bluuebunny/crossref_metadata_2025 huggingface dataset:
NIR Responsive Tumor Vaccine in Situ for Photothermal Ablation and Chemotherapy to Trigger Robust Antitumor Immune Responses
Authors: Zhang Lirong , Zhang Jingjing , Xu Lixia , Zhuang Zijian , Liu Jinajin , Liu Suwan , Wu Yunchao , Gong Aihua , Zhang Miaomiao , Du Fengyi
Published: February 2021

Background: Therapeutic tumor vaccine (TTV) that induces tumor-specific immunity has enormous potentials in tumor treatment, but high heterogeneity and poor immunogenicity of tumor seriously impaires its clinical efficacy. Herein, a novel NIR responsive tumor vaccine in situ (HA-PDA@IQ/DOX HG) was prepared by integrating hyaluronic acid functionalized polydopamine nanoparticles (HA-PDA NPs) with immune adjuvants (Imiquimod, IQ) and doxorubicin (DOX) into thermal-sensitive hydrogel. Results: HA-PDA@IQ NPs with high photothermal conversion efficiency (41.2%) and T1-relaxation efficiency were using HA as stabilizer by the one-pot oxidative polymerization. Then, HA-PDA@IQ loaded DOX via π-π stacking and mixed with thermal-sensitive hydrogel to form the HA-PDA@IQ/DOX HG. The hydrogel-confined delivery mode endowed HA-PDA@IQ/DOX NPs with multiple photothermal ablation performance once injection upon NIR irradiation due to the prolonged retention in tumor site. More importantly, this mode enabled HA-PDA@IQ/DOX NPs to promote the DC maturation, memory T cells in lymphatic node as well as cytotoxic T lymphocytes in spleen. Conclusion: Taken together, the HA-PDA@IQ/DOX HG could be served as a theranostic tumor vaccine for complete photothermal ablation to trigger robust antitumor immune responses.
Experimental Study on the Piping Erosion Mechanism of Gap-Graded Soils Under a Supercritical Hydraulic Gradient
Authors: Chen Liang , Wan Yu , He Jian-Jian , Luo Chun-Mu , Yan Shu-fa , He Xian-Feng
Published: February 2021

Seepage-induced piping erosion is observed in many geotechnical structures. This paper studies the piping mechanism of gap-graded soils during the whole piping erosion failure process under a supercritical hydraulic gradient. We define the supercritical ratio Ri and study the change in the parameters such as the flow velocity, hydraulic conductivity, and fine particle loss with Ri. Under steady flow, a formula for determining the flow velocity state of the sample with Ri according to the fine particle content and relative density of the sample was proposed; during the piping failure process, the influence of Rimax on the rate at which the flow velocity and hydraulic conductivity of the sample increase as Ri decreases was greater than that of the initial relative density and the initial fine particle content of the sample. Under unsteady flow, a larger initial relative density corresponds to a smaller amplitude of increase in the average value of the peak flow velocity with increasing Ri. Compared with the test under steady flow, the flow velocity under unsteady flow would experience abrupt changes. The relative position of the trend line L of the flow velocity varying with Ri under unsteady flow and the fixed peak water head height point A under steady flow were related to the relative density of the sample.
Characterization and Comparison of Intestinal Bacterial Microbiomes of Euschistus Heros and Piezodorus Guildinii Collected in Brazil and the United States
Authors: Moro Matheus Sartori , Wu Xing , Wei Wei , Mendes Lucas William , Allen Clint , Pinheiro José Baldin , Clough Steven John , Zucchi Maria Imaculada
Published: February 2021

Background: Herbaceous insects are one of the main biological threats to crops. One such group of insects, stink bugs, do not eat large amounts of tissue when feeding on soybean, but are extremely damaging to the quality of the seed yield as they feed directly on green developing seeds leading to poorly marketable harvests. In addition to causing physical damage to the seed during feeding, the insects can also transmit microbial pathogens, leading to even greater yield loss. Conducting surveys of the insect intestinal microbiome can help identify possible pathogens, as well as detail what healthy stink bug digestive systems have in common. Methods: We used the conserved V4 515-806 region of the 16S rRNA gene to characterize the bacterial microbiome of the red-banded stink bug Piezodorus guildinii collected in Brazil and the United States, as well as the neotropical brown stink bug Euschistus heros collected in Brazil. Results: After quality filtering of the data, 192 samples were kept for analyses: 117 samples from P. guildinii covering three sites in Brazil and four sites in the US, and 75 samples for E. heros covering 10 sites in Brazil. The most interesting observations were that the diversity and abundance of some bacterial families were different in the different ecoregions of Brazil and the United States. Conclusions: Some families may be related to the better adaptation in some localities in provide nutrients, break down cellulose, detoxify phytochemicals, and degrade organic compounds, which makes it difficult to control these species.
Attitude Survey of Medical School Staff After Simulated Patient Experiences
Authors: Harada Yoshimi , KUBOTA Yuki , HIRAYAMA Yoji , OTAKI Junji , MITOMA Hiroshi
Published: February 2021

Background: With the spread of medical communication education and objective structured clinical examination (OSCE), greater numbers of simulated patients/standardized patients (SPs) will likely be needed throughout Japan. At Tokyo Medical University, non-medical professional medical school staff have acted as SPs in post-clinical clerkship OSCE. There are no reports of any staff other than teaching staff and medical staff acting as SPs. The significance of large numbers of medical school staff acting as SPs needs to be clarified. Methods: We conducted a questionnaire survey of staff after acting as SPs. The questionnaire was developed from semi-structured interviews. Results: The majority of responses were positive, saying that they had learned about the testing and students and that they felt the importance of communication for doctors. Many respondents said that staff of a medical school should experience being an SP and that many staff should try it. Conclusions: For medical school staff, being an SP is one way to learn about student education. Japan has problems with SPs becoming older and fewer in number nationwide, but SP numbers may be supplemented by staff.
Overexpression of Cathepsin S Exacerbates Lupus Pathogenesis Through TLR7 and IFN-α in Transgenic Mice
Authors: Lee Jinhee , Choi Minjee , Jang Soyoung , Kang Mincheol , Lim Su-Geun , Kim SI-Young , Jang Soyeon , Yi Junkoo , choo Yeonsik , Kim Myoung Ok , Ryoo Zae Young
Published: February 2021

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs. Recent studies suggest relevance between cysteine protease cathepsin S (CTSS) expression and SLE. To investigate the mechanism of CTSS in SLE, CTSS-overexpressing transgenic (TG) mice were generated, and induced lupus-like symptoms. Eight months later, the TG mice spontaneously developed typical SLE symptoms regardless of the inducement. Furthermore, we observed increased toll-like receptor 7 (TLR7) expression with increased monocyte and neutrophil populations in the TG mice. In conclusion, overexpression of CTSS in mice influences TLR7 expression, autoantibodies and IFN-α, which leads to an autoimmune reaction and exacerbates lupus-like symptoms.
Upregulated Talin1 Synergistically Boosts β-estradiol-induced Proliferation and Pro-angiogenesis of Eutopic and Ectopic Endometrial Stromal Cells in Adenomyosis
Authors: Wang Yi-yi , Duan Hua , Wang Sha , Quan Yong-jun , Huang Jun-hua , Guo Zheng-chen
Published: February 2021

Adenomyosis (ADS) is an estrogen-dependent gynecological disease with unspecified etiopathogenesis. Local hyperestrogenism may serve a central role in contributing the origin of ADS. Talin1 is mostly identified to be overexpressed and involved in the progression of numerous human carcinomas through mediating cell proliferation, adhesion and motility. Whether Talin1 exerts an oncogenic role in the development of ADS and presents an extra impact on the efficacy of estrogen, no relevant data are available yet. Here we demonstrated that the adenomyotic eutopic and ectopic endometrial stromal cells (ADS_Eu_ESC and ADS_Ec_ESC) treated with β-estradiol (β-E2) presented stronger proliferative and proangiogenetic capacities, accompanied by increased expression of PCNA, Ki67, VEGFB and ANGPTL4 proteins, compared with the controls. Meanwhile, these promoting effects were abrogated in the presence of Fulvestrant (ICI 182780, an estrogen-receptor antagonist). Aberrantly Upregulation of Talin1 mRNA and protein level was observed in ADS endometrial specimens and stromal cells. Through performing functional experiments in vitro, we further determined that merely overexpression of Talin1 (OV-Talin1) also enhanced ADS stromal cell proliferation and pro-angiogenesis, while the most pronounced facilitating effects were found in the co-intervention group of Talin1 overexpression plus β-E2 treatment. Results from the xenograft model showed that the hypodermic endometrial lesions from the co-treatment group with OV-Talin1 and β-E2 had the highest mean weight and volume, compared with that of individual OV-Talin1 or β-E2 treatment. The expression levels of PCNA, Ki67, VEGFB and ANGPTL4 in the lesions were correspondingly elevated most significantly in the co-treated group. Our findings unveiled that abnormally overexpressed Talin1 cooperated with E2 in stimulating ADS endometrial stromal cell proliferation and neovascularization, synergistically promoting the growth and survival of ectopic lesions. These results may be beneficial to provide a new insight for clarifying the pathogenesis of ADS.
Metagenomic Analysis of a Throat Swab Sample Collected in China on A Patient Infected With Varicella Zoster Virus
Authors: Guo Hong , Rivailler Pierre , Wang Jiangxia , Wang Huanyu , Xu Wenbo , Xu Songtao , Xu Hongmei , Hu Ruiping
Published: February 2021

Varicella Zoster Virus (VZV) is endemic worldwide, causing varicella in children and zoster upon reactivation in adults. This study concerned a metagenomic analysis of a throat swab sample collected in China, on a young patient suffering from Systemic Lupus Erythematosus (SLE) and diagnosed with varicella. The complete genome sequence of a VZV strain of clade 2 has been generated. Clade 2 strains are the most prevalent in Asian countries. A comparison of 223 VZV genomes identified 77 clade specific markers, 20 of them specific to clade 2. The metagenomic analysis also identified sequences covering most of the genome of the bacteria Schaalia odontolytica also known as Actinomyces odontolyticus. VZV infection and bacterial infection in the context of SLE is further discussed. Even though the patient presented only mild symptoms, this study is a reminder that vaccination against VZV is critical to avoid severe complications like bacterial superinfection or even death in the case of immunodeficiency.
An Ethnobotanical Study of Traditional Medicinal Plants Used to Treat Human and Livestock Ailments From Diguna Fango District, Wolaita, Southern Ethiopia
Authors: Wendimu Abenezer , Tekalign Wondimagegnehu , Asfaw Biniyam
Published: February 2021

BackgroundPlants have been used as a traditional medicine for many years for the people of Wolaita, Ethiopia. The aim of the study was to record these local knowledge of the peoples who inhabit the Diguna Fango district. MethodsA semi-structured interview was conducted with a total of 60 informants. ResultsTotally, 50 species belonging to 24 families were identified to treat 28 human and livestock ailments. Solanaceae (14.3%) was the most abundant family whereas; the rosaceae (1.00) had the highest family use value (FUV). Most of the plants (82%) were reportedly used to treat human diseases. Herbs (34%) were the dominant growth habits, followed by trees (33%). The leaves (30%) were identified as the most used plant part. The most common methods of remedy preparations were eating and chewing (18.2% each) followed by grinding (13.61%). Oral (73.3%) was the major route of administration, followed by dermal (21.7%). The cardiovascular system diseases category (1.00) had a higher informant consensus factor value followed by the fever disease category (0.90). Croton macrostachyus Hochst. ex Delile, Commelina benghalensis L., Triticum dicoccon (Schrank) Schübl and Pentas spp. (100%) had a higher fidelity level to treat swelling, chirt (skin diseases), weight gain, and bone fractures, respectively. Persea americana Mill. was ranked highest as the most preferable medicinal plant for various purposes by local people, followed by Acacia abyssinica Benth. The principal threatening factors reported were charcoal production (26%), agricultural expansion (15%), and firewood (14%). Out of the plants and their uses documented, 16% of the medicinal plants and 28.6% of the uses were novel. ConclusionsThe present study indicated the existence of indigenous knowledge of medicinal plants to treat human and livestock ailments. Therefore, there should be mentoring for the local people in the study area to conserve their indigenous knowledge and resources.
Assessment Of Ecotoxicity Of Thallium By Biological Indicator Of Soil Condition
Authors: Kolesnikov Sergey , Kazeev Kamil , Akimenko Yuliya , Ter-Misakyants Tigran , Nevedomaya Elena
Published: February 2021

Thallium is a rare and highly toxic heavy metal. The scale and degree of soil contamination with thallium are increasing every year, and the associated environmental risks have been insufficiently investigated. Model laboratory experiments on the ordinary chernozem pollution with thallium oxide (III) have been carried out. It has been found that the ordinary chernozem pollution with thallium worsened its biological activity. The total bacterial count, the abundance of the Azotobacter bacteria, the activity of catalase, the activity of dehydrogenases, and the germination of radish seeds decreased. The degree of deterioration of the chernozem biological activity depends on the thallium concentrations in soil and the period from the moment of contamination. In the vast majority of cases there is a direct correlation between the thallium content in the soil and the level of soil biological activity reduction. The greatest negative impact of thallium pollution on chernozem biological activity has manifested itself 30 days after contamination. On the 90th day, there was a pronounced tendency to restore the chernozem biological activity. However, the chernozem biological activity did not restore to the initial uncontaminated soil values. At contamination of chernozem with thallium, microbiological indices (the bacterial count and the abundance of the Azotobacter bacteria) were more sensitive, and the enzyme activity indicators (catalase, dehydrogenase) and phytotoxicity (germination of plant seeds) were more informative. All used indicators of biological activity demonstrated high sensitivity to soil contamination with thallium and high correlation coefficients with the thallium content in the soil. Therefore, these biological indicators should be used for monitoring, diagnosis, indication and regulation of soil contamination with thallium.
Discovery and Validation of Novel Protein Markers in Mucosa of Portal Hypertensive Gastropathy
Authors: Zhu Ying , Xu Wen , Hu Wei , Wang Fang , Zhou Yan , Xu Jianguo , Gong Wei
Published: February 2021

Background: Portal hypertension induced esophageal and gastric varix bleeding is the main cause of death among patients of decompensated liver cirrhosis. Therefore, a standardized, biomarker-based test, to make an early-stage non-invasive risk assessment of portal hypertension, is highly desirable. However, no fit-for-purpose biomarkers have yet been identified. Methods: We conducted a pilot study consisting of 5 portal hypertensive gastropathy (PHG) patients and 5 normal controls, sampling the gastric mucosa of normal controls and PHG patients before and after endoscopic cyanoacrylate injection, using label-free quantitative (LFQ) mass spectrometry, to identify potential biomarker candidates in gastric mucosa from PHG patients and normal controls. Then we further used parallel reaction monitoring (PRM) to verify the abundance of the targeted protein. Results: LFQ analyses identified 423 significantly differentially expressed proteins. 17 protein that significantly elevated in the gastric mucosa of PHG patients were further validated using PRM. Conclusions: This is the first application of an LFQ-PRM workflow to identify and validate PHG–specific biomarkers in patient gastric mucosa samples. Our findings lay the foundation for comprehending the molecular mechanisms of PHG pathogenesis, and provide potential applications for useful biomarkers in early diagnosis and treatment.Trial Registration: Trial registration was completed (ChiCTR2000029840) on February 25, 2020.
Distribution of Human Papillomavirus in Precancerous and Cancerous Cervical Neoplasia in Tunisian Women
Authors: Rhouma Rahima Bel Haj , Ardhaoui Monia , Fehri Emna , Marzougui Asma , Assili Thalja , Guizani Ikram , Boubaker Med Samir , Ennaifer Emna
Published: February 2021

BackgroundHigh-risk human papillomavirus (HR-HPV) are responsible for cervical cancer (CC), that is a major health problem worldwide and the second most prevalent gynecological cancer among Tunisian women. Preventive tools against CC are based on screening and prophylactic vaccines. Improving the preventive strategies as well as the therapeutic algorithms needs the understanding of HPV distribution in cervical lesions in Tunisian women. MethodsA total of 200 formalin-fixed paraffine embedded biopsies were collected in our study. DNA was extracted using Qiagen Mini prep kit. DNA quality was controlled by Beta Globin PCR. Only positive samples for Beta Globin test were used. HPV detection was performed by a nested PCR using PYGMY and GP5+/6+ primers. Genotyping was performed by Reverse Line hybridization using 31 probes. ResultsThe mean age of participants was 38.97 years and 54.5% were over 40 years. Cervical neoplasia distribution according to age showed that CINII/CINIII was observed in women over 30 years old. All samples were positive for Beta Globin PCR. Global HPV prevalence in cervical lesions was 83% (166/200). HPV was present in 65% in CINI, 82% in CINII/CINIII and 85% in CC. HR-HPV was statically associated with cervical intraepithelial neoplasia (p<10-3). HR-HPV distribution according to lesion grade and cervical cancer showed that HPV16 and HPV18 were present in all lesions. For CINII/CINIII, HPV 35 (33,33%) was the most detected type, followed by HPV18 (28,6%), HPV 45 (25%) and HPV 16 (21,7%). HPV 45(62%), HPV 18 (47%) were the most detected in CC. HPV58, 59, 66 were only detected in CC and associated with HPV45,18 and HPV16. HPV39, 31, 33, 52, 56, 68 and HPV70 was associated only with CINI. ConclusionsThese findings show that HR-HPV represents 54,6 % of all infections in all cervical lesions. Five HR-HPV (35, 18, 45,16, 51) were detected in CINII/CINIII with a high incidence of HPV 35, 18, 45, and 16 that are included in the proposed vaccines. These findings give useful information for vaccine implementation consideration as well as personalized decision algorithms of intra-epithelial cervical lesions in Tunisian women.
WITHDRAWN: Model of Dependence Between the Parameters of Surface Roughness and the Parameters of Form and Location During the Machining by Drills with the use of Artificial Neural Networks
Authors: Krivokapić Zdravko , Vučurević Radoslav , Dasic Predrag V. , Ivanković Petar
Published: February 2021

This paper presents a model of dependence between the parameters of surface roughness and the parameters of cylindricity and eccentricity in drilling operation for the enhancing steel EN 42CrMo4, hardness 28 HRC, with twist drills DIN 338 made of high-speed steel EN HS6-5-2, with normal blade. The quality of machining, besides the accuracy of measures, completely determined with the values of the parameters of the surface roughness and the parameters of form and location, hence this paper is oriented to the creating models between parameters of the quality of a machined surface and parameters of deviations from form and position. By the developing models based on artificial neural networks and using experimental results, it is possible to analyse the quality of machining on the basis of parameters of a surface roughness.
Predictors of Congenital Anomalies Among Newborns in Arsi Zone Public Hospitals, Southeast Ethiopia: a Case-control Study
Authors: Jemal Sudi , Fentahun Engidaw , Oumer Mohammed , Muche Abebe
Published: February 2021

Background: Congenital anomaly is a partial or complete structural and/or functional defect during intrauterine life. Globally, major congenital anomalies account for 6% of all newborns among which about 94% of cases occurred in developing countries. In spite of its public health importance, very limited studies are reported in Ethiopia, and hardly any study in Arsi Zone.Objectives: To determine the predictors of congenital anomalies among newborns in Arsi Zone Public Hospitals, Southeast Ethiopia.Methods: A multi-center institutional-based case-control study was conducted in 418 (105 cases and 313 controls) of newborns in Arsi Zone Public Hospitals. Descriptive analysis, binary and multivariable logistic regressions were implemented.Results: In this study, women who have been drinking alcohol during pregnancy were 3.48 times more prone to have newborns with congenital anomalies than their counterparts (AOR=3.48; 95% CI: 1.38, 8.74). The likelihood of having a newborn with congenital anomalies was six and four times higher for women who had a maternal illness (AOR=6.10; 95%CI: 2.39, 15.57) and chewing khat during pregnancy (AOR=4; 95%CI: 1.49, 10.65), respectively. Moreover, the lack of folic acid supplementation and pesticides during pregnancy were 3.25 and 4.76 times more likely to experience a newborn with congenital anomalies, respectively. Conclusion: Alcohol drinking, maternal illness, khat chewing, and chemical exposure during pregnancy had a significant association with the occurrence of congenital anomalies. While, taking folic acid supplements had a protective effect. Health experts and the community should take these factors into consideration and act accordingly.
Maize and Common Bean Seed Exudates Mediate Part of Nonhost Resistance to Phytophthora Sojae before Infection
Authors: Zhang Zhuoqun , Zhao Yifan , An Tai , Yu Han , Bi Xiangqi , Liu Haixu , Xu Ying , Yang Zhiyue , Chen Yufei , Wen Jingzhi
Published: February 2021

Purpose: Phytophthora sojae does not infect the nonhost maize (Zea mays L.) but could infect the nonhost common bean (Phaseolus vulgaris L.). Soybean seed exudates participate in mediating host resistance to P. sojae before infection. This study aimed to elucidate the role of nonhost seed exudates in mediating nonhost resistance to P. sojae before infection. Methods: The response behavior of P. sojae zoospores to the seed exudates was determined using an assay chamber and a concave slide, and the proteomes of P. sojae zoospores treated with the seed exudates were analysed with the tandem mass tag (TMT) method. The key proteins were quantified by parallel reaction monitoring (PRM).Results: Maize seed exudates exerted a repellent effect on zoospores, whereas common bean seed exudates did not exhibit any attraction to zoospores but could dissolve the cysts. The key proteins related to zoospores chemotaxis showed no significant changes in response to maize seed exudates, but the key proteins in arachidonic acid pathway were downregulated and controlled the repellent behavior of zoospores. Proteins protecting the cell membrane structure were significantly downregulated in zoospores responding to common bean seed exudates, which confirmed the bacteriolytic effect of common bean seed exudates on cysts. Conclusion: Maize and common bean seed exudates mediate part of the nonhost resistance via different mechanisms prior to P. sojae infection. The immune of maize to P. sojae is due to the repellent effect of maize seed exudates on zoospores. Common bean seed exudates participate in mediating nonhost resistance by dissolving cysts.
The Difference of Acetabular Cup Orientation Between Two Surgical Sides After Primary Total Hip Arthroplasty by Right-handed Surgeons
Authors: Xiong Ao , liu su , Li Guoqing , Weng Jian , Wang Deli , Zeng Hui
Published: February 2021

Background: We performed the retrospective cohort study to compare the acetabular cup orientation, including anteversion angle (AA) and inclination angle (IA), of dominant hand side and non-dominant hand side after primary total hip arthroplasty (THA) by right-handed orthopedic surgeons. Methods: Between January 2018 and December 2018, 290 patients who aged below 60 years and underwent primary THA were retrospective screened. Patients who had hemiarthroplasty, previous hip surgery, ankylosing spondylitis, developmental dysplasia of hip (DDH, Crowe type-Ⅲ and type-Ⅳ), severe comorbidity, missing information, inferior quality radiographs were excluded. According to the surgery side, all patients were divided into left group and right group. Postoperative plain radiographs were analyzed to compare the AA and IA between left and right side. Univariate and stepwise multivariable linear regression to control included confounding factors. Stratified analysis was performed to identify whether the operation approach can affect the result, including anterolateral (ALA) and posterolateral approach (PLA). Results: The mean AA was 17.7° (range 6.0° to 30.0°) and 21.0° (range 9.5° to 35.0°) for the left and right side respectively. The mean difference was 3.28° (95% CI: 1.92 – 4.64; P<0.001). The mean IA was 41.1° (range 24.0° to 59.0°) and 40.1° (range 20.5° to 56.0°) for the left and right side respectively (P=0.314). 113 patients' AA within the “safe zone” in the left (93.4 %), while the right was 93 patients (82.3 %) (P=0.009). 95 patients' IA within the “safe zone” in the left (78.5 %), while the right was 97 patients (85.8 %) (P=0.144). The IA of ALA group was smaller than PLA group in both sides. The mean difference was 3.98° (95% CI: 1.22 - 6.74; P=0.005). Conclusions: We concluded that AA in left side may be more accurate than right side after primary THA by right-handed surgeons. The IA was no difference between the two sides, while it was smaller in ALA than in PLA. The results are still needed to be verified in future.
PUMILIO Proteins in Colorectal Cancer: Tumor Growth Promoting Function and Potential as Therapeutic Targets
Authors: Gong Yuanyuan , Liu Zukai , Yuan Yihang , Yang Zhenzhen , Zhang Jiawei , Lu Qin , Wang Wei , Fang Chao , Lin Haifan , Liu Sanhong
Published: February 2021

PUMILIO (PUM) proteins belong to the highly conserved PUF family post-transcriptional regulators involved in diverse biological processes. However, their function in carcinogenesis remains under explored. Here, we found that the expression of Pum1 and Pum2 are increased in clinical colorectal cancer (CRC). Intestine-specific knockout of Pum1 and Pum2 significantly inhibited the progression of colitis associated cancer in the AOM/DSS model. Knockout or knockdown of Pum1 and/or Pum2 resulted in a significant decrease in the tumorigenicity. In addition, delayed G1/S transition was observed. We identified p21/Cdkn1a as direct target of PUM1, and abrogation of the PUM1 binding site in p21 resulted in decreased tumor cell growth as well as delayed G1/S transition. Furthermore, intravenous injection of nanoparticle-encapsulated anti-Pum1 and Pum2 siRNAs reduced colorectal tumor growth in murine orthotopic colon cancer models. These findings reveal a tumor growth promoting role of PUM proteins in CRC and its potential as therapeutic targets.
A Ferroptosis-Related Gene Signature for Lung Function and Quality of Life in Patients with Idiopathic Pulmonary Fibrosis
Authors: Li Yupeng , Ning Shangwei , Yang Yi , Chen Hong , Wang Chen
Published: February 2021

Background: Rapid advances in genetic and genomic technologies have begun to reshape our understanding of idiopathic pulmonary fibrosis (IPF). Ferroptosis, an iron-dependent form of regulated cell death, play an important role in the development of IPF. Therefore, our study aimed to explore the role of ferroptosis-related genes (FRGs) and their correlation with lung dysfunction and quality of life in patients with IPF. Methods: Datasets were acquired by researching the Gene Expression Omnibus. FRGs were acquired by researching GeneCard database and PubMed. Ferroptosis-related differentially expressed genes (FRDEGs) were identified according to integrating FRGs and the DEGs identified in the GSE110147 dataset. Candidate key genes were identified from the miRNA-target FRDEGs network and protein-protein interactions (PPI) network. The relationship between key genes and lung function or quality of life was calculated using the GSE32537 datasets.Results: 293 FRGs were obtained, and 71 FRDEGs were identified. According to enrichment analysis, cell growth and death and pathways associated cancer were the important pathways, and significant biological processes were mainly consisted of cellular responses to stimulus and various situations. In addition, this study constructed an PPI network and a miRNA-target network based on the 71 FRDEGs, determined 19 candidate key genes. Furthermore, acyl-CoA synthetase long chain family member 1 (ACSL1), integrin subunit beta 8 (ITGB8) and ceruloplasmin (CP) were identified as the key genes. The expression level of ACSL1 was the strongest predictor for lung function (negatively) including percent predicted forced vital capacity (FVC% predicted) and percent predicted diffusion capacity of the lung for carbon monoxide (Dlco% predicted) and quality of life (negatively). In addition, ITGB8 and CP were negatively associated with FVC% predicted. According to DrugBank and PubMed, 4 drugs and 16 drugs have been found to act on ACSL1 and CP, respectively. Conclusion: These results imply that FRGs may shed new understanding on disease mechanism and provide potential biomarkers and therapy target to predict IPF progression.
WITHDRAWN: N6-Methyladenosine Modification of PTTG3P Contributes to Colorectal Cancer Progression via IGF2BP2
Authors: zheng yang , yu guilin , xie longfei , wang yue , zhao guohua
Published: February 2021

Background N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) emerged as crucial players in colorectal cancer (CRC) progression, but the m6A modified lncRNA PTTG3P in CRC are still need to be systematically defined. Methods qRT-PCR was adopted to measure the PTTG3P expression. Survival analysis was used to explore the correlation between the expression of PTTG3P and CRC patients prognosis. Receiver operating curve (ROC) was tested to evaluate the PTTG3P predictive ability. Functional studies were examined by CCK-8, glucose uptake, lactate assay, ATP assay, ECAR assay and xenograft mice model. Mechanistic studies were explored by GSEA, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and RNA immunoprecipitation (RIP).Results PTTG3P was upregulated in CRC and closely related to poor prognosis. Through gain and loss of function approaches, PTTG3P facilitated proliferation and glycolysis through Hippo pathway, and glycolysis inhibitor (2-DG ,3-BG) and LDHA knockdown could rescue cell proliferation. Mechanically, m6A methylation induced the elevation of PTTG3P by increasing its stability , and insulin like growth factor-2 mRNA binding proteins 2 (IGF2BP2) involved in the progression. Finally, rescue assays validated the effect of METTL3/PTTG3P/YAP1 axis in CRC progression. Conclusions m6A-induced PTTG3P could facilitates CRC development via interacting with IGF2BP2, which provides a predictive biomarker and theraperutic target for CRC.
CBX2 Induces Glioma Cell Proliferation and Invasion Through the Akt/PI3K Pathway
Authors: Wang Le , Ren Bingcheng , Zhong Yue , NAN Yang
Published: February 2021

Background Glioma is the most common primary intracranial tumor. Abnormal expression of CBX2(ChromoBox2) is associated with tumorigenesis and tumor development. Methods TCGA data in UALCAN showed that CBX2 was overexpressed in glioma tissue. To confirm the role of CBX2 in glioma, we regulated the level of CBX2 and conducted colony formation, Transwell, and CCK-8 assays to verify the effect of CBX2. Results The results showed that CBX2 knockdown reduced glioma cell proliferation and invasion and that the cells were less tumorigenic. CBX2 overexpression induced glioma cell proliferation and invasion and glioma stem cell self-renewal. The animal experiments showed that CBX2 knockdown inhibited glioma growth and improved survival time. CBX2 knockdown inhibited activation of the Akt/PI3K pathway. EGF rescued the effects of CBX2. Conclusion We hypothesized that CBX2 induced the growth and invasion of glioma cells via the Akt/PI3K pathway.
Design, implementation and Evaluation of Self-Care Program in the Prevention of Breast Cancer Among Women in Isfahan: A Community-Based Participatory Action Research Protocol
Authors: kianpour Maryam , Taleghani Fariba , Noroozi Mahnaz , Savabi-Esfahani Mitra , boroumandfar Zahra , Hashemi Maryam , Changiz Tahereh , Javanmard Shaghayegh Haghjooy
Published: February 2021

Background: Breast cancer is one of the most prevalent cancers among women in Isfahan, Iran but unfortunately its prevention is not desirable in this city. This disease poses several healths, social and economic burdens upon women. In order to promote women's self-care in breast cancer prevention, this study aims to design, implement and evaluate a self-care program in the prevention of breast cancer among women in Isfahan through using a community-based participatory action research method.Methods: The present study will be conducted based on a community-based participatory action research in Isfahan, Iran. The participatory action research in this study will include four general phases of organizing, action planning, action and rethinking. The mentioned phases will be as follows: In the organizing phase, the needs of the participants and the action research settings are examined. This means that the current situation is identified and the views of the process owners are evaluated. In the action planning phase, using the results of the first phase, some strategies are designed in order to promote self-care behaviors in the prevention of breast cancer among women in Isfahan. In the implementation phase, the selected strategies are implemented with the help of the process owners. Finally, in the rethinking phase, the results of the implementation of the strategies are monitored and evaluated, and this cycle continues until the intended results are achieved. Discussion: Changing the role of individuals from a passive state in the care process to an aware and active state requires motivation, responsibility and active participation of people in the disease control process. Moreover, there are many cultural and social factors which affect the active participation of Iranian women. As such, using a community-based participatory action research, people can be involved in promoting their health.
Enhancing the Performance and Recyclability of Polyaniline/TiO2 Hybrid Nanocomposite by Immobilizing with Zein/Hydroxyethyl cellulose Composites for Removal of Anionic dyes
Authors: Gelaw Tadesse Bassie , Sarojini Balladka Kunhanna
Published: February 2021

Fabricating a stable, recyclable, and eco-friendly photocatalyst for dye treatment is vital in sustaining a clean ecosystem. In this regard, polyaniline/TiO2 (PANI/TiO2) photocatalyst was immobilized by zein/hydroxyethyl cellulose (zein/HEC) adhesive to enhance recyclability and catalytic activity. The blending of zein/HEC/PANI/TiO2 photocatalyst involves insitu oxidative polymerization, followed by immobilization with zein/HEC functionalized composites. The PANI/TiO2 composite was successfully grafted with the adhesive through physicochemical interaction, as evidenced by field emission scanning electron microscope (FESEM), Fourier transform infrared spectroscopy (FTIR), and Powder X-ray diffractometer (XRD). The simultaneous thermal analysis (STA) results show that the photocatalyst has the best thermal stability relative to PANI and PANI/TiO2 in the recommended range of dye degradation temperature. The effect of external factors like TiO2 nanoparticle proportion, pH of the solution, and catalyst dosage was studied in response to dye degradation capacity. The synthesized catalyst is efficient to degrade methyl orange in a wide range of pH. The kinetics of the catalysis reaction obeys first order kinetics. The maximum degradation efficiency achieved was 97.9 and 84.3% in the presence and absence of light, respectively. The catalyst was easily recovered by decantation, and its catalytic efficacy was more than 94% after five cycles. Hence, it is a promising alternative for decolorizing anionic dyes from wastewater.
Prevalence of Antibiotic Resistance in Vibrio cholerae: A Meta-analysis
Authors: Bagheri-Josheghani Sareh , Bakhshi Bita , Mousavi Maryam
Published: February 2021

Background:Cholera could cause severe watery diarrhea and even death, but in patients diagnosed with severe dehydration, treatment with an appropriate antimicrobial agent could decrease the volume of diarrhea and shorten the duration of V. cholerae shedding. Unfortunately, due to the high antibiotic’s consumption, antibiotic resistance in V. cholerae strains is progressively increasing worldwide. The present systematic review and meta-analysis study aimed to investigate the incidence of antibiotic resistance in V. cholerae strains worldwide.Methods: The incidence of antibiotic resistance in V. cholerae strains was assessed by conducting a systematic review and searching international databases including PubMed and Google Scholar for articles published from Jan 1, 1990 to Sept 30, 2016 using related keywords. Studies were selected to be included in this systematic review according to a predefined eligibility criteria. International databases were searched for articles evaluating V. cholerae strains resistance rates to antibiotics. Pooled estimates of antibiotics resistance and 95% confidence intervals (CIs) were categorized based on WHO regions. Results:V. cholerae was the most common bacterium showing high resistance rates to various antibiotics including furazolidone (83%), trimethoprim-sulfamethoxazole (67%), nitrofurantoin (66%), streptomycin (64%), and nalidixic acid (58%).Conclusions: According to this meta-analysis results, the high resistance of V. cholerae strains to antibiotics could be considered as a global public health threat. Therefore, it is recommended to select appropriate antibiotic treatment regimens for each region based on antibiotic resistance patterns of local strains in that region.
Treatment Outcome With Fosravuconazole L-lysine Ethanolate (F-RVCZ) for Onychomycosis
Authors: Shimoyama Harunari , Yo Ayaka , Sei Yoshihiro , Kuwano Yoshihiro
Published: February 2021

Fosravuconazole L-lysine ethanolate (F-RVCZ), a ravuconazole prodrug, is a newly available agent with high expectations for efficacy in the treatment of onychomycosis. However, clinical data regarding the efficacy of F-RVCZ are limited because the drug was launched only in Japan in 2018. Therefore, we analyzed the outcome of F-RVCZ therapy in the treatment of onychomycosis at outpatient dermatology clinics in Japan. We examined data for 109 patients (68 male, 41 female) with varying clinical type, including total dystrophic onychomycosis and dermatophytoma, and a wide range of age groups, including the elderly. The complete cure rate at 12 weeks was 6.4% (7/109) and 67.9% (74/109) at the last visit (mean time to last visit: 32±14.2 weeks). Mean rate of improvement in the affected nail area was 49.1±23.3% at 12 weeks and 86.8±22.4% at the last visit. Efficacy at 12 weeks and the last visit, respectively, was as follows: none, 4 cases and 1 case; slight, 35 cases and 4 cases; moderate, 51 cases and 21 cases; significant, 12 cases and 9 cases; complete cure, 7 cases and 74 cases. There were no serious adverse events. This retrospective survey was the first large-scale analysis of actual clinical practice outcomes and had minimal exclusions. Compared to previous reports, our results demonstrated excellent efficacy of F-RVCZ therapy in a variety of patients. Considering our results and the ease of oral administration (1 capsule/day for 12 weeks) and few adverse events, F-RVCZ therapy appears to be a useful option for the treatment of onychomycosis.
Tribological interaction of plasma functionalized CaCO3 nanoparticles with zinc and ashless dithiophosphate additives
Authors: Vyavhare Kimaya P , Timmons Richard B. , Erdemir Ali , Aswath Pranesh B.
Published: February 2021

Surface-modified CaCO3 nanoparticles, synthesized through plasma-enhanced chemical vapor deposition (PECVD), were employed to improve lubricant additive technology for internal combustion engines via reduction and/or replacement of additives, such as zinc dialkyl dithiophosphate (ZDDP), in engine oil. Various oil formulations were prepared with functionalized CaCO3 nanoparticles, in combination with ashless dialkyl dithiophosphate (DDP) and ZDDP at low concentrations of phosphorus. Tribological test results indicate synergistic interaction of functionalized CaCO3 nanoparticles with ZDDP and DDP, providing enhanced friction and wear performance under boundary lubrication. A comparative study of the tribo-surfaces morphology and chemistry was assessed via atomic force microscopy and X-ray absorption near-edge spectroscopy. Improved wear protection by functionalized CaCO3BM (borate and methacrylate coated) nanoparticles under boundary lubrication was attributed to the formation of calcium and boron-rich 50–80 nm thick tribofilms on the worn surfaces. XANES results revealed that plasma functionalized CaCO3 nanoparticles interact with ZDDP and DDP and participate in tribofilm formation through tribo-chemical reactions and metal cation supply to form stable and wear-resistant tribofilms. These results provide strong support for the potential application of plasma functionalized CaCO3 nano-additives to reduce the concentration of harmful P-based additives in automotive lubricants.
Identification of a nine ferroptosis-related lncRNA prognostic signature for lung adenocarcinoma
Authors: Tong Xiwen , Zhang Yujiao , Yang Guodong , Yi Guanghui
Published: February 2021

Background

Recently, mounting of studies has shown that lncRNA affects tumor progression through the regulation of ferroptosis. The current study aims to construct a robust ferroptosis-related lncRNAs signature to increase the predicted value of lung adenocarcinoma (LUAD) by bioinformatics analysis.
Methods

The transcriptome data were abstracted from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were screened by comparing 535 LAUD tissues with 59 adjacent non-LAUD tissues. Univariate Cox regression, lasso regression, multivariate Cox regression were conducted to design a ferroptosis-related lncRNA signature. This signature’s prognosis was verified by the log-rank test of Kaplan-Meier curve and the area under curve (AUC) of receiver operating characteristic (ROC) in train set, test set, and entire set. Furthermore, univariate and multivariate Cox regression were used to analyze its independent prognostic ability. The relationship of the ferroptosis-linked lncRNAs' expression and clinical variables was demonstrated by Wilcoxon rank-sum test and Kruskal-Wallis test. Gene set enrichment analysis (GSEA) was performed to signaling pathways it may involve.
Results

1224 differentially expressed lncRNAs were idendified, of which 195 are ferroptosis-related lncRNAs. A nine ferroptosis-related lncRNAs (AC099850.3, NAALADL2-AS2, AL844908.1, AL365181.2, SMIM25, FAM83A-AS1, LINC01116, AL049836.1, C20orf197) prognostic signature was constucted. This model's prognosis in the high-risk group is obviously worse than that of the low-risk group in train set, test set, and entire set. The AUC of ROC predicting the three years survival in the train set, test set, and entire set was 0.754, 0.716, and 0.738, respectively. Moreover, the designed molecular signature was found to be an independent prognostic variable. The expression of these lncRNAs and the lncRNA signature are related to clinical stage, T stage, Lymph-node status, distant metastasis. Finally, GSEA analysis results show that the signature is involved in eight tumor-related and metabolism-related signaling pathways
Conclusion

The current study constructed, validated, and evaluated a nine ferroptosis-related lncRNA signature which can independently be used to predict the prognosis of LAUD patients, and may become a new therapeutic target.
Immediate and lasting impact of combining restrictive and enabling interventions to reduce aztreonam consumption in a community hospital
Authors: Mody Dviti , Burke Christopher , Minson Quentin
Published: February 2021

Background. Antimicrobial stewardship initiatives combining restrictive and enabling components may be an effective strategy to achieve short- and long-term objectives. Aztreonam, a relatively high-cost antipseudomonal antibiotic, is an appropriate target for stewardship initiatives based on propensity for overuse in penicillin allergy, an activity profile often warranting additional empiric gram-negative and gram-positive coverage, and a unique durability to Ambler class B metallo-beta-lactamases.Objective. Analyze the immediate and long-term impact on aztreonam prescribing of combining restrictive and enabling interventions.Setting. Single 233-bed community hospital with 45 adult intensive care unit beds in Nashville, Tennessee.Method. Retrospective, interrupted time series analysis comparing all patients receiving aztreonam prior to intervention between January 1, 2010 and September 30, 2011 and following intervention between October 1, 2011 and September 30, 2019. Quarterly defined daily doses/1000 adjusted patient days and microbiology laboratory annual surveillance data were utilized for analysis. Main outcome measure. Post-intervention change in trend of aztreonam consumption. Results. Following intervention, a significant decline in aztreonam consumption was observed (-1.97 defined daily doses/1000 adjusted patient days; p = 0.003) resulting in a sustained decrease in aztreonam consumption from 2011 (3rd quarter) to 2019 (3rd quarter) from 15.2 to 0.26 defined daily doses/1000 adjusted patient days. Short-term group 2 carbapenem consumption increased (p = 0.044). Pseudomonas aeruginosa susceptibility to aztreonam improved from 2011 to 2018 (72% vs. 84%; p = 0.0004) without deleterious effects to alternative antipseudomonal beta-lactams. Conclusion. Combining restrictive and enabling interventions had immediate and sustained impact on aztreonam consumption with Pseudomonas aeruginosa susceptibility improvement.Impacts on practice: ● A pharmacist-driven intervention combining restrictive and enabling strategies produced an immediate and sustained decrease in aztreonam prescribing at a community hospital.● Following the sustained reduction of aztreonam consumption, susceptibility rates for Pseudomonas aeruginosa improved without producing deleterious effects on alternative antipseudomonal beta-lactams.