bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Wnt Signaling in Postnatal Tooth Root Development
Authors: Tokavanich Nicha , Wein Marc N. , English Jeryl D. , Ono Noriaki , Ono Wanida
Published: November 2021

Appropriate tooth root formation and tooth eruption are critical for achieving and maintaining good oral health and quality of life. Tooth eruption is the process through which teeth emerge from their intraosseous position to their functional position in the oral cavity. This temporospatial process occurs simultaneously with tooth root formation through a cascade of interactions between the epithelial and adjoining mesenchymal cells. Here, we will review the role of the Wnt system in postnatal tooth root development. This signaling pathway orchestrates the process of tooth root formation and tooth eruption in conjunction with several other major signaling pathways. The Wnt signaling pathway is comprised of the canonical, or Wnt/β-catenin, and the non-Canonical signaling pathway. The expression of multiple Wnt ligands and their downstream transcription factors including β-catenin is found in the cells in the epithelia and mesenchyme starting from the initiation stage of tooth development. The inhibition of canonical Wnt signaling in an early stage arrests odontogenesis. Wnt transcription factors continue to be present in dental follicle cells, the progenitor cells responsible for differentiation into cells constituting the tooth root and the periodontal tissue apparatus. This expression occurs concurrently with osteogenesis and cementogenesis. The conditional ablation of β-catenin in osteoblast and odontoblast causes the malformation of the root dentin and cementum. On the contrary, the overexpression of β-catenin led to shorter molar roots with thin and hypo-mineralized dentin, along with the failure of tooth eruption. Therefore, the proper expression of Wnt signaling during dental development is crucial for regulating the proliferation, differentiation, as well as epithelial-mesenchymal interaction essential for tooth root formation and tooth eruption.
Numerical Simulation of Shale Reservoir Fluid-Driven Fracture Network Morphology Based on Global CZM
Authors: Yang Yang , Jiao Zixi , Du Longhuan , Fan Hua
Published: November 2021

There are a large number of natural fractures in shale reservoirs, which create great challenges to hydraulic fracturing. Activating the natural fractures in reservoirs can form a complex fracture network, enhance fracturing effects, and increase shale gas production. Reservoir geological conditions (low in situ stress, natural fracture distribution, and cement strength) and operation parameters (fracturing fluid viscosity and injection rate) have an important influence on fracture network propagation. In this article, a two-dimensional hydraulic fracturing fluid-mechanic coupling numerical model for shale reservoirs with natural fractures was established. Based on the global cohesive zone model, the influence of geological conditions and operation parameters on the propagation of the hydraulic fracture network and fracturing process is investigated. The numerical simulation results show that when the horizontal in situ stress difference, approach angle, and cement strength are low, it is easier to form a complex fracture network. Research on the construction parameters indicated that when the viscosity of the fracturing fluid is low, it is easier to form a complex network of fractures, but the length of the fractures is shorter; in contrast, the fractures are straight and long. In addition, increasing the injection rate is beneficial for increasing the complexity of the fracture network while increasing the initiation pressure and width of the principal fracture reduces the risk of sand plugging. This article also proposes an optimization solution for hydraulic fracturing operations based on numerical simulation results.
Regulatory and Policy Analysis of Production, Development and Use of Sustainable Aviation Fuels in the United States
Authors: Korkut Ekrem , Fowler Lara B.
Published: November 2021

The United States, spurred in part by international developments, is expanding its law and policy to incentivize the use of sustainable aviation fuels. While the U.S. has agreed to participate in the International Civil Aviation Organization’s (ICAO’s) Carbon Offsetting and Reduction Scheme for International Aviation (CORSIA), it has only recently adopted federal rules that define greenhouse gas emission reduction standards for certain classes of airplanes (effective January 2021). However, such standards focus on engine efficiency rather than the fuel burned. For sustainable aviation fuels, the U.S. continues to rely on voluntary programs at a federal, state, and regional level. The federal Renewable Fuel Standard program allows producers to opt in. In addition, states have started to allow sustainable aviation fuel producers to “opt in” to their programs; this includes California’s Low Carbon Fuel Standard, Oregon’s Clean Fuels Program, and Washington’s newly adopted Clean Fuels Program. Other states are also starting to consider such programs. Elsewhere, states like Hawaii are starting to support SAF production in other ways, including through tax mechanisms. In addition, regional and private efforts to adopt and/or promote sustainable aviation fuels are underway. This piecemeal approach—due in part to the lack of cohesive U.S. federal policy—stands in contrast to the European Union’s Renewable Energy Directive and Emissions Trading System, and adoption of policies by European countries. Because of aviation’s international nature, tracking what is happening in Europe matters greatly for U.S. carriers. As the U.S. works to meet its international obligations through CORSIA, finding a way forward with sustainable aviation fuel in the United States may depend on a more defined federal policy. Actions taken by both the EU and European countries offers some guidance for actions that could be taken by the U.S. Even in the absence of more defined measures, better tracking of voluntary measures is a critical step.
A Comparative Study of the Optimal Sizing and Management of Off-Grid Solar/Wind/Diesel and Battery Energy Systems for Remote Areas
Authors: Thirunavukkarasu M. , Sawle Yashwant
Published: November 2021

Electrification in rural areas is relatively costly compared to urban areas. Therefore, the aim of this research is to identify the best combination of hybrid renewable energy systems (HRESs) to satisfy the load demand in a sustainable and cost-efficient way. The techno-economic study of stand-alone hybrid photovoltaic–wind turbine–diesel–battery-converter energy systems based on the hybrid optimization model for electric renewable (HOMER) simulation has been analyzed for various locations in the Tamil Nadu state, India. Various combinations of the systems have been compared and analyzed based on the performance of their technical parameters, costs, the electrical power production of each source, and unmet load. The findings indicated that the off-grid solar–wind–diesel–battery configuration is the most economical for all the sites among other system configurations. Comparing with conventional diesel generators among all the locations, a combination of solar/wind/diesel/battery is the economically best design for Thoothukudi, with the least and most reliable solution in terms of net present cost and cost of energy. Also, the impact of intermittent variables becomes significant, so sensitivity analysis for the various parameters has been carried out. The study finds that the least cost of electricity and the net present cost of electricity for Thoothukudi are achieved at 0.266 $/kWh and 138,197 $, respectively. This is economical compared to a stand-alone diesel system where the obtained COE is $1.88 and the NPC is $977523. In the stand-alone diesel operating mode, 41854 kg of CO2is produced, which is higher than CO2emissions associated with any other renewable energy systems. According to the results, the Kanyakumari location outperforms in terms of producing environmental pollutants with emission of 1,020 kg/y CO2at their best. Moreover, the results of the proposed study imply that the proposed renewable energy system in remote sites could be a more economical measure.
Research on Influence Factors of Air Quality in the Host Area of the 24th Winter Olympic Games Based on Grey Relational Analysis
Authors: Wang Wei , Chen Yan , Xie Yuhan , Wu Lifeng
Published: November 2021

In recent years, the continuous development of the economy and science and technology of China has caused a certain degree of pollution to the atmospheric environment on which the people depend. The current air pollution problem is actively a concern by the government and all walks of life. Based on the 2015–2019 air quality indicators and some socioeconomic indicators, this paper uses the grey correlation analysis method to analyze the Beijing and Zhangjiakou cities that will host the Winter Olympics in 2022. The study found that the three factors most closely related to the Beijing Air Quality Index (AQI) are the permanent population (0.831), energy consumption (0.801), the number of motor vehicles (0.79), and the permanent population (0.916) and industrial added value (0.905). The total output value of agriculture, forestry, and animal husbandry and fishery (0.89) are the three factors most closely related to the air quality index (AQI) of Zhangjiakou City, and the permanent population is the common factor affecting the two cities. Considering that the factors that affect the air quality of the two cities are not exactly the same, this paper combines the development positioning of the two cities and their own characteristics, and puts forward specific suggestions and opinions on the different problems faced by the two cities. The aim is to promote the continuous improvement of air quality in the two cities to reach an excellent level through scientific and feasible air management programs before the opening of the 2022 Winter Olympic Games, and help the 2022 Winter Olympics to be held smoothly.
Catalytic Oxidation of Methylene Blue by Attapulgite/TiO2
Authors: Shang Jianping , Jiang Yu , Qin Xiaoping , Zhao Bin , Li Xuefei
Published: November 2021

Methylene blue (MB) is a common pollutant in wastewater of printing and dyeing industry. At present, ozone oxidation is commonly used in the treatment of printing and dyeing wastewater. Ozone is used for oxidation reaction directly and indirectly. However, the reaction rate is not fast enough. In this study, the attapulgite (ATP) was modified by tetrabutyl titanate-ethanol solution. The TiO2/ATP nanocomposite with high catalytic activity was prepared. The synthesized samples were subjected to characterized by X-ray diffraction (XRD) and Fourier Transform infrared spectroscopy (FTIR). The morphology and particle size of the particles were observed by scanning electron microscopy (SEM). The TiO2/ATP nanocomposite was calcined at 300°C for 2 h, and the degradation rate of 80 mg/L methylene blue was 99.8%. The experimental results show that the ozone, temperature and mass transfer factors are excluded, and the effects of temperature, MB concentration and pH on the degradation of methylene blue are investigated. The optimal reaction conditions are as follows: The ozone concentration is 0.067 g/min; the ozone flow rate is 0.15 NL/min; the stirrer rotation speed is 550 r/min; the catalyst is 0.1 g; the temperature is 50°C; Based on the results, the reaction mechanism was derived and the kinetic study of the experiment was carried out.
Chemosensory Exploitation and Predator-Prey Arms Races
Authors: Zimmer Richard K. , Ferrier Graham A. , Zimmer Cheryl Ann
Published: November 2021

Thousands of armed predatory species, distributed widely across the metazoan tree-of-life, consume only hard-shell or exoskeleton-bearing organisms (called “durophagy”). Prey armor clearly has evolved in response to selection by predators, but there is little evidence of the contrary, counter-adaptation by predators. Evolved consumer responses to prey, in general, might be more readily expressed in ways other than morphological traits, including via sensory cues. Here, we explored the chemosensory basis for durophagy in a model predator-prey system, and identified intimate associations between durophagous predators and their shelled prey. Barnacles (Balanus glandula and Semibalanus cariosus) bear hard shells and secrete, respectively, a 199 or 201 kDa glycoprotein ortholog (named “MULTIFUNCin”), with expression limited to the body armor (epidermis, cuticle, and live shell). To test for effects of MULTIFUNCin on predators, we constructed faux prey to mimic meaningful physical and chemical characteristics of live barnacles. In separate experiments, each consumer species was presented MULTIFUNCin, purified from either B. glandula or S. cariosus, at a typical armor concentration. All six predatory species (sea star, Pisaster ochraceus; whelks, Acanthinucella spirata, Nucella emarginata, N. ostrina, N. canaliculata, and N. lamellosa) attacked and ate MULTIFUNCin-infused faux prey significantly more than controls. Akin to barnacles, secretion of glycoprotein-rich extracellular matrices is common among armored prey species—from marine sponges to terrestrial vertebrates. Our results, therefore, suggest that chemosensory exploitation of glycoproteins could be widespread, with notable consequences for life on land and in the sea.
piggyPrime: High-Efficacy Prime Editing in Human Cells Using piggyBac-Based DNA Transposition
Authors: Wolff Jonas Holst , Haldrup Jakob , Thomsen Emil Aagaard , Andersen Sofie , Mikkelsen Jacob Giehm
Published: November 2021

Prime editing is a novel genome editing technology that allows a wide range of tailored genomic alterations. Prime editing does not involve homologous recombination, but suffers from low efficacy. Here, we demonstrate piggyPrime, a transfected single-vector system based on piggyBac DNA transposition for genomic integration of all prime editing components in human cells allowing easy and effective transgenesis with prime editing efficacies up to 100% in cell lines.
Isobaric Tags for Relative and Absolute Quantification-Based Proteomics Reveals Candidate Proteins of Fat Deposition in Chinese Indigenous Sheep With Morphologically Different Tails
Authors: Zhu Caiye , Cheng Heping , Li Na , Liu Tiaoguo , Ma Youji
Published: November 2021

Background: Chinese indigenous sheep can be classified into two types according to their tail morphology: fat-rumped and thin-tailed sheep, of which the typical breeds are Altay sheep and Tibetan sheep, respectively.

Methods: To identify the differentially expressed proteins (DEPs) underlying the phenotypic differences between tail types, we used isobaric tags for relative and absolute quantification (iTRAQ) combined with multi-dimensional liquid chromatography tandem-mass spectrometry (LC-MS/MS) technology to detect candidate proteins. We then subjected these to a database search and identified the DEPs. Finally, bioinformatics technology was used to carry out Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.

Results: A total of 3,248 proteins were identified, of which 44 were up-regulated and 40 were down-regulated DEPs. Analyzing their GO function terms and KEGG pathways revealed that the functions of these DEPs are mainly binding, catalytic activity, structural molecule activity, molecular function regulator, and transporter activity. Among the genes encoding the DEPs, APOA2, GALK1, ADIPOQ, and NDUFS4 are associated with fat formation and metabolism.

Conclusion: The APOA2, GALK1, ADIPOQ, and NDUFS4 genes may be involved in the deposition of fat in the tail of sheep. This study provides a scientific basis for the breeding of thin-tailed sheep.
Comprehensive Analysis of the Tumor Microenvironment and Ferroptosis-Related Genes Predict Prognosis with Ovarian Cancer
Authors: Li Xiao-xue , Xiong Li , Wen Yu , Zhang Zi-jian
Published: November 2021

The early diagnosis of ovarian cancer (OC) is critical to improve the prognosis and prevent recurrence of patients. Nevertheless, there is still a lack of factors which can accurately predict it. In this study, we focused on the interaction of immune infiltration and ferroptosis and selected the ESTIMATE algorithm and 15 ferroptosis-related genes (FRGs) to construct a novel E-FRG scoring model for predicting overall survival of OC patients. The gene expression and corresponding clinical characteristics were obtained from the TCGA dataset (n = 375), GSE18520 (n = 53), and GSE32062 (n = 260). A total of 15 FRGs derived from FerrDb with the immune score and stromal score were identified in the prognostic model by using least absolute shrinkage and selection operator (LASSO)–penalized COX regression analysis. The Kaplan–Meier survival analysis and time-dependent ROC curves performed a powerful prognostic ability of the E-FRG model via multi-validation. Gene Set Enrichment Analysis and Gene Set Variation Analysis elucidate multiple potential pathways between the high and low E-FRG score group. Finally, the proteins of different genes in the model were verified in drug-resistant and non–drug-resistant tumor tissues. The results of this research provide new prospects in the role of immune infiltration and ferroptosis as a helpful tool to predict the outcome of OC patients.
Complement-Mediated Differential Immune Response of Human Macrophages to Sporothrix Species Through Interaction With Their Cell Wall Peptidorhamnomannans
Authors: Neves Gabriela W. P. , Wong Sarah Sze Wah , Aimanianda Vishukumar , Simenel Catherine , Guijarro J. Iñaki , Walls Catriona , Willment Janet A. , Gow Neil A. R. , Munro Carol A. , Brown Gordon D. , Lopes-Bezerra Leila M.
Published: November 2021

In this study, the human immune response mechanisms againstSporothrix brasiliensisandSporothrix schenckii, two causative agents of human and animal sporotrichosis, were investigated. The interaction ofS. brasiliensisandS. schenckiiwith human monocyte-derived macrophages (hMDMs) was shown to be dependent on the thermolabile serum complement protein C3, which facilitated the phagocytosis ofSporothrixyeast cells through opsonization. The peptidorhamnomannan (PRM) component of the cell walls of these twoSporothrixyeasts was found to be one of their surfaces exposed pathogen-associated molecular pattern (PAMP), leading to activation of the complement system and deposition of C3b on theSporothrixyeast surfaces. PRM also showed direct interaction with CD11b, the specific component of the complement receptor-3 (CR3). Furthermore, the blockade of CR3 specifically impacted the interleukin (IL)-1β secretion by hMDM in response to bothS. brasiliensisandS. schenckii, suggesting that the host complement system plays an essential role in the inflammatory immune response against theseSporothrixspecies. Nevertheless, the structural differences in the PRMs of the twoSporothrixspecies, as revealed by NMR, were related to the differences observed in the host complement activation pathways. Together, this work reports a new PAMP of the cell surface of pathogenic fungi playing a role through the activation of complement system andviaCR3 receptor mediating an inflammatory response toSporothrixspecies.
Pulmonary Eosinophils at the Center of the Allergic Space-Time Continuum
Authors: Schetters Sjoerd T. T. , Schuijs Martijn J.
Published: November 2021

Eosinophils are typically a minority population of circulating granulocytes being released from the bone-marrow as terminally differentiated cells. Besides their function in the defense against parasites and in promoting allergic airway inflammation, regulatory functions have now been attributed to eosinophils in various organs. Although eosinophils are involved in the inflammatory response to allergens, it remains unclear whether they are drivers of the asthma pathology or merely recruited effector cells. Recent findings highlight the homeostatic and pro-resolving capacity of eosinophils and raise the question at what point in time their function is regulated. Similarly, eosinophils from different physical locations display phenotypic and functional diversity. However, it remains unclear whether eosinophil plasticity remains as they develop and travel from the bone marrow to the tissue, in homeostasis or during inflammation. In the tissue, eosinophils of different ages and origin along the inflammatory trajectory may exhibit functional diversity as circumstances change. Herein, we outline the inflammatory time line of allergic airway inflammation from acute, late, adaptive to chronic processes. We summarize the function of the eosinophils in regards to their resident localization and time of recruitment to the lung, in all stages of the inflammatory response. In all, we argue that immunological differences in eosinophils are a function of time and space as the allergic inflammatory response is initiated and resolved.
Development of a Novel Nomogram for Predicting Premature Rupture of Membrane in Pregnant Women With Vulvovaginal Candidiasis
Authors: Yang Lilin , Wang Haikuan , Li Yanfang , Zeng Cheng , Lin Xi , Gao Jie , Luo Songping
Published: November 2021

Objective: The aim of this study was to develop a nomogram to predict the risk of premature rupture of membrane (PROM) in pregnant women with vulvovaginal candidiasis (VVC).

Patients and methods: We developed a prediction model based on a training dataset of 417 gravidas with VVC, the data were collected from January 2013 to December 2020. The least absolute shrinkage and selection operator regression model was used to optimize feature selection for the model. Multivariable logistic regression analysis was applied to build a prediction model incorporating the feature selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the prediction model were assessed using the C-index, calibration plot, and decision curve analysis. Internal validation was assessed using bootstrapping validation.

Results: Predictors contained in the prediction nomogram included age, regular perinatal visits, history of VVC before pregnancy, symptoms with VVC, cured of VVC during pregnancy, and bacterial vaginitis. The model displayed discrimination with a C-index of 0.684 (95% confidence interval: 0.631–0.737). Decision curve analysis showed that the PROM nomogram was clinically useful when intervention was decided at a PROM possibility threshold of 13%.

Conclusion: This novel PROM nomogram incorporating age, regular perinatal visits, history of VVC before pregnancy, symptoms with VVC, cured of VVC during pregnancy, and bacterial vaginitis could be conveniently used to facilitate PROM risk prediction in gravidas.
Does Cannabis Extract Obtained From Cannabis Flowers With Maximum Allowed Residual Level of Aflatoxins and Ochratoxin a Have an Impact on Human Safety and Health?
Authors: Serafimovska Tijana , Stefanovski Sasho , Erler Joachim , Keskovski Zlatko , Stefkov Gjoshe , Mitevska Marija , Darkovska Serafimovska Marija , Balkanov Trajan , Tonic Ribarska Jasmina
Published: November 2021

Aim: The aim of this study was to investigate whether the cannabis extract obtained from cannabis flowers that contain the maximum allowed level of mycotoxins affects human safety and health. For that purpose, a novel liquid chromatography with tandem mass spectrometry (LC/MS/MS) method was developed and validated for the determination of aflatoxins and ochratoxin A (OchA) in cannabis extracts to demonstrate that this analytical method is suitable for the intended experimental design.

Methods: Experimental design was done by adding maximum allowed concentration of aflatoxins (B1, B2, G1, G2) and OchA according to the European Pharmacopeia related to cannabis flowers. The concentration of aflatoxins and OchA was determined using the same LC/MS/MS analytical method in the starting material (dry flower) before preparing the spiked sample and after obtaining decarboxylated extract with ethanol 96%.

Results: The results obtained indicate that aflatoxins and OchA, primarily added to the cannabis dried flowers, were also determined into the obtained final extract in amounts much higher (m/m) than in the starting plant material.

Conclusion: With this experiment, we have shown that mycotoxins, especially aflatoxins, which are extremely toxic secondary metabolites, can reach critical values in cannabis extracts obtained from dry cannabis flowers with the maximum allowed quantity of mycotoxins. This can pose a great risk to consumers and their health especially to those with compromised immune systems.
Unilateral Corneal Insult Also Alters Sensory Nerve Activity in the Contralateral Eye
Authors: Luna Carolina , Quirce Susana , Aracil-Marco Adolfo , Belmonte Carlos , Gallar Juana , Acosta M. Carmen
Published: November 2021

After the unilateral inflammation or nerve lesion of the ocular surface, the ipsilateral corneal sensory nerve activity is activated and sensitized, evoking ocular discomfort, irritation, and pain referred to the affected eye. Nonetheless, some patients with unilateral ocular inflammation, infection, or surgery also reported discomfort and pain in the contralateral eye. We explored the possibility that such altered sensations in the non-affected eye are due to the changes in their corneal sensory nerve activity in the contralateral, not directly affected eye. To test that hypothesis, we recorded the impulse activity of the corneal mechano- and polymodal nociceptor and cold thermoreceptor nerve terminals in both eyes of guinea pigs, subjected unilaterally to three different experimental conditions (UV-induced photokeratitis, microkeratome corneal surgery, and chronic tear deficiency caused by removal of the main lacrimal gland), and in eyes of naïve animalsex vivo. Overall, after unilateral eye damage, the corneal sensory nerve activity appeared to be also altered in the contralateral eye. Compared with the naïve guinea pigs, animals with unilateral UV-induced mild corneal inflammation, showed on both eyes an inhibition of the spontaneous and stimulus-evoked activity of cold thermoreceptors, and increased activity in nociceptors affecting both the ipsilateral and the contralateral eye. Unilateral microkeratome surgery affected the activity of nociceptors mostly, inducing sensitization in both eyes. The removal of the main lacrimal gland reduced tear volume and increased the cold thermoreceptor activity in both eyes. This is the first direct demonstration that unilateral corneal nerve lesion, especially ocular surface inflammation, functionally affects the activity of the different types of corneal sensory nerves in both the ipsilateral and contralateral eyes. The mechanisms underlying the contralateral affectation of sensory nerves remain to be determined, although available data support the involvement of neuroimmune interactions. The parallel alteration of nerve activity in contralateral eyes has two main implications: a) in the experimental design of both preclinical and clinical studies, where the contralateral eyes cannot be considered as a control; and, b) in the clinical practice, where clinicians must consider the convenience of treating both eyes of patients with unilateral ocular conditions to avoid pain and secondary undesirable effects in the fellow eye.
Technological and Safety Characterization of Kocuria rhizophila Isolates From Traditional Ethnic Dry-Cured Ham of Nuodeng, Southwest China
Authors: Shi Qiao , Wang Xinrui , Ju Zijing , Liu Biqin , Lei Changwei , Wang Hongning , Li Hong
Published: November 2021

Nuodeng ham is known for its unique processing techniques and flavor. In the present study, proteolytic microorganisms from cured artisanal Nuodeng ham were investigated in order to identify and select potential starter cultures for its faster and safer fermentation. Eight isolates, accounting for 57% of proteolytic microorganisms, were found to be related to Kocuria rhizophila. Relevant properties of K. rhizophila as potential starter culture were evaluated in vitro for the first time. Intra-species diversities were found in phylogenetic and physiological properties of K. rhizophila isolates. Nevertheless, desirable attributes, such as halo-tolerance, nitrate reductase and protease activity, as well as the absence of antimicrobial resistance and amino acid decarboxylase activity, were observed in selected isolates. Moreover, genome analysis of isolates K24 and K45 confirmed their lack of typical genes for virulence, antimicrobial resistance and amino acid decarboxylase. K. rhizophila may thus represent a novel starter candidate of coagulase-negative cocci group and contribute to color and flavor development of fermented meats.
The Antioxidant Guaiacol Exerts Fungicidal Activity Against Fungal Growth and Deoxynivalenol Production in Fusarium graminearum
Authors: Gao Tao , Zhang Yao , Shi Jianrong , Mohamed Sherif Ramzy , Xu Jianhong , Liu Xin
Published: November 2021

The main component of creosote obtained from dry wood distillation—guaiacol—is a natural antioxidant that has been widely used in pharmaceutical and food preservation applications. However, the antifungal mechanism of guaiacol against phytopathogens remains unclear. In this study, we found that guaiacol exerts inhibitory effects against mycelial growth, conidial formation and germination, and deoxynivalenol (DON) biosynthesis in Fusarium graminearum in a dose-dependent manner. The median effective concentration (EC50) value of guaiacol for the standard F. graminearum strain PH-1 was 1.838 mM. Guaiacol strongly inhibited conidial production and germination. The antifungal effects of guaiacol may be attributed to its capability to cause damage to the cell membrane by disrupting Ca2+ transport channels. In addition, the decreased malondialdehyde (MDA) levels and catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) activity by guaiacol treatment indicate that guaiacol displays activity against DON production by modulating the oxidative response in F. graminearum. Taken together, this study revealed the potentials of antioxidant in inhibiting mycotoxins in F. graminearum.
Comparative Genomic and Pan-Genomic Characterization of Staphylococcus epidermidis From Different Sources Unveils the Molecular Basis and Potential Biomarkers of Pathogenic Strains
Authors: Lin Shudan , Sun Bianjin , Shi Xinrui , Xu Yi , Gu Yunfeng , Gu Xiaobin , Ma Xueli , Wan Tian , Xu Jie , Su Jianzhong , Lou Yongliang , Zheng Meiqin
Published: November 2021

Coagulase-negative Staphylococcus (CoNS) is the most common pathogen causing traumatic endophthalmitis. Among which, Staphylococcus epidermidis is the most common species that colonizes human skin, eye surfaces, and nasal cavity. It is also the main cause of nosocomial infection, specially foreign body-related bloodstream infections (FBR-BSIs). Although some studies have reported the genome characteristics of S. epidermidis, the genome of ocular trauma-sourced S. epidermidis strain and a comprehensive understanding of its pathogenicity are still lacking. Our study sequenced, analyzed, and reported the whole genomes of 11 ocular trauma-sourced samples of S. epidermidis that caused traumatic endophthalmitis. By integrating publicly available genomes, we obtained a total of 187 S. epidermidis samples from healthy and diseased eyes, skin, respiratory tract, and blood. Combined with pan-genome, phylogenetic, and comparative genomic analyses, our study showed that S. epidermidis, regardless of niche source, exhibits two founder lineages with different pathogenicity. Moreover, we identified several potential biomarkers associated with the virulence of S. epidermidis, including essD, uhpt, sdrF, sdrG, fbe, and icaABCDR. EssD and uhpt have high homology with esaD and hpt in Staphylococcus aureus, showing that the genomes of S. epidermidis and S. aureus may have communicated during evolution. SdrF, sdrG, fbe, and icaABCDR are related to biofilm formation. Compared to S. epidermidis from blood sources, ocular-sourced strains causing intraocular infection had no direct relationship with biofilm formation. In conclusion, this study provided additional data resources for studies on S. epidermidis and improved our understanding of the evolution and pathogenicity among strains of different sources.
The Association Between Lysosomal Storage Disorder Genes and Parkinson’s Disease: A Large Cohort Study in Chinese Mainland Population
Authors: Zhao Yu-wen , Pan Hong-xu , Liu Zhenhua , Wang Yige , Zeng Qian , Fang Zheng-huan , Luo Teng-fei , Xu Kun , Wang Zheng , Zhou Xun , He Runcheng , Li Bin , Zhao Guihu , Xu Qian , Sun Qi-ying , Yan Xin-xiang , Tan Jie-qiong , Li Jin-chen , Guo Ji-feng , Tang Bei-sha
Published: November 2021

Background: Recent years have witnessed an increasing number of studies indicating an essential role of the lysosomal dysfunction in Parkinson’s disease (PD) at the genetic, biochemical, and cellular pathway levels. In this study, we investigated the association between rare variants in lysosomal storage disorder (LSD) genes and Chinese mainland PD.

Methods: We explored the association between rare variants of 69 LSD genes and PD in 3,879 patients and 2,931 controls from Parkinson’s Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) using next-generation sequencing, which were analyzed by using the optimized sequence kernel association test.

Results: We identified the significant burden of rare putative LSD gene variants in Chinese mainland patients with PD. This association was robust in familial or sporadic early-onset patients after excluding the GBA variants but not in sporadic late-onset patients. The burden analysis of variant sets in genes of LSD subgroups revealed a suggestive significant association between variant sets in genes of sphingolipidosis deficiency disorders and familial or sporadic early-onset patients. In contrast, variant sets in genes of sphingolipidoses, mucopolysaccharidoses, and post-translational modification defect disorders were suggestively associated with sporadic late-onset patients. Then, SMPD1 and other four novel genes (i.e., GUSB, CLN6, PPT1, and SCARB2) were suggestively associated with sporadic early-onset or familial patients, whereas GALNS and NAGA were suggestively associated with late-onset patients.

Conclusion: Our findings supported the association between LSD genes and PD and revealed several novel risk genes in Chinese mainland patients with PD, which confirmed the importance of lysosomal mechanisms in PD pathogenesis. Moreover, we identified the genetic heterogeneity in early-onset and late-onset of patients with PD, which may provide valuable suggestions for the treatment.
N-Acetyl Cysteine Restores Sirtuin-6 and Decreases HMGB1 Release Following Lipopolysaccharide-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Mice
Authors: Singh-Mallah Gagandeep , Kawamura Takuya , Ardalan Maryam , Chumak Tetyana , Svedin Pernilla , Arthur Peter G. , James Christopher , Hagberg Henrik , Sandberg Mats , Mallard Carina
Published: November 2021

Inflammation and neonatal hypoxia-ischemia (HI) are important etiological factors of perinatal brain injury. However, underlying mechanisms remain unclear. Sirtuins are a family of nicotinamide adenine dinucleotide (NAD)+-dependent histone deacetylases. Sirtuin-6 is thought to regulate inflammatory and oxidative pathways, such as the extracellular release of the alarmin high mobility group box-1 (HMGB1). The expression and role of sirtuin-6 in neonatal brain injury are unknown. In a well-established model of neonatal brain injury, which encompasses inflammation (lipopolysaccharide, LPS) and hypoxia-ischemia (LPS+HI), we investigated the protein expression of sirtuin-6 and HMGB1, as well as thiol oxidation. Furthermore, we assessed the effect of the antioxidant N-acetyl cysteine (NAC) on sirtuin-6 expression, nuclear to cytoplasmic translocation, and release of HMGB1 in the brain and blood thiol oxidation after LPS+HI. We demonstrate reduced expression of sirtuin-6 and increased release of HMGB1 in injured hippocampus after LPS+HI. NAC treatment restored sirtuin-6 protein levels, which was associated with reduced extracellular HMGB1 release and reduced thiol oxidation in the blood. The study suggests that early reduction in sirtuin-6 is associated with HMGB1 release, which may contribute to neonatal brain injury, and that antioxidant treatment is beneficial for the alleviation of these injurious mechanisms.
The Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Patients With Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Shi Min , Yang Chao , Tang Qing-wen , Xiao Ling-fei , Chen Zu-han , Zhao Wen-yuan
Published: November 2021

The neutrophil–to-lymphocyte ratio (NLR), as an essential systemic inflammation factor, has been widely used as a prognostic indicator in various diseases, such as malignant tumors, cardiovascular disease, and intracranial hemorrhage. An increasing number of studies have believed that NLR is a valuable predictor of prognosis for patients with aneurysmal subarachnoid hemorrhage (aSAH). However, these results remain controversial. In the current study, we planned to carry out a systematic review and meta-analysis to investigate the association between NLR and poor outcome, and the occurrence of delayed cerebral ischemia (DCI). We carried out a comprehensive search for published literatures on PubMed, EMBASE, Cochrane Library, and Web of Science databases from inception to April 1, 2021. We conducted an assessment of all included studies based on the principles proposed in the Newcastle-Ottawa Quality Assessment Scale (NOS). Poor outcome and the occurrence of DCI were considered as the main outcome measure. We calculated the pooled odds ratio (OR) and corresponding 95% confidence interval (CI) to examine the strength of the association of NLR with poor outcome or the occurrence of DCI. We strictly selected a total of 10 studies comprising 4,989 patients. Nine studies reported the association between NLR and poor outcome, and five studies reported the association between NLR and the occurrence of DCI. The pooled results indicated higher NLR was significantly associated with both poorer outcomes (OR = 1.32, 95%CI 1.11–1.57; P = 0.002, I2 = 87%), and the occurrence of DCI (OR = 1.72, 95%CI 1.22–2.41; P = 0.002, I2 = 82%) in aSAH patients. The NLR is a valuable indicator of inflammation to independently predict poor outcome and occurrence of DCI after aSAH, where a higher NLR is significantly associated with poor outcomes and occurrence of DCI. These findings suggest that the NLR can help clinicians evaluate the prognosis and identify potentially severe patients early, which may contribute to better management and improve poor prognosis of aSAH patients.
How Does the Gradient Measure of the Lung SBRT Treatment Plan Depend on the Tumor Volume and Shape?
Authors: Duan Yanhua , Lin Yang , Wang Hao , Kang Bodong , Feng Aihui , Ma Kui , Chen Hua , Huang Ying , Gu Hengle , Shao Yan , Zhou Tao , Kong Qing , Xu Zhiyong
Published: November 2021

Purpose

Gradient measure (GM) is a critical index related to normal tissue sparing in radiosurgery. This study aims to describe the dependence of GM on target volume and target shape for lung stereotactic body radiation therapy (SBRT) treatment plans.

Methods

A total of 307 peripheral and 119 central lung SBRT treatment plans were enrolled for this study. A least-squares regression was used for data analysis. First, the equations with different functional forms were established to determine the dependence of GM on a univariaty (VP or Sp) and bivariaty (VP and Sp), respectively. Then, the correlation coefficients and p-values of variables for all equations were compared and analyzed to determine the dependence of GM on PTV volume (VP) and sphericity (Sp).

Results

The power equations had the highest coefficient of determination (R2) in the dependence results of GM on univariate VP. The equations were GM=0.674VP0.178 and GM=0.660VP0.185 for peripheral and central lesions, respectively. On the other hand, the R2 of all functional forms were less than 0.25 when the relationship of GM versus univariate Sp was analyzed. Similarly, the power equation also obtained the highest R2 in bivariaty VP and Sp analysis, whether for central or peripheral. However, the R2 of the bivariate equations were not improved compared with those of univariate equations. Moreover, the p-values of the variable Sp were greater than 0.05.

Conclusions

The GM of the lung SBRT plan is shape-independent and volume-dependent. The dependence of GM on PTV volume for peripheral and central lung cancer can be described by two different power equations. The results of this study can be used as a potential tool to assist dosimetric quality control during the radiosurgery process.
Clinical Characteristics and Outcomes of Severe Pneumonia in Children Under 5 Years Old With and Without Adenovirus Infection in Guangzhou
Authors: Zheng Lingling , Liao Weiyao , Liang Feng , Li Kuanrong , Li Ling , Liang Huiying
Published: November 2021

Objectives:To identify the differences of clinical characteristics and outcomes of severe pneumonia in children under 5 years old with and without adenovirus infection.

Methods:A retrospective cohort study was conducted in three pediatric hospitals in Guangzhou, China. In total, 1,595 children under the age of 5 with WHO-defined severe pneumonia had adenovirus testing performed between January 1, 2009 and December 31, 2019. Demographics, complications, the first routine laboratory findings, therapeutic records, and clinical outcome were collected from electronic medical records. We compared characteristics of children with and without adenovirus infection.

Results:Adenovirus was detected in 75 (4.7%) out of 1,595 children with severe pneumonia. Cases with adenovirus infection were more likely to be boys (74.7 vs. 63.0%), older than 1 year old (78.7 vs. 25.1%), but less likely to have mixed virus infections (25.3 vs. 92.9%) and combined with cardiovascular disease (12.0 vs. 39.7%), and had more abnormal laboratory results than cases without adenovirus infection. Antiviral therapy (4.9%) was rarely used in children with severe pneumonia, but antibiotic therapy (65.3%) was commonly used, especially in cases with adenovirus infection (91.9%). Children infected with adenovirus (9.3 vs. 2.5%) were also hospitalized longer and had a higher mortality within 30 days of hospitalization.

Conclusions:Children with severe pneumonia under 5 years old with adenovirus infection had more abnormal laboratory findings and more severe clinical outcomes than cases without adenovirus infection. More attention should be focused on the harm caused by adenovirus infection.
A New Case of de novo Variant c.892C>T (p.Arg298Trp) in NACC1: A First Case Report From China
Authors: Lyu Baiyu , Dong Yan , Kang Juan
Published: November 2021

Background: The nucleus accumbens associated 1 (NACC1) gene is a transcription factor member of the BTB/POZ family. A de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 may define a syndrome characterized by intellectual disability, infantile epilepsy, congenital cataract, and feeding difficulties.

Case Presentation: We report a new case with a neurodevelopmental disorder characterized by severe intellectual disability, infantile epilepsy, congenital cataract, and feeding difficulties. Brain MRI reveals brain dysplasia. We observe a de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 gene in this case. Now, the child regularly goes to the hospital for rehabilitation training (once a month). Sodium Valproate (10 mg/kg/day) and Clobazam (10 mg/kg/day) are used in the treatment of epilepsy. A total of three articles were screened, and two papers were excluded. The search revealed one article related to a syndrome caused by a de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1; they screened the main clinical features of eight cases of a syndrome, which were summarized and analyzed.

Conclusions: The NACC1 gene is a member of the BTB/POZ family of transcription factors. A de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 may define a syndrome characterized by intellectual disability, infantile epilepsy, congenital cataract, and feeding difficulties. At present, there is no effective cure. In the future, we need more cases to determine the phenotype–genotype correlation of NACC1 variants. Many questions remain to be answered, and many challenges remain to be faced. Future transcriptional studies may further clarify this rare, recurrent variant, and could potentially lead to targeted therapies.
Granulocyte Colony-Stimulating Factor Treatment Before Radiotherapy Protects Against Radiation-Induced Liver Disease in Mice
Authors: Ramos Isalira Peroba Rezende , Dias Marlon Lemos , Nunes De Moraes Alan Cesar , Meireles Ferreira Fernanda Guimarães , Souza Sergio Augusto Lopes , Gutfilen Bianca , Barboza Thiago , Ferreira Pimentel Cibele , Paz Batista Cintia Marina , Kasai-Brunswick Tais Hanae , Fortes Fabio Da Silva De Azevedo , De Andrade Cherley Borba Vieira , Goldenberg Regina Coeli dos Santos
Published: November 2021

Radiation-induced liver disease (RILD) remains a major problem resulting from radiotherapy. In this scenario, immunotherapy with granulocyte colony-stimulating factor (G-CSF) arises as an attractive approach that might improve the injured liver. Here, we investigated G-CSF administration’s impact before and after liver irradiation exposure using an association of alcohol consumption and local irradiation to induce liver disease model in C57BL/6 mice. Male and female mice were submitted to a previous alcohol-induced liver injury protocol with water containing 5% alcohol for 90 days. Then, the animals were treated with G-CSF (100 μg/kg/d) for 3 days before or after liver irradiation (18 Gy). At days 7, 30, and 60 post-radiation, non-invasive liver images were acquired by ultrasonography, magnetic resonance, and computed tomography. Biochemical and histological evaluations were performed to verify whether G-CSF could prevent liver tissue damage or reverse the acute liver injury. Our data showed that the treatment with G-CSF before irradiation effectively improved morphofunctional parameters caused by RILD, restoring histological arrangement, promoting liver regeneration, preserving normal organelles distribution, and glycogen granules. The amount of OV-6 and F4/80-positive cells increased, and α-SMA positive cells’ presence was normalized. Additionally, prior G-CSF administration preserved serum biochemical parameters and increased the survival rates (100%). On the other hand, after irradiation, the treatment showed a slight improvement in survival rates (79%) and did not ameliorate RILD. Overall, our data suggest that G-CSF administration before radiation might be an immunotherapeutic alternative to radiotherapy planning to avoid RILD.