undoubtedly also play a role in MDD, monoaminergic boosting drugs nonetheless have clearly demonstrated antidepressant properties. There is also, however, a body of studies in the preclinical literature suggesting that monoaminergic transmission reducing drugs, including noradrenergic ones, also have antidepressant-like behavioral properties in rodents. Given that there is increasing evidence that the monoamines have u-shaped or Janus-faced dose-response properties, in which a mid-range value is “optimal” in a variety of behavioral and physiological processes, it is plausible that either too much or too little synaptic norepinephrine in key circuits may exacerbate MDD in some individuals. Here we briefly review rodent depression-related behavioral data, focusing on the forced swim test, from three major classes of noradrenergic transmission reducing drugs (alpha2 agonists, beta blockers, alpha1 antagonists), and find much support for the hypothesis that they have antidepressant-like properties. Whether these drugs are antidepressants in human subjects remains to be determined.
Chronic Social Defeat During Adolescence Induces Short- and Long-Term Behavioral and Neuroendocrine Effects in Male Swiss-Webster Mice
Authors: Mancha-Gutiérrez Héctor Miguel , Estrada-Camarena Erika , Mayagoitia-Novales Lilian , López-Pacheco Elena , López-Rubalcava Carolina
Published: September 2021

Chronic stress exposure during adolescence is a significant risk factor for the development of depression. Chronic social defeat (CSD) in rodents is an animal model of depression with excellent ethological, predictive, discriminative, and face validity. Because the CSD model has not been thoroughly examined as a model of stress-induced depression within the adolescence stage, the present study analyzed the short- and long-term behavioral and neuroendocrine effects of CSD during early adolescence. Therefore, adolescent male Swiss-Webster (SW) mice were exposed to the CSD model from postnatal day (PND) 28 to PND37. Twenty-four hours (mid-adolescence) or 4 weeks (early adulthood) later, mice were tested in two models of depression; the social interaction test (SIT) and forced swimming test (FST); cognitive deficits were evaluated in the Barnes maze (BM). Finally, corticosterone and testosterone content was measured before, during, and after CSD exposure, and serotonin transporter (SERT) autoradiography was studied after CSD in adolescent and adult mice. CSD during early adolescence induced enduring depression-like behaviors as inferred from increased social avoidance and immobility behavior in the SIT and FST, respectively, which correlated in an age-dependent manner with SERT binding in the hippocampus; CSD during early adolescence also induced long-lasting learning and memory impairments in the Barnes maze (BM). Finally, CSD during early adolescence increased serum corticosterone levels in mid-adolescence and early adulthood and delayed the expected increase in serum testosterone levels observed at this age. In conclusion: (1) CSD during early adolescence induced long-lasting depression-like behaviors, (2) sensitivity of SERT density during normal brain development was revealed, (3) CSD during early adolescence induced enduring cognitive deficits, and (4) results highlight the vulnerability of the adolescent brain to social stressors on the adrenal and gonadal axes, which emphasizes the importance of an adequate interaction between both axes during adolescence for normal development of brain and behavior.
Zika Virus and Neuropathogenesis: The Unanswered Question of Which Strain Is More Prone to Causing Microcephaly and Other Neurological Defects
Authors: King Emily Louise , Irigoyen Nerea
Published: September 2021

Despite being perceived to be a relatively innocuous pathogen during its circulation in Africa in the 20th century, consequent outbreaks in French Polynesia and Latin America revealed the Zika virus (ZIKV) to be capable of causing severe neurological defects. Foetuses infected with the virus during pregnancy developed a range of pathologies including microcephaly, cerebral calcifications and macular scarring. These are now collectively known as Congenital Zika syndrome (CZS). It has been established that the neuropathogenesis of ZIKV results from infection of neural progenitor cells in the developing cerebral cortex. Following this, two main hypotheses have emerged: the virus causes either apoptosis or premature differentiation of neural progenitor cells, reducing the final number of mature neurons in the cerebral cortex. This review describes the cellular processes which could potentially cause virus induced apoptosis or premature differentiation, leading to speculation that a combination of the two may be responsible for the pathologies associated with ZIKV. The review also discusses which specific lineages of the ZIKV can employ these mechanisms. It has been unclear in the past whether the virus evolved its neurotropic capability following circulation in Africa, or if the virus has always caused microcephaly but public health surveillance in Africa had failed to detect it. Understanding the true neuropathogenesis of ZIKV is key to being prepared for further outbreaks in the future, and it will also provide insight into how neurotropic viruses can cause profound and life-long neurological defects.
White Matter Abnormalities in Patients With Typhoon-Related Posttraumatic Stress Disorder
Authors: Chen Hui Juan , Qi Rongfeng , Ke Jun , Qiu Jie , Xu Qiang , Zhong Yuan , Lu Guang Ming , Chen Feng
Published: September 2021

Patients with posttraumatic stress disorder (PTSD) might have white matter abnormalities. However, less is known about white matter changes after exposing a specific traumatic event. The purpose of this study was to explore the abnormalities of diffusion in cerebral white matter and its relationship with the clinical symptoms in patients with PTSD by using diffusion tensor imaging (DTI). Diffusion-weighted imaging of the cerebrum was performed in typhoon survivors with (n = 27) and without PTSD (n = 33) and healthy controls (HCs) (n = 30). Differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated among groups using voxel-based analysis of the DTI data. Correlations between diffusion indices and clinical symptoms in patients with PTSD were also assessed. Both patients with PTSD and trauma-exposed control (TEC) group showed increased FA in the anterior limb of the internal capsule, forceps of the corpus callosum, and corona radiata relative to the HC group. Additionally, there was a negative correlation between FA values in the white matter and the clinical symptoms. Trauma exposure may result in disruption of cerebral white matter in individuals with or without PTSD, particularly in the frontal fibers. Aberrant white matter alterations may be associated with the severity of PTSD symptoms.
The Implicit Aesthetic Preference for Mobile Marketing Interface Layout—An ERP Study
Authors: Wang Shu , Xu Chonghuan , Xiao Liang , Ding Austin Shijun
Published: September 2021

Businesses and scholars have been trying to improve marketing effect by optimizing mobile marketing interfaces aesthetically as users browse freely and aimlessly through mobile marketing interfaces. Although the layout is an important design factor that affects interface aesthetics, whether it can trigger customer's aesthetic preferences in mobile marketing remains unexplored. To address this issue, we employ an empirical methodology of event-related potentials (EPR) in this study from the perspective of cognitive neuroscience and psychology. Subjects are presented with a series of mobile marketing interface images of different layouts with identical marketing content. Their EEG waves were recorded as they were required to distinguish a target stimulus from the others. After the experiment, each of the subjects chose five stimuli interfaces they like and five they dislike. By analyzing the ERP data derived from the EEG data and the behavioral data, we find significant differences between the disliked interfaces and the other interfaces in the ERP component of P2 from the frontal-central area in the 200–400 ms post-stimulus onset time window and LPP from both the frontal-central and parietal-occipital area in the 400–600 ms time window. The results support the hypothesis that humans do make rapid implicit aesthetic preferences for interface layouts and suggest that even under a free browsing context like the mobile marketing context, interface layouts that raise high emotional arousal can still attract more user attention and induce users' implicit aesthetic preference.
Immune-Related Genetic Overlap Between Regional Gray Matter Reductions and Psychiatric Symptoms in Adolescents, and Gene-Set Validation in a Translational Model
Authors: Penninck Lukas , Ibrahim El Chérif , Artiges Eric , Gorgievski Victor , Desrivières Sylvane , Farley Severine , Filippi Irina , de Macedo Carlos E. A. , Belzeaux Raoul , Banaschewski Tobias , Bokde Arun L. W. , Quinlan Erin Burke , Flor Herta , Grigis Antoine , Garavan Hugh , Gowland Penny , Heinz Andreas , Brühl Rüdiger , Nees Frauke , Papadopoulos Orfanos Dimitri , Paus Tomáš , Poustka Luise , Fröhner Juliane H. , Smolka Michael N. , Walter Henrik , Whelan Robert , Grenier Julien , Schumann Gunter , Paillère Martinot Marie-Laure , Tzavara Eleni T. , Martinot Jean-Luc ,   for the IMAGEN Consortium
Published: September 2021

Adolescence is a period of vulnerability for the maturation of gray matter (GM) and also for the onset of psychiatric disorders such as major depressive disorder (MDD), bipolar disorder and schizophrenia. Chronic neuroinflammation is considered to play a role in the etiology of these illnesses. However, the involvement of neuroinflammation in the observed link between regional GM volume reductions and psychiatric symptoms is not established yet. Here, we investigated a possible common immune-related genetic link between these two phenomena in european adolescents recruited from the community. Hippocampal and medial prefrontal cortex (mPFC) were defineda priorias regions of interest (ROIs). Their GM volumes were extracted in 1,563 14-year-olds from the IMAGEN database. We found a set of 26 SNPs that correlated with the hippocampal volumes and 29 with the mPFC volumes at age 14. We formed two ROI-Related Immune-gene scores (RRI) with the inflammation SNPs that correlated to hippocampal GM volume and to mPFC GM volume. The predictive ability of both RRIs with regards to the presence of psychiatric symptoms at age 18 was investigated by correlating the RRIs with psychometric questionnaires obtained at age 18. The RRIs (but not control scores constructed with random SNPs) correlated with the presence of depressive symptoms, positive psychotic symptoms, and externalizing symptoms in later adolescence. In addition, the effect of childhood maltreatment, one of the major environmental risk factors for depression and other mental disorders, interacted with the RRI effect. We next sought to validate this finding by investigating our set of inflammatory genes in a translational animal model of early life adversity. Mice were subjected to a protocol of maternal separation at an early post-natal age. We evaluated depressive behaviors in separated and non-separated mice at adolescence and their correlations with the concomitant expression of our genes in whole blood samples. We show that in mice, early life adversity affected the expression of our set of genes in peripheral blood, and that levels of expression correlated with symptoms of negative affect in adolescence. Overall, our translational findings in adolescent mice and humans provide a novel validated gene-set of immune-related genes for further research in the early stages of mood disorders.