bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Dietary Curcumin on Growth and Digestive Physiology of Seriola dumerili
Authors: Yang Jingru , Hong Jiawei , Fu Zhengyi , Ma Zhenhua
Published: April 2022

In order to understand the effects of dietary curcumin on the growth and digestive performance of Seriola dumerili, this study was conducted under laboratory conditions. The control group was added with 0% curcumin, and two treatment groups were added with 0.01% and 0.02% curcumin, respectively. Fish were fed with experimental diet for 8 weeks. The growth data, growth genes, intestinal digestive enzymes, tissue parameters, and blood lipid-related indicators were measured, and the correlation between digestive indicators, growth gene indicators, and growth characteristic indicators was analyzed. The results showed that the survival rate, visceral ratio, hepatosomatic ratio, and condition factor of Seriola dumerili increased first and then decreased with the increase of curcumin content in feed. The feed conversion ratio of the control group was significantly higher than that of the treatment group. With the increase of curcumin content in feed, lipase and trypsin increased first and then decreased with the increase of curcumin content. Compared with the control group, curcumin significantly increased the muscle thickness and the number of goblet cells of Seriola dumerili. High and low contents of curcumin can reduce the content of serum total cholesterol and triglyceride, and a low dose (0.01%) of curcumin has the strongest lipid-lowering effect. The relative gene expression of IGF1 and IGF2 reached the maximum in the 0.02% treatment group. The results showed that the addition of curcumin in feed could theoretically improve the survival rate, feed efficiency, and other growth characteristics of Seriola dumerili, improve intestinal digestion and structure, promote intestinal health, and reduce blood lipid levels. The best effect was achieved in the 0.01% treatment group. The results of this study provide a theoretical reference for the feasibility of adding curcumin to Seriola dumerili feed in production and realize the optimal proportion of feed additives for this species, which is beneficial to the sustainable development of aquaculture.
Simulation Study on Internal Short Circuits in a Li-Ion Battery Depending on the Sizes, Quantities, and Locations of Li Dendrites
Authors: Kim Suhwan , Song Jihun , Lee Hyobin , Jung Seungwon , Park Joonam , Lee Hongkyung , Lee Yong Min
Published: April 2022

The internal short circuit caused by the Li dendrite is well known to be a major cause for fire or explosion accidents involving state-of-the-art lithium-ion batteries (LIBs). However, post-mortem analysis cannot identify the most probable cause, which is initially embedded in the cell, because the original structure of the cell totally collapses after the accident. Thus, multiphysics modeling and simulation must be an effective solution to investigate the effect of a specific cause in a variety of conditions. Herein, we reported an electrochemical-thermal model to simulate the internal short circuit depending on Li dendrite’s sizes (1, 3, 5, 7, and 9 μm), quantities (1–9), relative locations (0, 25, 50, 100, and 150 μm), and external temperature (−10, 10, 30, and 50°C). Through monitoring the temperature change affected by the joule and reaction heats for each case, we suggested critical conditions that led to unavoidable thermal runaway. Thus, this model can be a steppingstone in understanding the correlation between internal short circuits and Li dendrites.
Prevalence, Associated Factors, and Survival Outcomes of Small-Cell Neuroendocrine Carcinoma of the Gynecologic Tract: A Large Population-Based Analysis
Authors: Pang Li , Wang Shizhuo
Published: April 2022

Small-cell carcinomas are highly malignant tumors with neuroendocrine function and which often occur in the lungs. Primary small-cell neuroendocrine carcinomas of the gynecologic tract are extremely rare. This study aimed to evaluate the prevalence of independent predictors related to the prognosis and overall survival of patients with small-cell neuroendocrine carcinomas of the gynecologic tract. Patients with gynecologic small-cell neuroendocrine carcinomas diagnosed between 1973 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox risk regression analyses were performed to determine the independent predictors of overall survival. Overall survival was calculated using the Kaplan–Meier method, and the log-rank test was used for comparison. We included 5,15,393 eligible carcinomas in the present study; the prevalence of gynecologic small-cell neuroendocrine carcinomas was 0.121% (N = 622). Multivariate analysis indicated that advanced age, stage III and IV cancer, and no chemotherapy treatment may be predictors of poor small-cell neuroendocrine cervical carcinoma prognosis. Stage III and IV cancer and lack of surgery, radiotherapy, or chemotherapy were identified as potential predictors of poor prognosis in patients with ovarian small-cell neuroendocrine carcinoma. Kaplan–Meier analysis suggested that the median survival was 19, 11, and 12 months for cervical, ovarian, and endometrial small-cell neuroendocrine carcinomas, respectively. The 1-, 3-, and 5-year overall survival rates were as follows: 58.8, 31.4, and 26.1%, respectively, for small-cell neuroendocrine cervical carcinoma; 46.3, 23.5, and 22.0%, respectively, for ovarian small-cell neuroendocrine carcinoma; and 49.4, 29.4, and 25.9%, respectively, for endometrial small-cell neuroendocrine carcinoma. Our findings indicate that comprehensive and individualized treatment of small-cell neuroendocrine carcinomas of the gynecologic tract may prolong patient survival, although further studies are required.
Clinical Manifestations and Outcomes of Renal Transplantation Patients With Pneumocystis jirovecii Pneumonia and Cytomegalovirus Co-infection
Authors: Zou Jilin , Qiu Tao , Zhou Jiangqiao , Wang Tianyu , Ma Xiaoxiong , Jin Zeya , Xu Yu , Zhang Long , Chen Zhongbao
Published: April 2022

Background

Pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV) infection are common opportunistic infections among renal transplantation (RT) recipients, and both can increase the risk of graft loss and patient mortality after RT. However, few studies had evaluated PJP and CMV co-infection, especially among RT patients. Therefore, this study was performed to evaluate the impact of CMV co-infection with PJP among RT recipients.

Methods

We retrospectively analyzed the clinical data of patients with confirmed diagnosis of PJP between 2015 and 2021 in our hospital. We divided patients into PJP and PJP+CMV groups according to their CMV infection status, and the clinical severity and outcomes of the two groups were evaluated.

Results

A total of 80 patients after RT were diagnosed with PJP. Of these, 37 (46.2%) patients had co-existing CMV viremia. There were no statistically significant intergroup differences in age, sex, diabetes, onset time of PJP after RT and postoperative immunosuppressant. Compared to serum creatinine (Cr) at admission, the serum Cr at discharge in both the PJP and PJP+CMV groups were decreased. The PJP+CMV group had a higher C-reactive protein level, higher procalcitonin level, and lower albumin level than the PJP group. The PJP+CMV group showed a higher PSI score than the PJP group. Moreover, the initial absorption time of the lesion was longer in the PJP+CMV group. However, the duration of hospitalization showed no significant differences between the two groups. The mortality rate was 9.4-times higher in the PJP+CMV group than in the PJP group. The rate of admittance to the intensive care unit was 3.2-times higher in the PJP+CMV group than in the PJP group.

Conclusion

CMV co-infection may result in more serious inflammatory response. RT patients with PJP+CMV infection had more severe clinical symptoms, slower recovery from pneumonia, and higher mortality than those with PJP alone. Therefore, when RT patients present with severe PJP, the possibility of CMV co-infection should be considered. Short-term withdrawal of immunosuppressants in case of severe infection is safe for the renal function of RT patients.
Preliminary Analysis of Burn Degree Using Non-invasive Microwave Spiral Resonator Sensor for Clinical Applications
Authors: Rangaiah Pramod K. B. , Mandal Bappaditya , Avetisyan Erik , Chezhian Arvind Selvan , Augustine Bobins , Perez Mauricio David , Augustine Robin
Published: April 2022

The European “Senseburn” project aims to develop a smart, portable, non-invasive microwave early effective diagnostic tool to assess the depth(d) and degree of burn. The objective of the work is to design and develop a convenient non-invasive microwave sensor for the analysis of the burn degree on burnt human skin. The flexible and biocompatible microwave sensor is developed using a magnetically coupled loop probe with a spiral resonator (SR). The sensor is realized with precise knowledge of the lumped element characteristics (resistor (R), an inductor (L), and a capacitor (C) RLC parameters). The estimated electrical equivalent circuit technique relies on a rigorous method enabling a comprehensive characterization of the sensor (loop probe and SR). The microwave resonator sensor with high quality factor (Q) is simulated using a CST studio suite, AWR microwave office, and fabricated on the RO 3003 substrate with a standard thickness of 0.13 mm. The sensor is prepared based on the change in dielectric property variation in the burnt skin. The sensor can detect a range of permittivity variations (εr 3–38). The sensor is showing a good response in changing resonance frequency between 1.5 and 1.71 GHz for (εr 3 to 38). The sensor is encapsulated with PDMS for the biocompatible property. The dimension of the sensor element is length (L) = 39 mm, width (W) = 34 mm, and thickness (T) = 1.4 mm. The software algorithm is prepared to automate the process of burn analysis. The proposed electromagnetic (EM) resonator based sensor provides a non-invasive technique to assess burn degree by monitoring the changes in resonance frequency. Most of the results are based on numerical simulation. We propose the unique circuit set up and the sensor device based on the information generated from the simulation in this article. The clinical validation of the sensor will be in our future work, where we will understand closely the practical functioning of the sensor based on burn degrees. The senseburn system is designed to support doctors to gather vital info of the injuries wirelessly and hence provide efficient treatment for burn victims, thus saving lives.
Bridging Disciplines: Applications of Forensic Science and Industrial Hemp
Authors: Finley Sheree J. , Javan Gulnaz T. , Green Robert L.
Published: April 2022

Forensic laboratories are required to have analytical tools to confidently differentiate illegal substances such as marijuana from legal products (i.e., industrial hemp). The Achilles heel of industrial hemp is its association with marijuana. Industrial hemp from the Cannabis sativa L. plant is reported to be one of the strongest natural multipurpose fibers on earth. The Cannabis plant is a vigorous annual crop broadly separated into two classes: industrial hemp and marijuana. Up until the eighteenth century, hemp was one of the major fibers in the United States. The decline of its cultivation and applications is largely due to burgeoning manufacture of synthetic fibers. Traditional composite materials such as concrete, fiberglass insulation, and lumber are environmentally unfavorable. Industrial hemp exhibits environmental sustainability, low maintenance, and high local and national economic impacts. The 2018 Farm Bill made way for the legalization of hemp by categorizing it as an ordinary agricultural commodity. Unlike marijuana, hemp contains less than 0.3% of the cannabinoid, Δ9-tetrahydrocannabinol, the psychoactive compound which gives users psychotropic effects and confers illegality in some locations. On the other hand, industrial hemp contains cannabidiol found in the resinous flower of Cannabis and is purported to have multiple advantageous uses. There is a paucity of investigations of the identity, microbial diversity, and biochemical characterizations of industrial hemp. This review provides background on important topics regarding hemp and the quantification of total tetrahydrocannabinol in hemp products. It will also serve as an overview of emergent microbiological studies regarding hemp inflorescences. Further, we examine challenges in using forensic analytical methodologies tasked to distinguish legal fiber-type material from illegal drug-types.
Metagenomic and Transcriptomic Analyses Reveal the Differences and Associations Between the Gut Microbiome and Muscular Genes in Angus and Chinese Simmental Cattle
Authors: Zheng Ya , Chen Juanjuan , Wang Xiaoxuan , Han Ling , Yang Yayuan , Wang Qi , Yu Qunli
Published: April 2022

Gut microbiome and heredity are two important factors affecting the intramuscular fat (IMF) of cattle, excluding age, sex, and nutrition. This study aimed at deciphering these two differences by analyzing the gut microbiome and intramuscular differentially expressed genes (DEGs) in the Angus and Chinese Simmental cattle. Feces and longissimus dorsi were collected from the two groups of animals (n = 20/group) for multiomics analysis. Angus holds a significantly higher diversity than Chinese Simmental, and the relative abundance of Roseburia, Prevotella, Coprococcus, etc., was obviously higher in Angus. Chinese Simmental had higher levels of isobutyrate, isovalerate, and valerate, although similar levels of acetate, propionate, and butyrate were observed for the two groups. The DEGs upregulated in Chinese Simmental were mainly involved in immune and inflammatory responses, while those in Angus were associated with the regulation of muscle system and myofibril. We finally identified 17 species, including Eubacterium rectale, etc., which were positively correlated to muscle and fat metabolism genes (MSTN, MYLPF, TNNT3, and FABP3/4) and illustrate the associations between them. Our study unveils the gut microbial differences and significant DEGs as well as their associations between the two breeds, providing valuable guidance for future mechanism research and development of intervention strategies to improve meat quality.
Changes in Rumen Bacterial Community Induced by the Dietary Physically Effective Neutral Detergent Fiber Levels in Goat Diets
Authors: Xue Benchu , Wu Mei , Yue Shuangming , Hu Anhai , Li Xiang , Hong Qionghua , Wang Zhisheng , Wang Lizhi , Peng Quanhui , Xue Bai
Published: April 2022

Physically effective neutral detergent fiber (peNDF) is a concept that accounts for the particle length of NDF in a feed, sustaining the normal chewing behavior and rumen fermentation of ruminants. This study aimed to elucidate the effects of dietary peNDF on growth performance and bacterial communities in the rumen of goats through a high-throughput sequencing technique. A total of 30 male Lezhi black goats were randomly assigned to five groups, corresponding to five diets with identical compositions and nutrient levels but with varying forage lengths (the peNDF1.18 contents of the diets were 33.0, 29.9, 28.1, 26.5, and 24.8%, respectively). The whole trial lasted for 44 days. As results show, feed intake and average daily gain were highest when peNDF1.18 content was 26.5%, in which the papilla length of the dorsal sac in rumen was the highest. Chao1 and ACE indexes were similar among the treatments, while Shannon and Simpson indexes of the peNDF1.18 = 28.1% group were the highest (p < 0.05). As the level of dietary peNDF1.18 decreased, the dominant phylum transitioned from Bacteroidetes to Firmicutes. The top three dominant genera of rumen bacteria were Prevotella 1, Ruminococcaceae NK4A214 group, and Christensenellaceae R-7 group. They all showed a quadratic correlation with dietary peNDF1.18 level (p < 0.05). The relative abundance of Ruminococcaceae UCG-011 was positively correlated, while that of Prevotella 1 was negatively correlated, with amino acid metabolism and energy metabolism (p < 0.01). In conclusion, dietary peNDF level influenced goat growth performance, rumen development, and rumen bacterial community structures, and a peNDF1.18 level between 26.5 and 28.1% was considered optimal for goat diet.
Bacterial Dynamics and Their Influence on the Biogeochemical Cycles in a Subtropical Hypereutrophic Lake During the Rainy Season
Authors: Díaz-Torres Osiris , Lugo-Melchor Ofelia Yadira , de Anda José , Pacheco Adriana , Yebra-Montes Carlos , Gradilla-Hernández Misael Sebastián , Senés-Guerrero Carolina
Published: April 2022

Lakes in subtropical regions are highly susceptible to eutrophication due to the heavy rainfall, which causes significant runoff of pollutants (e.g., nutrients) to reach surface waters, altering the water quality and influencing the microbial communities that regulate the biogeochemical cycles within these ecosystems. Lake Cajititlán is a shallow, subtropical, and endorheic lake in western Mexico. Nutrient pollution from agricultural activity and wastewater discharge have affected the lake’s water quality, leading the reservoir to a hypereutrophic state, resulting in episodes of fish mortality during the rainy season. This study investigated the temporal dynamics of bacterial communities within Lake Cajititlán and their genes associated with the nitrogen, phosphorus, sulfur, and carbon biogeochemical cycles during the rainy season, as well as the influences of physicochemical and environmental variables on such dynamics. Significant temporal variations were observed in the composition of bacterial communities, of which Flavobacterium and Pseudomonas were the dominant genera. The climatological parameters that were most correlated with the bacterial communities and their functional profiles were pH, DO, ORP, turbidity, TN, EC, NH4+, and NO3–. The bacterial communities displayed variations in their functional composition for nitrogen, phosphorus, and sulfur metabolisms during the sampling months. The bacterial communities within the lake are highly susceptible to nutrient loads and low DO levels during the rainy season. Bacterial communities had a higher relative abundance of genes associated with denitrification, nitrogen fixation, assimilatory sulfate reduction, cysteine, SOX system, and all phosphorus metabolic pathways. The results obtained here enrich our understanding of the bidirectional interactions between bacterial communities and major biogeochemical processes in eutrophic subtropical lakes.
Methanotrophs Contribute to Nitrogen Fixation in Emergent Macrophytes
Authors: Cui Jing , Zhang Meng , Chen Linxia , Zhang Shaohua , Luo Ying , Cao Weiwei , Zhao Ji , Wang Lixin , Jia Zhongjun , Bao Zhihua
Published: April 2022

Root-associated aerobic methanotroph plays an important role in reducing methane emissions from wetlands. In this study, we examined the activity of methane-dependent nitrogen fixation and active nitrogen-fixing bacterial communities on the roots of Typha angustifolia and Scirpus triqueter using a 15N-N2 feeding experiment and a cDNA-based clone library sequence of the nifH gene, respectively. A 15N-N2 feeding experiment showed that the N2 fixation rate of S. triqueter (1.74 μmol h–1 g–1 dry weight) was significantly higther than that of T. angustifolia (0.48 μmol h–1 g–1 dry weight). The presence of CH4 significantly increased the incorporation of 15N-labeled N2 into the roots of both plants, and the rate of CH4-dependent N2 fixation of S. triqueter (5.6 μmol h–1 g–1 dry weight) was fivefold higher than that of T. angustifolia (0.94 μmol h–1 g–1 dry weight). The active root-associated diazotrophic communities differed between the plant species. Diazotrophic Methylosinus of the Methylocystaceae was dominant in S. triqueter, while Rhizobium of the Rhizobiaceae was dominant in T. angustifolia. However, there were no significant differences in the copy numbers of nifH between plant species. These results suggest that N2 fixation was enhanced by the oxidation of CH4 in the roots of macrophytes grown in natural wetlands and that root-associated Methylocystacea, including Methylosinus, contribute to CH4 oxidation-dependent N2 fixation.
MicroRNA Profile of MA-104 Cell Line Associated With the Pathogenesis of Bovine Rotavirus Strain Circulated in Chinese Calves
Authors: Elkady Gehad , Chen Yingyu , Hu Changmin , Chen Jianguo , Chen Xi , Guo Aizhen
Published: April 2022

Bovine rotavirus (BRV) causes massive economic losses in the livestock industry worldwide. Elucidating the pathogenesis of BRV would help in the development of more effective measures to control BRV infection. The MA-104 cell line is sensitive to BRV and is thereby a convenient tool for determining BRV–host interactions. Thus far, the role of the microRNAs (miRNAs) of MA-104 cells during BRV infection is still ambiguous. We performed Illumina RNA sequencing analysis of the miRNA libraries of BRV-infected and mock-infected MA-104 cells at different time points: at 0 h post-infection (hpi) (just after 90 min of adsorption) and at 6, 12, 24, 36, and 48 hpi. The total clean reads obtained from BRV-infected and uninfected cells were 74,701,041 and 74,184,124, respectively. Based on these, 579 were categorized as known miRNAs and 144 as novel miRNAs. One hundred and sixty differentially expressed (DE) miRNAs in BRV-infected cells in comparison with uninfected MA-104 cells were successfully investigated, 95 of which were upregulated and 65 were downregulated. The target messenger RNAs (mRNAs) of the DE miRNAs were examined by bioinformatics analysis. Functional annotation of the target genes with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested that these genes mainly contributed to biological pathways, endocytosis, apoptotic process, trans-Golgi membrane, and lysosome. Pathways such as the mammalian target of rapamycin (mTOR) (mml-miR-486-3p and mml-miR-197-3p), nuclear factor kappa B (NF-κB) (mml-miR-204-3p and novel_366), Rap1 (mml-miR-127-3p), cAMP (mml-miR-106b-3p), mitogen-activated protein kinase (MAPK) (mml-miR-342-5p), T-cell receptor signaling (mml-miR-369-5p), RIG-I-like receptor signaling (mml-miR-504-5p), AMP-activated protein kinase (AMPK) (mml-miR-365-1-5p), and phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling (mml-miR-299-3p) were enriched. Moreover, real-time quantitative PCR (qPCR) verified the expression profiles of 23 selected DE miRNAs, which were consistent with the results of deep sequencing, and the 28 corresponding target mRNAs were mainly of regulatory pathways of the cellular machinery and immune importance, according to the bioinformatics analysis. Our study is the first to report a novel approach that uncovers the impact of BRV infection on the miRNA expressions of MA-104 cells, and it offers clues for identifying potential candidates for antiviral or vaccine strategies.
Overview of Salmonella Genomic Island 1-Related Elements Among Gamma-Proteobacteria Reveals Their Wide Distribution Among Environmental Species
Authors: Siebor Eliane , Neuwirth Catherine
Published: April 2022

The aim of this study was to perform an in silico analysis of the available whole-genome sequencing data to detect syntenic genomic islands (GIs) having homology to Salmonella genomic island 1 (SGI1), analyze the genetic variations of their backbone, and determine their relatedness. Eighty-nine non-redundant SGI1-related elements (SGI1-REs) were identified among gamma-proteobacteria. With the inclusion of the thirty-seven backbones characterized to date, seven clusters were identified based on integrase homology: SGI1, PGI1, PGI2, AGI1 clusters, and clusters 5, 6, and 7 composed of GIs mainly harbored by waterborne or marine bacteria, such as Vibrio, Shewanella, Halomonas, Idiomarina, Marinobacter, and Pseudohongiella. The integrase genes and the backbones of SGI1-REs from clusters 6 and 7, and from PGI1, PGI2, and AGI1 clusters differed significantly from those of the SGI1 cluster, suggesting a different ancestor. All backbones consisted of two parts: the part from attL to the origin of transfer (oriT) harbored the DNA recombination, transfer, and mobilization genes, and the part from oriT to attR differed among the clusters. The diversity of SGI1-REs resulted from the recombination events between GIs of the same or other families. The oriT appeared to be a high recombination site. The multi-drug resistant (MDR) region was located upstream of the resolvase gene. However, most SGI1-REs in Vibrio, Shewanella, and marine bacteria did not harbor any MDR region. These strains could constitute a reservoir of SGI1-REs that could be potential ancestors of SGI1-REs encountered in pathogenic bacteria. Furthermore, four SGI1-REs did not harbor a resolvase gene and therefore could not acquire an integron. The presence of mobilization genes and AcaCD binding sites indicated that their conjugative transfer could occur with helper plasmids. The plasticity of SGI1-REs contributes to bacterial adaptation and evolution. We propose a more relevant classification to categorize SGI1-REs into different clusters based on their integrase gene similarity.
Cyclic Attractors Are Critical for Macrophage Differentiation, Heterogeneity, and Plasticity
Authors: Ordaz-Arias Manuel Azaid , Díaz-Alvarez Laura , Zúñiga Joaquín , Martinez-Sánchez Mariana Esther , Balderas-Martínez Yalbi Itzel
Published: April 2022

Adaptability, heterogeneity, and plasticity are the hallmarks of macrophages. How these complex properties emerge from the molecular interactions is an open question. Thus, in this study we propose an actualized regulatory network of cytokines, signaling pathways, and transcription factors to survey the differentiation, heterogeneity, and plasticity of macrophages. The network recovers attractors, which in regulatory networks correspond to cell types, that correspond to M0, M1, M2a, M2b, M2c, M2d, M2-like, and IL-6 producing cells, including multiple cyclic attractors that are stable to perturbations. These cyclic attractors reproduce experimental observations and show that oscillations result from the structure of the network. We also study the effect of the environment in the differentiation and plasticity of macrophages, showing that the observed heterogeneity in macrophage populations is a result of the regulatory network and its interaction with the micro-environment. The macrophage regulatory network gives a mechanistic explanation to the heterogeneity and plasticity of macrophages seen in vivo and in vitro, and offers insights into the mechanism that allows the immune system to react to a complex dynamic environment.
Establishment of a Prognostic Model of Lung Adenocarcinoma Based on Tumor Heterogeneity
Authors: Zheng Pengdou , Zhang Huojun , Jiang Weiling , Wang Lingling , Liu Lu , Zhou Yuhao , Zhou Ling , Liu Huiguo
Published: April 2022

Lung cancer is one of the main cancer types due to its persistently high incidence and mortality, yet a simple and effective prognostic model is still lacking. This study aimed to identify independent prognostic genes related to the heterogeneity of lung adenocarcinoma (LUAD), generate a prognostic risk score model, and construct a nomogram in combination with other pathological characteristics to predict patients’ overall survival (OS). A significant amount of data pertaining to single-cell RNA sequencing (scRNA-seq), RNA sequencing (RNA-seq), and somatic mutation were used for data mining. After statistical analyses, a risk scoring model was established based on eight independent prognostic genes, and the OS of high-risk patients was significantly lower than that of low-risk patients. Interestingly, high-risk patients were more sensitive and effective to immune checkpoint blocking therapy. In addition, it was noteworthy that CCL20 not only affected prognosis and differentiation of LUAD but also led to poor histologic grade of tumor cells. Ultimately, combining risk score, clinicopathological information, and CCL20 mutation status, a nomogram with good predictive performance and high accuracy was established. In short, our research established a prognostic model that could be used to guide clinical practice based on the constantly updated big multi-omics data. Finally, this analysis revealed that CCL20 may become a potential therapeutic target for LUAD.
Serum NMR Profiling Reveals Differential Alterations in the Lipoproteome Induced by Pfizer-BioNTech Vaccine in COVID-19 Recovered Subjects and Naïve Subjects
Authors: Ghini Veronica , Maggi Laura , Mazzoni Alessio , Spinicci Michele , Zammarchi Lorenzo , Bartoloni Alessandro , Annunziato Francesco , Turano Paola
Published: April 2022

1H NMR spectra of sera have been used to define the changes induced by vaccination with Pfizer-BioNTech vaccine (2 shots, 21 days apart) in 10 COVID-19-recovered subjects and 10 COVID-19-naïve subjects at different time points, starting from before vaccination, then weekly until 7 days after second injection, and finally 1 month after the second dose. The data show that vaccination does not induce any significant variation in the metabolome, whereas it causes changes at the level of lipoproteins. The effects are different in the COVID-19-recovered subjects with respect to the naïve subjects, suggesting that a previous infection reduces the vaccine modulation of the lipoproteome composition.
Transcriptomic Changes of Photoperiodic Response in the Hypothalamus Were Identified in Ovariectomized and Estradiol-Treated Sheep
Authors: He Xiaoyun , Di Ran , Guo Xiaofei , Cao Xiaohan , Zhou Mei , Li Xiaoyu , Xia Qing , Wang Xiangyu , Zhang Jinlong , Zhang Xiaosheng , Liu Qiuyue , Chu Mingxing
Published: April 2022

Accurate timing of seasonal changes is an essential ability for an animal’s survival, and the change in the photoperiod is the key factor affecting reproductive seasonality in mammals. Emerging evidence has suggested that multiple hypothalamic genes participate in the photoperiod-induced regulation of reproductive activities in sheep, but the mechanism is still unclear. In this study, we initially examined the plasma level of two major reproductive hormones, namely, follicle-stimulating hormone (FSH) and prolactin (PRL), under different photoperiods in ovariectomized and estradiol-treated (OVX + E2) sheep using radioimmunoassay (RIA). Of the two hormones, the concentration of PRL significantly increased with the extension of the photoperiod, while FSH showed the opposite trend. Subsequently, an examination of the transcriptomic variation between the short photoperiod (SP) and long photoperiod (LP) was conducted. Differential expression analyses and functional annotation showed that several key genes in the insulin secretion (VAMP2, PRKACB, PRKCG, and PLCB1), GnRH (MAPK13, CGA, CDC42, ATF4, and LHB) pathways, and circadian entrainment (KCNJ5, PER1, GNB2, MTNR1A, and RASD1), as well as numerous lncRNAs, including XR_173257.3, XR_173415.3, XR_001435315.1, XR_001024596.2, and XR_001023464.2, were shown potentially vital for the hypothalamic photoperiodic response. Four of the differentially expressed mRNAs and lncRNAs were validated by qPCR. The constructed mRNA–mRNA interaction networks further revealed that transcripts potentially participated in hypothalamic thyroid hormone synthesis, endocrine resistance, and neuroactive ligand–receptor interactions. The interactome analysis of lncRNAs and their targets implied that XR_173257.3 and its target arylalkylamine N-acetyltransferase (AANAT) and XR_173415.3 and its target TH might participate in the regulation of seasonal reproduction. Together, the changes in reproductive hormones and transcriptome will help to determine the important photoperiod-induced lncRNAs and mRNAs and provide a valuable resource for further research on reproductive seasonality in sheep.
Experiences From Developing Software for Large X-Ray Crystallography-Driven Protein-Ligand Studies
Authors: Pearce Nicholas M. , Skyner Rachael , Krojer Tobias
Published: April 2022

The throughput of macromolecular X-ray crystallography experiments has surged over the last decade. This remarkable gain in efficiency has been facilitated by increases in the availability of high-intensity X-ray beams, (ultra)fast detectors and high degrees of automation. These developments have in turn spurred the development of several dedicated centers for crystal-based fragment screening which enable the preparation and collection of hundreds of single-crystal diffraction datasets per day. Crystal structures of target proteins in complex with small-molecule ligands are of immense importance for structure-based drug design (SBDD) and their rapid turnover is a prerequisite for accelerated development cycles. While the experimental part of the process is well defined and has by now been established at several synchrotron sites, it is noticeable that software and algorithmic aspects have received far less attention, as well as the implications of new methodologies on established paradigms for structure determination, analysis, and visualization. We will review three key areas of development of large-scale protein-ligand studies. First, we will look into new software developments for batch data processing, followed by a discussion of the methodological changes in the analysis, modeling, refinement and deposition of structures for SBDD, and the changes in mindset that these new methods require, both on the side of depositors and users of macromolecular models. Finally, we will highlight key new developments for the presentation and analysis of the collections of structures that these experiments produce, and provide an outlook for future developments.
Applications of Alginate-Based Nanomaterials in Enhancing the Therapeutic Effects of Bee Products
Authors: Al-Hatamleh Mohammad A. I. , Alshaer Walhan , Hatmal Ma’mon M. , Lambuk Lidawani , Ahmed Naveed , Mustafa Mohd Zulkifli , Low Siew Chun , Jaafar Juhana , Ferji Khalid , Six Jean-Luc , Uskoković Vuk , Mohamud Rohimah
Published: April 2022

Since the ancient times, bee products (i.e., honey, propolis, pollen, bee venom, bee bread, and royal jelly) have been considered as natural remedies with therapeutic effects against a number of diseases. The therapeutic pleiotropy of bee products is due to their diverse composition and chemical properties, which is independent on the bee species. This has encouraged researchers to extensively study the therapeutic potentials of these products, especially honey. On the other hand, amid the unprecedented growth in nanotechnology research and applications, nanomaterials with various characteristics have been utilized to improve the therapeutic efficiency of these products. Towards keeping the bee products as natural and non-toxic therapeutics, the green synthesis of nanocarriers loaded with these products or their extracts has received a special attention. Alginate is a naturally produced biopolymer derived from brown algae, the desirable properties of which include biodegradability, biocompatibility, non-toxicity and non-immunogenicity. This review presents an overview of alginates, including their properties, nanoformulations, and pharmaceutical applications, placing a particular emphasis on their applications for the enhancement of the therapeutic effects of bee products. Despite the paucity of studies on fabrication of alginate-based nanomaterials loaded with bee products or their extracts, recent advances in the area of utilizing alginate-based nanomaterials and other types of materials to enhance the therapeutic potentials of bee products are summarized in this work. As the most widespread and well-studied bee products, honey and propolis have garnered a special interest; combining them with alginate-based nanomaterials has led to promising findings, especially for wound healing and skin tissue engineering. Furthermore, future directions are proposed and discussed to encourage researchers to develop alginate-based stingless bee product nanomedicines, and to help in selecting suitable methods for devising nanoformulations based on multi-criteria decision making models. Also, the commercialization prospects of nanocomposites based on alginates and bee products are discussed. In conclusion, preserving original characteristics of the bee products is a critical challenge in developing nano-carrier systems. Alginate-based nanomaterials are well suited for this task because they can be fabricated without the use of harsh conditions, such as shear force and freeze-drying, which are often used for other nano-carriers. Further, conjunction of alginates with natural polymers such as honey does not only combine the medicinal properties of alginates and honey, but it could also enhance the mechanical properties and cell adhesion capacity of alginates.
Comparative Study on Topological Properties of the Whole-Brain Functional Connectome in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease Without RBD
Authors: Chen Shuai , Wang Sheng-Hui , Bai Ying-Ying , Zhang Jie-Wen , Zhang Hong-Ju
Published: April 2022

Purpose

Idiopathic rapid eye movement Sleep Behavior Disorder (iRBD) is considered as a prodromal and most valuable warning symptom for Parkinson’s disease (PD). Although iRBD and PD without RBD (nRBD-PD) are both α-synucleinopathies, whether they share the same neurodegeneration process is not clear enough. In this study, the pattern and extent of neurodegeneration were investigated and compared between early-stage nRBD-PD and iRBD from the perspective of whole-brain functional network changes.

Methods

Twenty-one patients with iRBD, 23 patients with early-stage nRBD-PD, and 22 matched healthy controls (HCs) were enrolled. Functional networks were constructed using resting-state functional MRI (fMRI) data. Network topological properties were analyzed and compared among groups by graph theory approaches. Correlation analyses were performed between network topological properties and cognition in the iRBD and nRBD-PD groups.

Results

Both patients with iRBD and patients with early-stage nRBD-PD had attention, executive function, and some memory deficits. On global topological organization, iRBD and nRBD-PD groups still presented small-worldness, but both groups exhibited decreased global/local efficiency and increased characteristic path length. On regional topological organization, compared with HC, nRBD-PD presented decreased nodal efficiency, decreased degree centrality, and increased nodal shortest path length, while iRBD presented decreased nodal efficiency and nodal shortest path. For iRBD, brain regions with decreased nodal efficiency were included in the corresponding regions of nRBD-PD. Nodal shortest path changes were significantly different in terms of brain regions and directions between nRBD-PD and iRBD. Attention deficits were correlated with local topological properties of the occipital lobe in both iRBD and nRBD-PD groups.

Conclusion

Both global and local efficiency of functional networks declined in nRBD-PD and iRBD groups. The overlaps and differences in local topological properties between nRBD-PD and iRBD indicate that iRBD not only shares functional changes of PD but also presents distinct features.
Brevican and Neurocan Cleavage Products in the Cerebrospinal Fluid - Differential Occurrence in ALS, Epilepsy and Small Vessel Disease
Authors: Hußler Wilhelm , Höhn Lukas , Stolz Christopher , Vielhaber Stefan , Garz Cornelia , Schmitt Friedhelm C. , Gundelfinger Eckart D. , Schreiber Stefanie , Seidenbecher Constanze I.
Published: April 2022

The neural extracellular matrix (ECM) composition shapes the neuronal microenvironment and undergoes substantial changes upon development and aging, but also due to cerebral pathologies. In search for potential biomarkers, cerebrospinal fluid (CSF) and serum concentrations of brain ECM molecules have been determined recently to assess ECM changes during neurological conditions including Alzheimer’s disease or vascular dementia. Here, we measured the levels of two signature proteoglycans of brain ECM, neurocan and brevican, in the CSF and serum of 96 neurological patients currently understudied regarding ECM alterations: 16 cases with amyotrophic lateral sclerosis (ALS), 26 epilepsy cases, 23 cerebral small vessel disease (CSVD) patients and 31 controls. Analysis of total brevican and neurocan was performed via sandwich Enzyme-linked immunosorbent assays (ELISAs). Major brevican and neurocan cleavage products were measured in the CSF using semiquantitative immunoblotting. Total brevican and neurocan concentrations in serum and CSF did not differ between groups. The 60 kDa brevican fragment resulting from cleavage by the protease ADAMTS-4 was also found unchanged among groups. The presumably intracellularly generated 150 kDa C-terminal neurocan fragment, however, was significantly increased in ALS as compared to all other groups. This group also shows the highest correlation between cleaved and total neurocan in the CSF. Brevican and neurocan levels strongly correlated with each other across all groups, arguing for a joint but yet unknown transport mechanism from the brain parenchyma into CSF. Conclusively our findings suggest an ALS-specific pattern of brain ECM remodeling and may thus contribute to new diagnostic approaches for this disorder.
Activation of the Mesencephalic Trigeminal Nucleus Contributes to Masseter Hyperactivity Induced by Chronic Restraint Stress
Authors: Zhao Ya-Juan , Liu Yang , Wang Jian , Li Qiang , Zhang Zhou-Ming , Tu Teng , Lei Rong , Zhang Min , Chen Yong-Jin
Published: April 2022

Psychological stress is commonly accepted to be closely associated with masticatory muscle disorder, which is the main symptom of temporomandibular disorder (TMD). Previous studies have confirmed that exposure to stress may cause masticatory muscle hyperactivity. However, the central mechanism underlying this process remains unclear. The mesencephalic trigeminal nucleus (Vme), which resides in the brainstem, is the primary afferent center for masticatory proprioception and plays a key role in oral–motor movements by projecting to the trigeminal motor nucleus (Vmo). Therefore, the present study was designed to examine the role of Vme neurons in masseter overactivity induced by chronic stress. We found that subjecting mice to restraint stress (6 h/day) for 14 days caused significant anxiety-like behavior, obvious masseter overactivity, and markedly enhanced electrophysiological excitability of Vme neurons. By using anterograde tract tracing combined with immunofluorescence staining methods, we observed vesicular glutamate transporter 1 (VGLUT1)-positive glutamatergic projections from the Vme to the Vmo. Moreover, chronic restraint stress (CRS) elevated the expression of VGLUT1 and choline acetyltransferase (ChAT) in Vmo. Furthermore, administration of VGLUT1-targeted short hairpin RNA (shRNA) into the bilateral Vme significantly suppressed the enhanced overexcitability of Vme neurons, downregulated the overexpression of VGLUT1 and ChAT in the Vmo, and attenuated the elevated overactivity of the masseter caused by CRS. Taken together, we showed that CRS can excite neurons in the Vme, enhancing glutamatergic excitatory projections from the Vme to the Vmo and resulting in masseter muscle overactivity. These findings provide us with a novel central mechanism underlying the correlation between psychological factors and TMD.
Using Single-Photon Emission Computerized Tomography on Patients With Positive Quantitative Electroencephalogram to Evaluate Chronic Mild Traumatic Brain Injury With Persistent Symptoms
Authors: Gosset Alexi , Wagman Hayley , Pavel Dan , Cohen Philip Frank , Tarzwell Robert , Bruin Simon de , Siow Yin Hui , Numerow Leonard , Uszler John , Rossiter-Thornton John F. , McLean Mary , Lierop Muriel van , Waisman Zohar , Brown Stephen , Mansouri Behzad , Basile Vincenzo Santo , Chaudhary Navjot , Mehdiratta Manu
Published: April 2022

Background

Following mild traumatic brain injury (mTBI), also known as concussion, many patients with chronic symptoms (>3 months post injury) receive conventional imaging such as computed tomography (CT) or magnetic resonance imaging (MRI). However, these modalities often do not show changes after mTBI. We studied the benefit of triaging patients with ongoing symptoms >3 months post injury by quantitative electroencephalography (qEEG) and then completing a brain single positron emission computed tomography (SPECT) to aid in diagnosis and early detection of brain changes.

Methods

We conducted a retrospective case review of 30 outpatients with mTBI. The patients were assessed by a neurologist, consented, and received a qEEG, and if the qEEG was positive, they consented and received a brain SPECT scan. The cases and diagnostic tools were collectively reviewed by a multidisciplinary group of physicians in biweekly team meetings including neurology, nuclear medicine, psychiatry, neuropsychiatry, general practice psychotherapy, neuro-ophthalmology, and chiropractic providers. The team noted the cause of injury, post injury symptoms, relevant past medical history, physical examination findings, and diagnoses, and commented on patients' SPECT scans. We then analyzed the SPECT scans quantitatively using the 3D-SSP software.

Results

All the patients had cerebral perfusion abnormalities demonstrated by SPECT that were mostly undetectable by conventional imaging (CT/MRI). Perfusion changes were localized primarily in the cerebral cortex, basal ganglia, and cingulate cortex, and correlated with the patients' symptoms and examination findings. Qualitative and quantitative analyses yielded similar results. Most commonly, the patients experienced persistent headache, memory loss, concentration difficulties, depression, and cognitive impairment post mTBI. Because of their symptoms, most of the patients were unable to return to their previous employment and activity level.

Conclusion

Our findings outline the physical basis of neurological and psychiatric symptoms experienced by patients with mTBI. Increased detection of mTBI can lead to development of improved targeted treatments for mTBI and its various sequelae.
Associations Among Food Delay of Gratification, Cognitive Measures, and Environment in a Community Preschool Sample
Authors: Giuliani Nicole R. , Kelly Nichole R.
Published: April 2022

Much of the work on the development of appetite self-regulation in early childhood employs tasks assessing Delay of Gratification (DoG). While this skill is thought to rely on “cool” cognitive processes like effortful control, executive functioning, and self-regulation, demonstration of how laboratory measures of food DoG relate to common assessments of those cognitive processes in community samples of children is needed. This study presents secondary data investigating the associations between two laboratory tasks of food DoG, the Snack Delay and Tongue Tasks, and an array of laboratory and parent-report cognitive measures in a sample of 88 children ages 3-6 (M age = 4.05, SD = 0.76), as well as how four measures of the child's environment were associated with food DoG. Results indicated that both measures of food DoG were positively correlated with performance on the cognitive tasks, with stronger associations observed for the Tongue Task. Family income was positively associated with food DoG as measured by the Tongue Task, and child negative life events in the past year were negatively correlated with food DoG as measured by the Snack Delay Task. These findings present the pattern of associations between cognitive tasks and food DoG, the development of which may be meaningfully affected by specific aspects of family environment.