bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Genetic Diversity and Population Structure of Wheat Landrace Population Conserved at ICARDA Genebank
Authors: Tehseen Muhammad Massub , Tonk Fatma Aykut , Tosun Muzaffer , Istipliler Deniz , Amri Ahmed , Sansaloni Carolina P. , Kurtulus Ezgi , Mubarik Muhammad Salman , Nazari Kumarse
Published: June 2022

Landraces are considered a valuable source of potential genetic diversity that could be used in the selection process in any plant breeding program. Here, we assembled a population of 600 bread wheat landraces collected from eight different countries, conserved at the ICARDA's genebank, and evaluated the genetic diversity and the population structure of the landraces using single nucleotide polymorphism (SNP) markers. A total of 11,830 high-quality SNPs distributed across the genomes A (40.5%), B (45.9%), and D (13.6%) were used for the final analysis. The population structure analysis was evaluated using the model-based method (STRUCTURE) and distance-based methods [discriminant analysis of principal components (DAPC) and principal component analysis (PCA)]. The STRUCTURE method grouped the landraces into two major clusters, with the landraces from Syria and Turkey forming two clusters with high proportions of admixture, whereas the DAPC and PCA analysis grouped the population into three subpopulations mostly according to the geographical information of the landraces, i.e., Syria, Iran, and Turkey with admixture. The analysis of molecular variance revealed that the majority of the variation was due to genetic differences within the populations as compared with between subpopulations, and it was the same for both the cluster-based and distance-based methods. Genetic distance analysis was also studied to estimate the differences between the landraces from different countries, and it was observed that the maximum genetic distance (0.389) was between the landraces from Spain and Palestine, whereas the minimum genetic distance (0.013) was observed between the landraces from Syria and Turkey. It was concluded from the study that the model-based methods (DAPC and PCA) could dissect the population structure more precisely when compared with the STRUCTURE method. The population structure and genetic diversity analysis of the bread wheat landraces presented here highlight the complex genetic architecture of the landraces native to the Fertile Crescent region. The results of this study provide useful information for the genetic improvement of hexaploid wheat and facilitate the use of landraces in wheat breeding programs.
Research on Adoption Behavior and Influencing Factors of Intelligent Pension Services for Elderly in Shanghai
Authors: Luo Juan , Meng Lingqi
Published: June 2022

With the rapid development of artificial intelligence and Internet-of-Things technology, the traditional pension service mode has changed, and intelligent pension services have become a new direction of development. Descriptive statistical analysis is conducted on the supply status and demand of intelligent pension services. It is believed that the current intelligent pension services are still in the initial stage of development, and the contradiction between supply and demand is prominent. The demand for intelligent pension of the elderly is high, but the user acceptance and satisfaction are not high. On this basis, variables were selected from individual characteristics, family situation, economic status, education level, living conditions, and other indicators for multivariate unconditional logistic regression analysis. It was found that the adoption behavior of intelligent pension service users was most significantly affected by age, number of children, living conditions, service cost, service docking channel, and equipment operation difficulty. Based on the conclusion, this article puts forward some suggestions such as taking the government as the center to realize the multi-governance of intelligent pension services, improving the supply of intelligent pension service-related facilities guided by demand, optimizing the service mode based on the platform to realize dynamic combination, and taking talents as the core to promote the high-quality development of intelligent pension services.
Exploring the Relationship Between Senescence and Colorectal Cancer in Prognosis, Immunity, and Treatment
Authors: Dong Kechen , Liu Jianping , Zhou Wei , Zhang Guanglin
Published: June 2022

Background: Senescence, as an effective barrier against tumorigenesis, plays a critical role in cancer therapy. However, the role of senescence in colorectal cancer (CRC) has not yet been reported. This study aimed to build a prognostic signature for the prognosis of patients with CRC based on senescence-related genes.

Methods: A prognostic signature was built from TCGA based on differentially expressed senescence-related genes by the least absolute shrinkage and selection operator (LASSO) and Cox regression analyses, which were further validated using two Gene Expression Omnibus (GEO) cohorts. The CIBERSORT and ssGSEA algorithms were utilized to analyze the infiltrating abundance of immune cells. The relationship of signature with the immune therapy and the sensitivity of different therapies was explored.

Results: We found 93 genes associated with senescence that were differentially expressed. Based on expression and clinical parameters, we developed a senescence-related prognostic signature and its effectiveness was verified using two external validation cohorts. Overall survival was predicted using a prognostic nomogram that incorporated the predictive values of the risk score and clinical traits. Additionally, the risk score was significantly correlated with immune cells infiltration, tumor immune microenvironment (TME) score, immune checkpoints, immunotherapeutic efficacy, and chemotherapy sensitivity.

Conclusion: The senescence-related prognostic model can well predict the prognosis, immunotherapeutic response, and identify potential drug targets, which can help guide individualized treatment.
Elevated Expression of Growth Differentiation Factor-15 Is Associated With Acute Exacerbation of Idiopathic Pulmonary Fibrosis
Authors: Cao Mengshu , Gu Lina , Guo Lili , Liu Mengying , Wang Tianzhen , Zhang Ji , Zhang Huizhe , Zhang Yufeng , Shi Yanchen , Zhao Yichao , Qiu Xiaohua , Gui Xianhua , Ma Miao , Tian Yaqiong , Liu Xiaoqin , Meng Fanqing , Xiao Yonglong , Sun Lingyun
Published: June 2022

Backgrounds

Growth differentiation factor 15 (GDF-15) is a highly divergent member of the TGF-β superfamily and has been implicated in various biological functions. However, the expression of GDF-15 in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is unclear.

Method

The study included 47 AE-IPF patients, 61 stable IPF (S-IPF) subjects, and 31 healthy controls (HCs). Serum GDF-15 levels and their expression in the lung were measured. The correlation between serum GDF-15 and other clinical parameters and the risk factors for AE occurrence and the survival of IPF patients were analyzed.

Results

Serum GDF-15 levels were significantly elevated in AE-IPF patients (1279.22 ± 540.02 pg/ml) as compared with HCs (891.30 ± 479.90 pg/ml) or S-IPF subjects (107.82 ± 14.21 pg/ml) (both p < 0.001). The protein and mRNA expressions of GDF-15 in the lung of AE-IPF patients were significantly increased as compared with S-IPF cases (p = 0.007 and p = 0.026, respectively). The serum GDF-15 level was correlated with the clinical variables of inflammation, metabolism, and disease severity in IPF subjects (all p < 0.05). The GDF-15 serum concentration was significantly higher in decedents than in survivors (p = 0.005). A serum GDF-15 level above 989.3 pg/ml was a risk factor for AE occurrence (p = 0.04), and the level above 1,075.76 pg/ml was an independent predictor for survival in IPF cases (p = 0.007).

Conclusions

The GDF-15 level was significantly elevated in subjects with AE-IPF. GDF-15 could be a promising biomarker for AE occurrence and survival in IPF patients.
Inhaled or Ingested, Which Is Worse, E-Vaping or High-Fat Diet?
Authors: Chen Hui , Chan Yik Lung , Thorpe Andrew E. , Pollock Carol A. , Saad Sonia , Oliver Brian G.
Published: June 2022

Long term e-cigarette vaping induces inflammation, which is largely nicotine independent. High-fat diet (HFD) consumption is anoter cause of systemic low-grade inflammation. The likelihood of using e-cigarettes as a weight control strategy is concomitant with the increase in obesity. In Australia, only nicotine-free e-fluid is legal for sale. Therefore, this study aimed to investigate how nicotine-free e-cigarette vapour exposure affects inflammatory responses in mice with long term HFD consumption. Mice were fed a HFD for 16 weeks, while in the last 6 weeks, half of the chow and HFD groups were exposed to nicotine-free e-vapour, while the other half to ambient air. Serum, lung, liver and epididymal fat were collected to measure inflammatory markers. While both e-vapour exposure and HFD consumption independently increased serum IFN-γ, CX3CL1, IL-10, CCL20, CCL12, and CCL5 levels, the levels of IFN-γ, CX3CL1, and IL-10 were higher in mice exposed to e-vapour than HFD. The mRNA expression pattern in the epididymal fat mirrors that in the serum, suggesting the circulating inflammatory response to e-vapour is from the fat tissue. Of the upregulated cytokines in serum, none were found to change in the lungs. The anti-inflammatory cytokine IL-10 was increased by combining e-vapour and HFD in the liver. We conclude that short-term nicotine-free e-vapour is more potent than long term HFD consumption in causing systemic inflammation. Future studies will be needed to examine the long-term health impact of nicotine-free e-cigarettes.
The Emerging Roles of Human Gut Microbiota in Gastrointestinal Cancer
Authors: Guo Qianqian , Qin Hai , Liu Xueling , Zhang Xinxin , Chen Zelong , Qin Tingting , Chang Linlin , Zhang Wenzhou
Published: June 2022

The gut microbiota is composed of a large number of microorganisms with a complex structure. It participates in the decomposition, digestion, and absorption of nutrients; promotes the development of the immune system; inhibits the colonization of pathogens; and thus modulates human health. In particular, the relationship between gut microbiota and gastrointestinal tumor progression has attracted widespread concern. It was found that the gut microbiota can influence gastrointestinal tumor progression in independent ways. Here, we focused on the distribution of gut microbiota in gastrointestinal tumors and further elaborated on the impact of gut microbiota metabolites, especially short-chain fatty acids, on colorectal cancer progression. Additionally, the effects of gut microbiota on gastrointestinal tumor therapy are outlined. Finally, we put forward the possible problems in gut microbiota and the gastrointestinal oncology field and the efforts we need to make.
Duck LGP2 Downregulates RIG-I Signaling Pathway-Mediated Innate Immunity Against Tembusu Virus
Authors: Li Tianxu , Ren Yanyan , Zhang Tingting , Zhai Xinyu , Wang Xiuyuan , Wang Jinchao , Xing Bin , Miao Runchun , Li Ning , Wei Liangmeng
Published: June 2022

In mammals, the retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) has been demonstrated to play a critical role in activating downstream signaling in response to viral RNA. However, its role in ducks’ antiviral innate immunity is less well understood, and how gene-mediated signaling is regulated is unknown. The regulatory role of the duck laboratory of genetics and physiology 2 (duLGP2) in the duck RIG-I (duRIG-I)-mediated antiviral innate immune signaling system was investigated in this study. In duck embryo fibroblast (DEF) cells, overexpression of duLGP2 dramatically reduced duRIG-I-mediated IFN-promotor activity and cytokine expression. In contrast, the knockdown of duLGP2 led to an opposite effect on the duRIG-I-mediated signaling pathway. We demonstrated that duLGP2 suppressed the duRIG-I activation induced by duck Tembusu virus (DTMUV) infection. Intriguingly, when duRIG-I signaling was triggered, duLGP2 enhanced the production of inflammatory cytokines. We further showed that duLGP2 interacts with duRIG-I, and this interaction was intensified during DTMUV infection. In summary, our data suggest that duLGP2 downregulated duRIG-I mediated innate immunity against the Tembusu virus. The findings of this study will help researchers better understand the antiviral innate immune system’s regulatory networks in ducks.
Geochemistry of Hydrothermal Fluids From the E2-Segment of the East Scotia Ridge: Magmatic Input, Reaction Zone Processes, Fluid Mixing Regimes and Bioenergetic Landscapes
Authors: Pereira Samuel I. , Diehl Alexander , McDermott Jill M. , Pape Thomas , Klose Lukas , Strauss Harald , Bohrmann Gerhard , Bach Wolfgang
Published: June 2022

The compositions of hydrothermal fluids in back-arc basins (BABs) can be affected by the influx of magmatic fluids into systems that are dominated by reactions between basement rocks and seawater-derived fluids. The East Scotia Ridge (ESR) in the Scotia Sea hosts such hydrothermal systems where the role of magmatic fluid influx has not yet been addressed. During expedition PS119 in 2019, three chimneys were sampled from the E2 segment. These samples were analysed for their chemical and isotopic composition along with fluid inclusions in corresponding precipitates. Our data provide evidence for the temporal evolution of hydrothermal fluids in this remote back-arc system. Salinity variations in anhydrite-hosted fluid inclusions indicate that phase separation takes place in the subseafloor. Moderate-temperature (<53°C) fluids from the newly discovered E2-West hydrothermal vent field and high-temperature (>320°C) fluids from the E2-South area were sampled. Depletions in fluid-mobile elements, ΣREE and low δ18OH2O show that the basement in this root zone has been leached since the previous sampling in 2010. The results indicate that high-temperature fluid-rock interactions are key in setting the composition of the fluids with cation-to-chloride ratios suggesting a common root zone for both vent sites. The concentrations of dissolved gases provide new insights in the connection between magmatic degassing and its influence on endmember vent fluid composition. Specifically, stable isotope (O, H) data and elevated CO2 concentrations point to a minor influx of magmatic vapour. Stable sulphur isotopes provide no evidence for SO2 disproportionation suggesting a H2O-CO2 dominated nature of these vapours. The concentrations of conservative elements in the E2-W fluid reflects subseafloor mixing between E2-S endmember fluid and seawater. In contrast, non-conservative behaviour, and depletion of Fe, H2, and H2S point to a combination of sub-surface abiotic and biotic reactions affecting these fluids. Similarly, E2-W fluids show evidence for H2S and CH4 being metabolized in the subseafloor. Thermodynamic computations confirm that the E2 system is dominated by sulphide oxidation as a major catabolic pathway. Our results indicate that the conditions at E2 are favourable to hosting a robust subseafloor biosphere.
The Effect of Elevated Alanine Transaminase on Non-invasive Prenatal Screening Failures
Authors: Chen Ping , Qiao Longwei , Zhang Sheng , Jin Jieyu , Cao Jun , Zhang Yuqiong , Tang Haoyu , Yu Zheng , Shi Jingye , Yin JingPing , Liang Yuting , Wu Xiao
Published: June 2022

Objective

To determine the effects of alanine transaminase (ALT) levels on the screening failure rates or “no calls” due to low fetal fraction (FF) to obtain a result in non-invasive prenatal screening (NIPS).

Methods

NIPS by sequencing and liver enzyme measurements were performed in 7,910 pregnancies at 12–26 weeks of gestation. Univariate and multivariable regression models were used to evaluate the significant predictors of screening failure rates among maternal characteristics and relevant laboratory parameters.

Results

Of the 7,910 pregnancies that met the inclusion criteria, 134 (1.69%) had “no calls.” Multiple logistic regression analysis demonstrated that increased body mass index, ALT, prealbumin, albumin levels, and in vitro fertilization (IVF) conception rates were independently associated with screening failures. The test failure rate was higher (4.34 vs. 1.41%; P < 0.001) in IVF pregnancies relative to those with spontaneous conceptions. Meanwhile, the screening failure rates increased with increasing ALT levels from 1.05% at ≤10 U/L to 3.73% at >40 U/L. In particular, IVF pregnancies with an ALT level of >40 U/L had a higher test failure rate (9.52%). Compared with that for an ALT level of ≤10 U/L, the adjusted odds ratio of “no calls” for ALT levels of 10–20, 21–40, and >40 U/L was 1.204 [95% confidence interval (CI), 0.709–2.045], 1.529 (95% CI, 0.865–2.702), and 2.764 (95% CI, 1.500–5.093) (Ptrend < 0.001), respectively.

Conclusions

Increased ALT and IVF conceptions were associated with a higher screening failure rates in NIPS. Therefore, a feasible strategy to adjust these factors to reduce the probability of “no calls” due to low FF would be of great clinical significance.
Effectiveness of Perioperative Cardiopulmonary Rehabilitation in Patients With Lung Cancer Undergoing Video-Assisted Thoracic Surgery
Authors: Chao Wei-Hao , Tuan Sheng-Hui , Tang En-Kuei , Tsai Yi-Ju , Chung Jing-Hui , Chen Guan-Bo , Lin Ko-Long
Published: June 2022

Objectives

Patients with lung cancer pose a high risk of morbidity and mortality after lung resection. Those who receive perioperative cardiopulmonary rehabilitation (PRCR) have better prognosis. Peak oxygen consumption (peak VO2), VO2 at the ventilatory threshold (VO2 at VT), and slope of minute ventilation to carbon dioxide production (VE/VCO2 slope) measured during pre-surgical cardiopulmonary exercise testing (CPET) have prognostic values after lung resection. We aimed to investigate the influence of individualized PRCR on postoperative complications in patients undergoing video-assisted thoracic surgery (VATS) for lung cancer with different pre-surgical risks.

Methods

This was a retrospective study. We recruited 125 patients who underwent VATS for lung cancer between 2017 and 2021. CPET was administered before surgery to evaluate the risk level and PRCR was performed based on the individual risk level defined by peak VO2, VO2 at VT, and VE/VCO2 slope, respectively. The primary outcomes were intensive care unit (ICU) and hospital lengths of stay, endotracheal intubation time (ETT), and chest tube insertion time (CTT). The secondary outcomes were postoperative complications (PPCs), including subcutaneous emphysema, pneumothorax, pleural effusion, atelectasis, infection, and empyema.

Results

Three intergroup comparisons based on the risk level by peak VO2 (3 groups), VO2 at VT (2 groups), and VE/VCO2 slope (3 groups) were done. All of the comparisons showed no significant differences in both the primary and secondary outcomes (p = 0.061–0.910).

Conclusion

Patients with different risk levels showed comparable prognosis and PPCs after undergoing CPET-guided PRCR. PRCR should be encouraged in patients undergoing VATS for lung cancer.
A Computational Approach to Elucidate the Interactions of Chemicals From Artemisia annua Targeted Toward SARS-CoV-2 Main Protease Inhibition for COVID-19 Treatment
Authors: Johnson Titilayo Omolara , Adegboyega Abayomi Emmanuel , Ojo Oluwafemi Adeleke , Yusuf Amina Jega , Iwaloye Opeyemi , Ugwah-Oguejiofor Chinenye Jane , Asomadu Rita Onyekachukwu , Chukwuma Ifeoma Felicia , Ejembi Stephen Adakole , Ugwuja Emmanuel Ike , Alotaibi Saqer S. , Albogami Sarah M. , Batiha Gaber El-Saber , Rajab Bodour S. , Conte-Junior Carlos Adam
Published: June 2022

The inhibitory potential of Artemisia annua, a well-known antimalarial herb, against several viruses, including the coronavirus, is increasingly gaining recognition. The plant extract has shown significant activity against both the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the novel SARS-CoV-2 that is currently ravaging the world. It is therefore necessary to evaluate individual chemicals of the plant for inhibitory potential against SARS-CoV-2 for the purpose of designing drugs for the treatment of COVID-19. In this study, we employed computational techniques comprising molecular docking, binding free energy calculations, pharmacophore modeling, induced-fit docking, molecular dynamics simulation, and ADMET predictions to identify potential inhibitors of the SARS-CoV-2 main protease (Mpro) from 168 bioactive compounds of Artemisia annua. Rhamnocitrin, isokaempferide, kaempferol, quercimeritrin, apigenin, penduletin, isoquercitrin, astragalin, luteolin-7-glucoside, and isorhamnetin were ranked the highest, with docking scores ranging from −7.84 to −7.15 kcal/mol compared with the −6.59 kcal/mol demonstrated by the standard ligand. Rhamnocitrin, Isokaempferide, and kaempferol, like the standard ligand, interacted with important active site amino acid residues like HIS 41, CYS 145, ASN 142, and GLU 166, among others. Rhamnocitrin demonstrated good stability in the active site of the protein as there were no significant conformational changes during the simulation process. These compounds also possess acceptable druglike properties and a good safety profile. Hence, they could be considered for experimental studies and further development of drugs against COVID-19.
Review: The Development of Risk Factors and Cytokines in Retinal Vein Occlusion
Authors: Tang Yi , Cheng Yan , Wang Shuo , Wang Yongjie , Liu Pengjia , Wu Hong
Published: June 2022

Retinal vein occlusion (RVO) is the second most prevalent retinal disease. Despite this, the pathogenic mechanisms and risk factors are not entirely clear. In this article, we review recent publications on the classification, pathogenesis, risk factors, ischemic changes, cytokines, and vital complications of RVO. Risk factors and cytokines are important for exploring the mechanisms and new treatment targets. Furthermore, risk factors are interrelated, making RVO mechanisms more complex. Cytokines act as powerful mediators of pathological conditions, such as inflammation, neovascularization, and macular edema. This review aims to summarize the updated knowledge on risk factors, cytokines of RVO and signaling in order to provide valuable insight on managing the disease.
The Involvement of ALPK3 in Hypertrophic Cardiomyopathy in East Asia
Authors: Dai Jiaqi , Li Ke , Huang Man , Sun Yang , Liu Hao , Li Zongzhe , Chen Peng , Wang Hong , Wu Dongyang , Chen Yanghui , Xiao Lei , Wei Haoran , Li Rui , Peng Liyuan , Yu Ting , Wang Yan , Wang Dao Wen
Published: June 2022

Objective

ALPK3 is associated with a recessive form of pediatric cardiomyopathy accompanied by musculoskeletal and craniofacial abnormalities. Heterozygous truncating variants in this gene (ALPK3tv) have recently been confirmed as a cause of autosomal dominant hypertrophic cardiomyopathy (HCM). Whether ALPK3 is also implicated in HCM in East Asia and the effect of missense variants in ALPK3 on HCM remains unresolved.

Methods

We compared the frequency of rare deleterious variants in ALPK3 in a study cohort comprised of 793 HCM cases of East Asian descent to that in the controls subset of Genome Aggregation Database (gnomAD). Gene burden test was used to assess this association. The involvement of these variants in HCM was further validated by independent cohort. The clinical characteristics and prognoses of these carriers were compared with sarcomere-positive and negative patients.

Results

Rare deleterious variants in ALPK3 were significantly enriched in HCM compared with gnomAD controls (truncating: 4/793 vs. 4/4523, P = 0.02; missense: 25/793 vs. 46/4523, P = 2.56e-5). Replication in an independent cohort provided more supporting evidence. Further comparisons revealed that ALPK3 carriers displayed more severe hypertrophy in interventricular septum (IVS) and apex, as well as greater maximal left ventricular wall thickness, relative to sarcomere negatives.

Conclusion

Heterozygous rare variants in ALPK3, both missense and truncating variants, are associated with HCM in East Asians.
Multicellular Tumor Spheroids in Nanomedicine Research: A Perspective
Authors: Rossi Martina , Blasi Paolo
Published: June 2022

Multicellular tumor spheroids are largely exploited in cancer research since they are more predictive than bi-dimensional cell cultures. Nanomedicine would benefit from the integration of this three-dimensional in vitro model in screening protocols. In this brief work, we discuss some of the issues that cancer nanomedicine will need to consider in the switch from bi-dimensional to three-dimensional multicellular tumor spheroid models.
Genomic Characterization of Mobile Genetic Elements Associated With Carbapenem Resistance of Acinetobacter baumannii From India
Authors: Vijayakumar Saranya , Jacob Jobin John , Vasudevan Karthick , Mathur Purva , Ray Pallab , Neeravi Ayyanraj , Baskaran Ashtawarthani , Kirubananthan Agilandeeswari , Anandan Shalini , Biswas Indranil , Walia Kamini , Veeraraghavan Balaji
Published: June 2022

With the excessive genome plasticity, Acinetobacter baumannii can acquire and disseminate antimicrobial resistance (AMR) genes often associated with mobile genetic elements (MGEs). Analyzing the genetic environment of resistance genes often provides valuable information on the origin, emergence, evolution, and spread of resistance. Thus, we characterized the genomic features of some clinical isolates of carbapenem-resistant A. baumannii (CRAb) to understand the role of diverse MGEs and their genetic context responsible for disseminating carbapenem resistance genes. For this, 17 clinical isolates of A. baumannii obtained from multiple hospitals in India between 2018 and 2019 were analyzed. AMR determinants, the genetic context of resistance genes, and molecular epidemiology were studied using whole-genome sequencing. This study observed an increased prevalence of blaOXA–23 followed by dual carbapenemases, blaOXA–23, and blaNDM. This study identified three novel Oxford MLST sequence types. The majority of the isolates belonged to the dominant clone, IC2, followed by less prevalent clones such as IC7 and IC8. This study identified variations of AbaR4 and AbGRI belonging to the IC2 lineage. To the best of our knowledge, this is the first study that provides comprehensive profiling of resistance islands, their related MGEs, acquired AMR genes, and the distribution of clonal lineages of CRAb from India.
Integrated Omics Analysis Reveals Alterations in the Intestinal Microbiota and Metabolites of Piglets After Starvation
Authors: Ma Yijia , Lu Chang , Ji Bingzhen , Qin Junjun , Cai Chunbo , Yang Yang , Zhao Yan , Liang Guoming , Guo Xiaohong , Cao Guoqing , Li Bugao , Gao Pengfei
Published: June 2022

Obesity is a serious public health problem. Short-term starvation is an effective way to lose weight but can also cause harm to the body. However, a systematic assessment of the relationship between the intestinal microbiota and metabolites after complete fasting is lacking. Pigs are the best animal models for exploring the mechanisms of human nutrition digestion and absorption, metabolism, and disease treatment. In this study, 16S rRNA sequencing and liquid chromatography-mass spectrometry were used to analyze the changes in the intestinal microbiota and metabolite profiles in piglets under starvation stress. The results show that the microbial composition was changed significantly in the starvation groups compared with the control group (P < 0.05), suggesting that shifts in the microbial composition were induced by starvation stress. Furthermore, differences in the correlation of the intestinal microbiota and metabolites were observed in the different experimental groups. Starvation may disrupt the homeostasis of the intestinal microbiota and metabolite profile and affect the health of piglets. However, piglets can regulate metabolite production to compensate for the effects of short-term starvation. Our results provide a background to explore the mechanism of diet and short-term hunger for intestinal homeostasis.
The Seasonal Patterns, Ecological Function and Assembly Processes of Bacterioplankton Communities in the Danjiangkou Reservoir, China
Authors: Chen Zhao-Jin , Liu Yong-Qi , Li Yu-Ying , Lin Li-An , Zheng Bao-Hai , Ji Ming-Fei , Li B. Larry , Han Xue-Mei
Published: June 2022

As the water source for the Middle Route Project of the South-to-North Water Diversion Project (MR-SNWD) of China, the Danjiangkou Reservoir (DJR) is in the process of ecosystem reassembly, but the composition, function, and assembly mechanisms of bacterioplankton communities are not yet clear. In this study, the composition, distribution characteristics and influencing factors of bacterioplankton communities were analyzed by high-throughput sequencing (HTS); PICRUSt2 was used to predict community function; a molecular ecological network was used to analyze bacterioplankton interactions; and the assembly process of bacterioplankton communities was estimated with a neutral model. The results indicated that the communities, function and interaction of bacterioplankton in the DJR had significant annual and seasonal variations and that the seasonal differences were greater than that the annual differences. Excessive nitrogen (N) and phosphorus (P) nutrients in the DJR are the most important factors affecting water quality in the reservoir, N and P nutrients are the main factors affecting bacterial communities. Season is the most important factor affecting bacterioplankton N and P cycle functions. Ecological network analysis indicated that the average clustering coefficient and average connectivity of the spring samples were lower than those of the autumn samples, while the number of modules for the spring samples was higher than that for the autumn samples. The neutral model explained 66.3%, 63.0%, 63.0%, and 70.9% of the bacterioplankton community variations in samples in the spring of 2018, the autumn of 2018, the spring of 2019, and the autumn of 2019, respectively. Stochastic processes dominate bacterioplankton community assembly in the DJR. This study revealed the composition, function, interaction, and assembly of bacterioplankton communities in the DJR, providing a reference for the protection of water quality and the ecological functions of DJR bacterioplankton.
Evidence of SARS-CoV-2 Antibodies and RNA on Autopsy Cases in the Pre-Pandemic Period in Milan (Italy)
Authors: Lai Alessia , Tambuzzi Stefano , Bergna Annalisa , Battistini Alessio , Della Ventura Carla , Galli Massimo , Zoja Riccardo , Zehender Gianguglielmo , Cattaneo Cristina
Published: June 2022

In this study, we analyzed blood samples obtained from 169 cadavers subjected to an autopsy from 1 October 2019 to 27 March 2020. The presence of anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies was searched by lateral flow immunochromatographic assay (LFIA) and ELISA tests and the SARS-CoV-2 RNA was tested in blood and available lung tissues by real-time PCR (RT-PCR) and droplet digital PCR (ddPCR). Five cases resulted in positives at the serological screening for anti-SARS-CoV-2. Three results were weakly positive for IgM while only one showed strong reactivity for IgG antibodies. The fifth subject (who died in December 2019) resulted positive for the ELISA test. The detection of SARS-CoV-2 RNA resulted in positive only in the blood and lung tissues of such cases. These data suggest that cadaveric blood may be a suitable substrate for the assessment of SARS-CoV-2 infection; moreover, they extend the observations of sporadic cases of SARS-CoV-2 infection in North Italy prior to the first confirmed cases.
Sanguinarine, Isolated From Macleaya cordata, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Inhibiting Ergosterol Synthesis
Authors: Hu Ziwei , Hu Hao , Hu Zhili , Zhong Xiaojun , Guan Yifu , Zhao Yunshi , Wang Lu , Ye Liang , Ming Liliang , Riaz Rajoka Muhammad Shahid , He Zhendan , Wang Yan , Song Xun
Published: June 2022

In recent decades, infections caused by the opportunistic fungus Candida albicans have increased, especially in patients with immunodeficiency. In this study, we investigated the mechanism of action of sanguinarine (SAN) against C. albicans both in vitro and in vivo. SAN exhibited antifungal activity against C. albicans clinical isolates, with MICs in the range of 112.8–150.5 μM. Furthermore, scanning electron and transmission electron microscopy showed that SAN induced morphological changes as well as structure disruption in C. albicans cells, including masses of cellular debris, ruptured cell walls, and membrane deformation. Flow cytometry revealed that SAN could lead to cell membrane damage, and ergosterol content analysis indicated that SAN could cause ergosterol content reduction exceeding 90%. Further, we validated the efficacy of SAN against candidiasis caused by C. albicans in a murine model, and SAN significantly improved survival and reduced weight loss compared to vehicle. The treatment of 1.5 and 2.5 mg/kg/d SAN obviously reduced the fungal burden in the kidney. In addition, histopathological examination indicated that no fungal cells were observed in lung and kidney tissues after SAN treatment. Hence, this study suggests that SAN is a promising plant-derived compound for the development of an effective anticandidal agent.
Expression of ALG3 in Hepatocellular Carcinoma and Its Clinical Implication
Authors: Zhao Zhen , Zheng Zehao , Huang Jianfeng , Wang Jianxi , Peng Tianyi , Lin Ye , Jian Zhixiang
Published: June 2022

Background: Recent studies have shown that alpha-1,3-mannosyltransferase (ALG3) promoted tumorigenesis and progression in multiple cancer types. Our study planned to explore the clinical implication and potential function of ALG3 in hepatocellular carcinoma.

Materials and Methods: Data from public databases were used to analyze the ALG3 expression and its impact on the clinical significance of patients with HCC. The ALG3 expression was confirmed by qRT-PCR and Western blot. Immunohistochemistry was used to confirm the ALG3 expression and explore its clinical implication in HCC. KEGG, GO, and GSEA enrichment analyses were utilized to explore the biological pathways related to ALG3 in HCC. TIMER2.0 was applied to assess the association between ALG3 and immune infiltration. CCK8, MTT, and transwell assays were used to investigate the role of ALG3 downregulation in HCC cell lines.

Results: qRT-PCR, WB, and IHC proved ALG3 was highly overexpressed in HCC tissues. The Kaplan–Meier analysis verified the overexpression of ALG3 was related to poor overall survival (p < 0.001). Multivariate cox regression analysis showed that the high ALG3 expression was an independent risk prognostic factor. GSEA and TIMER2.0 predicted that ALG3 participates in cell differentiation and cycle and correlates with immune cell infiltration. Transwell assay results showed that ALG3 silencing also impaired the invasion ability of HCC cells.

Conclusion: ALG3 was overexpressed and considered a potential indicator of survival in HCC, and our findings provided a novel therapeutic target for HCC.
Plasticity of Membrane Binding by the Central Region of α-Synuclein
Authors: Navarro-Paya Carlos , Sanz-Hernandez Maximo , De Simone Alfonso
Published: June 2022

Membrane binding by α-synuclein (αS), an intrinsically disordered protein whose aggregation is associated with Parkinson’s disease, is a key step in determining its biological properties under both physiological and pathological conditions. Upon membrane interaction, αS retains a partial level of structural disorder despite acquiring α-helical content. In the membrane-bound state, the equilibrium between the helical-bound and disordered-detached states of the central region of αS (residues 65–97) has been involved in a double-anchor mechanism that promotes the clustering of synaptic vesicles. Herein, we investigated the underlying molecular bases of this equilibrium using enhanced coarse-grained molecular dynamics simulations. The results enabled clarifying the conformational dependencies of the membrane affinity by this protein region that, in addition to playing a role in physiological membrane binding, has key relevance for the aggregation of αS and the mechanisms of the toxicity of the resulting assemblies.
Williams-Beuren Syndrome Related Methyltransferase WBSCR27: From Structure to Possible Function
Authors: Mariasina Sofia S. , Chang Chi-Fon , Navalayeu Tsimafei L. , Chugunova Anastasia A. , Efimov Sergey V. , Zgoda Viktor G. , Ivlev Vasily A. , Dontsova Olga A. , Sergiev Petr V. , Polshakov Vladimir I.
Published: June 2022

Williams-Beuren syndrome (WBS) is a genetic disorder associated with the hemizygous deletion of several genes in chromosome 7, encoding 26 proteins. Malfunction of these proteins induce multisystemic failure in an organism. While biological functions of most proteins are more or less established, the one of methyltransferase WBSCR27 remains elusive. To find the substrate of methylation catalyzed by WBSCR27 we constructed mouse cell lines with a Wbscr27 gene knockout and studied the obtained cells using several molecular biology and mass spectrometry techniques. We attempted to pinpoint the methylation target among the RNAs and proteins, but in all cases neither a direct substrate has been identified nor the protein partners have been detected. To reveal the nature of the putative methylation substrate we determined the solution structure and studied the conformational dynamic properties of WBSCR27 in apo state and in complex with S-adenosyl-L-homocysteine (SAH). The protein core was found to form a canonical Rossman fold common for Class I methyltransferases. N-terminus of the protein and the β6–β7 loop were disordered in apo-form, but binding of SAH induced the transition of these fragments to a well-formed substrate binding site. Analyzing the structure of this binding site allows us to suggest potential substrates of WBSCR27 methylation to be probed in further research.
RecQ Helicase Somatic Alterations in Cancer
Authors: Thakkar Megha K. , Lee Jamie , Meyer Stefan , Chang Vivian Y.
Published: June 2022

Named the “caretakers” of the genome, RecQ helicases function in several pathways to maintain genomic stability and repair DNA. This highly conserved family of enzymes consist of five different proteins in humans: RECQL1, BLM, WRN, RECQL4, and RECQL5. Biallelic germline mutations inBLM,WRN, andRECQL4have been linked to rare cancer-predisposing syndromes. Emerging research has also implicated somatic alterations in RecQ helicases in a variety of cancers, including hematological malignancies, breast cancer, osteosarcoma, amongst others. These alterations in RecQ helicases, particularly overexpression, may lead to increased resistance of cancer cells to conventional chemotherapy. Downregulation of these proteins may allow for increased sensitivity to chemotherapy, and, therefore, may be important therapeutic targets. Here we provide a comprehensive review of our current understanding of the role of RecQ DNA helicases in cancer and discuss the potential therapeutic opportunities in targeting these helicases.
Inconsistencies in Modeling the Efficacy of the Oncolytic Virus HSV1716 Reveal Potential Predictive Biomarkers for Tolerability
Authors: Howard Faith , Conner Joe , Danson Sarah , Muthana Munitta
Published: June 2022

Treatment with HSV1716viaintralesional administration has proven successful for melanoma patients with the hope that oncolytic virotherapy would become another weapon in the systemic anticancer therapy (SACT) arsenal. In addition to challenges surrounding the systemic delivery of oncolytic viruses (OVs), problems associated with itsin vivomodeling have resulted in low predictive power, contributing to the observed disappointing clinical efficacy. As OV’s efficacy is elicited through interaction with the immune system, syngeneic orthotopic mouse models offer the opportunity to study these with high reproducibility and at a lower cost; however, inbred animals display specific immune characteristics which may confound results. The systemic delivery of HSV1716 was, therefore, assessed in multiple murine models of breast cancer. Tolerability to the virus was strain-dependent with C57/Bl6, the most tolerant and Balb/c experiencing lethal side effects, when delivered intravenously. Maximum tolerated doses were not enough to demonstrate efficacy against tumor growth rates or survival of Balb/c and FVB mouse models; therefore; the most susceptible strain (Balb/c mice) was treated with immunomodulators prior to virus administration in an attempt to reduce side effects. These studies demonstrate the number of variables to consider when modeling the efficacy of OVs and the complexities involved in their interpretation for translational purposes. By reporting these observations, we have potentially revealed a role for T-cell helper polarization in viral tolerability. Importantly, these findings were translated to human studies, whereby a Th1 cytokine profile was expressed in pleural effusions of patients that responded to HSV1716 treatment for malignant pleural mesothelioma with minimal side effects, warranting further investigation as a biomarker for predictive response.
Statistical Analysis of Protein-Ligand Interaction Patterns in Nuclear Receptor RORγ
Authors: Pham Bill , Cheng Ziju , Lopez Daniel , Lindsay Richard J. , Foutch David , Majors Rily T. , Shen Tongye
Published: June 2022

The receptor RORγ belongs to the nuclear receptor superfamily that senses small signaling molecules and regulates at the gene transcription level. Since RORγ has a high basal activity and plays an important role in immune responses, inhibitors targeting this receptor have been a focus for many studies. The receptor-ligand interaction is complex, and often subtle differences in ligand structure can determine its role as an inverse agonist or an agonist. We examined more than 130 existing RORγ crystal structures that have the same receptor complexed with different ligands. We reported the features of receptor-ligand interaction patterns and the differences between agonist and inverse agonist binding. Specific changes in the contact interaction map are identified to distinguish active and inactive conformations. Further statistical analysis of the contact interaction patterns using principal component analysis reveals a dominant mode which separates allosteric binding vs. canonical binding and a second mode which may indicate active vs. inactive structures. We also studied the nature of constitutive activity by performing a 100-ns computer simulation of apo RORγ. Using constitutively active nuclear receptor CAR as a comparison, we identified a group of conserved contacts that have similar contact strength between the two receptors. These conserved contact interactions, especially a couple key contacts in H11–H12 interaction, can be considered essential to the constitutive activity of RORγ. These protein-ligand and internal protein contact interactions can be useful in the development of new drugs that direct receptor activity.
Grounding Context in Embodied Cognitive Robotics
Authors: Valenzo Diana , Ciria Alejandra , Schillaci Guido , Lara Bruno
Published: June 2022

Biological agents are context-dependent systems that exhibit behavioral flexibility. The internal and external information agents process, their actions, and emotions are all grounded in the context within which they are situated. However, in the field of cognitive robotics, the concept of context is far from being clear with most studies making little to no reference to it. The aim of this paper is to provide an interpretation of the notion of context and its core elements based on different studies in natural agents, and how these core contextual elements have been modeled in cognitive robotics, to introduce a new hypothesis about the interactions between these contextual elements. Here, global context is categorized as agent-related, environmental, and task-related context. The interaction of their core elements, allows agents to first select self-relevant tasks depending on their current needs, or for learning and mastering their environment through exploration. Second, to perform a task and continuously monitor its performance. Third, to abandon a task in case its execution is not going as expected. Here, the monitoring of prediction error, the difference between sensorimotor predictions and incoming sensory information, is at the core of behavioral flexibility during situated action cycles. Additionally, monitoring prediction error dynamics and its comparison with the expected reduction rate should indicate the agent its overall performance on executing the task. Sensitivity to performance evokes emotions that function as the driving element for autonomous behavior which, at the same time, depends on the processing of the interacting core elements. Taking all these into account, an interactionist model of contexts and their core elements is proposed. The model is embodied, affective, and situated, by means of the processing of the agent-related and environmental core contextual elements. Additionally, it is grounded in the processing of the task-related context and the associated situated action cycles during task execution. Finally, the model proposed here aims to guide how artificial agents should process the core contextual elements of the agent-related and environmental context to give rise to the task-related context, allowing agents to autonomously select a task, its planning, execution, and monitoring for behavioral flexibility.
Startle-Induced Epileptic Spasms: A Clinical and Video-EEG Study
Authors: Xu Zhao , Jiao Xianru , Gong Pan , Niu Yue , Yang Zhixian
Published: June 2022

Objective

This study aimed to delineate the detailed characteristics of startle-induced epileptic spasms (ES) and explore the brain regions where startle-induced ES originated.

Methods

Among 581 patients with ES registered in our database, 30 were diagnosed with startle-induced ES according to video-electroencephalogram (EEG) and seizure semiology and were included in this study. Patients' clinical characteristics and ictal high-frequency oscillations (HFOs) were analyzed.

Results

Mean age at the onset of startle-induced ES was 28.1 months. Half of the patients had structural etiology, two of whom were diagnosed with co-existing structural and genetic etiologies. The focal neuroimaging abnormalities were predominant in the frontal cortex (9/15, 60.0%). Fifteen patients (50%) had prominent interictal epileptiform discharges in the frontal and anterior temporal. Ictal HFOs counts of the startle-induced ES in the anterior region were significantly higher than those in the posterior regions (p< 0.05). Five patients (16.7%) became seizure-free ≥6 months, and ten (33.3%) showed startle-induced ES cessation ≥6 months. All patients except one had mild to severe psychomotor developmental delay after the onset of seizures.

Conclusion

Patients with startle-induced ES typically had brain lesions and showed drug-resistant. The neuroimaging and EEG findings, including ictal HFOs, support that startle-induced ES often originates from the frontal cortex.