bluuebunny/crossref_metadata_2025 huggingface dataset:
Linear and Non-linear Associations Between Platelet Count and Metabolic Parameters in Non-Diabetic and Non-Obese Elderly
Authors: Chen Szu-Han , Lu Chieh-Hua , Chiang Yi-Lun , Chen Yen-Lin , Hsieh Chang-Hsun , Wu Chung-Ze , Lin Jiunn-Diann , Chen Ying-Chung , Hsia Te-Lin , Pei Dee
Published: July 2021

Background: High platelet count was noted in people with metabolic syndrome. A significant association between platelet count and various metabolic parameters had also been reported. However, all the studies hypothesized that these associations are linear relationships. This work investigated the potential non-linear relationships between platelet count and various metabolic parameters.Methods: A cross-sectional analysis of data from 11198 non-diabetic, non-obese elderly in a Health Screening Center was undertaken to explore the relationship between platelet count and metabolic parameters, including metabolic syndrome, body mass index, waist circumference, body fat, systolic and diastolic blood pressure, fasting plasma glucose, cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, C-reactive protein, insulin resistance, glucose effectiveness, and first-phase and second-phase insulin secretion. The linear relationship between platelet count and metabolic parameters was examined by linear and logistic regression. The non-linear relationship was investigated by the restricted cubic spline model.Results: Multivariable regression analyses showed that a greater PC level was significantly associated with a greater risk of metabolic syndrome (odds ratio 1.025, 95% CI 1.017 to 1.032), a higher body fat, waist circumference, cholesterol, low-density lipoprotein, triglyceride, C-reactive protein, and insulin resistance, and lower high-density lipoprotein cholesterol and glucose effectiveness. The restricted cubic spline analysis adjusted for age and gender demonstrated a strong non-linearity on the relationship between platelet count and all the metabolic parameters, except systolic blood pressure, diastolic blood pressures, fasting plasma glucose, first-phase insulin secretion, and metabolic syndrome. The overall findings suggested a significant linear relationship between platelet count with the risk of metabolic syndrome, and a significant non-linear relationship between platelet count with many metabolic variables.Conclusions: Platelet count is significantly associated with metabolic syndrome, metabolic parameters, and CRP in a linear or non-linear manner. The overall findings hint potential link between high platelet count, metabolic abnormalities, and chronic inflammatory status.
Trends in Online Searches for Oral and Maxillofacial Surgery During the COVID-19 Pandemic
Authors: sato shinichi , Takahashi Masato , Takahashi Tetsu
Published: July 2021

Background: Dentists and dental staff involved in oral and maxillofacial surgery (OMS) are at high risk of infection during the coronavirus disease (COVID-19) pandemic. Therefore, prevention of viral infection is essential in OMS, and attention should be paid to the trends in OMS during COVID-19. In this study, we aimed to investigate the search trends in OMS during the COVID-19 pandemic using Google Trends (GT). Methods: COVID-19 was considered prevalent from December 2019, and the search period on GT was set to 1 year (January 1, 2020–January 1, 2021). We observed trends for the following OMS-related terms: “wisdom teeth,” “TMJ” (temporomandibular joint), “dental implants,” “jaw surgery,” and “jaw fracture.” Additionally, the terms “aerosol” and “PPE” (personal protective equipment) were also used in the study. We identified the top five countries for all the aforementioned terms to confirm the trends by country. The multivariate Steel–Dwass test was used to compare the relative search volume (RSV) of the OMS-related terms, and the Mann–Whitney U test was used for comparison between the two groups of the COVID-19 prevention terms “aerosol” and “PPE.” Results: The RSV showed a decreasing trend from March to April for the terms “wisdom teeth,” “TMJ,” and “dental implants”; however, there was an increasing trend for the same terms from May onward. The term “PPE” showed a sharp increase from March to April. In comparison by country during the 1-year period, the United States had the highest RSV for “wisdom teeth” and “jaw fracture,” and Malaysia had the highest RSV for “TMJ.” Similarly, the highest RSV for “dental implants” and “jaw surgery” was in Laos and Canada, respectively. Conclusions: The COVID-19 pandemic may have altered the search trends for the terms “wisdom teeth,” “TMJ,” and “dental implants”.
WNT16 Elevation Induced Cell Senescence of Osteoblasts in Ankylosing Spondylitis
Authors: Jo Sungsin , Weon Subin , Nam Bora , Jang Mi-Ae , Kang Hyundeok , Kim Tae-Jong , Kim Tae-Hwan
Published: July 2021

Background: WNT16 is critical for bone homeostasis, but the effect of WNT16 in ankylosing spondylitis (AS) is still unknown. Here, we investigated whether WNT16 influences bone formation and pathophysiological changes of AS in an in vitro model.Methods: Bone tissue from facet joints was obtained from five disease control and six AS patients. Primary osteoprogenitor cells of the facet joints were isolated using an outgrowth method. Isolated osteoprogenitor cells from both control and AS tissues were analysed by microarray, RT-qPCR, immunoblotting, and immunohistochemistry. Bone-forming activity of osteoprogenitor cells was assessed by various in vitro assays. β-galactosidase staining and senescence-associated secretory phenotype (SASP) using RT-qPCR were used to assess cell senescence.Results: In microarray analysis, WNT16 expression was significantly elevated in AS osteoprogenitor cells compared to the control. We also validated that WNT16 expression was elevated in AS-osteoprogenitor cells and human AS-bone tissues. WNT16 treatment inhibited bone formation in AS-osteoprogenitor cells but not in the control. Intriguingly, β-galactosidase for cell senescence was strongly stained in AS-osteoprogenitor cells treated with WNT16. Furthermore, in an H2O2 stress-induced premature senescence condition, WNT16 treatment increased cell senescence in AS-osteoprogenitor cells and WNT16 treatment under the H2O2 stress condition showed an increase in p21 protein and SASP mRNA expression. The WNT16-induced SASP expression in AS-osteoprogenitor cells was reduced in WNT16 knockdown cultures. Conclusion: WNT16 is highly expressed in AS and WNT16 treatment facilitated cell senescence in AS-osteoprogenitor cells during osteoblast differentiation accompanied by suppression of bone formation. The identified role of WNT16 in AS could reflect the bone loss in AS patients.
Prediction of The CYP2D6 Enzymatic Activity Based on Investigating of The CYP2D6 Genotypes Around The Vivax Malaria Patients in Yunnan Province, China
Authors: Dong Ying , Huang Herong , Deng Yan , Xu Yanchun , Chen Mengni , Liu Yan , Zhang Canglin
Published: July 2021

BackgroundTo preliminary explore CYP2D6 enzyme activity in patients with recurrent vivax malaria in Yunnan Province by analyzing mutational polymorphism in the coding region of CYP2D6 gene.Methods Blood samples were collected from vivax malaria patients with suspected relapse (SR) malaria and non-relapsed (NR) in Yunnan Province. The DNA fragments containing 9 exons region of human CYP2D6 gene were amplified by performing PCR and sequenced. The sequencing results were compiled by using DNAStar 11.0 to obtain the coding DNA sequence (CDS) of CYP2D6 gene. DnaSP 6.11.01 software was used to identify mutant polymorphisms and haplotypes of the CDS chain. The waterfall function of GenVisR package in R was utilized to visualize the mutational landscape. The allelic forms of CYP2D6 gene were identified according to the criteria prescribed by "Human Cytochrome P450 (CYP) Allele Nomenclature Committee Database" and the CYP2D6 enzyme activity was predicted based on diploid genotype. Results A total of 320 maternal CDS chains, including 63 from SR group and 257 from NR group, were obtained. Twelve mutant loci, including c.31 (rs769259), c.100 (rs1065852), c.271 (rs28371703), c.281 (rs28371704), c.294 (rs28371705), c.297 (rs200269944), c.336 (rs1081003), c.408 (rs1058164), c.505 (rs5030865), c.801 (rs28371718), c.886 (rs16947), and c.1457 (rs1135840) were observed on the 640 CDS chains (including 320 maternal and 320 paternal chains). High-frequency mutation at rs1135840 (0.703) and low-frequency mutation, such as rs28371703, were detected only in the SR group. The frequency of mutant rs1058164 and rs1135840 were significantly increased in the SR group (x2 = 4.468, 5.889, P < 0.05), as opposed to the NR group. Of the 23 haplotypes (from Hap_1 to Hap_23), the nomenclatures of 11 allelic forms could be found: Hap_3 was non-mutant, Hap_2 accounted for the highest frequency (36.9%, 236/640), and Hap_9 had the most complex sequence structure, containing 7 loci mutations. *10 allele was the most frequent among these genotypes (0.423). Among the 10 standard named genotypes, *1/*10, *1/*1 and *2/*10 were significantly more frequent in the NR group (x2 = 3.911, P < 0.05) and all showed uncompromised enzyme activity; the impaired genotype *10/*39 was more frequent in the SR group (x2 = 10.050, P < 0.05), and genotype *4/*4 was detected only in the SR group. Conclusion In the patients receiving primaquine dosage in Yunnan Province, both rs1135840 single nucleotide polymorphism and *10 allele form was the common in the coding region CYP2D6 gene. Low-frequency mutation sites, such as rs28371703, were only presented in patients with vivax malaria relapse patients.
The Neuroprotective Mechanism of Lithium after Ischaemic Stroke.
Authors: Chen Beina , Zhang Manman , Ji Ming , Chen Benjie , Gong Wenliang , Zhang Dianjun , Li Xinyu , Zhou Yuefei , Dong Chengyi , Wen Gehua , Zhan Xiaoni , Wu Xiafang , Yuan Huiya , Xu Enyu , Xia Maosheng , Verkhratsky Alexei , Li Baoman
Published: July 2021

Stroke causes degeneration and death of neurones leading to the loss of motor function and frequent occurrence of cognitive impairment and depression. Lithium (Li+), the archetypal mood stabiliser, is neuroprotective in animal models of stroke, albeit underlying mechanisms remain unknown. We found that Li+ inhibits activation of nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes in the middle cerebral artery occlusion (MCAO) stroke model in mice. This action of Li+ is mediated by two signalling pathways of AKT/GSK3β/β-catenin and AKT/FoxO3a/β-catenin which converge in suppressing the production of reactive oxygen species (ROS). Using immunocytochemstry, MRI imaging, and cell sorting with subsequent mRNA and protein quantification we demonstrate that Li+ decreases the infarct volume, improves motor function, and alleviates associated cognitive and depressive impairments. In conclusion, this study reveals molecular mechanisms of Li+ neuroprotection during brain ischaemia thus providing the theoretical background to extend clinical applications of Li+ for treatment of ischemic stroke.
The association between lymphocyte-monocyte ratio and postoperative acute kidney injury in patients with acute type A aortic dissection
Authors: Chen Wenxiu , Song Xiaochun , Hong Liang , Xu Huan , Qian Yan , Zhang Wenhao , Sun Jiakui , Shen Xiao , Liu Ying , Wang Xiang , Shi Qiankun , Liu Han , Mu Xinwei , Zhang Cui
Published: July 2021

Background
The aim of this study was to investigate the relationship between baseline lymphocyte-monocyte ratio (LMR) and postoperative acute kidney injury (AKI) in patients with acute type A aortic dissection (ATAAD).
Methods
ATAAD patients undergoing surgery in Nanjing First Hospital were enrolled from January 2019 to April 2021. Lymphocyte and monocyte were measured on admission. Multivariable logistic regression analyses were performed to explore the relationship between LMR and postoperative AKI. We also used receiver operating characteristic (ROC), net reclassification index (NRI) and integrated discrimination improvement (IDI) analyses to assess the predictive ability of LMR.
Results
Among the 159 recruited patients, 47 (29.6%) were diagnosed with AKI. Univariate logistic regression analysis indicated that ATAAD patients with higher levels of LMR were prone to have lower risk to develop AKI (odds ratio [OR], 0.493; 95% confidence interval [CI] 0.284–0.650, P = 0.001). After adjustment for the potential confounders, LMR remained an independent related factor with postoperative AKI (OR, 0.527; 95% CI 0.327–0.815,P = 0.006). The cutoff value for LMR to predict AKI was determined to be 2.67 in the ROC curve analysis (area under curve: 0.719). NRI and IDI further confirmed the predictive capability of LMR in postoperative AKI.
Conclusion
Elevated baseline LMR levels were independently associated with lower risk of postoperative AKI in ATAAD patients.
LncRNA NEAT1 Regulates Cementogenic Differentiation of Periodontal Ligament Stem Cells Under Hypoxia by Targeting miR-214-5p/SMAD4 in an HIF-1α-Dependent Manner
Authors: Ye Yu , Hou Liguang , Tang Hui , Liu Liu , Xu Yan , Yu Jinhua
Published: July 2021

Background: Human periodontal ligament stem cells (PDLSCs)-mediated regenerative periodontal therapy is a promising method for periodontitis. Besides, odontogenic stem cells are exposed to hypoxia in both physiological and pathological conditions. The behaviour of stem cells under hypoxia is worth exploring. So far, whether long noncoding RNAs (lncRNAs) can affect the proliferation and cementogenesis of PDLSCs, as well as their specific mechanism, remains to be elucidated. This study investigates lncRNA NEAT1 and its possible regulatory mechanisms of cementogenic differentiation of PDLSCs under hypoxia.Methods: CCK-8 assay, flow cytometry (FCM) and EdU assay was adopted to test the proliferation ability. Osteoblastic/cementogenic differentiation of PDLSCs under hypoxia was detected by western blot assay (WB), quantitative real-time polymerase chain reaction (RT-PCR), alkaline phosphatase (ALP) activity, alcian blue staining (ABS), alizarin red staining (ARS). The relationship between them was proved by dual-luciferase reporter assay and rescue experiments.Results: PDLSCs exhibited a more powerful cementogenic differentiation potential in hypoxic conditions. miR-214-5p may regulate SMAD4, while Lnc NEAT1 acts as a sponge, forming a ceRNA mechanism in which HIF-1α plays an important role. It may act as an enabler, jointly constitute the regulatory axis of Lnc NEAT1/ miR-214-5p/ SMAD4, and affect the cementogenic differentiation of PDLSCs under hypoxia.Conclusions: Our results showed that hypoxia could enhance the cementogenic differentiation potential of PDLSCs in vitro. In addition, we found that Lnc NEAT1 may be a potential target for improving the function of PDLSCs in regenerative periodontiology, and Lnc NEAT1/miR-214-5p/SMAD4 could regulate the cementogenic differentiation ability of PDLSCs under hypoxia.
Research on Multi-Point Connection of Under-Chassis Equipment Suspension System in High-Speed Trains
Authors: SUN Yu , Zhou Jinsong , Gong Dao , Ji Yuanjin , You Taiwen , Chen Jiangxue , Wang Qiushi , Wang Tengfei
Published: July 2021

A power dispersive high-speed electric multiple-unit (EMU) train requires the installation of traction equipment under the carbody. As the speed of high-speed trains increases, the demand for traction power is increasing, and the weight and size of the equipment have increased accordingly. To adapt to the research and development of higher-speed EMU trains, this research proposes the use of a multi-point connection scheme for installing the under-chassis equipment. First, the static deflection and supporting reaction force of each hanging point are obtained based on static analysis, and it is found that increasing the number of connection points is beneficial for reducing the static stiffness requirement of each rubber element. Then, an energy decoupling degree is introduced, and an optimisation design method for the hanging point stiffness is proposed based on the energy decoupling degree and optimal vertical suspension frequency. Finally, a rigid-flexible coupling dynamics simulation model is established to analyse the vibration characteristics of the carbody and equipment after decoupling and optimisation of the multi-point suspension schemes. The research results show that after the decoupling optimisation, the vibration amplitude in the middle of the carbody is effectively reduced, and the ride quality of the carbody is improved. The difference in the number of hanging points has little effect on the vibration performance of the carbody, but increasing the number of hanging points is beneficial for reducing the dynamic supporting reaction forces of the hanging components, thereby reducing the dynamic stress of the rubber elements, and improving the fatigue resistance.
The Effect of Mitochondrial Fusion on Chondrogenic Differentiation of Cartilage Progenitor Cells via Notch2 Signal Pathway
Authors: Moqbel Safwat Adel Abdo , Zeng Rong , Ma Diana , Ran Jisheng , Lin Changjian , He Yuzhe , Ma Chiyuan , Xu Kai , Xu Langhai , Jiang Lifeng , wu lidong
Published: July 2021

Background: Osteoarthritis (OA) is a debilitating disease that inflicts intractable pain, a major problem that humanity faces, especially in aging populations. Stem cells have been used in the treatment of many chronic diseases, including OA. Cartilage progenitor cells (CPCs) are a type of stem cells with the ability to self- renew and differentiate. They hold a promising future for the understanding of the progression of OA and for its treatment. Previous studies have reported the relationship between mitochondrial dynamics and mesenchymal stem cell (MSC) proliferation, differentiation and aging. Mitochondrial dynamic and morphology change during stem cell differentiation. Methods: This study was performed to access the relationship between mitochondrial dynamics and chondrogenic differentiation of CPCs. Mitochondrial fusion and fission levels were measured during the chondrogenic differentiation process of CPCs. After that, we used mitochondrial fusion promoter to induce fusion in CPCs and then the chondrogenic markers were measured. Using Transmission Elecron Microscopy (TEM) and confocal microscopy to capture the mass and fusion status of mitochondria. Lentiviruses were used to detect the role of mitofusin 2 (MFN2) in CPC chondrogenic differentiation. In vivo, MNF2 was over-expressed in sheets of rCPCs, which were then injected intra-articularly into the knees of rats. Results: Mitochondrial fusion markers were upregulated during the chondrogenic induction process of CPCs. The mass of mitochondria was higher in differentiated CPC and the fusion status was obvious relative to un-differentiated CPC. Chondrogenesis of CPCs was upregulated with the induction by mitochondrial fusion promoter. MFN2 over-expression significantly increased chondrocyte-specific gene expression and reversed OA through Notch2 signal pathway.Conclusions: Our study demonstrated that the mitochondrial fusion promotes chondrogenesis differentiation of CPCs. MFN2 accelerates the chondrogenesis differentiation of CPCs through Notch2. In vivo, MNF2-OE in sheets of rCPCs ameliorated OA in the rat model.
3D U-Net With Attention and Focal Loss for Coronary Tree Segmentation
Authors: Liang Riming , huang xingsheng , Ma Jun , Ma Guomin , Wang Kunhua
Published: July 2021

The semantic segmentation of coronary artery is important in clinical diagnosis and treatment of coronary artery disease (CAD). The problems of intra-class inconsistency and inter-class indistinction in coronary artery and vein are very prominent. In this paper, we propose a 3D U-Net model improvement plan using attention mechanism and focal loss. U-Net is combined with channel attention and spatial attention to distinguish confusing categories and targets with similar appearance features. We use focal loss to optimize the loss function to solve the problem of category imbalance between coronary artery and background category.
Fabrication of Mechanically Enhanced Hydroxyapatite Scaffold With the Assistance of Numerical Analysis
Authors: Abifarin Johnson Kehinde , Suleiman Muhammad Uhuotu , Abifarin Emmanuel Alaba , Fidelis Fredah Batale , Oyelakin Opeyemi Kolawole , Jacob David Ifeakachukwu , Abdulrahim Moshood Yemi
Published: July 2021

Hydroxyapatite (HAp) has been found to be incompetent as it relates to its mechanical integrity, which somewhat restricts its use for load bearing clinical applications. In this study, synthesis and Taguchi grey relational analysis were conducted in the fabrication of mechanically enhanced HAp scaffold for load bearing application. The XRD and FTIR of raw cow bones (RB) and HAp sintered at 900, 1000, and 1100 oC show calcium phosphate contents of the bulk materials. It was also observed that increase in sintering temperature made prominent characteristic peaks of HAp phase to become narrower on the XRD patterns. Taguchi design analysis on the individual hardness and compressive strength revealed 1100 oC as the optimal sintering temperature, but a disparity in compaction load displaying 5 KN for high hardness and 15 K for high compressive strength. Conversely, Taguchi-grey relational analysis gave a common optimal processing parameter levels for high hardness and compressive strength to produce mechanically enhanced HAp scaffold, and are 1100 oC sintering temperature and 5 KN compaction load. Significantly, this study revealed that compaction load has a very high percentage of contribution of 90.15% compared to sintering temperature having a contribution of 7.79%. Confirmation analysis also proved that the experimental grey relational grade of 0.7824 is within 95% confidence interval.
A High Index of Malaria Suspicion is Necessary for Febrile Episodes in Travellers and Migrants Coming from Endemic Areas
Authors: de Morales Alejandro Garcia-Ruiz , Morcate Covadonga , Isaba-Ares Elena , Perez-Tanoira Ramon , Perez-Molina Jose A.
Published: July 2021

Objectives: We aimed to analyse the likelihood of imported malaria in people with a suggestive clinical picture and its distinctive characteristics in a hospital in the south of Madrid, Spain.Methods: This retrospective study consisted of a review of all medical files of patients with any malaria test registered at Móstoles University Hospital between April 2013 and April 2018. All suspected malaria cases were confirmed by Plasmodium spp. polymerase chain reaction (PCR).Results: Of the 328 patients with suspected malaria (53.7% migrant-travellers; 38.7% visitors; 7.6% travellers), 108 cases were confirmed (101 by P. falciparum), accounting for a 33% positive sample rate. Sixteen cases were diagnosed only by PCR. Patients with malaria, compared to those without, presented predominantly with fever (84% vs 65%), were older (34 vs 24 years), sought medical attention earlier (17d vs 32d), had a greater number of previous malaria episodes (74% vs 60%), lower levels of platelets (110,500µL vs 250,000µL), and higher of bilirubin (0.6mg/dL vs 0.5mg/dL). Severe malaria was present in 13 cases; no deaths were recorded. Malaria diagnosis showed a bimodal distribution with two peaks: June to September and November to January. Conclusion: Malaria is still a common diagnosis among febrile patients coming from the tropics specially among migrant travellers. Fever, thrombocytopenia, and/or high bilirubin levels should raise suspicion for this parasitosis. Prompt diagnosis is crucial to avoid severe cases and deaths. We suggest a proportion around 30% of positive samples as a potential adequate index of suspicion for malaria diagnosis.
Fungal Infections Lead to Shifts in Thermal Tolerance and Voluntary Exposure to Extreme Temperatures in Both Prey and Predator Insects
Authors: Porras Mitzy F. , Agudelo-Cantero Gustavo A. , Santiago Geovanni , Navas Carlos A. , Loeschcke Volker , Sørensen Jesper G. , Rajotte Edwin G.
Published: July 2021

Pathogens can alter the thermal tolerances of insects; these changes can have cascading impacts across trophic levels in terrestrial food webs. However, the effects of fungal infections on thermal tolerances and behavioral responses to extreme temperatures (ET) across trophic levels have rarely been studied. We examined how a fungal pathogen, Beauveria bassiana, affects the thermal physiology and behavior of an herbivorous insect, Acyrthosiphon pisum, and a predator beetle, Hippodamia convergens. We compared thermal tolerance limits (CTMin and CTMax), thermal boldness (voluntary exposure to ET), energetic cost (ATP) posed by each response (thermal tolerance and boldness) between healthy and infected insects with two fungal loads. Results showed that fungal infection reduced upper thermal tolerance (CTMax) of aphids and beetles, as well as lower thermal tolerance (CTMin) of beetles. CTMin of aphids was not altered by infection. Healthy aphids and beetles crossed warm ET zones (ETZ). Fungal infection modified the tendency, or boldness, of aphids and predator beetles to either cross warm or cold ETZ. ATP levels increased with pathogen infection in insect species, and the highest ATP levels were found in individuals that crossed cold ETZ. Fungal infection narrows the thermal tolerance range and inhibited thermal boldness behaviors to cross ET which may have implications for predator-pay interactions, food web structures, and species distributions. As environmental temperature rises, response to thermal stress will be asymmetric among members of a food web at different trophic levels.
The Molecular Mechanisms of Suanzaoren Prescription for Anti-Anxiety Were Investigated Based on Network Pharmacology
Authors: Bao Xiaohong , Ye Tianyuan , Wang Xiaolong , Han Lu , Wang Tongxing , Qi Dongmei , Wang Xin , Cheng Xiaorui
Published: July 2021

Anxiety is a common, universal disease caused by psychological and environmental factors. There are medications available to treat anxiety disorders, but these are accompanied by problems such as addiction and withdrawal difficulties. Suanzaoren Prescription (SZRP) is often used to treat anxiety disorders in traditional Chinese medicine clinical practice. However, its therapeutic mechanism remains unclear. This work aims to identify potential core therapeutic targets and predict major bioactive compounds by means of network pharmacology, screen compounds that may bind to anxiety targets by molecular docking methods, and validate and evaluate possible therapeutic mechanisms of compounds for anxiety in vitro cell experiments. Datebase TCMSP, BATMAN-TCM, ETCM, TCMGeneDIT and TCMID was used to obtain SZRP compounds, while TCMSP, BATMAN-TCM and ETCM were used to obtain target of compounds. The targets of anxiety disorders were obtained through database TTD, OMIM, PharmgKB, CTD, DrugBank and Metacore. The network diagram is drawn by Cytoscape 3.7.2 software and STRING. Biological process and KEGG pathway analysis were conducted by MetaCore and NIMNT. AutoDock Vina software was used to conduct molecular docking. The calcium Flux assay was employed to detect the activation of compounds on CNR1 in cell line CHO-K1/CNR1/Gα15. The 545 compounds in SZRP were collected. We found there were 1050 potential targets of these compounds in SZRP which involved in brain disease, mood disorder, endocrine system disease, bipolar disorder, etc. There were 117 potential targets of SZRP against anxiety (such as DRD2, BDNF, COMT, SLC6A4, HTR1A, etc.), which played the roles in regulation of membrane potential and synaptic transmission, nicotine addiction, retinol metabolism, GABAergic and serotonergic synapse, etc. The results of molecular docking indicated there were the biggest affinity between Jujuboside B and DRD2, BDNF, COMT, SLC6A4, Anemarsaponin B_qt and HTR1A, n-methylasimilobine and MAPK3. Based on cell CHO-K1/CNR1/Gα15 and calcium flux technique, we found Chrysophanol, Kaempferol and Emodin have activation effects on CNR1 with EC50 138.3µM, 52.28µM and 56.86µM respectively. These results indicated that the effects of SZRP against anxiety were correlated with synaptic transmission, substance addiction and retinol metabolism, especially targeted on CNR1. It suggested that the therapeutic mechanism of SZRP treating anxiety might be due to the weak action of multiple compounds on multiple pathways and biological processes.
In vivo metabolomic study uncovers distinct metabolic phenotypes of host tissues and predicts oxidative state of acute myeloid leukemia
Authors: Cognet Guillaume , Stuani Lucille , Farge Thomas , Gotanègre Mathilde , Heuillet Maud , Gales Lara , Rocher Amandine , Lager-Lachaud Nina , Bosc Claudie , Sabatier Marie , Saland Estelle , Sahal Ambrine , Poillet-Perez Laura , Vergez Francois , de Mas Véronique , Récher Christian , Portais Jean-Charles , Bellvert Floriant , Sarry Jean-Emmanuel
Published: July 2021

Background

Metabolic adaptation is a hallmark of cancer including acute myeloid leukemia (AML). Tumor microenvironment is also described as an essential support of leukemic metabolism. We explored how systemic and tissue metabolism was rewired in leukemia-bearing mice and upon chemotherapy.
Methods

Using AML cell line- and primary patient-derived xenograft models, we developed in vivo metabolomics to uncover the metabolic pattern of 10 tissues including plasma, bone marrow, spleen, liver, adipose tissue, lung, pancreas, kidney, heart and muscle.
Results

In vivo targeted mass spectrometry allowed metabolic characterization of tissues from naïve and AML-xenografted immunocompromised mice. AML xenotransplantation and cytarabine treatment induced AML cell type-dependent global changes in tissue metabolomes. Infiltration of high OxPHOS MOLM14 cells that are intrinsically chemoresistant, induced minor changes in tissue metabolomes. In contrast, low OxPHOS U937 xenograft led to major reprogramming of metabolic tissue niches for survival upon chemotherapy. Interestingly, plasma metabolite signatures could predict the oxidative phenotype of leukemic cells.
Conclusion

Major metabolic changes in host tissues play a crucial role in tumor xenotransplantation and define their OxPHOS state in AML. Since mitochondrial phenotype is an essential determinant of drug response in AML, plasma metabolite signatures might be novel biomarkers for patient stratification.
Development and Validation of a New Risk Scoring System for Cancer Patients with Suspected Infection
Authors: Chae Bora , Kim Seonok , Lee Yoon-Seon
Published: July 2021

Purpose: This study aimed to develop a new prognostic model for predicting 30-day mortality in cancer patients with suspected infection.Methods: This study is a retrospective cohort study and was conducted from August 2019 to December 2019 at a single center. Adult active cancer patients with suspected infection were enrolled among visitors to the emergency room (ER). Logistic regression analysis was used to identify potential predictors for a new model. Results: A total of 899 patients were included; 450 in the development cohort and 449 in the validation cohort. Six independent variables predicted 30-day mortality: Eastern Cooperative Oncology Group (ECOG) performance status (PS), peripheral oxygen saturation (SpO2), creatinine, bilirubin, C-reactive protein (CRP), and lactate. The C-statistic of the new scoring system was 0.799 in the development cohort and 0.793 in the validation cohort. The C-statistics in the development cohort was significantly higher than those of SOFA [0.723 (95% CI: 0.663–0.783)], qSOFA [0.596 (95% CI: 0.537–0.655)], and SIRS [0.547 (95% CI: 0.483–0.612)]. Conclusions: The discriminative capability of the new cancer-specific risk scoring system was good in cancer patients with suspected infection. The new scoring system was superior to SOFA, qSOFA, and SIRS in predicting mortality.
LATS1 Knockdown with SiRNA Induces Pyroptosis via the Activation of TNF-α/NF-κB Signaling in Bladder Cancer Cells
Authors: Gao Shuting , Chi Ming , Jiang Xuefeng , Liu Nanqi , Liu Chang , Yang Zhe , Yang Yi , Wu yanju , Sun Xun , Yin Bo , Meng Xin , Wang Biao
Published: July 2021

Background: Traditionally, it is believed that large tumor suppressor 1 (LATS1) is a negative regulator of oncogene. But the latest research showed that LATS1 has an opposite effect in some tumors. We found that LATS1 has a cancer-promoting effect in BLCA, but the specific mechanism is unknown. Methods: RNAi method was used for the related genetic functional analysis. CCK-8 method and colony formation assay were used to explore the cellular viabilities and proliferation of BLCA cells transfected with LATS1 siRNAs (si-LATS1), in vitro. Flow Cytometry (FCM) was used to analyze the cell cycle and cellular apoptosis of the BLCA cells or the expression of CD68, CD86, CD11b, and CD163 in PMA-treated THP-1 macrophages incubated with conditioned medium (CM) from the si-LATS1 cells or in the THP-1 macrophages cultured directly with BLCA cells. RT-qPCR method was used to detect the mRNA levels of IL-1β, IL-2/4/6/10/18, TNF-α, and IFN-γ in the BLCA cells. Western Blot was performed to detect the expressions of LATS1, Yap1, Bcl-2, Bax, caspase-1/3, GSDMD, TNF-α IL-1β, IL-18, NF-κB, AIM2, NLRC4 and NLRP3 in the BLCA cell lines. For in vivo experiments, a xenograft model was used to investigate the inhibitory effects of LATS1 knockdown on BLCA cells in nude mice.Results: LATS1 knockdown via siRNA inhibited the proliferation of the BLCA cells, neither changing cell cycle distribution nor inducing apoptosis. Via further analysis, we found that the expressions of TNF-α, p-NF-κB/RelA, NLRP3, NLRC4, and AIM2 in si-LATS1 BLCA cells were significantly increased. The activity of caspase-1 and the expressions of IL-1β, IL-18 and GSDMD were obviously increased in the si-LATS1 BLCA cells, which was restored by the addition of NF-κB inhibitor PS341. In the LATS1 over-expression cells (OE-LATS1), the expressions of TNF-α, p-NF-κB/p65, NLRP3, NLRC4 and AIM2 were notably inhibited, and the expressions of IL-1β, IL-18 and GSDMD were significantly decreased. THP-1 macrophages exhibited an M1 phenotype polarization in the presence of si-LATS1 BUC-87 cell supernatant or when cocultured with the BLCA cells transfected with LATS1 siRNA, represented by an increase in the surface expression of CD86. Furthermore, we observed that LATS1 knockdown inhibited the cell proliferation in xenograft model. Conclusion: Our findings showed that LATS1 knockdown via siRNA induces BLCA cell pyrolysis due to the enhanced formation of inflammasomes by activation of TNF-α/NF-κB pathway; and inflammatory factors released by the pyrolytic cells promote M1 polarization of THP-1-derived macrophages in vitro, providing a therapeutic target for BLCA and a brand-new idea for the development of BLCA immunotherapy drugs.
Complete Genome Sequence of a Novel Marafivirus Infecting Pearl Millet in Burkina Faso
Authors: Palanga Essowè , Tibiri Ezechiel Bionimian , Bangratz Martine , Filloux Denis , Julian Charlotte , Pinel-Galzi Agnès , Koala Moustapha , Néya James Bouma , Brugidou Christophe , Tiendrébéogo Fidèle , Roumagnac Philippe , Hébrard Eugénie
Published: July 2021

Pearl millet (Pennisetum glaucum (L.) R. Br.) is a staple food that is widely cultivated in sub-Saharan Africa. In August 2018, a survey was conducted in the main producing regions of Burkina Faso and leaf samples were analyzed using virion-associated nucleic acid (VANA)-based metagenomic approach and Illumina sequencing. A new virus, tentatively named “pennisetum glaucum marafivirus” (PGMV), was detected and its complete nucleotide sequence of 6364 nucleotides was determined. The sequence contains a large open reading frame (ORF) encoding a polyprotein of 224.2 kDa with five domains (methyltransferase, papain-like protease, helicase, RNA-dependent RNA polymerase and coat proteins), typical of members of the marafiviruses. Additionally, a characteristic conserved marafibox domain was detected in the genome. The nucleotide sequence of the PGMV complete genome shares 68.5% identity with Sorghum bicolor marafivirus and its coat protein shares 58.5% identity with Oat blue dwarf virus. Phylogenetic analyses confirmed that the pearl millet virus is unambiguously grouped with members of the genus Marafivirus in the family Tymoviridae. This is the first report on the occurrence of a marafivirus on pearl millet.
IL-1β Primed Mesenchymal Stromal Cells Alleviate Chronic Prostatitis/chronic Pelvic Pain Syndrome Through Systemic Immunity
Authors: Liu Hanchao , Zhu Xinning , Chi Ani , Dai Jian , Wang Zhenqing , Deng Chunhua , Zhang Min
Published: July 2021

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) seriously affects patient health. Despite the elusiveness of innate therapeutic effects, mesenchymal stromal cells (MSCs) hold great promise for inflammation-related diseases. Recent evidence indicates that disease-specific inflammatory cytokines could enhance the therapeutic effects of MSCs.Methods: By establishing a CP/CPPS mouse model and pretreating MSCs with the cytokine interleukin-1β (IL-1β), we studied the IL-1β-primed MSC immunoregulatory ability and targeted migration ability in vitro and in CP/CPPS mice.Results: IL-1β levels significantly increased in the prostate tissue and serum of experimental autoimmune prostatitis (EAP) mice. Pretreatment with IL-1β enhanced the immunomodulatory potential and targeted migration of MSCs in vitro. Furthermore, intravenous infusion of IL-1β-primed MSCs dampened inflammation in prostate tissues and alleviated hyperalgesia in EAP mice. The infused MSCs inhibited monocyte infiltration and promoted regulatory T lymphocyte formation in prostate tissue, thus remodeling the local environment. Surprisingly, IL-1β-primed MSCs exhibited improved accumulation in the spleen but not in prostate tissue. Accordingly, infused MSCs reshaped systemic immunity by reducing the proportion of Ly6ChighCD11b+ monocytes and boosting the proportion of CD4+Foxp3+ regulatory T lymphocytes in the spleen and lung. Inflammatory chemokine (C-C motif) ligand 2 (CCL2) decreased through the downregulation of the NF-κB and JNK/MAPK pathways by inflammatory resolution via MSCs infusion to alleviate pain.Conclusion: In summary, IL-1β primed MSCs restored systemic immunologic homeostasis to alleviate CP/CPPS by modulating systemic immunity. These findings provide a novel strategy to boost the therapeutic effects of MSC-based therapy for CP/CPPS and reveal the essential role of systematic immunity in the treatment of CP/CPPS with MSC infusion.
Efficacy of Dihydroartemisinin-piperaquine Versus Artemether-lumefantrine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria Among Children in Africa: a Systematic Review and Meta-analysis of Randomized Control Trials
Authors: Assefa Dawit Getachew , Yesmaw Gizachew , Makonnen Eyasu
Published: July 2021

Background: Emergence of Plasmodium falciparum resistance to artemisinin and its derivatives poses a threat to global effort in controlling malaria. Meanwhile the emergence of antimalarial resistance has become a great public health challenge and continues to be a leading threat to ongoing malaria control efforts. The aim of this review was to synthesize available evidence on the efficacy of dihydroartemisinin-piperaquine compared to artemether-lumefantrine for the treatment of uncomplicated P.falciparum malaria among children in Africa.Method: A systematic literature search was done to identify relevant articles from online databases PubMed/ MEDLINE, Embase, and Cochrane Center for Clinical Trial database (CENTRAL) for retrieving randomized control trials comparing efficacy of DHA-PQ and AL for treatment of uncomplicated P.falciparum malaria in African children. The search was performed from August 2020 to 30 April 2021. Using Rev-Man software (V5.4.1), R-studio, and Comprehensive Meta-analysis software version 3, the extracted data from eligible studies were pooled as risk ratio (RR) with 95% confidence interval (CI).Result: In this review, 25 studies which involved a total of 13,198 participants were included. PCR unadjusted treatment failure in children aged between 6 months and 15 years was significantly lower in DHA-PQ treatment arm on day 28 than that of AL (RR 0.14, 95% CI 0.08 to 0.26; participants = 1302; studies = 4; I2 = 0%, high quality of evidence). Consistently, the PCR adjusted treatment failure was significantly lower with DHA-PQ treatment group on day 28 (RR 0.45, 95% CI 0.29 to 0.68; participants = 8508; studies = 16; I2 = 51%, high quality of evidence) and on day 42 (RR 0.60, 95% CI 0.47 to 0.78; participants = 5959; studies = 17; I2 = 0%, high quality of evidence). However, the efficacy was ≥95% in both treatment groups on day 28. Conclusion: From this review, it can be concluded that DHA-PQ reduces new infection and recrudescence on days 28 and 42 more than AL. This may trigger DHA–PQ to become the first-line treatment option.
Synthesize of Poly (Acrylamide-Co-Itaconic/TiO2) Nanocomposite for Ce(III) Sorption from Monazite Leachate
Authors: Dakrorury Gehan AbdelRahman , Maree Ragab mohasab , Shazly Ehab Abu El Soud Abdel Halim El , Allan Karam Fatwhi
Published: July 2021

In this study, Acrylamide (AAM), Itaconic acid (IA) and nano TiO2 were copolymerized using gamma irradiation with 60Co γ-rays at a dose of 25 KGy to form a novel nanocomposite; Poly(acrylamide-co-Itaconic acid/TiO2) (P(AAM-co-IA/TiO2)) for Ce(III) sorption from monazite leachate. P(AAM-co-IA/TiO2) nanocomposite is characterized by different physicochemical techniques. The optimum pH for the sorption process at 298 K is 6 and the equilibrium attained after 60 min. Different kinetics and isothermal models is applied. The monolayer adsorption capacity is 76.04 mgg-1 at 298 K. The sorption reaction follows a pseudo−2nd - order mechanism. The process is spontaneous and endothermic.
Comparison of Surface Wind Speed and Wind Speed Profiles in the Taklimakan Desert
Authors: Xinchun Liu , yongde kang , Hongna Chen , Hui Lu
Published: July 2021

Near-surface (10 m) wind speed (NWS) plays a crucial role in many areas, including the hydrological cycle, wind energy production, and the dispersion of air pollution. Based on wind speed data from Tazhong and the northern margins of the Taklimakan Desert in Xiaotang in spring, summer, autumn, and winter of 2014 and 2015, statistical methods were applied to determine the characteristics of the diurnal changes in wind speed near the ground and the differences in the wind speed profiles between the two sites. The average wind speed on a sunny day increased slowly with height during the day and rapidly at night. At heights below 4 m the wind speed during the day was higher than at night, whereas at 10 m the wind speed was lower during the day than at night. The semi-empirical theory and Monin-Obukhov (M-O) similarity theory were used to fit the NWS profile in the hinterland of the Tazhong Desert. A logarithmic law was applied to the neutral stratification wind speed profile, and an exponential fitting correlation was used for non-neutral stratification. The more unstable the stratification, the smaller the n. Using M-O similarity theory, the “linear to tens of” law was applied to the near-neutral stratification. According to the measured data, the distribution of with stability was obtained. The was obtained when the near-surface stratum was stable in the hinterland of Tazhong Desert and the was obtained when it was unstable. In summer, and were 5.84 and 15.1, respectively, while in winter, and were 1.9 and 27.1, respectively.
Event-triggered neuroadaptive output-feedback control for nonstrict-feedback nonlinear systems with given performance specifications
Authors: Yang Di , Liu Weijun , Guo Chen
Published: July 2021

This paper focuses on the event-triggered neuroadaptive output-feedback tracking control issue for nonstrict-feedback nonlinear systems with given performance specifications. By constructing a neural observer to estimate unmeasurable states, a novel event-triggered controller is presented together with a piecewise threshold rule. The presented event-triggered mechanism has two thresholds to reduce communication resources between the controller and actuator. An improved speed transformation function is introduced to make the output tracking error converge to a preassigned small region at predesigned converging mode within preset finite time. Combining the variable separation method based on the structural property of radial basis function (RBF) and backstepping technology, the algebraic loop problem caused by the nonstrict-feedback structure is overcome. The command filtered technology with filtering error compensating signal is applied to address the “explosion of complexity” problem. Furthermore, Lyapunov stability analysis demonstrates that under the presented event-triggered controller, all signals in the closed-loop system are semiglobally bounded, and the Zeno-behaviour is ruled out strictly. Numerical simulations are finally provided to illustrate the presented control scheme.
High Serum Uric Acid Trajectories are Associated with Risk of Myocardial Infarction and All-Cause Mortality in General Chinese Population
Authors: Tian Xue , Zuo Yingting , Chen Shuohua , Wu Shouling , Wang Anxin , Luo Yanxia
Published: July 2021

Background: Long-term patterns of serum uric acid (SUA) and their association with the risk of myocardial infarction (MI) and mortality are poorly characterized as prior studies measured SUA at a single time point. This study aimed to identify SUA trajectories and determine their associations with incident MI and all–cause mortality.Methods: We included 85,503 participants who were free of MI in or prior 2012 from the Kailuan study. SUA trajectories during 2006-2012 were identified by group-based trajectory modeling. Cox proportional hazard models were used to assess the association of SUA trajectories with MI and all–cause mortality.Results: We identified three SUA trajectories during 2006-2012: low-stable (n=44,124, mean SUA: 236.55-249.53 μmmol/L), moderate-stable (n=34,431, mean SUA: 324.38 -354.24 μmmol/L) and high-stable (n=6,984, mean SUA: 425.16-463.25 μmmol/L). During a median follow-up of 6.76 years, we documented 817 (0.96%) incident MI and 6,498 (7.60%) mortality. Compared with the low-stable group, high-stable group experienced a higher risk of MI (hazard ratio [HR], 1.35; 95% confidence [CI], 1.07-1.71) and all–cause mortality (HR, 1.22; 95% CI, 1.12-1.33). Multiple sensitivity analyses yielded similar results. Additionally, the association of SUA trajectory with MI and all–cause mortality was more pronounced in individuals without a history of hypertension (P-interaction=0.0359) and those aged <60 years (P-interaction<0.0001), respectively.Conclusions: Higher SUA trajectories were associated with altered risk of MI and all–cause mortality, suggesting that monitoring SUA trajectory may assist in identifying subpopulations at higher risk of MI and all-cause mortality.